bluuebunny/crossref_metadata_2025 huggingface dataset:
While they wait: A cross-sectional survey on wait times for mental health treatment for anxiety and depression for Australian adolescents
Authors: Subotic-Kerry Mirjana , Borchard Thomas , Parker Belinda , Li Sophie H. , Choi Jayden , Long Emma V. , Batterham Philip J , Whitton Alexis E. , Gokiert Aniela , Spencer Lucinda , O’Dea Bridianne
Published: August 2023

Background

Wait times are reported to impede adolescents’ access to mental health treatment for anxiety and depression. However, there is limited quantitative research on current wait times for the treatment of anxiety and depression for Australian adolescents and the impact of these on young help-seekers.

Aims

This study examined Australian adolescents’ experiences of wait times for the treatment of anxiety and depression, including the providers they were waiting to access, the self-reported duration and perceived acceptability of wait times, the association between these wait times and psychological distress, and the support and coping behaviours used by adolescents during this time.

Method

From April to June 2022, 375 Australian adolescents aged 13-17 years who were currently waiting, or had previously waited in the past 12 months, for mental health treatment for anxiety and depression completed an anonymous cross-sectional online survey.

Results

The mean wait time across all treatment providers was 94.1 days (SD: 69.65). Psychologists and psychiatrists were the most utilised services. Most participants felt their wait times were ‘too long’ and longer wait times were significantly associated with increased psychological distress. Many participants perceived their mental health to have worsened during the wait time and engaged in maladaptive and risky coping behaviours while waiting. Most participants did not receive any support from their healthcare providers during the wait time. However, self-reported treatment attendance remained high.

Conclusions

Many Australian adolescents face lengthy wait periods when trying to access mental health treatment and this period may exacerbate distress and maladaptive coping.
Experiences of children’s self-wetting (including incontinence) in Cox’s Bazar’s Rohingya refugee camps, Bangladesh
Authors: Alam Mahbub-Ul , Gupta Sudipta Das , Rosato-Scott Claire , Shoaib Dewan Muhammad , Ritu Asmaul Husna , Nowshin Rifat , Rahat Md Assaduzzaman , Akram Nowshad , Rose Joanne , Evans Barbara E. , Barrington Dani J.
Published: August 2023

Self-wetting, including incontinence, affects people of all ages, ethnicities, and cultural backgrounds, and can have a significant negative impact on quality of life. We thus explored the attitudes towards self-wetting and experiences of children (ages five to 11), their caregivers, and humanitarian experts in the Rohingya refugee camps in Cox’s Bazar, Bangladesh.

We purposively selected participants from two camps where our partner organisation, World Vision Bangladesh - Cox’s Bazar, works. We conducted Key Informant Interviews (KIIs) with community members and camp officials, Story Book (SB) sessions with Rohingya children and in-depth Interviews (IDIs) with caregivers of children who participated in the SB sessions, as well as surveying the communal toilets used by children of the caregivers.

Self-wetting was commonly seen among the children. Due to self-wetting, children were likely to feel embarrassed, upset and uncomfortable, and frightened to use the toilet at night; many also indicated that they would be punished by their caregivers for self-wetting. Key informants indicated that caregivers have difficulty handling children’s self-wetting because they have a limited amount of clothing, pillows, and blankets, and difficulty cleaning these items. In the sanitation survey it was evident that the toilets are not appropriate and/or accessible for children.

Children in the Rohingya camps studied self-wet due to both urinary incontinence (when unable to reach a toilet in time) and because the sanitation facilities offered are inappropriate. They are teased by their peers and punished by their caregivers. The lives of children who self-wet in these camps could be improved by increasing awareness on self-wetting to decrease stigma and ease the concerns of caregivers, as well as increasing the number of toilets, ensuring they are well-lit, providing child-friendly toilets and cubicles, fixing the roads/paths that lead to sanitation to facilities and increasing the provision of relevant continence management materials.
Variant-to-function analysis of the childhood obesity chr12q13 locus implicates rs7132908 as a causal variant within the 3’ UTR ofFAIM2
Authors: Littleton Sheridan H. , Trang Khanh B. , Volpe Christina M. , Cook Kieona , DeBruyne Nicole , Maguire Jean Ann , Weidekamp Mary Ann , Boehm Keith , Chesi Alessandra , Pippin James A. , Anderson Stewart A. , Wells Andrew D. , Pahl Matthew C. , Grant Struan F.A.
Published: August 2023

The ch12q13 obesity locus is among the most significant childhood obesity loci identified in genome-wide association studies. This locus resides in a non-coding region withinFAIM2; thus, the underlying causal variant(s) presumably influence disease susceptibility via an influence oncis-regulation within the genomic region. We implicated rs7132908 as a putative causal variant at this locus leveraging a combination of our inhouse 3D genomic data, public domain datasets, and several computational approaches. Using a luciferase reporter assay in human primary astrocytes, we observed allele-specificcis-regulatory activity of the immediate region harboring rs7132908. Motivated by this finding, we went on to generate isogenic human embryonic stem cell lines homozygous for either rs7132908 allele with CRISPR-Cas9 homology-directed repair to assess changes in gene expression due to genotype and chromatin accessibility throughout a differentiation to hypothalamic neurons, a key cell type known to regulate feeding behavior. We observed that the rs7132908 obesity risk allele influenced the expression ofFAIM2along with other genes, decreased the proportion of neurons produced during differentiation, up-regulated cell death gene sets, and conversely down-regulated neuron differentiation gene sets. We have therefore functionally validated rs7132908 as a causal obesity variant which temporally regulates nearby effector genes at the ch12q13 locus and influences neurodevelopment and survival.
One Method to Sequence Them All? Comparison between Whole-Genome Sequencing (WGS) and Target Enrichment (TE) of museum specimens from the moth families Epicopeiidae and Sematuridae (Lepidoptera)
Authors: Call Elsa , Twort Victoria , Espeland Marianne , Wahlberg Niklas
Published: August 2023

There are various possibilities for sequencing highly degraded DNA, such as target enrichment (TE), or whole-genome sequencing (WGS). Here we compare TE and WGS methods using old museum specimens of two families of moths in the superfamily Geometroidea: Epicopeiidae and Sematuridae. Until recently, the relationships of these two families were unclear, as few studies had been done. Recently two studies used the TE approach, either on relatively fresh specimens, or on old museum specimens. Here, we aim to increase the sampling of the families Epicopeiidae and Sematuridae from museum specimens using the WGS method. We show that both sequencing methods give comparable results, but, unsurprisingly, WGS recovers more data. By combining TE and WGS data, we confirm that Sematuridae are sister to Pseudobistonidae+Epicopeiidae. Relationships of genera within the families are well supported. With the costs of WGS decreasing, we suggest that using low-coverage whole genome sequencing is becoming an increasingly viable option in the phylogenomics of insects.
How a reaction-diffusion signal can control spinal cord regeneration in axolotls: A modelling study
Authors: Caliaro Valeria , Peurichard Diane , Chara Osvaldo
Published: August 2023

Axolotls are uniquely able to completely regenerate the spinal cord after amputation. The underlying governing mechanisms of this regenerative response have not yet been fully elucidated. We previously found that spinal cord regeneration is mainly driven by cell cycle acceleration of ependymal cells, recruited by a hypothetical signal propagating from the injury. However, the nature of the signal and its propagation remain unknown. In this theoretical study, we investigated whether the regeneration-inducing signal can follow a reaction-diffusion process. We developed a computational model, validated it with experimental data and showed that the signal dynamics can be understood in terms of reaction-diffusion mechanism. By developing a theory of the regenerating outgrowth in the limit of fast reaction-diffusion, we demonstrate that control of regenerative response solely relies on cell-to-signal sensitivity and the signal reaction-diffusion characteristic length. This study lays foundations for further identification of the signal controlling regeneration of the spinal cord.
Starvation resistance in the nematodePristionchus pacificusrequires a conserved supplementary nuclear receptor
Authors: Theska Tobias , Renahan Tess , Sommer Ralf J.
Published: August 2023

Nuclear hormone receptors (NHRs) are a deeply-conserved superfamily of metazoan transcription factors, which fine-tune the expression of their regulatory target genes in response to a plethora of sensory inputs. In nematodes, NHRs underwent an explosive expansion and many species have hundreds ofnhrgenes, most of which remain functionally uncharacterized. However, recent studies elucidated that two sister receptors,Ppa-NHR-1 andPpa-NHR-40, are crucial regulators of feeding-structure morphogenesis in the diplogastrid model nematodePristionchus pacificus. In this study, we functionally characterizePpa-NHR-10, the sister paralog ofPpa-NHR-1 andPpa-NHR-40, aiming to reveal whether it too regulates aspects of feeding-structure development. We used CRISPR/CAS9-mediated mutagenesis to create knock-out mutations of this receptor and applied a combination of geometric morphometrics and unsupervised clustering to characterize potential mutant phenotypes. However, we found thatPpa-NHR-10 does not affect feeding-structures morphogenesis. Instead, multiple RNA-seq experiments revealed that many of the target genes of this receptor are involved in lipid catabolic processes. We hypothesized that their mis-regulation could affect the survival of mutant worms during starvation, where lipid catabolism is often essential. Indeed, using novel survival assays, we found that mutant worms show drastically decreased starvation resistance, both as young adults and as dauer larvae. We also characterized genome-wide changes to the transcriptional landscape inP. pacificuswhen exposed to 24hrs of acute starvation, and found thatPpa-NHR-10 partially regulates some of these responses. Taken together, we were able to demonstrate thatPpa-NHR-10 is broadly required for starvation resistance and regulates different biological processes than its closest paralogsPpa-NHR-1 andPpa-NHR-40.
Reconstructing the genetic relationship between ancient and present-day Siberian populations
Authors: Gill Haechan , Lee Juhyeon , Jeong Choongwon
Published: August 2023

Human populations across a vast area in northern Eurasia, from Fennoscandia to Chukotka, share a distinct genetic component often referred to as the Siberian ancestry. Most enriched in present-day Samoyedic-speaking populations such as Nganasans, its origins and history still remain elusive despite the growing list of ancient and present-day genomes from Siberia. Here we reanalyze published ancient and present-day Siberian genomes focusing on the Baikal and Yakutia, resolving key questions regarding their genetic history. First, we show a long-term presence of a unique genetic profile in southern Siberia, up to 6,000 years ago, which distinctly shares a deep ancestral connection with Native Americans. Second, in the Baikal we find no direct contribution of the Early Neolithic Kitoi people to Late Neolithic and Early Bronze Age Serovo-Glazkovo ones. Third, the Middle Neolithic individual from Yakutia, belonging to the Belkachi culture, serves as the best source so far available for the spread of the Siberian ancestry into Fennoscandia and Greenland. These findings shed light on the genetic legacy of the Siberian ancestry and provide insights into the complex interplay between different populations in northern Eurasia throughout history.
Comparison of the cattle rumen bacterial community and drinker water in different livestock farm buildings using NGS sequencing
Authors: Yildirim E.A. , Ilina L.A. , Filippova V.A.
Published: August 2023

The aim of the study was to analyze samples of ruminal fluid from highly productive lactating cows of black-motley Holsteinized breed and water from drinkers from three livestock farm buildings using the molecular genetic method NGS -sequencing. The experiment was carried out in a commercial farm of the Tula region of Russia. The composition of microorganisms in samples of rumen fluid and water from drinking bowls was studied using the molecular genetic method of NGS-sequencing. In all samples, including water samples from drinking bowls, a variety of pathogenic microorganisms were found, including campylobacter, mycoplasma, pathogenic Clotridia, leptotrichia, Salmonella and others. Interestingly, a number of these microorganisms were also found in the rumen of cows. Thus, the proportion of pathogenic Campylobacter in samples of cicatricial contents ranged from 0.01±0.0006% to 0.03±0.0009%. Also, these bacteria were found in water samples from the drinking bowls of two buildings: in the amount of 0.02±0.0015% and 0.002±0.0001%.Improper sanitary condition of water in cowsheds creates the risk of various diseases.
Switching Gō-Martinifor Investigating Protein Conformational Transitions and Associated Protein-Lipid Interactions
Authors: Yang Song , Song Chen
Published: August 2023

Proteins are dynamic biomolecules that can transform between different conformational states when exerting physiological functions, which is difficult to simulate by using all-atom methods. Coarse-grained Gō-like models are widely-used to investigate large-scale conformational transitions, which usually adopt implicit solvent models and therefore cannot explicitly capture the interaction between proteins and surrounding molecules, such as water and lipid molecules. Here, we present a new method, namedSwitching Gō-Martini, to simulate large-scale protein conformational transitions between different states, based on the switching Gō method and the coarse-grained Martini 3 force field. The method is straight-forward and efficient, as demonstrated by the benchmarking applications for multiple protein systems, including glutamine binding protein (GlnBP), adenylate kinase (AdK), andβ2-adrenergic receptor (β2AR). Moreover, by employing theSwitching Gō-Martinimethod, we can not only unveil the conformational transition from the E2Pi-PL state to E1 state of the Type 4 P-type ATPase (P4-ATPase) flippase ATP8A1-CDC50, but also provide insights into the intricate details of lipid transport.
Bromodomain Factor 5 as a Target for Antileishmanial Drug Discovery
Authors: Russell Catherine N. , Carter Jennifer L. , Borgia Juliet M. , Bush Jacob , Calderon Felix , Gabarro Raquel , Conway Stuart J. , Mottram Jeremy C , Wilkinson Anthony J , Jones Nathaniel Gadsby
Published: August 2023

Leishmaniases are a collection of neglected tropical diseases caused by kinetoplastid parasites in the genus Leishmania. Current chemotherapies are severely limited and the need for new antileishmanials is of pressing international importance. Bromodomains are epigenetic reader domains that have shown promising therapeutic potential for cancer therapy and may also present an attractive target to treat parasitic diseases. Here, we investigate Leishmania donovani bromodomain factor 5 (LdBDF5) as a target for antileishmanial drug discovery. LdBDF5 contains pair of bromodomains (BD5.1 and BD5.2) in an N-terminal tandem repeat. We purified recombinant bromodomains of L. donovani BDF5 and determined the structure of BD5.2 by X-ray crystallography. Using a histone peptide microarray and fluorescence polarisation assay, we identified binding interactions of LdBDF5 bromodomains with acetylated peptides derived from histones H2B and H4. In orthogonal biophysical assays including thermal shift assays, fluorescence polarisation and NMR, we showed that BDF5 bromodomains bind to human bromodomain inhibitors SGC-CBP30, bromosporine and I-BRD9, moreover, SGC-CBP30 exhibited activity against Leishmania promastigotes in cell viability assays. These findings exemplify the potential BDF5 holds as a drug target in Leishmania and provide a foundation for the future development of optimised antileishmanial compounds targeting this epigenetic reader protein.
Improved taxonomic annotation of Archaea communities using LotuS2, the Genome Taxonomy Database and RNAseq data
Authors: Grant Alastair , Aleidan Abdullah , Davies Charli S. , Udochi Solomon C. , Fritscher Joachim , Bahram Mohammad , Hildebrand Falk
Published: August 2023

Metabarcoding is increasingly used to uncover diversity and characterise communities of Archaea In various habitats, but taxonomic annotation of their sequences remains more challenging than for bacteria. Fewer reference sequences are available; widely used databases do not reflect recent revisions of higher level archaeal taxonomy and a substantial fraction of their phylogenetic diversity remains to be fully characterised. We address these gaps with a systematic and tractable approach based around the Genome Taxonomy Database (GTDB). GTDB provides a standardized taxonomy with normalized ranks based on protein coding genes, allowing us to identify and remove incongruent SSU sequences. We then use this in combination with the eukaryote PR2 database to annotate a collection of near full length rRNA sequences and the Archaea SSU sequences in SILVA, creating a new reference database, KSGP (Karst,Silva,GTDB andPR2). GTDB SSUs alone provides a small improvement in annotation of an example marine Archaea OTU data set over standardized SSU databases such as SILVA and Greengenes2, while KSGP increases Class and Order assignments by 145% and 280% respectively and is likely to provide some improvement in annotation of bacterial sequences too.

We make the KSGP database and a cleaned and deduplicated subset of GTDB SSU sequences available at ksgp.earlham.ac.uk; integrate them into a metabarcoding pipeline, LotuS2 and outline rapid and robust strategies to generate a set of annotated Archaea OTUs and to determine the proportion of Archaea sequences in metatranscriptomic data. We also demonstrate simple tools to visualise the completeness of database coverage and outline strategies to further understand poorly characterised components of the archaeal community which will be equally applicable to bacteria.
Timing the Evolution of Phosphorus-Cycling Enzymes Through Geological Time
Authors: Boden Joanne S. , Zhong Juntao , Anderson Rika E. , Stüeken Eva E.
Published: August 2023

SUMMARY PARAGRAPH

Phosphorus plays a crucial role in controlling biological productivity, but geological estimates of phosphate concentrations in the Precambrian ocean, during life’s origin and early evolution, vary over several orders of magnitude1-10. While reduced phosphorus species may have served as alternative substrates to phosphate11, their bioavailability on the early Earth remains unknown. Here, we reconstruct the phylogenomic record of life on Earth and find that phosphate transporting genes (pnas) evolved in the mid-Archean (ca. 3.2 Ga) and are consistent with phosphate concentrations above modern levels (>3 μM). The first gene optimized for low phosphate levels (pstS; <1 μM) appeared around 2.9 Ga. Most enzymatic pathways for metabolising reduced phosphorus emerged and expanded across the tree of life in the Neoarchean to Paleoproterozoic (ca. 2.6 to 1.8 Ga). This includes phosphonate-catabolising CP-lyases, phosphite-oxidising pathways and hypophosphite-oxidising pathways. CP-lyases are particularly abundant in dissolved phosphate concentrations below 0.1 μM. Our results thus indicate declining phosphate levels through the Archean, possibly linked to increasing deposition of phosphate-scavenging iron oxides, which may have limited productivity. However, reduced phosphorus species did not become widely used until after the Paleoproterozoic Great Oxidation Event (2.3 Ga), possibly linked to an expansion of the biosphere at that time.
Synaptopodin is required for long-term depression at Schaffer collateral-CA1 synapses
Authors: Inglebert Yanis , Wu Pei You , Tourbina-Kolomiets Julia , Dang Cong Loc , McKinney R. Anne
Published: August 2023

Synaptopodin (SP), an actin-associated protein found in telencephalic neurons, affects synaptic and structural plasticity. While being required for longterm depression (LTD) mediated by metabotropic glutamate receptor (mGluR-LTD), little is known about its role in other forms of LTD induced by low frequency stimulation (LFS-LTD) or spike-timing dependent plasticity (STDP). Using SP-deficient mice (SPKO), we have here demonstrated that the presence of SP is mandatory for normal LTD expression. On the contrary, long-term potentiation (LTP), albeit diminished in SPKO, is still present and can be easily recovered by increasing the stimulation frequency. Our study shows, for the first time, the role of SP in a more physiological form of induction of synaptic plasticity.
Soft-metal(loid)s induce protein aggregation inEscherichia coli
Authors: Cornejo Fabián A. , Muñoz-Villagrán Claudia M. , Luraschi Roberto A. , Sandoval-Díaz María P. , Cancino Camila A. , Pugin Benoit , Morales Eduardo H. , Piotrowski Jeff S. , Sandoval Juan M. , Vásquez Claudio C. , Arenas Felipe A.
Published: August 2023

Metal(loid) salts have been used to treat infectious diseases due to their exceptional biocidal properties at low concentrations. However, the mechanism of their toxicity has yet to be fully elucidated. The production of reactive oxygen species (ROS) has been linked to the toxicity of soft metal(loid)s such as Ag(I), Au(III), As(III), Cd(II), Hg(II), and Te(IV). Nevertheless, few reports have described the direct, or ROS-independent, effects of some of these soft-metal(loid)s on bacteria, including the dismantling of iron-sulphur clusters [4Fe-4S] and the accumulation of porphyrin IX. Here, we used genome-wide genetic, proteomic, and biochemical approaches under anaerobic conditions to evaluate the direct mechanisms of toxicity of these metal(loid)s inEscherichia coli. We found that certain soft-metal(loid)s promote protein aggregation in a ROS-independent manner. This aggregation occurs during translation in the presence of Ag(I), Au(III), Hg(II), or Te(IV) and post-translationally in cells exposed to Cd(II) or As(III). We determined that aggregated proteins were involved in several essential biological processes that could lead to cell death. For instance, several enzymes involved in amino acid biosynthesis were aggregated after soft-metal(loid) exposure, disrupting intracellular amino acid concentration. We also propose a possible mechanism to explain how soft-metal(loid)s act as proteotoxic agents.
Moderate Endurance Exercise Increases Arrhythmia Susceptibility and modulates Cardiac Structure and Function in a Sexually Dimorphic manner
Authors: George Sharon A , Trampel Katy Anne , Brunner Kelsey , Efimov Igor R
Published: August 2023

Background

While moderate endurance exercise has been reported to improve cardiovascular health, its effects on cardiac structure and function are not fully characterized, especially with respect to sexual dimorphism. We aimed to assess the effects of moderate endurance exercise on cardiac physiology in male versus female mice.

Methods

C57BL/6J mice of both sexes were run on a treadmill for six weeks. ECG and echocardiography were performed every two weeks. After six weeks of exercise, mice were euthanized, and triple parametric optical mapping was performed on Langendorff perfused hearts to assess cardiac electrophysiology. Arrhythmia inducibility was tested by programmed electrical stimulation. Left ventricular (LV) tissue was fixed, and RNA sequencing was performed to determine exercise-induced transcriptional changes.

Results

Exercise-induced LV dilatation was observed in female mice alone, as evidenced by increased LV diameter and reduced LV wall thickness. Increased cardiac output was also observed in female exercised mice but not males. Optical mapping revealed further sexual dimorphism in exercise-induced modulation of cardiac electrophysiology. In female mice, exercise prolonged action potential duration and reduced voltage-calcium influx delay. In male mice, exercise reduced the calcium decay constant, suggesting faster calcium reuptake. Exercise increased arrhythmia inducibility in both male and female mice, however, arrhythmia duration was increased only in females. Lastly, exercise-induced transcriptional changes were sex-dependent: females and males exhibited the most significant changes in contractile versus metabolism-related genes, respectively.

Conclusions

Our data suggest that moderate endurance exercise can significantly alter multiple aspects of cardiac physiology in a sex-dependent manner. While some of these effects are beneficial, like improved cardiac mechanical function, others are potentially pro-arrhythmic.
A data-driven approach for timescale decomposition of biochemical reaction networks
Authors: Akbari Amir , Haiman Zachary B. , Palsson Bernhard O.
Published: August 2023

Understanding the dynamics of biological systems in evolving environments is a challenge due to their scale and complexity. Here, we present a computational framework for timescale decomposition of biochemical reaction networks to distill essential patterns from their intricate dynamics. This approach identifies timescale hierarchies, concentration pools, and coherent structures from time-series data, providing a system-level description of reaction networks at physiologically important timescales. We apply this technique to kinetic models of hypothetical and biological pathways, validating it by reproducing analytically characterized or previously known concentration pools of these pathways. Moreover, by analyzing the timescale hierarchy of the glycolytic pathway, we elucidate the connections between the stoichiometric and dissipative structures of reaction networks and the temporal organization of coherent structures. Specifically, we show that glycolysis is a cofactor driven pathway, the slowest dynamics of which are described by a balance between high-energy phosphate bond and redox trafficking. Overall, this approach provides more biologically interpretable characterizations of network dynamics than large-scale kinetic models, thus facilitating model reduction and personalized medicine applications.
CFM: Confinement Force Microscopy-a dynamic, precise and stable microconfiner for traction force microscopy in spatial confinement
Authors: Abbasi Fatemeh , Rieck Katharina , Brandt Matthias , Matis Maja , Betz Timo
Published: August 2023

In vivo, cells experience complex tissue environments with various chemical and physical features. They sense and respond to tissue morphology and mechanical properties and adjust their behavior and function based on the surrounding. In contrast to the free environment experienced on 2D substrates commonly used in research, the 3D natural environment represents a major physical obstacle for cells. Here, cells are usually confined either by the extracellular matrix (ECM) or neighboring cells. The importance of such confinements has been demon-strated in the past decades by showing its influence on cell decision-making in many vital biological processes such as migration, division and cytoskeletal reorganization. Despite these insights, the sheer level of complexity faced when studying cell biological questions in biomimetic confined situations, led to an indispensable need for a 3D system which can simulate thein vivoconfined condition, while being capable of providing microenvironments with different chemical and physical properties for the cells and capturing the mechanical forces and properties of the studied biological sample. Here we introduce a microconfiner that finally provides a new imaging capacity, namely the confine-ment force microscopy (CFM). We are able to adjust the confinement level in real time during microscopy while measuring not only the the cellular traction but also the cellular compression forces. Furthermore, the chemical and physical properties of the microenvironment can be optimized for the respective questions. We demonstrate the power of this confinement system by the mechanical response of cells, migration analysis of immune cells, the timed force generation during durotaxis driven adhesion switching and the viscoelastic properties of cancer tissue.
Reprogramming of breast tumor-associated macrophages with modulation of arginine metabolism
Authors: Fernando Veani , Zheng Xunzhen , Sharma Vandana , Furuta Saori
Published: August 2023

HER2+ breast tumors have abundant immune-suppressive cells, including M2-type tumor associated macrophages (TAMs). While TAMs consist of the immune-stimulatory M1-type and immune-suppressive M2-type, M1/M2-TAM ratio is reduced in immune-suppressive tumors, contributing to their immunotherapy refractoriness. M1 vs. M2-TAM formation depends on differential arginine metabolism, where M1-TAMs convert arginine to nitric oxide (NO) and M2- TAMs convert arginine to polyamines (PAs). We hypothesize that such distinct arginine metabolism in M1- vs M2-TAMs is attributed to different availability of BH4(NO synthase cofactor) and that its replenishment would reprogram M2-TAMs to M1-TAMs. Recently, we reported that sepiapterin (SEP), the endogenous BH4precursor, elevates the expression of M1- TAM markers within HER2+ tumors. Here, we show that SEP restores BH4levels in M2-TAMs, which then redirects arginine metabolism to NO synthesis and converts M2-TAMs to M1-TAMs. The reprogrammed TAMs exhibit full-fledged capabilities of antigen presentation and induction of effector T cells to trigger immunogenic cell death of HER2+ cancer cells. This study substantiates the utility of SEP in metabolic shift of HER2+ breast tumor microenvironment as a novel immunotherapeutic strategy.
The impact of inclusive leadership on task performance: a moderated mediation model of resilience capacity and work meaningfulness
Authors: Gong Lei , Zhang Shuqin , Liu Zhiying
Published: August 2023

Purpose

This study aims to understand the relationships between inclusive leadership, work meaningfulness, resilience capacity and task performance during a pandemic, thereby providing strategies to address future crises more effectively.

Design/methodology/approach

Data were collected via a survey of 391 healthcare workers from 77 teams in primary hospitals in China.

Findings

The results indicate that inclusive leadership positively drives task performance through resilience capacity, and work meaningfulness amplifies this effect by strengthening the relationship between inclusive leadership and resilience capacity.

Originality/value

Workers face increased work pressure and requirements during a crisis, and understanding how to promote their task performance in such a context is of paramount importance. Although inclusive leadership is theorized to stimulate various positive employee outcomes, little is known about the mechanisms by which inclusive leadership affects task performance. The authors find that resilience capacity is a key mechanism responsible for the effect of inclusive leadership on the task performance of workers in high-stress situations. This positive indirect effect of inclusive leadership on task performance is amplified by a high level of work meaningfulness.
The influence of management innovation on the organisational performance of KIBS: the mediating role of service innovation and technology
Authors: Simao Lurdes Barroso , Carvalho Luisa , Madeira Maria Jose
Published: August 2023

Purpose

Based on the socio-technical systems theory, this study aims to investigate the impact of management innovation (MI) on organisational performance (OP), as well as the mediating role of technology (TEC) use and service innovation (SI) in linking MI and OP.

Design/methodology/approach

The research data was derived from 163 knowledge-intensive business services firms and analysed through structural equation modelling using SmartPLS software.

Findings

This study found a significant impact of MI on OP. The analysis also revealed that TEC use and SI influence OP and that MI influences performance indirectly through TEC use and SI.

Practical implications

This research reinforces the role of MI in firms aiming at improving their performance. The findings of this study suggest that managers’ regular initiatives in management practices, processes and structures influence the enabling role of TEC use and SI on OP.

Originality/value

Since not every MI lead to the planned performance, this research contributes to the literature on the influence of MI on OP by providing empirical evidence on the role of TEC use and SI on OP. TEC use and SI serve as complementary mediators. Higher levels of MI directly increase OP but also increase TEC use and SI, leading to OP.
Designing online delivery of Lean education during COVID-19
Authors: McDermott Olivia
Published: August 2023

Purpose

This study describes how two organisations transitioned to teaching Lean online during and post Covid-19. This study aims to establish how Lean teaching and training can be designed and delivered effectively online without adverse effects on the student’s learning experience of Lean concepts.

Design/methodology/approach

A case study approach was used to review the design, application and results of the transition to online Lean teaching and training. Qualitative and quantitative methods were deployed to assess the results.

Findings

Online Lean learning and application were assured via the design of practical problem-based teaching environments, aided by using the virtual classroom as an obeya room and as a kaizen environment where students worked in teams. Students were enabled to learn and apply Lean tools practically and reflect on their learnings.

Practical implications

This study demonstrates that effective online design can ensure. Lean methods are understood without affecting the student's learning, classroom experience and grasp of concepts.

Originality/value

To the best of the author’s knowledge, this is one of the first studies on implementing Lean training and education online during COVID-19 under the lens of both a training provider and university education viewpoint. The changes validated best practices for virtual Lean education and training in the organisations under study, maintained post-COVID.
Social enterprises’ objectives and choices of legal forms under the framework of Sustainable Development Goals – an analysis of 80 cases in Zhejiang Province, China
Authors: Li Wei , Liu Huan , Chen Yingshi
Published: August 2023

Purpose

This study aims to measure social enterprises’ (SEs’) social objectives under the United Nation’s 17 Sustainable Development Goals (SDGs) framework, and explore the impact of SEs’ social objectives on their choices of legal forms.

Design/methodology/approach

This study used semi-structured questionnaires followed up by field interviews and observations of the sampled SEs. The survey sample includes 80 participants of Social Entrepreneurs Stars Competition in Zhejiang Province of China. The authors conduct content analysis to measure the objectives of SEs. The authors also perform descriptive analysis, chi-square test and regression analysis on the data.

Findings

The findings confirm the theoretical discussions that SEs’ choices of legal forms reflect SEs’ strategies toward achieving social objectives. Similar to certain countries, some SEs in China register as nonprofit entities to concentrate on nonprofitable sustainability objectives, while others register as commercial enterprises or hybrid organizations to generate profits. However, some SEs focus on profitable non-sustainability issues and fail to prioritize social objectives over economic objectives. There are positive effects of social entrepreneurs’ background similarity and negative effects of social entrepreneurs’ educational level on their SEs’ choices to register as commercial enterprises.

Research limitations/implications

Due to the small size and nonrepresentative sample this study is based on, the findings need be further tested by a larger sample. SEs in different service domains rely on different types of financial resources (Mair et al., 2012; Doherty et al., 2014). In future research, the model can be expanded to test the effects of service domains and types of financial sources on SEs’ choices of legal forms.

Practical implications

To encourage more societal resources being allocated toward achieving the United Nations’ SDGs, policymakers and SE certification programs are recommended to explicitly incorporate sustainability objectives into the evaluation standards and supportive policies for SEs. Social entrepreneurs who aim to balance the social and economic objectives in their business are suggested to target the population with whom they share similar community background. Training or consulting programs for social entrepreneurs are suggested to provide advice tailored to their socio-economic background and personal experiences.

Originality/value

To the best of the authors’ this study is the first quantitative analysis to identify factors that associate with SEs’ choice of legal forms in China. The authors developed new instruments to measure SEs’ social objectives and service targets, access to financial resources and social entrepreneurs’ social-economic backgrounds.
Are credit ratings forward-looking? – Evidence from India
Authors: Sharma Chandan
Published: August 2023

Purpose

This paper aims to examine the informational value of credit rating changes for investors. The article analyses whether credit rating changes indicate the future financial performance of a firm.

Design/methodology/approach

The study employs pooled time-series cross-section regression technique and two-sample t-test for analysis. The paper utilizes a firm's operating profit as a proxy of its future financial performance to understand what inference can be drawn about future financial performance from a change in a firm's credit rating.

Findings

The paper finds that a firm operating profit declines in the year after a credit rating downgrade. However, no such significant relationship is evident in the case of a rating upgrade. The results are consistent across rating categories and individual years of the sample period.

Research limitations/implications

The study uses non-financial corporate rating data; hence, the findings may not apply to credit rating changes in financial corporates and structured finance.

Practical implications

Investors and analysts can incorporate credit rating downgrade by CRAs as a key input in a firm's future financial forecast. Analysts and investment managers can also look at credit rating changes of firms in the same industry and draw a definite conclusion about which firm is likely to see a higher deterioration in performance.

Originality/value

The author has not come across any literature that directly investigates credit rating changes from the perspective of information content about future financial performance.
Exploring the usage intention of AI-powered devices in smart homes among millennials and zillennials: the moderating role of trust
Authors: Chin Chee-Hua , Wong Winnie Poh Ming , Cham Tat-Huei , Thong Jun Zhou , Ling Jill Pei-Wah
Published: August 2023

Purpose

This study aims to investigate how artificial intelligence (AI)-powered smart home devices affect young consumers' requirements for convenience, support, security and monitoring, as well as their ability to advance environmental sustainability. This study also examines the variables that impact users' motivation to use AI-powered smart home devices, such as perceived value, ease of use, social presence, identity, technology security and the moderating impact of trust.

Design/methodology/approach

The responses from residents of Sarawak, Malaysia, were collected through online questionnaires. This study aimed to examine the perceptions of millennials and zillennials towards their trust and adoption of AI-powered devices. This study used a quantitative approach, and the relationships among the study constructs were analysed using partial least squares - structural equation modelling.

Findings

The present study found that perceived usefulness, ease of use and social presence were the main motivators among actual and potential users of smart home devices, especially in determining their intentions to use and actual usage. Additionally, there was a moderating effect of trust on the relationship between perceived ease of use, social presence, social identity and intention to use AI-powered devices in smart homes.

Originality/value

To the best of the authors’ knowledge, this is one of the first studies to examine the factors influencing smart technology adoption. This study provided meaningful insights on the development of strategies for the key stakeholders to enhance the adoption and usage of AI-powered smart home devices in Sarawak, one of the promising Borneo states. Additionally, this study contributed to the growing body of knowledge on the associations between technology acceptance model dimensions, intention and actual usage of smart technology, with the moderating impact of trust.
Nutrient enrichment alters seasonal β‐diversity in global grasslands
Authors: Garbowski Magda , Boughton Elizabeth , Ebeling Anne , Fay Philip , Hautier Yann , Holz Hanna , Jentsch Anke , Jurburg Stephanie , Ladouceur Emma , Martina Jason , Ohlert Timothy , Raynaud Xavier , Roscher Christiane , Sonnier Grégory , Tognetti Pedro Maximiliano , Yahdjian Laura , Wilfahrt Peter , Harpole Stan
Published: August 2023

Intra‐annual (i.e. seasonal) temporal niche partitioning is essential to the maintenance of biodiversity in many plant communities. However, understanding of how climate and global change drivers such as eutrophication influence seasonal niche partitioning in plant assemblages remains limited.

We used early‐season and late‐season compositional data collected from 10 grassland sites around the world to explore relationships between climate variability and intra‐annual species segregation (i.e. seasonal β‐diversity) and to assess how nutrient enrichment alters seasonal β‐diversity in plant communities. We then assessed whether changes in seasonal β‐diversity in response to nutrient enrichment are underpinned by species turnover or nestedness and determined how specific functional groups (i.e. annual forbs, perennial forbs, C3 and C4 graminoids and legumes) respond to eutrophication within and across early and late sampling dates.

We found a positive relationship between intra‐annual temperature variability and seasonal β‐diversity but observed no relationship between intra‐annual precipitation variability and seasonal β‐diversity. Nutrient enrichment increased seasonal β‐diversity and increased turnover of species between early‐ and late‐season communities. Nutrient enrichment reduced the abundance of C4 graminoids and legumes within and across sampling timepoints and eliminated intra‐annual differences in these groups. In contrast, nutrient enrichment resulted in seasonal differences in C3 graminoids, which were not observed in control conditions and increased abundance of C3 graminoids and annual forbs within and across early and late sampling dates.

Synthesis: Our understanding of how grasslands respond to various components of global change is primarily based on studies that document community changes at inter‐annual scales. Using early‐season and late‐season compositional data from 10 grassland sites around the world, we show that nutrient enrichment increases seasonal β‐diversity and alters intra‐annual dynamics of specific functional groups in unique ways.
Drivers of plant community (in)stability along a sea–inland gradient
Authors: La Bella Greta , Carboni Marta , Sperandii Marta Gaia , de Bello Francesco , Stanisci Angela , Acosta Alicia T. R.
Published: August 2023

Global change pressures are highlighting the need to better understand the mechanisms driving the temporal stability of natural communities under different environmental conditions. There is ample evidence that species richness helps communities to withstand environmental fluctuations and stabilise over time. However, it is still debated whether richness promotes stability through the diversity of species functional traits, phylogenetic lineages and ecological strategies in the community or because of the likelihood of including stable species. Furthermore, it is unclear whether the positive effect of diversity on stability is maintained in conditions of strong environmental fluctuations (e.g. frequent disturbances and stress).

To address these questions, we analysed long‐term monitoring data of 84 permanent plots in coastal dune plant communities distributed along a gradient of natural stress and disturbance, with communities closer to the sea subject to greater stress and more frequent disturbances. Specifically, we used structural equation models to disentangle the relative influence of the environmental gradient and the different diversity components (species richness, functional and phylogenetic diversity; SR, FD and PD), as well as of the dominant ecological strategy (captured by species lifespan) on community stability, through their effect on two key stability mechanisms (population stability and species asynchrony).

We found that the sea–inland environmental gradient was the main driver of stability mechanisms. Stress and disturbance decreased both population stability and species asynchrony, but also reduced species richness, which thus exerted a stabilising effect only on the communities in more favourable environmental conditions.

Surprisingly, we did not find an effect of FD and PD on community stability, neither directly nor via asynchrony. However, the dominance of perennial species mitigated the instability generated by stress and disturbance. Perennial species were on average more stable than annuals and displayed a wider range of species fluctuations, including compensatory dynamics among species (i.e. asynchrony).

Synthesis: Overall, our results highlight the importance of accounting for the environmental context when examining mechanisms of community stability. Species richness remains a useful direct predictor of community stability. Species ecological strategies, like the acquisitive–conservative trade‐off connected to lifespan, however, should also be routinely considered as drivers of both population stability and compensatory dynamics.
Berberine interacts with gut microbiota and its potential therapy for polycystic ovary syndrome
Authors: Zhu Ting‐Wei , Li Xue‐Lian
Published: August 2023

Berberine (BBR) is an isoquinoline alkaloid extracted from Chinese medicinal plants showing a tight correlation with gut microbiota. Polycystic ovary syndrome (PCOS) is a prevalent reproductive and endocrine disorder syndrome among women of childbearing age. Dysbiosis, the imbalance of intestinal microorganisms, is a potential factor that takes part in the pathogenesis of PCOS. Recent evidence indicates that berberine offers promise for treating PCOS. Here, we review the recent research on the interaction between berberine and intestinal microorganisms, including the changes in the structure of gut bacteria, the intestinal metabolites after BBR treatment, and the effect of gut microbiota on the bioavailability of BBR. We also discuss the therapeutic effect of BBR on PCOS in terms of gut microbiota and its potential mechanisms.