bluuebunny/crossref_metadata_2025 huggingface dataset:
Ion exchange biomaterials to capture daptomycin and prevent resistance evolution in off-target bacterial populations
Authors: Yeh Shang-Lin , Narasimhalu Naveen , vom Steeg Landon G. , Muthami Joy , LeConey Sean , He Zeming , Pitcher Mica , Cassady Harrison , Morley Valerie J. , Cho Sung Hyun , Bator Carol , Koshani Roya , Woods Robert J. , Hickner Michael , Read Andrew F. , Sheikhi Amir
Published: June 2022

Daptomycin (DAP), a cyclic anionic lipopeptide antibiotic, is among the last resorts to treat multidrug resistant (vancomycin resistant Enterococcus faecium or methicillin resistant Staphylococcus aureus) Gram-positive bacterial infections. DAP is administered intravenously and biliary excretion results in the introduction of DAP (∼5-10 % of the intravenous DAP dose) arriving in the gastrointestinal (GI) tract where it drives resistance evolution in off-target populations of Enterococcus faecium bacteria. Previously, we have shown that the oral administration of cholestyramine, an ion exchange biomaterial (IXB) sorbent, prevents DAP treatment from enriching DAP-resistance in populations of E. faecium shed from mice. Here, we engineer the biomaterial-DAP interfacial interactions to uncover the antibiotic removal mechanisms. The IXB-mediated DAP capture from aqueous media was measured in both controlled pH/electrolyte solutions and in simulated intestinal fluid (SIF) to uncover the molecular and colloidal mechanisms of DAP removal from the GI tract. Our findings show that the IXB electrostatically adsorbs the anionic antibiotic via a time-dependent diffusion-controlled process. Unsteady-state diffusion-adsorption mass balance describes the dynamics of adsorption well, and the maximum removal capacity is beyond the electric charge stoichiometric ratio because of DAP self-assembly. This study may open new opportunities for optimizing cholestyramine adjuvant therapy to prevent DAP resistance, as well as designing novel biomaterials to remove off-target antibiotics from the GI tract.

TOC
A lipopolysaccharide-dependent phage infects a pseudomonad phytopathogen and can evolve to evade phage resistance
Authors: Warring Suzanne L. , Malone Lucia M. , Jayaraman Jay , Easingwood Richard A. , Rigano Luciano A. , Frampton Rebekah A. , Visnovsky Sandra B. , Addison Shea M. , Hernandez Loreto , Pitman Andrew R. , Acedo Elena Lopez , Kleffmann Torsten , Templeton Matthew D. , Bostina Mihnea , Fineran Peter C.
Published: June 2022

Bacterial pathogens are major causes of crop diseases, leading to significant production losses. For instance, kiwifruit canker, caused by the phytopathogen Pseudomonas syringae pv. actinidiae (Psa), has posed a global challenge to kiwifruit production. Treatment with copper and antibiotics, whilst initially effective, is leading to the rise of bacterial resistance, requiring new biocontrol approaches. Previously, we isolated a group of closely related Psa phages with biocontrol potential, which represent environmentally sustainable antimicrobials. However, their deployment as antimicrobials requires further insight into their properties and infection strategy. Here, we provide an in-depth examination of the genome of ΦPsa374-like phages and show that they use lipopolysaccharides (LPS) as their main receptor. Through proteomics and cryo-electron microscopy of ΦPsa374, we revealed the structural proteome and that this phage possess a T=9 capsid triangulation, unusual for myoviruses. Furthermore, we show that ΦPsa374 phage resistance arises in planta through mutations in a glycosyltransferase involved in LPS synthesis. Lastly, through in vitro evolution experiments we showed that phage-resistance is overcome by mutations in a tail fiber and structural protein of unknown function in ΦPsa374. This study provides new insight into the properties of ΦPsa374-like phages that informs their use as antimicrobials against Psa.

Originality-Significance Statement

The rise of phytopathogen resistance to agrichemicals poses a significant threat to crop production, and requires urgent attention. The work presented here examines a phage genus, members of which utilize LPS as a receptor, and show potential as biocontrol agents of Psa. Studies in planta showed the development of Psa resistance to the phage, whilst maintaining bacterial virulence. This finding underscores the importance of examining phages in their ecological context for the informed design of phage cocktails that are effective in phytopathogen control.
A universal stress protein acts as a metabolic rheostat controlling carbon flux in mycobacteria
Authors: Lougheed Kathryn E. , Thomson Michael , Koziej Lukasz S. , Larrouy-Maumus Gerald , Williams Huw D
Published: June 2022

Universal stress proteins (USPs) are ubiquitous amongst prokaryotes and have empirically determined roles in adaptation to stress, while their specific biochemical function in cellular processes is opaque. The most frequently encountered USP is a small ~15kDa protein comprised of a single domain (PF00582). In Mycobacterium tuberculosis Rv1636 is the sole single domain protein amongst its 10 USPs. We were unable to delete rv1636 from M. tuberculosis, supporting previous data that it is essential for growth. We deleted its orthologue, MS3811, from M. smegmatis, and in exponential phase competition experiments we observed that the advantage switched between wildtype and the mutant depending on the growth environment. In rich medium the wildtype had the competitive advantage, but in a defined medium with a single carbon source the competitive advantage switched, with the mutant rapidly taking over the culture. We hypothesised the USP is regulating metabolic flux, with its deletion leading to increased flux and more rapid turn-over of central-carbon metabolites. We tested this by performing 13C-stable isotope tracing, using [U-13C6] glucose as sole carbon source for growth of the parental and deletion strains. The findings were unequivocal; deletion of the USP led to an increase in label incorporation in central carbon metabolites and a profound change in the isotopologue distribution. Furthermore, in vivo protein-crosslinking provided evidence that Rv1636 interacts directly with key central metabolic enzymes, including the glycolytic enzymes pyruvate kinase, pyruvate dehydrogenase, pyruvate synthase. We propose the mycobacterial single domain USP acts as a metabolic rheostat to regulate central carbon metabolism.

Importance

There are more than 62,000 universal stress proteins (USPs) found mostly in prokaryotes, but very few examples where the role of a USP is unequivocally linked to a specific biological or biochemical function. For the first time we were able to assign a role in metabolic regulation to a bacterial single domain universal stress protein. We demonstrate a mycobacterial USP regulates flux through central catabolic pathways, and our evidence, based on 13C-stable isotope tracing, indicates that the USP acts as a brake on carbon flux, and we assign to it a role as a metabolic rheostat.
A two-step in vivo CRISPR screen unveils pervasive RNA binding protein dependencies for leukemic stem cells and identifies ELAVL1 as a therapeutic target
Authors: Vujovic Ana , de Rooij Laura P.M.H. , Chahi Ava Keyvani , Chen He Tian , Yee Brian , Loganathan Sampath K , Liu Lina , Chan Derek C.H. , Tajik Amanda , Tsao Emily , Moreira Steven , Joshi Pratik , Xu Joshua , Wong Nicholas , Zandi Sasan , Aigner Stefan , Dick John E. , Minden Mark D. , Schramek Daniel , Yeo Gene W. , Hope Kristin J.
Published: June 2022

Acute myeloid leukemia (AML) progression and relapse is fueled by self-renewing leukemic stem cells (LSCs) whose molecular determinants have been difficult to discern from normal hematopoietic stem cells (HSCs) or to uncover in screening approaches focused on general AML cell properties. We have identified a unique set of RNA binding proteins (RBPs) that are enriched in human AML LSCs but repressed in HSCs. Using an in vivo two step CRISPR-Cas9-mediated screening approach to specifically score for cancer stem cell functionality, we found 32 RBPs essential for LSC propagation and self-renewal in MLL-AF9 translocated AML. Using knockdown or small molecule approaches we show that targeting key hit RBP ELAVL1 impaired LSC-driven in vivo leukemic reconstitution and selectively depleted primitive AML cells vs. normal hematopoietic stem and progenitors. Importantly, knockdown of Elavl1 spared HSCs while significantly reducing LSC numbers across genetically diverse leukemias. Integrative RNA-seq and eCLIP-seq profiling revealed hematopoietic differentiation, RNA splicing and mitochondrial metabolism as key features defining the leukemic ELAVL1-mRNA interactome with the mitochondrial import protein TOMM34 being a direct ELAVL1-stabilized target whose inhibition impairs AML propagation. Altogether, through the use of a stem cell-adapted in vivo CRISPR dropout screening strategy, this work demonstrates that a wide variety of post-transcriptionally acting RBPs are important regulators of LSC-survival and self-renewal and, as exemplified by ELAVL1, highlights their potential as therapeutic targets in AML.
Molecular phenotyping of colorectal neoplasia shows dynamic and adaptive cancer stem cell population admixture
Authors: Vazquez Ester Gil , Nasreddin Nadia , Valbuena Gabriel N , Mulholland Eoghan J , Belnoue-Davis Hayley L , Eggington Holly , Schenck Ryan O , Wouters Valérie M , Wirapati Pratyaksha , Gilroy Kathryn , Lannagan Tamsin R M , Flanagan Dustin J , Najumudeen Arafath K , Omwenga Sulochana , McCorry Amy M B , Easton Alistair , Koelzer Viktor H , East James E , Morton Dion , Trusolino Livio , Maughan Timothy , Campbell Andrew D , Loughrey Maurice B , Dunne Philip D , Tsantoulis Petros , Huels David J , Tejpar Sabine , Sansom Owen , Leedham Simon J
Published: June 2022

Intestinal homeostasis is underpinned by LGR5+ve crypt-base columnar stem cells (CBCs), but following injury, dedifferentiation results in the emergence of LGR5-ve regenerative stem cell populations (RSCs), characterised by fetal transcriptional profiles. Neoplasia hijacks regenerative signalling, so we assessed the distribution of CBCs and RSCs in mouse and human intestinal tumors. Using combined molecular-morphological analysis we demonstrate variable expression of stem cell markers across a range of lesions. The degree of CBC-RSC admixture was associated with both epithelial mutation and microenvironmental signalling disruption, and could be mapped across disease molecular subtypes. The CBC-RSC equilibrium was adaptive, with a dynamic response to acute selective pressure, and adaptability was associated with chemoresistance. We propose a fitness landscape model where individual tumors have equilibrated stem cell population distributions along a CBC-RSC phenotypic axis. Cellular plasticity is represented by position shift along this axis, and is influenced by cell-intrinsic, extrinsic and therapeutic selective pressures.
Distinguishing biophysical stochasticity from technical noise in single-cell RNA sequencing usingMonod
Authors: Gorin Gennady , Pachter Lior
Published: June 2022

We present the Python packageMonodfor the analysis of single-cell RNA sequencing count data through biophysical modeling.Monodnaturally “integrates” unspliced and spliced count matrices, and provides a route to identifying and studying differential expression patterns that do not cause changes in average gene expression. TheMonodframework is open-source and modular, and may be extended to more sophisticated models of variation and further experimental observables.

TheMonodpackage can be installed from the command line using pip install monod. The source code is available and maintained athttps://github.com/pachterlab/monod. A separate repository, which contains sample data and Python notebooks for analysis withMonod, is accessible athttps://github.com/pachterlab/monod_examples/. Structured documentation and tutorials are hosted athttps://monod-examples.readthedocs.io/.
Neural plate progenitors give rise to both anterior and posterior pituitary cells
Authors: Chen Qiyu , Leshkowitz Dena , Li Hanjie , van Impel Andreas , Schulte-Merker Stefan , Amit Ido , Rizzoti Karine , Levkowitz Gil
Published: June 2022

The pituitary is the master neuroendocrine gland, which regulates body homeostasis. It consists of the anterior pituitary/adenohypophysis (AH), which harbors hormones producing cells and the posterior pituitary/neurohypophysis (NH), which relays the direct passage of hormones from the brain to the periphery. It is widely accepted that the AH originates from the oral ectoderm (Rathke’s pouch) whereas the neural ectoderm contributes to the NH. Using single cell transcriptomics of the zebrafish pituitary we characterizedcyp26b1-positive pituicyte of the NH andprop1-positive adenohypophyseal progenitors. We found that these cell types expressed common markers implying lineage relatedness. Genetic tracing revealed that in contrast to the prevailing dogma, neural plate precursors of both zebrafish (her4.3+) and mouse (Sox1+) contribute to both the neurohypophyseal and adenohypophyseal cells. We further show that pituicytes andprop1+progenitors reside in close anatomical proximity and pituicyte-derived RA-degrading enzyme Cyp26b1 fine-tunes differentiation ofprop1+progenitors into hormone-producing cells. These results challenge the notion that AH cells are exclusively derived from non-neural ectoderm and demonstrate that a cross-talk between neuro- and adeno-hypophyseal cells fine-tunes the development of pituitary neuroendocrine cells.
Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis
Authors: Jing Haoyuan , Ogunmowo Tyler , Raychaudhuri Sumana , Kusick Grant F. , Imoto Yuuta , Li Shuo , Itoh Kie , Chapman Edwin R. , Ha Taekjip , Watanabe Shigeki , Liu Jian
Published: June 2022

Compensatory endocytosis keeps the surface area of secretory cells constant following exocytosis. At chemical synapses, clathrin-independent ultrafast endocytosis maintains such homeostasis. This endocytic pathway is temporally and spatially coupled to exocytosis, initiating within 50 ms at the region immediately next to where vesicles fuse: the active zone. How synaptic vesicle exocytosis induces ultrafast endocytosis is unknown. Here, we demonstrate that actin filaments are enriched in the region surrounding active zone at mouse hippocampal synapses and that the membrane area conservation due to this actin corral is necessary for exo-endocytic coupling. Simulations suggest that flattening of fused vesicles exerts lateral membrane pressure in the plasma membrane against the actin corral, resulting in rapid formation of endocytic pits at the border between the active zone and the surrounding actin-enriched region. Consistent with our simulations, ultrafast endocytosis does not initiate when actin organization is disrupted, either pharmacologically or by ablation of the actin-binding protein Epsin1. These data suggest that endocytosis is mechanically coupled to exocytosis at synapses.
Rapid Development of a Mucosal Nanoparticle Flu Vaccine by Genetic Engineering of Bacteriophage T4 using CRISPR-Cas
Authors: Li Mengling , Chen Cen , Wang Xialin , Guo Pengju , Feng Helong , Zhang Xueqi , Zhang Wanpo , Gu Changqin , Zhu Jingen , Wen Guoyuan , Rao Venigalla B. , Tao Pan
Published: June 2022

Mucosal vaccines that can induce local mucosal immune responses and combat the pathogens at entry sites are considered to be the most effective way to prevent infection. A universal platform that can be customized for development of mucosal vaccines against any given pathogen is therefore highly desired. Here, we demonstrate an efficient approach to develop nasal mucosal vaccines through genetic engineering of T4 phage to generate antigen-decorated nanoparticles. The antigen coding sequence was inserted into T4 genome in-frame at the C terminus of Soc (small outer capsid protein) using the CRISPR-Cas phage editing technology. During the propagation of recombinant T4 phages in E. coli, the Soc-antigen fusion proteins self-assemble on T4 capsids to form antigen-decorated nanoparticles that have intrinsic adjuvant activity and mucosal adhesive property. As a proof of concept, we showed that intranasal immunization with Flu viral M2e-decorated T4 nanoparticles efficiently induced local mucosal as well as systemic immune responses and provided complete protections against divergent influenza viruses in a mouse model. Potentially, our platform can be customized for any respiratory pathogen to rapidly generate mucosal vaccines against future emerging epidemics and pandemics.
Structural basis for the unique multifaceted interaction of DPPA3 with the UHRF1 PHD finger
Authors: Hata Keiichi , Kobayashi Naohiro , Sugimura Keita , Qin Weihua , Haxholli Deis , Chiba Yoshie , Yoshimi Sae , Hayashi Gosuke , Onoda Hiroki , Ikegami Takahisa , Mulholland Christopher B. , Nishiyama Atsuya , Nakanishi Makoto , Leonhardt Heinrich , Konuma Tsuyoshi , Arita Kyohei
Published: June 2022

Ubiquitin-like with PHD and RING finger domain-containing protein 1 (UHRF1)-dependent DNA methylation is essential for maintaining cell fate during cell proliferation. Developmental pluripotency-associated 3 (DPPA3) is an intrinsically disordered protein that specifically interacts with UHRF1 and promotes passive DNA demethylation by inhibiting UHRF1 chromatin localization. However, the molecular basis of how DPPA3 interacts with and inhibits UHRF1 remains unclear. We aimed to determine the structure of the mouse UHRF1 plant homeodomain (PHD) complexed with DPPA3 using nuclear magnetic resonance. Induced α- helices in DPPA3 upon binding of UHRF1 PHD contribute to stable complex formation with multifaceted interactions, unlike canonical ligand proteins of the PHD domain. Mutations in the binding interface and unfolding of the DPPA3 helical structure inhibited binding to UHRF1 and its chromatin localization. Our results provide structural insights into the mechanism and specificity underlying the inhibition of UHRF1 by DPPA3.
Dynamic regulatory module networks for inference of cell type–specific transcriptional networks
Authors: Siahpirani Alireza Fotuhi , Knaack Sara , Chasman Deborah , Seirup Morten , Sridharan Rupa , Stewart Ron , Thomson James , Roy Sushmita
Published: June 2022

Changes in transcriptional regulatory networks can significantly alter cell fate. To gain insight into transcriptional dynamics, several studies have profiled bulk multi-omic data sets with parallel transcriptomic and epigenomic measurements at different stages of a developmental process. However, integrating these data to infer cell type–specific regulatory networks is a major challenge. We present dynamic regulatory module networks (DRMNs), a novel approach to infer cell type–specific cis-regulatory networks and their dynamics. DRMN integrates expression, chromatin state, and accessibility to predict cis-regulators of context-specific expression, where context can be cell type, developmental stage, or time point, and uses multitask learning to capture network dynamics across linearly and hierarchically related contexts. We applied DRMNs to study regulatory network dynamics in three developmental processes, each showing different temporal relationships and measuring a different combination of regulatory genomic data sets: cellular reprogramming, liver dedifferentiation, and forward differentiation. DRMN identified known and novel regulators driving cell type–specific expression patterns, showing its broad applicability to examine dynamics of gene regulatory networks from linearly and hierarchically related multi-omic data sets.
Opaque selling vs traditional selling: optimal decisions for service providers in a competitive market
Authors: Chen Ting , Yang Feng , Shan Feifei , Xu Fengmei
Published: June 2022

Purpose

Opaque selling has become popular among service providers in recent years. Although many researchers have investigated the optimality of opaque selling for service providers focusing on heterogeneous consumers, one question remaining unexplored is how the service providers’ optimal decisions are impacted by competitive intensity in a heterogeneous market. This paper aims to determine the conditions under which opaque selling is optimal for competing service providers.

Design/methodology/approach

The paper takes a Hotelling model to characterize the competition between two service providers. The authors also consider the interaction between the service providers and intermediary. Service providers act as game leaders and determine whether they should cooperate with the intermediary to introduce the opaque service.

Findings

The authors find that two competing service providers do not always benefit from opaque selling in a heterogeneous market consisting of leisure and business consumers, and the competitive intensity plays a significant role in the service providers’ decision optimization. Opaque selling allows service providers to acquire more profit in a highly competitive market or when the market contains a large proportion of leisure consumers. Otherwise, it is optimal for service providers without introducing the opaque selling.

Practical implications

The paper examines the optimality of opaque selling for competing service providers, and provides the suggestions to optimize the service providers’ decisions.

Originality/value

The paper investigates how the service providers’ optimal decisions are impacted by competitive intensity, considering the interaction between the service providers and intermediary.
Real-time estimation of the heat transfer coefficient of pitot tubes undergoing freezing
Authors: Diniz Steve B. , Pacheco César C.
Published: June 2022

Purpose

The purpose of this paper is to identify freezing in pitot tubes at real-time, by means of the estimated heat transfer coefficient (HTC) at the tip of the probe. The prompt identification of such freezing is paramount to activate and control mechanisms for ice removal, which in turn are essential for the safety of the aircraft and its passengers.

Design/methodology/approach

The proposed problem is solved by means of an inverse analysis, performed within the Bayesian approach of inverse problems, with temperature measurements assumed available along the pitot probe over time. A heat conduction model is used for describing the average temperature of the pitot tube, which is then rewritten in the form of a state estimation problem. The model is linear and time invariant, so that the inverse problem can be solved using the steady-state Kalman filter (SSKF), a computationally efficient algorithm.

Findings

The results show that the SSKF is fully capable of recovering the HTC information from the temperature measurements. Any variation of the HTC – either smooth or discontinuous – is promptly detected with high accuracy. Computational effort is significantly lower than the physical time, so that the proposed methodology is fully capable of estimating the HTC at real-time.

Originality/value

The methodology herein solves the proposed problem not only by estimating the HTC accurately but also doing so with a very small computational effort, so that real-time estimation and freezing control become possible. To the best of the authors’ knowledge, no likewise publications have been found so far.
E-records management practices in public universities: a developing country perspective
Authors: Chaputula Aubrey Harvey
Published: June 2022

Purpose

This study aims to investigate the management of electronic records (e-records) in public universities in Malawi.

Design/methodology/approach

This study adopted a case study research design that made use of predominantly qualitative research methods. Data was collected at three study sites, namely, Mzuzu University, Malawi University of Science and Technology and the Malawi University of Business and Applied Sciences. A purposive sample of three officers per institution (and nine in total) comprising executive officers, deputy university registrar, records clerk, information and communication technology (ICT) directors and ICT manager was attained. The researcher personally conducted the interviews with the research subjects with the aid of interview guides. Observations were also done, whose findings were recorded in the observation protocols. The data collected was transcribed in MS Word, coded and analysed thematically.

Findings

This study concluded that e-records are at high risk in public universities in Malawi. Irrespective of this situation, this study found that there were some areas for e-records to potentially thrive in public universities in Malawi.

Research limitations/implications

This study covers three of the six public universities in Malawi. Although public universities in Malawi have similar governance structures, there are some noticeable differences that distinguish one institution from the other. It is, therefore, possible that findings made in this study may not completely represent the prevailing situation in all public universities.

Originality/value

Studies of this nature have not been done before in public universities in Malawi. It is, therefore, hoped that besides filling the existing knowledge gap, its findings will contribute to policy and practical interventions that will lead to efficiency of the universities involved.
Miniaturized triple notch metamaterial sensor for solid dielectric characterization with improved sensitivity
Authors: Singh Kunal Kumar , Kumar Mahto Santosh , Sinha Rashmi , Priye Vishnu
Published: June 2022

Purpose

The purpose of this paper is to retrieve the dielectric constant of the material under test (MUT) by using an empirical relationship, which relates the dielectric properties with all three resonant frequencies of the proposed sensor. Each notch of the sensor is analyzed for sensitivity by using 15 different MUTs with relative permittivity ranging from 1.006 to 16.5 with a fixed dimension of 12 mm × 12 mm × 1.2 mm.

Design/methodology/approach

In this paper, we present a triple-notch metamaterial-based sensor for the solid dielectric characterization based on a microstrip transmission line and a direct coupled-double split ring resonator (DC-DSRR). The proposed sensor is designed, and its response is measured using a vector network analyzer to verify the concept. The shift in the resonant frequencies of the proposed sensor owing to contact with MUT is depicted as a function of permittivity using the curve fitting tool.

Findings

The proposed sensors have three notches, with the third notch being more sensitive than the first and second notch because of the high resonance frequency. For the first, second and third resonances, the proposed sensor has sensitivity ranges from 4.9% to 14.68%, 8.97% to 23.95% and 15.48% to 29.36%, respectively. The findings of the simulations, measurements and formulations are all in good accord.

Originality/value

In comparison to previous solid dielectric metamaterial sensors, the proposed triple-notch sensor based on a microstrip transmission line and DC-DSRR has the following advantages: it has a simple unit-cell structure and meets the needs of miniaturization, compact size, low cost and improved sensitivity. It determines the relative permittivity using all three notches so that the accuracy of the measurement is enhanced as compared with single- and double-notch sensors.
Resistance exercise attenuates IKKε phosphorylation and hepatic fat accumulation of obese mice
Authors: Antunes Gabriel Calheiros , de Lima Robson Damasceno , Vieira Renan Fudoli Lins , Macêdo Ana Paula Azevêdo , Muñoz Vitor Rosetto , Zambalde Erika Pereira , Romeiro Caio Felipe , Simabuco Fernando Moreira , Prada Patricia Oliveira , da Silva Adelino Sanchez Ramos , Ropelle Eduardo Rochete , Cintra Dennys Esper , Pauli José Rodrigo
Published: June 2022

Obesity is associated with low‐grade inflammation and disturbances in hepatic metabolism. This study aimed to investigate the effects of resistance exercise on inflammatory signalling related to IκB kinase (IKK) ɛ protein (IKKɛ) and on hepatic fat accumulation in obese mice. Male Swiss mice were distributed into three groups: control (CTL) fed with standard chow; obese (OB) mice induced by a high‐fat diet (HFD); obese exercised (OB + RE) mice fed with HFD and submitted to a resistance exercise training. The resistance exercise training protocol consisted of 20 sets/3 ladder climbs for 8 weeks, three times/week on alternate days. The training overload was equivalent to 70% of the maximum load supported by the rodent. Assays were performed to evaluate weight gain, hepatic fat content, fasting glucose, insulin sensitivity, IKKɛ phosphorylation and proteins related to insulin signalling and lipogenesis in the liver. Mice that received the high‐fat diet showed greater adiposity, impaired insulin sensitivity, increased fasting glucose and increased hepatic fat accumulation. These results were accompanied by an increase in IKKɛ phosphorylation and lipogenesis‐related proteins such as cluster of differentiation 36 (CD36) and fatty acid synthase (FAS) in the liver of obese mice. In contrast, exercised mice showed lower body weight and adiposity evolution throughout the experiment. In addition, resistance exercise suppressed the effects of the high‐fat diet by reducing IKKɛ phosphorylation and hepatic fat content. In conclusion, resistance exercise training improves hepatic fat metabolism and glycaemic homeostasis, which are, at least in part, linked to the anti‐inflammatory effect of reduced IKKɛ phosphorylation in the liver of obese mice.
Writing motivation in Chinese children with developmental dyslexia
Authors: Yeung Pui‐sze
Published: June 2022

Background

Recent models of writing acknowledge the influential role of motivation in writing development. There has been a paucity of research on writing motivation in children. This study investigated writing motivation among Chinese children with developmental dyslexia.

Methods

Forty‐one Chinese children with developmental dyslexia (RD) in Grades 3 to 5 and their typically developing counterparts matched on age (CA controls) (n = 41) were administered tasks assessing their writing motivation (perceived value of writing and writing apprehension), cognitive‐linguistic skills (word dictation, syntactic skills and working memory), and writing abilities (quality and productivity).

Results

The results showed that the RD group performed significantly less well than the CA group in all cognitive‐linguistic skills and writing abilities measures. No significant between‐group differences were found in writing motivation measures. Multiple regression analysis results showed that perceived value of writing significantly predicted writing productivity in the RD group and writing quality in the CA group. Word dictation was the only significant predictor of writing quality in both the RD and the CA group.

Conclusions

These findings suggest that writing motivation influences writing performance in Chinese children with developmental dyslexia in elementary grades. Specifically, perceived value of writing predicts writing quality in typically developing Chinese children but predicts only writing productivity, not writing quality, in Chinese children with developmental dyslexia. The impact of writing motivation on writing performance becomes stronger with advances in component skills acquisition.
Understanding autonomy and relationality in men's lives
Authors: Elliott Karla , Roberts Steven , Ralph Brittany , Robards Brady , Savic Michael
Published: June 2022

Masculinities scholarship tends toward describing autonomy as bound up with hegemonic masculine ideals such as independence, atomization, and self‐sufficiency, without fully delving into the concept of autonomy. This article offers a more in‐depth conceptual treatment of autonomy, compared to its more simplified rendering in the literature on the dominant relational conceptualizations of masculinities. In doing so, we follow recent calls to avoid categorizing men according to typologies of masculinity, drawing instead on feminist theorizations ofmasculine autonomyandrelationalityto explore how both manifest in men's lives. We draw on a study of men's drinking practices, with our data coming from focus groups with 101 men in metropolitan and regional/rural Victoria, Australia; but the issues we attend to have relevance, and can be an impetus, for further scholarly thinking about autonomy in men's lives well beyond drinking practices, and in other similar industrialized nations. We explore how masculine autonomy remains an influential and harmful discourse, often impeding possibilities for men's greater intimacy, connection and care and reproducing gendered hierarchies. However, we simultaneously highlight how men are inescapably relationally situated, exposing masculine autonomy as a discursive ideal of valorized forms of masculinity rather than an achievable state in practice. We argue that acknowledging how men are relationally embedded and interdependent in practice offers potential avenues for further fostering men's care, intimacy and relationality, and might work toward ameliorating gendered inequalities that see care work and the work of sustaining relational networks disproportionately falling to women and marginalized men.
The social origins and schooling of a scientific elite: Fellows of the Royal Society born from 1900
Authors: Bukodi Erzsébet , Goldthorpe John H. , Steinberg Inga
Published: June 2022

We present an analysis of the social composition of the UK scientific elite, as represented by Fellows of the Royal Society, in terms of Fellows' social class origins and type of secondary schooling. From various sources, we have assembled data for 1691 Fellows, representing 80% of our target population of all Fellows born from 1900 onwards whose scientific careers were spent predominantly in the UK. We find that while these elite scientists come largely from more advantaged class backgrounds, it is professional rather than business or managerial families that are the main source of their recruitment—and, increasingly, such families where a parent is in a STEM occupation. Recruitment from working‐class families has declined and for most recent birth cohorts almost ceased. The scientific elite is thus now more homogeneous as regards the social origins of its members than it was in the second half of the twentieth century. At the same time, little change is evident in the secondary schooling of Fellows. In all birth cohorts, between two‐fifths and a half of all—and over two‐thirds of those from more advantaged class backgrounds—were privately educated, although the proportion attending Clarendon schools would seem low compared with that in other elites. A further finding of interest is that some variation in Fellows' class origins and type of schooling exists across different research fields.
Resilience building during the management of the COVID‐19 crisis in Lithuania: Major breakthroughs and incremental change
Authors: Nakrošis Vitalis , Bortkevičiūtė Rasa
Published: June 2022

Modern societies are facing an increasing number of transboundary systemic threats. The sudden spread of the coronavirus disease 2019 (COVID‐19) pandemic has once again highlighted concerns about governments' capacity to deal with disruptions and stressed the need for more resilient governance arrangements. Besides the usual policymaking, the latter might emerge from decisions, made during the crisis management as well. Building on ideas of the new institutionalism, more specifically, the normative logic of appropriateness and the rational logic of consequentiality, we examine how different mechanisms in varying contexts lead to different types of resilience building. Based on the results of pattern matching applied to the Lithuanian case of COVID‐19 crisis management in 2020, we argue that in environments where the logic of consequentiality was dominant, resilience was mostly strengthened because of major breakthroughs, stemming from coercive pressures as well as top‐down policy action from the centre of government. In contrast, more incremental developments contributed to resilience building through normative or mimetic pressures, professionalization, network‐based and bottom‐up practices in environments, where the logic of appropriateness prevailed. We claim that, while the logic of consequentiality helps to strengthen resilience in the context of turbulence, the logic of appropriateness is especially important for ensuring its sustainability.
Design of multi‐pad electrotactile system envisioned as a feedback channel for supernumerary robotic limbs
Authors: Boljanić Tanja , Isaković Milica , Malešević Jovana , Formica Domenico , Di Pino Giovanni , Keller Thierry , Štrbac Matija
Published: June 2022

Background

Providing real‐time haptic feedback is an important, but still not sufficiently explored aspect of the use of supernumerary robotic limbs (SRLs). We present a multi‐pad electrode for conveying multi‐modal proprioceptive and sensory information from SRL to the user's thigh and propose a method for stimuli calibration.

Methods

Within two pilot tests, we investigated return electrode configuration and active electrode discrimination in three healthy subjects to select the appropriate electrode pad topology. Based on the obtained results and anthropometric data from the literature, the electrode was designed to have three branches of 10 pads and two additional pads that can be displaced over/under the electrode branches. The electrode was designed to be connected to the stimulator that allows full multiplexing so that specific branches can serve as a common return electrode. To define the procedure for application of this system, the sensation, localization, and discomfort thresholds applicable for the novel electrode were determined and analyzed in 10 subjects.

Results

The results showed no overlaps between the three thresholds for individual pads, with significantly different average values, suggesting that the selected electrode positioning and design provide a good active range of useful current amplitude. The results of the subsequent analysis suggested that the stimuli intensity level of 200% of the sensation threshold is the most probable value of the localization threshold. Furthermore, this level ensures a low chance (i.e., 0.7%) of reaching the discomfort.

Conclusions

We believe that envisioned electrotactile system could serve as a high bandwidth feedback channel that can be easily set up to provide proprioceptive and sensory feedback from supernumerary limbs.
Stunting, age at school entry and academic performance in developing countries: A systematic review and meta‐analysis
Authors: Gansaonré Rabi Joël , Moore Lynne , Bleau Louis‐Philippe , Kobiané Jean‐François , Haddad Slim
Published: June 2022

Aim

To review evidence of the effects of stunting, or height‐for‐age, on schooling level and schooling trajectories, defined as the combination of school entry age, grade repetition and dropouts.

Methods

We conducted a systematic review of studies (last update 20 March 2021) that assessed the association between stunting, or height‐for‐age, and at least one component of school trajectory using five databases (PubMed, Embase, Education Resources Information Center [ERIC], Web of Science and PsycINFO). Two independent reviewers performed study selection and data extraction. Pooled effects were calculated using the generic inverse variance weighting random‐effect model. The risk of bias was assessed using the ROBINS‐I tool (PROSPERO ID: CRD42020198346).

Results

We screened 3944 articles, and 16 were eligible for the qualitative and quantitative syntheses. Meta‐analysis showed that an increase in height‐for‐age leads to an increase in early enrolment [OR = 1.34 (95% CI, 1.07–1.67)], a reduction in late enrolment [OR = 0.63 (95% CI, 0.51–0.78)], an increase in schooling level [MD = 0.24 (95% CI, 0.14–0.34)] and a reduction in school overage [OR = 0.79 (95% CI, 0.70–0.90)]. Stunted children were more likely to repeat a grade than non‐stunted [OR = 1.59 (95% CI, 1.18–2.14)].

Conclusion

This review suggests that stunting in childhood might negatively affect school trajectories. Future research should evaluate the effect of stunting on school trajectories and the modification effect of socioeconomic status.
Still disease with persistent atypical dermatomyositis-like skin eruption: two cases associated with macrophage activation syndrome
Authors: Fernández Camporro Ángel , Rodriguez Diaz Eloy , Beteta Gorriti Valia , Gonzalvo Rodríguez Pablo , Alvarez-Cuesta César
Published: June 2022

The typical rash of Still disease is an asymptomatic, salmon-coloured, macular, or maculopapular eruption that appears along with the fever spikes and fades when the body temperature drops. Although not included in the diagnostic criteria, there are other frequent, persistent, pruritic and polymorphic skin manifestations of Still disease that have distinctive clinical features and specific histological findings. Among these atypical persistent pruritic eruptions (PPEs), periorbital erythema and linear flagellate papules and plaques can resemble the cutaneous manifestations of dermatomyositis (DM). The presence of these lesions in adult-onset Still disease has been associated with worse prognosis and higher mortality rates, perhaps due to the development of a secondary macrophage activation syndrome (MAS). We report two cases of Still disease with persistent atypical DM-like eruption, one in a paediatric patient (a very underreported finding) and the other in an adult. Both cases developed a secondary MAS.
The magic in the (extra)ordinary: Intensive validation to recalibrate the life‐worlds of adolescents exposed to abuse
Authors: Kolb Helen , Dovran Anders , Fernee Carina Ribe , Bøe Tore Dag
Published: June 2022

This qualitative case study aimed to explore environmental circumstances and interactional processes that appeared to be relevant for the dynamics of resilience in adolescents exposed to child abuse. Fieldwork at a learning and coping centre for children and their families was combined with semi‐structured interviews with adolescent participants aged 12 to 18 years. A critical realist approach was used to unpack what has been called the ‘ordinary magic’ of resilience. We found that intensively validating qualities of both the environment and relationships seemed to be driving components for resilience. Borrowing ideas from the sociometer theory, we propose that particularly the consistent intensiveness may offer a recalibration of the adolescents' immediate life‐worlds, in terms of how they perceive the people they meet and the environments they step into. In keeping with the transactional‐ecological model of resilience, we suggest that such a recalibration leads to altered social agency that becomes visible through their immediate social participation.
Microsecretory adenocarcinoma of the skin harboring recurrent SS18 fusions: A cutaneous analog to a newly described salivary gland tumor
Authors: Bishop Justin A. , Williams Erik A. , McLean Anne C. , Gagan Jeffrey , Rooper Lisa M. , Jordan Richard C. K. , LeBoit Philip E.
Published: June 2022

Background

Microsecretory adenocarcinoma (MSA) is a newly described salivary gland neoplasm characterized by MEF2C::SS18 fusions. MSA was previously thought to occur exclusively in salivary glands. Here, we expand the spectrum of known primary sites of this tumor by describing a series of cutaneous tumors with analogous findings.

Methods

We identified four cutaneous primary tumors with histopathologic features identical to MSA of the salivary glands. These cases were evaluated by immunohistochemistry, fluorescence in situ hybridization (FISH) for SS18 rearrangement and targeted RNA‐sequencing. We also queried a pan‐tumor database of advanced carcinomas for MEF2C::SS18.

Results

The cases occurred in men ranging from 61 to 74 years (mean, 68). They arose from the skin of the nose, chin, scalp, and external auditory canal. All included cords/microcysts of eosinophilic cells with bland oval nuclei and bluish mucin within fibromyxoid stroma. The scalp tumor also exhibited high‐grade transformation (marked atypia, elevated mitotic rate, and necrosis), a feature unreported in salivary MSA. By immunohistochemistry, all cases were positive for S100. Two showed a myoepithelial component positive for p40 and smooth muscle actin or calponin. Three cases harbored MEF2C::SS18 by RNA sequencing, while one with limited tissue had SS18 rearrangement via FISH. Two patients had no evidence of recurrence or metastasis in limited follow‐up (3 and 6 months). The pan‐tumor database query also did not identify MEF2C::SS18 in any advanced cutaneous carcinomas.

Conclusion

This report expands the sites that can be involved by MSA. Similar to salivary cases, MEF2C::SS18 represents a recurrent fusion in MSA of the skin. Unusual features in cutaneous cases not seen in salivary MSA include one case with high‐grade transformation and two cases with a myoepithelial cell component. Identification of this fusion expands the spectrum of salivary‐analog cutaneous tumors and aids in precise tumor classification.
Can disorders of subjective time inform the differential diagnosis of psychiatric disorders? A transdiagnostic taxonomy of time
Authors: Kent Lachlan , Nelson Barnaby , Northoff Georg
Published: June 2022

Aim

Time is a core aspect of psychopathology with potential for clinical use and early intervention. Temporal experience, perception, judgement and processing are distorted in various psychiatric disorders such as mood (depression and mania), anxiety, autistic, impulse‐control, dissociative and attention‐deficit/hyperactivity disorders. Can these disorders of time be used as early diagnostic or predictive markers? To answer this question, we develop a Transdiagnostic Taxonomy of (disordered) Time (TTT) that maps on to the symptomatological, phenomenal, perceptual and functional descriptions of each underlying disorder in a 2 × 2 × 2 state space. Temporal distortions may precede functional decline, and so assist efforts at early detection and intervention in at‐risk groups.

Method

Firstly, this article integrates a psychological model of how time is processed with a subjective or phenomenological model of how time is experienced or perceived. Secondly, the integrated combined model of time is then used to heuristically map major psychiatric disorders on to the basic elements of temporal flow and integration.

Results

The TTT systematically describes the basic temporal nature of eight diagnostic categories of psychiatric illness. It differentiates between diagnoses primarily associated with distorted “macro‐level” phenomenal temporal experiences (i.e. anxiety, dissociation/PTSD, depression, and mania) from those primarily related to distorted ‘micro‐level’ temporal processing (i.e. psychotic, impulse‐control, autistic and attention‐deficit/hyperactivity disorders).

Conclusions

The TTT allows differential diagnostic classification of various psychiatric disorders in terms of a possible underlying time disorder, making it useful for future diagnostic and predictive purposes using novel techniques of temporal processing, time perception, passage of time, and time perspective.