bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved identification of abdominal aortic aneurysm using the Kernelized Expectation Maximization algorithm
Authors: Deidda Daniel , Akerele Mercy I. , Aykroyd Robert G. , Dweck Marc R. , Ferreira Kelley , Forsythe Rachael O. , Heetun Warda , Newby David E. , Syed Maaz , Tsoumpas Charalampos
Published: May 2021

Abdominal aortic aneurysm (AAA) monitoring and risk of rupture is currently assumed to be correlated with the aneurysm diameter. Aneurysm growth, however, has been demonstrated to be unpredictable. Using PET to measure uptake of [
18
F]-NaF in calcified lesions of the abdominal aorta has been shown to be useful for identifying AAA and to predict its growth. The PET low spatial resolution, however, can affect the accuracy of the diagnosis. Advanced edge-preserving reconstruction algorithms can overcome this issue. The kernel method has been demonstrated to provide noise suppression while retaining emission and edge information. Nevertheless, these findings were obtained using simulations, phantoms and a limited amount of patient data. In this study, the authors aim to investigate the usefulness of the anatomically guided kernelized expectation maximization (KEM) and the hybrid KEM (HKEM) methods and to judge the statistical significance of the related improvements. Sixty-one datasets of patients with AAA and 11 from control patients were reconstructed with ordered subsets expectation maximization (OSEM), HKEM and KEM and the analysis was carried out using the target-to-blood-pool ratio, and a series of statistical tests. The results show that all algorithms have similar diagnostic power, but HKEM and KEM can significantly recover uptake of lesions and improve the accuracy of the diagnosis by up to 22% compared to OSEM. The same improvements are likely to be obtained in clinical applications based on the quantification of small lesions, like for example cancer.

This article is part of the theme issue ‘Synergistic tomographic image reconstruction: part 1’.
Clinical outcomes and cost-effectiveness of COVID-19 vaccination in South Africa
Authors: Reddy Krishna P. , Fitzmaurice Kieran P. , Scott Justine A. , Harling Guy , Lessells Richard J. , Panella Christopher , Shebl Fatma M. , Freedberg Kenneth A. , Siedner Mark J.
Published: May 2021

Low- and middle-income countries are implementing COVID-19 vaccination strategies in light of varying vaccine efficacies and costs, supply shortages, and resource constraints. Here, we use a microsimulation model to evaluate clinical outcomes and cost-effectiveness of a COVID-19 vaccination program in South Africa. We varied vaccination coverage, pace, acceptance, effectiveness, and cost as well as epidemic dynamics. Providing vaccines to at least 40% of the population and prioritizing vaccine rollout prevented >9 million infections and >73,000 deaths and reduced costs due to fewer hospitalizations. Model results were most sensitive to assumptions about epidemic growth and prevalence of prior immunity to SARS-CoV-2, though the vaccination program still provided high value and decreased both deaths and health care costs across a wide range of assumptions. Vaccination program implementation factors, including prompt procurement, distribution, and rollout, are likely more influential than characteristics of the vaccine itself in maximizing public health benefits and economic efficiency.
Household overcrowding and risk of SARS-CoV-2: analysis of the Virus Watch prospective community cohort study in England and Wales
Authors: Aldridge Robert W , Pineo Helen , Fragaszy Ellen , Eyre Max , Kovar Jana , Nguyen Vincent , Beale Sarah , Byrne Thomas , Aryee Anna , Smith Colette , Devakumar Delanjathan , Taylor Jonathon , Katikireddi Srinivasa Vittal , Erica Fong Wing Lam , Geismar Cyril , Patel Parth , Shrotri Madhumita , Braithwaite Isobel , Navaratnam Annalan M D , Johnson Anne M , Hayward Andrew
Published: May 2021

Background

Household overcrowding is associated with increased risk of infectious diseases across contexts and countries. Limited data exist linking household overcrowding and risk of COVID-19. We used data collected from the Virus Watch cohort to examine the association between overcrowded households and SARS-CoV-2.

Methods

The Virus Watch study is a household community cohort of acute respiratory infections in England & Wales that began recruitment in June 2020. We calculated the persons per room for each household and classified accommodation as overcrowded when the number of rooms□was fewer than the number of people. We considered two primary outcomes - PCR-confirmed positive SARS-CoV-2 antigen tests and laboratory confirmed SARS-CoV-2 antibodies (Roche Elecsys anti-N total immunoglobulin assay). We used mixed effects logistic regression models that accounted for household structure to estimate the association between household overcrowding and SARS-CoV-2 infection.

Results

The proportion of participants with a positive SARS-CoV-2 PCR result was highest in the overcrowded group (6.6%; 73/1,102) and lowest in the under-occupied group (2.9%; 682/23,219). In a mixed effects logistic regression model that included age, sex, ethnicity, household income and geographical region, we found strong evidence of an increased odds of having a positive PCR SARS-CoV-2 antigen result (Odds Ratio 3.72; 95% CI: 1.92, 7.13; p-value < 0.001) and increased odds of having a positive SARS-CoV-2 antibody result in individuals living in overcrowded houses (2.96; 95% CI: 1.13, 7.74; p-value =0.027) compared to people living in under-occupied houses. The proportion of variation at the household level was 75.1% and 74.0% in the PCR and antibody models respectively.

Discussion

Public health interventions to prevent and stop the spread of SARS-CoV-2 should consider the much greater risk of infection for people living in overcrowded households and pay greater attention to reducing household transmission. There is an urgent need to better recognise housing as a leading determinant of health in the context of a pandemic and beyond.
Quantifying the potential dominance of immune-evading SARS-CoV-2 variants in the United States
Authors: Sah Pratha , Vilches Thomas N. , Shoukat Affan , Fitzpatrick Meagan C. , Pandey Abhishek , Singer Burton H. , Moghadas Seyed M. , Galvani Alison P.
Published: May 2021

Recent evidence suggests that some new SARS-CoV-2 variants with spike mutations, such as P.1 (Gamma) and B.1.617.2 (Delta), exhibit partial immune evasion to antibodies generated by natural infection or vaccination. By considering the Gamma and Delta variants in a multi-variant transmission dynamic model, we evaluated the dominance of these variants in the United States (US) despite mounting vaccination coverage and other circulating variants. Our results suggest that while the dominance of the Gamma variant is improbable, the Delta variant would become the most prevalent variant in the US, driving a surge in infections and hospitalizations. Our study highlights the urgency for accelerated vaccination and continued adherence to non-pharmaceutical measures until viral circulation is driven low.
Contribution of white matter hyperintensities to ventricular enlargement in older adults
Authors: Jochems Angela CC , Maniega Susana Muñoz , del C Valdés Hernández Maria , Barclay Gayle , Anblagan Devasuda , Ballerini Lucia , Meijboom Rozanna , Wiseman Stewart , Taylor Adele M , Corley Janie , Chappell Francesca M , Backhouse Ellen V , Stringer Michael S , Dickie David Alexander , Bastin Mark E , Deary Ian J , Cox Simon R , Wardlaw Joanna M
Published: May 2021

Background and Purpose

Ventricular enlargement, especially enlargement of the lateral ventricles, is thought to be positively associated with white matter hyperintensities (WMH). Possible mechanisms behind the association are unclear. Lateral ventricles might increase due to generalised brain tissue loss not specific to periventricular WMH. Alternatively, they may expand into areas of tissue loss related to WMH, take up space and grow in size.

Methods

We investigated relations between longitudinal lateral ventricle and WMH volume changes, alongside vascular risk factors, in community-dwelling older people. We assessed lateral ventricle and WMH volumes, accounting for total brain volume, blood pressure, medical assessments and self-reported history of stroke, cardiovascular disease, diabetes and smoking. We used longitudinal data at three time points, each three years apart, between ages 73 to 79, including MRI data from all available time points.

Results

Lateral ventricle volume increased steadily with age in all participants, WMH volume change was more variable. Decrease of WMH volume was found in around 20% and increase in remaining subjects. Using a repeated-measurements linear mixed model we found that over 6 years, lateral ventricle volume increased by 3% per year of age, 0.1% per mm Hg increase in mean blood pressure, 3.2% per 1% decrease of total brain volume, and 4.5% per 1% increase of WMH volume. Over time, lateral ventricle volumes were 19% smaller in women than men. No associations were found with other variables.

Conclusions

Changes in lateral ventricle volumes and WMH volumes over time are only modestly associated, independent of general brain atrophy.
Clinicopathological features and outcome of COVID-19- early experiences from three covid hospitals, Chittagong, Bangladesh
Authors: Biswas Rajat Sanker Roy , Nath Jishu Deb , Barua Pranab Kumar , Karim Md Rejaul , Safatujjahan  , Islam Mohammad Saiful , Ahmed Kazi Farhad
Published: May 2021

Introduction

COVID 19 is an unknown virus affecting mankind creating a deadly experience to all. It is true for Bangladesh also. So the objectives of the present study is to find the clinicopathological features and outcome of COVID patients admitted in three COVID dedicated hospitals of Chittagong, Bnagladesh.

Methods

This was an observational study where a total of 209 patients admitted in three COVID dedicated hospital were recruited. Clinicopathological data were recorded and patients were under observation till discharge and thus outcome were recorded. Prior consent was taken from the patients and ethical clearance was also taken. Data was compiled and analyzed by SPSS-20.

Results

Among 209 patients most of them were male 139(66.5%) and male to female ratio was 1.98:1. Age group distribution revealed more were aggregated in age group 41-50 years 36(17.2%), 51-60 years 54(25.8%) and 61-70 years 57(27.3%). Among all 92(44%) patients were RT-PCR positive and 117(56%) were probable cases. Fever was present in 195(93.3%) cases, cough in 180(86.1%), respiratory distress in 105(50.2%) anosmia in 123(58.8%), aguesea in 112 (53.58%) and lethargy was present in 143(68.42%). Chest X-ray findings revealed 73(34.9%) had bilateral patchy opacities, 20(9.6%) had unilateral opacities 65(31.1%) had consolidations, 6(2.9%) had ground glass opacities and 2(1.0%) had pleural effusion. Supplemental O2 was given in 173(82.8%) patients, Favipiravir in 59(28.2%), Remdisivir in 111(53.1%), Methylprednisolone in 87(41.6%), Dexamethasone in 93(44.5%), Antibiotics in 204(97.60%), Toccilizumab in 34(16.3%), plasma in 18(8.6%) and LMWH in 200(95.7%) patients. Regarding outcome of the COVID patients admitted, 85(92.4%) patients improved, 6(6.5%) died who were RT-PCR positive and 107(91.15%) improved, 9(7.7%) died who were probable cases. Total death rate was 7.1%.

Conclusion

Present study findings were some early activities among COVID patients in the years 2020. Male were more affected and middle age group people were the most victims.
Mental health of Adolescents in the Pandemic: Long-COVID19 or Long-Pandemic Syndrome?
Authors: Blankenburg Judith , Wekenborg Magdalena K. , Reichert Jörg , Kirsten Carolin , Kahre Elisabeth , Haag Luise , Schumm Leonie , Czyborra Paula , Berner Reinhard , Armann Jakob P.
Published: May 2021

Backround

Post-COVID19 complications such as pediatric inflammatory multisystem syndrome (PIMS) and Long-COVID19 move increasingly into focus, potentially causing more harm in this age group than the acute infection. To better understand the symptoms of long-COVID19 in adolescents and to distinguish infection-associated symptoms from pandemic-associated symptoms, we conducted a Long-COVID19 survey, comparing responses from seropositive and seronegative adolescents. To our knowledge, data of Long-COVID19 surveys with seronegative control groups have not been published yet.

Methods

Since May 2020 students grade 8-12 in fourteen secondary schools in Eastern Saxony were enrolled in the SchoolCovid19 study. Seroprevalence was assessed via serial SARS-CoV-2 antibody testing in all participants. Furthermore, during the March/April 2021 study visit all participants were asked to complete a 12 question Long-COVID19 survey regarding the occurrence and frequency of difficulties concentrating, memory loss, listlessness, headache, abdominal pain, myalgia/ arthralgia, fatigue, insomnia and mood (sadness, anger, happiness and tenseness).

Findings

1560 students with a median age of 15 years participated in this study. 1365 (88%) were seronegative, 188 (12%) were seropositive. Each symptom was present in at least 35% of the students within the last seven days before the survey. However, there was no statistical difference comparing the reported symptoms between seropositive students and seronegative students. Whether the infection was known or unknown to the participant did not influence the prevalence of symptoms.

Interpretation

The lack of differences comparing the reported symptoms between seropositive and seronegative students suggests that Long-COVID19 might be less common than previously thought and emphasizing the impact of pandemic-associated symptoms regarding the well-being and mental health of young adolescents.

Funding

This study was supported by a grant by the Federal State of Saxony. M.K.W. was supported by the Else Kröner-Fresenius Center for Digital Health (EKFZ), TU Dresden, Germany.
COVID-19 Pandemic and Academic Speculation of Medical Students of Bangladesh: A Cross-sectional, Comparative Study
Authors: Johora Fatema , Abbasy Asma Akter , Jeenia Fatiha Tasmin , Bhowmik Mithun Chandro , Moitra Priyanka , Mahboob Sabiha , Ferdous Jannatul
Published: May 2021

Background

COVID-19 pandemic has caused unprecedented disruptions worldwide including education system. While the necessary focus has been on patient care andwellbeing of healthcare professionals, the impacts on medical students need to be discussed.

Methods

This cross-sectional comparative study was conducted to evaluate the academic speculation of medical students studying in government and non-government institute during COVID-19 pandemic. A structured questionnaire survey linked in the google form was used as study instrument and was distributed among study population through email, messenger, whatsapp and other social media. Total 1020 students were participated in the study

Results

In this research, 441 (43.24%) and 579 (56.77%) students were from government and non-government medical colleges respectively. Opinion of both group was almost similar regarding disruption of medical education, loss of clinical skills and competency, future career plan, and stress and anxiety but significant differences were observed between both group regarding issue of financial burden, meaningful learning opportunities, fear of getting infected and maintenance of social distancing in hostel.

Conclusion

The study revealed similar kind of viewpoint about disruption of education, loss of clinical skill and competency, changing aspects of future career plan and increased level of stress and anxiety among medical students of government and non-government institutes of Bangladesh but different speculations were found regarding issue of financial burden, meaningful learning opportunities, fear of getting infected and possibility of maintenance of social distancing in hostel.
Mechanosensitivity of amoeboid cells crawling in 3D
Authors: Gaertner Florian , Reis-Rodrigues Patricia , de Vries Ingrid , Hons Miroslav , Aguilera Juan , Riedl Michael , Leithner Alexander , Merrin Jack , Zheden Vanessa , Kaufmann Walter Anton , Hauschild Robert , Sixt Michael
Published: May 2021

Efficient immune-responses require migrating leukocytes to be in the right place at the right time. When crawling through the body amoeboid leukocytes must traverse complex three-dimensional tissue-landscapes obstructed by extracellular matrix and other cells, raising the question how motile cells adapt to mechanical loads to overcome these obstacles. Here we reveal the spatio-temporal configuration of cortical actin-networks rendering amoeboid cells mechanosensitive in three-dimensions, independent of adhesive interactions with the microenvironment. In response to compression, Wiskott-Aldrich syndrom protein (WASp) assembles into dot-like structures acting as nucleation sites for actin spikes that in turn push against the external load. High precision targeting of WASp to objects as delicate as collagen fibers allows the cell to locally and instantaneously deform its viscoelastic surrounding in order to generate space for forward locomotion. Such pushing forces are essential for fast and directed leukocyte migration in fibrous and cell-packed tissues such as skin and lymph nodes.

In Brief

WASp-driven actin spikes counter compressive loads of crowded tissue-landscapes.
Integrated phospho-proteogenomic and single-cell transcriptomic analysis of meningiomas establishes robust subtyping and reveals subtype-specific immune invasion
Authors: Blume Christina , Dogan Helin , Schweizer Lisa , Peyre Matthieu , Doll Sophia , Picard Daniel , Sankowski Roman , Hovestadt Volker , Okonechnikov Konstantin , Sievers Philipp , Patel Areeba , Reuss David , Friedrich Mirco , Stichel Damian , Schrimpf Daniel , Beck Katja , Wirsching Hans-Georg , Jungwirth Gerhard , Hanemann C Oliver , Lamszus Katrin , Westphal Manfred , Etminan Nima , Unterberg Andreas , Mawrin Christian , Remke Marc , Ayrault Olivier , Lichter Peter , Pfister Stefan M , Reifenberger Guido , Platten Michael , Milde Till , Jones David TW , Grossmann Rachel , Ram Zvi , Ratliff Miriam , Herold-Mende Christel , Mallm Jan-Philipp , Neidert Marian C , Wick Wolfgang , Prinz Marco , Weller Michael , Mann Matthias , Kalamarides Michel , von Deimling Andreas , Schlesner Matthias , Sahm Felix
Published: May 2021

Meningiomas are the most frequent primary intracranial tumors. They can follow a wide clinical spectrum from benign to highly aggressive clinical course. No specific therapy exists for refractory cases or cases not amenable to resection and radiotherapy. Identification of risk of recurrence and malignant transformation for the individual patients is challenging. However, promising molecular markers and prognostic subgrouping by DNA methylation are emerging. Still, the biological underpinnings of these diagnostic subgroups are elusive, and, consequently, no novel therapeutic options arise thereof. Here we establish robust subgroups across the full landscape of meningiomas, consistent through DNA methylation, mutations, the transcriptomic, proteomic and phospho-proteomic level. Pronounced proliferative stress and DNA damage repair signals in malignant cells and in clusters exclusive to recurrent tumors are in line with their higher mitotic activity, but also provide an explanation for the accumulation of genomic instability in anaplastic meningiomas. Although homozygous deletion of CDKN2A/B is a diagnostic marker of high-grade meningioma, the expression of its gene product increased from low to non-deleted high-grade cases. Differences between subgroups in lymphocyte and myeloid cell infiltration, representing a majority of tumor mass in low-grade NF2 tumors, could be assigned to cluster-specific interaction with tumor cells. Activation to a more proinflammatory phenotype and decreased infiltration of myeloid cells in high-grade cases correlated with lower expression of CSF1, located on chromosome arm 1p, whose deletion is known as prognostic marker, with no proposed mechanism before. Our results demonstrate a robust molecular subclassification of a tumor type across multiple layers, provide insight into heterogeneous growth dynamics despite shared pathognomonic mutations, and highlight immune infiltration modulation as a novel target for meningioma therapy.
Marine biofilms on different fouling control coating types reveal differences in microbial community composition and abundance
Authors: Papadatou Maria , Robson Samuel C. , Dobretsov Sergey , Watts Joy E.M. , Longyear Jennifer , Salta Maria
Published: May 2021

Marine biofouling imposes serious environmental and economic impacts on marine applications, especially in the shipping industry. To combat biofouling, protective coatings are applied on vessel hulls which are divided into two major groups: biocidal and non-toxic fouling-release. The aim of the current study was to explore the effect of coating type on microbial biofilm community profiles to better understand the differences between the communities developed on fouling control biocidal antifouling and biocidal-free coatings. Biocidal (Intersmooth® 7460HS SPC), fouling-release (Intersleek® 900), and inert surfaces were deployed in the marine environment for 4 months and the biofilms that developed on these surfaces were investigated using Illumina NGS sequencing, targeting the prokaryotic 16S rRNA gene. The results confirmed differences in the community profiles between coating types. The biocidal coating supported communities dominated by Alphaproteobacteria (Loktanella, Sphingorhabdus, Erythrobacter) and Bacteroidetes (Gilvibacter), whilst other taxa such as Portibacter and Sva0996 marine group, proliferated on the fouling-release surface. Knowledge of these marine biofilm components on fouling control coatings will serve as a guide for future investigations of marine microfouling as well as informing the coatings industry of potential microbial targets for robust coating formulations.
Spontaneous formation of prebiotic compartment colonies on Hadean Earth and pre-Noachian Mars
Authors: Köksal Elif S. , Põldsalu Inga , Friis Henrik , Mojzsis Stephen , Bizzarro Martin , Gözen Irep
Published: May 2021

The primitive cells that emerged at the origin of life are commonly viewed as spherical biosurfactant shells, freely suspended in aqueous media1–3. This model explains initial, but not subsequent events in the development process towards structured protocells. Taking into consideration the involvement of naturally occurring surfaces, which were abundant on the early Earth4, we report feasible and productive pathways for the development of primitive cells. Surfaces intrinsically possess energy, easily utilized by the interfacing amphiphiles, such as lipids, to attain self-organization and spontaneous transformations5–7. We show that the physical interaction of phospholipid pools with 20 Hadean Earth analogue materials as well as a Martian meteorite composed of fused regolith representing the ancient crust of Mars, consistently lead to the shape transformation and autonomous formation of surfactant compartment assemblies. Dense, colony-like protocell populations grow from these lipid deposits, predominantly at the grain boundaries or cleavages of the investigated natural surfaces, and remain there for several days. The model protocells in our study are able to autonomously develop, transform and pseudo-divide, and encapsulate RNA as well as DNA. We also demonstrate that they can accommodate non-enzymatic, DNA strand displacement reactions. Our findings suggest a feasible route towards the transformation from nonliving to living entities, and provide fresh support for the ‘Lipid World’ hypothesis8.
Phase separation of both a plant virus movement protein and cellular factors support virus-host interactions
Authors: Brown Shelby L. , May Jared P.
Published: May 2021

Phase separation concentrates biomolecules, which should benefit RNA viruses that must sequester viral and host factors during an infection. Here, the p26 movement protein from Pea enation mosaic virus 2 (PEMV2) was found to phase separate and partition in nucleoli and G3BP stress granules (SGs) in vivo. Electrostatic interactions drive p26 phase separation as mutation of basic (R/K-G) or acidic (D/E-G) residues either blocked or reduced phase separation, respectively. During infection, p26 must partition inside the nucleolus and interact with fibrillarin (Fib2) as a pre-requisite for systemic trafficking of viral RNAs. Partitioning of p26 in pre-formed Fib2 droplets was dependent on p26 phase separation suggesting that phase separation of viral movement proteins supports nucleolar partitioning and virus movement. Furthermore, viral ribonucleoprotein complexes containing p26, Fib2, and PEMV2 RNA were formed via phase separation in vitro and could provide the basis for self-assembly in planta. Interestingly, both R/K-G and D/E-G p26 mutants failed to support systemic trafficking of a Tobacco mosaic virus (TMV) vector in Nicotiana benthamiana suggesting that p26 phase separation, proper nucleolar partitioning, and systemic movement are intertwined. p26 also partitioned in SGs and G3BP over-expression restricted PEMV2 accumulation >20-fold. Expression of phase separation-deficient G3BP only restricted PEMV2 5-fold, demonstrating that G3BP phase separation is critical for maximum antiviral activity.

AUTHOR SUMMARY

Phase separation of several cellular proteins is associated with forming pathological aggregates and exacerbating neurodegenerative disease progression. In contrast, roles for viral protein phase separation in RNA virus lifecycles are less understood. Here, we demonstrate that the p26 movement protein from Pea enation mosaic virus 2 phase separates and partitions with phase-separated cellular proteins fibrillarin and G3BP. The related orthologue from Groundnut rosette virus has been extensively studied and is known to interact with fibrillarin in the nucleolus as a pre-requisite for virus movement. We determined that basic residues and electrostatic interactions were critical for p26 phase separation. Furthermore, mutation of charged residues prevented the rescue of a movement-deficient Tobacco mosaic virus vector in Nicotiana benthamiana. Stress granules form through phase separation and we found that p26 could partition inside stress granules following heat shock. Phase separation of the stress granule nucleator G3BP was required for maximum antiviral activity and constitutes a host response that is dependent on cellular protein phase separation. Collectively, we demonstrate that phase separation of a plant virus protein facilitates virus-host interactions that are required for virus movement and phase separation of cellular proteins can simultaneously restrict virus replication.
The Aspartyl Protease Ddi1 Is Essential for Erythrocyte Invasion by the Malaria Parasite
Authors: Ridewood Sophie , Dirac-Svejstrup A. Barbara , Howell Stephen , Weston Anne , Lehmann Christine , Patel Asha Parbhu , Collinson Lucy , Bingham Ryan , Powell David , Snijder Ambrosius , Svejstrup Jesper Q. , Deu Edgar
Published: May 2021

Malaria pathology is caused by the exponential replication of Plasmodium parasites in the blood stream. The bottleneck of the parasite life cycle is the invasion of erythrocytes immediately after parasites egress from infected red blood cells. DNA damage-inducible protein 1 (Ddi1) is a conserved eukaryotic proteasome shuttle protein containing an internal retroviral-like protease domain. Using conditional genetics, we now show that the proteolytic activity of the P. falciparum homologue, PfDdi1, is critically required for invasion of red blood cells. Furthermore, PfDdi1 disruption results in the accumulation of highly polyubiquitinated proteins that can be processed by purified PfDdi1 or distant eukaryotic homologues. We also show that PfDdi1 interacts with multiple components of the ubiquitin-proteasome system and that parasites lacking PfDdi1 are more sensitive to proteasome inhibition. Overall, this study establishes PfDdi1 as a key component of the eukaryotic ubiquitin-proteasome system and as a promising antimalarial target.
The macrophage reprogramming ability of antifolates reveals soluble CD14 as a potential biomarker for methotrexate response in rheumatoid arthritis
Authors: Fuentelsaz-Romero Sara , Alonso Celia Barrio , Campos Raquel García , Torresano Mónica Torres , Muller Ittai , Triguero-Martínez Ana , Nuño Laura , Villalba Alejandro , García-Vicuña Rosario , Jansen Gerrit , Miranda-Carús María-Eugenia , González-Álvaro Isidoro , Puig-Kröger Amaya
Published: May 2021

The physio-pathological relevance of the one-carbon metabolism (OCM) is illustrated by the chemotherapeutic and anti-inflammatory effects of the antifolates Pemetrexed (PMX) and Methotrexate (MTX) in cancer and rheumatoid arthritis (RA). We report that OCM determines the functional and gene expression profile of human macrophages. PMX induces the acquisition of a p53-dependent proinflammatory gene signature in human monocyte-derived macrophages (GM-MØ). Indeed, OCM blockade reprograms GM-MØ towards a state of LPS-tolerance at the signaling and functional levels, an effect abolished by folinic acid. Importantly, OCM blockade led to reduced expression of membrane-bound and soluble CD14 (sCD14), whose exogenous addition restores LPS sensitivity. The therapeutic relevance of these results was confirmed in early RA patients, as MTX-responder RA patients exhibit lower sCD14 serum levels, with baseline sCD14 levels predicting MTX response. Our results indicate that OCM is a metabolic circuit that critically mediates the acquisition of innate immune tolerance, and positions sCD14 as a valuable tool to predict MTX-response in RA patients.
Effect of plant tubulin kinetic diversification on microtubule lengths
Authors: Jain Kunalika , Roy Megha , Athale Chaitanya A.
Published: May 2021

Microtubules (MTs) are dynamic polymers vital for cellular physiology. Bulk tubulin polymerization is nucleation dependent, while individual filaments exhibit ‘dynamic instability’ driven by GTP hydrolysis rates. Although MTs assembled from well-studied animal brain tubulins have very comparable nucleation and GTP-hydrolysis rates, the kinetic rates of evolutionarily more distant species could diverge. Here we focus on a plant tubulin, the legume Vigna sp. (mung bean) to test the effect of kinetic diversification on MT polymerization. We activity purify tubulin from seedlings and find MT filaments are fewer and shorter than animal brain tubulin. We find mung tubulin polymerization kinetics is nucleation dependent with a high rate of GTP hydrolysis and a critical concentration lower than previously reported for tubulins. A computational model of the kinetics based on the relative influence of rates of nucleation and hydrolysis demonstrates increased rates of hydrolysis can affect MT filament numbers and their lengths, as compared to increasing nucleation rates. Our approach provides a framework to compare the effect of evolutionary diversification of MT nucleation and elongation.
Epigenetic Inheritance is Gated by Naïve Pluripotency and Dppa2
Authors: Carlini Valentina , Policarpi Cristina , Hackett Jamie A.
Published: May 2021

Environmental factors can trigger cellular responses that propagate across mitosis or even generations. Perturbations to the epigenome could underpin such acquired changes, however, the extent and contexts in which modified chromatin states confer heritable memory in mammals is unclear. Here we exploit a modular epigenetic editing strategy to establish de novo heterochromatin domains (epialleles) at endogenous loci and track their inheritance in a developmental model. We find that naïve pluripotent phases systematically erase ectopic domains of heterochromatin via active mechanisms, which acts as an intergenerational safeguard against transmission of epialleles. Upon lineage specification however, acquired chromatin states can be probabilistically inherited under selectively favourable conditions, including propagation of p53 silencing through in vivo development. Using genome-wide CRISPR screening, we identify the mechanisms that block heritable silencing memory in pluripotent cells, and demonstrate removal of Dppa2 unlocks the potential for epigenetic inheritance uncoupled from DNA sequence. Our study outlines a mechanistic basis for how epigenetic inheritance is restricted in mammals, and reveals genomic- and developmental-contexts in which heritable memory is feasible.
Exploiting noise, non-linearity, and feedback for differential control of multiple synthetic cells with a single optogenetic input
Authors: May Michael P , Munsky Brian
Published: May 2021

Synthetic biology seeks to develop modular bio-circuits that combine to produce complex, controllable behaviors. These designs are often subject to noisy fluctuations and uncertainties, and most modern synthetic biology design processes have focused to create robust components to mitigate the noise of gene expression and reduce the heterogeneity of single-cell responses. However, deeper understanding of noise can achieve control goals that would otherwise be impossible. We explore how an “Optogenetic Maxwell Demon” could selectively amplify noise to control multiple cells using single-input-multiple-output (SIMO) feedback. Using data-constrained stochastic model simulations and theory, we show how an appropriately selected stochastic SIMO controller can drive multiple different cells to different user-specified configurations irrespective of initial condition. We explore how controllability depends on cells’ regulatory structures, the amount of information available to the controller, and the accuracy of the model used. Our results suggest that gene regulation noise, when combined with optogenetic feedback and non-linear biochemical auto-regulation, can achieve synergy to enable precise control of complex stochastic processes.
O-GlcNAcylation reduces phase separation and aggregation of the EWS
N-terminal low complexity region
Authors: Nosella Michael L. , Tereshchenko Maria , Pritišanac Iva , Chong P. Andrew , Toretsky Jeffrey A. , Lee Hyun O. , Forman-Kay Julie D.
Published: May 2021

Many membraneless organelles are thought to be biomolecular condensates
formed by phase separation of proteins and other biopolymers. Post-translational
modifications (PTMs) can impact protein phase separation behavior, although for
many PTMs this aspect of their function is unknown.
O-linked
β-D-N-acetylglucosaminylation
(O-GlcNAcylation) is an abundant form of
intracellular glycosylation whose roles in regulating biomolecular condensate
assembly and dynamics have not been delineated. Using an in
vitro approach, we found that
O-GlcNAcylation reduces the phase separation
propensity of the EWS N-terminal low complexity
region (LCRN) under different conditions, including in the
presence of the arginine-and glycine-rich RNA-binding domains (RBD).
O-GlcNAcylation enhances fluorescence recovery
after photobleaching (FRAP) within EWS LCRN condensates and
causes the droplets to exhibit more liquid-like relaxation following fusion.
Following extended incubation times, EWS LCRN+RBD
condensates exhibit diminished FRAP, indicating a loss of fluidity, while
condensates containing the O-GlcNAcylated
LCRN do not. In HeLa cells, EWS is less
O-GlcNAcylated following
OGT knockdown and more prone to aggregation based
on a filter retardation assay. Relative to the human proteome,
O-GlcNAcylated proteins are enriched with regions
that are predicted to phase separate, suggesting a general role of
O-GlcNAcylation in regulation of biomolecular
condensates.

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Generation and timing of graded responses to morphogen gradients
Authors: Carmon Shari , Jonas Felix , Barkai Naama , Schejter Eyal D. , Shilo Ben-Zion
Published: May 2021

Morphogen gradients are known to subdivide a naïve cell field into distinct zones of gene expression. Here we examine whether morphogens can also induce a graded response within such domains. To this end we explore the role of the Dorsal protein nuclear gradient along the dorso-ventral axis in defining the graded pattern of actomyosin constriction that initiates gastrulation in early Drosophila embryos. Two complementary mechanisms for graded accumulation of mRNAs of critical zygotic target genes were identified. First, activation of target-gene expression expands over time from the ventral-most region of high nuclear Dorsal to lateral regions where the levels are lower, due to a Dorsal-dependent priming probability of transcription sites. Thus, sites that are activated earlier will lead to more mRNA accumulation. Second, once the sites are primed, the rate of Pol II loading is also dependent on Dorsal levels. Morphological restrictions require that translation of the graded mRNA be delayed until completion of embryonic cell formation. Such timing is achieved by large introns, that provide a delay in production of the mature mRNAs.
Bacteriophage adaptation to a mammalian mucosa reveals a trans-domain evolutionary axis
Authors: Chin Wai Hoe , Kett Ciaren , Cooper Oren , Müseler Deike , Zhang Yaqi , Bamert Rebecca , Patwa Ruzeen , Woods Laura C. , Devendran Citsabehsan , Tiralongo Joe , Lithgow Trevor , McDonald Mike J. , Neild Adrian , Barr Jeremy J.
Published: May 2021

The majority of viruses within the human gut are obligate bacterial viruses known as bacteriophages (phages)1. Their bacteriotropism underscores the study of phage ecology in the gut, where they sustain top-down control2–4 and co-evolve5 with gut bacterial communities. Traditionally, these were investigated empirically via in vitro experimental evolution6–8 and more recently, in vivo models were adopted to account for gut niche effects4,9. Here, we probed beyond conventional phage-bacteria co-evolution to investigate the potential evolutionary interactions between phages and the mammalian “host”. To capture the role of the mammalian host, we recapitulated a life-like mammalian gut mucosa using in vitro lab-on-a-chip devices (to wit, the gut-on-a-chip) and showed that the mucosal environment supports stable phage-bacteria co-existence. Next, we experimentally evolved phage populations within the gut-on-a-chip devices and discovered that phages adapt by de novo mutations and genetic recombination. We found that a single mutation in the phage capsid protein Hoc – known to facilitate phage adherence to mucus10 – caused altered phage binding to fucosylated mucin glycans. We demonstrated that the altered glycan-binding phenotype provided the evolved mutant phage a competitive fitness advantage over their ancestral wildtype phage in the gut-on-a-chip mucosal environment. Collectively, our findings revealed that phages – in addition to their evolutionary relationship with bacteria – are also able to engage in evolution with the mammalian host.
How Korean universities portray themselves in the global marketplace: text-mining analysis of university president's messages
Authors: Lee Soo Jeung , Park Soowon
Published: May 2021

Purpose

This study aims to examine university president's messages (PMs) on Korean university websites to analyze how Korean universities present their image and position themselves in the global marketplace.

Design/methodology/approach

Assuming that visions, missions and strategies might vary depending on the characteristics of a university, the study analyzed PMs according to university type: research, teaching and technology. The authors applied text analysis to 105 Korean universities' PMs to understand the images they project. The authors also used text mining on the PMs to examine the frequencies of keywords, to create word clouds, to investigate the keywords' degrees of centrality and to conduct sentiment analysis.

Findings

The findings show that Korean universities' PMs project hybrid images, simultaneously portraying the universities as public institutes that produce public goods and as globally competitive strategic actors. In addition, while Korean university PMs explicitly position the universities as education-oriented, they nonetheless reveal that the universities pursue both research-oriented and education-oriented goals.

Originality/value

This is the study to examine PMs using text mining with Python to extract information and reveal hidden meanings regarding how universities portray themselves on their websites. Highlighting current challenges faced by universities, this article argues for continued discussion on their societal roles and their strategies for positioning themselves in today's globalized and marketized higher education environment.
The impact of climate change on the Mpumalanga Provincial Archives and records management activities
Authors: Netshakhuma Nkholedzeni Sidney
Published: May 2021

Purpose

The purpose of this paper is to investigate the impact of climate change on South Africa’s Mpumalanga Provincial Archives (MPA) and related records management activities.

Design/methodology/approach

A qualitative research approach/method was used to collect data from the source, including purposive sampling and expert knowledge solicited through semi-structured interviews. A review was undertaken to source climate data and related archival sector literature.

Findings

Recent extreme weather events in Mpumalanga seem to bear out climate change projections. The current absence of relevant strategies and plans implies that the MPA and provincial departments are not yet prepared for emergencies. The lack of a plan, an implementation strategy and related training may increase the impact of disasters on the provincial archives’ environment. Without disaster plans and robust preparedness, the question of how the MPA is going to preserve archives for future generations is raised. In addition, due to a lack of guidance for registry staff, appraisal is not allowing for identification and processing of archival materials, so combined with a lack of disaster management strategies and plans contributes to the loss of archives.

Research limitations/implications

This research is limited to the MPA; however, the findings may be extended to other South Africa provincial archives and parts of the world experiencing similar issues. There is a need to conduct similar research on a larger scale so as to explore the impact of climate change in other provincial archives to provide a wider context of the problem within South Africa.

Practical implications

When archivists accept holdings into their repositories, they take the responsibility for their archival custody. But, these efforts may come to nothing if the archives are lost. Disaster management is the key to the protection of the archives.

Originality/value

This paper contributes to the literature on the impact of climate change on archives. The results achieved should be seen as a first step towards identification of the issue.
Worldwide aflatoxin contamination of agricultural products and foods: From occurrence to control
Authors: Jallow Abdoulie , Xie Huali , Tang Xiaoqian , Qi Zhang , Li Peiwu
Published: May 2021

Aflatoxins represent a global public health and economic concern as they are responsible for significant adverse health and economic issues affecting consumers and farmers worldwide. Produced by fungal species from the Aspergillus genus, aflatoxins are a toxic, mutagenic, and carcinogenic group of fungal metabolites that routinely contaminate food and agricultural products. Climate and diet are essential factors in the aflatoxin contamination of food and subsequent human exposure process. Countri

es with warmer climates and staple foods that are aflatoxin‐susceptible shoulder a substantial portion of the global aflatoxins burden. Enactment of regulations, prevention of pre‐ and postharvest contamination, decontamination, and detoxification have been used to prevent human dietary exposure to aflatoxin. Exploiting their chemical and structural properties, means are devised to detect and quantify aflatoxin presence in foods. Herein, recent developments in several important aspects impacting aflatoxin contamination of the food supply, including: fungal producers of the toxin, occurrence in food, worldwide regulations, detection methods, preventive strategies, and removal and degradation methods were reviewed and presented. In conclusion, aflatoxin continues to be a major food safety problem, especially in developing countries where regulatory limits do not exist or are not adequately enforced. Finally, knowledge gaps and current challenges in each discussed aspect were identified, and new solutions were proposed.
The effect of person, treatment and prescriber characteristics on retention in opioid agonist treatment: a 15‐year retrospective cohort study
Authors: Bharat Chrianna , Larney Sarah , Barbieri Sebastiano , Dobbins Timothy , Jones Nicola R. , Hickman Matthew , Gisev Natasa , Ali Robert , Degenhardt Louisa
Published: May 2021

Background and Aims

There is limited evidence on the relationship between retention in opioid agonist treatment for opioid dependence and characteristics of treatment prescribers. This study estimated retention in buprenorphine and methadone treatment and its relationship with person, treatment and prescriber characteristics.

Design

Retrospective longitudinal study.

Setting

New South Wales, Australia.

Participants

People entering the opioid agonist treatment programme for the first time between August 2001 and December 2015.

Measurements

Time in opioid agonist treatment (primary outcome) was modelled using a generalized estimating equation model to estimate associations with person, treatment and prescriber characteristics.

Findings

The impact of medication type on opioid agonist treatment retention reduced over time; the risk of leaving treatment when on buprenorphine compared with methadone was higher among those who entered treatment earlier [e.g. 2001–03: odds ratio (OR) = 1.59, 95% confidence interval (CI) = 1.45–1.75] and lowest among those who entered most recently (2013–15: OR = 1.23, 95% CI = 1.11–1.36). In adjusted analyses, risk of leaving was reduced among people whose prescriber had longer tenure of prescribing (e.g. 3 versus 8 years: OR = 0.94, 95% CI = 0.93–0.95) compared with prescribers with shorter tenure. Aboriginal and Torres Strait Islander people, being of younger age, past‐year psychosis disorder and having been convicted of more criminal charges in the year prior to treatment entry were associated with increased risk of leaving treatment.

Conclusion

In New South Wales, Australia, retention in buprenorphine treatment for opioid dependence, compared with methadone, has improved over time since its introduction in 2001. Opioid agonist treatment retention is affected not only by characteristics of the person and his or her treatment, but also of the prescriber, with those of longer prescribing tenure associated with increased retention of people in opioid agonist treatment.