bluuebunny/crossref_metadata_2025 huggingface dataset:
Revisiting regulatory decoherence and phenotypic integration: accounting for temporal bias in co-expression analyses
Authors: Cai Haoran , Des Marais David L.
Published: April 2021

Environment can alter the degree of phenotypic variation and covariation, potentially influencing evolutionary trajectories. However, environment-driven changes in phenotypic variation remain understudied. In an effort to exploit the abundance of RNASequencing data now available, an increasing number of ecological studies rely on population-level correlation to characterize the plastic response of the entire transcriptome and to identify environmentally responsive molecular pathways. These studies are fundamentally interested in identifying groups of genes that respond in concert to environmental shifts. We show that population-level differential co-expression exhibits biases when capturing changes of regulatory activity and strength in rice plants responding to elevated temperature. One possible cause of this bias is regulatory saturation, the observation that detectable co-variance between a regulator and its target may be low as their transcript abundances are induced. This phenomenon appears to be particularly acute for rapid-onset environmental stressors. However, our results suggest that temporal correlations may be a reliable means to detect transient regulatory activity following rapid onset environmental perturbations such as temperature stress. Such temporal bias is likely to confound the studies of phenotypic integration, where high-order organismal traits are hypothesized to be more integrated with strong correlation under stressful conditions, while recent transcriptome studies exhibited weaker coexpression between genes under stressful conditions. Collectively, our results point to the need to account for the nuances of molecular interactions and the possibly confounding effects that these can introduce into conventional approaches to study transcriptome datasets.
Flexible control of Pavlovian-instrumental transfer based on expected reward value
Authors: Marshall Andrew T. , Halbout Briac , Munson Christy N. , Hutson Collin , Ostlund Sean B.
Published: April 2021

The Pavlovian-instrumental transfer (PIT) paradigm is widely used to assay the motivational influence of reward-predictive cues, reflected by their ability to invigorate instrumental behavior. Leading theories assume that a cue’s motivational properties are tied to predicted reward value. We outline an alternative view which recognizes that reward-predictive cues may suppress rather than motivate instrumental behavior under certain conditions, an effect termed positive conditioned suppression. We posit that cues signaling imminent reward delivery tend to inhibit instrumental behavior, which is exploratory by nature, in order to facilitate efficient retrieval of the expected reward. According to this view, the motivation to engage in instrumental behavior during a cue should beinverselyrelated to the value of the predicted reward, since there is more to lose by failing to secure a high-value reward than a low-value reward. We tested this hypothesis in rats using a PIT protocol known to induce positive conditioned suppression. In Experiment 1, cues signaling different reward magnitudes elicited distinct response patterns. Whereas the 1-pellet cue increased instrumental behavior, cues signaling 3 or 9 pellets suppressed instrumental behavior and elicited high levels of food-port activity. Experiment 2 found that reward-predictive cues suppressed instrumental behavior and increased food-port activity in a flexible manner that was disrupted by post-training reward devaluation. Further analyses suggest that these findings were not driven by overt competition between the instrumental and food-port responses. We discuss how the PIT task may provide a useful tool for studying cognitive control over cue-motivated behavior in rodents.
Exploring the metastatic role of the inhibitor of apoptosis BIRC6 in Breast Cancer
Authors: Gómez Bergna Santiago M. , Marchesini Abril , Morales Leslie C. Amorós , Arrías Paula N. , Farina Hernán G. , Romanowski Víctor , Gottardo M. Florencia , Pidre Matias L.
Published: April 2021

Breast cancer is the most common cancer as well as the first cause of death by cancer in women worldwide. BIRC6 (baculoviral IAP repeat-containing protein 6) is a member of the inhibitors of apoptosis protein family thought to play an important role in the progression or chemoresistance of many cancers. The aim of the present work was to investigate the role of apoptosis inhibitor BIRC6 in breast cancer, focusing particularly on its involvement in the metastatic cascade.

We analyzed BIRC6 mRNA expression levels and Copy Number Variations (CNV) in three breast cancer databases from The Cancer Genome Atlas (TCGA) comparing clinical and molecular attributes. Genomic analysis was performed using CBioportal platform while transcriptomic studies (mRNA expression levels, correlation heatmaps, survival plots and Gene Ontology) were performed with USC Xena and R. Statistical significance was set at p-values less than 0.05.

Our analyses showed that there was a differential expression of BIRC6 in cancer samples when compared to normal samples. CNV that involve amplification and gain of BIRC6 gene were correlated with negative hormone receptor tumors, higher prognostic indexes, younger age at diagnosis and both chemotherapy and radiotherapy administration. Transcriptomic and gene-ontology analyses showed that, in conditions of high BIRC6 mRNA levels, there are differential expression patterns in apoptotic, proliferation, and metastatic pathways.

In summary, ourin silicoanalyses suggest that BIRC6 exhibits an antiapoptotic, pro-proliferative and an apparent pro-metastatic role and could be a relevant molecular target for treatment of Breast Cancer tumors.
Using camera traps to determine occupancy and breeding in burrowing seabirds
Authors: Bird Jeremy P. , Fuller Richard A. , Pascoe Penny P. , Shaw Justine D. S.
Published: April 2021

Burrowing seabirds are important in commercial, ecological and conservation terms. Many populations are in flux owing to both negative and positive anthropogenic impacts, but their ecology makes measuring changes difficult. Reliably recording key metrics, the proportion of burrows with breeding pairs, and the success of breeding attempts, requires burrow-level information on occupancy. We investigated the use of camera traps positioned at burrow entrances for determining the number of breeding pairs in a sample to inform population estimates, and for recording breeding success. Linear Discriminant Analyses of time series activity patterns from camera traps successfully partitioned breeding and non-breeding burrows at different stages of the breeding season and had reasonable predictive ability to determine breeding status on a small test dataset. Compared with traditional techniques for determining burrow occupancy (e.g. manual burrow inspection and playback of conspecific calls at burrow entrances), camera traps can reduce uncertainty in estimated breeding success and potentially breeding status of burrows. Significant up-front investment is required in terms of equipment and human resources but for long-term studies camera traps can deliver advantages, particularly when unanticipated novel observations and the potential for calibrating traditional methods with cameras are factored in.
Behavioral and Neural Representations en route to Intuitive Action Understanding
Authors: Tarhan Leyla , De Freitas Julian , Konkle Talia
Published: April 2021

When we observe another person’s actions, we process many kinds of information – from how their body moves to the intention behind their movements. What kinds of information underlie our intuitive understanding about how similar actions are to each other? To address this question, we measured the intuitive similarities among a large set of everyday action videos using multi-arrangement experiments, then used a modeling approach to predict this intuitive similarity space along three hypothesized properties. We found that similarity in the actors’ inferred goals predicted the intuitive similarity judgments the best, followed by similarity in the actors’ movements, with little contribution from the videos’ visual appearance. In opportunistic fMRI analyses assessing brain-behavior correlations, we found suggestive evidence for an action processing hierarchy, in which these three kinds of action similarities are reflected in the structure of brain responses along a posterior-to-anterior gradient on the lateral surface of the visual cortex. Altogether, this work joins existing literature suggesting that humans are naturally tuned to process others’ intentions, and that the visuo-motor cortex computes the perceptual precursors of the higher-level representations over which intuitive action perception operates.
Single-cell transcriptomics of peripheral blood in the aging mouse
Authors: Teo Yee Voan , Webb Ashley , Neretti Nicola
Published: April 2021

Compositional and transcriptional changes in the hematopoietic system have been used as biomarkers of immunosenescence and aging. Here, we use single-cell RNA-sequencing to study the aging peripheral blood in mice, and characterize the changes in cell-type composition and transcriptional profiles associated with age. We identified 17 clusters from a total of 14,588 single cells. We detected a general upregulation of antigen processing and presentation and chemokine signaling pathways and a downregulation of genes involved in ribosome pathways with age. We also observed increased percentage of cells expressing markers of senescence, Cdkn1a and Cdkn2a, in old peripheral blood. In addition, we detected a cluster of activated T cells that are exclusively found in old blood, with lower expression of Cd28 and higher expression of Bcl2 and Cdkn2a, suggesting that the cells are senescent and resistant to apoptosis.
Expression of cell-adhesion molecules inE. coli: a high-throughput method to identify paracellular modulators
Authors: Rollins Jay , Worthington Tyler , Hooke Emily , Hobson Joseph , Wengler Jacob , Hope Sandra , Mizrachi Dario
Published: April 2021

Cell-adhesion molecules (CAM) are membrane proteins responsible for cell-cell interactions or cell-extracellular matrix interactions. Among these proteins, claudins (CLDN), occludin (OCLN), and junctional adhesion molecules (JAM) are components of the tight junction (TJ), the single proteic structure tasked with safeguarding the paracellular space. The TJ is responsible for controlled permeability of blood-tissue barriers, regulating the passage of molecule passage by size and charge. Currently there is no translational solution to manipulate the TJ with the exception of Focused Ultra-sound (FUS) and Micro bubbling (MB) techniques, still in clinical trials. Here we describe the expression of TJ proteins in the outer membrane ofE. coliand report its consequences. When expression is induced, the unicellular behavior ofE. coliis replaced with multicellular aggregations that can be quantified using Flow Cytometry (FC). The adhesion properties of the aggregates are representative of the individual membrane proteins expressed. This method, called iCLASP (inspection of cell-adhesion molecules aggregation through FC protocols), allows the high-throughput interrogation of small-molecules influence on paracellular permeability, enabling for the first time the discovery of its modulators for therapeutic strategies.
Active Cytoskeletal Composites Display Emergent Tunable Contractility and Restructuring
Authors: Lee Gloria , Leech Gregor , Lwin Pancy , Michel Jonathan , Currie Christopher , Rust Michael J. , Ross Jennifer L. , McGorty Ryan J. , Das Moumita , Robertson-Anderson Rae M.
Published: April 2021

The cytoskeleton is a model active matter system that controls diverse cellular processes from division to motility. While both active actomyosin dynamics and actin-microtubule interactions are key to the cytoskeleton’s versatility and adaptability, an understanding of their interplay is lacking. Here, we couple microscale experiments with mechanistic modeling to elucidate how connectivity, rigidity, and force-generation affect emergent material properties in in vitro composites of actin, tubulin, and myosin. We use time-resolved differential dynamic microscopy and spatial image autocorrelation to show that ballistic contraction occurs in composites with sufficient flexibility and motor density, but that a critical fraction of microtubules is necessary to sustain controlled dynamics. Our active double-network models reveal that percolated actomyosin networks are essential for contraction, but that networks with comparable actin and microtubule densities can uniquely resist mechanical stresses while simultaneously supporting substantial restructuring. Our findings provide a much-needed blueprint for designing cytoskeleton-inspired materials that couple tunability with resilience and adaptability.
Septins regulate border cell shape and surface geometry downstream of Rho
Authors: Gabbert Allison M. , Mondo James A. , Campanale Joseph P. , Mitchell Noah P. , Myers Adele , Streichan Sebastian J. , Miolane Nina , Montell Denise J.
Published: April 2021

Septins self-assemble into polymers that bind and deform membranesin vitroand regulate diverse cell behaviorsin vivo. How theirin vitroproperties relate to theirin vivofunctions is under active investigation. Here we uncover requirements for septins in detachment and motility of border cell clusters in theDrosophilaovary. Septins and myosin colocalize dynamically at the cluster periphery and share phenotypes, but surprisingly do not impact each other. Instead, Rho independently regulates myosin activity and septin localization. Active Rho recruits septins to membranes while inactive Rho sequesters septins in the cytoplasm. Mathematical analyses reveal how manipulating septin expression alters cluster shape and surface geometry. This study shows that the level of septin expression regulates surface properties at different scales. This work suggests that downstream of Rho, septins tune surface deformability while myosin controls contractility, the combination of which govern cluster shape and movement.
Differential variation of NSCs in root branch orders ofFraxinus mandshuricaRupr. seedlings across different drought intensities and soil substrates
Authors: Ji Li , Liu Yue , Wang Jun , Lu Zhimin , Yang Yuchun , Zhang Lijie
Published: April 2021

Non-structural carbohydrates (NSCs) facilitate plants adapt to drought stress, could characterize trees growth and survival ability and buffer against external disturbances. Previous studies have focused on the distribution and dynamics of NSCs among different plant organs under drought conditions. However, discussion about the NSC levels of fine roots in different root branch order were little, especially the relationship between fine root trait variation and NSCs content. The aim of the study is to shed light into the synergistic variation of fine root traits and NSC content in different root branch order under different drought and soil substrate conditions. 2-year-oldFraxinus mandshuricaRupr. potted seedlings were planted in three different soil substrates (humus, loam and sandy-loam soil) and conducted to four drought intensities (CK, mild drought, moderate drought and severe drought) for two months. With the increase of drought intensity, the biomass of fine roots decreased significantly. Under the same drought intensity, seedlings in sandy-loam soil have higher root biomass, and the coefficient of variation of fifth-order roots (37.4%, 44.5% and 53.0% in humus, loam and sandy loam, respectively) is higher than that of lower-order roots. With the increase of drought intensity, the specific root length (SRL) and average diameter (AD) of all five orders increased and decreased, respectively. The fine roots in humus soil had higher soluble sugar content and lower starch content. Also, the soluble sugar and starch content of fine roots showed decreasing and increasing tendency respectively. Soluble sugar and starch explain the highest degree of total variation of fine root traits, that is 32.0% and 32.1% respectively. With ascending root order, the explanation of the variation of root traits by starch decreased (only 6.8% for fifth-order roots). The response of different root branch order fine root morphological traits ofF. mandshuricaseedlings to resource fluctuations ensures that plants maintain and constructure the root development by an economical way to obtain more resources.
Single-cell analysis of early chick hypothalamic development reveals that hypothalamic cells are induced from prethalamic-like progenitors
Authors: Kim Dong Won , Place Elsie , Chinnaiya Kavitha , Manning Elizabeth , Sun Changyu , Dai Weina , Ohyama Kyoji , Burbridge Sarah , Placzek Marysia , Blackshaw Seth
Published: April 2021

The hypothalamus is an evolutionarily ancient brain region that regulates many innate behaviors, but its development is still poorly understood. To identify molecular mechanisms controlling hypothalamic specification and patterning, we used single-cell RNA-Seq to profile multiple stages of early hypothalamic development in the chick. We observe that hypothalamic neuroepithelial cells are initially induced from prethalamic-like cells. Two distinct hypothalamic progenitor populations emerge later, which give rise to paraventricular/mammillary and tuberal hypothalamus. At later developmental stages, the regional organization of the chick and mouse hypothalamus closely resembles one another. This study identifies selective markers for major subdivisions of the developing chick hypothalamus and many uncharacterized candidate regulators of hypothalamic patterning and neurogenesis. As proof of concept for the power of the dataset, we demonstrate that follistatin, a novel prethalamic progenitor-like marker, inhibits hypothalamic induction. This study both clarifies the organization of the early developing hypothalamus and identifies novel molecular mechanisms controlling hypothalamic induction, regionalization, and neurogenesis.

Highlights

Early hypothalamic development was profiled in chick using scRNA-Seq and multiplexed HCR.

Hypothalamic cells are induced from prethalamic-like neuroepithelial cells.

Distinct paraventricular/mammillary and tuberal progenitor populations emerge later, and hypothalamic organization is evolutionarily conserved.

Prethalamic progenitor-derived follistatin inhibits hypothalamic specification.

Graphical Abstract
Candelabrum cells are molecularly distinct, ubiquitous interneurons of the cerebellar cortex with specialized circuit properties
Authors: Osorno Tomas , Rudolph Stephanie , Nguyen Tri , Kozareva Velina , Nadaf Naeem , Macosko Evan Z. , Lee Wei-Chung Allen , Regehr Wade G.
Published: April 2021

To understand how the cerebellar cortex transforms mossy fiber (MF) inputs into Purkinje cell (PC) outputs, it is vital to delineate the elements of this circuit. Candelabrum cells (CCs) are enigmatic interneurons of the cerebellar cortex that have been identified based on their morphology, but their electrophysiological properties, synaptic connections, and function remain unknown. Here we clarify these properties using electrophysiology, snRNA sequencing,in situhybridization, and serial electron microscopy. We find that CCs are the most abundant PC layer interneuron. They are GABAergic, molecularly distinct, and present in all cerebellar lobules. Their high resistance renders CC firing highly sensitive to synaptic inputs. CCs are excited by MFs and granule cells, and strongly inhibited by PCs. CCs in turn inhibit molecular layer interneurons, which leads to PC disinhibition. Thus, inputs, outputs and local signals all converge onto CCs to allow them to assume a unique role in controlling cerebellar output.
Multiple 9-1-1 complexes promote homolog synapsis, DSB repair, and ATR signaling during mammalian meiosis
Authors: Pereira Catalina , Arroyo-Martinez Gerardo A. , Guo Matthew Z. , Downey Michael S. , Kelly Emma R. , Grive Kathryn J. , Mahadevaiah Shantha K. , Sims Jennie , Faça Vitor Marcel , Tsai Charlton , Schiltz Carl J. , Wit Niek , Jacobs Heinz , Clark Nathan L. , Freire Raimundo , Turner James M. A. , Lyndaker Amy M. , Brieño-Enríquez Miguel A. , Cohen Paula E. , Smolka Marcus B. , Weiss Robert S.
Published: April 2021

DNA damage response mechanisms have meiotic roles that ensure successful gamete formation. While completion of meiotic double-strand break (DSB) repair requires the canonical RAD9A-RAD1-HUS1 (9A-1-1) complex, mammalian meiocytes also express RAD9A and HUS1 paralogs, RAD9B and HUS1B, predicted to form alternative 9-1-1 complexes. The RAD1 subunit is shared by all predicted 9-1-1 complexes and localizes to meiotic chromosomes even in the absence of HUS1 and RAD9A. Here we report that testis-specific RAD1 disruption resulted in impaired DSB repair, germ cell depletion and infertility. UnlikeHus1orRad9adisruption,Rad1loss also caused defects in homolog synapsis, ATR signaling and meiotic sex chromosome inactivation. Comprehensive testis phosphoproteomics revealed that RAD1 and ATR coordinately regulate numerous proteins involved in DSB repair, meiotic silencing, synaptonemal complex formation, and cohesion. Together, these results establish critical roles for both canonical and alternative 9-1-1 complexes in meiotic ATR activation and successful prophase I completion.
Sub-millisecond conformational transitions of short single-stranded DNA lattices by photon correlation single-molecule FRET
Authors: Israels Brett , Albrecht Claire S. , Dang Anson , Barney Megan , von Hippel Peter H. , Marcus Andrew H.
Published: April 2021

Thermally-driven conformational fluctuations (or ‘breathing’) of DNA plays important roles in the function and regulation of the ‘macromolecular machinery of genome expression.’ Fluctuations in double-stranded (ds) DNA are involved in the transient exposure of pathways to protein binding sites within the DNA framework, leading to the binding of regulatory proteins to single-stranded (ss) DNA templates. These interactions often require that the ssDNA sequences, as well as the proteins involved, assume transient conformations critical for successful binding. Here we use microsecond-resolved single-molecule Förster Resonance Energy Transfer (smFRET) experiments to investigate the backbone fluctuations of short oligothymidine [oligo(dT)n] templates within DNA constructs that can also serve as models for ss-dsDNA junctions. Such junctions, as well as the attached ssDNA sequences, are involved in the binding of ssDNA binding (ssb) proteins that control and integrate the mechanisms of DNA replication complexes. We have used these data to determine multi-order time-correlation functions (TCFs) and probability distribution functions (PDFs) that characterize the kinetic and thermodynamic behavior of the system. We find that the oligo(dT)ntails of ss-dsDNA constructs inter-convert, on sub-millisecond time-scales, between three macrostates with distinctly different end-to-end distances. These are: (i) a ‘compact’ macrostate that represents the dominant species at equilibrium; (ii) a ‘partially extended’ macrostate that exists as a minority species; and (iii) a ‘highly extended’ macrostate that is present in trace amounts. We propose a model for ssDNA secondary structure that advances our understanding of how spontaneously formed nucleic acid conformations may facilitate the activities of ssDNA associating proteins.

Significance Statement

The genetic information of living organisms is encoded as sequences of nucleic acid bases in DNA, and is protected by the thermodynamically stable secondary structure of the Watson-Crick double helix. The processing and manipulation of gene sequences by ‘macromolecular machines’ requires that stable segments of duplex DNA be disrupted, and that single-stranded (ss) DNA templates be transiently exposed to the binding sites of DNA associating proteins within the cellular environment. Here we elucidate some of the defining features that control the stability and dynamics of ssDNA secondary structure, using time-resolved methods to detect the presence of transient unstable conformations. Understanding the nature of these instabilities is central to elucidating the mechanisms by which ssDNA templates facilitate protein binding and function.
Fulfilment of technical and hygienic requirements among street food vendors in Slovenia
Authors: Prevolšek Vanja , Ovca Andrej , Jevšnik Mojca
Published: April 2021

Purpose

This cross-sectional study aimed to evaluate the compliance of hygienic and technical standards of street food vendors in Slovenia with the requirements of the general hygienic food principals set in the Codex Alimentarius and Regulation (EC) No. 852/2004 on the hygiene of foodstuffs.

Design/methodology/approach

Food vendors were observed directly and discretely using a semi-structured observation sheet that allowed fast evaluation. The employee's behaviour was not affected during the observations because they were not aware of being observed. Each observation lasted approximately 30 min. Food vendors were divided into groups according to their location, type of facility, number of employees and type of food sold.

Findings

Depending on the type of street vendor, more inconsistencies were found amongst food stands compared to food trucks and kiosks. Most food trucks and kiosks scored very high in both personal and hygienic-technical standards. Some of the major inconsistencies were lack of suitably located washbasins, improper hand-washing technique, improper waste management, working surfaces that were inadequately separated from consumers, and inconsistent maintenance of the cold chain. Food handlers have been confirmed as a critical risk factor.

Research limitations/implications

Despite methodology validation, the data was collected by a single observer, limiting the ability to obtain a more reliable estimate of the observations. The sample was disproportionate according to the type of street food facilities.

Practical implications

The results provide a basis for (1) national professional guidelines of good hygiene practices for food business operators, which should cover street food vendors more extensively in future updates, and (2) the development of food safety training programmes tailored for street vendors.

Originality/value

The study provides valuable insights into current hygienic-technical conditions of the street food vending sector.
Eastern European immigrants in the UK
Authors: Rosso Anna
Published: April 2021

Purpose

The paper aims at examining wage developments among Eastern European immigrants vs UK natives before and after the 2004 enlargement by measuring the extent to which inter-group wage differentials are explainable by these groups' changing attributes or by differences in returns to these characteristics. The enlargement has been a defining moment in British recent history and may have contributed to the unfolding of the events that have culminated in Brexit.

Design/methodology/approach

The paper uses a quantitative analysis of the immigrant–native wage gap across the entire distribution by applying the methodology known as the unconditional quantile regression. The analysis is performed before and after the 2004 European Union enlargement to Eastern countries. The data used is the British Labour Force Survey (UK LFS) from 1998 to 2008.

Findings

At all distribution points, a major role is played by occupational downgrading, which increases over time. The results further suggest that the decreased wage levels at the top of the distribution stem mainly from low transferability of skills acquired in the source country.

Research limitations/implications

The UK LFS does not allow to follow individuals for a long period of time. For this reason, the main limitation of the study is the impossibility to measure for individual-level trajectories in their labour market integration and to account for return migration.

Originality/value

The analysis provides a detailed picture of the wage differences between Eastern European immigrants and natives along the whole wage distribution. The paper also identifies possible causes of the wage gap decrease for EU8 immigrant workers after 2008.
Impact of interpersonal justice and information accuracy in a pharmaceutical supply chain: a survey-based analysis
Authors: Lee Changjoon
Published: April 2021

Purpose

This study aims to investigate the influence of interpersonal justice, a sub-concept of interactional justice, on information accuracy and logistics performance in the pharmaceutical supply chain.

Design/methodology/approach

For this purpose, 600 pharmacies in Korea were surveyed through questionnaires distributed via mail and direct visits and 293 valid responses were used for statistical analysis.

Findings

According to the results, the perception of interpersonal justice between buyers and sellers showed a positive effect on information accuracy, which, in turn, had a positive effect on logistics performance within the supply chain. In contrast, interpersonal justice showed an insignificant effect on logistics performance.

Practical implications

This signifies that if buyers treat sellers with respect and politeness, the accuracy of the information provided by the seller will improve, which may ultimately have a positive effect on performance. In addition, ethical behavior by both parties ensures information accuracy in the supply chain, even though it does not directly affect performance.

Originality/value

In contrast to previous research, which has focused on distributive and procedural justice, the study investigates interpersonal justice and its effects on information accuracy and logistics performance in the pharmaceutical supply chain.
Social transformation interventions at South African public universities
Authors: Abed Sameera , Ackers Barry
Published: April 2021

Purpose

The purpose of this study was to identify the transformation disclosures in the publicly available annual reports of South African public universities and to establish the extent to which universities account to their stakeholders about how they have discharged their transformation obligations.

Design/methodology/approach

This exploratory qualitative study involves a thematic content analysis of publicly available annual reports using ATLAS.ti software to identify and categorise transformation interventions disclosed by South African public universities.

Findings

This empirical study identifies several interventions that universities have introduced to facilitate access to and successful completion of tertiary studies by students. Some of the disclosed mechanisms include the provision of financial aid, student support and counselling, tutoring and mentoring and ICT enhancements and the introduction of language policies. The results also highlighted several challenges to sustainable transformation including funding, social and academic barriers and infrastructural challenges experienced by universities.

Originality/value

According to the authors’ knowledge, this study represents one of the first studies to use the public disclosures in the annual reports of public universities to identify interventions introduced to facilitate transformation of the student body. Despite its South African orientation, the observations have implications for universities worldwide experiencing similar challenges, especially in developing countries.
Assessing social-psychological functioning between Malaysian and Indonesian undergraduates: a Rasch model analysis
Authors: Khairani Ahamd Zamri , Ahmad Nor Shafrin , Sutatminingsih Raras
Published: April 2021

Purpose

The purpose of this study is to assess the psychometric properties of the Flourishing Scale (FS) by employing samples of Malaysian and Indonesian undergraduates. In addition, the present study seeks to identify aspects of the social-psychological functioning that were perceived differently by both samples.

Design/methodology/approach

The present study employs the descriptive design to provide descriptions about psychometric properties of the FS. In total, 351 first-year undergraduates were employed as samples of the study. The authors employed the Rasch measurement model framework using the quantitative approach to analyze the data.

Findings

Generally, the results showed that the FS demonstrated acceptable psychometric properties for both samples. However, the Malaysian and Indonesian samples differ significantly in half of the social-psychological functioning aspects.

Research limitations/implications

One limitation of the study was the relatively small sample size students in one higher education institution in each country. In addition, in both countries, the undergraduates demonstrated obligatory roles toward their lecturers. Therefore, their response might not be truthful and only respond as requested.

Originality/value

Whilst social psychological functioning has been identified as important aspects of well-being, the construct has yet to be studied in the eastern culture in Malaysia and Indonesia.
Understanding the elements of a quality rural/remote interprofessional education activity: A rough guide
Authors: Waller Susan , Walker Lorraine , Farthing Annie , Brown Leanne , Moran Monica
Published: April 2021

Aims

To offer a rough guide to a quality rural/remote interprofessional educational activity.

Context

Australian remote and rural interprofessional undergraduate placements offered in Modified Monash Model 3‐6 locations.

Approach

Biggs' triple P framework from the interprofessional educational literature and Allport's contact hypothesis are used to describe map, and explore the educational dimensions and positive elements, of a quality rural/remote interprofessional educational activity.

Conclusion

Delivery of a quality interprofessional educational activity requires attention to all dimensions of the activity with acknowledgement of the value of the remote or rural contexts. Interprofessional learning requires constructive alignment and positive contact conditions to ensure a quality and sustained experience.
Silencing of SARS‐CoV‐2 with modified siRNA‐peptide dendrimer formulation
Authors: Khaitov Musa , Nikonova Alexandra , Shilovskiy Igor , Kozhikhova Ksenia , Kofiadi Ilya , Vishnyakova Lyudmila , Nikolskii Alexander , Gattinger Pia , Kovchina Valeria , Barvinskaia Ekaterina , Yumashev Kirill , Smirnov Valeriy , Maerle Artem , Kozlov Ivan , Shatilov Artem , Timofeeva Anastasiia , Andreev Sergey , Koloskova Olesya , Kuznetsova Nadezhda , Vasina Daria , Nikiforova Maria , Rybalkin Sergei , Sergeev Ilya , Trofimov Dmitriy , Martynov Alexander , Berzin Igor , Gushchin Vladimir , Kovalchuk Aleksey , Borisevich Sergei , Valenta Rudolf , Khaitov Rakhim , Skvortsova Veronica
Published: April 2021

Background

First vaccines for prevention of Coronavirus disease 2019 (COVID‐19) are becoming available but there is a huge and unmet need for specific forms of treatment. In this study we aimed to evaluate the anti‐SARS‐CoV‐2 effect of siRNA both in vitro and in vivo.

Methods

To identify the most effective molecule out of a panel of 15 in silico designed siRNAs, an in vitro screening system based on vectors expressing SARS‐CoV‐2 genes fused with the firefly luciferase reporter gene and SARS‐CoV‐2‐infected cells was used. The most potent siRNA, siR‐7, was modified by Locked nucleic acids (LNAs) to obtain siR‐7‐EM with increased stability and was formulated with the peptide dendrimer KK‐46 for enhancing cellular uptake to allow topical application by inhalation of the final formulation – siR‐7‐EM/KK‐46. Using the Syrian Hamster model for SARS‐CoV‐2 infection the antiviral capacity of siR‐7‐EM/KK‐46 complex was evaluated.

Results

We identified the siRNA, siR‐7, targeting SARS‐CoV‐2 RNA‐dependent RNA polymerase (RdRp) as the most efficient siRNA inhibiting viral replication in vitro. Moreover, we showed that LNA‐modification and complexation with the designed peptide dendrimer enhanced the antiviral capacity of siR‐7 in vitro. We demonstrated significant reduction of virus titer and lung inflammation in animals exposed to inhalation of siR‐7‐EM/KK‐46 in vivo.

Conclusions

Thus, we developed a therapeutic strategy for COVID‐19 based on inhalation of a modified siRNA‐peptide dendrimer formulation. The developed medication is intended for inhalation treatment of COVID‐19 patients.
Predictive mapping of plant diversity in an arid mountain environment (Gebel Elba, Egypt)
Authors: Abutaha Maged M. , El‐Khouly Ahmed A. , Jürgens Norbert , Oldeland Jens
Published: April 2021

Aim

This study aimed to predict the alpha and beta plant diversity of an arid mountain based on environmental variables derived from remotely sensed and ground truth data.

Location

Gebel Elba, Egypt.

Methods

Based on 133 vegetation plots of 100 m2, we calculated alpha (Shannon index) and beta [the first ordination axis of nonmetric multidimensional scaling (NMDS1)] plant diversity. Generalized additive models (GAMs) were used to map alpha and beta diversity based on various environmental variables derived from a digital elevation model, the SoilGrids dataset, and very high resolution PlanetScope satellite imagery. The predictive models for alpha and beta diversity were mapped within the northern slopes of Gebel Elba. An ANOVA post hoc test was used to compare Shannon index and NMDS1 values among plant communities.

Results

The selected models revealed the importance of altitude, landforms, solar insolation, catchment area, and modified soil‐adjusted vegetation index for Shannon diversity and NMDS1. The GAMs explained 54.9% of Shannon diversity and 80.6% of NMDS1. The predicted diversity maps showed that the mountainous area was more diverse and substantially different from the open desert. The post‐hoc test revealed a clear separation of mountain and desert vegetation.

Conclusions

Employing remotely sensed variables combined with ground truth data offers great opportunities for exploring spatial patterns of biodiversity. By mapping alpha and beta diversity, it was possible to determine the spatial distribution of plant diversity in Gebel Elba; the results highlighted the importance of the wadi systems and higher slopes of this mountain area. We expect our findings can be generalized to similar arid mountains in the region.
Fatal adverse drug reactions: A worldwide perspective in the World Health Organization pharmacovigilance database
Authors: Montastruc Jean‐Louis , Lafaurie Margaux , de Canecaude Claire , Durrieu Geneviève , Sommet Agnès , Montastruc François , Bagheri Haleh
Published: April 2021

Aims

Adverse drug reactions (ADRs) are important causes of death. However, the main involved drugs are relatively unknown. The present study was performed to characterise death‐related drugs recorded in a large pharmacovigilance database during the last 10 years.

Methods

A retrospective analysis of VigiBase, the World Health Organization pharmacovigilance database, was performed investigating fatal ADRs registered between 1 January 2010 and 31 December 2019 in male and female patients aged ≥18 years and reported by physicians. Analyses were descriptive investigating age, sex and suspected drugs. Differences in reporting according to sex, age and continents were investigated using disproportionality analysis with calculation of reporting odds ratio and its 95% confidence interval.

Results

Among the 23 millions ADRs recorded in VigiBase, 3 250 967 were included with 43 685 fatal. They were reported mainly in patients older than 75 years. The 3 most frequently involved drug classes were antineoplastic/immunomodulating drugs followed by nervous system and cardiac drugs. The top 3 individual drugs were denosumab, lenalidomide and thalidomide with marked differences according to age, sex, continents and countries. The risk of reporting fatal ADRs was higher in males, in the Americas and in patients ≥65 years.

Conclusion

Fatal ADRs registered in a large pharmacovigilance database during the last 10 years correspond to just over 1% of the total number of ADRs. They occurred more in males, after 65 years and with antineoplastic/immunomodulating drugs in general. Our study also highlighted, for the first time, important differences in fatal ADRs between continents and countries.
Novel positive allosteric modulator of protease‐activated receptor 1 promotes skin wound healing in hairless mice
Authors: Seo Yohan , Heo Yunkyung , Jo Sungwoo , Park So‐Hyeon , Lee Chulho , Chang Jiwon , Jeon Dong‐Kyu , Kim Tae Gun , Han Gyoonhee , Namkung Wan
Published: April 2021

Background and Purpose

Protease‐activated receptor 1 (PAR1) is a GPCR expressed in several skin cell types, including keratinocyte and dermal fibroblast. PAR1 activation plays a crucial role in the process of skin wound healing such as thrombosis, inflammation, proliferation and tissue repair. In the present study, we identified a novel positive allosteric modulator of PAR1, GB83, and investigated its effect on skin wound healing.

Experimental Approach

The enhancement of PAR1 activity by GB83 was measured using Fluo‐4 calcium assay. In silico docking analysis of GB83 in PAR1 was performed using dock ligands method (CDOCKER) with CHARMm force field. Effects of GB83 on cell viability and gene expression were observed using MTS assay and quantitative real‐time PCRs, respectively. SKH‐1 hairless mice were used to investigate the wound healing effect of GB83.

Key Results

We demonstrated that GB83 did not activate PAR1 by itself but strongly enhanced PAR1 activation by thrombin and PAR1‐activating peptide (AP). In silico docking analysis revealed that GB83 can bind to the PAR1 binding site of vorapaxar. GB83 significantly promoted PAR1‐mediated cell viability and migration. In addition, the enhancement of PAR1 activity by GB83 strongly increased gene expression of TGF‐β, fibronectin and type I collagen in vitro and promoted skin wound healing in vivo.

Conclusion and Implications

Our results revealed that GB83 is the first positive allosteric modulator of PAR1 and it can be a useful pharmacological tool for studying PAR1 and a potential therapeutic agent for skin wound healing.
Cutaneous involvement by T‐cell prolymphocytic leukemia presenting as livedoid vasculopathy
Authors: Leckey Bruce D. , Kheterpal Meenal K. , Selim M. Angelica , Al‐Rohil Rami N.
Published: April 2021

T‐cell prolymphocytic leukemia (T‐PLL) is a rare, aggressive neoplasm derived from post‐thymic T‐cells. Patients are typically middle aged with a slight male predominance who present with a high white blood cell count, hepatosplenomegaly, lymphadenopathy, and other symptoms typically associated with leukemia. Although cutaneous involvement has been reported in up to 30% of cases of T‐PLL, to our knowledge, none have presented with a presentation resembling livedoid vasculopathy. In the correct clinical context, an underlying hematolymphoid neoplasm should be included in the differential diagnosis of a patient presenting with livedoid vasculopathy.
Dental students’ experience of conscious sedation: A qualitative review of student reflections
Authors: Crowe Hannah L. , Woolley Stephen M.
Published: April 2021

Introduction

The UK General Dental Council (GDC) requires dental graduates to competently identify, manage and refer patients with dental pain and anxiety. This study aimed to explore sedation training experience quantitatively and qualitatively through individual reflective logs.

Materials & Methods

A single‐centred mixed‐methods evaluation of teaching, within a UK university conscious sedation department. Fourth‐year dental students undertook lectures and supervised clinical sessions following the undergraduate curriculum. Patient attendance patterns, individual experience and group experience were analysed descriptively. Reflective log sheets were analysed by Thematic Framework Analysis.

Results

Seventy‐two students participated. Of 153 booked patients, 79 (51.6%) attended of which 74 (48.4%) were treated by undergraduates. The mean performed inhalation sedation and intravenous sedation cases per student were 1 and 0.8, respectively. Three students (4%) assisted only. Group experience varied. Three themes arose from reflections: consolidation of theory and learning; confidence through experience; and responding to challenges.

Discussion

Whilst experience quotas were not met, GDC requirements for increasing students’ knowledge and confidence within CS were met. Practical experience enhanced learning. “Hands‐on” experience was most valuable for self‐reported confidence but learning by proxy also aided development. Students recognised challenges, but not the implications for themselves or their career. Strategies to reduce barriers to experience require research.

Conclusion

Whilst variable, all students were provided learning opportunities. Physical experience gave the greatest confidence. Opportunities afforded by the undergraduate curriculum allowed students to learn and develop through consolidation of theory, response to challenges and ultimately the gaining of confidence.
Fatigue fracture assessment of 10CrNi3MoV welded load‐carrying cruciform joints considering mismatch effect
Authors: Song Wei , Liu Xuesong , Xu Jie , Fan Yu , Shi Duanhu , He Min , Wang Xiaoxi , Berto Filippo
Published: April 2021

Fatigue experiments and numerical simulations based on the linear elastic fracture mechanics (LEFM) theory were conducted on the evenmatched (EM) and undermatched (UM) 10CrNi3MoV load‐carrying cruciform welded joints (LCWJs). The study firstly experimentally investigated the fatigue crack growth rate (FCGR) of base metal, EM, and UM weldments. The corresponding Paris parameters as essential input data are provided to assess the fatigue crack propagation behavior for weld toe and weld root failure caused by notch stress concentration variations. On the one hand, the stress intensity factors (SIFs) at weld toe and weld root were calculated considering the effects of LCWJ specimen geometries, initial crack types, and sizes. The comparisons between simulated results and standards analytical solutions were executed, which exhibit good accordance. It proved that the fatigue fracture simulation procedure based on LEFM is appropriate for the fatigue assessment of LCWJs. Eventually, it conducted the parametric analysis by predicted S–N curves, which included in the weld length, initial crack shape, initial crack size, penetration length, and materials fracture parameter, to explore some safety assessment reference lines for both failure modes of LCWJ.