bluuebunny/crossref_metadata_2025 huggingface dataset:
Chromosome-Level Genome Assembly Provides Insights into the Evolution of the Special Morphology and Behaviour of Lepturacanthus savala
Authors: Wu Ren-Xie , Miao Ben-Ben , Han Fang-Yuan , Niu Su-Fang , Liang Yan-Shan , Liang Zhen-Bang , Wang Qing-Hua
Published: June 2023

Savalani hairtail Lepturacanthus savala is a widely distributed fish along the Indo-Western Pacific coast, and contributes substantially to trichiurid fishery resources worldwide. In this study, the first chromosome-level genome assembly of L. savala was obtained by PacBio SMRT-Seq, Illumina HiSeq, and Hi-C technologies. The final assembled L. savala genome was 790.02 Mb with contig N50 and scaffold N50 values of 19.01 Mb and 32.77 Mb, respectively. The assembled sequences were anchored to 24 chromosomes by using Hi-C data. Combined with RNA sequencing data, 23,625 protein-coding genes were predicted, of which 96.0% were successfully annotated. In total, 67 gene family expansions and 93 gene family contractions were detected in the L. savala genome. Additionally, 1825 positively selected genes were identified. Based on a comparative genomic analysis, we screened a number of candidate genes associated with the specific morphology, behaviour-related immune system, and DNA repair mechanisms in L. savala. Our results preliminarily revealed mechanisms underlying the special morphological and behavioural characteristics of L. savala from a genomic perspective. Furthermore, this study provides valuable reference data for subsequent molecular ecology studies of L. savala and whole-genome analyses of other trichiurid fishes.
Genome-Wide Association Analysis for Resistance to Coniothyrium glycines Causing Red Leaf Blotch Disease in Soybean
Authors: Lukanda Musondolya Mathe , Dramadri Isaac Onziga , Adjei Emmanuel Amponsah , Badji Arfang , Arusei Perpetua , Gitonga Hellen Wairimu , Wasswa Peter , Edema Richard , Ochwo-Ssemakula Mildred , Tukamuhabwa Phinehas , Muthuri Harun Murithi , Tusiime Geoffrey
Published: June 2023

Soybean is a high oil and protein-rich legume with several production constraints. Globally, several fungi, viruses, nematodes, and bacteria cause significant yield losses in soybean. Coniothyrium glycines (CG), the causal pathogen for red leaf blotch disease, is the least researched and causes severe damage to soybean. The identification of resistant soybean genotypes and mapping of genomic regions associated with resistance to CG is critical for developing improved cultivars for sustainable soybean production. This study used single nucleotide polymorphism (SNP) markers generated from a Diversity Arrays Technology (DArT) platform to conduct a genome-wide association (GWAS) analysis of resistance to CG using 279 soybean genotypes grown in three environments. A total of 6395 SNPs was used to perform the GWAS applying a multilocus model Fixed and random model Circulating Probability Unification (FarmCPU) with correction of the population structure and a statistical test p-value threshold of 5%. A total of 19 significant marker–trait associations for resistance to CG were identified on chromosomes 1, 5, 6, 9, 10, 12, 13, 15, 16, 17, 19, and 20. Approximately 113 putative genes associated with significant markers for resistance to red leaf blotch disease were identified across soybean genome. Positional candidate genes associated with significant SNP loci-encoding proteins involved in plant defense responses and that could be associated with soybean defenses against CG infection were identified. The results of this study provide valuable insight for further dissection of the genetic architecture of resistance to CG in soybean. They also highlight SNP variants and genes useful for genomics-informed selection decisions in the breeding process for improving resistance traits in soybean.
Identification and Molecular Characterization of a Novel Large-Scale Variant (Exons 4_18 Loss) in the LDLR Gene as a Cause of Familial Hypercholesterolaemia in an Italian Family
Authors: Concolino Paola , De Paolis Elisa , Moffa Simona , Onori Maria Elisabetta , Soldovieri Laura , Ricciardi Tenore Claudio , De Bonis Maria , Rabacchi Claudio , Santonocito Concetta , Rinelli Martina , Calandra Sebastiano , Giaccari Andrea , Urbani Andrea , Minucci Angelo
Published: June 2023

Next-generation sequencing (NGS) is nowadays commonly used for clinical purposes, and represents an efficient approach for the molecular diagnosis of familial hypercholesterolemia (FH). Although the dominant form of the disease is mostly due to the low-density lipoprotein receptor (LDLR) small-scale pathogenic variants, the copy number variations (CNVs) represent the underlying molecular defects in approximately 10% of FH cases. Here, we reported a novel large deletion in the LDLR gene involving exons 4–18, identified by the bioinformatic analysis of NGS data in an Italian family. A long PCR strategy was employed for the breakpoint region analysis where an insertion of six nucleotides (TTCACT) was found. Two Alu sequences, identified within intron 3 and exon 18, could underlie the identified rearrangement by a nonallelic homologous recombination (NAHR) mechanism. NGS proved to be an effective tool suitable for the identification of CNVs, together with small-scale alterations in the FH-related genes. For this purpose, the use and implementation of this cost-effective, efficient molecular approach meets the clinical need for personalized diagnosis in FH cases.
Enhancer Function in the 3D Genome
Authors: Razin Sergey V. , Ulianov Sergey V. , Iarovaia Olga V.
Published: June 2023

In this review, we consider various aspects of enhancer functioning in the context of the 3D genome. Particular attention is paid to the mechanisms of enhancer-promoter communication and the significance of the spatial juxtaposition of enhancers and promoters in 3D nuclear space. A model of an activator chromatin compartment is substantiated, which provides the possibility of transferring activating factors from an enhancer to a promoter without establishing direct contact between these elements. The mechanisms of selective activation of individual promoters or promoter classes by enhancers are also discussed.
Liminality, Madness, and Narration in Hassan Blasim’s “The Nightmares of Carlos Fuentes” and “Why Don’t You Write a Novel Instead of Talking about All These Characters?”
Authors: Sadek Rima
Published: June 2023

The fiction of Hassan Blasim addresses the horrors of contemporary Iraq and centers on the crisis of identity that is part of the immigrant’s experience. Blasim’s protagonists try to forget past traumas related to their homeland by developing new identities ingrained solely in the present. Yet, the past resurfaces in the form of nightmarish dreams, madness, and fractured narratives where fiction and reality intersect and overlap. Inhabiting a constant state of liminality imprints itself on the body and psyche of the border crossers and leads to their physical or mental demise. Drawing on theories of madness, liminality, and narration advanced by Shoshana Felman and Michel Foucault, I analyze Blasim’s two short stories “The Nightmares of Carlos Fuentes” and “Why Don’t You Write a Novel Instead of Talking About All These Characters?” I argue that the imaginative space of literary narration, an in-between, liminal space between reality and fiction, is the space where ethico-political paradoxes and the absurdity of real-life trauma, death, and chaos are transformed into a meaningful literary dialogue that can expand reality and offer new spheres of understanding of the trauma that shapes the lives of Blasim’s characters.
Sounding War: Subverting Jim Crow in Not Only War and Sula
Authors: Fairchild Candice Marie
Published: June 2023

A sound-studies-centered reading of Victor Daly’s Not Only War: A Story of Two Great Conflicts (1932) and Toni Morrison’s Sula (1973) sheds light on the sonic realities of WWI, both before and after, for Black soldiers. Both novels, set during and after WWI, utilize music to subvert the codified system of Jim Crow through sonic resistance. The term generative entropy offers a theoretical intervention in the field of sound studies to enable a better understanding and identification of the emphasis both novels place on narrative possibility rooted in sonic and physical spaces of ambiguity.
Engaging Industry in Health Professions’ Education: Benefits and Challenges
Authors: Kenny Belinda , O'Connor David , Sugden Ellie , Tang Clarice Y. , Tannous Caterina , Thyer Elizabeth
Published: June 2023

Effective partnerships between universities and industry facilitate health-profession students’ learning and work readiness. However, developing sustainable industry engagement in academic curricula remains challenging. This study utilised Social Exchange Theory (SET) to explore the benefits of and barriers to industry engagement within health-profession preparation programs. A realist evaluation framework was used to consider factors that impacted experiences and outcomes for academics and clinicians who engaged in the development and delivery of curriculum for a new health professional preparation program in speech pathology. A sequential mixed-methods design was adopted to explore factors influencing clinicians’ motivation to engage with the university, using an online survey (n = 18) and focus group (n = 5). Clinicians rated “personal development” and contributing to the “future workforce” as the highest personal benefits. “Sharing knowledge” was the highest team benefit, and “staff satisfaction” was the highest employer benefit. Time and workload were perceived barriers. Academics (n = 2) and clinicians (n = 3) who collaborated in learning and teaching experiences also participated in a post-engagement focus group. Three Context Mechanism Outcome configurations were shown to facilitate engagement outcomes: engagement as opportunity, partnership, and work readiness. In accordance with SET, the nature of exchange processes and professional relationships contributed to positive engagement outcomes for clinicians, academics, and enhanced health-profession education.
Dark Personality Traits and Online Behaviors: Portuguese Versions of Cyberstalking, Online Harassment, Flaming and Trolling Scales
Authors: Leite Ângela , Cardoso Susana , Monteiro Ana Paula
Published: June 2023

The main objective of this study is to assess moderation effects of online behaviors between personality traits and addiction to Internet. To this end, four instruments were validated for Portuguese version through confirmatory factor analysis and exploratory factor analysis (Study 1) Multiple regression analysis was applied to examine the personality predictors of specific online behaviors while controlling for gender and age; and moderation effects were assessed (Study 2). Results showed good psychometric properties for the four validated scales. Machiavellianism is positively associated with all the dimensions of this study. Psychopathy is positively associated with total Cyberstalking, Cyberstalking Control, Flaming and Trolling. Narcissism is positively associated with all the dimensions, except Online Harassment and Flaming. Machiavellianism is positively associated with Addiction to Internet through Cyberstalking, Flaming and Trolling. Psychopathy is positively associated with Addiction to Internet through Cyberstalking Control and Flaming. Narcissism is also positively associated with Addiction to Internet through Cyberstalking and Trolling. This study demonstrates that dimensions of the dark triad of personality play an important role in Internet addiction through online behaviors. The results of this study have theoretical and practical implications: on the one hand, they reinforces the findings of other studies showing that dimensions of the dark personality triad play an important role in Internet and social network addition, contributing to the literature; and, on the other hand, on a practical level, they allow to conduct awareness campaigns in communities, schools, and work to understand that one can be exposed to unpleasant situations due to behaviors that some people with personality traits of Machiavellianism, narcissism and/or psychopathy that may cause problems affecting the mental, emotional and psychological health of others.
Assessing the Integrity of Clinical Trials Included in Evidence Syntheses
Authors: Núñez-Núñez María , Cano-Ibáñez Naomi , Zamora Javier , Bueno-Cavanillas Aurora , Khan Khalid Saeed
Published: June 2023

Evidence syntheses of randomized clinical trials (RCTs) offer the highest level of scientific evidence for informing clinical practice and policy. The value of evidence synthesis itself depends on the trustworthiness of the included RCTs. The rising number of retractions and expressions of concern about the authenticity of RCTs has raised awareness about the existence of problematic studies, sometimes called “zombie” trials. Research integrity, i.e., adherence to ethical and professional standards, is a multi-dimensional concept that is incompletely evaluated for the RCTs included in current evidence syntheses. Systematic reviewers tend to rely on the editorial and peer-review system established by journals as custodians of integrity of the RCTs they synthesize. It is now well established that falsified and fabricated RCTs are slipping through. Thus, RCT integrity assessment becomes a necessary step in systematic reviews going forward, in particular because RCTs with data-related integrity concerns remain available for use in evidence syntheses. There is a need for validated tools for systematic reviewers to proactively deploy in the assessment of integrity deviations without having to wait for RCTs to be retracted by journals or expressions of concern issued. This article analyzes the issues and challenges in conducting evidence syntheses where the literature contains RCTs with possible integrity deficits. The way forward in the form of formal RCT integrity assessments in systematic reviews is proposed, and implications of this new initiative are discussed. Future directions include emphasizing ethical and professional standards, providing tailored integrity-specific training, and creating systems to promote research integrity, as improvements in RCT integrity will benefit evidence syntheses.
Self-Medication during the COVID-19 Pandemic in Brazil: Findings and Implications to Promote the Rational Use of Medicines
Authors: Bazoni Patrícia Silva , Faria Ronaldo José , Cordeiro Francisca Janiclecia Rezende , Timóteo Élida da Silva , da Silva Alciellen Mendes , Horsth Ana Luisa , Meira Eduardo Frizzera , dos Santos Jéssica Barreto Ribeiro , da Silva Michael Ruberson Ribeiro
Published: June 2023

Self-medication is identified by the consumption of medications without a prescription or guidance from a qualified prescribing professional. This study estimated the prevalence, profile, and associated factors with self-medication during the COVID-19 pandemic in Brazil. A cross-sectional study was conducted through a household survey in the Alegre city, from November to December 2021. Descriptive analysis was performed for the sociodemographic and clinical characteristics of the interviewees. Poisson regression with robust variance was used to identify the association of sociodemographic and clinical variables with self-medication. A total of 654 people were interviewed, of whom 69.4% were self-medicating. The younger age group (PR = 1.13; 95% CI = 1.01–1.26), female gender (PR = 1.19; 95% CI = 1.04–1.37), consumption of alcoholic beverages (PR = 1.13; 95% CI = 1.01–1.25), and problems with adherence to pharmacological treatment (PR = 1.15; 95% CI = 1.04–1.28) were associated with self-medication, while the occurrence of polypharmacy (PR = 0.80; 95% CI = 0.68–0.95) was a protective factor for self-medication. Self-medication was directly related to over-the-counter drugs, with analgesics dipyrone and paracetamol being the most commonly used. Self-medication consumption of prescription drugs, including those under special control, was identified to a lesser extent.
Effects of Alpine Natural Health Resources on Human Health and Wellbeing
Authors: Hartl Arnulf Josef , Freidl Johanna , Huber Daniela
Published: June 2023

As humanity becomes progressively urban, a huge number of people could lose the opportunity to benefit from or develop an appreciation for nature [...]
A New Model of Learning: Environmental Health in a Global World
Authors: Rom William N. , Rao Aishwarya , Hoepner Lori , Dickey Chris
Published: June 2023

Introduction. Environmental Health in a Global World at New York University was re-designed as a class participatory effort, challenging undergraduate students to understand environmental hazards and the resultant adverse health outcomes by embracing the inherent complexity of environmental risks and proposing solutions. Methods. Following introductory lectures, students are placed into teams and assigned a specific perspective, or avatar, which includes learning to see the challenge from the perspective of a technical expert such as a biologist, an engineer, or an anthropologist. The teams then design specific systems maps to visualize the complex interactions that lead to adverse health outcomes after a given environmental exposure. The maps highlight potential leverage points where relatively minor interventions can provide a disproportionate benefit in health outcomes. The teams then explore potential interventions and identify the potential unintended consequences of those actions, develop and advocate for innovative new strategies to mitigate risk and improve outcomes. Results and Discussion. Over the past 5 years, we have taught this methodology to over 680 students with strong, student-oriented results. The teams created and presented more than 100 strategies, addressing a diverse set of environmental challenges that include water contamination, gun violence, air pollution, environmental justice, health security, and climate change. Developing the strategies helped the students understand environmental threats in a more holistic way, provided them with some agency in finding solutions, and offered an opportunity for them to improve their presentation skills. The responses in course evaluations have been enthusiastic, with many students reporting a deep impact on their college experience.
Sensitivity and Attachment in an Italian Sample of Hikikomori Adolescents and Young Adults
Authors: Santona Alessandra , Lionetti Francesca , Tognasso Giacomo , Fusco Chiara , Maccagnano Graziana , Barreca Danila , Gorla Laura
Published: June 2023

Hikikomori is a severe form of social withdrawal increasing among the young Italian population. Hikikomori has been connected to psychological problems and high environmental sensitivity. Nevertheless, only a few studies have been carried out in the Italian context, and they did not analyze several aspects strictly related to the hikikomori phenomenon, such as the role of attachment and sensitivity. We aimed to investigate the relationship between attachment, sensitivity, and psychological problems in a sample of Italian hikikomori. Our sample comprised 72 Italian adolescents and young adults (49 males and 23 females), meanly aged 22.5 years, recruited through online forums and clinical centers for the hikikomori phenomenon. Our participants fulfilled the Highly Sensitive Person Scale (HSPS), the Attachment Style Questionnaire (ASQ), and the Hopkins Symptom Checklist (SCL-90-R). The results showed high psychological issues (i.e., depression and anxiety), environmental sensitivity, and insecure attachment orientations. Moreover, we discovered a significant relationship between attachment dimensions, environmental sensitivity, and psychopathology. Our study sheds light on a novel research path and could help both the researchers and the clinicians who work with people suffering from social withdrawal.
Influence of Manure as a Complex Mixture on Soil Sorption of Pharmaceuticals—Studies with Selected Chemical Components of Manure
Authors: Thiele-Bruhn Sören , Zhang Wei
Published: June 2023

Pharmaceutically active compounds (PhACs) enter soil with organic waste materials such as manure. Such complex substrates differently affect PhACs’ soil sorption. For the first time, batch experiments were conducted using five selected chemicals as model constituents to elucidate the effects. Urea, phosphate (KH2PO4), acetic acid, phenol and nonadecanoic acid (C:19) altered the sorption strength and/or nonlinearity of sulfadiazine, caffeine, and atenolol in an arable Cambisol topsoil. The nonlinear Freundlich model best described sorption. Overall, the PhACs’ Freundlich coefficients (sorption strength) increased in the sequence urea < phosphate < phenol < C:19 < acetic acid, while the Freundlich exponents largely decreased, indicating increasing sorption specificity. The effects on sulfadiazine and caffeine were rather similar, but in many cases different from atenolol. Phosphate mobilized sulfadiazine and caffeine and urea mobilized sulfadiazine, which was explained by sorption competition resulting from specific preference of similar sorption sites. Soil sorbed phenol strongly increased the sorption of all three PhACs; phenolic functional groups are preferred sorption sites of PhACs in soil. The large increase in sorption of all PhACs by acetic acid was attributed to a loosening of the soil organic matter and thus the creation of additional sorption sites. The effect of C:19 fatty acid, however, was inconsistent. These results help to better understand the sorption of PhACs in soil–manure mixtures.
A Forty-Year Analysis of the Literature on Babesia Infection (1982–2022): A Systematic Bibliometric Approach
Authors: Malgwi Samson Anjikwi , Ogunsakin Ropo Ebenezer , Oladepo Abolade David , Adeleke Matthew Adekunle , Okpeku Moses
Published: June 2023

Babesia infection is a tick-borne protozoan disease associated with significant veterinary, economic, and medical importance. This infection affects many hosts, ranging from wild to domestic animals and including man. All vertebrates serve as potential carriers due to the huge diversity of the species. Babesiosis has been associated with severe economic loss in livestock production, especially in cattle farming, and is also a major public health concern in man, which could be fatal. The infection is usually opportunistic, ranging from asymptomatic to symptomatic, usually in immunocompromised subjects or under conditions of stressful management. This study was designed to uncover trends in relation to publication growth and further explore research output regarding babesiosis from data indexed in the WoS. The WoS is the only platform used to map publications on Babesia infection. The search term “babesiosis” or “Babesia infection” was used to extract articles published across the study period from 1982 to 2022. The inclusion criteria were restricted to only articles for the analysis. The results from the search query showed that a total of 3763 articles were published during the study period with an average of 91.70 ± 43.87 articles annually and an average total citation (n = 1874.8). An annual growth rate of 2.5% was recorded during the study period. The year 2021 had the highest number of published articles (n = 193, 5.1%) and citations (n = 7039). The analysis of the most relevant keywords and titles showed that infection (n = 606, 16.1%), babesiosis (n = 444, 11.7%), and Babesia (n = 1302, 16%) were the most relevant keyword plus (ID), author keyword (DE), and title, respectively. The common conceptual framework analysis through K-means clustering showed two clusters comprising 4 and 41 elements, respectively. The United States of America is the top-performing country in terms of article production (n = 707, 20.8%) and the leading funder for babesiosis research, with two of its agencies ranked at the top. These are the Department of Health and Human Services (n = 254, 6.7%) and the National Institute of Health (n= 238,6.3%). Igarashi I. is the top-performing author (n = 231, 6.1%), while Veterinary Parasitology is ranked the top journal (n = 393, 10.4%) in terms of babesiosis publications. Overall, an increase in publications was observed in the study period, with significant output from developed nations.
Genome-Wide Identification of the YABBY Gene Family in Dendrobium Orchids and Its Expression Patterns in Dendrobium chrysotoxum
Authors: Zheng Qinyao , Zhao Xuewei , Huang Ye , Zhang Meng-Meng , He Xin , Ke Shijie , Li Yuanyuan , Zhang Cuili , Ahmad Sagheer , Lan Siren , Li Minghe , Liu Zhong-Jian
Published: June 2023

The small plant-specific YABBY gene family plays key roles in diverse developmental processes in plants. Dendrobium chrysotoxum, D. huoshanense, and D. nobile are perennial herbaceous plants belonging to Orchidaceae with a high ornamental value. However, the relationships and specific functions of the YABBY genes in the Dendrobium species remain unknown. In this study, six DchYABBYs, nine DhuYABBYs, and nine DnoYABBYs were identified from the genome databases of the three Dendrobium species, which were unevenly distributed on five, eight, and nine chromosomes, respectively. The 24 YABBY genes were classified into four subfamilies (CRC/DL, INO, YAB2, and FIL/YAB3) based on their phylogenetic analysis. A sequence analysis showed that most of the YABBY proteins contained conserved C2C2 zinc-finger and YABBY domains, while a gene structure analysis revealed that 46% of the total YABBY genes contained seven exons and six introns. All the YABBY genes harbored a large number of Methyl Jasmonate responsive elements, as well as anaerobic induction cis-acting elements in the promoter regions. Through a collinearity analysis, one, two, and two segmental duplicated gene pairs were identified in the D. chrysotoxum, D. huoshanense, and D. nobile genomes, respectively. The Ka/Ks values of these five gene pairs were lower than 0.5, indicating that the Dendrobium YABBY genes underwent negative selection. In addition, an expression analysis revealed that DchYABBY2 plays a role in ovary and early-stage petal development, while DchYABBY5 is essential for lip development and DchYABBY6 is crucial for early sepal formation. DchYABBY1 primarily regulates sepals during blooming. Furthermore, there is the potential involvement of DchYABBY2 and DchYABBY5 in gynostemium development. The results of a comprehensive genome-wide study would provide significant clues for future functional investigations and pattern analyses of YABBY genes in different flower parts during flower development in the Dendrobium species.
Extended Depth of Focus Two-Photon Light-Sheet Microscopy for In Vivo Fluorescence Imaging of Large Multicellular Organisms at Cellular Resolution
Authors: Saitou Takashi , Imamura Takeshi
Published: June 2023

Two-photon excitation in light-sheet microscopy advances applications to live imaging of multicellular organisms. In a previous study, we developed a two-photon Bessel beam light-sheet microscope with a nearly 1-mm field of view and less than 4-μm axial resolution, using a low magnification (10×), middle numerical aperture (NA 0.5) detection objective. In this study, we aimed to construct a light-sheet microscope with higher resolution imaging while maintaining the large field of view, using low magnification (16×) with a high NA 0.8 objective. To address potential illumination and detection mismatch, we investigated the use of a depth of focus (DOF) extension method. Specifically, we used a stair-step device composed of five-layer annular zones that extended DOF two-fold, enough to cover the light-sheet thickness. Resolution measurements using fluorescent beads showed that the reduction in resolutions was small. We then applied this system to in vivo imaging of medaka fish and found that image quality degradation at the distal site of the beam injection could be compensated. This demonstrates that the extended DOF system combined with wide-field two-photon light-sheet microscopy offers a simple and easy setup for live imaging application of large multicellular organism specimens with sub-cellular resolution.
Oxidative Stress Response Kinetics after 60 Minutes at Different Levels (10% or 15%) of Normobaric Hypoxia Exposure
Authors: Leveque Clément , Mrakic Sposta Simona , Theunissen Sigrid , Germonpré Peter , Lambrechts Kate , Vezzoli Alessandra , Gussoni Maristella , Levenez Morgan , Lafère Pierre , Guerrero François , Balestra Costantino
Published: June 2023

In this study, the metabolic responses of hypoxic breathing for 1 h to inspired fractions of 10% and 15% oxygen were investigated. To this end, 14 healthy nonsmoking subjects (6 females and 8 males, age: 32.2 ± 13.3 years old (mean ± SD), height: 169.1 ± 9.9 cm, and weight: 61.6 ± 16.2 kg) volunteered for the study. Blood samples were taken before, and at 30 min, 2 h, 8 h, 24 h, and 48 h after a 1 h hypoxic exposure. The level of oxidative stress was evaluated by considering reactive oxygen species (ROS), nitric oxide metabolites (NOx), lipid peroxidation, and immune-inflammation by interleukin-6 (IL-6) and neopterin, while antioxidant systems were observed in terms of the total antioxidant capacity (TAC) and urates. Hypoxia abruptly and rapidly increased ROS, while TAC showed a U-shape pattern, with a nadir between 30 min and 2 h. The regulation of ROS and NOx could be explained by the antioxidant action of uric acid and creatinine. The kinetics of ROS allowed for the stimulation of the immune system translated by an increase in neopterin, IL-6, and NOx. This study provides insights into the mechanisms through which acute hypoxia affects various bodily functions and how the body sets up the protective mechanisms to maintain redox homeostasis in response to oxidative stress.
Different Roles of Apoptosis and Autophagy in the Development of Human Colorectal Cancer
Authors: Orlandi Giulia , Roncucci Luca , Carnevale Gianluca , Sena Paola
Published: June 2023

Colorectal cancer (CRC) remains a major life-threatening malignancy, despite numerous therapeutic and screening attempts. Apoptosis and autophagy are two processes that share common signaling pathways, are linked by functional relationships and have similar protein components. During the development of cancer, the two processes can trigger simultaneously in the same cell, causing, in some cases, an inhibition of autophagy by apoptosis or apoptosis by autophagy. Malignant cells that have accumulated genetic alterations can take advantage of any alterations in the apoptotic process and as a result, progress easily in the cancerous transformation. Autophagy often plays a suppressive role during the initial stages of carcinogenicity, while in the later stages of cancer development it can play a promoting role. It is extremely important to determine the regulation of this duality of autophagy in the development of CRC and to identify the molecules involved, as well as the signals and the mechanisms behind it. All the reported experimental results indicate that, while the antagonistic effects of autophagy and apoptosis occur in an adverse environment characterized by deprivation of oxygen and nutrients, leading to the formation and development of CRC, the effects of promotion and collaboration usually involve an auxiliary role of autophagy compared to apoptosis. In this review, we elucidate the different roles of autophagy and apoptosis in human CRC development.
Bromotyrosine-Derived Metabolites from a Marine Sponge Inhibit Pseudomonas aeruginosa Biofilms
Authors: Tran Tam M. T. , Addison Russell S. , Davis Rohan A. , Rehm Bernd H. A.
Published: June 2023

Pseudomonas aeruginosa forms stable biofilms, providing a major barrier for multiple classes of antibiotics and severely impairing treatment of infected patients. The biofilm matrix of this Gram-negative bacterium is primarily composed of three major exopolysaccharides: alginate, Psl, and Pel. Here, we studied the antibiofilm properties of sponge-derived natural products ianthelliformisamines A–C and their combinations with clinically used antibiotics. Wild-type P. aeruginosa strain and its isogenic exopolysaccharide-deficient mutants were employed to determine the interference of the compounds with biofilm matrix components. We identified that ianthelliformisamines A and B worked synergistically with ciprofloxacin to kill planktonic and biofilm cells. Ianthelliformisamines A and B reduced the minimum inhibitory concentration (MIC) of ciprofloxacin to 1/3 and 1/4 MICs, respectively. In contrast, ianthelliformisamine C (MIC = 53.1 µg/mL) alone exhibited bactericidal effects dose-dependently on both free-living and biofilm populations of wild-type PAO1, PAO1ΔpslA (Psl deficient), PDO300 (alginate overproducing and mimicking clinical isolates), and PDO300Δalg8 (alginate deficient). Interestingly, the biofilm of the clinically relevant mucoid variant PDO300 was more susceptible to ianthelliformisamine C than strains with impaired polysaccharide synthesis. Ianthelliformisamines exhibited low cytotoxicity towards HEK293 cells in the resazurin viability assay. Mechanism of action studies showed that ianthelliformisamine C inhibited the efflux pump of P. aeruginosa. Metabolic stability analyses indicated that ianthelliformisamine C is stable and ianthelliformisamines A and B are rapidly degraded. Overall, these findings suggest that the ianthelliformisamine chemotype could be a promising candidate for the treatment of P. aeruginosa biofilms.
Intra-Varietal Diversity and Its Contribution to Wheat Evolution, Domestication, and Improvement in Wheat
Authors: Li Tianbao , Kong Chuizheng , Deng Pingchuan , Li Chengdao , Zhao Guangyao , Li Hongjie , Gao Lifeng , Cui Dangqun , Jia Jizeng
Published: June 2023

Crop genetic diversity is essential for adaptation and productivity in agriculture. A previous study revealed that poor allele diversity in wheat commercial cultivars is a major barrier to its further improvement. Homologs within a variety, including paralogs and orthologs in polyploid, account for a large part of the total genes of a species. Homolog diversity, intra-varietal diversity (IVD), and their functions have not been elucidated. Common wheat, an important food crop, is a hexaploid species with three subgenomes. This study analyzed the sequence, expression, and functional diversity of homologous genes in common wheat based on high-quality reference genomes of two representative varieties, a modern commercial variety Aikang 58 (AK58) and a landrace Chinese Spring (CS). A total of 85,908 homologous genes, accounting for 71.9% of all wheat genes, including inparalogs (IPs), outparalogs (OPs), and single-copy orthologs (SORs), were identified, suggesting that homologs are an important part of the wheat genome. The levels of sequence, expression, and functional variation in OPs and SORs were higher than that of IPs, which indicates that polyploids have more homologous diversity than diploids. Expansion genes, a specific type of OPs, made a great contribution to crop evolution and adaptation and endowed crop with special characteristics. Almost all agronomically important genes were from OPs and SORs, demonstrating their essential functions for polyploid evolution, domestication, and improvement. Our results suggest that IVD analysis is a novel approach for evaluating intra-genomic variations, and exploitation of IVD might be a new road for plant breeding, especially for polyploid crops, such as wheat.
Optogenetic and Chemogenic Control of Pain Signaling: Molecular Markers
Authors: Espinosa-Juárez Josue Vidal , Chiquete Erwin , Estañol Bruno , Aceves José de Jesús
Published: June 2023

Pain is a complex experience that involves physical, emotional, and cognitive aspects. This review focuses specifically on the physiological processes underlying pain perception, with a particular emphasis on the various types of sensory neurons involved in transmitting pain signals to the central nervous system. Recent advances in techniques like optogenetics and chemogenetics have allowed researchers to selectively activate or inactivate specific neuronal circuits, offering a promising avenue for developing more effective pain management strategies. The article delves into the molecular targets of different types of sensory fibers such as channels, for example, TRPV1 in C-peptidergic fiber, TRPA1 in C-non-peptidergic receptors expressed differentially as MOR and DOR, and transcription factors, and their colocalization with the vesicular transporter of glutamate, which enable researchers to identify specific subtypes of neurons within the pain pathway and allows for selective transfection and expression of opsins to modulate their activity.
Effects of Hydrophobic Gold Nanoparticles on Structure and Fluidity of SOPC Lipid Membranes
Authors: Santhosh Poornima Budime , Tenev Tihomir , Šturm Luka , Ulrih Nataša Poklar , Genova Julia
Published: June 2023

Gold nanoparticles (AuNPs) are promising candidates in various biomedical applications such as sensors, imaging, and cancer therapy. Understanding the influence of AuNPs on lipid membranes is important to assure their safety in the biological environment and to improve their scope in nanomedicine. In this regard, the present study aimed to analyze the effects of different concentrations (0.5, 1, and 2 wt.%) of dodecanethiol functionalized hydrophobic AuNPs on the structure and fluidity of zwitterionic 1-stearoyl-2-oleoyl-sn-glycerol-3-phosphocholine (SOPC) lipid bilayer membranes using Fourier-transform infrared (FTIR) spectroscopy and fluorescent spectroscopy. The size of AuNPs was found to be 2.2 ± 1.1 nm using transmission electron microscopy. FTIR results have shown that the AuNPs induced a slight shift in methylene stretching bands, while the band positions of carbonyl and phosphate group stretching were unaffected. Temperature-dependent fluorescent anisotropy measurements showed that the incorporation of AuNPs up to 2 wt.% did not affect the lipid order in membranes. Overall, these results indicate that the hydrophobic AuNPs in the studied concentration did not cause any significant alterations in the structure and membrane fluidity, which suggests the suitability of these particles to form liposome–AuNP hybrids for diverse biomedical applications including drug delivery and therapy.
Lost and Found: The Family of NF-κB Inhibitors Is Larger than Assumed in Salmonid Fish
Authors: van Muilekom Doret R. , Collet Bertrand , Rebl Henrike , Zlatina Kristina , Sarais Fabio , Goldammer Tom , Rebl Alexander
Published: June 2023

NF-κB signalling is largely controlled by the family of ‘inhibitors of NF-κB’ (IκB). The relevant databases indicate that the genome of rainbow trout contains multiple gene copies coding for iκbα (nfkbia), iκbε (nfkbie), iκbδ (nkfbid), iκbζ (nfkbiz), and bcl3, but it lacks iκbβ (nfkbib) and iκbη (ankrd42). Strikingly, three nfkbia paralogs are apparently present in salmonid fish, two of which share a high sequence identity, while the third putative nfkbia gene is significantly less like its two paralogs. This particular nfkbia gene product, iκbα, clusters with the human IκBβ in a phylogenetic analysis, while the other two iκbα proteins from trout associate with their human IκBα counterpart. The transcript concentrations were significantly higher for the structurally more closely related nfkbia paralogs than for the structurally less similar paralog, suggesting that iκbβ probably has not been lost from the salmonid genomes but has been incorrectly designated as iκbα. In the present study, two gene variants coding for iκbα (nfkbia) and iκbε (nfkbie) were prominently expressed in the immune tissues and, particularly, in a cell fraction enriched with granulocytes, monocytes/macrophages, and dendritic cells from the head kidney of rainbow trout. Stimulation of salmonid CHSE-214 cells with zymosan significantly upregulated the iκbα-encoding gene while elevating the copy numbers of the inflammatory markers interleukin-1-beta and interleukin-8. Overexpression of iκbα and iκbε in CHSE-214 cells dose-dependently quenched both the basal and stimulated activity of an NF-κB promoter suggesting their involvement in immune-regulatory processes. This study provides the first functional data on iκbε—versus the well-researched iκbα factor—in a non-mammalian model species.
Assessment of Mechanical/Chemical Properties and Cytotoxicity of Resin-Modified Glass Ionomer Cements Containing Sr/F-Bioactive Glass Nanoparticles and Methacrylate Functionalized Polyacids
Authors: Potiprapanpong Wisitsin , Naruphontjirakul Parichart , Khamsuk Chutikarn , Channasanon Somruethai , Toneluck Arnit , Tanodekaew Siriporn , Monmaturapoj Naruporn , Young Anne M. , Panpisut Piyaphong
Published: June 2023

This study prepared low-toxicity, elemental-releasing resin-modified glass ionomer cements (RMGICs). The effect of 2-hydroxyethyl methacrylate (HEMA, 0 or 5 wt%) and Sr/F-bioactive glass nanoparticles (Sr/F-BGNPs, 5 or 10 wt%) on chemical/mechanical properties and cytotoxicity were examined. Commercial RMGIC (Vitrebond, VB) and calcium silicate cement (Theracal LC, TC) were used as comparisons. Adding HEMA and increasing Sr/F-BGNPs concentration decreased monomer conversion and enhanced elemental release but without significant effect on cytotoxicity. Rising Sr/F-BGNPs reduced the strength of the materials. The degree of monomer conversion of VB (96%) was much higher than that of the experimental RMGICs (21–51%) and TC (28%). The highest biaxial flexural strength of experimental materials (31 MPa) was significantly lower than VB (46 MPa) (p < 0.01) but higher than TC (24 MPa). The RMGICs with 5 wt% HEMA showed higher cumulative fluoride release (137 ppm) than VB (88 ppm) (p < 0.01). Unlike VB, all experimental RMGICs showed Ca, P, and Sr release. Cell viability in the presence of extracts from experimental RMGICs (89–98%) and TC (93%) was significantly higher than for VB (4%). Experimental RMGICs showed desirable physical/mechanical properties with lower toxicity than the commercial material.
In Silico and In Vitro Identification of P-Glycoprotein Inhibitors from a Library of 375 Phytochemicals
Authors: Schäfer Julia , Klösgen Vincent Julius , Omer Ejlal A. , Kadioglu Onat , Mbaveng Armelle T. , Kuete Victor , Hildebrandt Andreas , Efferth Thomas
Published: June 2023

Cancer therapy with clinically established anticancer drugs is frequently hampered by the development of drug resistance of tumors and severe side effects in normal organs and tissues. The demand for powerful, but less toxic, drugs is high. Phytochemicals represent an important reservoir for drug development and frequently exert less toxicity than synthetic drugs. Bioinformatics can accelerate and simplify the highly complex, time-consuming, and expensive drug development process. Here, we analyzed 375 phytochemicals using virtual screenings, molecular docking, and in silico toxicity predictions. Based on these in silico studies, six candidate compounds were further investigated in vitro. Resazurin assays were performed to determine the growth-inhibitory effects towards wild-type CCRF-CEM leukemia cells and their multidrug-resistant, P-glycoprotein (P-gp)-overexpressing subline, CEM/ADR5000. Flow cytometry was used to measure the potential to measure P-gp-mediated doxorubicin transport. Bidwillon A, neobavaisoflavone, coptisine, and z-guggulsterone all showed growth-inhibitory effects and moderate P-gp inhibition, whereas miltirone and chamazulene strongly inhibited tumor cell growth and strongly increased intracellular doxorubicin uptake. Bidwillon A and miltirone were selected for molecular docking to wildtype and mutated P-gp forms in closed and open conformations. The P-gp homology models harbored clinically relevant mutations, i.e., six single missense mutations (F336Y, A718C, Q725A, F728A, M949C, Y953C), three double mutations (Y310A-F728A; F343C-V982C; Y953A-F978A), or one quadruple mutation (Y307C-F728A-Y953A-F978A). The mutants did not show major differences in binding energies compared to wildtypes. Closed P-gp forms generally showed higher binding affinities than open ones. Closed conformations might stabilize the binding, thereby leading to higher binding affinities, while open conformations may favor the release of compounds into the extracellular space. In conclusion, this study described the capability of selected phytochemicals to overcome multidrug resistance.
Open-Spaced Ridged Hydrogel Scaffolds Containing TiO2-Self-Assembled Monolayer of Phosphonates Promote Regeneration and Recovery Following Spinal Cord Injury
Authors: Siddiqui Ahad M. , Thiele Frederic , Stewart Rachel N. , Rangnick Simone , Weiss Georgina J. , Chen Bingkun K. , Silvernail Jodi L. , Strickland Tammy , Nesbitt Jarred J. , Lim Kelly , Schwarzbauer Jean E. , Schwartz Jeffrey , Yaszemski Michael J. , Windebank Anthony J. , Madigan Nicolas N.
Published: June 2023

The spinal cord has a poor ability to regenerate after an injury, which may be due to cell loss, cyst formation, inflammation, and scarring. A promising approach to treating a spinal cord injury (SCI) is the use of biomaterials. We have developed a novel hydrogel scaffold fabricated from oligo(poly(ethylene glycol) fumarate) (OPF) as a 0.08 mm thick sheet containing polymer ridges and a cell-attractive surface on the other side. When the cells are cultured on OPF via chemical patterning, the cells attach, align, and deposit ECM along the direction of the pattern. Animals implanted with the rolled scaffold sheets had greater hindlimb recovery compared to that of the multichannel scaffold control, which is likely due to the greater number of axons growing across it. The immune cell number (microglia or hemopoietic cells: 50–120 cells/mm2 in all conditions), scarring (5–10% in all conditions), and ECM deposits (Laminin or Fibronectin: approximately 10–20% in all conditions) were equal in all conditions. Overall, the results suggest that the scaffold sheets promote axon outgrowth that can be guided across the scaffold, thereby promoting hindlimb recovery. This study provides a hydrogel scaffold construct that can be used in vitro for cell characterization or in vivo for future neuroprosthetics, devices, or cell and ECM delivery.
Navigability, Walkability, and Perspicacity Associated with Canonical Ensembles of Walks in Finite Connected Undirected Graphs—Toward Information Graph Theory
Authors: Volchenkov Dimitri
Published: June 2023

Canonical ensembles of walks in a finite connected graph assign the properly normalized probability distributions to all nodes, subgraphs, and nodal subsets of the graph at all time and connectivity scales of the diffusion process. The probabilistic description of graphs allows for introducing the quantitative measures of navigability through the graph, walkability of individual paths, and mutual perspicacity of the different modes of the (diffusion) processes. The application of information theory methods to problems about graphs, in contrast to geometric, combinatoric, algorithmic, and algebraic approaches, can be called information graph theory. As it involves evaluating communication efficiency between individual systems’ units at different time and connectivity scales, information graph theory is in demand for a wide range of applications, such as designing network-on-chip architecture and engineering urban morphology within the concept of the smart city.