bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-parameter phenotyping of platelets and characterisation of the effects of agonists using machine learning
Authors: Vadgama Ami , Boot James , Allan Harriet E. , Mein Charles A. , Armstrong Paul C. , Warner Timothy D.
Published: December 2023

Background

Platelets are crucial for thrombosis and haemostasis, with their function driven by the expression of specialised surface markers. The concept of distinct circulating sub-populations of platelets has emerged in recent years, but their exact nature remains debatable. We reasoned that a more comprehensive characterisation of surface marker changes at rest and upon activation would be valuable in determining this.

Objective

To use a full spectrum flow cytometry-based panel, together with parameters of physical properties, to describe surface marker changes in healthy platelets at rest and on activation, and to observe how these responses differ according to platelet age.

Methods

A 14-marker flow cytometry panel was developed and applied to vehicle- or agonist-stimulated platelet-rich plasma samples obtained from healthy volunteers, or to platelets sorted according to SYTO-13 staining intensity as an indicator of platelet age. Data were analysed using both user-led and independent approaches incorporating novel machine learning-based algorithms.

Results

The assay detected changes in marker expression in healthy platelets, at rest and on agonist activation, that are consistent with the literature. Machine learning identified stimulated populations of platelets with high accuracy (>80%). Similarly, differentiation between young and old platelet populations achieved 76% accuracy, primarily weighted by FSC-A, CD41, SSC-A, GPVI, CD61, and CD42b expression patterns.

Conclusions

Our findings provide a novel assay to phenotype platelets coupled with a robust bioinformatics and machine learning workflow for deep analysis of the data. This could be valuable in characterising platelets in disease.(240 words)

Essentials

Platelet function is directed by the expression of specialised surface markers

Circulating platelet sub-populations are incompletely characterised

Multi-parameter spectral flow cytometry allows robust and comprehensive phenotyping of platelets

Coupling multi-parameter spectral flow cytometry with machine learning offers a powerful method to determine platelet sub-populations
Non Parametric Differential Network Analysis for Biological Data
Authors: Guzzi Pietro Hiram , Roy Arkaprava , Veltri Pierangelo
Published: December 2023

Rewiring of molecular interactions under different conditions causes different phenotypic responses. Differential Network Analysis (also indicated as DNA) aims to investigate the rewiring of gene and protein networks. DNA algorithms combine statistical learning and graph theory to explore the changes in the interaction patterns starting from experimental observation. Despite there exist many methods to model rewiring in networks, we propose to use age and gender factors to guide rewiring algorithms. We present a novel differential network analysis method that consider the differential expression of genes by means of sex and gender attributes. We hypothesise that the expression of genes may be represented by using a non-gaussian process. We quantify changes in nonparametric correlations between gene pairs and changes in expression levels for individual genes. We apply our method to identify the differential networks between males and females in public expression datasets related to mellitus diabetes in liver tissue. Results show that this method can find biologically relevant differential networks.
The Relationship Between Preference and Switching in Flower Foraging by Bees
Authors: Papaj Daniel R. , Russell Avery L.
Published: December 2023

It seems self-evident that generalist foragers switch more between resources than specialists but despite diverse ecological and evolutionary implications, how variation in switching relates to variation in preference warrants additional study. Here we tested predictions based on a simple probability model, using flower-foraging bees as a model system. In laboratory assays, we presented bumble bee (Bombus impatiens) workers with flowers of two species,Tecoma stansandT. alata, from which they could collect nectar and/or pollen. We quantified landing preference and occurrence of switching between species in successive visits. Bees varied greatly in floral preference. Almost half showed statistically significant preferences for one or the other species, while the rest were generalists. As expected, generalists using both flower species switched more in successive visits than bees that were more specialized, a pattern fit to a quadratic function. However, generalist individuals switched more than expected based on null expectation. A Modified Jacob’s Index (MJI) of switching was significantly positively correlated with degree of preference: generalist bees had more negative MJI’s than specialist bees, indicating that even after the expected statistical effect of preference on switching was accounted for, they switched more than specialists. A simulation ruled out the possibility that the pattern was due to bias in MJI. Generalist-specialist differences in which food was collected (nectar versus pollen) were also ruled out. We discuss possible explanations for our observed pattern and outline possible ways in which preference and switching frequency will interact to shape pollinator behavior and the floral resource.

Significance statement

Behavioral preference is the subject of a large literature in areas such as foraging, mating and communication. However, a preference measure alone does not necessarily tell us if choices for one alternative are made in runs or intermingled with choices for another alternative. The distinction between preference and the sequential pattern of choices is relevant in many contexts in behavioral ecology but has been a particular focus of study in flower foraging by pollinators. Even in that literature, the relationship between preference and sequential pattern in switching warrants further examination. In our study, bees were shown to vary in preference for flowers of two species. Some were generalists; some were specialists on one or the other species. Generalist bees switched more than specialist bees, even after controlling for statistical effects of preference on switching frequency. The report of this generalist-specialist pattern in switching may be novel and has far-reaching implications throughout the field of behavioral ecology.
Mitochondrial mutation spectrum in Chordates: damage versus replication signatures, causes, and dynamics
Authors: Iliushchenko Dmitrii , Efimenko Bogdan , Mikhailova Alina G. , Shamanskiy Victor , Saparbaev Murat K. , Mazunin Ilya , Knorre Dmitrii , Kunz Wolfram S. , Kapranov Philipp , Denisov Stepan , Fellay Jacques , Khrapko Konstantin , Gunbin Konstantin , Popadin Konstantin
Published: December 2023

To elucidate the primary factors shaping mitochondrial DNA (mtDNA) mutagenesis, we derived a comprehensive 192-component mtDNA mutational spectrum using 86,149 polymorphic synonymous mutations reconstructed from the CytB gene of 967 chordate species. The mtDNA spectrum analysis provided numerous findings on repair and mutation processes, breaking it down into three main signatures: (i) symmetrical, evenly distributed across both strands, mutations, induced by gamma DNA polymerase (about 50% of all mutations); (ii) asymmetrical, heavy-strand-specific, C>T mutations (about 30%); and (iii) asymmetrical, heavy-strand-specific A>G mutations, influenced by metabolic and age-specific factors (about 20%). We propose that both asymmetrical signatures are driven by single-strand specific damage coupled with inefficient base excision repair on the lagging (heavy) strand of mtDNA. Understanding the detailed mechanisms of this damage is crucial for developing strategies to reduce somatic mtDNA mutational load, which is vital for combating age-related diseases.
KinAce: a web portal for exploring kinase-substrate interactions
Authors: Sekar John A. P. , Li Yan Chak , Schlessinger Avner , Pandey Gaurav
Published: December 2023

Interactions between protein kinases and their substrates are critical for the modulation of complex signaling pathways. Currently, there is a large amount of information available about kinases and their substrates in disparate public databases. However, these data are difficult to interpret in the context of cellular systems, which can be facilitated by examining interactions among multiple proteins at once, such as the network of interactions that constitute a signaling pathway. We present KinAce, a user-friendly web portal that integrates and shares information about kinase-substrate interactions from multiple databases of post-translational modifications. KinAce enables the visual exploration of these interactions in systems contexts, such as pathways, domain families, and custom protein set inputs, in an interactive fashion. We expect KinAce to be useful as a knowledge discovery tool for kinase-substrate interactions, and the aggregated KinAce dataset to be useful for protein kinase studies and systems-level analyses. The portal is available athttps://kinace.kinametrix.com/.
Rapid long-distance migration of RPA on single stranded DNA occurs through intersegmental transfer utilizing multivalent interactions
Authors: Pangeni Sushil , Biswas Gargi , Kaushik Vikas , Kuppa Sahiti , Yang Olivia , Lin Chang-Ting , Mishra Garima , Levy Yaakov , Antony Edwin , Ha Taekjip
Published: December 2023

Replication Protein A (RPA) is a single stranded DNA (ssDNA) binding protein that coordinates diverse DNA metabolic processes including DNA replication, repair, and recombination. RPA is a heterotrimeric protein with six functional oligosaccharide/oligonucleotide (OB) domains and flexible linkers. Flexibility enables RPA to adopt multiple configurations and is thought to modulate its function. Here, using single molecule confocal fluorescence microscopy combined with optical tweezers and coarse-grained molecular dynamics simulations, we investigated the diffusional migration of single RPA molecules on ssDNA under tension. The diffusion coefficientDis the highest (20,000 nucleotides2/s) at 3 pN tension and in 100 mM KCl and markedly decreases when tension or salt concentration increases. We attribute the tension effect to intersegmental transfer which is hindered by DNA stretching and the salt effect to an increase in binding site size and interaction energy of RPA-ssDNA. Our integrative study allowed us to estimate the size and frequency of intersegmental transfer events that occur through transient bridging of distant sites on DNA by multiple binding sites on RPA. Interestingly, deletion of RPA trimeric core still allowed significant ssDNA binding although the reduced contact area made RPA 15-fold more mobile. Finally, we characterized the effect of RPA crowding on RPA migration. These findings reveal how the high affinity RPA-ssDNA interactions are remodeled to yield access, a key step in several DNA metabolic processes.

Significance

Replication Protein A (RPA) binds to the exposed single stranded DNA (ssDNA) during DNA metabolism. RPA dynamics are essential to reposition RPA on ssDNA and recruit downstream proteins at the bound site. Here in this work, we perform a detailed biophysical study on dynamics of yeast RPA on ssDNA. We show that RPA can diffuse on ssDNA and is affected by tension and salt. Our observations are best explained by the intersegmental transfer model where RPA can transiently bridge two distant DNA segments for its migration over long distances. We further dissect the contributions of the trimerization core of RPA and other adjacent RPA molecules on RPA migration. This study provides detailed experimental and computational insights into RPA dynamics on ssDNA.
Umbrella toxin particles produced by Streptomyces block mycelial growth of competing species
Authors: Zhao Qinqin , Bertolli Savannah , Park Young-Jun , Tan Yongjun , Cutler Kevin J. , Srinivas Pooja , Asfahl Kyle L. , Garcia Citlali F. , Gallagher Larry A. , Li Yaqiao , Wang Yaxi , Coleman-Derr Devin , DiMaio Frank , Zhang Dapeng , Peterson S. Brook , Veesler David , Mougous Joseph D.
Published: December 2023

TheStreptomycesare a genus of ubiquitous soil bacteria from which the majority of clinically utilized antibiotics derive. The production of these antibacterial molecules reflects the relentless competitionStreptomycesengage in with other bacteria, including otherStreptomycesspecies. Here we show that in addition to small molecule antibiotics, Streptomyces produce and secrete antibacterial protein complexes that feature a large, degenerate repeat-containing polymorphic toxin protein. A cryo-EM structure of these particles reveals an extended stalk topped by a ringed crown comprising the toxin repeats scaffolding five lectin-tipped spokes, leading to our naming them umbrella particles.S. coelicolorencodes three umbrella particles with distinct toxin and lectin composition, and supernatant containing these toxins specifically and potently inhibits the growth of selectStreptomycesspecies from among a diverse collection of bacteria screened. For one target,S. griseus, we find inhibition relies on a single toxin and that intoxication manifests as rapid cessation of vegetative mycelial growth. Our data show thatStreptomycesumbrella particles mediate competition between vegetative mycelia of related species, a function distinct from small molecule antibiotics, which are produced at the onset of reproductive growth and act broadly. Sequence analyses suggest this role of umbrella particles extends beyondStreptomyces, as we find umbrella loci in nearly one-thousand species across Actinobacteria.
Young adults accelerate their arms significantly faster and earlier than old adults resulting in improved center of mass dynamics during an overground slip perturbation
Authors: Lee-Confer Jonathan S. , Lo Matthew K. , Troy Karen L.
Published: December 2023

Arm motions reduce the likelihood of falling from a slip in young adults, and injuries to older adults from falls are known to occur from a frontal plane fall. Therefore, the purpose of this study was to quantify the frontal plane trunk and arm motion in older and younger adults during a slip. Eleven older adults (age: 72.0 ± 5.0) and 11 younger adults (age: 25.17 ± 5.94) were subjected to a slip during walking. 27% of the older adults and 11% of the younger adults experienced a fall from the slip incident. The arm excursion did not significantly differ between groups, however younger adults’ average peak arm abduction occurred 310 ms prior to older adults (p = 0.03). There were no significant differences in peak trunk between groups. The arm abduction acceleration was significantly higher in younger adults compared to older adults (3593.2 ± 1144.8 vs. 2309.8 ± 1428.5 degrees/s2, p = 0.03). Furthermore, young adults exhibited a significantly reduced CoM excursion compared to old adults (4.55 ± 3.45 vs. 10.27 ± 6.62 cm, p < 0.01). Young adults may have exhibited lower fall rates due to the significantly higher acceleration of their arms compared to old adults.
Uncovering network mechanism underlying thalamic deep brain stimulation
Authors: Tian Yupeng , Bello Edward , Crompton David , Paraskevopoulos Zoe , Kalia Suneil K. , Hodaie Mojgan , Lozano Andres M. , Hutchison William D. , Johnson Matthew D. , Popovic Milos R. , Milosevic Luka , Lankarany Milad
Published: December 2023

Thalamic ventral intermediate nucleus (Vim) is the primary surgical target of deep brain stimulation (DBS) for reducing symptoms of essential tremor. High-frequency Vim-DBS (≥100Hz) has been clinically effective, generating two experimentally-observed features in Vim spiking activity: 1) a large transient excitatory response (lasting <1s), followed by 2) a suppressed steady-state consisting of oscillations. Yet, mechanisms underlying these observations have not been fully understood by previous studies. In this work, we developed a network rate model and a novel parameter optimization method that accurately fit in-vivo single-unit recordings of Vim in human patients with essential tremor receiving a wide range of DBS frequencies (5∼200Hz). Our model incorporates both the DBS-induced synaptic plasticity of Vim neurons, and the recurrent connections among excitatory and inhibitory neurons in Vim-network. We hypothesized that besides inducing synaptic depression, the therapeutic mechanism of high-frequency Vim-DBS could be to engage more inhibitory neurons in stabilizing the underlying circuits.

Graphical abstract
A One-Step Plasma Assisted Synthesis of Gold Nanoparticles and Simultaneous Linker-Free Conjugation with Nestin: An In Vitro Study of Cellular toxicity
Authors: Shokri Babak , Aalikhani Kimia , Sanavandi Melika , Shafiee Mojtaba , Rabbani Hodjattallah , Fazli Ghazaleh , Sadeghi Nilufar
Published: December 2023

We introduce a method for conjugating antigens to gold nanoparticles (GNPs) while synthesizing them using gas plasma, which eliminates the need for chemical linkers intended to facilitate the conjugation procedure for immunotherapy purposes. We report a physical approach to conjugate antigen Nestin (NES) as a marker in malignant tumors to GNPs. Two approaches were used to perform the conjugation of GNPs and NES. The first method involved using citrate to synthesize GNPs, and then NES was conjugated onto the GNPs surface by plasma. In the second method, GNPs were simultaneously synthesized and linker-freely conjugated to NES by plasma treatment.Enzyme-linked immunosorbent assaywith the protocol defined in this study,Zeta-sizer, Ultraviolet-visible spectroscopy, andTransmission Electron Microscopyresults confirmed NES conjugation to GNPs. In addition, the toxicity of the prepared samples was investigated in vitro using peripheral blood mononuclear cells (PBMCs) andflow cytometry, which proved the non-toxicity of the samples.

Abstract Figure
Solar Bird Banding: Notes on Changes in Avian Behavior While Mist-netting During an Eclipse
Authors: DeNiro Adara , Kittelberger Kyle D. , Samani Atoosa M. , Hakkı Şekercioğlu Çağan
Published: December 2023

Solar eclipses present rare celestial events that can elicit unique behavioral responses in animals, yet comprehensive studies on these phenomena, particularly concerning bird behavior, remain limited. This study, conducted at the Red Butte Canyon Research Natural Area in Utah during the annular solar eclipse on October 14, 2023, aimed to document and analyze avian activity using bird banding data. Leveraging 11 years of banding records, we observed a surprising positive peak in bird captures, indicating increased activity during the eclipse, challenging conventional expectations of decreased activity during peak totality. The unexpected, record-breaking captures on the eclipse day at this location, which also surpassed the average trend in captures over time for 18 other banding days in mid-October, highlights the complexity of bird behavior during celestial events. This study marks the first known published effort to conduct bird banding during a solar eclipse. Quantitative analyses, including species composition and capture trends, contribute to a nuanced understanding of avian responses to the eclipse. This study underscores the importance of empirical research in unraveling the intricacies of how birds navigate and adapt to unique environmental conditions created by solar eclipses.
Disease signatures in the gut metagenome of a prospective family cohort of inflammatory bowel disease
Authors: Rühlemann Malte , Waschina Silvio , Wacker Eike Matthias , Rausch Philipp , Schaan Ana , Zafroon Zaira , Franzpötter Katrin , Jacobs Gunnar , Ellinghaus David , Kruse Robert , Bergemalm Daniel , Halfvarson Jonas , Ziemann Malte , Görg Siegfried , Lieb Wolfgang , Schreiber Stefan , Poyet Mathilde , Bang Corinna , Franke Andre , Groussin Mathieu
Published: December 2023

Inflammatory bowel disease (IBD) is associated with dysbiotic microbiomes. However, whether microbiomes of family members of IBD patients harbour microbial disease signatures of IBD is unknown. Here, we generate shotgun metagenomic data of an IBD family cohort and treatment-naive IBD cases, which we combine with published IBD metagenomes, to perform a meta-analysis of IBD-microbiome associations. Our study reveals microbial shifts that are specific to IBD or IBD subtypes (Crohn’s disease and ulcerative colitis). We find that IBD cohorts share signatures of association with disease irrespective of geography, and we report novel species-level identifications of microbial taxa that are universal markers of Crohn’s disease. We further demonstrate that the microbiome of healthy family members at high risk for IBD represent transitional states between the microbiome of unrelated healthy controls and IBD cases, and harbor diversity, compositional and ecological features that are also observed among IBD microbiomes. Overall, our study provides valuable insights into the intricate relationship between the gut microbiome and IBD, with implications for better predicting disease onset among individuals with high susceptibility for IBD.
Complex genomes of early nucleocytoviruses revealed by ancient origins of viral aminoacyl-tRNA synthetases
Authors: Kijima Soichiro , Hikida Hiroyuki , Delmont Tom O. , Gaïa Morgan , Ogata Hiroyuki
Published: December 2023

Aminoacyl-tRNA synthetases (aaRSs), also known as tRNA ligases, are essential enzymes in translation. Owing to their functional essentiality, these enzymes are conserved in all domains of life and used as informative markers to trace the evolutionary history of cellular organisms. Unlike cellular organisms, viruses generally lack aaRSs because of their obligate parasitic nature, but several large and giant DNA viruses in the phylumNucleocytoviricotaencode aaRSs in their genomes. The discovery of viral aaRSs led to the idea that the phylogenetic analysis of aaRSs can shed light on ancient viral evolution. However, conflicting results have been reported from previous phylogenetic studies: one posited that nucleocytoviruses recently acquired their aaRSs from their host eukaryotes, while another hypothesized that the viral aaRSs have ancient origins. Here, we investigated 4,168 nucleocytovirus genomes, including metagenome-assembled genomes derived from large-scale metagenomic studies. In total, we identified 780 viral aaRS sequences in 273 viral genomes. We generated and examined phylogenetic trees of these aaRSs with a large set of cellular sequences to trace evolutionary relationships between viral and cellular aaRSs. The analyses firmly establish that the origins of some viral aaRSs predate the last common eukaryotic ancestor. Inside viral aaRS clades, we identify intricate evolutionary trajectories of viral aaRSs with horizontal transfers, losses, and displacements. Overall, these results suggest that ancestral nucleocytoviruses already developed complex genomes with an expanded set of aaRSs in the proto-eukaryotic era.
Atenolol reduces cardiac-mediated mortality in genetic mouse model of sudden unexpected death in epilepsy
Authors: Soh Ming S. , Kuanyshbek Alibek , Mohamed Syazwan Erlina S. , Lee Hian M. , McKenzie Chaseley E. , Phillips A. Marie , Hu Amanda , Scheffer Ingrid E. , Semsarian Christopher , Berkovic Samuel F. , Reid Christopher A.
Published: December 2023

Sudden Unexpected Death in Epilepsy (SUDEP) is the leading cause of premature mortality in epilepsy. Genetic cardiac risk factors, including loss-of-functionKCNH2variants, have been linked to SUDEP. We hypothesised that seizures and LQTS interact to increase SUDEP risk. To investigate this, we crossedKcnh2+/-andGabrg2R43Q/+mice that model LQTS and genetic epilepsy, respectively. Electrocorticography and electrocardiogram confirmed thatKcnh2+/-mice had a LQTS phenotype, whileGabrg2R43Q/+mice displayed spontaneous seizures. Double mutant mice (Gabrg2R43Q/+/Kcnh2+/-) had both seizure and LQTS phenotypes that were indistinguishable from the respective single mutant mice. Survival analysis revealed thatGabrg2R43Q/+/Kcnh2+/-mice experienced a disproportionate higher rate of seizure-related death. Long-term oral administration of atenolol, a cardiac-selective β-blocker, significantly improved survival in theGabrg2R43Q/+/Kcnh2+/-mice. An additional mouse model,Hcn1M294L/+/Kcnh2+/-, based on aHCN1developmental epileptic encephalopathy variant, also experienced a disproportionately higher rate of premature death that was rescued by atenolol.Kcnh2+/-mice also spent more time in ventricular arrhythmia during proconvulsant-induced seizures. Overall, the data implicates cardiac and loss-of-functionKCNH2variants as an important risk factor, and the potential repurposing of β- blockers as a prevention strategy, for SUDEP in a subset of epilepsy patients.
Protein-specific crowding accelerates aging in phase-separated droplets
Authors: Brzezinski Mateusz , Argudo Pablo G. , Scheidt Tom , Yu Miao , Lemke Edward A. , Michels Jasper J. , Parekh Sapun H.
Published: December 2023

Crowding agents, such as polyethylene glycol (PEG, are often used to mimic the cellular cytoplasm in protein assembly studies. Despite the perception that crowding agents have an inert nature, recent work has shown they are not bystanders while proteins interact. Here, we explore the diverse effects of PEG on the phase separation and maturation of proteins. We use two proteins, the FG domain of Nup98 and bovine serum albumin (BSA), which represent an intrinsically disordered protein and a protein with well-established secondary structure, respectively. PEG expedites the maturation of Nup98, enhancing denser protein packing and fortifying hydrophobic interactions which hasten beta-sheet formation and subsequent droplet gelation. In contrast for BSA, PEG appears to enhance droplet stability and limits available solvent for the protein solubilization, without inducing significant changes to the secondary structure, pointing towards a significantly different behavior of the crowding agent. Interestingly, we detect almost no presence of PEG in Nup droplets whereas PEG is detectable within BSA droplets. Our findings demonstrate a nuanced interplay between crowding agents and proteins. PEG can accelerate protein maturation in LLPS systems but its partitioning and effect on protein structure in droplets is protein specific. This suggests that crowding phenomena are specific to each protein-crowding agent pair.
Nucleolar Pol II interactome reveals TBPL1, PAF1, and Pol I at intergenic rDNA drive rRNA biogenesis
Authors: Khosraviani Negin , Yerlici V. Talya , St-Germain Jonathan , Hou Yi Yang , Cao Shi Bo , Ghali Carla , Krishnan Rehna , Hakem Razqallah , Raught Brian , Mekhail Karim
Published: December 2023

Nucleolar ribosomal DNA (rDNA) repeats control ribosome manufacturing. rDNA harbors a ribosomal RNA (rRNA) gene and an intergenic spacer (IGS). RNA polymerase (Pol) I transcribes rRNA genes yielding the rRNA components of ribosomes. Pol II at the IGS induces rRNA production by preventing Pol I from excessively synthesizing IGS non-coding RNAs (ncRNAs) that can disrupt nucleoli. At the IGS, Pol II regulatory processes and whether Pol I function can be beneficial remain unknown. Here, we identify IGS Pol II regulators, uncovering nucleolar optimization via IGS Pol I. Compartment-enriched proximity-dependent biotin identification (compBioID) showed enrichment of the TATA-less promoter-binding TBPL1 and transcription regulator PAF1 with IGS Pol II. TBPL1 localizes to TCT motifs, driving Pol II and Pol I and maintaining its baseline ncRNA levels. PAF1 promotes Pol II elongation, preventing unscheduled R-loops that hyper-restrain IGS Pol I and its ncRNAs. PAF1 or TBPL1 deficiency disrupts nucleolar organization and rRNA biogenesis. In PAF1-deficient cells, repressing unscheduled IGS R-loops rescues nucleolar organization and rRNA production. Depleting IGS Pol I-dependent ncRNAs is sufficient to compromise nucleoli. We present the interactome of nucleolar Pol II and show its control by TBPL1 and PAF1 ensures IGS Pol I ncRNAs maintaining nucleolar structure and operation.
A rapid review of physical health risks associated with special procedures (tattooing, body piercing, acupuncture, electrolysis)
Authors: Kiseleva Meg , Csontos Judit , Edwards Deborah , Gillen Elizabeth , Mann Mala , Searchfield Lydia , Sha’aban Abubakar , Lewis Ruth , Cooper Alison , Edwards Adrian
Published: December 2023

Special procedures, such as tattooing (including semi-permanent make-up), body piercing, acupuncture and electrolysis involve piercing the skin and carry a potential risk of infection and other complications. This review provides an up-to-date evidence base on the main physical health risks associated with these special procedures.

Searches were conducted for research published between 2015 and 2023. Where possible, existing reviews were used. For tattooing, one systematic review including 55 studies was identified. For semi-permanent make-up, 37 cases presented in 31 case reports were identified. For body piercing, four systematic reviews were identified, which covered 174 studies. For acupuncture, one evidence map of 535 systematic reviews without age limits and one overview of 24 systematic reviews focused on children were included. For electrolysis, one case report was identified.

Complications and adverse events resulting from special procedures include fungal infections, bacterial infections, viral infections, blood-borne infections, allergic reactions, malignant growths, benign growths, sarcoidosis-related reactions, and a range of other skin and eye-related adverse reactions and dental issues.

Research Implications and Evidence Gaps

Most of the primary evidence for the physical health risks associated with the special procedures came from case reports and case series, which do not allow causal inferences or provide information on the prevalence of adverse events. Future primary research should employ more robust designs to gather evidence about the causal links between special procedures and adverse physical health events as well as about the prevalence of such events in people receiving special procedures. More evidence is needed to identify physical health risks associated with electrolysis.

Policy and Practice Implications

The evidence contained in this review will be used to inform the training of local authority enforcement officers and special procedures practitioners and to educate members of the public who seek to use these services. Due to the nature of the special procedures which involves piercing the skin and poses the risk of introducing infections to the body, high standards of hygiene may reduce the rate of infection.

Funding statement

The Wales Centre for Evidence Based Care, and the Specialist Unit for Review Evidence, were funded for this work by the Health and Care Research Wales Evidence Centre, itself funded by Health and Care Research Wales on behalf of Welsh Government.
Cytokinetic abscission requires actin-dependent microtubule severing
Authors: Advedissian Tamara , Frémont Stéphane , Echard Arnaud
Published: December 2023

Cell division is completed by the abscission of the intercellular bridge connecting the daughter cells. Abscission requires the polymerization of an ESCRT-III cone close to the midbody to both recruit the microtubule severing enzyme spastin and scission the plasma membrane. Contrary to the common assumption, we found that the microtubule and the membrane cuts are two separate events and are regulated differently. We uncovered that the F-actin disassembling protein Cofilin-1 controls the disappearance of a transient pool of branched F-actin which is precisely assembled at the tip of the ESCRT-III cone just before the microtubule cut. Functionally, Cofilin-1 and Arp2/3-mediated branched F-actin favor abscission by promoting local severing of the microtubules but do not participate later in the membrane scission event. Mechanistically, branched F-actin functions as a physical barrier that limits ESCRT-III cone elongation and thereby favors stable spastin recruitment. Our work thus reveals that F-actin unexpectedly controls the timely and local disassembly of microtubules required for cytokinetic abscission.
An integrated G-MACONT approach for healthcare supplier selection
Authors: Chakraborty Santonab , Raut Rakesh D. , Rofin T.M. , Chakraborty Shankar
Published: December 2023

Purpose

Supplier selection along with continuous evaluation of their performance is a crucial activity in healthcare supply chain management for effective utilization of scarce resources while providing quality service at an affordable price, and minimizing chances of stock-out, avoiding serious consequences on the illness or fatality of the patients. Presence of both qualitative and quantitative evaluation criteria, set of potential suppliers and participation of different stakeholders with varying interest make healthcare supplier selection a challenging task which can be effectively solved using any of the multi-criteria decision making (MCDM) methods.

Design/methodology/approach

To deal with various qualitative criteria, like cost, quality, delivery performance, reliability, responsiveness and flexibility, this paper proposes integration of grey system theory with a newly developed MCDM tool, i.e. mixed aggregation by comprehensive normalization technique (MACONT) to identify the best performing supplier for pharmaceutical items in a healthcare unit from a pool of six competing alternatives based on the opinions of three healthcare professionals.

Findings

While assessing importance of the six evaluation criteria and performance of the alternative healthcare suppliers against those criteria using grey numbers, and exploring use of three normalization procedures and two aggregation operations of MACONT method, this integrated approach singles out S5 as the most compromised healthcare supplier for the considered problem. A sensitivity analysis of its ranking performance against varying values of both balance parameters and preference parameters also validates its solution accuracy and robustness.

Originality/value

This integrated approach can thus efficiently solve healthcare supplier selection problems based on qualitative evaluation criteria in uncertain group decision making environment. It can also be deployed to deal with other decision making problems in the healthcare sector, like supplier selection for healthcare devices, performance evaluation of healthcare units, ranking of physicians etc.
Inventory and financial performance in the pharmaceutical industry: what transpired over the last two decades?
Authors: Choi Jeong Hoon , Choi Sangdo , Suresh Nallan C.
Published: December 2023

Purpose

The objective of this study is to explore the structural attributes of the pharmaceutical industry before the onset of the COVID-19 pandemic by examining the relationship between inventory and firm performance and developing a taxonomy of pharmaceutical firms based on the earns-turns matrix.

Design/methodology/approach

This study examines the inventory–firm performance linkage, considering both total inventory and its discrete inventory components in pharmaceutical firms. In addition, this research develops a new taxonomy of pharmaceutical firms based on the earns-turns matrix. A large panel dataset of firms in the US pharmaceutical industry was collected for the period 2000–2019.

Findings

The results reveal that strategic groups identified based on this taxonomy show different levels of profitability and inventory turns in the earns-turns matrix. Most pharmaceutical firms moved from the low-right to the top-left section in the earns-turns matrix, indicating that these firms have generally pursued profitability rather than effective inventory management.

Research limitations/implications

This study explores the structural attributes of the pharmaceutical industry using the earns-turns matrix. This two-dimensional analysis may not, however, capture the full complexity of inventory–firm performance dynamics.

Practical implications

The mapping of strategic groups on the earns-turns matrix provides a useful tool for visual representations of the dynamics of strategic groups in terms of financial performance and inventory management performance. Practitioners can use the earns-turns matrix to benchmark their firm's position against their competitors.

Originality/value

This study broadens the scope of operations management research by introducing the earns-turns matrix as an empirical validation tool for operational and strategic management theories. This study emphasizes the effectiveness of the earns-turns matrix in analyzing strategic groups of pharmaceutical firms.
Decolonising doctoral education in an era of pandemic
Authors: Manathunga Catherine
Published: December 2023

Purpose

The purpose of this paper is to investigate the impact of the COVID-19 pandemic on doctoral education. Pandemics throughout history have generated new educational theories and practices, accelerated some trends and signalled the abrupt end of others. The unpredictable effects of the COVID-19 pandemic have particularly impacted upon First Nations and transcultural communities and People of Colour throughout the globe. A second significant recent global trend that occurred at the height of the pandemic was the reignited #BlackLivesMatter (#BLM) protest campaign. This campaign drew attention to the vast inequities faced by black, transcultural (migrant, refugee, culturally diverse and international) and Indigenous peoples and triggered rapid action in higher education institutions against racism and unconscious bias.

Design/methodology/approach

This conceptual paper draws upon postcolonial/decolonial theory to demonstrate how the COVID pandemic and #BLM movement prompts us to revitalise doctoral education.

Findings

These two issues have created renewed urgency around the need to decolonise higher education and a desire to transform the “business-as-usual” geopolitical power dynamics that continue to privilege Northern knowledge over culturally diverse knowledge systems from First Nations and transcultural contexts. A key site where special opportunities exist to effect this transformation lies in doctoral education. Doctoral education is a significant location of new knowledge creation and the development of the world’s future researchers.

Research limitations/implications

Applying post/decolonial theory enables one to rethink how doctoral education should be changed to work towards greater decolonisation.

Originality/value

This study applies Santos’ ideas about “the sociologies of emergence” in the global South to think about how doctoral education should be reconstructed as a liberated zone of decolonisation and epistemic justice.
Front-desk workforce cultural diversity and its implications for service quality in the accommodation sector: a case from Australia
Authors: Suwarto Titania , Pforr Christof , Volgger Michael
Published: December 2023

Purpose

Language and dialect, customs and service attitudes are just a few of the characteristics that make each culture unique. Consequently, the presence of people from different cultures during a service encounter may impact service quality, as what constitutes good service quality is perceived differently across cultures. As a country with a multicultural society, culturally diverse migrants from non-English speaking backgrounds (NESB) play an increasingly important role in the Australian hospitality and accommodation sector. Within this regional context, this study aims to contribute to a more robust understanding of the influence of workforce cultural diversity on different aspects of front-desk accommodation service quality in the accommodation industry.

Design/methodology/approach

In this qualitative study, 31 semi-structured in-depth interviews with guests, front-desk staff and managers at service apartments in Western Australia were conducted, followed by validation interviews with five hospitality human resource management experts.

Findings

The results of the interviews suggest that cultural diversity of NESB staff affects several aspects of Australian accommodation front-desk services, including communication quality, staff-guest interaction and guest satisfaction. Findings point out that culturally diverse NESB front-desk staff may face cross-cultural communication barriers due to different foreign accents and the presence of local slang, improve guest-staff interaction and the overall guest experience in case of similar cultural backgrounds with guests and provide authentic representations of multiculturalism in Australia.

Originality/value

The study sheds new light on tourists’ shifting perceptions and expectations of authenticity, particularly in Australia, where cultural diversity has increased in prominence. Moreover, in the Australian accommodation service, many NESB employees who have learned American/British English have difficulty conversing with people with Australian accents, especially when Australian slang is also present.
Patient preferences for disposable and reusable vaginal specula and their willingness to compromise in the era of climate change: A cross‐sectional study
Authors: Ten Buuren Amber A. A. , Poolman Tessa B. , Bongers Marlies Y. , Bullens Lauren M. , Van Hanegem Nehalennia , Klerkx Wenche M. , Timmermans Anne , Zuithoff Nicolaas P. A. , Kwee Anneke
Published: December 2023

Objective

To evaluate patient satisfaction on gynaecological examination with metal, plastic and biobased plastic vaginal specula, and to investigate whether patients are willing to compromise on comfort for a more sustainable healthcare system.

Design

Cross‐sectional study: population‐based survey.

Setting

Gynaecological outpatient clinics in five Dutch hospitals.

Population

Patients during general gynaecology consultation hours.

Methods

A survey containing two questions about patient demographics, four about comfort and five about sustainability and healthcare was distributed.

Main outcome measures

Comfort score (scale 1–10). Secondary outcomes: (1) temperature, size and ease of insertion, (2) willingness to compromise for a more sustainable healthcare system.

Results

In all, 196 patients completed the survey. Biobased plastic vaginal specula scored significantly higher on comfort than the metal ones (mean 8.03 ± 1.65 versus 7.26 ± 1.51 respectively; P < 0.001). The biobased plastic vaginal speculum is significantly the most comfortable on temperature, whereas the metal speculum is the least comfortable (P < 0.007). Most patients are willing to compromise on comfort or are open to the reuse of disposables to contribute to a more sustainable healthcare. The majority of patients (77%) urge healthcare organisations to combat climate change.

Conclusions

There is a small but statistically significant difference in favour of a biobased plastic speculum regarding comfort score, although it might be questioned whether this is clinically relevant. Furthermore, patients are willing to compromise on comfort for a more sustainable healthcare, which should be a contributing factor in speculum selection.
Extracellular ATP inhibits excitatory synaptic input on parvalbumin positive interneurons and attenuates gamma oscillations via P2X4 receptors
Authors: Wildner Florian , Neuhäusel Tim S. , Klemz Alexander , Kovács Richard , Ulmann Lauriane , Geiger Jörg R. P. , Gerevich Zoltan
Published: December 2023

Background and Purpose

P2X4 receptors (P2X4R) are ligand gated cation channels that are activated by extracellular ATP released by neurons and glia. The receptors are widely expressed in the brain and have fractional calcium currents comparable with NMDA receptors. Although P2X4Rs have been reported to modulate synaptic transmission and plasticity, their involvement in shaping neuronal network activity remains to be elucidated.

Experimental Approach

We investigated the effects of P2X receptors at network and synaptic level using local field potential electrophysiology, whole cell patch clamp recordings and calcium imaging in fast spiking parvalbumin positive interneurons (PVINs) in rat and mouse hippocampal slices. The stable ATP analogue ATPγS, selective antagonists and P2X4R knockout mice were used.

Key Results

The P2XR agonist ATPγS reversibly decreased the power of gamma oscillations. This inhibition could be antagonized by the selective P2X4R antagonist PSB‐12062 and was not observed in P2X4−/− mice. The phasic excitatory inputs of CA3 PVINs were one of the main regulators of the gamma power. Associational fibre compound excitatory postsynaptic currents (cEPSCs) in CA3 PVINs were inhibited by P2X4R activation. This effect was reversible, dependent on intracellular calcium and dynamin‐dependent internalization of AMPA receptors.

Conclusions and Implications

The results indicate that P2X4Rs are an important source of dendritic calcium in CA3 PVINs, thereby regulating excitatory synaptic inputs onto the cells and presumably the state of gamma oscillations in the hippocampus. P2X4Rs represent an effective target to modulate hippocampal network activity in pathophysiological conditions such as Alzheimer's disease and schizophrenia.
Graft survival and postoperative complications following orthotopic renal transplantation
Authors: Territo Angelo , Selvi İsmail , Malçok Aydan , Boissier Romain , Campi Riccardo , Prudhomme Thomas , Pecoraro Alessio , Piana Alberto , Lopez‐Abad Alicia , Bañuelos Marco Beatriz , Breda Alberto , Dönmez M. İrfan
Published: December 2023

The iliac fossa is the most commonly used site to place the graft in renal transplantation in adults. However, iliac fossa may not be used in various conditions. Thus, orthotopic renal transplantation becomes a viable alternative for these selected patients. Given the technically challenging surgery and limited number of patients, data on the long‐term outcomes on this regard are scarce. This narrative review serves as an update on the clinical outcomes after orthotopic renal transplantation, focusing on overall recipient survival and renal graft survival, as well as postoperative complications. We found that studies to date showed a comparable survival rate in both recipients and renal grafts in the postoperative follow‐up period after orthotopic renal transplantation with a lower complication rate compared to the published data on heterotopic renal transplantation. The results of our review may encourage transplant centers to reevaluate their policies to consider orthotopic renal transplantation as an alternative technique in cases where heterotopic kidney transplantation is not possible.