bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical implications of somatic allele expansion in female FMR1 premutation carriers
Authors: Aishworiya Ramkumar , Hwang Ye Hyun , Santos Ellery , Hayward Bruce , Usdin Karen , Durbin-Johnson Blythe , Hagerman Randi , Tassone Flora
Published: April 2023

Carriers of a premutation allele (PM) in the FMR1 gene are at risk of developing a number of Fragile X premutation asssociated disorders (FXPAC), including Fragile X-associated Tremor/Ataxia Syndrome (FXTAS), Fragile X-associated Primary Ovarian Insufficiency (FXPOI), and Fragile X-associated neuropsychiatric disorders (FXAND). We have recently reported somatic CGG allele expansion in female PM; however, its clinical significance remains unclear. The aim of this study was to examine the potential clinical association between somatic FMR1 allele instability and PM associated disorders. Participants comprised of 424 female PM carriers age 0.3– 90 years. FMR1 molecular measures and clinical information on the presence of medical conditions, were determined for all subjects for primary analysis. Two sub-groups of participants (age ≥ 25, N = 377 and age ≥ 50, N = 134) were used in the analysis related to presence of FXPOI and FXTAS, respectively. Among all participants (N = 424), the degree of instability (expansion) was significantly higher (median 2.5 vs 2.0, P = 0.026) in participants with a diagnosis of attention deficit hyperactivity disorder (ADHD) compared to those without. FMR1 mRNA expression was significantly higher in subjects with any psychiatric disorder diagnosis (P = 0.0017); specifically, in those with ADHD (P = 0.009), and with depression (P = 0.025). Somatic FMR1 expansion was associated with the presence of ADHD in female PM and FMR1 mRNA levels were associated with the presence of mental health disorders. The findings of our research are innovative as they suggest a potential role of the CGG expansion in the clinical phenotype of PM and may potentially guide clinical prognosis and management.
Preliminary investigation on the effect of insect-based chitosan on preservation of coated fresh cherry tomatoes
Authors: Tafi Elena , Triunfo Micaela , Guarnieri Anna , Ianniciello Dolores , Salvia Rosanna , Scieuzo Carmen , Ranieri Annamaria , Castagna Antonella , Lepuri Samuel , Hahn Thomas , Zibek Susanne , De Bonis Angela , Falabella Patrizia
Published: April 2023

Chitosan was produced from Hermetia illucens pupal exuviae by heterogeneous and homogeneous deacetylation. Tomato fruits (Solanum lycopersicum), that are one of the most grown and consumed food throughout the world, were coated with 0.5 and 1% chitosan, applied by dipping or spraying, and stored at room temperature or 4 °C, for a storage period of 30 days. Statistical analysis give different results depending on the analysed parameters: heterogeneous chitosan, indeed, had a better effect than the homogenous one in maintaining more stable physico-chemical parameters, while the homogenous chitosan improved the total phenols, flavonoids and antioxidant activity. Chitosan coatings applied by spraying were more effective in all the analyses. Chitosan derived from H. illucens always performed similarly to the commercial chitosan. However, a general better performance of insect-derived chitosan on the concentration of phenolics and flavonoids, and the antioxidant activity was observed as compared to the commercial one. Chitosan coating has already been successfully used for preservation of fresh fruits, as alternative to synthetic polymers, but this is the first investigation of chitosan produced from an insect for this application. These preliminary results are encouraging regarding the validation of the insect H. illucens as a source of chitosan.
Effect of remote ischemic conditioning on the immune-inflammatory profile in patients with traumatic hemorrhagic shock in a randomized controlled trial
Authors: Leung C. H. , Rizoli S. B. , Trypcic S. , Rhind S. G. , Battista A. P. , Ailenberg M. , Rotstein O. D.
Published: April 2023

Resuscitation induced ischemia/reperfusion predisposes trauma patients to systemic inflammation and organ dysfunction. We investigated the effect of remote ischemic conditioning (RIC), a treatment shown to prevent ischemia/reperfusion injury in experimental models of hemorrhagic shock/resuscitation, on the systemic immune-inflammatory profile in trauma patients in a randomized trial. We conducted a prospective, single-centre, double-blind, randomized, controlled trial involving trauma patients sustaining blunt or penetrating trauma in hemorrhagic shock admitted to a Level 1 trauma centre. Patients were randomized to receive RIC (four cycles of 5-min pressure cuff inflation at 250 mmHg and deflation on the thigh) or a Sham intervention. The primary outcomes were neutrophil oxidative burst activity, cellular adhesion molecule expression, and plasma levels of myeloperoxidase, cytokines and chemokines in peripheral blood samples, drawn at admission (pre-intervention), 1 h, 3 h, and 24 h post﻿-admission. Secondary outcomes included ventilator, ICU and hospital free days, incidence of nosocomial infections, 24 h and 28 day mortality. 50 eligible patients were randomized; of which 21 in the Sham group and 18 in the RIC group were included in the full analysis. No treatment effect was observed between Sham and RIC groups for neutrophil oxidative burst activity, adhesion molecule expression, and plasma levels of myeloperoxidase and cytokines. RIC prevented significant increases in Th2 chemokines﻿ TARC/CCL17 (P < 0.01) and MDC/CCL22 (P < 0.05) at 24 h post-intervention in comparison to the Sham group. Secondary clinical outcomes were not different between groups. No adverse events in relation to the RIC intervention were observed. Administration of RIC was safe and did not adversely affect clinical outcomes. While trauma itself modified several immunoregulatory markers, RIC failed to alter expression of the majority of markers. However, RIC may influence Th2 chemokine expression in the post resuscitation period. Further investigation into the immunomodulatory effects of RIC in traumatic injuries and their impact on clinical outcomes is warranted.

ClinicalTrials.gov number: NCT02071290.
Peristaltic transfer of nanofluid with motile gyrotactic microorganisms with nonlinear thermic radiation
Authors: Mostapha Doaa R. , El-dabe Nabil T. M.
Published: April 2023

In situated theoretical article, a study of peristaltic transition of Jeffery nanofluid comprising motile gyrotactic microorganisms is exposed. The movement floods due to anisotropically stenosed endoscope influenced by Hall current, Joule heating during Darcy-Forchheimer feature. Influences of nonlinear thermic radiation, chemical interactions as well as Soret and Dufour scheme are exhibited. To ameliorate the competence of this article, activation energy has been appended to concentration of nano-particles due to the amended Arrhenius scheme and Buongiorno type. The slip stipulation is deemed relative to the speed scheme. Meanwhile, convective stipulation is reckoned for temperature. The proposition of protracted wavelength besides subdued Reynolds numeral is regulated to transit the manner of partial differential formulations that judges the fluid movement to ordinary one. Homotopy perturbation manner is tackled to manage the traditional solutions of generated neutralizations. Influences of assorted factors of the issue are debated and schematically showed with a class of charts. The situated study grants a medication for the malign cells and clogged arteries of the heart by manner of penetrating a slender tube (catheter). Also, this study may represent the depiction of the gastric juice movement in small intestine when an endoscope is permeating across it.
Highly-conserved regulatory activity of the ANR family in the virulence of diarrheagenic bacteria through interaction with master and global regulators
Authors: Rodriguez-Valverde Diana , Giron Jorge A. , Hu Yang , Nataro James P. , Ruiz-Perez Fernando , Santiago Araceli E.
Published: April 2023

ANR (AraC negative regulators) are a novel class of small regulatory proteins commonly found in enteric pathogens. Aar (AggR-activated regulator), the best-characterized member of the ANR family, regulates the master transcriptional regulator of virulence AggR and the global regulator HNS in enteroaggregative Escherichia coli (EAEC) by protein–protein interactions. On the other hand, Rnr (RegA-negative regulator) is an ANR homolog identified in attaching and effacing (AE) pathogens, including Citrobacter rodentium and enteropathogenic Escherichia coli (EPEC), sharing only 25% identity with Aar. We previously found that C. rodentium lacking Rnr exhibits prolonged shedding and increased gut colonization in mice compared to the parental strain. To gain mechanistic insights into this phenomenon, we characterized the regulatory role of Rnr in the virulence of prototype EPEC strain E2348/69 by genetic, biochemical, and human organoid-based approaches. Accordingly, RNA-seq analysis revealed more than 500 genes differentially regulated by Rnr, including the type-3 secretion system (T3SS). The abundance of EspA and EspB in whole cells and bacterial supernatants confirmed the negative regulatory activity of Rnr on T3SS effectors. We found that besides HNS and Ler, twenty-six other transcriptional regulators were also under Rnr control. Most importantly, the deletion of aar in EAEC or rnr in EPEC increases the adherence of these pathogens to human intestinal organoids. In contrast, the overexpression of ANR drastically reduces bacterial adherence and the formation of AE lesions in the intestine. Our study suggests a conserved regulatory mechanism and a central role of ANR in modulating intestinal colonization by these enteropathogens despite the fact that EAEC and EPEC evolved with utterly different virulence programs.
Sustainable development goals as unifying narratives in large UK firms’ Twitter discussions
Authors: Patuelli Alessia , Saracco Fabio
Published: April 2023

To achieve sustainable development worldwide, the United Nations set 17 Sustainable Development Goals (SDGs) for humanity to reach by 2030. Society is involved in the challenge, with firms playing a crucial role. Thus, a key question is to what extent firms engage with the SDGs. Efforts to map firms’ contributions have mainly focused on analysing companies’ reports based on limited samples and non-real-time data. We present a novel interdisciplinary approach based on analysing big data from an online social network (Twitter) with complex network methods from statistical physics. By doing so, we provide a comprehensive and nearly real-time picture of firms’ engagement with SDGs. Results show that: (1) SDGs themes tie conversations among major UK firms together; (2) the social dimension is predominant; (3) the attention to different SDGs themes varies depending on the community and sector firms belong to; (4) stakeholder engagement is higher on posts related to global challenges compared to general ones; (5) large UK companies and stakeholders generally behave differently from Italian ones. This paper provides theoretical contributions and practical implications relevant to firms, policymakers and management education. Most importantly, it provides a novel tool and a set of keywords to monitor the influence of the private sector on the implementation of the 2030 Agenda.
Tracing the human movements of three thousand years ago by volcanic grinding tools in the Final Bronze Age settlement of Monte Croce Guardia (Arcevia-Marche Region, central Italy)
Authors: Santi P. , Cardarelli A. , Bettelli M. , Di Renzoni A. , Cardarelli L. , Paniccia C. , Renzulli A.
Published: April 2023

Volcanic rocks were among the most sought-after materials to produce grinding tools in antiquity because lavas lithologies, either mafic or felsic, ensured good wear resistance and grinding capacity with respect to many other kinds of rocks. The interest in findings made of vesciculated lavas, referable to parts of querns, mortars, and/or pestles of the Final Bronze Age site of Monte Croce Guardia (Arcevia) lies in the fact that this settlement was built upon limestones belonging to the sedimentary sequence of the Marche-Umbria Apennines (central Italy) and far away from potential raw materials of volcanic rocks. A petrologic study of 23 grinding tool fragments clearly indicates a provenance from the volcanic provinces of central Italy: Latium and Tuscany Regions. Few leucite tephrites (5) and one leucite phonolite lavas have a clear magmatic affinity with the high-K series of the Roman Volcanic Province (Latium) whereas the most abundant volcanic lithotype (17 samples) is represented by shoshonites (K-series) whose thin section texture, modal mineralogy and major-trace elements contents closely match with the shoshonite lavas from the Radicofani volcanic centre in the Tuscan Magmatic Province. At Radicofani (a volcanic neck in the eastern sector of Tuscany) a Final Bronze Age site coeval to that of Arcevia is present and a potential pathway corridor from that site towards Arcevia (air-line distance of ca. 115 km) is dotted with many settlements of the same age. Through analytical algorithms based on the slope and the different human-dependent cost-functions which can be applied to determine non-isotropic accumulated cost surface, least-cost paths and least-cost corridors, the best route from Radicofani to Monte Croce Guardia, approximately 140 km long, was simulated, with a walking time of 25–30 h, possibly using pack animals and wheel chariots. Three thousand years ago the Apennine Mountains did not thus constitute a barrier for human movements. This study also shed light on some other possible patterns of interactions between Final Bronze Age communities of central Italy through the present-day regions of Tuscany, Umbria and Marche, aimed towards the best performance of strategic economic activities at that time such as that of the transformation of cereals, and accompanied to cultural and social reasons.
The DNA cytosine methylome revealed two methylation motifs in the upstream regions of genes related to morphological and physiological differentiation in Streptomyces coelicolor A(3)2 M145
Authors: Pisciotta Annalisa , Sampino Alessia Maria , Presentato Alessandro , Galardini Marco , Manteca Angel , Alduina Rosa
Published: April 2023

DNA methylation is an epigenetic modification detected in both prokaryotic and eukaryotic genomic DNAs. In bacteria, the importance of 5-methylcytosine (m5C) in gene expression has been less investigated than in eukaryotic systems. Through dot-blot analysis employing m5C antibodies against chromosomal DNA, we have previously demonstrated that m5C influences the differentiation of Streptomyces coelicolor A(3)2 M145 in solid sporulating and liquid non-sporulating complex media. Here, we mapped the methylated cytosines of the M145 strain growing in the defined Maltose Glutamate (MG) liquid medium. Sequencing of the M145 genome after bisulfite treatment (BS-sequencing) evidenced 3360 methylated cytosines and the two methylation motifs, GGCmCGG and GCCmCG, in the upstream regions of 321 genes. Besides, the role of cytosine methylation was investigated using the hypo-methylating agent 5′-aza-2′-deoxycytidine (5-aza-dC) in S. coelicolor cultures, demonstrating that m5C affects both growth and antibiotic biosynthesis. Finally, quantitative reverse-transcription polymerase-chain-reaction (RT-qPCR) analysis of genes containing the methylation motifs in the upstream regions showed that 5-aza-dC treatment influenced their transcriptional levels and those of the regulatory genes for two antibiotics. To the best of our knowledge, this is the first study that reports the cytosine methylome of S. coelicolor M145, supporting the crucial role ascribed to cytosine methylation in controlling bacterial gene expression.
Evolution of fairness in the divide-a-lottery game
Authors: Kim Jeong-Yoo , Lee Kyu-Min
Published: April 2023

In this paper, we show that fairness can evolve in the divide-a-lottery game which is more general than the divide-a-dollar game by using an indirect evolutionary approach. In the divide-a-lottery game, the size of a pie is uncertain. Two players sequentially bid for a share and they get their bid if the allocation based on the bids turns out to be feasible and otherwise neither gets anything. In this game, rational players over-compete for a higher share, resulting in a high probability of failure in agreement, whereas fair players who dislike the disparity between shares lower their bids thereby reducing the failure probability and thus increasing the expected payoff. As a result, fairness strictly dominates rationality. This is the mechanism through which fairness evolves. However, this result is not robust against even a slight uncertainty about the opponent’s type. Surprisingly, we show a contrasted simulation result that only rational players who are strictly dominated by fair players survive evolutionarily for most of the parameter values if players have even a slight chance of not knowing the opponent’s type. Our simulation results in a local interaction model in which players only know the type of closer neighbors capture both insights and demonstrate that moderate proportions of both types coexist evolutionarily over time, and that the population average fitness of this polymorphic population is higher than monomorphic population consisting only of fair types or rational types.
Clinical validation for automated geographic atrophy monitoring on OCT under complement inhibitory treatment
Authors: Mai Julia , Lachinov Dmitrii , Riedl Sophie , Reiter Gregor S. , Vogl Wolf-Dieter , Bogunovic Hrvoje , Schmidt-Erfurth Ursula
Published: April 2023

Geographic atrophy (GA) represents a late stage of age-related macular degeneration, which leads to irreversible vision loss. With the first successful therapeutic approach, namely complement inhibition, huge numbers of patients will have to be monitored regularly. Given these perspectives, a strong need for automated GA segmentation has evolved. The main purpose of this study was the clinical validation of an artificial intelligence (AI)-based algorithm to segment a topographic 2D GA area on a 3D optical coherence tomography (OCT) volume, and to evaluate its potential for AI-based monitoring of GA progression under complement-targeted treatment. 100 GA patients from routine clinical care at the Medical University of Vienna for internal validation and 113 patients from the FILLY phase 2 clinical trial for external validation were included. Mean Dice Similarity Coefficient (DSC) was 0.86 ± 0.12 and 0.91 ± 0.05 for total GA area on the internal and external validation, respectively. Mean DSC for the GA growth area at month 12 on the external test set was 0.46 ± 0.16. Importantly, the automated segmentation by the algorithm corresponded to the outcome of the original FILLY trial measured manually on fundus autofluorescence. The proposed AI approach can reliably segment GA area on OCT with high accuracy. The availability of such tools represents an important step towards AI-based monitoring of GA progression under treatment on OCT for clinical management as well as regulatory trials.
Synthetic lethality prediction in DNA damage repair, chromatin remodeling and the cell cycle using multi-omics data from cell lines and patients.
Authors: Markowska Magda , Budzinska Magdalena A. , Coenen-Stass Anna , Kang Senbai , Kizling Ewa , Kolmus Krzysztof , Koras Krzysztof , Staub Eike , Szczurek Ewa
Published: April 2023

Discovering synthetic lethal (SL) gene partners of cancer genes is an important step in developing cancer therapies. However, identification of SL interactions is challenging, due to a large number of possible gene pairs, inherent noise and confounding factors in the observed signal. To discover robust SL interactions, we devised SLIDE-VIP, a novel framework combining eight statistical tests, including a new patient data-based test iSurvLRT. SLIDE-VIP leverages multi-omics data from four different sources: gene inactivation cell line screens, cancer patient data, drug screens and gene pathways. We applied SLIDE-VIP to discover SL interactions between genes involved in DNA damage repair, chromatin remodeling and cell cycle, and their potentially druggable partners. The top 883 ranking SL candidates had strong evidence in cell line and patient data, 250-fold reducing the initial space of 200K pairs. Drug screen and pathway tests provided additional corroboration and insights into these interactions. We rediscovered well-known SL pairs such as RB1 and E2F3 or PRKDC and ATM, and in addition, proposed strong novel SL candidates such as PTEN and PIK3CB. In summary, SLIDE-VIP opens the door to the discovery of SL interactions with clinical potential. All analysis and visualizations are available via the online SLIDE-VIP WebApp.
Heavy metals in the sediments of urban sinkholes in Cancun, Quintana Roo
Authors: Ortega-Camacho Daniela , Acosta-González Gilberto , Sánchez-Trujillo Fernanda , Cejudo Eduardo
Published: April 2023

Soils in urban areas can accumulate heavy metals as a result of anthropogenic inputs. This research focuses on a young coastal tourist city that has been urbanized over the last 52 years and shows accelerated demographic growth and urban development. Deposition of heavy metals in soils is caused by human economic activities, which has significant implications for the environment. We evaluated heavy metal concentrations in urban sinkholes, which are sites for the natural accumulation of water and sediments. These locations also receive rainfall runoff or have been used as unregulated dumps. By performing a multistage extraction to address availability and risk, we found that Zn, Fe and Al were the predominant metals; Cu, Pb and Ni were only detected in some sinkholes. The contamination factor was high for Zn and moderate for Pb. The geoaccumulation index showed that Zn is the most abundant and available metal in urban sinkholes and the metal with the highest potential ecological risk. Between 12 and 50% of the total concentration of all metals was extracted from the organic matter phase. Correlations were found between the degree of urbanization of the city and the degree of pollution, and the trends were stronger in older sections of the city. Zn is the most prevalent element and has high concentrations. The metal concentrations in the sediments can be used as warning signs for their potential risk to environmental and human health, and these results can be compared with those of other tourist cities in karstic environments around the world.
Occupational exposure to HIV and utilization of post-exposure prophylaxis among healthcare workers at St. Peter’s specialized hospital in Addis Ababa, Ethiopia
Authors: Tsega Dejen , Gintamo Binyam , Mekuria Zelalem Negash , Demissie Negesu Gizaw , Gizaw Zemichael
Published: April 2023

Healthcare workers are susceptible to blood borne pathogens, such as human immunodeficiency virus (HIV). Occupational exposure to HIV infection among healthcare workers is becoming a global public health concern. However, there is limited evidence about occupational exposure of healthcare workers to HIV and utilization of post-exposure prophylaxis in Addis Ababa, Ethiopia. Accordingly, this study was conducted to assess the prevalence of occupational exposure to HIV and utilization of post exposure prophylaxis among healthcare workers at St. Peter’s specialized hospital, Addis Ababa, Ethiopia. A health facility-based cross-sectional study was conducted among 308 randomly selected healthcare workers in April 2022. Structured and pretested self-administered questioner was used to collect data. Occupational exposure to HIV was taken as any percutaneous injury or blood or other body fluids exposure while administering medications, specimen collection, and other procedures with HIV confirmed patients. Multivariable binary logistic regression analysis was used to identify factors associated with occupational exposure to HIV and utilization of post-exposure prophylaxis. Statistically significant association was declared on the basis of adjusted odds ratio with 95% confidence interval and p-value less than 0.05. The study found that 42.3% (95% CI 36.6, 47.9%) of the healthcare workers had occupational exposure to HIV during their career time, out of whom 16.1% (95% CI 11.9, 20.3%) used post-exposure prophylaxis. Healthcare workers with lower-level education such as diploma (AOR: 0.41, 95% CI 0.17, 0.96) and BSc (AOR: 0.51, 95% CI 0.26, 0.92), and healthcare workers who received infection prevention training (AOR: 0.55, 95% CI 0.33, 0.90) had less risk of exposure to HIV. On the other hand, nurses (AOR: 1.98, 95% CI 1.07, 3.67), midwifes (AOR: 3.79, 95% CI 1.21, 11.9), and physicians (AOR: 2.11, 95% CI 1.05, 4.22) had high risk of exposure to HIV compared with other professionals. Moreover, healthcare workers with BSc degree compared with healthcare workers with masters degree (AOR: 3.69, 95% CI 1.08, 12.6), healthcare workers with long service year (AOR: 3.75, 95% CI 1.64, 8.57), and healthcare workers who are working in facilities where prophylaxis is available (AOR: 3.41, 95% CI 1.47, 7.91) had higher odds to utilize post-exposure prophylaxis. Significant proportion of healthcare workers included in the current study had occupational exposure to HIV and very few of them used post-exposure prophylaxis. Healthcare workers need to use appropriate personal protective equipment, safely manage contaminated equipment, and safely administered medications and collect specimen to protect themselves from exposure to HIV. Moreover, use of post-exposure prophylaxis should be promoted when exposure exists.
Acute effect of moderate and high-intensity interval exercises on asprosin and BDNF levels in inactive normal weight and obese individuals
Authors: Ceylan Halil İbrahim , Öztürk Mehmet Ertuğrul , Öztürk Deniz , Silva Ana Filipa , Albayrak Mevlüt , Saygın Özcan , Eken Özgür , Clemente Filipe Manuel , Nobari Hadi
Published: April 2023

This study aimed to examine the acute effects of moderate-intensity aerobic and high-intensity interval exercise protocols on Asprosin and Brain-Derived Neurotrophic Factor (BDNF) levels in inactive normal weight and obese individuals. A total of 20 male individuals aged 18–65 years, ten normal weight (NW) (Body Mass Index (BMI): 18.5–24.99 kg/m2) and 10 obese (Ob) (BMI: 24.99–35.00 kg/m2) participated in this study, voluntarily. Moderate aerobic exercise (AE) (main circuit 30 min, between 40 and 59% of Heart Rate Reserve: HRR) and High-Intensity Interval exercise (HIIE) running protocols (main circuit 20 min, between 75 and 90% of the HRR for 1 min*10 times, and 1-min active rest at 30% of the HRR) was applied to the volunteer participants in the morning hours (08.00–10.00 a.m.), following the night fasting (at least 8–10 h) for at least 3 days between each other. Blood samples were collected from the participants before and immediately after each exercise protocol, and serum asprosin and BDNF hormone levels were determined by Enzyme-Linked Immunosorbent Assay” method. Basal serum asprosin was found to be significantly higher in the Ob group compared to the NW group (p < .001), while the basal serum BDNF hormone was found to be lower (p < 0.05). It was observed that the serum asprosin level of both groups decreased significantly after both AE and HIIE protocols (p < 0.05). In addition, there was a significantly higher decrease in serum asprosin level in the Ob group compared to the NW group after HIIE protocol. For the Ob group, serum BDNF level increased considerably after HIIE protocol compared to AE protocol (p < 0.05). Serum asprosin was found to be higher in the Ob group, while the serum BDNF was found to be lower. In addition, the acute exercises of different intensity significantly affected hormones that regulate appetite metabolism. In particular, it was observed that the HIIE protocol had a greater effect on the regulation of appetite (hunger-satiety) in the Ob group. This result can be taken into account when planning training programs for these individuals.
In vivo imaging of MmpL transporters reveals distinct subcellular locations for export of mycolic acids and non-essential trehalose polyphleates in the mycobacterial outer membrane
Authors: Thouvenel Laurie , Rech Jérôme , Guilhot Christophe , Bouet Jean-Yves , Chalut Christian
Published: April 2023

The mycobacterial cell envelope consists of a typical plasma membrane, surrounded by a complex cell wall and a lipid-rich outer membrane. The biogenesis of this multilayer structure is a tightly regulated process requiring the coordinated synthesis and assembly of all its constituents. Mycobacteria grow by polar extension and recent studies showed that cell envelope incorporation of mycolic acids, the major constituent of the cell wall and outer membrane, is coordinated with peptidoglycan biosynthesis at the cell poles. However, there is no information regarding the dynamics of incorporation of other families of outer membrane lipids during cell elongation and division. Here, we establish that the translocation of non-essential trehalose polyphleates (TPP) occurs at different subcellular locations than that of the essential mycolic acids. Using fluorescence microscopy approaches, we investigated the subcellular localization of MmpL3 and MmpL10, respectively involved in the export of mycolic acids and TPP, in growing cells and their colocalization with Wag31, a protein playing a critical role in regulating peptidoglycan biosynthesis in mycobacteria. We found that MmpL3, like Wag31, displays polar localization and preferential accumulation at the old pole whereas MmpL10 is more homogenously distributed in the plasma membrane and slightly accumulates at the new pole. These results led us to propose a model in which insertion of TPP and mycolic acids into the mycomembrane is spatially uncoupled.
Stereocomplexed microparticles loaded with Salvia cadmica Boiss. extracts for enhancement of immune response towards Helicobacter pylori
Authors: Gonciarz Weronika , Chmiela Magdalena , Kost Bartłomiej , Piątczak Ewelina , Brzeziński Marek
Published: April 2023

Controlled delivery of therapeutic substance gives numerous advantages (prevents degradation, improves uptake, sustains concentration, lowers side effects). To encapsulate Salvia cadmica extracts (root or aerial part), enriched with polyphenols with immunomodulatory activity, in stereocomplexed microparticles (sc-PLA), for using them to enhance the immune response towards gastric pathogen Helicobacter pylori. Microparticles were made of biodegradable poly(lactic acid) (PLA) and poly(d-lactic acid) (PDLA). Their stereocomplexation was used to form microspheres and enhance the stability of the obtained particles in acidic/basic pH. The release of Salvia cadmica extracts was done in different pH (5.5, 7.4 and 8.0). The obtained polymers are safe in vitro and in vivo (guinea pig model). The sc-PLA microparticles release of S. cadmica extracts in pH 5.5, 7.4, and 8.0. S. cadmica extracts enhanced the phagocytic activity of guinea pig bone marrow-derived macrophages, which was diminished by H. pylori, and neutralized H. pylori driven enhanced production of tumor necrosis factor (TNF)-α and interleukin (IL)-10. The sc-PLA encapsulated S. cadmica extracts can be recommended for further in vivo study in guinea pigs infected with H. pylori to confirm their ability to improve an immune response towards this pathogen.
Reputation risk during dishonest social decision-making modulates anterior insular and cingulate cortex activity and connectivity
Authors: Dupont Lennie , Santangelo Valerio , Azevedo Ruben T. , Panasiti Maria Serena , Aglioti Salvatore Maria
Published: April 2023

To explore the neural underpinnings of (dis)honest decision making under quasi-ecological conditions, we used an fMRI adapted version of a card game in which deceptive or truthful decisions are made to an opponent, with or without the risk of getting caught by them. Dishonest decisions were associated to increased activity in a cortico-subcortical circuit including the bilateral anterior cingulate cortex (ACC), anterior insula (AI), left dorsolateral prefrontal cortex, supplementary motor area, and right caudate. Crucially, deceptive immoral decisions under reputation risk enhanced activity of – and functional connectivity between – the bilateral ACC and left AI, suggesting the need for heightened emotional processing and cognitive control when making immoral decisions under reputation risk. Tellingly, more manipulative individuals required less involvement of the ACC during risky self-gain lies but more involvement during other-gain truths, pointing to the need of cognitive control only when going against one’s own moral code.
HOPE-SIM, a cryo-structured illumination fluorescence microscopy system for accurately targeted cryo-electron tomography
Authors: Li Shuoguo , Jia Xing , Niu Tongxin , Zhang Xiaoyun , Qi Chen , Xu Wei , Deng Hongyu , Sun Fei , Ji Gang
Published: April 2023

Cryo-focused ion beam (cryo-FIB) milling technology has been developed for the fabrication of cryo-lamella of frozen native specimens for study by in situ cryo-electron tomography (cryo-ET). However, the precision of the target of interest is still one of the major bottlenecks limiting application. Here, we have developed a cryo-correlative light and electron microscopy (cryo-CLEM) system named HOPE-SIM by incorporating a 3D structured illumination fluorescence microscopy (SIM) system and an upgraded high-vacuum stage to achieve efficiently targeted cryo-FIB. With the 3D super resolution of cryo-SIM as well as our cryo-CLEM software, 3D-View, the correlation precision of targeting region of interest can reach to 110 nm enough for the subsequent cryo-lamella fabrication. We have successfully utilized the HOPE-SIM system to prepare cryo-lamellae targeting mitochondria, centrosomes of HeLa cells and herpesvirus assembly compartment of infected BHK-21 cells, which suggests the high potency of the HOPE-SIM system for future in situ cryo-ET workflows.
Fabrication of helix–fiber composites with mechanically coupled core-wrapping for programmable properties
Authors: Li Dan , Zhu Zhiwei , Zhao Ziyu , Ji Yuan , Fu Xuewei , Liu Zunfeng , Yang Wei , Wang Yu
Published: April 2023

Helix-fiber composites (HFCs), which involve wrapping a material around a flexible core, are of interest for intelligent stretchable functional materials or devices. Here, we reveal that mechanical coupling between the core and wrapping plays a critical role in controlling the structure and mechanical properties. Our results show that the mechanical properties of the HFC can be programmed by precisely tuning the mechanical coupling strength among them. Interestingly, the HFC also shows unique pseudo-elastic behavior under large strain due to the mechanical coupling effects. The HFC is demonstrated as an elastic metal conductor, programmable sensor, and finally as an elastic mold for structure transplantation by mechanically decoupling the elastomer core from the helix fiber. The results not only deepen the fundamental understanding of HFCs, but also may promote future structure-properties and fabrication studies on helix-structured functional composite and devices.
Eastern Mediterranean water outflow during the Younger Dryas was twice that of the present day
Authors: Trias-Navarro Sergio , Pena Leopoldo David , de la Fuente Maria , Paredes Eduardo , Garcia-Solsona Ester , Frigola Jaime , Català Albert , Caruso Antonio , Lirer Fabrizio , Haghipour Negar , Pérez-Asensio José Noel , Cacho Isabel
Published: April 2023

Eastern Mediterranean deep-intermediate convection was highly sensitive to varying inputs of fresh water fluxes associated with increased rainfall during the African Humid period (15-6 kyr Before Present). Here we investigate changes in the water-outflow from the Eastern Mediterranean Sea since the last deglaciation using neodymium isotope ratios. Our results indicate enhanced outflow during the Younger Dryas, two times higher than present-day outflow and about three times higher than during the last Sapropel. We propose that the increased outflow into the western Mediterranean over the Younger Dryas was the result of the combined effect of 1) enhanced climate-driven convection in the Aegean Sea and 2) reduced convection of western deep water during this period. Our results provide solid evidence for an enhanced Younger Dryas westward flow of Eastern Mediterranean sourced waters in consonance with an intensification of Mediterranean water-outflow during a weakened state of the Atlantic circulation.
Physics-Informed Bayesian learning of electrohydrodynamic polymer jet printing dynamics
Authors: Oikonomou Athanasios , Loutas Theodoros , Fan Dixia , Garmulewicz Alysia , Nounesis George , Chaudhuri Santanu , Tourlomousis Filippos
Published: April 2023

Calibration of highly dynamic multi-physics manufacturing processes such as electrohydrodynamics-based additive manufacturing (AM) technologies (E-jet printing) is still performed by labor-intensive trial-and-error practices. Such practices have hindered the broad adoption of these technologies, demanding a new paradigm of self-calibrating E-jet printing machines. Here we develop an end-to-end physics-informed Bayesian learning framework (GPJet) which can learn the jet process dynamics with minimum experimental cost. GPJet consists of three modules: the machine vision module, the physics-based modeling module, and the machine learning (ML) module. GPJet was tested on a virtual E-jet printing machine with in-process jet monitoring capabilities. Our results show that the Machine Vision module can extract high-fidelity jet features in real-time from video data using an automated parallelized computer vision workflow. The Machine Vision module, combined with the Physics-based modeling module, can also act as closed-loop sensory feedback to the Machine Learning module of high- and low-fidelity data. This work extends the application of intelligent AM machines to more complex working conditions while reducing cost and increasing computational efficiency.
Imagining sustainable futures for the high seas by combining the power of computation and narrative
Authors: Lübker Hannah Marlen , Keys Patrick W. , Merrie Andrew , Pereira Laura M. , Rocha Juan C. , Ortuño Crespo Guillermo
Published: April 2023

The high seas are experiencing a stark increase in industrial activities, with resources being exploited unsustainably and shared unequally. This suggests the need for a transformation, a shift in the deeper structures of the system such as underlying paradigms and mind-sets. We created future visions by combining computational text analysis with a structured, yet creative futuring approach. This process resulted in four science fiction stories, which aim to capture the complexity of the system, embrace the inherent uncertainty of the future and question current unsustainable trajectories, while emphasizing the vastness of future option space. The visions are analyzed using the concept of imaginaries, demonstrating that futuristic stories can be traced back to current realities and the scientific evidence they were based upon. We argue that engaging with alternative futures can open up transformative spaces to rethink the relationships between humans and the high seas, from which novel imaginaries can emerge.
Alternating co-synthesis of glycol nucleic acid (GNA) monomers with dicarboxylic acids via drying
Authors: Yi Ruiqin , Jia Tony Z. , Meringer Markus , Marshall Luke K. , Chen Chen , McGlynn Shawn Erin , Fahrenbach Albert C. , Cleaves H. James
Published: April 2023

Co-polymerization of glycol nucleic acid monomers with dicarboxylic acid linkers under plausible early Earth dry-down scenario conditions.
How areN-methylcarbamates encapsulated by β-cyclodextrin: insight into the binding mechanism
Authors: Bao Xiaofang , Liu Xiao , Dou Ran , Xu Sen , Liu Dabin , Luo Jun , Gong Xuedong , Wong Chung F. , Zhou Baojing
Published: April 2023

Based on the measured ICD data and binding constants, the representative binding conformations of β-CD/N-methylcarbamates are identified and the competition between the non-covalent interaction and solvent effect is revealed by a MD/QM/CSM approach.
In‐depth investigation of inter‐turn short‐circuit faults of surface‐mounted permanent magnet machines with series‐parallel coil connections
Authors: Mei Zeting , Li Guang‐jin , Zhu Zi‐Qiang , Clark Richard , Thomas Arwyn , Azar Ziad
Published: April 2023

A general analytical model is developed in a concise block matrix form for surface‐mounted permanent magnet (SPM) machines with series‐parallel coil connections under inter‐turn short circuit (ITSC) fault. In the model, branch currents are used as state variables and inductances of different series‐parallel coil connections are calculated using an analytical method, namely winding function approach (WFA) together with slot permeance method. Based on the characteristics of the calculated inductances and the developed fault model, the multiphase Clarke transformation has been proposed to simplify the fault model. In the process of model simplification, the healthy machine model using branch currents as state variables have been proven to be equivalent to that using 3‐phase currents as state variables. The proposed fault models of a 3kW 96‐slot 32‐pole SPM machine with different series‐parallel coil connections have been built in Matlab/Simulink and validated by time‐stepping 2D FE simulations. Simulation results show that different series‐parallel coil connections have little influence on the amplitude of the ITSC current. Finally, a small scale 24‐slot 8‐pole SPM machine prototype has been built to further validate the accuracy of the proposed fault model.
Reliability analysis of multilevel and matrix converters used in more electric aircraft
Authors: Verma Aanchal , Singh Aditya , Anand Kumar Kyadsandra , Saket Ram Khelawan , Khan Baseem
Published: April 2023

This paper presents the current scenario related to the application of power electronics converters in aviation industries, major challenges and their reliability aspects. Recent developments in power electronics have given a major breakthrough in the aviation industry. These developments are not only limited to the more electric aircraft (MEA) but also in the field of electric propulsion, popularised as electric propulsion aircraft (EPA). The aircraft requires a well‐established protection scheme of these converter topologies. The overall reliability of aircraft solely depends on its protection and fast mitigation of any fault if occurs in the cruise time. This paper aims to provide a comprehensive analysis of power converters applications in MEA and EPA. Further, a review of various topologies of Power Converters and their reliability assessment is also described in detail. The physics of Failure of switches, their lifetime estimation and thermal cycling have also been discussed. Finally, the reliability assessment of different topologies and their comparison has been discussed for overall performance enhancement of the MEA and EPA.
High step‐up quasi‐Z‐source converter with full soft switching range, continuous input current and low auxiliary elements
Authors: Hajilou Maryam , Packnezhad Mohsen , Farzanehfard Hosein
Published: April 2023

This paper presents a fully soft switched high step‐up DC–DC converter based on quasi‐Z‐source converter. The voltage gain is boosted by combining coupled inductors and switched capacitor techniques. Moreover, a ZVT cell comprising of only a single switch and an inductor coupled to the quasi‐Z‐source inductor is utilized to reduce the magnetic cores and realize soft switching for all semiconductors without imposing any extra voltage or current stress on the converter elements. The main switch operates at zero voltage switching and zero current switching (ZCS) at turn‐on which is independent of the load and duty cycle variations. Hence, soft switching condition for the main switch at turn‐off is easily provided by a snubber capacitor. In addition, the reverse recovery problem of all the converter diodes is significantly mitigated by ZCS at turn‐off while the continuous current at the input source is maintained. In order to verify the theoretical analysis and the proposed converter operation, a converter prototype is implemented at 300 W and 100 kHz. Finally, a comprehensive comparison is performed between the proposed converter and other high step‐up converters based on quasi‐Z‐source structure, to demonstrate the merits of the proposed converter.
A research on data integration and application technology of urban comprehensive pipe gallery based on three‐dimensional geographic information system platform
Authors: Huang Yufang , Peng Hongtao , Fang Xiaoxiao , Xing Tingyan
Published: April 2023

Three‐dimensional Geographic Information System (3D GIS) technology is often used in geology, mining, hydrology and other fields. It is also used in intelligent management of urban comprehensive pipe gallery projects, because the real environment with the sky, ground, and underground can be intuitively simulated in the virtual reality environment by 3D GIS platform. Through the research on data integration and application technology of urban comprehensive pipe gallery, the 3D model of comprehensive pipe gallery project data can be created based on Building Information Modelling and GIS technologies, and a comprehensive underground pipelines network management information system has been developed to realise the integration of various data, including 3D data of comprehensive pipe gallery model and underground pipe network model, 2D or 3D GIS data of the ground and underground etc. On this basis, the functions of intelligent planning and approval management, the safety analysis and disaster prevention planning and decision‐making of urban comprehensive pipe gallery projects can be further realised. The research results have been applied to the planning and construction process management of the comprehensive pipe gallery project in the sub‐centre of Beijing.
Hub genes and pathways in gastric cancer: A comparison between studies that used normal tissues adjacent to the tumour and studies that used healthy tissues as calibrator
Authors: Sadegh Khadijeh , Ahmadi Amirhossein
Published: April 2023

Several bioinformatics studies have been performed on high‐throughput expression data to determine the cellular pathways and hub genes affected by Gastric cancer (GC). However, these studies differ in using a healthy tissue or normal tissue adjacent to the tumour (NAT) as calibrator tissues. This study was designed to find how using healthy or NAT tissues as calibrator tissues could affect pathway enrichment data and hub genes in GC. Two gene expression datasets with NAT tissues (GSE79973 and GSE118916) and one dataset with healthy tissues (GSE54129) were downloaded and processed by the limma package to screen the differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analysis were performed by the Enrichr online tool. Protein‐protein interaction network construction, module analysis, and hub genes selection were performed by Cytoscape software, Molecular Complex Detection plugin, and cytoHubba plugin, respectively. The gene expression profiling interactive analysis web server was used to analyse RNA sequencing expression data from The Cancer Genome Atlas Program. The Kaplan—Meier plotter was used to perform survival analysis. Our results showed that some KEGG and GO pathways were shared between studies with NAT and the study with healthy tissues. However, some terms, especially inflammation‐related terms, were missed when NAT tissues were used as calibrator tissues. Also, only FN1 and COL1A1 are common hub genes between DEGs of the studies with NAT and healthy tissues. Since hub genes are usually extracted and suggested as candidate targets for GC diagnosis, prognosis, or treatment, selecting healthy or NAT tissues may affect the hub genes selection.