bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaccination and Variants: retrospective model for the evolution of Covid-19 in Italy
Authors: Fierro Annalisa , Romano Silvio , Liccardo Antonella 
Published: March 2022

AbstractThe last year of Covid-19 pandemic has been characterized by the continuous chase between the vaccination campaign and the appearance of new variants that put further obstacles to the possibility of eradicating the virus and returning to normality in a short period. In the present paper we consider a deterministic compartmental model to discuss the evolution of the Covid-19 in Italy as a combined effect of vaccination campaign, new variant spreading, waning immunity and mobility restrictions. We analyze the role that different mechanisms, such as behavioral changes due to variable risk perception, variation of the population mobility, seasonal variability of the virus infectivity, and spreading of new variants have had in shaping the epidemiological curve. The fundamental impact of vaccines in drastically reducing the total increase in infections and deaths is also estimated. This work further underlines the crucial importance of vaccination and adoption of adequate individual protective measures in containing the pandemic.
Effect of an Integrated Maternal and Neonatal Health Intervention on Maternal Healthcare Utilization addressing Inequity in Rural Bangladesh
Authors: Ahmed Anisuddin , Huq Nafisa Lira , Rahman Fariya , Tanwi Tania Sultana , Siddique Md. Abu Bakkar , Hossain Aniqa Tasnim , Ether Saraban Tahura , Akter Ema , Tahsina Tazeen , Arifeen Shams El , Rahman Ahmed Ehsanur 
Published: March 2022

AbstractBackgroundAlthough Bangladesh has made significant improvements in maternal, neonatal, and child health, the disparity between rich and poor remains a matter for concern.ObjectiveThe study aimed to increase coverage of women in seeking skilled maternal healthcare services while minimizing inequity gap among different socioeconomic groups.Methodsicddr, b implemented an integrated maternal and neonatal health (MNH) intervention between 2009 and 2012, in Shahjadpur sub-district of Shirajganj district, Bangladesh. The study was pre- and post-test in design for evaluation including baseline and endline surveys. The baseline and endline surveys were conducted among 3158 and 3540 recently delivered mothers respectively. Asset index derived from household assets using principal component analysis was categorized into five ordinal categories, i.e. Poor, Less poor, Middle, Upper middle, Rich. Inequity in maternal healthcare utilization was calculated for the baseline and endline periods using rich- to-poor ratio and the concentration index.ResultMean age of mothers were 23.5 and 24.3 years in baseline and endline, respectively. Reduction in rich-poor ratio was quite large in utilization of skilled 4+ antenatal care (ANC) (2.4:1 to 1.1:1), childbirth (1.7:1 to 1.0:1), and postnatal care (PNC) (2.5:1 to 1.0:1) from trained providers between these two surveys. The concentration indices (CI) in endline for skilled 4+ ANC (CI: 0.220 and 0.013), delivery (CI: 0.161 and -0.021), and PNC (CI: 0.197 and -0.004) were found to be lower than the indices in baseline period respectively.ConclusionThe MNH intervention was successful in reducing inequity in receiving skilled 4+ ANC, delivery, and PNC in rural Bangladesh. Improvements in maternal healthcare utilizations by poor mothers would be influenced by the properly designed and integrated demand- and supply-side MNH interventions package.
A cooperative switch within the KaiC hexamer revealed by cryo-EM
Authors: Han Xu , Zhang Dongliang , Hong Lu , Yu Daqi , Wu Zhaolong , Yang Tian , Rust Michael , Tu Yuhai , Ouyang Qi 
Published: March 2022

AbstractThe circadian clock of cyanobacteria is based on an approximately 24h rhythm in the phosphorylation level of KaiC, a hexameric ATPase. This oscillation can be reconstituted in vitro by incubating three proteins together with ATP. Like all chemical oscillators, this system must include a nonlinear, or switch-like, feedback loop, whose nature has been unclear. Here, by using single particle cryo-EM at near-atomic resolution we identified two major conformational states of KaiC subunits, denoted as the exposed state and the buried state, which may provide a structural basis of how the KaiC hexamer changes its conformation during the (day-night) phosphorylation-dephosphorylation cycle. We classify the abundance and pattern of exposed and buried states within hexamers for more than 160,000 KaiC particles. The statistics of the spatial arrangement of the two states in hexamers can be quantitatively fit by a simple statistical physics model with an interaction energy between neighboring subunits and a local field that depends on phosphorylation state. Our study shows that phosphorylation shifts the probability of each conformation and reveals that there is substantial cooperativity between neighboring subunits, which can allow a KaiC hexamer to respond in an ultrasensitive, switch-like manner to changes in the phosphorylation level.
Mechanistic insights into the functioning of GMP synthetase: a two-subunit, allosterically regulated, ammonia tunnelling enzyme
Authors: Shivakumaraswamy Santosh , Kumar Sanjeev , Bellur Asutosh , Polisetty Satya Dev , Balaram Hemalatha 
Published: March 2022

AbstractGuanosine 5’-monophosphate (GMP) synthetases, enzymes that catalyze the conversion of xanthosine 5’-monophosphate (XMP) to GMP are comprised of two different catalytic units, which are either two domains of a polypeptide chain or two subunits that associate to form a complex. The glutamine amidotransferase (GATase) unit hydrolyzes glutamine generating ammonia and the ATP pyrophosphatase (ATPPase) unit catalyzes the formation of AMP-XMP intermediate. The substrate-bound ATPPase allosterically activates GATase and the ammonia thus generated is tunnelled to the ATPPase active site where it reacts with AMP-XMP generating GMP. In ammonia tunnelling enzymes reported thus far, a tight complex of the two subunits is observed, while the interaction of the two subunits of Methanocaldococcus jannaschii GMP synthetase (MjGMPS) is transient with the underlying mechanism of allostery and substrate channelling largely unclear. Here, we present a mechanistic model encompassing the various steps in the catalytic cycle of MjGMPS based on biochemical experiments, crystal structure and cross-linking mass spectrometry guided integrative modelling. pH dependence of enzyme kinetics establish that ammonia is tunnelled across the subunits with the lifetime of the complex being ≤ 0.5 s. The crystal structure of XMP-bound ATPPase subunit reported herein highlights the role of conformationally dynamic loops in enabling catalysis. The structure of MjGMPS derived using restraints obtained from cross-linking mass spectrometry has enabled the visualization of subunit interactions that enable allostery under catalytic conditions. We integrate the results and propose a functional mechanism for MjGMPS detailing the various steps involved in catalysis.Graphical Abstract
A high-performance genetically encoded fluorescent indicator for in vivo cAMP imaging
Authors: Wang Liang , Wu Chunling , Peng Wanling , Zhou Ziliang , Zeng Jianzhi , Li Xuelin , Yang Yini , Yu Shuguang , Zou Ye , Huang Mian , Liu Chang , Chen Yefei , Li Yi , Ti Panpan , Liu Wenfeng , Gao Yufeng , Zheng Wei , Gao Shangbang , Lu Zhonghua , Ren Pei-Gen , Ng Ho Leung , He Jie , Chen Shoudeng , Xu Min , Li Yulong , Chu Jun 
Published: March 2022

AbstractcAMP is a key second messenger that regulates diverse cellular functions including neural plasticity. However, the spatiotemporal dynamics of intracellular cAMP in intact organisms are largely unknown due to low sensitivity and/or brightness of current genetically encoded fluorescent cAMP indicators. Here, we report the development of the new circularly permuted GFP (cpGFP)-based cAMP indicator G-Flamp1, which exhibits a large fluorescence increase (a maximum ΔF/F0 of 1100% in HEK293T cells), relatively high brightness, appropriate affinity (a Kd of 2.17 µM) and fast response kinetics (an association and dissociation half-time of 0.20 s and 0.087 s, respectively). Furthermore, the crystal structure of the cAMP-bound G-Flamp1 reveals one linker connecting the cAMP-binding domain to cpGFP adopts a distorted β-strand conformation that may serve as a fluorescence modulation switch. We demonstrate that G-Flamp1 enables sensitive monitoring of endogenous cAMP signals in brain regions that are implicated in learning and motor control in living organisms such as fruit flies and mice.
Influence of age and cognitive performance on resting-state functional connectivity of dopaminergic and noradrenergic centres
Authors: Zareba Michal Rafal , Furman Wiktoria , Binder Marek 
Published: March 2022

AbstractThe process of ageing is associated with structural and functional changes in the brain, with a decline in cognitive functions observed as its inevitable symptom, even in the absence of neurodegenerative changes. A body of literature suggests dopamine and noradrenaline as prominent candidate molecules to mediate these effects, however, the knowledge regarding the underlying mechanisms is scarce. To fill this gap, we compared local and distant resting-state functional connectivity patterns of ventral tegmental area, substantia nigra pars compacta and locus coeruleus in healthy young (20-35 years; N = 37) and older adults (55-80 years; N = 27). Additionally, we sought long-range functional connectivity patterns of these structures associated with performance in tasks probing executive, attentional and reward functioning, as well as compared the functional coupling of the left and right substantia nigra. The results showed that each substantia nigra had stronger coupling with ipsilateral cortical and subcortical areas along with contralateral cerebellum, and that strength of functional connections of this structure with angular gyrus and lateral orbitofrontal cortex predicted the visuomotor search abilities. In turn, ageing was associated with increased local synchronisation in the ventral tegmental area, and differences in functional connectivity of the dopaminergic midbrain with numerous cortical and subcortical structures. Locus coeruleus functional coupling showed no differences between the groups and was not associated with any of the behavioural functions. To the best of our knowledge, this work is the first one to report the age-related effects on midbrain local synchronisation and its connectivity with key recipients of dopaminergic innervation, such as striatum, anterior cingulate and insula.
Imported SARS-COV-2 Variants of Concern Drove Spread of Infections Across Kenya During the Second Year of the Pandemic
Authors: Nasimiyu Carolyne , Matoke-Muhia Damaris , Rono Gilbert K. , Osoro Eric , Obado Daniel O. , Mwangi J. Milkah , Mwikwabe Nicholas , Thiong’o Kelvin , Dawa Jeanette , Ngere Isaac , Gachohi John , Kariuki Samuel , Amukoye Evans , Mureithi Marianne , Ngere Philip , Amoth Patrick , Were Ian , Makayotto Lyndah , Nene Vishvanath , Abworo Edward O. , Njenga M. Kariuki , Seifert Stephanie N. , Oyola Samuel O. 
Published: March 2022

ABSTRACTBackgroundUsing classical and genomic epidemiology, we tracked the COVID-19 pandemic in Kenya over 23 months to determine the impact of SARS-CoV-2 variants on its progression.MethodsSARS-CoV-2 surveillance and testing data were obtained from the Kenya Ministry of Health, collected daily from 306 health facilities. COVID-19-associated fatality data were also obtained from these health facilities and communities. Whole SARS-CoV-2 genome sequencing were carried out on 1241 specimens.ResultsOver the pandemic duration (March 2020 - January 2022) Kenya experienced five waves characterized by attack rates (AR) of between 65.4 and 137.6 per 100,000 persons, and intra-wave case fatality ratios (CFR) averaging 3.5%, two-fold higher than the national average COVID-19 associated CFR. The first two waves that occurred before emergence of global variants of concerns (VoC) had lower AR (65.4 and 118.2 per 100,000). Waves 3, 4, and 5 that occurred during the second year were each dominated by multiple introductions each, ofAlpha(74.9% genomes),Delta(98.7%), andOmicron(87.8%) VoCs, respectively. During this phase, government-imposed restrictions failed to alleviate pandemic progression, resulting in higher attack rates spread across the country.ConclusionsThe emergence ofAlpha, Delta, andOmicronvariants was a turning point that resulted in widespread and higher SARS-CoV-2 infections across the country.
Discriminatory ability of gas chromatography-ion mobility spectrometry to identify patients hospitalised with COVID-19 and predict prognosis
Authors: Nazareth Joshua , Pan Daniel , Kim Jee Whang , Leach Jack , Brosnan James G , Ahmed Adam , Brodrick Emma , Wicaksono Alfian , Daulton Emma , Williams Caroline , Haldar Pranabashis , Covington James A. , Pareek Manish , Sahota Amandip 
Published: March 2022

AbstractBackgroundTests that can diagnose COVID-19 rapidly and predict prognosis would be significantly beneficial. We studied the ability of breath analysis using gas chromatography-ion mobility spectrometry (GC-IMS) for diagnosis of COVID-19 and as a predictor for subsequent requirement for Continuous Positive Airway Pressure (CPAP).MethodsWe undertook a single centre prospective observational study in patients with COVID-19, other respiratory tract infections and healthy controls. Participants provided one breath sample for GC-IMS analysis. We used cross validation analysis to create models that were then tested against the original cohort data. Further multivariable analysis was undertaken to adjust for differences between the comparator groups.ResultsBetween 01/02/2021 and 24/05/2021 we recruited 113 participants, of whom 72 (64%) had COVID-19, 20 (18%) had another respiratory tract infection and 21 (19%) were healthy controls. Differentiation between patients with COVID-19 and healthy controls, and patients with COVID-19 and those with other respiratory tract infections, was achieved with high accuracy. Identification of patients with subsequent requirement for CPAP was completed with moderate accuracy and was not independently associated on multivariable analysis.ConclusionsWe have shown that GC-IMS has a high capability to distinguish between acute COVID-19 infection and other disease states. Breath analysis shows promise as a predictor of subsequent requirement for CPAP in hospitalised patients with COVID-19. This platform has considerable benefits due to the test being rapid, non-invasive and not requiring specialist laboratory processing.
Influence of landscape patterns on the exposure of LASV across diverse regions within the Republic of Guinea
Authors: Longet Stephanie , Leggio Cristina , Bore Joseph Akoi , Tipton Tom , Hall Yper , Koundouno Fara Raymond , Key Stephanie , Bower Hilary , Bhattacharyya Tapan , Magassouba N’Faly , Günther Stephan , Henao-Restrapo Ana-Maria , Rossman Jeremy S. , Konde Mandy Kader , Fornace Kimberly , Carroll Miles W. 
Published: March 2022

AbstractLassa fever virus (LASV) is the causative agent of Lassa fever, a disease endemic in West Africa. Exploring the relationships between environmental factors and LASV transmission across ecologically diverse regions can provide crucial information for the design of appropriate interventions and disease monitoring. We measured LASV-specific IgG seropositivity in 1286 sera collected in Coastal and Forested Guinea. Our results showed that exposure to LASV was heterogenous between the sites. The LASV IgG seropositivity was 11.9% (95% CI 9.7-14.5) in Coastal site, while it was 59.6% (95% CI 55.5-63.5) in Forested region. Interestingly, exposure was significantly associated with age, with seropositivity increasing with age in the Coastal site. Finally, we also found significant associations between exposure risk to LASV and landscape fragmentation in Coastal and Forested regions. This study may help to define the regions with an increased exposure risk to LASV where a close surveillance of LASV circulation is needed.
Dendrites use mechanosensitive channels to proofread ligand-mediated guidance during morphogenesis
Authors: Tao Li , Coakley Sean , Shi Rebecca , Shen Kang 
Published: March 2022

SummaryLigand-receptor interactions guide axon navigation and dendrite arborization. Mechanical forces also influence guidance choices. However, the nature of such mechanical stimulations, the mechanosensors identity and how they interact with guidance receptors are unknown. Here, we demonstrate that mechanosensitive DEG/ENaC channels are required for dendritic arbor morphogenesis in Caenorhabditis elegans. Inhibition of DEG/ENaC channels causes reduced dendritic outgrowth and branching in vivo, a phenotype that is alleviated by overexpression of the mechanosensitive channels PEZO-1/Piezo or YVC1/TrpY1. DEG/ENaCs trigger local Ca2+ transients in growing dendritic filopodia via activation of L-type voltage-gated Ca2+ channels. Anchoring of filopodia by guidance ligand/receptor is required for the mechanical activation of DEG/ENaC channels. Therefore, mechanosensitive channels serve as a checkpoint for appropriate chemoaffinity by activating Ca2+ transients required for neurite growth.
Human UFSP1 is an active protease that regulates UFM1 maturation and UFMylation
Authors: Millrine David , Cummings Thomas , Matthews Stephen P. , Peter Joshua J. , Magnussen Helge , Macartney Thomas , Lamoliatte Frederic , Knebel Axel , Kulathu Yogesh 
Published: March 2022

AbstractAn essential first step in the posttranslational modification of proteins with UFM1, UFMylation, is the proteolytic cleavage of pro-UFM1 to expose a C-terminal glycine. Of the two UFM1-specific proteases (UFSPs) identified in humans, only UFSP2 is reported to be active since the annotated sequence of UFSP1 lacks critical catalytic residues. Nonetheless, efficient UFM1 maturation occurs in cells lacking UFSP2 suggesting the presence of another active protease. We hereby identify a long isoform of UFSP1 to be this protease. Cells lacking both UFSPs show complete loss of UFMylation resulting from an absence of mature UFM1. While UFSP2, but not UFSP1, removes UFM1 from the ribosomal subunit RPL26, UFSP1 acts earlier in the pathway to mature UFM1 and cleave a potential auto-inhibitory modification on UFC1, thereby controlling activation of UFMylation. In summary, our studies reveal important distinctions in substrate specificity and localization-dependent functions for the two proteases in regulating UFMylation.
First report of kdr L1014F and ace-1 G119S insecticide resistance in Belgian Culex (Diptera: Culicidae) mosquitoes
Authors: Wang Lanjiao , Soto Alina , Remue Laure , Rosas Ana Lucia Rosales , De Coninck Lander , Verwimp Sam , Bouckaert Johanna , Vanwinkel Mathias , Matthijnssens Jelle , Delang Leen 
Published: March 2022

AbstractThe emergence of West Nile virus and Usutu virus in Europe poses a significant risk to public health. In the absence of efficient antiviral therapy or vaccine candidates, the only strategy to control these arboviruses is to target the Culex (Diptera: Culicidae) mosquito vector. However, the selection pressure caused by exposure to insecticides for vector control or agricultural pest control can lead to insecticide resistance, thereby reducing the efficacy of insecticide-based vector control interventions. In Culex mosquitoes, two of the most common amino acid substitutions associated with insecticide resistance are the kdr L1014F in voltage gated sodium channels and G119S in acetylcholinesterase.In this study, Culex pipiens biotype pipiens, Culex torrentium, and Culex modestus were sampled from 2019 to 2021 in three distinct environmental habitats (urban, peri-urban, and agricultural) in and around the city of Leuven, Belgium. Individual mosquitoes were screened for two mutations resulting in L1014F and G119S amino acid substitutions. Both mutations were observed in Culex pipiens and Culex modestus but not in Culex torrentium mosquitoes across the four collection sites. Furthermore, multi-resistance or cross-resistance in Culex pipiens could be a threat in these areas, as both mutations were observed at low frequencies.These results provide the first report of kdr L1014F and ace-1 G119S resistance in Culex pipiens and Culex modestus mosquitoes from Belgium, highlighting the importance of mosquito surveillance to design effective arbovirus outbreak control strategies.
Synthetic oxepanoprolinamide iboxamycin is highly active against human pathogen Listeria monocytogenes
Authors: Brodiazhenko Tetiana , Turnbull Kathryn Jane , Wu Kelvin J.Y. , Takada Hiraku , Tresco Ben I.C. , Tenson Tanel , Myers Andrew G. , Hauryliuk Vasili 
Published: March 2022

AbstractListeriosis is a dangerous food-borne bacterial disease caused by the Gram-positive Bacillota (Firmicute) bacterium Listeria monocytogenes. In this report, we show that the synthetic lincosamide iboxamycin is highly active against L. monocytogenes and can overcome the intrinsic lincosamide resistance mediated by VgaL/Lmo0919, a member of ABCF ATPase resistance determinants that act by directly removing the antibiotic from the ribosome. While iboxamycin is not bactericidal against L. monocytogenes, it displays a pronounced postantibiotic effect, which is a valuable pharmacokinetic feature. Experiments in L. monocytogenes infection models are necessary to further assess the potential of iboxamycin as a novel drug for treatment of listeriosis. We demonstrate that VmlR ARE ABCF of Bacillota bacterium Bacillus subtilis grants significant (33-fold increase in MIC) protection from iboxamycin, while LsaA ABCF of Enterococcus faecalis grants an 8-fold protective effect. Furthermore, the VmlR-mediated iboxamycin resistance is cooperative with that mediated by the Cfr 23S rRNA methyltransferase resistance determinant, resulting in up to a 512-fold increase in MIC. Therefore, emergence and spread of ABCF ARE variants capable of defeating next-generation lincosamides in the clinic is possible and should be closely monitored.
Label-free three-photon imaging of intact human cerebral organoids: tracking early events in brain development and deficits in Rett Syndrome
Authors: Yildirim Murat , Delepine Chloe , Feldman Danielle , Pham Vincent , Chou Stephanie , Kan Ip Jacque Pak , Nott Alexi , Tsai Li-Huei , Ming Guo-li , So Peter T. C. , Sur Mriganka 
Published: March 2022

ABSTRACTHuman cerebral organoids are unique in their development of progenitor-rich zones akin to ventricular zones from which neuronal progenitors differentiate and migrate radially. Analyses of cerebral organoids thus far have been performed in sectioned tissue or in superficial layers due to their high scattering properties. Here, we demonstrate label-free three-photon imaging of whole, uncleared intact organoids (∼2 mm depth) to assess early events of early human brain development. Optimizing a custom-made three-photon microscope to image intact cerebral organoids generated from Rett Syndrome patients, we show defects in the ventricular zone volumetric structure of mutant organoids compared to isogenic control organoids. Long-term imaging live organoids reveals that shorter migration distances and slower migration speeds of mutant radially migrating neurons are associated with more tortuous trajectories. Our label-free imaging system constitutes a particularly useful platform for tracking normal and abnormal development in individual organoids, as well as for screening therapeutic molecules via intact organoid imaging.