bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementing front-of-pack nutrition warning labels in Mexico: important lessons for low- and middle-income countries
Authors: Crosbie Eric , Otero Alvarez Margarita Gabriela , Cao Michelle , Vejar Renteria Lesly Samara , Rodriguez Estefania , Larrañaga Flota Ana , Carriedo Angela
Published: July 2023

Objective:

To analyse the implementation of front-of-pack nutrition labelling (FOPNL) in Mexico.

Design:

Review of publicly accessible documents, including legislative websites, news sources, and government, intergovernmental, and advocacy reports. Usage of the policy cycle model to analyse the implementation and evaluation stages of Mexico’s General Health Law, amended with FOPNL (2019–2022).

Results:

In October 2019, the government published a draft modification of the Norma Oficial Mexicana (Official Mexican Standard) to regulate and enforce a new FOPNL warning label system. A 60-d public consultation period followed (October–December 2019), and the regulation was published in March 2020 and implementation began in October 2020. An analysis of nine key provisions of the Standard revealed that the food and beverage industry and its allies weakened some original provisions including health claims, warnings for added sweeteners and display areas. On the other hand, local and international public health groups maintained key regulations including the ban on cartoon character advertisements, standardised portions and nutrient criteria following international best practices. Early implementation appears to have high compliance and helped contribute to reformulating unhealthy products. Continued barriers to implementation include industry efforts to create double fronts and market their cartoon characters on social media and through digitalised marketing.

Conclusion:

Early success in implementing the new FOPNL system in Mexico was the result of an inclusive and participatory regulatory process dedicated to maintaining public health advances, local and international health advocacy support, and continued monitoring. Other countries proposing and enacting FOPNL should learn from the Mexican experience to maintain scientifically proven best practices, counter industry barriers and minimise delays in implementation.
Outer Rainband Formation on Land Ahead of Typhoon Hato (2017)
Authors: Ruan Tianming , Chen Guixing , Bai Lanqiang
Published: July 2023

An outer rainband develops rapidly on land of South China from afternoon to evening of 22 August 2017 when Typhoon Hato is approaching, leading to an early arrival of convective storms prior to typhoon's landfall. The convective cells initiate on the eastern coasts and move to the western inland region where they grow upscale into a fully fledged outer rainband. Convective‐permitting simulations suggest that the new‐born convective cells on the eastern coasts are associated with the increasing convective instability and low‐level lifting by the land‐sea differences of non‐gradient winds. Such differences are established by the horizontal and vertical components of thermal contrasts. In the following stage of convection organization, the convectively induced cold pools in turn strengthen the updrafts at their leading edges, which help to organize the convective cells on rainband as a fast‐moving squall line in the western region. Such storm‐feedback processes of rainband convection and cold pools strongly respond to the changing convective instability and mid‐level dry conditions on land. These regional environmental conditions are closely associated with the large‐scale subsidence in the outer region of typhoon. The results highlight that the new outer rainband can form rapidly on land due to surface heating, and the storm‐feedback processes in response to the changing environmental conditions when a tropical cyclone is approaching land.
Porous Melt Flow in Continental Crust—A Numerical Modeling Study
Authors: Maierová P. , Hasalová P. , Schulmann K. , Štípská P. , Souček O.
Published: July 2023

In continental crust, rapid melt flow through macroscopic conduits is usually envisaged as the most efficient form of melt transport. In contrast, there is growing evidence that in hot continental crust, grain‐scale to meso‐scale porous melt flow may operate over long distances and over millions of years. Here, we investigate the dynamics of such porous melt flow by means of two‐dimensional thermo‐mechanical numerical models using the code ASPECT. Our models are crustal‐scale and describe the network of pores through which the melt flows by permeability that depends on the spacing of the pores. Our results suggest that assuming realistic material properties, melt can slowly migrate in the hot and thick continental crust through pores with a characteristic spacing of 1 mm or larger. Despite its low velocity (millimeters to centimeters per year), over millions of years, such flow can create large partially molten zones in the middle‐lower crust and significantly affect its thermal state, deformation, and composition. We examined the role of the permeability, melt and solid viscosities, the slope of the melting curve and temperature conditions. We obtained contrasting styles of melt distribution, melt flow, and solid deformation, which can be categorized as melt‐enhanced convection, growth of partially molten diapirs and melt percolation in porosity waves. Our numerical experiments further indicate that grain‐scale porous flow is more likely in rocks where the melt productivity increases slowly with temperature, such as in metaigneous rocks.
Solar Energetic Particle Events Detected in the Housekeeping Data of the European Space Agency's Spacecraft Flotilla in the Solar System
Authors: Sánchez‐Cano Beatriz , Witasse Olivier , Knutsen Elise W. , Meggi Dikshita , Viet Shayla , Lester Mark , Wimmer‐Schweingruber Robert F. , Pinto Marco , Moissl Richard , Benkhoff Johannes , Opgenoorth Hermann , Auster Uli , de Brujine Jos , Collins Peter , De Marchi Guido , Fischer David , Futaana Yoshifumi , Godfrey James , Heyner Daniel , Holmstrom Mats , Johnstone Andrew , Joyce Simon , Lakey Daniel , Martinez Santa , Milligan David , Montagnon Elsa , Müller Daniel , Livi Stefano A. , Prusti Timo , Raines Jim , Richter Ingo , Schmid Daniel , Schmitz Peter , Svedhem Håkan , Taylor Matt G. G. T. , Tremolizzo Elena , Titov Dimitri , Wilson Colin , Wood Simon , Zender Joe
Published: July 2023

Despite the growing importance of planetary Space Weather forecasting and radiation protection for science and robotic exploration and the need for accurate Space Weather monitoring and predictions, only a limited number of spacecraft have dedicated instrumentation for this purpose. However, every spacecraft (planetary or astronomical) has hundreds of housekeeping sensors distributed across the spacecraft, some of which can be useful to detect radiation hazards produced by solar particle events. In particular, energetic particles that impact detectors and subsystems on a spacecraft can be identified by certain housekeeping sensors, such as the Error Detection and Correction (EDAC) memory counters, and their effects can be assessed. These counters typically have a sudden large increase in a short time in their error counts that generally match the arrival of energetic particles to the spacecraft. We investigate these engineering datasets for scientific purposes and perform a feasibility study of solar energetic particle event detections using EDAC counters from seven European Space Agency Solar System missions: Venus Express, Mars Express, ExoMars‐Trace Gas Orbiter, Rosetta, BepiColombo, Solar Orbiter, and Gaia. Six cases studies, in which the same event was observed by different missions at different locations in the inner Solar System are analyzed. The results of this study show how engineering sensors, for example, EDAC counters, can be used to infer information about the solar particle environment at each spacecraft location. Therefore, we demonstrate the potential of the various EDAC to provide a network of solar particle detections at locations where no scientific observations of this kind are available.
Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets
Authors: Di Xingpeng , Gao Xiaoshuai , Peng Liao , Ai Jianzhong , Jin Xi , Qi Shiqian , Li Hong , Wang Kunjie , Luo Deyi
Published: July 2023

Cellular mechanotransduction, a critical regulator of numerous biological processes, is the conversion from mechanical signals to biochemical signals regarding cell activities and metabolism. Typical mechanical cues in organisms include hydrostatic pressure, fluid shear stress, tensile force, extracellular matrix stiffness or tissue elasticity, and extracellular fluid viscosity. Mechanotransduction has been expected to trigger multiple biological processes, such as embryonic development, tissue repair and regeneration. However, prolonged excessive mechanical stimulation can result in pathological processes, such as multi-organ fibrosis, tumorigenesis, and cancer immunotherapy resistance. Although the associations between mechanical cues and normal tissue homeostasis or diseases have been identified, the regulatory mechanisms among different mechanical cues are not yet comprehensively illustrated, and no effective therapies are currently available targeting mechanical cue-related signaling. This review systematically summarizes the characteristics and regulatory mechanisms of typical mechanical cues in normal conditions and diseases with the updated evidence. The key effectors responding to mechanical stimulations are listed, such as Piezo channels, integrins, Yes-associated protein (YAP) /transcriptional coactivator with PDZ-binding motif (TAZ), and transient receptor potential vanilloid 4 (TRPV4). We also reviewed the key signaling pathways, therapeutic targets and cutting-edge clinical applications of diseases related to mechanical cues.
Patients with psychosis spectrum disorders hospitalized during the COVID-19 pandemic unravel overlooked SARS-CoV-2 past infection clustering with HERV-W ENV expression and chronic inflammation
Authors: Tamouza Ryad , Meyer Urs , Lucas Alexandre , Richard Jean Romain , Nkam Irène , Pinot Armand , Djonouma Ndilyam , Boukouaci Wahid , Charvet Benjamin , Pierquin Justine , Brunel Joanna , Fourati Slim , Rodriguez Christophe , Barau Caroline , Le Corvoisier Philippe , El Abdellati Kawtar , De Picker Livia , Perron Hervé , Leboyer Marion
Published: July 2023

Epidemiology has repeatedly associated certain infections with a risk of further developing psychiatric diseases. Such infections can activate retro-transposable genetic elements (HERV) known to trigger immune receptors and impair synaptic plasticity of neuroreceptors. Since the HERV-W ENV protein was recently shown to co-cluster with pro-inflammatory cytokines in a subgroup of patients with schizophrenia or bipolar disorder, we questioned the influence of the COVID-19 pandemic on patients with psychosis spectrum disorders (PSD). Present results revealed that (i) SARS-CoV-2 serology shows high prevalence and titers of antibodies in PSD, (ii) HERV-W ENV is detected in seropositive individuals only and (iii) SARS-CoV-2 and HERV-W ENV positivity co-clustered with high serum levels of pro-inflammatory cytokines in psychotic patients. These results thus suggest that SARS-CoV-2 infection in many patients with psychotic disorders now admitted in the psychiatry department did not cause severe COVID-19. They also confirm the previously reported association of elevated serum pro-inflammatory cytokines and HERV-W ENV in a subgroup of psychotic patients. In the context of the COVID-19 pandemic, this cluster is only found in SARS-CoV-2 seropositive PSD cases, suggesting a dominant influence of this virus on HERV-W ENV and cytokine expression, and/or patients’ greater susceptibility to SARS-CoV-2 infection. Further investigation on an interplay between this viral infection and the clinical evolution of such PSD patients is needed. However, this repeatedly defined subgroup of psychotic patients with a pro-inflammatory phenotype and HERV expression calls for a differential therapeutic approach in psychoses, therefore for further precision medicine development.
DEF6(differentially exprehomolog) exacerbates pathological cardiac hypertrophy via RAC1
Authors: Sun Yan , Xu Changlu , Jiang Zhongxiu , Jiang Xi
Published: July 2023

Pathological cardiac hypertrophy involves multiple regulators and several signal transduction pathways. Currently, the mechanisms of it are not well understood. Differentially expressed in FDCP 6 homolog (DEF6) was reported to participate in immunity, bone remodeling, and cancers. The effects of DEF6 on pathological cardiac hypertrophy, however, have not yet been fully characterized. We initially determined the expression profile of DEF6 and found that DEF6 was upregulated in hypertrophic hearts and cardiomyocytes. Our in vivo results revealed that DEF6 deficiency in mice alleviated transverse aortic constriction (TAC)-induced cardiac hypertrophy, fibrosis, dilation and dysfunction of left ventricle. Conversely, cardiomyocyte-specific DEF6-overexpression aggravated the hypertrophic phenotype in mice under chronic pressure overload. Similar to the animal experiments, the in vitro data showed that adenovirus-mediated knockdown of DEF6 remarkably inhibited phenylephrine (PE)-induced cardiomyocyte hypertrophy, whereas DEF6 overexpression exerted the opposite effects. Mechanistically, exploration of the signal pathways showed that the mitogen-activated extracellular signal-regulated kinase 1/2 (MEK1/2)-extracellular signal-regulated kinase 1/2 (ERK1/2) cascade might be involved in the prohypertrophic effect of DEF6. Coimmunoprecipitation and GST (glutathione S-transferase) pulldown analyses demonstrated that DEF6 can directly interact with small GTPase Ras-related C3 botulinum toxin substrate 1 (Rac1), and the Rac1 activity assay revealed that the activity of Rac1 is altered with DEF6 expression in TAC-cardiac hypertrophy and PE-triggered cardiomyocyte hypertrophy. In the end, western blot and rescue experiments using Rac1 inhibitor NSC23766 and the constitutively active mutant Rac1(G12V) verified the requirement of Rac1 and MEK1/2-ERK1/2 activation for DEF6-mediated pathological cardiac hypertrophy. Our study substantiates that DEF6 acts as a deleterious regulator of cardiac hypertrophy by activating the Rac1 and MEK1/2-ERK1/2 signaling pathways, and suggests that DEF6 may be a potential treatment target for heart failure.
NR1D1 deficiency in the tumor microenvironment promotes lung tumor development by activating the NLRP3 inflammasome
Authors: Kim Sun Mi , Jeon Yoon , Jang Ji Yun , Lee Ho
Published: July 2023

Nuclear receptor Rev-erbα (NR1D1) is a major negative regulator of the circadian clock. Numerous studies have investigated the role of circadian clock-related factors in the tumorigenesis of multiple cancer types, but little is known about the role of NR1D1 in cancer development. In this study, we identified the role of NR1D1 in lung tumorigenesis using genetically engineered mouse models of Nr1d1. Although NR1D1 overexpression or knockdown had little effect on the proliferation of NSCLC cells in vitro, NR1D1 deficiency in the tumor microenvironment increased lung cancer development compared with the control in the orthotopic model. NR1D1-deficient mice showed increased NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome activation, and conditioned medium (CM) from NR1D1-deficient macrophages increased the proliferation and epithelial–mesenchymal transition (EMT) of lung cancer cells. Treatment with MCC950, a specific inhibitor of NLRP3 inflammasome, blocked tumorigenesis in NR1D1-deficient mice in an orthotopic lung cancer model. In addition, MCC950 treatment blocked the increased proliferation and EMT of cancer cells induced by CM from NR1D1-deficient macrophages in vitro. Our results showed that NR1D1 in the tumor microenvironment functions as a tumor suppressor by negatively regulating the NLRP3 inflammasome, suggesting that the NLRP3 inflammasome blockade via NR1D1 activation could be a therapeutic strategy to overcome lung cancer.
Engineering tRNA abundances for synthetic cellular systems
Authors: Maheshwari Akshay J. , Calles Jonathan , Waterton Sean K. , Endy Drew
Published: July 2023

Routinizing the engineering of synthetic cells requires specifying beforehand how many of each molecule are needed. Physics-based tools for estimating desired molecular abundances in whole-cell synthetic biology are missing. Here, we use a colloidal dynamics simulator to make predictions for how tRNA abundances impact protein synthesis rates. We use rational design and direct RNA synthesis to make 21 synthetic tRNA surrogates from scratch. We use evolutionary algorithms within a computer aided design framework to engineer translation systems predicted to work faster or slower depending on tRNA abundance differences. We build and test the so-specified synthetic systems and find qualitative agreement between expected and observed systems. First principles modeling combined with bottom-up experiments can help molecular-to-cellular scale synthetic biology realize design-build-work frameworks that transcend tinker-and-test.
Schwann cells regulate tumor cells and cancer-associated fibroblasts in the pancreatic ductal adenocarcinoma microenvironment
Authors: Xue Meilin , Zhu Youwei , Jiang Yongsheng , Han Lijie , Shi Minmin , Su Rui , Wang Liwen , Xiong Cheng , Wang Chaofu , Wang Ting , Deng Shijie , Wu Dong , Cao Yizhi , Dong Lei , Bai Fan , Zhao Shulin , Deng Xiaxing , Peng Chenghong , Li Hongwei , Chen Jianjun , Shen Baiyong , Jiang Lingxi , Chen Hao
Published: July 2023

Neuropathy is a feature more frequently observed in pancreatic ductal adenocarcinoma (PDAC) than other tumors. Schwann cells, the most prevalent cell type in peripheral nerves, migrate toward tumor cells and associate with poor prognosis in PDAC. To unveil the effects of Schwann cells on the neuro-stroma niche, here we perform single-cell RNA-sequencing and microarray-based spatial transcriptome analysis of PDAC tissues. Results suggest that Schwann cells may drive tumor cells and cancer-associated fibroblasts (CAFs) to more malignant subtypes: basal-like and inflammatory CAFs (iCAFs), respectively. Moreover, in vitro and in vivo assays demonstrate that Schwann cells enhance the proliferation and migration of PDAC cells via Midkine signaling and promote the switch of CAFs to iCAFs via interleukin-1α. Culture of tumor cells and CAFs with Schwann cells conditioned medium accelerates PDAC progression. Thus, we reveal that Schwann cells induce malignant subtypes of tumor cells and CAFs in the PDAC milieu.
Knowledge-based mechanistic modeling accurately predicts disease progression with gefitinib in EGFR-mutant lung adenocarcinoma
Authors: L’Hostis Adèle , Palgen Jean-Louis , Perrillat-Mercerot Angélique , Peyronnet Emmanuel , Jacob Evgueni , Bosley James , Duruisseaux Michaël , Toueg Raphaël , Lefèvre Lucile , Kahoul Riad , Ceres Nicoletta , Monteiro Claudio
Published: July 2023

Lung adenocarcinoma (LUAD) is associated with a low survival rate at advanced stages. Although the development of targeted therapies has improved outcomes in LUAD patients with identified and specific genetic alterations, such as activating mutations on the epidermal growth factor receptor gene (EGFR), the emergence of tumor resistance eventually occurs in all patients and this is driving the development of new therapies. In this paper, we present the In Silico EGFR-mutant LUAD (ISELA) model that links LUAD patients’ individual characteristics, including tumor genetic heterogeneity, to tumor size evolution and tumor progression over time under first generation EGFR tyrosine kinase inhibitor gefitinib. This translational mechanistic model gathers extensive knowledge on LUAD and was calibrated on multiple scales, including in vitro, human tumor xenograft mouse and human, reproducing more than 90% of the experimental data identified. Moreover, with 98.5% coverage and 99.4% negative logrank tests, the model accurately reproduced the time to progression from the Lux-Lung 7 clinical trial, which was unused in calibration, thus supporting the model high predictive value. This knowledge-based mechanistic model could be a valuable tool in the development of new therapies targeting EGFR-mutant LUAD as a foundation for the generation of synthetic control arms.
Limits to the accurate and generalizable use of soundscapes to monitor biodiversity
Authors: Sethi Sarab S. , Bick Avery , Ewers Robert M. , Klinck Holger , Ramesh Vijay , Tuanmu Mao-Ning , Coomes David A.
Published: July 2023

Although eco-acoustic monitoring has the potential to deliver biodiversity insight on vast scales, existing analytical approaches behave unpredictably across studies. We collated 8,023 audio recordings with paired manual avifaunal point counts to investigate whether soundscapes could be used to monitor biodiversity across diverse ecosystems. We found that neither univariate indices nor machine learning models were predictive of species richness across datasets but soundscape change was consistently indicative of community change. Our findings indicate that there are no common features of biodiverse soundscapes and that soundscape monitoring should be used cautiously and in conjunction with more reliable in-person ecological surveys.
Telomere-to-telomere assemblies of 142 strains characterize the genome structural landscape in Saccharomyces cerevisiae
Authors: O’Donnell Samuel , Yue Jia-Xing , Saada Omar Abou , Agier Nicolas , Caradec Claudia , Cokelaer Thomas , De Chiara Matteo , Delmas Stéphane , Dutreux Fabien , Fournier Téo , Friedrich Anne , Kornobis Etienne , Li Jing , Miao Zepu , Tattini Lorenzo , Schacherer Joseph , Liti Gianni , Fischer Gilles
Published: July 2023

Pangenomes provide access to an accurate representation of the genetic diversity of species, both in terms of sequence polymorphisms and structural variants (SVs). Here we generated theSaccharomyces cerevisiaeReference Assembly Panel (ScRAP) comprising reference-quality genomes for 142 strains representing the species’ phylogenetic and ecological diversity. The ScRAP includes phased haplotype assemblies for several heterozygous diploid and polyploid isolates. We identified circa (ca.) 4,800 nonredundant SVs that provide a broad view of the genomic diversity, including the dynamics of telomere length and transposable elements. We uncovered frequent cases of complex aneuploidies where large chromosomes underwent large deletions and translocations. We found that SVs can impact gene expression near the breakpoints and substantially contribute to gene repertoire evolution. We also discovered that horizontally acquired regions insert at chromosome ends and can generate new telomeres. Overall, the ScRAP demonstrates the benefit of a pangenome in understanding genome evolution at population scale.
Antibody binding of amyloid beta peptide epimers/isomers and ramifications for immunotherapies and drug development
Authors: Readel Elizabeth R. , Patel Arzoo , Putman Joshua I. , Du Siqi , Armstrong Daniel W.
Published: July 2023

Extracellular deposition of amyloid beta (Aβ) peptide is a contributing factor of Alzheimer’s disease (AD). Considerable effort has been expended to create effective antibodies, or immunotherapies, targeting Aβ peptides. A few immunotherapies are thought to provide some benefit. It is possible that a contributing factor to the responses of such therapies may be the presence of modified, or aberrant, Aβ peptides found in AD patients. These aberrations include the isomerization and epimerization of L-Asp and L-Ser residues to form D-Asp, L/D-isoAsp, and D-Ser residues, respectively. An effective methodology is essential to isolate all Aβ peptides and then to quantify and locate the aberrant amino acids. Modifications to Aβ peptides may elevate the deposition of Aβ plaques and/or contribute to the neurodegeneration in AD patients, and may alter the binding affinity to antibodies. Herein, we used immunoprecipitation to examine the binding affinity of four antibodies against 18 epimeric and/or isomeric Aβ peptides compared to wild type (all L) Aβ peptide. Tandem mass spectrometry was used as a detection method, which also was found to produce highly variable results for epimeric and/or isomeric Aβ.
Gamma radiation-induced synthesis of novel PVA/Ag/CaTiO3 nanocomposite film for flexible optoelectronics
Authors: Abdel Maksoud M. I. A. , Abdelhaleem Soraya , Tawfik Eman K. , Awed A. S.
Published: July 2023

A flexible nanocomposite film based on polyvinyl alcohol (PVA), silver nanoparticles, and calcium titanate (CaTiO3) was synthesized using gamma radiation induced-reduction. Temperature-dependent structural, optical, DC electrical conductivity, electric modulus, and dielectric properties of PVA/Ag/CaTiO3nanocomposite film were investigated. The XRD pattern proved the successful preparation of the nanocomposite film. Also, as the temperature increases, the average crystallite sizes of CaTiO3and Ag nanoparticles decrease from 19.8 to 9.7 nm and 25 to 14.8 nm, respectively. Further, the optical band gap increased from 5.75 to 5.84 eV with increasing temperature. The thermal stability is improved, and the semiconductor behavior for PVA/Ag/CaTiO3nanocomposite film is confirmed by thermal activation energy ΔE with values in the 0.11–0.8 eV range. Furthermore, the maximum barrier Wmvalue was found of 0.29 eV. PVA/Ag/CaTiO3nanocomposite film exhibits a semicircular arc originating from the material’s grain boundary contributions for all temperatures. The optical, DC electrical conductivity, and dielectric properties of the PVA/Ag/CaTiO3nanocomposite film can be suitable for flexible electronic devices such as electronic chips, optoelectronics, and energy storage applications.
Studies on immunopathological changes induced by commercial IBD live vaccines in poultry birds
Authors: Kajal Sushma , Narang Gulshan , Jangir Babu Lal , Kundu Pooja , Lather Deepika , Chhabra Rajesh
Published: July 2023

Intermediate plus live strain infectious bursal disease virus (IBDV) vaccines are used to control IBDV endemic infections in India. In the present study, immunopathological changes induced by commercial infectious bursal disease live vaccines with different immunization regimes were compared. A total of days old 108 Cobb broiler chicks were randomly divided into five groups with 24 chicks each in groups I, II, III and 18 chicks each in group IV and V. Group I served as control I (no immunization) and group II and III chicks were immunized with a single dose of vaccines 1 and 2 on 17th day of age (DOA), respectively. The group IV and V chicks were immunized with vaccines 1 and 2, respectively with primary dose on 17th DOA followed by booster dose on 24th DOA. Both intermediate plus live vaccines produced gross and histopathological lesions in lymphoid organs (bursa of Fabricius, thymus, spleen and caecal tonsils). Increased CD4 + , CD8 + T cells in affected bursa of Fabricius was evidenced by immunohistochemistry. Further, up-regulation in relative mRNA expression of IFN-γ, IL-1β and IL-6 were observed in bursa of Fabricius of treated birds, with maximum alteration particularly on 14th day post single immunization and 7th day post booster immunization. The findings suggest that single immunization regime on the 17th day of age showed immunization equivalent to booster immunization with lesser lesions, therefore, may be practiced and promoted in the field conditions for the better economic returns and animal welfare.
Sugar restriction and blood ingestion shape divergent immune defense trajectories in the mosquito Aedes aegypti
Authors: Magistrado Dom , El-Dougdoug Noha K. , Short Sarah M.
Published: July 2023

Immune defense is comprised of (1) resistance: the ability to reduce pathogen load, and (2) tolerance: the ability to limit the disease severity induced by a given pathogen load. The study of tolerance in the field of animal immunity is fairly nascent in comparison to resistance. Consequently, studies which examine immune defense comprehensively (i.e. considering both resistance and tolerance in conjunction) are uncommon, despite their exigency in achieving a thorough understanding of immune defense. Furthermore, understanding tolerance in arthropod disease vectors is uniquely relevant, as tolerance is essential to the cyclical transmission of pathogens by arthropods. Here, we tested the effect(s) of dietary sucrose concentration and blood ingestion on resistance and tolerance to Escherichia coli infection in the yellow fever mosquito Aedes aegypti. Resistance and tolerance were measured concurrently and at multiple timepoints. We found that mosquitoes from the restricted sugar treatment displayed enhanced resistance at all timepoints post-infection compared to those from the laboratory standard sugar treatment. Blood also improved resistance, but only early post-infection. While sucrose restriction had no effect on tolerance, we show that consuming blood prior to bacterial infection ameliorates a temporal decline in tolerance that mosquitoes experience when provided with only sugar meals. Taken together, our findings indicate that different dietary components can have unique and sometimes temporally dynamic impacts on resistance and tolerance.
Heat and mass transfer with entropy optimization in hybrid nanofluid using heat source and velocity slip: a Hamilton–Crosser approach
Authors: Afzal Sidra , Qayyum Mubashir , Chambashi Gilbert
Published: July 2023

The modeling and analysis of hybrid nanofluid has much importance in industrial sector where entropy optimization is the key factor in different processes. This mechanism is also used in medical industry, where it can be used for separation of blood cells (red and white blood cells, platelets and plasma) by centrifuge process, treating cancers, and drug transport. In light of this importance, current study is focused on mathematical modeling and analysis of blood based hybrid nanofluid between rotating disks with various shapes of nanoparticles. The shape factors are taken into account with Hamilton–Crosser model as spherical, brick, cylinder and platelet in the current scenario, with special reference to entropy optimization. In order to solve modeled nonlinear and non-dimensional system, optimal homotopy analysis approach is utilized through Wolfram MATHEMATICA 11.3 software. Error estimation and convergence analysis confirms that obtained semi-analytical solutions are valid and reliable. Velocity, temperature and concentration profiles are analyzed against important fluid parameters. Fluid velocity decreased in all directions when unsteady parameter $$\mathbb {B}$$
B
and Darcy number Da increased while the slip parameters $$\zeta _{1}$$

ζ
1

and $$\zeta _{2}$$

ζ
2

decreased the nanofluid velocity. It is observed that in case of brick shaped nanoparticles, fluid temperature is enhanced as compared to other shape factors in the study. Minimal entropy generation is captured in case of spherical nanoparticles, while highest heat transfer is observed in platelet shaped nanoparticles. Furthermore, numerical optimization of entropy is performed against different values of $$\hbar$$
ħ
and volume fractions $$\varphi _{Rd}$$

φ

Rd

and $$\varphi _{Al}$$

φ

Al

. Minimized entropy is recovered to be zero when $$\hbar =-0.6$$

ħ
=
-
0.6

, $$\varphi _{Rd}=2\%$$

φ

Rd

=
2
%

and $$\varphi _{Al}=1\%$$

φ

Al

=
1
%

.
The toxic effects of electronic cigarette aerosol and cigarette smoke on cardiovascular, gastrointestinal and renal systems in mice
Authors: Xu Aijing , Duan Kun , Yang Wanchun , Feng Guodong , Wu Zehong , Jiang Xingtao , Li Min , Liu Peiqing , Chen Jianwen
Published: July 2023

Electronic cigarette (EC) has been suggested to be less harmful than cigarette smoking, but the research on the full extent of their harm reduction potential is still lacking. This study aimed to evaluate the influence of EC aerosol and cigarette smoke (CS) on cardiovascular, gastrointestinal, and renal functions in mice after prolonged exposure. Forty-eight C57BL/6J male mice were randomly grouped and then exposed to fresh air (control), mung bean-flavored EC aerosol with low and high dose (EC1L, 6 mg/kg; EC1H, 12 mg/kg), watermelon-flavored EC aerosol with low and high dose (EC2L, 6 mg/kg; EC2H, 12 mg/kg), and finally a cigarette smoke (CS, 6 mg/kg), respectively. After 10 weeks of exposure, the heart rate increased for both the EC and CS groups, and the effect of CS on blood oxygen saturation was significantly higher than that of the EC group (P < 0.01). Proteomic analysis of the heart tissue showed that the overlapped differential expression protein from the EC and CS exposures was Crip2. For the gastrointestinal system, oral mucosa was significantly damaged in CS group. Compare with CS, EC had significantly fewer negative effects on most of the indictors which focused on in this study.
Lack of orientation specific adaptation to vertically oriented Glass patterns in human visual cortex: an fMRI adaptation investigation
Authors: Pavan Andrea , Malloni Wilhelm M. , Frank Sebastian M. , Wein Simon , Donato Rita , Greenlee Mark W.
Published: July 2023

The perception of coherent form configurations in natural scenes relies on the activity of early visual areas that respond to local orientation cues. Subsequently, high-level visual areas pool these local signals to construct a global representation of the initial visual input. However, it is still debated whether neurons in the early visual cortex respond also to global form features. Glass patterns (GPs) are visual stimuli employed to investigate local and global form processing and consist of randomly distributed dots pairs called dipoles arranged to form specific global configurations. In the current study, we used GPs and functional magnetic resonance imaging (fMRI) adaptation to reveal the visual areas that subserve the processing of oriented GPs. Specifically, we adapted participants to vertically oriented GP, then we presented test GPs having either the same or different orientations with respect to the adapting GP. We hypothesized that if local form features are processed exclusively by early visual areas and global form by higher-order visual areas, then the effect of visual adaptation should be more pronounced in higher tier visual areas as it requires global processing of the pattern. Contrary to this expectation, our results revealed that adaptation to GPs is robust in early visual areas (V1, V2, and V3), but not in higher tier visual areas (V3AB and V4v), suggesting that form cues in oriented GPs are primarily derived from local-processing mechanisms that originate in V1. Finally, adaptation to vertically oriented GPs causes a modification in the BOLD response within early visual areas, regardless of the relative orientations of the adapting and test stimuli, indicating a lack of orientation selectivity.
Preclinical immunological characterization of rademikibart (CBP-201), a next-generation human monoclonal antibody targeting IL-4Rα, for the treatment of Th2 inflammatory diseases
Authors: Zhang Limin , Ding Ying , Wang Qingjian , Pan Wubin , Wei Zheng , Smith Paul A. , Yang Xin
Published: July 2023

Rademikibart (CBP-201) is a next-generation human monoclonal antibody targeting IL-4Rα, undergoing evaluation in Phase 2 clinical trials for the treatment of moderate-to-severe Th2 inflammatory diseases. We report the immunological characterization of rademikibart. Rademikibart and dupilumab were associated with KD of 20.7 pM and 45.8 pM, respectively, when binding to distinct human IL-4Rα epitopes. Rademikibart did not bind to IL-4Rα from other species. Rademikibart inhibited IL-4 and IL-13-mediated STAT6 signaling (mean ± SD IC50: 7.0 ± 2.5 and 6.6 ± 1.5 ng/mL, respectively), TF-1 cell proliferation (IC50: 8.0 ± 1.6 and 9.7 ± 0.8 ng/mL, respectively) and TARC production in PBMCs (IC50: 59.2 ± 3.9 and 13.5 ± 0.2 ng/mL, respectively). Rademikibart versus dupilumab was more potent in the STAT6 assays (IL-4, p < 0.01; IL-13, p = 0.03), with non-significant trends towards greater potency in the TF-1 cell assays (IL-4, p = 0.09; IL-13, p = 0.20), and similar potency in the TARC assays. In experiments with mice expressing human IL-4Rα and IL-4, rademikibart and dupilumab demonstrated similar potency; both monoclonal antibodies eliminated IL-4 (p < 0.0001) and IL-13 (p < 0.05) mediated B cell activation in vitro and ovalbumin-induced IgE (p < 0.01) and eosinophilic lung infiltration (p < 0.0001) in vivo. In Th2-stimulated human skin explants, rademikibart rapidly downregulated IL-4, IL-13, and TARC gene expression, with greater effectiveness than dupilumab for IL-4 (p < 0.01) and a non-significant trend towards superiority for IL-13. In summary, rademikibart bound to a distinct IL-4Rα epitope with high affinity and demonstrated reductions in Th2 inflammatory biomarkers with at least similar and potentially superior potency to dupilumab.
Hydrophilic and lipophilic statin use and risk of hearing loss in hyperlipidemia using a Common Data Model: multicenter cohort study
Authors: Song Insik , Kim Minjin , Choi Hangseok , Kim Jeong Hwan , Lim Kang Hyeon , Yoon Hee Soo , Rah Yoon Chan , Park Euyhyun , Im Gi Jung , Song Jae-Jun , Chae Sung-Won , Choi June
Published: July 2023

Hearing impairment, the third largest health burden worldwide, currently lacks definitive treatments or preventive drugs. This study compared the effects of hydrophilic and lipophilic statin on hearing loss using a common database model. This retrospective multicenter study was conducted in three hospitals in South Korea (Anam, Guro, Ansan). We enrolled patients with hyperlipidemia with an initial hearing loss diagnosis. Data were collected during January 1, 2022–December 31, 2021 using the Observational Health Data Science and Informatics open-source software and Common Data Model database. The primary outcome was the occurrence of first-time hearing loss following a hyperlipidemia diagnosis, as documented in the Common Data Model cohort database. The measures of interest were hearing loss risk between hydrophilic and lipophilic statin use. Variables were compared using propensity score matching, Cox proportional regression, and meta-analysis. Among 37,322 patients with hyperlipidemia, 13,751 (7669 men and 6082 women) and 23,631 (11,390 men and 12,241 women) were treated with hydrophilic and lipophilic statins, respectively. After propensity score matching, according to the Kaplan–Meier curve, hearing loss risk did not significantly differ among the hospitals. The hazard ratio (HR) of the male patients from Anam (0.29, [95% confidence interval (CI), 0.05–1.51]), Guro (HR, 0.56, [95% CI 0.18–1.71]), and Ansan (hazard ratio, 0.29, [95% CI 0.05–1.51]) hospitals were analyzed using Cox proportional regression. Overall effect size (HR, 0.40, [95% CI 0.18–0.91]) was estimated using meta-analysis, which indicated that hearing loss risk among hydrophilic statin users was less than that among lipophilic statin users and was statistically significant. Men in the hydrophilic statin group had a lower risk of hearing impairment than those in the lipophilic statin group.
Calgary score and modified calgary score in the differential diagnosis between syncope and genetic generalized epilepsy in children
Authors: Köle Mehmet Tolga , Sağer Safiye Günes , Batu Utku , Çetiner Çine Nilüfer , Çağ Yakup , Akin Yasemin
Published: July 2023

The purpose of the study is to explore the use of Calgary scoring (CS) and Modified Calgary scoring (MCS) in the differentiation of genetic generalized epilepsy and syncope in children. The study involved 117 patients aged < 18 years who presented to our hospital’s pediatric neurology outpatient clinic with TLOC between June 2020 and June 2022. In addition to CS and MCS scoring, all patients were subjected to statistical analysis based on their age, sex, number of episodes and distribution during the day, duration of syncope, and family history. Seventy-one patients with syncope and 46 with epilepsy were included in the study. At a CS value >  − 1, sensitivity was 86.9% and specificity 63.4%, while at an MCS value >  − 1, sensitivity was 76.1% and specificity 71.8%. CS had less specificity and sensitivity in predicting epilepsy when focal epilepsies were excluded. Abnormal behavior noted by bystanders, including witnessed unresponsive, unusual posturing, or limb jerking? (Q5) emerged as the most important question for the detection of epilepsy. Compared with other syncope findings, loss of consciousness during prolonged sitting or standing (Q9) emerged as the most important for the detection of syncope.
Effect of Trichoderma viride on insoluble phosphorus absorption ability and growth of Melilotus officinalis
Authors: Song Mingxia , Wang Xinyu , Xu Hongwei , Zhou Xiaofu , Mu Chunsheng
Published: July 2023

Phosphorus (Pi) deficiency is a major factor of limiting plant growth. Using Phosphate-solubilizing microorganism (PSM) in synergy with plant root system which supply soluble Pi to plants is an environmentally friendly and efficient way to utilize Pi. Trichoderma viride (T. viride) is a biocontrol agent which able to solubilize soil nutrients, but little is known about its Pi solubilizing properties. The study used T. viride to inoculate Melilotus officinalis (M. officinalis) under different Pi levels and in order to investigate the effect on Pi absorption and growth of seedlings. The results found that T. viride could not only solubilizate insoluble inorganic Pi but also mineralize insoluble organic Pi. In addition, the ability of mineralization to insoluble organic Pi is more stronger. Under different Pi levels, inoculation of T. viride showed that promoted the growth of aboveground parts of seedlings and regulated the morphology of roots, thus increasing the dry weight of seedlings. The effect of T. viride on seedling growth was also reflected the increasing of chlorophyll fluorescence parameters and photosynthetic pigment content. Moreover, compared to the uninoculated treatments, inoculation of T. viride also enhanced Pi content in seedlings. Thus, the T. viride was a beneficial fungus for synergistic the plant Pi uptake and growth.
A bioinformatics approach to identify a disulfidptosis-related gene signature for prognostic implication in colon adenocarcinoma
Authors: Hu Gunchu , Yao Hongliang , Wei Zuxing , Li Linye , Yu Zhuowen , Li Jian , Luo Xiong , Guo Zhushu
Published: July 2023

Colon adenocarcinoma (COAD) is a type of cancer that arises from the glandular epithelial cells that produce mucus in the colon. COAD is influenced by various factors, including genetics, environment and lifestyle. The outcome of COAD is determined by the tumor stage, location, molecular characteristics and treatment. Disulfidptosis is a new mode of cell death that may affect cancer development. We discovered genes associated with disulfidptosis in colon adenocarcinoma and proposed them as novel biomarkers and therapeutic targets for COAD. We analyzed the mRNA expression data and clinical information of COAD patients from The Cancer Genome Atlas (TCGA) database and Xena databases, extracted disulfidptosis-related genes from the latest reports on disulfidptosis. We used machine learning to select key features and build a signature and validated the risk model using data from the Gene Expression Omnibus (GEO) database and Human Protein Atlas (HPA). We also explored the potential biological functions and therapeutic implications of the disulfidptosis-related genes using CIBERSORTx and GDSC2 databases. We identified four disulfidptosis-related genes: TRIP6, OXSM, MYH3 and MYH4. These genes predicted COAD patient survival and modulated the tumor microenvironment, drug sensitivity and immune microenvironment. Our study reveals the importance of disulfidptosis-related genes for COAD prognosis and therapy. Immune infiltration and drug susceptibility results provide important clues for finding new personalized treatment options for COAD. These findings may facilitate personalized cancer treatment.
Tropical rock lobster (Panulirus ornatus) uses chemoreception via the antennular lateral flagellum to identify conspecific ecdysis
Authors: Kelly Tara R. , Fitzgibbon Quinn P. , Smith Gregory G. , Banks Thomas M. , Ventura Tomer
Published: July 2023

The tropical rock lobster, Panulirus ornatus, is a commercially important aquaculture species exhibiting complex social interactions in laboratory culture, including cannibalism of moulting conspecifics. Cannibalism of soft-shelled post-moult stage individuals is a major limitation during the juvenile stage of culture. Not limited to P. ornatus, cannibalism is widespread across farmed decapods, limiting stocking densities in crab, freshwater crayfish, and prawn species. To understand the mechanisms driving this behaviour and reduce its prevalence, we have investigated the role of chemoreception via the aesthetasc-bearing region of the lateral antennular flagellum, in the recognition of conspecific moulting cues. Differential expression analysis of several tissues in P. ornatus shows an upregulation of 70 ionotropic receptor isoforms, including co-receptors (IR25a and IR93a) and divergent receptors (IR4, IR7, and IR21a) in the aesthetasc-bearing region of the antennules. Deafferentation of the aesthetascs via deionised water exposure prevents juveniles from responding to conspecific moulting cues in a two-current choice flume, suggesting chemoreception, possibly olfaction, plays a role in identifying moulting juveniles. This is the first step in understanding the mechanisms via which cannibalism is triggered in juvenile P. ornatus culture. Further work in this area will help discover means to limit cannibalism in laboratory and commercial culture.
Optimizing an efficient ensemble approach for high-quality de novo transcriptome assembly of Thymus daenensis
Authors: Ahmadi Hosein , Sheikh-Assadi Morteza , Fatahi Reza , Zamani Zabihollah , Shokrpour Majid
Published: July 2023

Non-erroneous and well-optimized transcriptome assembly is a crucial prerequisite for authentic downstream analyses. Each de novo assembler has its own algorithm-dependent pros and cons to handle the assembly issues and should be specifically tested for each dataset. Here, we examined efficiency of seven state-of-art assemblers on ~ 30 Gb data obtained from mRNA-sequencing of Thymus daenensis. In an ensemble workflow, combining the outputs of different assemblers associated with an additional redundancy-reducing step could generate an optimized outcome in terms of completeness, annotatability, and ORF richness. Based on the normalized scores of 16 benchmarking metrics, EvidentialGene, BinPacker, Trinity, rnaSPAdes, CAP3, IDBA-trans, and Velvet-Oases performed better, respectively. EvidentialGene, as the best assembler, totally produced 316,786 transcripts, of which 235,730 (74%) were predicted to have a unique protein hit (on uniref100), and also half of its transcripts contained an ORF. The total number of unique BLAST hits for EvidentialGene was approximately three times greater than that of the worst assembler (Velvet-Oases). EvidentialGene could even capture 17% and 7% more average BLAST hits than BinPacker and Trinity. Although BinPacker and CAP3 produced longer transcripts, the EvidentialGene showed a higher collinearity between transcript size and ORF length. Compared with the other programs, EvidentialGene yielded a higher number of optimal transcript sets, further full-length transcripts, and lower possible misassemblies. Our finding corroborates that in non-model species, relying on a single assembler may not give an entirely satisfactory result. Therefore, this study proposes an ensemble approach of accompanying EvidentialGene pipelines to acquire a superior assembly for T. daenensis.