bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibitory Effect and Potential Antagonistic Mechanism of Isolated Epiphytic Yeasts against Botrytis cinerea and Alternaria alternata in Postharvest Blueberry Fruits
Authors: Li Jia , Yang Ting , Yuan Furong , Lv Xinyue , Zhou Yahan
Published: April 2024

This study evaluated the biocontrol effect of isolated epiphytic yeasts (Papiliotrema terrestris, Hanseniaspora uvarum, and Rhodosporidium glutinis) against Botrytis cinerea and Alternaria alternata in blueberry fruits and its possible mechanisms. Our findings indicated that the three tested yeasts exerted a good biocontrol effect on postharvest diseases in blueberry, and that H. uvarum was the most effective. In addition, the three tested yeasts could improve the postharvest storage quality of blueberry fruits to some extent. H. uvarum demonstrated the strongest direct inhibitory effect on pathogens by suppressing spore germination, mycelial growth, and antifungal volatile organic compound (VOC) production. P. terrestris showed the highest extracellular lytic enzymes activities. It also had better adaptation to low temperature in fruit wounds at 4 °C. The biofilm formation capacity was suggested to be the main action mechanism of R. glutinis, which rapidly colonized fruit wounds at 20 °C. Several action mechanisms are employed by the superb biocontrol yeasts, while yeast strains possess distinctive characteristics and have substantially different action mechanisms.
Event-Triggered Adaptive Neural Network Control for State-Constrained Pure-Feedback Fractional-Order Nonlinear Systems with Input Delay and Saturation
Authors: Wang Changhui , Yang Jiaqi , Liang Mei
Published: April 2024

In this research, the adaptive event-triggered neural network controller design problem is investigated for a class of state-constrained pure-feedback fractional-order nonlinear systems (FONSs) with external disturbances, unknown actuator saturation, and input delay. An auxiliary compensation function based on the integral function of the input signal is presented to handle input delay. The barrier Lyapunov function (BLF) is utilized to deal with state constraints, and the event-triggered strategy is applied to overcome the communication burden from the limited communication resources. By the utilization of a backstepping scheme and radial basis function neural network, an adaptive event-triggered neural state-feedback stabilization controller is constructed, in which the fractional-order dynamic surface filters are employed to reduce the computational burden from the recursive procedure. It is proven that with the fractional-order Lyapunov analysis, all the solutions of the closed-loop system are bounded, and the tracking error can converge to a small interval around the zero, while the state constraint is satisfied and the Zeno behavior can be strictly ruled out. Two examples are finally given to show the effectiveness of the proposed control strategy.
Some Properties of Normalized Tails of Maclaurin Power Series Expansions of Sine and Cosine
Authors: Zhang Tao , Yang Zhen-Hang , Qi Feng , Du Wei-Shih
Published: April 2024

In the paper, the authors introduce two notions, the normalized remainders, or say, the normalized tails, of the Maclaurin power series expansions of the sine and cosine functions, derive two integral representations of the normalized tails, prove the nonnegativity, positivity, decreasing property, and concavity of the normalized tails, compute several special values of the Young function, the Lommel function, and a generalized hypergeometric function, recover two inequalities for the tails of the Maclaurin power series expansions of the sine and cosine functions, propose three open problems about the nonnegativity, positivity, decreasing property, and concavity of a newly introduced function which is a generalization of the normalized tails of the Maclaurin power series expansions of the sine and cosine functions. These results are related to the Riemann–Liouville fractional integrals.
Complete Chloroplast Genome Sequence Structure and Phylogenetic Analysis of Kohlrabi (Brassica oleracea var. gongylodes L.)
Authors: Zhao Mengliang , Wu Yanxun , Ren Yanjing
Published: April 2024

Kohlrabi is an important swollen-stem cabbage variety belonging to the Brassicaceae family. However, few complete chloroplast genome sequences of this genus have been reported. Here, a complete chloroplast genome with a quadripartite cycle of 153,364 bp was obtained. A total of 132 genes were identified, including 87 protein-coding genes, 37 transfer RNA genes and eight ribosomal RNA genes. The base composition analysis showed that the overall GC content was 36.36% of the complete chloroplast genome sequence. Relative synonymous codon usage frequency (RSCU) analysis showed that most codons with values greater than 1 ended with A or U, while most codons with values less than 1 ended with C or G. Thirty-five scattered repeats were identified and most of them were distributed in the large single-copy (LSC) region. A total of 290 simple sequence repeats (SSRs) were found and 188 of them were distributed in the LSC region. Phylogenetic relationship analysis showed that five Brassica oleracea subspecies were clustered into one group and the kohlrabi chloroplast genome was closely related to that of B. oleracea var. botrytis. Our results provide a basis for understanding chloroplast-dependent metabolic studies and provide new insight for understanding the polyploidization of Brassicaceae species.
Novel Genome-Engineered H Alleles Differentially Affect Lateral Inhibition and Cell Dichotomy Processes during Bristle Organ Development
Authors: Mönch Tanja C. , Smylla Thomas K. , Brändle Franziska , Preiss Anette , Nagel Anja C.
Published: April 2024

Hairless (H) encodes the major antagonist in the Notch signaling pathway, which governs cellular differentiation of various tissues in Drosophila. By binding to the Notch signal transducer Suppressor of Hairless (Su(H)), H assembles repressor complexes onto Notch target genes. Using genome engineering, three new H alleles, HFA, HLLAA and HWA were generated and a phenotypic series was established by several parameters, reflecting the residual H-Su(H) binding capacity. Occasionally, homozygous HWA flies develop to adulthood. They were compared with the likewise semi-viable HNN allele affecting H-Su(H) nuclear entry. The H homozygotes were short-lived, sterile and flightless, yet showed largely normal expression of several mitochondrial genes. Typical for H mutants, both HWA and HNN homozygous alleles displayed strong defects in wing venation and mechano-sensory bristle development. Strikingly, however, HWA displayed only a loss of bristles, whereas bristle organs of HNN flies showed a complete shaft-to-socket transformation. Apparently, the impact of HWA is restricted to lateral inhibition, whereas that of HNN also affects the respective cell type specification. Notably, reduction in Su(H) gene dosage only suppressed the HNN bristle phenotype, but amplified that of HWA. We interpret these differences as to the role of H regarding Su(H) stability and availability.
Possible Interrelations of Space Weather and Seismic Activity: An Implication for Earthquake Forecast
Authors: Sorokin Valery , Novikov Victor
Published: April 2024

The statistical analysis of the impact of the top 50 X-class solar flares (1997–2024) on global seismic activity as well as on the earthquake preparation zones located in the illuminated part of the globe and in an area of 5000 km around the subsolar point was carried out. It is shown by a method of epoch superposition that for all cases, an increase in seismicity is observed, especially in the region around the subsolar point (up to 33%) during the 10 days after the solar flare in comparison with the preceding 10 days. The case study of the aftershock sequence of a strong Mw = 9.1 earthquake (Sumatra–Andaman Islands, 26 December 2004) after the solar flare of X10.16 class (20 January 2005) demonstrated that the number of aftershocks with a magnitude of Mw ≥ 2.5 increases more than 17 times after the solar flare with a delay of 7–8 days. For the case of the Darfield earthquake (Mw = 7.1, 3 September 2010, New Zealand), it was shown that X-class solar flares and M probably triggered two strong aftershocks (Mw = 6.1 and Mw = 5.9) with the same delay of 6 days on the Port Hills fault, which is the most sensitive to external electromagnetic impact from the point of view of the fault electrical conductivity and orientation. Based on the obtained results, the possible application of natural electromagnetic triggering of earthquakes is discussed for the earthquake forecast using confidently recorded strong external electromagnetic triggering impacts on the specific earthquake preparation zones, as well as ionospheric perturbations due to aerosol emission from the earthquake sources recorded by satellites.
Assessment of Site Effects and Numerical Modeling of Seismic Ground Motion to Support Seismic Microzonation of Dushanbe City, Tajikistan
Authors: Hakimov Farkhod , Havenith Hans-Balder , Ischuk Anatoly , Reicherter Klaus
Published: April 2024

In the territory of Dushanbe city, the capital of Tajikistan, detailed geological and geophysical data were collected during geophysical surveys in 2019–2020. The data comprise 5 microtremor array measurements, 9 seismic refraction tomography profiles, seismological data from 5 temporary seismic stations for standard spectral ratio calculations, 60 borehole datasets, and 175 ambient noise measurements. The complete dataset for Dushanbe was used to build a consistent 3D geologic model of the city with a size of 12 × 12 km2. The results of the seismological and geophysical surveys were compared and calibrated with borehole data to define the boundaries of each layer in the study area. The Leapfrog Works software was utilized to create a 3D geomodel. From the 3D geomodel, we extracted six 12 km long 2D geological cross-sections. These 2D geological cross-sections were used for 2D dynamic numerical modeling with the Universal Distinct Element Code software to calculate the local seismic response. Finally, the dynamic numerical modeling results were compared with the amplification functions obtained from the seismological and ambient noise data analysis. The 2D dynamic numerical modeling results allowed a better assessment of the site effects in the study area to support seismic microzonation and the determination of local peak ground acceleration changes in combination with regional seismic hazard maps. In addition, our results confirm the strong seismic amplification effects noted in some previous studies, which are attributed to the influence of local topographic and subsurface characteristics on seismic ground motions.
Periodontal Health among Individuals with Intellectual Disabilities Living in a Saudi Institutional Rehabilitation Centre
Authors: Alzahrani Abdullah Ali H.
Published: April 2024

The aim of this study was to explore periodontal health among intellectually disabled individuals living in an institutional rehabilitation centre in the Al-Baha Region of Saudi Arabia. A cross-sectional study was conducted from November 2023 to January 2024. Clinical oral examinations were carried out using the World Health Organization criteria for bleeding sites and the presence of periodontal pockets. Simplified oral hygiene and community periodontal indices were employed to evaluate participants’ oral health. A total of 89 participants, comprising both males and females with intellectual disabilities, were included in this study. Gender, severity of intellectual disability, type of additional physical disability, tooth brushing habits and oral hygiene status were significantly associated with the presence of periodontal disease. Additionally, poor oral hygiene, not brushing teeth and periodontal pockets of 4–5 mm and 6 mm or more were significantly more prevalent among individuals with severe and moderate intellectual disabilities (p = 0.001, p = 0.001, p = 0.001 and p = 0.001, respectively). The prevalence of periodontal disease among the studied population was 54%. The odds of having periodontal disease were significantly higher in the severe intellectual disability group compared to the mild intellectual disability group (OR = 2.328, 95% CI = 1.430–3.631, p = 0.03). It was also found that intellectually disabled participants with additional physical disabilities suffered more from periodontal disease than those without additional physical disabilities (OR = 0.971, 95% CI = 0.235–4.023, p = 0.025). Overall, individuals with intellectual disabilities had a significant demand for periodontal care. This study highlighted the need for more organised preventive programmes for individuals with intellectual disabilities. Dentists should be vigilant about improving periodontal health, focus on preventive programmes and provide comprehensive dental care with an emphasis on periodic recall and monitoring.
Hydropedological Characterization of a Coal Mining Waste Deposition Area Affected by Self-Burning
Authors: Espinha Marques Jorge , Narayan Aracelis , Santos Patrícia , Ribeiro Joana , Antunes Sara C. , Melo Armindo , Rocha Fernando , Flores Deolinda , Mansilha Catarina
Published: April 2024

Coal mining often produces severe environmental effects, including impacts on the soil system and, specifically, on hydropedological conditions that control the leaching of significant ions and Potentially Toxic Elements (PTEs). The research objective is to assess changes in the hydropedological conditions in an area with a coal mining waste pile that underwent self-burning. An integrative approach was implemented, starting with the definition of hydropedological zoning based on field observations of soil formation factors (namely, parent material, relief, biological activity, anthropic influence, and time). The soil profile in each hydropedological zone was characterized regarding morphological features. The upper mineral horizons were sampled and characterized in terms of mineralogy and PTE geochemistry. Field measurements of unsaturated hydraulic conductivity, soil water content, and hydrophobicity were performed. Afterwards, the hydrogeochemistry of leachates was determined, and the soil leaching potential was evaluated. The research outcomes express substantial differences regarding the hydropedological zones: development of different soil profiles, diverse mineralogy and PTE geochemistry, higher unsaturated hydraulic conductivity and leaching of major ions, and PTEs in soils affected by coal mining activities. Finally, a Principal Component Analysis confirmed the existence of significant contrasts according to hydropedological zoning.
A Mixed-Methods Evaluation of a Project ECHO Program for the Evidence-Based Management of Sickle Cell Disease
Authors: Mosley Cami , Farrell Christina Bennett , Quinn Charles T. , Shook Lisa Marie
Published: April 2024

Sickle cell disease (SCD) is a group of chronic, genetic disorders of the red blood cells with significant gaps in access to evidence-based clinical care. Sickle Treatment and Outcomes Research in the Midwest (STORM), a provider network, utilized Project ECHO (Extension for Community Health Outcomes), a telementoring model, to deliver evidence-based education about SCD management. The purpose of this mixed-methods study is to evaluate the utility of Project ECHO as an educational strategy for healthcare providers treating children and adults with SCD. Annual evaluations were administered to STORM TeleECHO participants from 2016 to 2021. Survey data showed a statistically significant change in self-reported provider confidence in the ability to provide care for adult patients with SCD; identify suitable candidates for disease-modifying therapies; and confidence to prescribe disease-modifying therapies. Participants who attended at least 10 sessions were invited to participate in a semi-structured interview. Qualitative data were analyzed using thematic analysis and several themes emerged about the benefits, including (1) increased confidence, (2) integrated best-practice care, (3) connection to provider network and access to experts, (4) high-quality educational presentations and (5) opportunities for collaboration and a sense of community. This suggests that Project ECHO is accessible and leads to increased confidence in providers caring for individuals with SCD. Overall, participant knowledge gains successfully demonstrated the utility of Project ECHO as an educational resource for providers.
Assessing the Vulnerability and Adaptation Needs of Mozambique’s Health Sector to Climate: A Comprehensive Study
Authors: Muleia Rachid , Maúre Genito , José Américo , Maholela Plácida , Adjei Isaac Akpor , Karim Md. Rezaul , Trigo Sónia , Kutane Waltaji , Inlamea Osvaldo , Kazembe Lawrence N. , Marrufo Tatiana
Published: April 2024

Climate change poses severe consequences, particularly in sub-Saharan Africa, where poverty rates may escalate by 2050 without significant climate and development action. The health impacts are diverse, encompassing communicable and non-communicable diseases. Mozambique, a climate-vulnerable nation, has experienced significant natural disasters in the past 42 years, impacting its health system. This study aims to assess Mozambique’s health sector’s vulnerability and adaptation needs to climate change. Following a methodology proposed by the World Health Organization and the Intergovernmental Panel for Climate Change, a six-step vulnerability and adaptation assessment was conducted to conduct the Health Vulnerability Index (HVI) for Mozambique’s regions (n=161). The HVI integrates historical climate, epidemiological, and socio-economic data at the district level, and was computed using exposure, sensitivity, and adaptive capacity dimensions. The results revealed spatial patterns in exposure to climate variables, extreme weather events, and variations in sensitivity and adaptive capacity across the country. The HVI mirrored the exposure findings. Notably, high vulnerability was observed in several districts, while major urban centers displayed lower vulnerability. These findings highlight the country’s vulnerability to climate change and underscore the potential for adverse impacts on livelihoods, the economy, and human health. The study provides a foundation for developing strategies and adaptation actions.
How Do Healthcare Professionals Develop the Communication Process to Promote Patients’ Health Literacy?
Authors: Cesar Flaviane Cristina Rocha , Oliveira Lizete Malagoni de Almeida Cavalcante , Galvão Mariana Cristyen , Lacerda Ana Luiza Andrade
Published: April 2024

This study aimed to analyze the communication process of healthcare professionals for the promotion of health literacy. It is a qualitative study that utilized individual online interviews with 46 healthcare professionals working in Brazil. The thematic content analysis technique proposed by Bardin was employed, and Atlas Ti software assisted in the assessment and interpretation of the texts. Content categorization revealed 26 sub-themes, and the coding of these identified nine themes and three categories. The communication process in health literacy education was composed of a set of interdependent and interrelated variables termed emotions, professional preparedness, interprofessional collaboration, patient needs assessment, building rapport, family inclusion in the educational process, environmental aspects, strategies, and resources for teaching and learning. These data may support the analysis of health communication in healthcare services, the creation of data collection instruments, and the development of training programs to enhance skills within the context of the identified variables.
Health-Related Physical Fitness Evaluation in HIV-Diagnosed Children and Adolescents: A Scoping Review
Authors: de Castro João Antônio Chula , de Lima Tiago Rodrigues , Silva Diego Augusto Santos
Published: April 2024

Background: Health-related physical fitness has been widely used to investigate the adverse effects of HIV infection/ART in children and adolescents. However, methods/protocols and cut-points applied for investigating health-related physical fitness are not clear. The aim of this scoping review was to map the literature to identify gaps in knowledge regarding the methods/protocols and cut-points. Methods: A scoping review, following the Joana Briggs Institute (JBI) guidelines, was conducted through ten major databases. Search followed the PCC strategy to construct block of terms related to population (children and adolescents), concept (health-related physical fitness components) and context (HIV infection). Results: The search resulted in 7545 studies. After duplicate removal, titles and abstracts reading and full text assessment, 246 studies were included in the scoping review. Body composition was the most investigated component (n = 244), followed by muscular strength/endurance (n = 23), cardiorespiratory fitness (n = 15) and flexibility (n = 4). The World Health Organization growth curves, and nationals’ surveys were the most reference values applied to classify body composition (n = 149), followed by internal cut-points (n = 30) and cut-points developed through small populations (n = 16). Cardiorespiratory fitness was classified through cut-points from three different assessment batteries, as well as cut-points developed through studies with small populations, muscular strength/endurance and flexibility were classified through the same cut-points from five different assessment batteries. Conclusions: The research on muscular strength/endurance, cardiorespiratory fitness and flexibility has been scarcely explored. The lack of studies that investigated method usability as well as reference values was evidenced.
Epidemiology of Musculoskeletal Injuries in Golf Athletes: A Championship in Portugal
Authors: Minghelli Beatriz , Soares Ana Sofia Palma , Cabrita Carolina Duarte , Martins Claudia Coelho
Published: April 2024

Although golf is a low-impact sport without physical contact, its movements are carried out over a large range of motion, and their repetition can predispose athletes to the development of injuries. This study aimed to investigate the epidemiology of musculoskeletal injuries in golf athletes who participated in championships in southern Portugal, determining the types, locations and mechanisms of injury and their associated risk factors. The sample consisted of 140 athletes aged between 18 and 72 years, 133 (95%) being male. The measuring instrument was a questionnaire about sociodemographics, modality and injuries’ characteristics. Throughout golf practice, 70 (50%) athletes reported injuries, totaling 133 injuries. In the 12-month period, 43 (30.7%) athletes suffered injuries, totaling 65 injuries. The injury proportion was of 0.31, and the injury rate was of 0.33 injuries per 1000 h of golf training. The most common injury type was muscle sprain or rupture (19; 30.9%), located in the lumbar spine (17; 27%), in which the repetitive movements were the main injury mechanism (42; 66.7%). The athletes who trained 4 times or more per week were 3.5 more likely (CI: 0.97–12.36; p = 0.056) to develop an injury while playing golf. Moderate injury presence was observed, with the high training frequency being an associated risk factor.
Investigating the Barriers and Facilitators to Using Antiretroviral Therapy among Women Living with HIV in Plateau State, Nigeria
Authors: Osayi Emmanuel O. , Blake Sarah C. , Afolaranmi Tolulope , Ajayi Oluseye , Onyeji John , Sagay Atiene S. , Anderson Albert , Obindo Taiwo J.
Published: April 2024

Background: Women and girls account for more than 50% of the global HIV population. In Nigeria, the proportion of women living with HIV on long-term antiretroviral therapy (ART) has been on the rise. Despite this, little research exists on their experiences regarding antiretroviral therapy use, especially for women living with HIV (WLHIV) in Plateau State, Nigeria. This study investigates the barriers and facilitators influencing antiretroviral therapy use among women living with HIV. Methods: This study employed a qualitative research design, using focus groups, and included women (female sex workers, pregnant and non-pregnant women living with HIV) and the male partners of serodiscordant couples. Eligibility criteria were being 18 years of age or older, on antiretroviral therapy for more than one year/on pre-exposure prophylaxis (PrEP) for more than one month, and speaking English, Hausa, or both. Data coding utilized both inductive and deductive approaches, and standard content analysis was applied to develop emerging themes. Results: Of the 106 participants, 88 were women living with HIV, and 18 were men in serodiscordant couples. The first facilitator shared by the participants was feeling healthier and stronger due to the antiretroviral therapy, which was also expressed by the male participants on PrEP as feeling good while taking the drug. Additional facilitators shared by the participants included weight gain and having a more positive outlook on life. Participants also disproportionately described barriers to using antiretroviral therapy, including experiences with emotional challenges, physical discomfort, and side effects of ART. Such barriers were linked to feelings of past regret, frustration, and disappointment. Conclusion: This study underscores the significance of maintaining a positive perspective on ART use, demonstrated by the connection between a positive outlook and weight gain, and highlights the hurdles that Plateau State’s women living with HIV face in adhering to antiretroviral therapy. Policymakers and healthcare providers can utilize these findings to formulate targeted strategies aimed at minimizing identified barriers and enhancing antiretroviral therapy utilization among this population via peer- support groups, economic empowerment, and psychosocial support.
Orthodontic Status and Association with Oral-Health-Related Quality of Life—A Study of 16-Year-Old Norwegians with a Cleft Lip and Palate
Authors: Saele Paul K. , Mustafa Manal , Åstrøm Anne N.
Published: April 2024

Objective: To assess the association between clinical orthodontic indicators and oral-health-related quality of life, adjusted for socio-demographic factors, focusing on 16-year-old patients with cleft lip and/or palate (CL/P). Participants: One hundred and twenty-two patients with CL/P, representing cleft-lip (CL), cleft-palate (CP), unilateral/bilateral cleft-lip-palate (UCLP/BCLP), enrolled in the national CLP-Team, Bergen, Norway. Method: A cross-sectional study by two orthodontists assessing the number of teeth, intermaxillary sagittal relation (ANB-angle), dental arch and occlusion of 16-year-old patients with CL/P. All completed a digital questionnaire including self-reported socio-demographic variables, OHIP-14 questionnaire and dental aesthetics. Cross-tabulations with Pearson’s Chi-square test were used to identify associations between self-reported OHRQoL and socio-demographic and clinical indicators. Multiple variable analyses were conducted with binary logistic regression analysis using the odds ratio (OR) and 95% confidence interval (CI) to assess associations between OHRQoL and clinical indicators adjusted for socio-demographic variables. Ethical approval was granted by the regional ethics committee. Results: Patients with UCLP and BCLP had poorer clinical indicators compared to patients with CL and CP (p < 0.05). A total of 80% of the patients had OHIP-14 > 0. The highest oral impact was reported for psychological domains and articulation and the least for functional domains. Respondents with BCLP and those with poor intermaxillary relationships (ANB < 0°) reported a high impact on OHRQoL (p < 0.05). No statistically significant associations between other clinical indicators and socio-demographic variables such as gender, educational aspiration, and place of residence were reported. Conclusions: The study revealed an association between severe cleft diagnosis, missing teeth, misaligned teeth, negative overjet, and poor OHRQoL, but a statistically significant association was found only between OHRQoL and poor intermaxillary sagittal relations (unfavorable profile). To improve OHRQoL among patients with clefts, there is a need for an individual follow-up and prioritization of oral healthcare.
Maternal Diet High in Linoleic Acid Alters Renal Branching Morphogenesis and mTOR/AKT Signalling Genes in Rat Fetal Kidneys
Authors: McClelland Connie , Holland Olivia J. , Shrestha Nirajan , Jukes Claire L. , Brandon Anna E. , Cuffe James S. M. , Perkins Anthony V. , McAinch Andrew J. , Hryciw Deanne H.
Published: April 2024

Linoleic acid (LA), an n-6 polyunsaturated fatty acid (PUFA), is obtained from the maternal diet during pregnancy, and is essential for normal fetal growth and development. A maternal high-LA (HLA) diet alters maternal and offspring fatty acids, maternal leptin and male/female ratio at embryonic (E) day 20 (E20). We investigated the effects of an HLA diet on embryonic offspring renal branching morphogenesis, leptin signalling, megalin signalling and angiogenesis gene expression. Female Wistar Kyoto rats were fed low-LA (LLA; 1.44% energy from LA) or high-LA (HLA; 6.21% energy from LA) diets during pregnancy and gestation/lactation. Offspring were sacrificed and mRNA from kidneys was analysed by real-time PCR. Maternal HLA decreased the targets involved in branching morphogenesis Ret and Gdnf in offspring, independent of sex. Furthermore, downstream targets of megalin, namely mTOR, Akt3 and Prkab2, were reduced in offspring from mothers consuming an HLA diet, independent of sex. There was a trend of an increase in the branching morphogenesis target Gfra1 in females (p = 0.0517). These findings suggest that an HLA diet during pregnancy may lead to altered renal function in offspring. Future research should investigate the effects an HLA diet has on offspring kidney function in adolescence and adulthood.
How to Personalize General Anesthesia—A Prospective Theoretical Approach to Conformational Changes of Halogenated Anesthetics in Fire Smoke Poisoning
Authors: Truicu Flavius Nicușor , Damian Roni Octavian , Butoi Mihai Alexandru , Belghiru Vlad Ionuț , Rotaru Luciana Teodora , Puticiu Monica , Văruț Renata Maria
Published: April 2024

Smoke intoxication is a central event in mass burn incidents, and toxic smoke acts at different levels of the body, blocking breathing and oxygenation. The majority of these patients require early induction of anesthesia to preserve vital functions. We studied the influence of hemoglobin (HMG) and myoglobin (MGB) blockade by hydrochloric acid (HCl) in an interaction model with gaseous anesthetics using molecular docking techniques. In the next part of the study, molecular dynamics (MD) simulations were performed on the top-scoring ligand–receptor complexes to investigate the stability of the ligand–receptor complexes and the interactions between ligands and receptors in more detail. Through docking analysis, we observed that hemoglobin creates more stable complexes with anesthetic gases than myoglobin. Intoxication with gaseous hydrochloric acid produces conformational and binding energy changes of anesthetic gases to the substrate (both the pathway and the binding site), the most significant being recorded in the case of desflurane and sevoflurane, while for halothane and isoflurane, they remain unchanged. According to our theoretical model, the selection of anesthetic agents for patients affected by fire smoke containing hydrochloric acid is critical to ensure optimal anesthetic effects. In this regard, our model suggests that halothane and isoflurane are the most suitable choices for predicting the anesthetic effects in such patients when compared to sevoflurane and desflurane.
Analysing the Cyanobacterial PipX Interaction Network Using NanoBiT Complementation in Synechococcus elongatus PCC7942
Authors: Jerez Carmen , Llop Antonio , Salinas Paloma , Bibak Sirine , Forchhammer Karl , Contreras Asunción
Published: April 2024

The conserved cyanobacterial protein PipX is part of a complex interaction network with regulators involved in essential processes that include metabolic homeostasis and ribosome assembly. Because PipX interactions depend on the relative levels of their different partners and of the effector molecules binding to them, in vivo studies are required to understand the physiological significance and contribution of environmental factors to the regulation of PipX complexes. Here, we have used the NanoBiT complementation system to analyse the regulation of complex formation in Synechococcus elongatus PCC 7942 between PipX and each of its two best-characterized partners, PII and NtcA. Our results confirm previous in vitro analyses on the regulation of PipX-PII and PipX-NtcA complexes by 2-oxoglutarate and on the regulation of PipX-PII by the ATP/ADP ratio, showing the disruption of PipX-NtcA complexes due to increased levels of ADP-bound PII in Synechococcus elongatus. The demonstration of a positive role of PII on PipX-NtcA complexes during their initial response to nitrogen starvation or the impact of a PipX point mutation on the activity of PipX-PII and PipX-NtcA reporters are further indications of the sensitivity of the system. This study reveals additional regulatory complexities in the PipX interaction network, opening a path for future research on cyanobacteria.
Uncovering the Unseen: Bordetella hinzii Emerges in a Lung Transplant Recipient
Authors: Vulturar Damiana-Maria , Pilmis Benoît , Rouzaud Claire , Gigandon Anne , Dauriat Gaëlle , Feuillet-Soummer Séverine , Moaca Liviu-Stefan , Fadel Elie , Mercier Olaf , Fabre Dominique , Lortholary Olivier , Le Pavec Jérôme
Published: April 2024

Bordetella hinzii (B. hinzii), a Gram-negative bacillus commonly associated with respiratory infections in animals, has garnered attention for its sporadic cases in humans, particularly in immunocompromised individuals. Despite its opportunistic nature, there remains limited understanding regarding its pathogenicity, diagnostic challenges, and optimal treatment strategies, especially in the context of immunosuppression. Herein, we present the first documented case of acute bronchitis caused by B. hinzii in an immunocompromised patient following double-lung transplantation. The patient, a former smoker with sarcoidosis stage IV, underwent transplant surgery and subsequently developed a febrile episode, leading to the identification of B. hinzii in broncho-alveolar lavage samples. Antimicrobial susceptibility testing revealed resistance to multiple antibiotics, necessitating tailored treatment adjustments. Our case underscores the importance of heightened awareness among clinicians regarding B. hinzii infections and the imperative for further research to elucidate its epidemiology and optimal management strategies, particularly in immunocompromised populations.
Dual Deletion of Keap1 and Rbpjκ Genes in Liver Leads to Hepatomegaly and Hypercholesterolemia
Authors: Wakabayashi Nobunao , Yagishita Yoko , Joshi Tanvi , Kensler Thomas W.
Published: April 2024

The hepatic deletion of Rbpjκ (RbpjF/F::AlbCre) in the mouse leads to exhibition of the Alagille syndrome phenotype during early postnatal liver development with hyperlipidemia and cholestasis due to attenuated disruption of NOTCH signaling. Given the roles of NRF2 signaling in the regulation of lipid metabolism and bile ductal formation, it was anticipated that these symptoms could be alleviated by enhancing NRF2 signaling in the RbpjF/F::AlbCre mouse by hepatic deletion of Keap1 in compound Keap1F/F::RbpjF/F::AlbCre mice. Unexpectedly, these mice developed higher hepatic and plasma cholesterol levels with more severe cholestatic liver damage during the pre-weaning period than in the RbpjF/F::AlbCre mice. In addition, hypercholesterolemia and hepatic damage were sustained throughout the growth period unlike in the RbpjF/F::AlbCre mouse. These enhanced abnormalities in lipid metabolism appear to be due to NRF2-dependent changes in gene expression related to cholesterol synthetic and subsequent bile acid production pathways. Notably, the hepatic expression of Cyp1A7 and Abcb11 genes involved in bile acid homeostasis was significantly reduced in Keap1F/F::RbpjF/F::AlbCre compared to RbpjF/F::AlbCre mice. The accumulation of liver cholesterol and the weakened capacity for bile excretion during the 3 pre-weaning weeks in the Keap1F/F::RbpjF/F::AlbCre mice may aggravate hepatocellular damage level caused by both excessive cholesterol and residual bile acid toxicity in hepatocytes. These results indicate that a tuned balance of NOTCH and NRF2 signaling is of biological importance for early liver development after birth.
Circadian Regulation of Bone Remodeling
Authors: Kikyo Nobuaki
Published: April 2024

Adult bones are continuously remodeled by the balance between bone resorption by osteoclasts and subsequent bone formation by osteoblasts. Many studies have provided molecular evidence that bone remodeling is under the control of circadian rhythms. Circadian fluctuations have been reported in the serum and urine levels of bone turnover markers, such as digested collagen fragments and bone alkaline phosphatase. Additionally, the expressions of over a quarter of all transcripts in bones show circadian rhythmicity, including the genes encoding master transcription factors for osteoblastogenesis and osteoclastogenesis, osteogenic cytokines, and signaling pathway proteins. Serum levels of calcium, phosphate, parathyroid hormone, and calcitonin also display circadian rhythmicity. Finally, osteoblast- and osteoclast-specific knockout mice targeting the core circadian regulator gene Bmal1 show disrupted bone remodeling, although the results have not always been consistent. Despite these studies, however, establishing a direct link between circadian rhythms and bone remodeling in vivo remains a major challenge. It is nearly impossible to repeatedly collect bone materials from human subjects while following circadian changes. In addition, the differences in circadian gene regulation between diurnal humans and nocturnal mice, the main model organism, remain unclear. Filling the knowledge gap in the circadian regulation of bone remodeling could reveal novel regulatory mechanisms underlying many bone disorders including osteoporosis, genetic diseases, and fracture healing. This is also an important question for the basic understanding of how cell differentiation progresses under the influence of cyclically fluctuating environments.
Gaining Insights into Key Structural Hotspots within the Allosteric Binding Pockets of Protein Kinases
Authors: Bhujbal Swapnil P. , Jun Joonhong , Park Haebeen , Moon Jihyun , Min Kyungbae , Hah Jung-Mi
Published: April 2024

Protein kinases are essential regulators of cell function and represent one of the largest and most diverse protein families. They are particularly influential in signal transduction and coordinating complex processes like the cell cycle. Out of the 518 human protein kinases identified, 478 are part of a single superfamily sharing catalytic domains that are related in sequence. The dysregulation of protein kinases due to certain mutations has been associated with various diseases, including cancer. Although most of the protein kinase inhibitors identified as type I or type II primarily target the ATP-binding pockets of kinases, the structural and sequential resemblances among these pockets pose a significant challenge for selective inhibition. Therefore, targeting allosteric pockets that are beside highly conserved ATP pockets has emerged as a promising strategy to prevail current limitations, such as poor selectivity and drug resistance. In this article, we compared the binding pockets of various protein kinases for which allosteric (type III) inhibitors have already been developed. Additionally, understanding the structure and shape of existing ligands could aid in identifying key interaction sites within the allosteric pockets of kinases. This comprehensive review aims to facilitate the design of more effective and selective allosteric inhibitors.
17β-Estradiol (E2) Activates Matrix Mineralization through Genomic/Nongenomic Pathways in MC3T3-E1 Cells
Authors: Suzuki Hiraku , Fujiwara Yuki , Ariyani Winda , Amano Izuki , Ishii Sumiyasu , Ninomiya Ayane Kate , Sato Seiichi , Takaoka Akinori , Koibuchi Noriyuki
Published: April 2024

Estrogen plays an important role in osteoporosis prevention. We herein report the possible novel signaling pathway of 17β-estradiol (E2) in the matrix mineralization of MC3T3-E1, an osteoblast-like cell line. In the culture media-containing stripped serum, in which small lipophilic molecules such as steroid hormones including E2 were depleted, matrix mineralization was significantly reduced. However, the E2 treatment induced this. The E2 effects were suppressed by ICI182,780, the estrogen receptor (ER)α, and the ERβ antagonist, as well as their mRNA knockdown, whereas Raloxifene, an inhibitor of estrogen-induced transcription, and G15, a G-protein-coupled estrogen receptor (GPER) 1 inhibitor, had little or no effect. Furthermore, the E2-activated matrix mineralization was disrupted by PMA, a PKC activator, and SB202190, a p38 MAPK inhibitor, but not by wortmannin, a PI3K inhibitor. Matrix mineralization was also induced by the culture media from the E2-stimulated cell culture. This effect was hindered by PMA or heat treatment, but not by SB202190. These results indicate that E2 activates the p38 MAPK pathway via ERs independently from actions in the nucleus. Such activation may cause the secretion of certain signaling molecule(s), which inhibit the PKC pathway. Our study provides a novel pathway of E2 action that could be a therapeutic target to activate matrix mineralization under various diseases, including osteoporosis.
Revealing Genetic Dynamics: scRNA-seq Unravels Modifications in Human PDL Cells across In Vivo and In Vitro Environments
Authors: Abdallah Ali T. , Peitz Michael , Konermann Anna
Published: April 2024

The periodontal ligament (PDL) is a highly specialized fibrous tissue comprising heterogeneous cell populations of an intricate nature. These complexities, along with challenges due to cell culture, impede a comprehensive understanding of periodontal pathophysiology. This study aims to address this gap, employing single-cell RNA sequencing (scRNA-seq) technology to analyze the genetic intricacies of PDL both in vivo and in vitro. Primary human PDL samples (n = 7) were split for direct in vivo analysis and cell culture under serum-containing and serum-free conditions. Cell hashing and sorting, scRNA-seq library preparation using the 10x Genomics protocol, and Illumina sequencing were conducted. Primary analysis was performed using Cellranger, with downstream analysis via the R packages Seurat and SCORPIUS. Seven distinct PDL cell clusters were identified comprising different cellular subsets, each characterized by unique genetic profiles, with some showing donor-specific patterns in representation and distribution. Formation of these cellular clusters was influenced by culture conditions, particularly serum presence. Furthermore, certain cell populations were found to be inherent to the PDL tissue, while others exhibited variability across donors. This study elucidates specific genes and cell clusters within the PDL, revealing both inherent and context-driven subpopulations. The impact of culture conditions—notably the presence of serum—on cell cluster formation highlights the critical need for refining culture protocols, as comprehending these influences can drive the creation of superior culture systems vital for advancing research in PDL biology and regenerative therapies. These discoveries not only deepen our comprehension of PDL biology but also open avenues for future investigations into uncovering underlying mechanisms.
Anatomical and Metabolome Features of Haloxylon aphyllum and Haloxylon persicum Elucidate the Resilience against Gall-Forming Insects
Authors: Terletskaya Nina V. , Mamirova Aigerim , Ashimuly Kazhybek , Vibe Yekaterina P. , Krekova Yana A.
Published: April 2024

Globally, gall-forming insects significantly contribute to the degradation of desert ecosystems. Recent studies have demonstrated that Haloxylon persicum suffers less damage from gall-formers compared to Haloxylon aphyllum. However, the mechanisms driving the long-term metabolic responses of these species to gall-forming biotic stress in their natural environment remain unclear. The current study comparatively analyzes the anatomical features and metabolomic changes in H. aphyllum and H. persicum damaged by gall-forming insects. This research aimed to uncover potential metabolic tolerance mechanisms through GC-MS analysis. The study findings indicate that gall-forming insects cause a reduction in nearly all the anatomical structures of Haloxylon shoots, with the effects being less severe in H. persicum than in H. aphyllum. Thus, the metabolic pathways responsible for the biosynthesis of biologically active substances that enhance resistance to gall inducers were different, specifically in H. aphyllum—the biosynthesis of fatty acids (+their derivatives) and γ-tocopherol (vitamin E) and H. persicum—the biosynthesis of fatty acids (+their derivatives), dialkyl ethers, carbohydrates (+their derivatives), aromatic acid derivatives, phytosterols, γ-tocopherol (vitamin E), phenols, and terpenoids. The results suggest that the modulation of metabolic pathways under biotic stress plays a crucial role in the enhanced survival and growth of H. persicum.
Clinical and Biologic Correlates of ADORA2A Transcriptomic Expression in Cancer
Authors: Shreenivas Aditya , Nishizaki Daisuke , Lee Suzanna , Pabla Sarabjot , Nesline Mary , Conroy Jeffrey M. , DePietro Paul , Kato Shumei , Kurzrock Razelle
Published: April 2024

ADORA2A (adenosine A2a receptor) and ADORA2B propagate immunoregulatory signals, including restricting both innate and adaptive immunity, though recent data also suggest a tumor suppressor effect in certain settings. We evaluated the RNA expression from 514 tumors in a clinical-grade laboratory; 489 patients with advanced/metastatic disease had clinical outcome correlates. Transcript expression was standardized to internal housekeeping genes and ranked (0–100 scale) relative to 735 specimens from 35 different cancer types. Transcript abundance rank values were defined as “low/moderate” (0–74) or “high” (75–100) percentile RNA expression ranks. Overall, 20.8% of tumors had high ADORA2A (≥75 percentile RNA rank). The greatest proportion of high ADORA2A expressors was found in neuroendocrine and breast cancers and sarcomas, whereas the lowest was found in colorectal and ovarian cancers, albeit with patient-to-patient variability. In multivariable logistic regression analysis, there was a significant positive correlation between high ADORA2A RNA expression and a high expression of the immune checkpoint-related molecules PD-1 (p = 0.015), VISTA (p ≤ 0.001), CD38 (p = 0.031), and CD39 (p ≤ 0.001). In 217 immunotherapy-treated patients, high ADORA2A did not correlate significantly with progression-free (p = 0.51) or overall survival (OS) (p = 0.09) from the initiation of the checkpoint blockade. However, high versus not-high ADORA2A transcript expression correlated with longer OS from the time of advanced/metastatic disease (N = 489 patients; (HR 0.69 (95% CI 0.51–0.95) (p = 0.02)). Therefore, high ADORA2A transcript levels may be a favorable prognostic factor, unrelated to immunotherapy. Importantly, ascertaining co-expression patterns of ADORA2A with PD-1 and VISTA in individual tumors as a basis for the precision co-targeting of ADORA2A and these other checkpoint-related molecules warrants investigation in clinical trials.