bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards a global investigation of transcriptomic signatures through co-expression networks and pathway knowledge for the identification of disease mechanisms
Authors: Figueiredo Rebeca Queiroz , Raschka Tamara , Kodamullil Alpha Tom , Hofmann-Apitius Martin , Mubeen Sarah , Domingo-Fernández Daniel
Published: March 2021

In this work, we attempt to address a key question in the joint analysis of transcriptomic data: can we correlate the patterns we observe in transcriptomic datasets to known molecular interactions and pathway knowledge to broaden our understanding of disease pathophysiology? We present a systematic approach that sheds light on the patterns observed in hundreds of transcriptomic datasets from over sixty indications by using pathways and molecular interactions as a template. Our analysis employs transcriptomic datasets to construct dozens of disease specific co-expression networks, alongside a human interactome network of protein-protein interactions described in the literature. Leveraging the interoperability between these two network templates, we explore patterns both common and particular to these diseases on three different levels. Firstly, at the node-level, we identify the most and least common proteins in these diseases and evaluate their consistency against the interactome as a proxy for their prevalence in the scientific literature. Secondly, we overlay both network templates to analyze common correlations and interactions across diseases at the edge-level. Thirdly, we explore the similarity between patterns observed at the disease level and pathway knowledge to identify pathway signatures associated with specific diseases and indication areas. Finally, we present a case scenario in the context of schizophrenia, where we show how our approach can be used to investigate disease pathophysiology.
High resolution profiling of MHC-II peptide presentation capacity, by Mammalian Epitope Display, reveals SARS-CoV-2 targets for CD4 T cells and mechanisms of immune-escape
Authors: Obermair Franz Josef , Renoux Florian , Heer Sebastian , Lee Chloe , Cereghetti Nastassja , Maestri Giulia , Haldner Yannick , Wuigk Robin , Iosefson Ohad , Patel Pooja , Triebel Katherine , Kopf Manfred , Swain Joanna , Kisielow Jan
Published: March 2021

Understanding the mechanisms of immune evasion is critical for formulating an effective response to global threats like SARS-CoV2. We have fully decoded the immune synapses for multiple TCRs from acute patients, including cognate peptides and the presenting HLA alleles. Furthermore, using a newly developed mammalian epitope display platform (MEDi), we determined that several mutations present in multiple viral isolates currently expanding across the globe, resulted in reduced presentation by multiple HLA class II alleles, while some increased presentation, suggesting immune evasion based on shifting MHC-II peptide presentation landscapes. In support, we found that one of the mutations present in B1.1.7 viral strain could cause escape from CD4 T cell recognition in this way. Given the importance of understanding such mechanisms more broadly, we used MEDi to generate a comprehensive analysis of the presentability of all SARS-CoV-2 peptides in the context of multiple common HLA class II molecules. Unlike other strategies, our approach is sensitive and scalable, providing an unbiased and affordable high-resolution map of peptide presentation capacity for any MHC-II allele. Such information is essential to provide insight into T cell immunity across distinct HLA haplotypes across geographic and ethnic populations. This knowledge is critical for the development of effective T cell therapeutics not just against COVID-19, but any disease.
High-quality complete genome resource of plant pathogenic bacteriumDickeya solanistrain IPO 2019 isolated fromHyacinthus orientalis
Authors: Czajkowski Robert , Rabalski Lukasz , Bartnik Przemysław , Jafra Sylwia
Published: March 2021

Dickeya solaniis an emerging plant pathogenic bacterium, causing disease symptoms in a variety of agriculturally relevant crop species worldwide. To date a number ofD. solanigenomes have been sequenced and characterized, the great majority of these genomes have however come fromD. solanistrains isolated from potato (Solanum tuberosumL.) and not from other plant hosts. Herewith, we present the first complete, high-quality genome ofD. solanistrain IPO 2019 (LMG 25990) isolated from ornamental plantHyacinthus orientalis. The genome ofD. solanistrain IPO 2019 consists of one chromosome of 4,919,542 bp., with a GC content of 56.2% and no plasmids. The genome contains 4502 annotated features, 22 rRNA genes, 73 tRNA genes and 1 CRISPRS. We believe that the information of this high-quality, complete, closed genome ofD. solanistrain isolated from host plant different than potato (i.e. hyacinth) will provide resources for comparative genomic studies as well as for analyses targeting adaptation and ecological fitness mechanisms present inDickeya solanispecies.
Arabidopsis annexin 5 controls plasma membrane properties in mature pollen grains
Authors: Lichocka Małgorzata , Krzymowska Magdalena , Górecka Magdalena , Hennig Jacek
Published: March 2021

In Arabidopsis, a dry stigma surface enables a gradual hydration of pollen grains by a controlled release of water. Occasionally the grains may be exposed to extreme precipitations that cause rapid water influx, swelling and eventually lead to pollen membrane (PM) rupture. In metazoans, calcium- and phospholipids-binding proteins, referred to as annexins participate in repair of the plasma membrane damages. It remains unclear, however, how this process is conducted in plants. Here, we examined whether the plant annexin 5 (ANN5), the most abundant member of the annexin family in pollen, is involved in the restoration of PM integrity. We analyzed a cellular dynamics of ANN5 in the pollen grains undergoingin vitroandin vivohydration. We observed a transient ANN5 association to PM during thein vitrohydration that did not occur in the pollen grains being hydrated on the stigma. To simulate a rainfall, we performed spraying of the pollinated stigma with deionized water that induced ANN5 accumulation at PM. Similarly, calcium or magnesium application affected PM properties and induced ANN5 recruitment to PM. Our data suggest a model, in which ANN5 is involved in the maintenance of membrane integrity in pollen grains exposed to osmotic or ionic imbalances.
Prostaglandin analog effects on cerebrospinal fluid reabsorption via nasal mucosa
Authors: Pedler Michelle G. , Petrash J. Mark , Subramanian Prem S.
Published: March 2021

Introduction

Cerebrospinal fluid (CSF) outflow has been demonstrated along nasal lymphatics via olfactory nerve projections; flow may be increased by stimulating lymphatic contractility using agents such as noradrenaline and the thromboxane A2 analog U46619. Lymphatics elsewhere in the body show increased contractility upon exposure to the prostaglandin F2alpha analog isoprostane-8-epi-prostaglandin. We investigated the ability of ophthalmic prostaglandin F2alpha analogs to increase CSF outflow when applied to the nasal mucosa by inhalation.

Methods

Latanoprost (0.1, 0.5, or 1mg/ml), bimatoprost (0.3 or 3mg/ml), travoprost (0.04 or 0.4mg/ml), latanoprostene bunod (0.24 or 2.4mg/ml), tafluprost (0.25 or 2.5mg/ml), or vehicle (10% DMSO) was administered to awake adult C57B/6 mice by nasal inhalation of 2μl droplets. A total of 67 animals were studied including controls. General anesthesia was induced by injection, and fluorescent tracer (AlexaFluor647-labelled ovalbumin) was injected under stereotaxic guidance into the right lateral ventricle. Nasal turbinate tissue was harvested and homogenized after 1 hour for tracer detection by ELISA and fluorometric analysis.

Results

Inhalation of latanoprost 0.5mg/ml and 1mg/ml led to a 11.5-fold increase in tracer recovery from nasal turbinate tissues compared to controls (3312 pg/ml vs 288 pg/ml, p<0.001 for 0.5mg/ml; 3355 pg/ml vs 288 pg/ml, p<0.001 for 1mg/ml), while latanoprost 0.1 mg/ml enhanced recovery 6-fold (1713 pg/ml vs 288 pg/ml, p<0.01). Tafluprost 0.25mg/ml and bimatoprost 0.3mg/ml showed a modest (1.4x, p<0.05) effect, and the remaining agents showed no significant effect on tracer recovery.

Conclusions

Prostaglandin F2alpha analogs delivered by nasal inhalation resulted in increased nasal recovery of a CSF fluorescent tracer, implying increased CSF outflow via the nasal lymphatics. The greatest effect, partially dose-dependent, was observed using latanoprost. Further studies are needed to determine the efficacy of these agents in reducing ICP in short and long-term applications.
Human parvovirus B19 interacts with globoside under acidic conditions as an essential step in endocytic trafficking
Authors: Bieri Jan , Leisi Remo , Bircher Cornelia , Ros Carlos
Published: March 2021

The glycosphingolipid (GSL) globoside (Gb4) is essential for parvovirus B19 (B19V) infection. Historically considered the cellular receptor of B19V, the role of Gb4 and its interaction with B19V are controversial. In this study, we applied artificial viral particles, genetically modified cells, and specific competitors to address the interplay between the virus and the GSL. Our findings demonstrate that Gb4 is not involved in the binding or internalization process of the virus into permissive erythroid cells, a function that corresponds to the VP1u cognate receptor. However, Gb4 is essential at a post-internalization step before the delivery of the single-stranded viral DNA into the nucleus. In susceptible erythroid Gb4 knockout cells, incoming viruses were arrested in the endosomal compartment, showing no cytoplasmic spreading of capsids as observed in Gb4-expressing cells. Hemagglutination and binding assays revealed that pH acts as a switch to modulate the affinity between the virus and the GSL. Capsids interact with Gb4 exclusively under acidic conditions and dissociate at neutral pH. Inducing a specific Gb4-mediated attachment to permissive erythroid cells by acidification of the extracellular environment led to a non-infectious uptake of the virus, indicating that low pH-mediated binding to the GSL initiates active membrane processes resulting in vesicle formation. In summary, this study provides mechanistic insight into the interaction of B19V with Gb4. The strict pH-dependent binding to the ubiquitously expressed GSL prevents the redirection of the virus to nonpermissive tissues while promoting the interaction in acidic intracellular compartments as an essential step in infectious endocytic trafficking.

Author summary

The neutral glycosphingolipid globoside (Gb4) has been historically considered the cellular receptor of B19V, however, its wide expression profile does not correlate well with the restricted tropism of the virus. Here, we show that Gb4 is essential for the infection at a step following virus uptake and before the delivery of the viral ssDNA into the nucleus. B19V interacts with Gb4 exclusively under acidic conditions, prohibiting the interaction on the plasma membrane and promoting it inside the acidic endosomal compartments, which are engaged by the virus and the GSL after internalization. In the absence of Gb4, incoming viruses are retained in the endocytic compartment and the infection is aborted. This study reveals the mechanism of the interaction between the virus and the glycosphingolipid and redefines the role of Gb4 as an essential intracellular partner required for infectious entry.
Microglia show differential transcriptomic response to Aβ peptide aggregatesex vivoandin vivo
Authors: McFarland Karen N. , Ceballos Carolina , Rosario Awilda , Ladd Thomas , Moore Brenda , Golde Griffin , Wang Xue , Allen Mariet , Ertekin-Taner Nilüfer , Funk Cory C , Robinson Max , Baloni Priyanka , Rappaport Noa , Chakrabarty Paramita , Golde Todd E.
Published: March 2021

Aggregation and accumulation of amyloid-β (Aβ) is a defining feature of Alzheimer’s disease (AD) pathology. To study microglial responses to Aβ, we applied exogenous Aβ peptide, in either oligomeric or fibrillar conformation, to primary mouse microglial cultures and evaluated system level transcriptional changes and then compared these to transcriptomic changes in the brains of CRND8 APP mice. We find that primary microglial cultures have rapid and massive transcriptional change to in response to Aβ. Transcriptomic responses to oligomeric or fibrillar Aβ in primary microglia, though partially overlapping, are distinct and are not recapitulatedin vivowhere Aβ progressively accumulates. Furthermore, though classic immune mediators show massive transcriptional changes in the primary microglial cultures, these changes are not observed in the mouse model. Together, these data extend previous studies which demonstrate that microglia responsesex vivoare poor proxies forin vivoresponses. Finally, these data demonstrate the potential utility of using microglia as biosensors of different aggregate conformation, as the transcriptional responses to oligomeric and fibrillar Aβ can be distinguished.
Distinct forms of synaptic plasticity during ascending vs. descending control of medial olivocochlear efferent neurons
Authors: Romero Gabriel E. , Trussell Laurence O.
Published: March 2021

Activity in each brain region is shaped by the convergence of ascending and descending axonal pathways, and the balance and characteristics of these determine neural output. The medial olivocochlear (MOC) efferent system is part of a reflex arc that critically controls auditory sensitivity. Multiple central pathways contact MOC neurons, raising the question of how a reflex arc could be engaged by diverse inputs. We examined functional properties of synapses onto brainstem MOC neurons from ascending (ventral cochlear nucleus, VCN), and descending (inferior colliculus, IC) sources in mice using an optogenetic approach. We found that these pathways exhibited opposing forms of short-term plasticity, with VCN input showing depression and IC input showing marked facilitation. By using a conductance clamp approach, we found that combinations of facilitating and depressing inputs enabled firing of MOC neurons over a surprisingly wide dynamic range, suggesting an essential role for descending signaling to a brainstem nucleus.
Daily changes in neuronal activities of the dorsal motor nucleus of the vagus under standard and short-term high fat diet – implications for circadian modulation of parasympathetic outflow
Authors: Chrobok Lukasz , Klich Jasmin D , Jeczmien-Lazur Jagoda S , Pradel Kamil , Palus-Chramiec Katarzyna , Sanetra Anna M , Piggins Hugh D , Lewandowski Marian H
Published: March 2021

The suprachiasmatic nuclei (SCN) of the hypothalamus functions as the brain’s primary circadian clock, but circadian clock genes are also rhythmically expressed in several extra-SCN brain sites where they can exert local temporal control over physiology and behaviour. Recently, we found that the hindbrain dorsal vagal complex possesses strong daily timekeeping capabilities, with the area postrema and nucleus of the solitary tract exhibiting the most robust clock properties. The possibility that the executory part of this complex – the dorsal motor nucleus of the vagus (DMV), also exhibits daily changes has not been extensively studied. The DMV is the source of vagal efferent motoneurons largely responsible for the regulation of gastric motility and emptying and consequently influence meal size and energy homeostasis. We used a combination of multi-channel electrophysiology and patch clamp recordings to gain insight into possible daily variation in these DMV cells and how this is influenced by diet. We found that DMV neurons increase their spontaneous activity, excitability and responsiveness to metabolic neuromodulators at late day which was paralleled with an enhanced synaptic input to these neurons. A high-fat diet typically damps circadian rhythms, but we found that short-term exposure to a high-fat diet paradoxically amplified daily variation of DMV neuronal activity, while blunting their responsiveness to metabolic neuromodulators. In summary, we show for the first time that neural activity at a source of vagal efferents varies with time of day and that this temporal variation is modulated by diet. These findings have clear implications for our understanding of the daily control of parasympathetic outflow.
Variation in bacterial composition, diversity, and activity across different subglacial basal ice types
Authors: Doyle Shawn M. , Christner Brent C.
Published: March 2021

Glaciers and ice sheets possess layers of basal ice characterized by high amounts of entrained debris that can serve as sources of nutrients and organic matter, providing habitat for microorganisms adapted to the frozen conditions. Basal ice forms through various mechanisms and is classified based on its ice and debris content; however, little is known about variation in microbial composition, diversity, and activity across different basal ice types. We investigated these parameters in four different types of basal ice from a cold-based and temperate glacier and used a meta-analysis to compare our findings with microbiome studies from other frozen environments. We found basal ice environments harbor a diverse range of microbiomes whose composition and activity can vary significantly between basal ice types, even within adjacent facies from the same glacier. In some debris-rich basal ices, elevated ATP concentrations, isotopic gas signatures, and high ratios of amplified sequences for 16S rRNA relative to that for 16S rRNA genes implicated certain bacterial taxa (e.g.,Paenisporosarcina,Desulfocapsa,Syntrophus, Desulfosporosinus) as being potentially active, with ice temperature appearing to be an important predictor for the diversity of taxa inferred to be active. Compared to those of other sympagic environments, these microbiomes often resembled those found in permafrost or perennial cave ice rather than other glacial ice environments. In contrast, debris-poor basal ices harbored microbiomes more like those found in oligotrophic englacial ice. Collectively, these results suggest that different basal ice types contain distinct microbiomes that are actively structured by the diagenesis of their habitat.

IMPORTANCE

The discharge of material from the basal ice zones of glaciers and ice sheets is an important source of dissolved organic matter, nutrients, and trace metals to downstream environments. Microorganisms with the ability to remain metabolically active while frozen have the potential to alter these substrates before they are released and may thus be a vital biogeochemical component of proglacial environments. However, basal ice environments are among the least explored areas of the cryosphere and information on their microbiology is limited. Here, we examine several basal ice types that were collected from different glaciers to investigate how their microbiomes varied. Our results indicate that sediment-rich basal ice from cold-based and temperate glaciers harbor microbiomes that conduct biogeochemical transformations at subzero temperatures and raises the intriguing possibility that subsurface regions of the cryosphere may be more biogeochemically active than previously thought.
No balance between glutamate+glutamine and GABA+ in visual and motor cortices of the human brain
Authors: Rideaux Reuben
Published: March 2021

Theoretical work, supported by electrophysiological evidence, asserts that a balance between excitation and inhibition (E/I) is critical for healthy brain function. In magnetic resonance spectroscopy (MRS) studies, the ratio of excitatory (glutamate) and inhibitory (γ-aminobutyric acid, GABA) neurotransmitters is often used as a proxy for this E/I balance. Recent MRS work found a positive correlation between GABA+ and Glx (glutamate+glutamine) in medial parietal cortex, providing validation for this proxy and supporting the link between the E/I balance observed in electrophysiology and that detected with MRS. Here we assess the same relationship, between GABA+ and Glx, in primary visual and motor cortices of resting male and female human participants. We find moderate to strong evidence that there is no positive correlation between these neurotransmitters in either location. We show this holds true when controlling for a range of other factors (i.e., demographics, signal quality, tissue composition, other neurochemicals) and regardless of the state of neural activity (i.e., resting/active). These results show that there is no brain-wide balance between excitatory and inhibitory neurotransmitters and indicates a dissociation between the E/I balance observed in electrophysiological work and the ratio of MRS-detected neurotransmitters.
Opposing motors provide mechanical and functional robustness in the human spindle
Authors: Neahring Lila , Cho Nathan H. , Dumont Sophie
Published: March 2021

At each cell division, the spindle self-organizes from microtubules and motors. How the spindle’s diverse motors, often acting redundantly or in opposition, collectively give rise to its emergent architecture, mechanics, and function is unknown. In human spindles, the motors dynein and Eg5 generate contractile and extensile stress, respectively. Inhibiting dynein or its targeting factor NuMA leads to unfocused, turbulent spindles and inhibiting Eg5 leads to monopoles, yet bipolar spindles form when both are inhibited together. What, then, are the roles of these opposing motors? Here we generate NuMA/dynein- and Eg5-doubly inhibited spindles that not only attain a typical metaphase shape and size, but also undergo anaphase. However, these spindles have reduced microtubule dynamics and are mechanically fragile, fracturing under force. Further, they exhibit lagging chromosomes and dramatic left-handed twist at anaphase. Thus, while these opposing motor activities are not required for the spindle’s shape, they are essential to its mechanical and functional robustness. Together, this work suggests a design principle whereby opposing active stresses provide robustness to force-generating cellular structures.
PEG10 viral aspartic protease domain is essential for the maintenance of fetal capillary structure in the mouse placenta
Authors: Shiura Hirosuke , Ono Ryuichi , Tachibana Saori , Kohda Takashi , Kaneko-Ishino Tomoko , Ishino Fumitoshi
Published: March 2021

The therian-specific gene paternally expressed 10 (Peg10) plays an essential role in placenta formation:Peg10knockout (KO) mice exhibit early embryonic lethality due to severe placental defects. The PEG10 protein exhibits homology to long terminal repeat (LTR) retrotransposon GAG and POL proteins, therefore mice harboring a mutation in its highly conserved viral aspartic protease motif in the POL-like region were generated because it is essential for LTR retrotransposons/retroviruses. Intriguingly, frequent perinatal lethality, not early embryonic lethality, was observed with fetal and placental growth retardation starting mid-gestation. In the mutant placentas, severe defects were observed in the fetal vasculature, where PEG10 is expressed in the three trophoblast cell layers that surround fetal capillary endothelial cells. Thus,Peg10has essential roles not only in early placenta formation, but also in placental vasculature maintenance from mid- to late-gestation. This implies that along the feto-maternal placenta interface an interaction occurs between two retrovirus-derived genes,Peg10and retrotransposon Gag like 1 (Rtl1,also calledPeg11), that is essential for the maintenance of fetal capillary endothelial cells.

Summary statement

Disruption of the highly conserved viral aspartic protease domain in PEG10 causes placental abnormality leading to perinatal lethality in mice.
Handcuffing intrinsically disordered regions in Mlh1-Pms1 disrupts mismatch repair
Authors: Furman Christopher M. , Wang Ting-Yi , Zhao Qiuye , Yugandhar Kumar , Yu Haiyuan , Alani Eric
Published: March 2021

The DNA mismatch repair (MMR) factor Mlh1-Pms1 contains long intrinsically disordered regions (IDRs). While essential for MMR, their exact functions remain elusive. We performed cross-linking mass spectrometry to identify the major interactions within the Mlh1-Pms1 heterodimer and used this information to insert FRB and FKBP dimerization domains into the IDRs of Mlh1 and Pms1. Yeast bearing these constructs were grown with rapamycin to induce dimerization. Strains containing FRB and FKBP domains in the Mlh1 IDR displayed complete MMR defects when grown with rapamycin, but removing rapamycin restored MMR functions. Furthermore, linking the Mlh1 and Pms1 IDRs through FRB-FKBP dimerization disrupted Mlh1-Pms1 binding to DNA, inappropriately activated Mlh1-Pms1, and caused MMR defectsin vivo. We conclude that dynamic and coordinated rearrangements of the MLH IDRs regulate how the complex clamps DNA to catalyze MMR. The application of the FRB-FKBP dimerization system to interrogatein vivofunctions of a critical repair complex will be useful for probing IDRs in diverse enzymes and to probe transient loss of MMR on demand.
Impact of COVID-19 pandemic on Black, Asian and Minority Ethnic (BAME)
communities: a qualitative study on the perspectives of BAME community
leaders
Authors: Mahmood Fesani , Acharya Dev , Kumar Kanta , Paudyal Vibhu
Published: March 2021

Objectives

The aim of this study was to explore the perspectives of BAME community
leaders in relation to - the impact of the COVID-19 pandemic on their
communities; and BAME community’s perception, understanding and adherence to
Government guidelines on COVID-19 public health measures.

Design

A phenomenological approach was adopted using qualitative
semi-structured interviews.

Settings

Community organisations and places of worships in the West Midlands
region of England.

Participants

Community leaders were recruited through organisations representing BAME
communities and religious places of worship.

Results

A total of 19 participants took part. Participants alluded to historical
and structural differences for the observed disparities in COVID-19
morbidity and mortality. Many struggled with lockdown measures which impeded
cultural and religious gatherings that were deemed to be integral to the
community. Cultural and social practices led to many suffering on their own
as discussion of mental health was still deemed a taboo within many
communities. Many expressed their community’s reluctance to report symptoms
for the fear of financial and physical health implications. They reported
increase in hate crime which was deemed to be exacerbated due to perceived
insensitive messaging from authority officials and historical structural
biases. Access and adherence to government guidelines was an issue for many
due to language and digital barriers. Reinforcement from trusted community
and religious leaders encouraged adherence. Points of support such as food
banks were vital in ensuring essential supplies during the pandemic. Many
could not afford masks and sanitisers.

Conclusion

The study highlights the perceived impact of COVID-19 pandemic on BAME
communities. Government agencies and public health agencies need to
integrate with the community, and community leaders to penetrate the key
messages and deliver targeted yet sensitive public health advice which
incorporates cultural and religious practices. Addressing route cause of
disparities is imperative to mitigate current and future pandemics.

Strengths and limitations of this study

To our knowledge, this is the first study in England to
investigate the understanding of risk and impact of COVID-19 using
the perspectives of BAME community leaders.

Participants represented diverse BAME community organisations
and places of worship.

Participant recruitment was limited to one of the seven regions
within England with the highest proportion of BAME
populations.

Results may not be generalizable to any BAME communities not
represented in the data.
Low-dose lung radiotherapy for COVID-19 lung disease: a preclinical efficacy study in a bleomycin model of pneumonitis
Authors: Jackson Mark R , Stevenson Katrina , Chahal Sandeep K , Curley Emer , Finney George E , Gutierrez-Quintana Rodrigo , Onwubiko Evarest , Rupp Angelika F , Strathdee Karen , MacLeod Megan KL , McSharry Charles , Chalmers Anthony J
Published: March 2021

Purpose

Low-dose whole lung radiotherapy (LDLR) has been proposed as a treatment for patients with acute respiratory distress syndrome associated with SARS-CoV-2 infection and clinical trials are underway. There is an urgent need for preclinical evidence to justify this approach and inform dose, scheduling and mechanisms of action.

Materials and methods

Female C57BL/6 mice were treated with intranasal bleomycin sulphate (7.5 or 11.25 units/kg, day 0), then exposed to whole lung radiation therapy (0.5, 1.0, 1.5 Gy or sham, day 3). Bodyweight was measured daily and lung tissue harvested for histology and flow cytometry on day 10. Computed tomography (CT) lung imaging was performed pre-radiation (day 3) and pre-endpoint (day 10).

Results

Bleomycin caused pneumonitis of variable severity which correlated with weight loss. LDLR at 1.0 Gy was associated with a significant increase in the proportion of mice recovering to 98% of initial bodyweight and a proportion of these mice exhibited less severe histopathological lung changes. Mice experiencing moderate initial weight loss were more likely to respond to LDLR than those experiencing severe initial weight loss. Additionally, LDLR (1.0 Gy) significantly reduced bleomycin-induced increases in interstitial macrophages, CD103+ dendritic cells and neutrophil-DC hybrids. Overall,bleomycin-treated mice exhibited significantly higher percentages of non-aerated lung in left than right lungs and LDLR (1.0 Gy) prevented further reductions in aerated lung volume in right but not left lungs. LDLR at 0.5 and 1.5 Gy did not modulate bodyweight or flow cytometric readouts of bleomycin-induced pneumonitis.

Conclusions

Our data support the concept that LDLR can ameliorate acute inflammatory lung injury, identify 1.0 Gy as the most effective dose and provide preliminary evidence that it is more effective in the context of moderate than severe pneumonitis. Mechanistically, LDLR at 1.0 Gy significantly suppressed bleomycin-induced accumulation of pulmonary interstitial macrophages, CD103+ dendritic cells and neutrophil-DC hybrids.
Structural analysis of the Sulfolobus solfataricus TF55β chaperonin by cryo-electron microscopy
Authors: Zeng Yi Cheng , Sobti Meghna , Stewart Alastair G.
Published: March 2021

Chaperonins are biomolecular complexes that assist in protein folding. Thermophilic factor 55 (TF55) is a group II chaperonin found in the archaeal genus Sulfolobus that has α, β and γ subunits. Using cryo-electron microscopy, structures of the β-only complex of S. solfataricus TF55 (TF55β) were determined to 3.6–4.2 Å resolution. The structures of the TF55β complexes formed in the presence of ADP or ATP highlighted an open state in which nucleotide exchange can occur before progressing in the refolding cycle.
Knowledge discovery in research on domestic violence: an overview of the last fifty years
Authors: Basilio Marcio Pereira , Pereira Valdecy , de Oliveira Max William Coelho Moreira , da Costa Neto Antonio Fernandes , Moraes Orlinda Claudia Rosa de , Siqueira Samya Cotta Brandão
Published: March 2021

Purpose

The database of the Web of Science (WoS) was searched for publications from January 1945–May 7, 2020 on the topic of domestic violence in titles, abstracts and keywords. The references were analyzed using the R bibliometrix package, and abstracts were analyzed using latent Dirichlet allocation (LDA) with collapsed Gibbs sampling to obtain topics related to domestic violence.

Design/methodology/approach

The aim of the study is to explore and provide an overview of research carried out on domestic violence, in its various aspects, over the past fifty years.

Findings

As a result of the research, the authors can assert that in the last fifty years, 32,298 authors have produced 19,495 documents on the theme of policing strategy and related subjects in 111 countries. Scientific production in this area grows at a rate of 12.81 per year. The United States of America is the leading country in publications with 48.14%, followed by the United Kingdom with 7.57% and Australia with 6.05%. Regarding universities, the highlight is the University of California with 664 publications, followed by the University of London with 515 and the University of North Carolina with 484. As for journals, the highlight is the Journal of Interpersonal Violence, Journal of Family Violence and Violence Against Women, which account for more than 14.32% of all indexed literature. Regarding the authors, the highlight is Campbell J.C and Feder G. Probabilistic topic modeling revealed that 18% of the topics concentrate 90% of all tokens. Topic 1 accounts for 27.9% of the sample and conducts research related to intimate partner violence.

Practical implications

As a practical implication of using the LDA in the bibliographic review, we infer that its capacity to explore large masses of data allows the researcher to explore an infinitely greater amount than the traditional methods of systematic literature review.

Originality/value

The value of these studies is summarized in the presentation of an overview on the theme in the last fifty years, offering the opportunity for other researchers to use this research as a starting point for other analyses.
Revisiting the life of Lucy Garvin, first principal of Sydney Girls High School: expanded biography and use of digital sources
Authors: May Josephine
Published: March 2021

Purpose

The article sets out primarily to fill in some of the gaps in the biography of Lucy Arabella Stocks Garvin (1851–1938), first principal of Sydney Girls High School. As a reflexive exercise stimulated by this biographical research, the second aim is to explore the transformative work of digital sources on the researcher's research processes that in turn generate possibilities for expanded biographical studies in the history of education.

Design/methodology/approach

This article encompasses two approaches: the first uses traditional historical methods in the digital sources to provide an expanded biography of Lucy Garvin. The second is a reflexive investigation of the effects of digitisation of sources on the historian's research processes.

Findings

The advent of digital technologies has opened up more evidence on the life of Lucy Garvin which enables a fuller account both within and beyond the school gate. Digital sources have helped to address important gaps in her life story that challenge current historiographical understandings about her: for example, regarding her initial travel to Australia; her previous career as a teacher in Australia and the circumstances of her appointment as principal; her private and family life; and her involvement in extra school activities. In the process of exploring Garvin's life, the researcher reflected on the work of digital sources and argues that such sources transform the research process by speeding up and de-situating the collection and selection of evidence, while at the same time expanding and slowing the scrutiny of evidence. The ever-expanding array of digital sources, despite its patchiness, can lead to finer grained expanded biographical studies while increasing the provisionality of historical accounts.

Originality/value

The article presents new biographical information about an important early female educational leader in Australia and discusses the impact of digital sources on archival and research processes in the history of women's education.
Female CEOs and corporate innovation
Authors: Prabowo Ronny , Setiawan Doddy
Published: March 2021

Purpose

We investigate the effect of female CEOs on corporate innovation using Indonesian companies. More specifically, this paper aims to answer the following research questions. First, do firms led by female CEOs innovate more or less than firms led by male CEOs? Second, does firm size positively moderate the effect of CEO gender on corporate innovation? Our research questions imply that female CEOs' innovative performance likely depends on the size of their firms.

Design/methodology/approach

Because the dependent variable is a dummy that equals one if the firm was an innovator and zero otherwise, this study employs probit analysis to test the hypotheses empirically. As an alternative test, we use a different measure of the dependent variable (INNOV-corporate innovation) by summing the firm's responses (yes/no) to nine innovation-related questions. Because this alternative measure of INNOV exhibits a count-data characteristic with non-negative integer values and more than 70% of the total sample did not engage in innovation activities at all, this study relies on the zero-inflated Poisson regression in the robustness test.

Findings

We have shown that firms led by female CEOs exhibit a greater probability of being innovators. Further, firm size increases the positive effect of female CEOs on firms' probability of engaging in innovation activities. Further, we also find that when female CEOs manage women-owned firms, their firms are more likely to engage in innovation activities.

Research limitations/implications

This study cannot further investigate the causal relationship between CEO gender and corporate innovation (e.g. by analyzing whether CEOs with different gender affects firm innovation) because it relies on the World Bank Enterprise Survey data. Nevertheless, this study suggests that stakeholders, especially in developing countries like Indonesia, need to encourage more women to hold CEO positions, especially in larger firms, because women-led firms perform better in innovation activities.

Originality/value

Our study thus highlights that female CEOs outperform their male counterparts in innovation activities. These results support the argument that because of gender-based discrimination that they receive, female CEOs are greatly motivated to exhibit greater innovation performance. Further, it is more difficult for women to hold the CEO positions in larger firms because of these firms' more intense managerial job market.
Kidney donation: bridging the gap in the shortage of kidney transplants in Malaysia
Authors: Islahudin Farida , Shahdan Intan Azura , Kua Li Ming
Published: March 2021

Purpose

The purpose of this study was to identify factors that affect willingness to donate kidneys posthumously among Malaysians.

Design/methodology/approach

A questionnaire-based cross-sectional study assessing demographics, attitude, spirituality, knowledge and willingness to donate a kidney was conducted among adult Malaysians with oral informed consent. The total number of samples was 1,001 respondents. Univariate and multivariate logistic regression was performed.

Findings

A total of 29.17% (n = 292) were willing to donate kidneys, while the remaining 70.83% (n = 709) were not. The mean spirituality score was 80.95 ± 13.79 (maximum score 100), mean attitude score was 52.88 ± 8.074 (maximum score 70) and mean knowledge score was 1.84 ± 0.99 (maximum score 5). A higher score demonstrated a stronger spiritual level, positive attitude and better knowledge. Factors affecting willingness to donate a kidney were ethnicity (odds ratio [OR] = 15.625, 95% confidence interval [CI] = 0.043–0.094) and attitude toward kidney donation score (OR = 0.924, 95% CI = 0.902–0.945).

Originality/value

Culture-specific steps to improve programs that may contribute toward improving kidney donation posthumously among Malaysians should be developed. Results drawn from this work demonstrate that policymakers, health-care workers and stakeholders should work together to promote effective policies and program implementation to reduce the ever-increasing gap between the need and shortage crisis of kidney donation.
A cannabis festival in urban space: visitors' motivation and travel activity
Authors: Kang Soo K. , Lee Jaeseok
Published: March 2021

Purpose

The present study aimed at classifying cannabis festival attendees based on their motivation and travel activities, profiling the resultant latent groups with demographic and travel characteristics and examining the association between the groups.

Design/methodology/approach

With a quantitative-exploratory approach, this study collected 392 out-of-state visitors' responses to a cannabis festival in Denver, Colorado and classified them according to their motivation and activity participation. Using the classification results, the study profiled the festival visitors based on their demographic and travel characteristics. Latent class analysis, analysis of variance (ANOVA) and cross-tabulation were employed.

Findings

The results revealed that festival visitors were categorized into four latent groups by motivation and three latent groups by travel activity participation. Regarding motivation, the cannabis seekers (relatively young, White/Caucasian and residents in liberal states) and multi-purpose seekers (relatively young, Black/African American and residents in conservative states) were strongly motivated by cannabis-related factors. For travel activity participation, moderate participants were more likely to be first-time visitors, whereas active and passive participants were classified as repeat visitors.

Originality/value

The current study filled the research gap in the quantitative exploration of cannabis tourism industry in general and cannabis festival segment specifically. The findings contribute to (1) better understanding of out-of-state visitors' motivation and travel behaviors while attending a cannabis themed festival and (2) serving as a seminal work in the context of cannabis tourism literature since the recreational cannabis legalization in the United States.
An investigation into the antecedents of frontline service employee guardianship behaviours
Authors: Potdar Balkrushna , Garry Tony , Gnoth Juergen , Guthrie John
Published: March 2021

Purpose

This study aims to provide empirically generated insights into the drivers of guardianship behaviour among frontline service employees (FLEs) within retail settings.

Design/methodology/approach

The research framework comprises a quantitative survey of 507 frontline service employees at national supermarkets within New Zealand.

Findings

The findings of the survey suggest that service employee perceptions of internal corporate social responsibility (CSR) activities, their level of psychological ownership towards the supermarket and personal moral beliefs, shape their guardianship behaviours and, consequentially, the prevention of in-store deviant behaviours by customers such as shoplifting.

Originality/value

The contribution of this paper is twofold. First, it offers both a conceptual foundation and an empirical-based evaluation of the antecedents and role of guardianship behaviour among frontline service employees. Second, the conceptual model derived from this research may aid practitioners in developing strategies that engender guardianship behaviours in their employees within service contexts.
Weather and distance to fire refugia limit landscape‐level occurrence of fungal disease in an exotic annual grass
Authors: Applestein Cara , Simler‐Williamson Allison B. , Germino Matthew J.
Published: March 2021

The enemy release hypothesis proposes that invasion by exotic plant species is driven by their release from natural enemies (i.e. herbivores and pathogens) in their introduced ranges. However, in many cases, natural enemies, which may be introduced or managed to regulate invasive species, may fail to impact target host populations. Landscape heterogeneity, which can affect both the population dynamics of the pathogen and the susceptibility and the density of hosts, may contribute to why pathogens fail to control hosts despite established negative disease impacts.

We explored patterns of post‐fire infection of the fungal head‐smut pathogenUstilago bullataon the invasive annual cheatgrassBromus tectorum, which has caused the notorious grass‐fire cycle and ecosystem degradation across Western North America. We asked whether infection level was a driver of host density or vice‐versa, and how weather affected infection and how spatial patterns of infection varied with time since fire, using a combination of structural equation modelling (SEM), proportional odds modelling and entropy‐based local indicator of spatial association (ELSA) on data from >700 plots spanning >100,000 ha remeasured annually for 4 years.

Observed infection levels increased with greater prior‐year cheatgrass cover, and disease severity did not suppress cheatgrass populations. Warm, humid fall/winters and proximity to fire refugia (unburned patches) were associated with more infections. Infection clustering was most evident 2–3 years following fire with warm‐wet fall–winter conditions and decreased after two drier, colder winters.

Synthesis. Severity of fungal disease did not result in measurable reductions of populations of a non‐native, invasive host species, cheatgrass, which suggests that natural enemies may not strongly regulate cheatgrass in its introduced range. Landscape heterogeneity associated with disturbance and weather limited population‐level infection of hosts by the fungal pathogen. Disturbance (specifically wildfire) and variable weather are key components of this and similar invasion systems, and likely need to be considered when evaluating disease dynamics and potential for natural enemies to influence invasion potential.
Vitronectin‐activated αvβ3 and αvβ5 integrin signalling specifies haematopoietic fate in human pluripotent stem cells
Authors: Shen Jun , Zhu Yaoyao , Zhang Shuo , Lyu Shuzhen , Lyu Cuicui , Feng Zicen , Hoyle Dixie L. , Wang Zack Z. , Cheng Tao
Published: March 2021

Objectives

Vitronectin (VTN) has been widely used for the maintenance and expansion of human pluripotent stem cells (hPSCs) as feeder‐free conditions. However, the effect of VTN on hPSC differentiation remains unclear. Here, we investigated the role of VTN in early haematopoietic development of hPSCs.

Materials and Methods

A chemically defined monolayer system was applied to study the role of different matrix or basement membrane proteins in haematopoietic development of hPSCs. The role of integrin signalling in VTN‐mediated haematopoietic differentiation was investigated by integrin antagonists. Finally, small interfering RNA was used to knock down integrin gene expression in differentiated cells.

Results

We found that the haematopoietic differentiation of hPSCs on VTN was far more efficient than that on Matrigel that is also often used for hPSC culture. VTN promoted the fate determination of endothelial‐haematopoietic lineage during mesoderm development to generate haemogenic endothelium (HE). Moreover, we demonstrated that the signals through αvβ3 and αvβ5 integrins were required for VTN‐promoted haematopoietic differentiation. Blocking αvβ3 and αvβ5 integrins by the integrin antagonists impaired the development of HE, but not endothelial‐to‐haematopoietic transition (EHT). Finally, both αvβ3 and αvβ5 were confirmed acting synergistically for early haematopoietic differentiation by knockdown the expression of αv, β3 or β5.

Conclusion

The established VTN‐based monolayer system of haematopoietic differentiation of hPSCs presents a valuable platform for further investigating niche signals involved in human haematopoietic development.