bluuebunny/crossref_metadata_2025 huggingface dataset:
An Unsupervised Approach to Identify Patient-Specific EMG Detector to Trigger Robot-Assisted Therapy
Authors: Yuvaraj Monisha , Prabakar A.T. , S.K.M Varadhan , Burdet Etienne , Ramos-Murgialday Ander , Balasubramanian Sivakumar
Published: December 2024

Abstract

In severely impaired stroke patients, implementing EMG-driven robot-assisted therapy requires the presence of sufficient residual EMG and a patient-specific detector for accurate and low-latency EMG detection. However, identifying such a detector is challenging, especially when the level of residual EMG in a given patient is unknown . This paper proposes an unsupervised approach to distinguish between EMG data when the patient is relaxed versus attempting a movement – themaximally separating detector. We investigated six different detector types and separation measures using EMG data from a previous randomized controlled trial. The results indicate that the approximate generalized likelihood ratio detector, along with the modified Hodges and modified Lidierth detectors, achieved the best separation. Using a subset of clinician annotated data to evaluate the detection performance, the modified Hodges detector employing the probability difference-sum ratio measure had the best detection performance in terms of detection accuracy and latency. Using the data from 30 participants, we propose a probability difference-sum ratio threshold of 0.7 for the modified Hodges detector to identify patients with sufficient residual EMG to trigger robotic assistance. From the results, we propose the use of modified Hodges detector along with a probability difference-sum ratio measure to learn the maximally separating detector for a given patient, which will screen the patient for sufficient residual EMG and provide a detector to trigger robotic assistance if sufficient EMG is present. The validation of this approach using a large dataset and investigating the quality of the human-machine interaction implemented with such a detector is warranted.
NucleoSeeker: Precision Filtering of RNA Databases to Curate High-Quality Datasets
Authors: Upadhyay Utkarsh , Pucci Fabrizio , Herold Julian , Schug Alexander
Published: December 2024

The structural prediction of biomolecules via computational methods complements the often involved wet-lab experiments. Un-like protein structure prediction, RNA structure prediction remains a significant challenge in bioinformatics, primarily due to the scarcity of annotated RNA structure data and its varying quality. Many methods have used this limited data to train deep learning models but redundancy, data leakage and bad data quality hampers their performance. In this work, we present NucleoSeeker, a tool designed to curate high-quality, tailored datasets from the Protein Data Bank (PDB) database. It is a unified framework that combines multiple tools and streamlines an otherwise complicated process of data curation. It offers multiple filters at structure, sequence and annotation levels, giving researchers full control over data curation. Further, we present several use cases. In particular, we demonstrate how NucleoSeeker allows the creation of a non-redundant RNA structure dataset to assess AlphaFold3’s performance for RNA structure prediction. This demonstrates NucleoSeeker’s effectiveness in curating valuable non-redundant tailored datasets to both train novel and judge existing methods. NucleoSeeker is very easy to use, highly flexible and can significantly increase the quality of RNA structure datasets.
Extreme lead tolerance in an urban lizard
Authors: Blanchette A , Su KJ , Frick AJ , Karubian J , Gunderson AR
Published: December 2024

Lead (Pb) is an extremely toxic heavy metal pollutant pervasive in many environments with serious health consequences for humans and wildlife. Identifying organisms that can serve as biomonitors of lead contamination and models to understand mechanisms of lead tolerance is therefore an important goal. We used the Cuban brown anole lizard (Anolis sagrei) in New Orleans, USA, to investigate the consequences of variation in environmental lead exposure at the physiological and gene regulatory levels. We found that brown anole blood lead levels are associated with soil lead contamination, and that their blood lead levels are extreme. At our most contaminated site, the mean and highest individual blood lead levels were over two times higher than the next highest values reported in free-living vertebrates. However, this lead exposure did not decrease performance in whole-organism traits commonly affected by lead (balance, sprint speed, endurance). A 60-day lead dosing experiment demonstrated that the brown anole blood lead threshold for decreased whole-organism performance is actually an order of magnitude higher than the highest mean field concentration. Transcriptomic analysis of brain and liver from lizards in high and low lead sites revealed relatively minor effects of lead exposure. However, several of the differentially expressed genes function in metal ion homeostasis and oxygen carrying capacity, pointing to cellular mechanisms that may contribute to high lead tolerance. The brown anole may be the most lead-tolerant vertebrate known to date and has the potential to be a powerful model system to help us better understand how organisms cope with heavy metal exposure.
Leaving Science: Attrition of Biologists in 38 OECD Countries
Authors: Kwiek Marek , Szymula Lukasz
Published: December 2024

This study examines biologists leaving science in 38 OECD countries in the past two decades. We use publication metadata from a global bibliometric database (raw Scopus data at the micro-level of individual scientists). In a cohort-based and longitudinal fashion, we follow individual men and women scientists over time, from their first to their last publication (N=86,178). We examine four academic disciplines: AGRI (agricultural and biological sciences), BIO (biochemistry, genetics, and molecular biology), IMMU (immunology and microbiology), and NEURO (neuroscience). We apply survival analysis, conceptualizing scientific life as a sequence of scholarly publishing events. Our Kaplan–Meier survival analysis shows how women disappear from science: in BIO, about 60% are still in science after 5 years, 40% after 10 years, and only 20% by the end of the period examined (i.e., after 19 years). The percentages are substantially higher for men: approximately 70%, 50%, and 30%, respectively. Kaplan–Meier estimations indicate that women in the largest discipline (BIO) are 23.26% more likely to leave science after 10 years and 39.74% more likely to leave science at the end of the study period. Gender difference in attrition, slightly visible after 5 years, increase consistently in later career stages. The probability of surviving for women after 15 years varies considerably, from 47.8% in AGRI to 27.6% in IMMU; for men, the probability is about a fifth higher. Our data show that with the passage of time, women disappear from science in ever-larger proportions compared to men. Gender differences in attrition in the four disciplines have been and continue to be high, but comparing the 2000 and 2010 cohorts, have slightly decreased over time.
Honest signalling in predator-prey interactions: testing the resource allocation hypothesis
Authors: Burdfield-Steel Emily , Ottocento Cristina , Furlanetto Miriam , Rojas Bibiana , Nokelainen Ossi , Mappes Johanna
Published: December 2024

Warning signals are honest if they reliably deliver information about prey unprofitability to predators. One potential mechanism that may create and maintain a positive relationship between the strength of signals and defence is the resource allocation between these costly traits. Here, we test this hypothesis using the wood tiger mothArctia plantaginis, whose females’ red hindwings are a warning signal to predators but show considerable variation in colouration within populations. These moths also produce a defensive chemical that is known to influence avian predator attack risk. Using dietary manipulations, image and chemical analyses, and experiments with ecologically relevant predators we demonstrate that protein availability during development can influence the strength of both the primary warning signal and the secondary defence. Our results show that females raised on a high-protein orad libitumnatural diet produced more distasteful defensive fluids than those raised on a low-protein diet or subjected to periodic food deprivation. While the patterning of the warning signal was unaffected by food deprivation, its efficacy was diminished in moths raised on a low-protein diet. However, this change was imperceptible to avian predators. Critically, resource availability influenced the relationship between signal strength and defence: moths on a high-protein diet displayed a positive correlation between warning signal strength and unpalatability, whereas this correlation was absent in moths raised on a natural diet. These findings show that resource availability can weaken the reliability of warning signals as an indicator of an individual’s defensive capabilities, highlighting the complex interplay between ecological conditions and the evolution of honest signalling.
Deep analysis of the Major Histocompatibility Complex associations using covariate analysis and haploblocks unravels new mechanisms for the molecular etiology of Elite Control in AIDS
Authors: Rahmouni Myriam , Clerc Sigrid Le , Spadoni Jean-Louis , Labib Taoufik , Tison Maxime , Medina-Santos Raissa , Bensussan Armand , Tamouza Ryad , Deleuze Jean-François , Zagury Jean-François
Published: December 2024

Introduction

We have reanalyzed the genomic data from the International Collaboration for the Genomics of HIV (ICGH), focusing on HIV-1 Elite Controllers (EC).

Methods

A genome-wide association study (GWAS) was performed, comparing 543 HIV-1 EC individuals with 3,272 uninfected controls (CTR) of European ancestry. 8 million single nucleotide polymorphisms (SNPs) and HLA class I and class II gene alleles were imputed to compare EC and CTR.

Results

2,626 SNPs were associated with EC (p<5.10-8), all located within the Major Histocompatibility Complex (MHC) region. Stepwise regression analysis narrowed this list to 17 SNPs. In parallel, 22 HLA class I and II alleles were associated with EC. Through meticulous mapping of the LD between all identified signals and employing reciprocal covariate analyses, we delineated a final set of 6 independent SNPs and 3 HLA class I gene alleles that accounted for most of the associations observed with EC. Our study revealed the presence of cumulative haploblock effects (SNP rs9264942 contributing to the HLA-B*57:01 effect) and that several HLA allele associations were in fact caused by SNPs in linkage disequilibrium (LD). Upon investigating SNPs in LD with the selected 6 SNPs and 3 HLA class I alleles for their impact on protein function (either damaging or differential expression), we identified several compelling mechanisms potentially explaining EC among which: a multi-action mechanism of HLA-B*57:01 involving MICA mutations and MICB differential expression overcoming the HIV-1 blockade of NK cell response, and overexpression of ZBTB12 with a possible anti-HIV-1 effect through HERV-K interference; a deleterious mutation in PPP1R18 favoring viral budding associated with rs1233396.

Conclusion

Our results show that MHC influence on EC likely extends beyond traditional HLA class I or class II allele associations, encompassing other MHC SNPs with various biological impacts. They point to the key role of NK cells in preventing HIV-1 infection. Our analysis shows that HLA-B*57:01 is indeed associated with a partially functional NK cell response which could also explain this marker’s involvement in other diseases such as psoriasis. More broadly, our findings suggest that within any HLA class I and II association in diseases, there may exist distinct causal SNPs within this crucial, gene-rich, and LD-rich MHC region.
GABAergic neurons from the ventral tegmental area represent and regulate force vectors
Authors: Jiang Qiaochu , Bakhurin Konstantin I. , Hughes Ryan N. , Lu Bryan , Ruan Shaolin , Yin Henry H.
Published: December 2024

The ventral tegmental area (VTA), a midbrain region associated with motivated behaviors, consists predominantly of dopaminergic (DA) neurons and GABAergic (GABA) neurons. Previous work has suggested that VTA GABA neurons provide a reward prediction, which is used in computing a reward prediction error. In this study, using in vivo electrophysiology and continuous quantification of force exertion in head-fixed mice, we discovered distinct populations of VTA GABA neurons that exhibited precise force tuning independently of learning, reward prediction, and outcome valence. Their activity usually preceded force exertion, and selective optogenetic manipulations of these neurons systematically modulated force exertion without influencing reward prediction. Together, these findings show that VTA GABA neurons continuously regulate force vectors during motivated behavior.
Chitin soil amendment triggers systemic plant disease resistance through enhanced pattern-triggered immunity
Authors: Makechemu Moffat , Goto Yukihisa , Zbinden Helen , Widrig Victoria , Keller Beat , Zipfel Cyril
Published: December 2024

Chitin triggers localised and systemic plant immune responses, making it a promising treatment for sustainable disease resistance. However, the precise molecular mechanisms underlying chitin-induced systemic effects in plants remain unknown. In this study, we investigated the effects of soil amendment with crab chitin flakes (hereafter chitin) on pattern-triggered immunity (PTI) and systemic disease resistance in various plant species. We found that soil amendment with chitin potentiates PTI and disease resistance against the bacterial pathogenPseudomonas syringaepv. tomato DC3000 in lettuce, tomato, and Arabidopsis as well as against the fungal pathogenBlumeria graminiscausing powdery mildew in wheat. Using micrografting in Arabidopsis, we demonstrated that this systemic effect is dependent on active chitin perception in the roots. We also showed that induced systemic resistance (ISR) and pattern-recognition receptors (PRRs)/co-receptors, but not systemic acquired resistance (SAR), are involved in the systemic effects triggered by chitin soil amendment. This systemic effect correlated with the transcriptional up-regulation of key PTI components in distal leaves upon chitin soil amendment. Notably, chitin-triggered systemic immunity was independent of microbes present in soil or chitin flakes. Together, these findings contribute to a better understanding of chitin-triggered systemic immunity, from active chitin perception in roots to the potentiation of PTI in the leaves, ultimately priming plants to mount enhanced defense responses against pathogen attacks. Our study provides valuable insights into the molecular mechanisms of chitin soil amendment and resulting induced immunity, and highlights its potential use for sustainable crop protection strategies.
Orchestration of SARS-CoV-2 Nsp4 and host-cell ESCRT proteins induces morphological changes of the endoplasmic reticulum
Authors: Kifer Allison , Pina Franciso , Codallos Nicholas , Herman Anita , Ziegler Lauren , Niwa Maho
Published: December 2024

Upon entry into the host cell, the non-structural proteins 3, 4, and 6 (Nsp3, Nsp 4, and Nsp6) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) facilitate the formation of double- membrane vesicles (DMVs) through extensive rearrangement of the host cell endoplasmic reticulum (ER) to replicate the viral genome and translate viral proteins. To dissect the functional roles of each Nsp and the molecular mechanisms underlying the ER changes, we exploited both yeastS. cerevisiaeand human cell experimental systems. Our results demonstrate that Nsp4 alone is sufficient to induce ER structural changes. Nsp4 expression led to robust activation of both the unfolded protein response (UPR) and the ER surveillance (ERSU) cell cycle checkpoint, resulting in cortical ER inheritance block and septin ring mislocalization. Interestingly, these ER morphological changes occurred independently of the canonical UPR and ERSU components but were mediated by the endosomal sorting complex for transport (ESCRT) proteins Vps4 and Vps24 in yeast. Similarly, ER structural changes occurred in human cells upon Nsp4 expression, providing a basis for a minimal experimental system for testing the involvement of human ESCRT proteins and ultimately advancing our understanding of DMV formation.
Unconventional structure and function of PHD domains from Additional Sex Combs-like proteins
Authors: Reddington CJ , Walsh AR , Göbl C , Mace PD
Published: December 2024

The Polycomb Repressive-Deubiquitinase (PR-DUB) complex removes ubiquitin from Lysine residue 119 on histone H2A (H2AK119Ub) in humans. The PR-DUB is composed of two central protein factors, the catalytic Breast Cancer type 1 susceptibility protein (BRCA1)-activating protein 1 (BAP1), and one of Additional Sex Combs-like 1–3 (ASXL1–3). A Plant Homeodomain (PHD) at the C-terminus of ASXL proteins is recurrently truncated in cancer, and was previously proposed to recognise epigenetic modifications on the N-terminal tail of histone H3. Here we demonstrate that the ASXL PHD domain lacks features required for histone tail recognition and is unable to bind histone H3 epigenetic marks. Modelling the structure of the ASXL PHD using AlphaFold3 suggests that the domain has an atypical fold and that the isolated ASXL PHD can chelate a single Zinc ionin vitro, compared to the two ions conventionally bound by PHD domains. Recently, the ASXL PHD was shown to bind an auxiliary set of PR-DUB interactors, named methyl CpG-binding domain proteins 5 (MBD5) and 6 (MBD6). We show that the ASXL PHD-MBD5 and -MBD6 complexes are stablein vitro,and surprisingly contain a composite Zinc-binding site at the interface between the two proteins. Overall, this data suggests an unconventional pairing of domains coordinate key functions of the PR-DUB — a non-canonical PHD domain from ASXL proteins obligately partners with MBD5 and 6, which were themselves misannotated because they cannot bind to methylated DNA.
Impact of Mass Distribution of Long-Lasting Insecticide Nets on Malaria Prevention in Lindi Region, Tanzania: A quasi experimental study
Authors: Mwanja Epafra Luka , Mwalyanzi Scola Anilozi , Khalfan Seif S. , Ambikile Ezekia Jasson , Mkama Mgole Eliud , Kisendi Dotto Daniel
Published: December 2024

Background

Malaria is a major public health issue with high rates of morbidity and mortality in the United Republic of Tanzania. To ensure that all households remain protected, national malaria control programs and partners in 2022 implemented free mass distribution of long-lasting insecticides nets to population at risk and high prevalent regions with malaria including Lindi region. The present study aimed to assess the effectiveness of free long-lasting insecticide-treated nets in reducing malaria burden among the population.

Methods

we conducted a quasi-experimental study from September 2021 to August 2022 and September 2022 to August 2023. The data were collected on District Health Information System version two in Lindi region and analysed with T-tests to compare the malaria positive rate before (September 2021 to August 2022) and after the distribution of long-lasting insecticides nets (September 2022 to August 2023). Malaria positive rate in the general population who attended outpatient department was reduced by 7.6% after distribution of long-lasting insecticides nets. A comparison of malaria cases recorded between September 2021 and August 2023 in the different area showed disparities. Before long lasting insecticides nets implementation, the malaria positive rate in all area combined was 20.6%. Whereas malaria positive rate in all area combined was 13% after implementation. The mean difference is 6.60, with a standard deviation of 2.47. The t-value is 6.55, with 5 degrees of freedom. The significance (2-tailed) value is <0.001, indicating a statistically significant difference between the malaria positive rate before and after long lasting insecticides nets implementation.

Conclusion

the long-lasting insectides nets distribution campaign synergy with other preventive interventions has had a significant impact on reducing the malaria positive rate in the population.
Mitigating norovirus spread on cruise ships: A model-based assessment of diagnostic timing and isolation
Authors: De Bellis Alfredo , Bizzotto Andrea , Anagnostopoulou Lemonia , Kourentis Leonidas , Marziano Valentina , Mouchtouri Varvara , Merler Stefano , Guzzetta Giorgio
Published: December 2024

Background

Acute gastroenteritis outbreaks caused by noroviruses are a common public health issue on cruise ships. Understanding the main drivers of sustained outbreaks is critical for evaluating the effectiveness of preventive interventions such as the isolation of infected individuals.

Methods

We analyzed a line-list of 121 cases from a norovirus outbreak on a cruise calling Mediterranean ports (cumulative incidence among passengers 9.7%). We used a Bayesian inference model to reconstruct likely transmission chains, taking into account different transmission settings and the isolation of cases after diagnosis. We then calibrated a branching process model to simulate alternative isolation scenarios and estimate their effectiveness in reducing transmission.

Results

Reconstructed transmission chains revealed a high heterogeneity in individual transmission, with 57% (95% CrI: 48%-65%) of secondary cases caused by 10% of infected individuals (here termed “superspreaders”). Superspreaders exhibited longer diagnostic delays (mean 83 hours, 95% CrI: 70-96 hours) compared to other infectors (mean 47 hours, 95% CrI: 44-50 hours) and a halved frequency of vomiting and diarrhea episodes. The 72-hour isolation protocol implemented during the outbreak averted 71% of potential cases compared to a no-intervention scenario, halving the effective reproduction number from 9.8 (95%CrI of the mean: 7.1-12.7) to 4.9 (95%CrI: 3.0-7.1). Reducing diagnostic delays further reduced the effective reproduction number, resulting in lower case numbers and probability of sustained outbreaks.

Conclusions

Timely diagnosis and isolation have a remarkable impact on norovirus containment on cruise ship outbreaks. Targeted information campaigns encouraging passengers to seek immediate medical assistance upon gastrointestinal symptoms can significantly improve outbreak management.
Self organisation of invasive breast cancer driven by the interplay of active and passive nematic dynamics
Authors: Gottheil Pablo , Bhattacharyya Saraswat , Lettl Kolya , Friedrich Philip , Roth Kilian , Rivera-Moreno Salvador , Merkel Mario , Aktas Bahriye , Sauer Igor , Daneshgar Assal , Wieland Jonas , Kubitschke Hans , Wegscheider Anne-Sophie , Yeomans Julia M. , Käs Josef A.
Published: December 2024

In invasive breast cancer, cell clusters of varying sizes and shapes are embedded in the fibrous extracellular matrix (ECM). Although the prevailing view attributes this structure to increasing disorder resulting from loss of function and dedifferentiation, our findings reveal that it arises through a process of active self-organization driven by cancer cell motility. Simulations and histological analyses of tumours from over 2,000 breast cancer patients reveal that motile, aligned cancer cells within clusters move as active nematic aggregates through the surrounding highly aligned ECM fibres, which form a confining, passive nematic phase. Cellular motion leads to cluster splitting and coalescence. The degree of cluster activity, combined with heterogeneity in cell motility, is reflected in specific scaling behaviours for cluster shape, size distribution, and the distance between cluster boundaries and nematic defects in ECM alignment. Increased activity estimates correlate with tumour progression and are associated with a poorer prognosis for patients.
To what extent can life history strategies inform species conservation planning?
Authors: Stevenson Emily A. , Lucas Sol , McGowan Philip J. K. , Smallegange Isabel M. , Mair Louise
Published: December 2024

Global policy aims to prevent species extinctions; to support these aims conservation planners must effectively target interventions to reduce the extinction risk of species. However, there is often a lack of knowledge on the magnitude and direction of species responses to interventions and in turn the extent to which a species extinction risk is reduced. If we can use a species’ life history strategies to predict their responses to interventions, this offers a promising approach to better understand species extinction risks and conservation potential. Here we apply Dynamic Energy Budget Integral Project Models to 23 reptile species to investigate whether their life history traits can be summarised into a life history strategy framework using principal component analysis, and whether species positions along these axes predict their population growth rate, demographic resilience, sensitivity to perturbations and extinction risk. We found that species positions on reproductive and pace of life axes predicted reptile population growth rate and demographic resilience but not sensitivity to perturbations or extinction risk. Our findings show that reptile life history strategies can inform our understanding of reptile species conservation potential and could be applied to influence management decisions such as establishing monitoring timelines.
Matrix Metalloproteinase-2 as a novel regulator of glucose utilization by adipocytes
Authors: Lempicki Melissa D. , Garrigues Ryan J. , Zeczycki Tonya N. , Garcia Brandon L. , Harris Thurl E. , Meher Akshaya K.
Published: December 2024

Glucose transporter 4 (GLUT4) expression on white adipocytes is critical for absorbing excess blood glucose, failure of which promotes hyperglycemia. Matrix metalloproteinases (MMPs) play a crucial role in remodeling the white adipose tissue (WAT) during obesity. MMPs have multiple protein substrates, and surprisingly, it is unknown if they can directly target GLUT4 on the adipocyte surface and impair glucose absorption. We identified MMP2 as the highly active gelatinase, a class of MMP, in the gonadal WAT of high-fat diet-induced obese mice.In vitro, metabolic studies in 3T3-L1 adipocytes revealed MMP2 attenuated glucose absorption and glycolysis, which were recovered by an MMP2 inhibitor.In silicostructural analysis using AlphaFold identified a putative MMP2 cleavage site on the extracellular domain of GLUT4. Further, in a substrate competition assay, a peptide mimicking the MMP2 cleavage motif on GLUT4 attenuated the cleavage of an MMP substrate by MMP2. Altogether, our results suggest a novel mechanism of impaired glucose absorption by adipocytes, which may contribute to hyperglycemia during obesity.

ARTICLE HIGHLIGHTS

It is unknown if MMPs directly affect adipocyte metabolismviatargeting adipocyte surface proteins.

We aimed to determine the highly active gelatinases, a class of MMP, in the white adipose tissue of obese mice, and examined its effect on adipocyte glucose metabolism.

MMP2 was the highly active gelatinase in obese adipose tissue and,in vitro, MMP2 reduced adipocyte glucose metabolism, in part, by targeting the GLUT4 receptor.

A harmful role of MMP2 is implicated in cardiometabolic diseases and our novel finding on the role of MMP2 on glucose metabolism may add to the pathogenesis of the diseases.
A novel menthol-DCMU bleaching method for foraminifera: Generating aposymbiotic hosts for symbiosis research
Authors: Schmidt Christiane , Puerto Rueda Diana N. , Nusser Moritz , Oakley Clinton A. , Pochon Xavier , Stuhr Marleen , Raposo Debora S. , Davy Simon K.
Published: December 2024

Predicting the response and resilience of coral reefs to climate change can only be achieved through better understanding the cellular symbiosis between coral reef holobionts and their associated endosymbiotic algae. Larger benthic foraminifera (LBF) are key calcium carbonate producers on reefs, of which two species were investigated for their suitability for menthol bleaching. The LBF Amphistegina lobifera, hosting diatoms, and Sorites orbiculus, hosting dinoflagellates of the family Symbiodiniaceae. This study aimed to rapidly generate symbiont-free (aposymbiotic) hosts via treatment with menthol and DCMU. The first experiment, Menthol Concentration Comparison (MCC), aimed to find a non-lethal and effective dose for both species. The second experiment, Bleaching Ecophysiology Assessment (BEA), used a larger sample size of both species to test the response to one concentration 0.19 mmol L-1 and measured growth, motility (an indicator for overall fitness) and mortality. Over the six-week time frame, menthol led to an aposymbiotic state in 100% of A. lobifera and only minimally impacted its motility and mortality. The method was also effective for S. orbiculus, where an aposymbiotic state, defined as no visible remains of symbiont cells inside the host at the end of the experimental period, occurred in 66% of specimens of the MCC experiment. Growth was strongly impacted by the bleaching protocol in both species, allowing no new calcite to be formed during the acute exposure. This method can be applied for testing aspects of symbiosis establishment in LBF as well as their potential to take up different symbionts in a short- to medium time frame.
Essential sterols from engineered yeast prevent honeybee colony population decline
Authors: Moore Elynor , de Sousa Raquel T , Felsinger Stella , Arnesen Jonathan A , Dyekjær Jane D , Farman Dudley I , Gonçalves Rui F S , Stevenson Philip C , Borodina Irina , Wright Geraldine A
Published: December 2024

Honeybees, the world’s most important crop pollinators, are increasingly facing pollen starvation arising from agricultural intensification and climate change. Frequent flowering dearth periods and high-density rearing conditions weaken colonies, often leading to their demise. Beekeepers provide colonies with pollen substitutes, but these feeds cannot sustain brood production because they lack essential sterols found in pollen. Here, we describe a technological breakthrough in honeybee nutrition with wide-reaching impacts on global food security. We first measured the quantity and proportion of sterols found in honeybee tissues. Using this information, we genetically engineered a strain of the oleaginous yeast,Yarrowia lipolytica, to produce a mixture of essential sterols for bees and incorporated it into an otherwise nutritionally complete diet. Colonies fed exclusively with this diet reared brood for significantly longer than those fed diets without suitable sterols. Incorporating sterol supplements into pollen substitutes using this method will enable beekeepers to rear healthier, longer-lived colonies to meet the growing demands for global crop pollination. It could also reduce competition between bee species for access to natural floral resources, stemming the decline of wild bee populations.
Pol II degradation activates cell death independently from the loss of transcription
Authors: Harper Nicholas W. , Birdsall Gavin A. , Honeywell Megan E. , Pai Athma A. , Lee Michael J.
Published: December 2024

Pol II-mediated transcription is essential for eukaryotic life. While loss of transcription is thought to be universally lethal, the associated mechanisms promoting cell death are not yet known. Here, we show that death following loss of Pol II is not caused by dysregulated gene expression. Instead, death occurs in response to the loss of Pol II protein itself, specifically loss of the enzymatic subunit, Rbp1. Loss of Pol II exclusively activates apoptosis, and expression of a transcriptionally inactive version of Rpb1 rescues cell viability. Using functional genomics, we identify a previously uncharacterized mechanism that regulates lethality following loss of Pol II, which we call thePol IIDegradation-dependentApoptoticResponse (PDAR). Using the genetic dependencies of PDAR, we identify clinically used drugs that owe their efficacy to a PDAR-dependent mechanism. Our findings unveil a novel apoptotic signaling response that contributes to the efficacy of a wide array of anti-cancer therapies.
The presence of an ESBL-encoding plasmid reported during aKlebsiella pneumoniaenosocomial outbreak in the United Kingdom
Authors: Fordham Stephen Mark Edward , Mantzouratou Anna , Anne Sheridan Elizabeth
Published: December 2024

The presence of extended-spectrum β-lactamase (ESBL) encoding plasmids in bacteria contributes towards rising resistance rates, mortality and healthcare costs in clinical settings. An EBSL-encoding plasmid, pESBL-PH was identified during a nosocomial outbreak ofKlebsiella pneumoniaeST628 at a United Kingdom general district hospital in 2018. A plasmid from the earliest 2018K. pneumoniaestrain discovered during the outbreak was assembled using both Oxford nanopore long reads and illumina short reads, yielding a fully closed plasmid, pESBL-PH-2018. pESBL-PH-2018 was queried against the complete NCBI RefSeq Plasmid Database, comprising 93,823 plasmids, downloaded on July 16, 2024. To identify structurally similar plasmids, strict thresholds were applied: both a shared hash ratio > 0.9 and a mash similarity ≥ 0.98. This returned 61 plasmids belonging to 13 unique sequence types (STs) hosts. The plasmids were detected in 13 unique countries, dating from 2012-2023, associated with a range of infections including bacteremia. Low numbers of single nucleotide polymorphisms (SNPs) were identified between pESBL-PH-2018 and query plasmids, further confirming their relatedness. The AMR region of the plasmids varied; interestingly IS26mediated-tandem amplification of resistance genes, including the ESBLblaCTX-M-15was identified in two independent strains raising their copy number to three. Furthermore, the genomic background of strains carrying a pESBL-PH-2018-like plasmid were analyzed, revealing truncation of the chromosomalompK36porin gene and carbapenemase resistance gene carriage on accessory plasmids in 17.85% and 26.78% of strains with a complete chromosome available. This analysis reveals the widespread dissemination of an ESBL-encoding plasmid in a background of resistance-encoding strains, requiring active surveillance.
Optimization of metagenomic detection method for human breast milk microbiome
Authors: Zhang Qiao , Zhang Yi , Zhu Jianjiang , Gao Yajun , Zeng Wen , Qi Hong
Published: December 2024

This study aims to optimize the metagenomic detection methodology of the human breast milk microbiome and analyze its composition. Twenty-two milk samples were collected from the left and right sides of lactating women during re-examinations at the Haidian Maternal and Child Health Hospital, Beijing. Microbial cell wall disruption parameters were optimized, and a nucleic acid extraction method was developed to construct a microbial DNA/RNA library. Metagenomic next-generation sequencing (mNGS) sequencing was performed, and microbial composition was analyzed using the k- mer Lowest Common Ancestor (LCA) method with a self-generated database constructed via Kraken2 software. Data showed Q20 > 95% and Q30 > 90%, with an average total data volume of 5,567 ± 376.6 Mb and non-human sequence data of 445.1 ± 63.75 Mb, significantly enhancing sequencing efficiency. The microbiome included 21 phyla, 234 genera, and 487 species, with Firmicutes and Proteobacteria as dominant phyla. Predominant genera includedStaphylococcusandStreptococcus, and major species wereStaphylococcus aureus,Streptococcus bradystis, andStaphylococcus epidermidis. Species levels exhibited significant variations among different individuals. Microbial profiles of left- and right-sided milk samples were consistent at the phylum, genus, and species levels. In addition to common bacteria, diverse viral, eukaryotic, and archaeal sequences were detected. This study refined metagenomic detection methods for human breast milk microbiota. Specific flora colonization occurred in healthy breast milk, with the left and right sides exhibiting both correlations and distinct flora environments.

Importance

Breast milk is a vital source of nutrition and immunity for infants, with its microbial composition playing a critical role in shaping the neonatal gut microbiome and supporting early development. However, technical challenges in detecting microorganisms in milk’s complex, lipid-rich environment have limited understanding of the diversity and function of these microbial communities. This study developed an optimized metagenomic sequencing method to analyze the microbial communities in breast milk from healthy mothers, identifying a wide array of bacteria, viruses, eukaryotes, and archaea. Key bacterial genera such asStaphylococcusandStreptococcuswere predominant, with specific flora exhibiting inter-individual variability. Additionally, the study revealed distinct yet correlated microbial environments in the milk from the left and right breasts. These findings advance the understanding of breast milk microbiota and provide a foundation for exploring its implications for maternal and infant health.
Continuous indices to assess the phenotypic spectrum of kidney transplant rejection
Authors: Vaulet Thibaut , Koshi Priyanka Joseph , Wellekens Karolien , Aubert Olivier , Bottomley Charlotte , Callemeyn Jasper , Cleenders Evert , Coemans Maarten , Cornell Lynn , de Vries Aiko P.J. , Divard Gillian , Emonds Marie-Paule , Florquin Florquin , Haas Mark , Halloran Philip F , Kers Jesper , Kuypers Dirk , Thangamani Muthukumar , Pagliazzi Angelica , Salvatore Steven , Thaunat Olivier , Seshan Surya V. , Van Loon Elisabet , Vanhoutte Thomas , Boehmig Georg , von Samson-Himmelstjerna Friedrich A. , Willicombe Michelle , Cherukuri Aravind , Loupy Alexandre , Roufosse Candice , Naesens Maarten
Published: December 2024

The international Banff classification for kidney transplant pathology discretizes the rejection continuum into distinct diagnostic categories, introducing artificial dichotomization and threshold effects. To better reflect the underlying disease spectrum, we developed, in this cohort study, two novel indices for quantifying antibody-mediated (AMR) and T-cell mediated rejection (TCMR) from histological lesion scores, and calculated indices for overall activity and chronicity. These indices were evaluated in one derivation cohort and two independent validation cohorts, totaling 19,500 biopsies from 8,873 kidney transplant patients across 10 centers worldwide. The AMR, TCMR, and activity indices demonstrated hierarchical ordering between No rejection, intermediate and complete rejection histology. The chronicity index showed limited association with the major diagnostic categories. In the derivation cohort, the AMR and TCMR indices discriminated AMR from absence of AMR, and TCMR from absence of TCMR, with an AUC of 0.98 (95% confidence interval 0.97 to 0.98) and 0.99 (0.99 to 1.00) respectively). This excellent discrimination was confirmed in the validation cohorts. Those indices strictly confined intermediate phenotypes to a range of low index values and related to graft failure rates even within the diagnostic categories, thus reflecting the underlying rejection continuum. The four continuous indices offer an implementable and interpretable global evaluation of kidney transplant biopsy histology while eliminating the need for intermediate diagnostic categories and enable more probabilistic reasoning in the diagnostic approach to the spectrum of kidney transplant rejection.
Compensatory justice and accountability for First Nations peoples: the Timber Creek case
Authors: Norris Ellie , Kutubi Shawgat , Finau Glenn
Published: December 2024

Purpose

This paper examines the state’s accountability to its citizens, in particular the First Peoples of settler colonial nations such as Australia, and how these responsibilities may be enacted via a process of compensatory justice in Native Title claims. We focus on the landmark Timber Creek ruling and the impacts of racialized preconceptions on the accountability outcomes of the case.

Design/methodology/approach

This study draws on critical race theory to reveal embedded racialised perspectives that perpetuate exclusion and discriminatory outcomes. Court documents including hearing transcripts, case judgements, witness statements, appellant and respondent submissions, expert reports and responses from First Nations leaders, form the basis of our analysis.

Findings

The case highlights how the compensation awarded to Native Title holders was based on racialised assumptions that prioritised neoliberal values, commercial activities and reaching a “socially acceptable” judgement over valuing Aboriginal uses of land. A critical analysis of court documents reveals the pervasiveness of presumed “objectivity” in the use of accounting tools to calculate economic value and the accountability implications of a process based on litigation, not negotiation. These findings reveal the hiding places offered by calculative practices that equate neoliberal priorities with accountability and reaffirm the importance of alternative accountings to resist inequitable distributive outcomes.

Originality/value

Novel insights, drawing on First Nations peoples’ connections to land and their perspectives on accountability and justice, are offered in this study. Our analysis of Native Title holders’ submissions to the courts alongside historical and anthropological sources leads to the conclusion that compensation decisions regarding Native Title land must be approached from the perspective of Aboriginal landowners if accountable outcomes are to be achieved.
A 3D printed microfluidic device for centrifugal droplet generation
Authors: Kubicki Wojciech , Thiha Aung , Janisz Tymon , Joseph Karunan , Jamaluddin Nurul Fauzani , Madou Marc , Walczak Rafał , Stojanovic Goran M. , Ibrahim Fatimah
Published: December 2024

Purpose

This study aims to use an additive process for the first time to develop a microfluidic device that uses centrifugal technique for precise and repeatable generation of microdroplets. Droplets have versatile applications in life sciences, but so far centrifugal devices for their production have been made mainly using standard subtractive techniques. This study focused on evaluating the applicability of 3D printing technology in the development of centrifugal microfluidic devices and investigating their properties and future applications.

Design/methodology/approach

First, the background of this interdisciplinary research, including the principle of droplet microfluidics and the centrifugal technique, is explained. The developed device has the form of a disc (similar to an audio CD), containing an integrated microfluidic system for droplet generation. The disc is rotated at a specific spin profile to induce controlled liquid flow and accurate production of oil-in-water microdroplets. The device was fabricated using material jetting technology. The design, operation principles, printing process parameters and post-processing steps are explained in detail.

Findings

The device was thoroughly characterised, including its mechanical properties, the impact of chemical treatment and the flow measurement of the liquids. The study confirms that the disc can be applied to produce various emulsions using centrifugal force alone. 3D printing technology enables potential mass production and other applications of the device.

Originality/value

The 3D printing process allowed for easy design, fabrication and duplication of the device. Compared to standard PMMA discs, a simpler fabrication protocol and a more flexible and monolithic structure were obtained. The device can be adapted to other microfluidic processes in a lab with high potential for point-of-care applications.
Collagen enhances stability and viability of diced cartilage as an injectable implant: An experimental study in rabbits
Authors: Fei Yanghonghong , Shen Shengxian , Chen Zhao , Lv Wenjia , Lu Haishan , Shi Lina , Hong Xudong , Jin Jian
Published: December 2024

The use of diced cartilage has become increasingly popular in rhinoplasty; however, the viability of the graft can vary. This study aimed to investigate the use of fillers for diced cartilage, evaluate their morphology and viability, and provide a foundation for their clinical use. Six rabbits were used in this experiment. Ear cartilage was excised and diced into pieces and mixed with different fillers, including collagen (COLD), hyaluronic acid (HAD), and normal saline (NSD), or used alone (COND) as a control. They were embedded in the backs of rabbits. After 3 months, the weight and volume of grafts were measured. The cellular viability and morphology were assessed. The HAD group showed the most significant volume change, followed by the NSD group. There was no significant weight change between the COLD and COND groups. Grossly, the COLD group appeared as a smooth block, while the COND and NSD groups appeared rough. Microscopically, fibrous tissue and collagen were arranged regularly in the COLD and HAD groups, and chondrocytes were arranged neatly. By contrast, collagen was less and arranged messily in the NSD and COND groups. There was better cell viability and angiogenesis around cartilage in the COLD group than in the HAD and NSD groups. When mixed with collagen, diced cartilage can maintain its basic shape and smooth appearance, and there is better cell viability and angiogenesis than when mixed with hyaluronic acid or normal saline, or used alone. These findings may provide implications for the clinical use of diced cartilage as injectable implants.
Electrochemical Detection of Carbon Steel Corrosion Induced by Fermentative Bacteria From Natural Gas Transmission Lines
Authors: Davis Joshua A. , Chinthala Sai Prasanna , Monty‐Bromer Chelsea N. , Senko John M.
Published: December 2024

The metabolic potential and corrosive activities of a fermentative bacterial enrichment culture from a natural gas transmission line were characterised. Three metagenome‐assembled genomes (MAGs) attributable to Cytobacillus, Lacrimispora and Staphylococcus spp. were obtained. These MAGs hosted genes involved in the fermentation of carbohydrates to organic acids, which was reflected in the acidification of the growth medium by the culture. To evaluate the corrosive activities of the culture, it was incubated in a split chamber‐zero resistance ammetry (SC‐ZRA) format. This involved deploying carbon steel coupons immersed in liquid medium in opposing chambers of an electrochemical cell. Measurement of current between the coupons indicated the extent and mechanism of corrosion. When the enrichment culture was added to one side of an SC‐ZRA incubation with bicarbonate‐buffered medium, pH change and corrosion were minimal. In bicarbonate‐free medium, the culture acidified the medium, induced electron transfer from the uninoculated chamber to the inoculated chamber, and caused mass loss. These results indicate that fermenter‐induced microbially influenced corrosion (MIC) is due to localised fluid acidification, inducing anodic reactions on the metal surface exposed to the microorganisms and mass loss of the non‐exposed metal.