bluuebunny/crossref_metadata_2025 huggingface dataset:
Views and experiences of Every Mind Matters, Public Health England’s adult mental health literacy campaign: a qualitative interview study
Authors: Stuart Ruth , Shah Prisha , Olive Rachel Rowan , Trevillion Kylee , Henderson Claire
Published: November 2022

Background

Every Mind Matters is a publicly funded health campaign, launched in England in 2019, to equip adults to look after their mental health, and that of others, by offering online information about common problems: anxiety, low mood, sleep, stress. This study is one component of an independent evaluation of Every Mind Matters conducted by the NIHR Mental Health Policy Research Unit. Its aim is to explore individuals’ experiences and views of the Every Mind Matters campaign and website.

Methods

Four researchers, including three with lived experience of using mental health services, conducted 20, one-off, semi-structured, online interviews with a range of adult participants, including a sample of EMM users and a purposively recruited sub-sample known to have severe or long-term mental health conditions. The team took a codebook approach to the analysis of the transcripts and identified four main themes.

Findings

There was an expectation from the name Every Mind Matters that its advice would address everyone. Almost all participants had experience of mental distress and looked to Every Mind Matters for help with a current problem for themselves.

All participants were complimentary about the Every Mind Matters website and found it to be user-friendly (theme 1) and personalised (theme 2) especially the interactive feature ‘Your Mind Plan quiz’ which responds with suggested actions to improve wellbeing and follows up with reminder emails. A few participants found this life changing.

Some participants wanted Every Mind Matters to better acknowledge the contexts in which they live (theme 3) such as the limitations of health conditions and health services, and difficulties of crowded housing, social policy, and climate change. Many participants would like Every Mind Matters to do more (theme 4), offer more interactivity, more choice, more information about available treatments, and more stratified advice to cover more severe mental health conditions so that everyone is included.

Conclusion

The population that experiences common mental health difficulties is not separate from the population that has severe mental health problems. Every Mind Matters could continue and build on its success by addressing a wider range of needs.
Preliminary Validation of a Structural Magnetic Resonance Imaging Metric for Tracking Dementia-Related Neurodegeneration and Future Decline
Authors: Kress Gavin T , Popa Emily S. , Thompson Paul M , Bookheimer Susan Y , Thomopoulos Sophia I , Ching Christopher RK , Zheng Hong , Merrill David A. , Panos Stella E , Siddarth Prabha , Bramen Jennifer E
Published: November 2022

Current Alzheimer’s disease (AD) research has a major focus on validating and discovering noninvasive biomarkers that can detect AD, benchmark disease severity, and aid in testing the efficacy of interventions. Structural magnetic resonance imaging (sMRI) is a well-validated tool used in diagnosis and for monitoring disease progression in AD. Much of the sMRI literature centers around hippocampal and other medial temporal lobe structure atrophy, which are strongly associated with cognition and diagnosis. Because atrophy patterns are complex and vary by patient, researchers have made efforts to condense more brain information into validated metrics. Many of these methods use machine learning (ML), which can be difficult to interpret clinically, hampering clinical adoption. Here, we introduce a practical, clinically meaningful and interpretable index which we call an “AD-NeuroScore.” Our approach is automated and uses multiple regional brain volumes associated with cognitive decline. We used a modified Euclidean inspired distance function to calculate the differences between each participant and a cognitively normal (CN) older adult template, adjusting for intracranial volume, age, sex, and scanner model. Here we report validation results, including sensitivity to diagnosis (CN, mild cognitive impairment (MCI), and AD) and disease severity (Clinical Dementia Rating Scale Sum of Boxes (CDR-SB), Mini Mental State Exam (MMSE), and Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-11) in 929 older adults (mean age=72.7 years, SD=6.3, Range=55.1-91.5, 50% Female) drawn from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. To determine if AD-NeuroScore might be predictive of disease progression, we assessed the relationship between the calculated AD-NeuroScore at baseline and change in both diagnosis and disease severity scores at 12, 24, 36, and 48-months. We performed additional validation in all analyses, benchmarking AD-NeuroScore against adjusted hippocampal volume (AHV). We found that AD-NeuroScore was significantly associated with diagnosis and all disease severity scores at baseline. Associations between AD-NeuroScore and disease severity (CDR-SB and ADAS-11) were significantly stronger than with AHV. Baseline AD-NeuroScore was also associated with change in diagnosis and changes in disease severity scores at all time points. Performance was equivalent, or in some cases superior, to AHV. These early validation results suggest that AD-NeuroScore has the potential to be a clinically meaningful biomarker for dementia.
Patterns of Polysubstance use in young Black and Latinx sexual minority men and transgender women in its association with sexual partnership factors: The PUSH study
Authors: Arrington-Sanders Renata , Galai Noya , Falade-Nwulia Oluwaseun , Hammond Christopher , Wirtz Andrea , Beyrer Christopher , Celentano David
Published: November 2022

Background

Young Black and Latinx sexual minority men (SMM) and transgender women (TW) continue to suffer some of the highest burdens of HIV in the United States. Disparities are partly attributed to suboptimal uptake of HIV prevention and treatment services negatively impacted by substance use. Adult studies have demonstrated that polysubstance use increases HIV acquisition risk through increased sexual behaviors, however there are few studies that have examined polysubstance in this population and how polysubstance use might increase young SMM and TW’s risk for HIV.

Methods

Cross-sectional data from 466 young Black and Latinx SMM and TW living in four US high HIV-burden cities enrolled in the PUSH Study, a status neutral randomized control trial to increase uptake of pre-exposure prophylaxis and treatment adherence. Examined data for patterns of polysubstance use comparing age differences of use; and exploring associations between substance use and HIV risk behaviors focusing on three core partnership factors - inconsistent condom use, pressure to have anal sex without a condom, and older partner.

Results

Most participants described prior substance use with alcohol and cannabis being most common (76%, respectively) and 23% describing other describing prior alcohol use, 76% (n=353) described cannabis use, and 23% described other illicit drug use (including stimulants, cocaine, hallucinogens, sedatives, opioids, and inhalants). Polysubstance use was common with nearly half (47%) of participants reported alcohol and cannabis use, 20% reporting alcohol, cannabis, and one other illicit drug use, and 19% reporting alcohol or cannabis use plus one other illicit drug use. Polysubstance use was associated with greater adjusted odds of pressure to have anal sex without a condom, having an older partner (> 5 years older), and inconsistent condom use.

Conclusions

High levels of substance use, polysubstance use and strong associations with high-risk sexual practices and sexual partnerships that are known to be predictors of HIV acquisition or transmission among Black and Latinx sexual and gender minority youth, call for combination interventions that include substance use treatment alongside ARV-based prevention and treatment and partner-based interventions.
Does the visual word form area split in bilingual readers? A millimeter-scale 7T fMRI study
Authors: Zhan Minye , Pallier Christophe , Dehaene Stanislas , Cohen Laurent
Published: November 2022

In expert readers, a brain region known as the visual word form area (VWFA) is highly sensitive to written words, exhibiting a posterior-to-anterior gradient of increasing sensitivity to orthographic stimuli whose statistics match those of real words. Using high-resolution 7T fMRI, we ask whether, in bilingual readers, distinct cortical patches specialize for different languages. In 21 English-French bilinguals, unsmoothed 1.2 mm fMRI revealed that the VWFA is actually composed of several small cortical patches highly selective for reading, with a posterior-to-anterior word similarity gradient, but with near-complete overlap between the two languages. In 10 English-Chinese bilinguals, however, while most word-specific patches exhibited similar reading specificity and word-similarity gradients for reading in Chinese and English, additional patches responded specifically to Chinese writing and, surprisingly, to faces. Our results show that the acquisition of multiple writing systems can indeed tune the visual cortex differently in bilinguals, sometimes leading to the emergence of cortical patches specialized for a single language.
WITHDRAWN: SETD2 deficiency promotes the transition from PKD to ccRCC by dysregulation of sphingomyelin metabolism
Authors: Zhang Yu , Liu Changwei , Ye Tianbao , Chen Lu , Yang Xiaoqun , Zhou Luting , An Huimin
Published: November 2022

Withdrawal Statement

bioRxiv has withdrawn this preprint as it was submitted and made public without the full consent of all the authors. 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.
Quantifying spatial dynamics and regulators ofMycobacterium tuberculosisphagocytosis by primary human macrophages using microfabricated patterns
Authors: Savulescu Anca F. , Peton Nashied , Oosthuizen Delia , Hazra Rudranil , Mhlanga Musa. M. , Coussens Anna K.
Published: November 2022

Macrophages provide a first line of defense against invading pathogens, including the leading cause of bacterial mortality,Mycobacterium tuberculosis(Mtb). Phagocytosing extracellular organisms mediate pathogen clearanceviaa multitude of antimicrobial mechanisms, uniquely designed against an array of pathogens. Macrophages are able to execute different programs of activation in response to pathogenic challenge with host mediators, polarizing them to a variety of differentiation states, including the pro-inflammatory M1 and anti-inflammatory M2 states. The functional polarization of a macrophage prior to infection, thus impacts the outcome of host-pathogen interaction. One of the limitations when usingin vitrodifferentiated human primary monocyte-derived macrophages (MDMs) is the heterogeneous nature of the mature population, which presents a challenge for quantitative characterization of various host-pathogen processes. Here, we describe an approach to minimize this heterogeneity, based on micropatterning of cells to reintroduce aspects of cellular homogeneity lost in a 2D tissue culture. Micropatterning consists of growing cells at the single cell level on microfabricated patterns, to constrain the size and shape of the cell, reducing cell-to-cell variation and mimicking the physiological spatial confinement that cells experience in tissues. We infected micropatterned GM-CSF- (M1) and M-CSF- (M2) derived human MDMs withMtb, which allowed us to study host-pathogen interactions at a single cell level, at high resolution and in a quantitative manner, across tens to hundreds of cells in parallel. Using our approach, we were able to quantify phagocytosis ofMtbin MDMs, finding phagocytic contraction is increased by interferon-gamma stimulation, whilst contraction and bacterial uptake is decreased following silencing of phagocytosis regulatorNHLRC2or Tween80 removal of bacterial surface lipids. We also identify alterations in host organelle position withinMtbinfected MDMs, as well as identifying differences inMtbsubcellular localization in relation to the microtubule organizing center (MTOC) and in line with the cellular polarity in M1 and M2 MDMs. Our approach described here can be adapted to study other host-pathogen interactions and co-infections in MDMs and can be coupled with downstream automated analytical approaches.
Integrative phosphoproteomics defines two biologically distinct groups of KMT2A rearranged acute myeloid leukaemia with different drug response phenotypes
Authors: Casado Pedro , Rio-Machin Ana , Miettinen Juho J. , Bewicke-Copley Findlay , Rouault-Pierre Kevin , Krizsan Szilvia , Parsons Alun , Rajeeve Vinothini , Miraki-Moud Farideh , Taussig David C , Bödör Csaba , Gribben John , Heckman Caroline , Fitzgibbon Jude , Cutillas Pedro R.
Published: November 2022

Acute myeloid leukaemia (AML) patients harbouring certain chromosome abnormalities have particularly adverse prognosis. For these patients, targeted therapies have not yet made a significant clinical impact. To understand the molecular landscape of poor prognosis AML we profiled 74 patients from two different centres (in UK and Finland) at the proteomic, phosphoproteomic and drug response phenotypic levels. These data were complemented with transcriptomics analysis for 39 cases. Data integration highlighted a phosphoproteomics signature that define two biologically distinct groups of KMT2A rearranged leukaemia, which we term MLLGA and MLLGB. MLLGA presented increased DOT1L phosphorylation, HOXA gene expression, CDK1 activity and phosphorylation of proteins involved in RNA metabolism, replication and DNA damage when compared to MLLGB and no KMT2A rearranged samples. MLLGA was particularly sensitive to 15 compounds including genotoxic drugs and inhibitors of mitotic kinases and inosine-5-monosphosphate dehydrogenase (IMPDH) relative to other cases. Intermediate-risk KMT2A-MLLT3 cases were mainly represented in a third group closer to MLLGA than to MLLGB. The expression of IMPDH2 and multiple nucleolar proteins was higher in MLLGA and correlated with the response to IMPDH inhibition in KMT2A rearranged leukaemia, suggesting a role of the nucleolar activity in sensitivity to treatment. In summary, our multilayer molecular profiling of AML with poor prognosis and KMT2A-MLLT3 karyotypes identified a phosphoproteomics signature that defines two biologically and phenotypically distinct groups of KMT2A rearranged leukaemia. These data provide a rationale for the potential development of specific therapies for AML patients characterised by the MLLGA phosphoproteomics signature identified in this study.
SEN1 is responsible for molybdate transport into nodule symbiosomes for nitrogen fixation inLotus japonicus
Authors: Chu Qingnan , Hakoyama Tsuneo , Hayashi Makoto , Toyooka Kiminori , Sato Mayuko , Kamiya Takehiro , Fujiwara Toru
Published: November 2022

Symbiotic nitrogen fixation (SNF) in legume root nodules requires a steady supply of molybdenum (Mo) for synthesis of the iron-Mo cofactor for nitrogenase in bacteroids. For this nutrient to be exported by the host plant it must cross the peribacteroid membrane (PBM), however, the molybdate transporter responsible has not yet been identified. ALotus japonicussymbiotic mutant,sen1, forms nodules that do not fix nitrogen; it has nodule defects and bacteroid degradation. The biochemical function and subcellular localization of SEN1 protein remains to be elucidated. Here, we found a new phenotype in which theSEN1mutation resulted in increased Mo accumulation in the nodule host fractions but decreased Mo accumulation in the bacteroids at 10 days post inoculation. We identified the molybdate efflux transport activity of SEN1 via heterologous expression in yeast.SEN1was expressed exclusively in nodules, and its expression was stable in response to varying Mo supply in nutrient solution.In situimmunostaining verified that the SEN1 protein is localized, in part, to the PBM in the rhizobium-infected cells. Taken together, these results confirmed that SEN1 is responsible for mediating molybdate efflux from the cytosol of nodule host cells to the symbiosomes for SNF. Furthermore,SEN1mutation reduced the expression ofnifDandnifK, suggesting thatSEN1may be pertinent to iron-Mo-cofactor assembly. This work fills the knowledge gap regarding how molybdate is allocated from the host plant to the bacteroids; such knowledge is critical for developing new SNF biological systems in non-legume plants.

One-sentence summary

SEN1 is localized partly in the peribacteroid membrane of nodule cells and mediates the molybdate exportation from the host plant cytosol to the symbiosomes for symbiotic nitrogen fixation.
The Arabidopsis ARID-HMG protein AtHMGB15 modulates JA signalling by regulating MYC2 during pollen development
Authors: Sachdev Sonal , Biswas Ruby , Roy Adrita , Chaudhuri Shubho
Published: November 2022

In flowering plants, jasmonic acid (JA) signalling regulates the complex process of male gametophyte development. JA signalling initiates with the activation of MYC2 transcription factor, for the expression of several JA responsive genes throughout stamen development and pollen maturation. However, the regulation of JA signalling during different developmental stages of male gametophytes is still less understood. In this study we have characterized T-DNA insertion line of AtHMGB15. Phenotypic characterization ofathmgb15-4mutant plants showed delayed bolting, shorter siliques and reduced seed set compared to wildtype. Moreover, deletion of AtHMGB15 resulted in defective pollen morphology, delayed pollen germination, abberant pollen tube growth and a higher percentage of non-viable pollen population inathmgb15-4compared to wildtype. Molecular analysis indicated down-regulation of JA-biosynthesis and JA-signalling genesvizMYC2, MYB21 and MYB24 inathmgb15-4mutant. Furthermore, jasmonic acid and its derivatives were found almost ten-fold lower inathmgb15-4flowers. However, exogenous application of jasmonate could restore pollen morphology and pollen germination, suggesting that impaired JA signalling is responsible for the pollen phenotype inathmgb15mutant. AtHMGB15 physically interacts with MYC2 protein to form the transcription activation complex for promoting transcription of genes responsible for JA signalling during stamen and pollen development. Collectively, our findings indicate that AtHMGB15, a plant specific DNA binding protein of the ARID-HMG group, acts as a positive regulator of JA signalling to control the spatiotemporal expression of key regulators responsible for stamen and pollen development.
Cell autonomous requirement of imprinted XCI in extra-embryonic polar trophoblast cells
Authors: Wang Feng , Chander Ashmita , Yoon Yeonsoo , Wallingford Mary C. , Espejo-Serrano Carmen , Bustos Francisco , Findlay Greg M. , Mager Jesse , Bach Ingolf
Published: November 2022

In female mice the gene dosage from X chromosomes is adjusted by a process called X chromosome inactivation (XCI) that occurs in two steps. An imprinted form of XCI (iXCI) silencing the paternally inherited X chromosome (Xp) is initiated at the 2-4 cell stages. As extraembryonic cells including trophoblasts keep the Xp silenced, epiblast cells that give rise to the embryo proper reactivate the Xp and undergo a random form of XCI (rXCI) during peri-implantation stages. Lack of X dosage compensation leads to peri-implantation lethality due to inhibition of trophoblast stem cells. However, as the epiblast regulates the trophoblast lineage, the roles of iXCI vs rXCI in the early lethal phenotype remains unclear. We have investigated functions and expression of Rlim (Rnf12), an E3 ubiquitin ligase, and its target protein Rex1 (Zfp42) that control iXCI. Consistent with functions specifically for iXCI, we show an inverse correlation in the expression of Rlim and Rex1 throughout pre-implantation development, but anRlim-independent downregulation of Rex1 in epiblast cells upon implantation. Moreover, disturbing the functional Rlim-Rex1 dynamics in females leads to cell fate confusion and premature differentiation specifically of the polar trophoblast stem cell pool. Thus, controlled by the Rlim-Rex1 axis, female mouse development requires iXCI in the polar trophoblast cell lineage.
Development of a mouse model for postresectional liver failure
Authors: van Mierlo Kim M.C. , Van Himbeeck Cathy , Lebrun Valérie , Jansen Peter L.M. , Dejong Cornelius H.C. , Leclercq Isabelle A. , Olde Damink Steven W.M. , Schaap Frank G.
Published: November 2022

Background

Postresectional liver failure (PLF) is a dreaded complication after extended liver resection. Post-operative hyperbilirubinemia suggests that impaired hepatobiliary transport with intrahepatic accumulation of harmful cholephiles plays an etiological role. Bile salts serve dual roles as signaling molecules engaged in liver regeneration after partial hepatectomy (PH) and biological detergents.

Aim

In this study we tested the hypothesis that excessive accumulation of bile salts in the regenerating liver results in PLF.

Methods

Twelve weeks old male C57BL6/J mice were subjected to 70% PH and post-operatively challenged with a diet supplemented with cholic acid (CA, 0.5 or 1.0%; n=5-6 per group) or a control diet. After 48 hours mice were sacrificed, and liver injury, secretory function, and regenerative indices were assessed.

Results

Mice fed a 1.0% CA diet displayed more pronounced weight loss following PH and had a deranged post-operative glucose course. Liver injury (aminotransferase elevations) and impaired hepatobiliary transport function (hyperbilirubinemia) were apparent in the group fed a 1.0% CA diet, but not in animals fed a 0.5% CA diet. No differences in liver mass recovery were observed among groups. However, the percentage of hepatocytes staining positive for the proliferation marker Ki-67 were reduced in mice receiving a 1.0% CA diet relative to animals fed a 0.5% CA diet. PH-induced expression of key factors involved in cell cycle progression (e.g. Foxm1b, Cdc25b) was abrogated in the 1.0% CA group.

Conclusion

A postresectional challenge with a 1.0% CA diet induces signs of liver injury and defective liver regeneration. A longer duration of the dietary challenge and/or secondary hits may further improve the model. Once validated, it can be used to evaluate pharmaceutical strategies to prevent or treat PLF.
Medicago truncatulaABCG40 is a cytokinin importer that negatively regulates lateral root density and nodule number
Authors: Jamruszka Tomasz , Banasiak Joanna , Pawela Aleksandra , Jarzyniak Karolina , Xia Jian , Biała-Leonhard Wanda , Plačková Lenka , Tsering Tashi , Iacobini Francesca Romana , Novák Ondřej , Geisler Markus , Jasiński Michał
Published: November 2022

Numerous studies suggest that cytokinin (CK) distribution plays a relevant role in shaping plant morphology in changing environments. Nonetheless, our knowledge about the involvement of short-distance CK translocation in root mineral nutrition remains scarce, and the specific role of CK transporters in root morphology has yet to be established. Therefore, the molecular identity of CK transporters should be determined to increase knowledge on root plasticity during soil fertility, as well as more frequently encountered plant nutrient deficiencies. In this work, we identified and characterized theMedicago truncatulafull-size ATP-binding cassette (ABC) transporter of the G subfamily MtABCG40 as a plasma membrane CK importer. Its expression is root-specific and is induced by nitrogen deprivation and CKs. Our analyses indicate that MtABCG40 exerts a negative impact on lateral root density by decreasing lateral root initiation and enhancing primary root elongation. Moreover, we also observed that this transporter negatively influenced the nodule number. Our results suggest that MtABCG40 action affects CK signalling, which impacts the cellular response to auxin. In summary, we identified a novel ABCG-type CK transporter that regulates lateral root density and nodule number.
Aliphatic residues contribute significantly to the phase separation of TDP-43 C-terminal domain
Authors: Mohanty Priyesh , Shenoy Jayakrishna , Rizuan Azamat , Ortiz José F Mercado , Fawzi Nicolas L. , Mittal Jeetain
Published: November 2022

TAR DNA binding protein 43 (TDP-43) is involved in key processes in RNA metabolism such as splicing, stability and transcription. TDP-43 dysfunction is frequently implicated in many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD). The prion-like, disordered C-terminal domain (CTD) of TDP-43 is aggregation-prone and harbors the majority (~90%) of all ALS-related mutations. Recent studies have established that TDP-43 CTD can undergo liquid-liquid phase separation (LLPS) in isolation and is important for phase separation (PS) of the full-length protein under physiological conditions. While a short conserved helical region (CR, spanning residues 319-341) promotes oligomerization and is essential for LLPS, aromatic residues in the flanking disordered regions (IDR1/2) have also been found to play a critical role in PS and aggregation. However, TDP-43 CTD has a distinct sequence composition compared with other phase separating proteins, including many aliphatic residues. These residues have been suggested to modulate the apparent viscosity of the resulting phases, but their direct contribution to phase separation has been relatively ignored. Here, we utilized a multiscale simulation and experimental approach to assess the residue-level determinants of TDP-43 CTD phase separation. Single chain and condensed phase simulations performed at the atomistic and coarse-grained level respectively, identified the importance of aromatic residues (previously established) while also suggesting an essential role for aliphatic methionine residues in LLPS.In vitroexperiments confirmed the role of phenylalanine, methionine, and leucine (but not alanine) residues in driving the phase separation of CTD, which have not been previously considered essential for describing the molecular grammar of PS. Finally, NMR experiments also showed that phenylalanine residues in the disordered flanking regions and methionine residues both within and outside the CR contribute important contacts to CTD interactions. Broadly, our work highlights the importance of non-alanine aliphatic residues such as methionine and leucine, and potentially valine and isoleucine, in determining the LLPS propensity, expanding the molecular grammar of protein phase separation to include critical contributions from aliphatic residues.
Mutations Affecting Polar Nuclei Number, Antipodal Cell Cluster Size, Cellularization, and Nuclear Localization in Maize Embryo Sacs
Authors: Chettoor Antony M. , Yang Bing , Evans Matthew M. S.
Published: November 2022

The maize female gametophyte is comprised of four cell types: two synergids, an egg cell, a central cell, and a variable number of antipodal cells. In maize, these cells are produced after three rounds of free-nuclear divisions followed by cellularization, differentiation, and proliferation of the antipodal cells. Cellularization of the eight-nucleate syncytium produces seven cells with two polar nuclei in the central cell. Nuclear localization is tightly controlled in the embryo sac as evidenced by the regular, stereotypical position of the nuclei in all syncytial stages of female gametophyte development. This leads to precise allocation of the nuclei into the cells upon cellularization. Nuclear positioning within the syncytium is highly correlated with their identity after cellularization. Two mutants are described with extra polar nuclei, abnormal antipodal cell morphology, and reduced antipodal cell number, which is correlated with a frequent loss of auxin signaling in the antipodal cell cluster. Mutations in one of these genes,indeterminate gametophyte2encoding a MICROTUBULE ASSOCIATED PROTEIN65-3 homolog, shows a requirement for MAP65-3 in cellularization of the syncytial embryo sac and that the identity of the nuclei in the syncytial female gametophyte can be changed very late before cellularization.
Transcriptional reprogramming of natural killer cells by vaccinia virus shows both distinct and conserved features with mCMV
Authors: Depierreux Delphine M , Smith Geoffrey L , Ferguson Brian J
Published: November 2022

Natural killer (NK) cells have an established role in controlling poxvirus infection and there is a growing interest to exploit their capabilities in the context of poxvirus-based oncolytic therapy and vaccination. How NK cells recognise poxvirus-infected cells to become activated remains unclear. To address this knowledge gap, we studied the NK cell response to vaccinia virus (VACV)in vivo, using a systemic infection murine model. We found broad alterations in NK cells transcriptional activity in VACV-infected mice, consistent with both direct target cell recognition and cytokine exposure. There were also alterations in the expression levels of specific NK surface receptors (NKRs), including the Ly49 family and SLAM receptors, as well as upregulation of memory-associated NK markers. Despite the latter observation, adoptive transfer of NK memory populations did not confer protection from re-infection. Comparison with the NK cell response to murine cytomegalovirus (MCMV) infection highlighted common features, but also distinct NK transcriptional programmes initiated by VACV. Finally, there was a clear overlap between the NK transcriptional response in humans vaccinated with an attenuated VACV, modified vaccinia Ankara (MVA), demonstrating conservation between the NK response in these different host species. Overall, this study provides new data about NK cell activation, function, and homeostasis during VACV infection, and may have implication for the design of VACV-based therapeutics.
Ciliary tip actin dynamics regulate the cadence of photoreceptor disc formation
Authors: Megaw Roly , Moye Abigail , Zhang Zhixian , Newton Fay , McPhie Fraser , Murphy Laura C. , McKie Lisa , He Feng , Jungnickel Melissa K. , von Kriegsheim Alex , Machesky Laura M. , Wensel Theodore , Mill Pleasantine
Published: November 2022

As signalling organelles, primary cilia regulate their membrane G protein-coupled receptor (GPCR) content by ectocytosis, a process requiring localised actin dynamics at their tip to alter membrane shape.(1, 2) Mammalian photoreceptor outer segments comprise an expanse of folded membranes (discs) at the tip of highly-specialised connecting cilia (CC), in which photosensitive GPCRs like rhodopsin are concentrated. In an extraordinary feat of biology, outer segment discs are shed and remade daily.(3) Defects in this process, due to genetic mutations, cause retinitis pigmentosa (RP), an untreatable, blinding disease. The mechanism by which photoreceptor cilia generate outer segments is therefore fundamental for vision yet poorly understood. Here, we show the membrane deformation required for outer segment disc genesis is driven by dynamic changes in the actin cytoskeleton in a process akin to ectocytosis. Further, we showRPGR, a leading causal RP gene, regulates activity of actin binding proteins crucial to this process. Disc genesis is compromised inRpgrmouse models, slowing the actin dynamics required for timely disc formation, leading to aborted membrane shedding as ectosome-like vesicles, photoreceptor death and visual loss. Manipulation of actin dynamics partially rescues the phenotype, suggesting this pathway could be targeted therapeutically. These findings help define how actin-mediated dynamics control outer segment turnover.
CosTaL: An Accurate and Scalable Graph-Based Clustering Algorithm for High-Dimensional Single-Cell Data Analysis
Authors: Li Yijia , Nguyen Jonathan , Anastasiu David , Arriaga Edgar A.
Published: November 2022

With the aim of analyzing large-sized multidimensional single-cell datasets, we are describing our method for Cosine-based Tanimoto similarity-refined graph for community detection using Leiden’s algorithm (CosTaL). As a graph-based clustering method, CosTaL transforms the cells with high-dimensional features into a weighted k-nearest-neighbor (kNN) graph. The cells are represented by the vertices of the graph, while an edge between two vertices in the graph represents the close relatedness between the two similar cells. Specifically, CosTaL builds an exact kNN graph using cosine similarity and uses the Tanimoto coefficient as the refining strategy to re-weight the edges in order to improve the effectiveness of clustering. We demonstrate that CosTaL generally achieves equivalent or higher effectiveness scores on seven benchmark cytometry datasets and six single-cell RNA-sequencing datasets using six different evaluation metrics, compared with other state-of-the-art graph-based clustering methods, including PhenoGraph, Scanpy, and PARC. CosTaL is also the most efficient algorithm on large datasets, suggesting that CosTaL generally has better scalability than the other methods, which is beneficial for large-scale analysis.
Topological changes of fast large-scale brain dynamics in Mild Cognitive Impairment predict the decay of the hippocampal memory
Authors: Romano Antonella , Lopez Emahnuel Troisi , Cipriano Lorenzo , Liparoti Marianna , Minino Roberta , Polverino Arianna , Cavaliere Carlo , Aiello Marco , Granata Carmine , Sorrentino Giuseppe , Sorrentino Pierpaolo
Published: November 2022

Functional connectivity has been widely used as a framework to investigate widespread brain interactions underlying cognitive deficits in Mild Cognitive Impairment (MCI). However, one of the main constraints of functional connectivity is that it is averaged over a time interval and therefore may not take into account the aperiodic and scale-free burst of activity (i.e., the neuronal avalanches) characterising the large-scale dynamic activity of the brain. Here, we used the recently proposed Avalanche Transition Matrix framework to source-reconstructed magnetoencephalography signals in a cohort of 32 MCI patients and 32 healthy controls (HC) to deepen the spatio-temporal features of neuronal avalanches and explore their topological properties. Our results showed that MCI patients exhibited a more centralised network (as assessed by higher values of degree divergence and leaf fraction) compared to HC. Furthermore, we found that the degree divergence (in the theta band) was predictive of the episodic memory impairment, assessed by FCSRT immediate total recall. These findings highlight the role of dynamical features in detecting functional and structural changes in clinical conditions. Hopefully, the proposed framework may be helpful in monitoring the development of the disease by adding subtle information that contributes to a more thorough phenotypical assessment of patients.
Systematic mining and functional analysis of factors regulating wheat spike development for breeding selection
Authors: Lin Xuelei , Xu Yongxin , Wang Dongzhi , Yang Yiman , Zhang Xiaoyu , Bie Xiaomin , Chen Zhongxu , Ding Yiliang , Mao Long , Zhang Xueyong , Lu Fei , Zhang Xiansheng , Uauy Cristobal , Fu Xiangdong , Xiao Jun
Published: November 2022

The spike architecture of wheat plays a crucial role in determining grain number, making it a key trait to optimize in wheat breeding programs. In this study, through a multi-omic approach, we analyzed the transcriptome and epigenome profiles of the shoot apex at eight developmental stages, revealing coordinated changes in chromatin accessibility and H3K27me3 abundance during the flowering transition. We constructed a core transcriptional regulatory network (TRN) that drives wheat spike formation, and experimentally validated a multi-layer regulatory module involving TaSPL15, TaAGLG1, and TaFUL2. By integrating the TRN with genome-wide association analysis (GWAS), we identified 227 transcription factors (TFs), including 42 with known functions and 185 with unknown functions. Further investigation of 61 novel TFs using multiple homozygous mutant lines uncovered 36 TFs with altered spike architecture or flowering time, such as TaMYC2-A1, TaMYB30-A1, and TaWRKY37-A1. Of particular interest, TaMYB30-A1, downstream and repressed by WFZP, was found to regulate fertile spikelet number. Notably, during the domestication and breeding process in China, the excellent haplotype ofTaMYB30-A1containing a C allele at the WFZP binding site was enriched, leading to improved agronomic traits. Our study presents novel and high-confidence regulators and offers an effective strategy for understanding the genetic basis of wheat spike development, with practical impact for wheat breeding applications.
’Simple Tidy GeneCoEx’: a gene co-expression analysis workflow powered by tidyverse and graph-based clustering in R
Authors: Li Chenxin , Buell C. Robin
Published: November 2022

Gene co-expression analysis is an effective method to detect groups (or modules) of co-expressed genes that display similar expression patterns, which may function in the same biological processes. Here, we present ‘Simple Tidy GeneCoEx’, a gene co-expression analysis workflow written in the R programming language. The workflow is highly customizable across multiple stages of the pipeline including gene selection, edge selection, clustering resolution, and data visualization. Powered by the tidyverse package ecosystem and network analysis functions provided by the igraph package, the workflow detects gene co-expression modules whose members are highly interconnected. Step-by-step instructions with two use case examples as well as source code are available athttps://github.com/cxli233/SimpleTidy_GeneCoEx.

Core Ideas

An R-based workflow that performs gene co-expression analysis was developed.

The workflow is based on tidyverse packages and graph theory.

The workflow is highly customizable, detects tight gene co-expression modules, and generates publication quality figures.

Two plant gene expression datasets were used to benchmark the workflow.
Preparation and crystallographic characterization of 1H-tetrazole/NaClO4 energetic cocrystal
Authors: Inoue Kazuki , Matsumoto Shinya , Kumasaki Mieko
Published: November 2022

Cocrystallization is a promising method for generating new energetic materials with improved performances. Herein, a novel energetic cocrystal composed of 1H-tetrazole/sodium perchlorate was prepared using the solvent evaporation method. This cocrystal is characterized as containing organic azole derivatives and an ionic perchlorate salt, which is used as an oxidizer in pyrotechnics. The crystal structure was determined via single-crystal X-ray diffraction. The as-prepared crystal exhibited a lamellar structure consisting of 1H-tetrazole and sodium perchlorate layers. A molecular structure comparison between the cocrystal and pristine ingredients revealed variations in the bond lengths and angles owing to the cocrystallization. The hydrogen bond formed by adjacent tetrazole rings was strengthened. The 1H-tetrazole/sodium perchlorate cocrystal was structurally compared with crystals previously reported to the Cambridge Structural Database including sodium perchlorate in lamellar structures. The lamellar structure of the cocrystal exhibited weak layer-to-layer interactions compared with those of the other crystals. Fourier transform infrared and Raman spectroscopy analyses were conducted, and the relationship between the spectroscopy results and the crystal/molecular structure are discussed. The results of the spectroscopic analyses exhibited peak shifts that indicate structural changes in bond lengths and angles owing to the cocrystallization.
Introduction of a weighting scheme for the X-ray restrained wavefunction approach: advantages and drawbacks
Authors: Macetti Giovanni , Genoni Alessandro
Published: November 2022

In a quite recent study [Genoniet al.(2017).IUCrJ,4, 136–146], it was observed that the X-ray restrained wavefunction (XRW) approach allows a more efficient and larger capture of electron correlation effects on the electron density if high-angle reflections are not considered in the calculations. This is due to the occurrence of two concomitant effects when one uses theoretical X-ray diffraction data corresponding to a single-molecule electron density in a large unit cell: (i) the high-angle reflections are generally much more numerous than the low- and medium-angle ones, and (ii) they are already very well described at unrestrained level. Nevertheless, since high-angle data also contain important information that should not be disregarded, it is not advisable to neglect them completely. For this reason, based on the results of the previous investigation, this work introduces a weighting scheme for XRW calculations to up-weight the contribution of low- and medium-angle reflections, and, at the same time, to reasonably down-weight the importance of the high-angle data. The proposed strategy was tested through XRW computations with both theoretical and experimental structure-factor amplitudes. The tests have shown that the new weighting scheme works optimally if it is applied with theoretically generated X-ray diffraction data, while it is not advantageous when traditional experimental X-ray diffraction data (even of very high resolution) are employed. This also led to the conclusion that the use of a specific external parameter λJfor each resolution range might not be a suitable strategy to adopt in XRW calculations exploiting experimental X-ray data as restraints.
Social media analytics in tourism: a review and agenda for future research
Authors: Mukhopadhyay Shameek , Jain Tinu , Modgil Sachin , Singh Rohit Kr
Published: November 2022

Purpose

The significance of social media in our lives is manifold. The tourism sector closely interacts with existing and potential tourists through social media, and therefore, social media analytics (SMA) play a critical role in the uplift of the sector. Hence, this review focus on the role of SMA in tourism as discussed in different studies over a period of time. The purpose of this paper to present the state of the art on social media analytics in tourism.

Design/methodology/approach

The review focuses on identifying different SMA techniques to explore the trends and approaches adopted in the tourism sector. The review is based on 83 papers and discuss the studies related to different social media platforms, the travelers' reactions to a particular place and how the tourism experience is enriched by the way of SMA.

Findings

Findings indicate different sentiments associated with tourism and provides a review of tourists’ use of social media for choosing a travel destination. The various analytical approaches, areas such as social network analysis, content analysis, sentiment analysis and trend analysis were found most prevalent. The theoretical and practical implications of SMA are discussed. The paper made an effort to bridge the gap between different studies in the field of tourism and SMA.

Originality/value

SMA facilitate both tourists and tourism companies to understand the trends, sentiments and desires of tourists. The use of SMA offers value to companies for designing quick and adequate services to tourists.
The rise of digital capitalism and the social changes it caused: how to develop the digital economy in socialist China
Authors: Ding Xiaoqin , Chai Qiaoyan
Published: November 2022

Purpose

The study aims to take a step back and take the big picture of how digital capitalism is changing people's ways of living and production. On that basis, China should enhance its digital governance rationally and develop the digital economy efficiently, thereby bringing its socialist economy to new heights.

Design/methodology/approach

The rise of digital capitalism in the 1990s has profoundly changed the ways of consumption, employment, production organization and investment in the realm of capitalism.

Findings

Digital Capitalism has not changed the nature of capitalism, that is, exploitation and capital accumulation, which continue only in a more profound, extensive and covert way.

Originality/value

For the economy of socialist China to grow in the new era, China should tap into digital economy platforms, take a people-centered approach and let the people jointly develop the digital economy, share the fruits of development and participate in the governance of the digital economy. The government should leverage its modern digital governance and a high-quality digital economy to meet people's ever-growing demand for a better life.
Indispensable skills for human employees in the age of robots and AI
Authors: Chuang Szufang
Published: November 2022

Purpose

Based on sociotechnical systems theory, social (human) and technological sub-systems in an organization should be taken in account when making strategic decisions and designed to fit the demands of the environment for organizational effectiveness. Yet there is very limited information in literature on whether employees are well equipped with indispensable (human) skills to prepare them combating challenges caused by advanced technology. The purpose of this study is to empirically investigate employees’ human skills that are critical for success in the Age of Robots and Artificial Intelligence from human resource development’s perspective.

Design/methodology/approach

A questionnaire was developed for the purpose of this exploratory study. A total of 422 US Midwest employees were surveyed on their human skills level that are critical for success in the Industry 4.0 transformation.

Findings

In general, the respondents could perform all the measured human skills (which can be categorized into social skillset and decision-making skillset) more than adequate but may vary by education level and gender. To strengthen one’s human skills, organizations may begin with facilitating employees on relationship building to create a support system and a strong sense of belonging, which will promote their social sensitivity and collaboration skill development, as well as decision-making skillset.

Originality/value

The findings of this study can be used for techno-structural interventions and employee development programs. This study highlights the importance of investigating human skills to cope with the changing nature of work and make upskilling more feasible and flexible for workers to be robot-proof.
Two-dimensional deformations in an initially stressed nonlocal micropolar thermoelastic porous medium subjected to a moving thermal load
Authors: Kundu Sandeep , Kalkal Kapil Kumar , Sangwan Monika , Sheoran Devender
Published: November 2022

Purpose

The purpose of the present paper is to investigate the thermo-mechanical interactions in an initially stressed nonlocal micropolar thermoelastic half-space having void pores under Lord–Shulman model. A moving thermal shock is applied to the formulation.

Design/methodology/approach

The normal mode technique is adopted to obtain the exact expressions of the physical quantities.

Findings

Numerical computations for stresses, displacement components, temperature field and change in the volume fraction field are performed for suitable material and are depicted graphically. Some comparisons have been shown in figures to estimate the effects of micropolarity, initial stress, voids, nonlocal parameter and time on the resulting quantities.

Originality/value

The exact expressions for the displacement components, stresses, temperature and change in the volume fraction field are obtained in the physical domain. Although numerous investigations do exist to observe the disturbances in a homogeneous, isotropic, initially stressed, micropolar thermoelastic half-space, the work in its current form has not been established by any scholar till now. The originality of the present work lies in the formulation of a fresh research problem to investigate the dependence of different physical fields on nonlocality parameters, micropolarity, initial stress, porosity and time due to the application of a moving thermal shock.