Biological Meaning Research Articles

Foxg1 regulates translation of neocortical neuronal genes, including the main NMDA receptor subunit gene, Grin1

BackgroundMainly known as a transcription factor patterning the rostral brain and governing its histogenesis, FOXG1 has been also detected outside the nucleus; however, biological meaning of that has been only partially clarified.ResultsPrompted by FOXG1 expression in cytoplasm of pallial neurons, we investigated its implication in translational control. We documented the impact of FOXG1 on ribosomal recruitment of Grin1-mRNA, encoding for the main subunit of NMDA receptor. Next, we showed that FOXG1 increases GRIN1 protein level by enhancing the translation of its mRNA, while not increasing its stability. Molecular mechanisms underlying this activity included FOXG1 interaction with EIF4E and, possibly, Grin1-mRNA. Besides, we found that, within murine neocortical cultures, de novo synthesis of GRIN1 undergoes a prominent and reversible, homeostatic regulation and FOXG1 is instrumental to that. Finally, by integrated analysis of multiple omic data, we inferred that FOXG1 is implicated in translational control of hundreds of neuronal genes, modulating ribosome engagement and progression. In a few selected cases, we experimentally verified such inference.ConclusionsThese findings point to FOXG1 as a key effector, potentially crucial to multi-scale temporal tuning of neocortical pyramid activity, an issue with profound physiological and neuropathological implications.

Complex Dynamics of a Simple Tumor-Immune Model with Tumor Malignancy

One main feature of a malignant tumor is its uncontrolled growth. In this paper, we propose a simple tumor-immune model to study the progressive characteristics of malignant and benign tumors, where the anti-tumor immunity can be described by the Michaelis–Menten function or the mass action law. The model includes only two state variables for the tumor cells and the effector cells representing the immune system. Three quantities with clear biological meanings are given to determine the asymptotic states of the tumor progression. Moreover, differences in asymptotic states between the two anti-tumor immunity descriptions are drawn. Differently from existing simple models, on the one hand, the model exhibits rich dynamical behaviors including super-critical and sub-critical Bogdanov–Takens bifurcations (consisting of Hopf bifurcation, saddle–node bifurcation, and homoclinic bifurcation) and saddle–node bifurcation of nonconstant periodic solutions (leading to the appearance of two periodic orbits) as the parameters vary; on the other hand, the malignant feature, dormancy, and immune escape of the tumor are revealed with numerical simulations. Furthermore, from the perspective of qualitative analysis and numerical simulations, how the obtained results can be applied to the treatment and control of tumors is illustrated.

TermineR: Extracting information on endogenous proteolytic processing from shotgun proteomics data.

State-of-the-art mass spectrometers combined with modern bioinformatics algorithms for peptide-to-spectrum matching (PSM) with robust statistical scoring allow for more variable features (i.e., post-translational modifications) being reliably identified from (tandem-) mass spectrometry data, often without the need for biochemical enrichment. Semi-specific proteome searches, that enforce a theoretical enzymatic digestion to solely the N- or C-terminal end, allow to identify of native protein termini or those arising from endogenous proteolytic activity (also referred to as "neo-N-termini" analysis or "N-terminomics"). Nevertheless, deriving biological meaning from these search outputs can be challenging in terms of data mining and analysis. Thus, we introduce TermineR, a data analysis approach for the (1) annotation of peptides according to their enzymatic cleavage specificity and known protein processing features, (2) differential abundance and enrichment analysis of N-terminal sequence patterns, and (3) visualization of neo-N-termini location. We illustrate the use of TermineR by applying it to tandem mass tag (TMT)-based proteomics data of a mouse model of polycystic kidney disease, and assess the semi-specific searches for biological interpretation of cleavage events and the variable contribution of proteolytic products to general protein abundance. The TermineR approach and example data are available as an R package at https://github.com/MiguelCos/TermineR.

Experiences of menopause among non-binary and trans people

Background Conventional categorizations of menopause can be difficult to apply to trans, gender non-conforming and non-binary (TGNB) populations. Menopause has biological, psychological and social meanings that may be hard to clearly apply within a context of diverse experiences of sex and gender. Nonetheless, some TGNB people do experience menopause, and their experiences may be different from those of other groups due to those diverse biopsychosocial understandings and experiences. Method This paper thematically analyses the responses of 15 TGNB respondents who responded to a larger survey about LGBTQ+ experiences of menopause. Results Two key themes were identified: Menopause and embodied identities, and Navigating gender normativity and gender binarism. The first of these contains two sub-themes, shifting and (un)settled gender identities, and embodied dis/connections with femaleness. Conclusions These findings appear to be comparatively novel within the published academic literature but potentially have some parallels with prior observations regarding interactions between puberty and gender identity, and also regarding TGNB people’s experiences of challenges in navigating other health and life experiences normatively understood as female. These explorations raise a number of potentially sensitive questions, given the current debate and controversies around gender, sex and identity. Nonetheless, they point to a need for further research and practice into menopause that is inclusive and supportive of a range of gender and sexual identities.

A Comparison of Tools That Identify Tumor Cells by Inferring Copy Number Variations from Single-Cell Experiments in Pancreatic Ductal Adenocarcinoma.

Single-cell RNA sequencing (scRNA-seq) technique has enabled detailed analysis of gene expression at the single cell level, enhancing the understanding of subtle mechanisms that underly pathologies and drug resistance. To derive such biological meaning from sequencing data in oncology, some critical processing must be performed, including identification of the tumor cells by markers and algorithms that infer copy number variations (CNVs). We compared the performance of sciCNV, InferCNV, CopyKAT and SCEVAN tools that identify tumor cells by inferring CNVs from scRNA-seq data. Sequencing data from Pancreatic Ductal Adenocarcinoma (PDAC) patients, adjacent and healthy tissues were analyzed, and the predicted tumor cells were compared to those identified by well-assessed PDAC markers. Results from InferCNV, CopyKAT and SCEVAN overlapped by less than 30% with InferCNV showing the highest sensitivity (0.72) and SCEVAN the highest specificity (0.75). We show that the predictions are highly dependent on the sample and the software used, and that they return so many false positives hence are of little use in verifying or filtering predictions made via tumor biomarkers. We highlight how critical this processing can be, warn against the blind use of these software and point out the great need for more reliable algorithms.

Artificial intelligence, adversarial attacks, and ocular warfare

PurposeWe explore the potential misuse of artificial intelligence (AI), specifically large language models (LLMs), in generating harmful content related to ocular warfare. By examining the vulnerabilities of AI systems to adversarial attacks, we aim to highlight the urgent need for robust safety measures, enforceable regulation, and proactive ethics. DesignA viewpoint paper discussing the ethical challenges posed by AI, using ophthalmology as a case study. It examines the susceptibility of AI systems to adversarial attacks and the potential for their misuse in creating harmful content. MethodsThe study involved crafting adversarial prompts to test the safeguards of a well-known LLM, OpenAI's ChatGPT-4.0. The focus was on evaluating the model's responses to hypothetical scenarios aimed at causing ocular damage through biological, chemical, and physical means. ResultsThe AI provided detailed responses on using Onchocerca volvulus for mass infection, methanol for optic nerve damage, mustard gas for severe eye injuries, and high-powered lasers for inducing blindness. Despite significant safeguards, the study revealed that with enough effort, it was possible to bypass these constraints and obtain harmful information, underscoring the vulnerabilities in AI systems. ConclusionAI holds the potential for both positive transformative change and malevolent exploitation. The susceptibility of LLMs to adversarial attacks and the possibility of purposefully trained unethical AI systems present significant risks. This paper calls for improved robustness of AI systems, global legal and ethical frameworks, and proactive measures to ensure AI technologies benefit humanity and do not pose threats.

Unstable states and the biologization of mental illness

We critically examine how biological narratives of mental illness mediate relations between personal experiences and socio-structural conditions of distress in crisis contexts. Using three case studies of contemporary crises in Russia, the Republic of Cameroon, and Bangladesh, we showcase the ways in which biological meanings of mental illness carry political and structural significance as authorities employ “biologization” for political ends. In Russia, biologization is strategically useful to authorities seeking to control a populace, as chronic “conditions” can be “treated” indefinitely. In Cameroon, state psychiatrists in Yaoundé incentivize patient citizenship through biological frameworks of illness and intervention. In Bangladesh, the embodied presence of Rohingya refugees is a medium by which they can engage politically; therapeutic intervention becomes a site of political consensus in which Rohingya enact a “fictive biological citizenship.” Biologization of mental illness forms a basis for reinforcing or challenging the power of the state and the meaning of citizenship in distinct ways across these three contexts, highlighting the importance of attending to its political implications as it is invoked in frameworks of diagnosis, explanation, prognosis, and treatment in global contexts of ostensible crisis.

Targeted co-expression networks for the study of traits

Weighted Gene Co-expression Network Analysis (WGCNA) is a widely used approach for the generation of gene co-expression networks. However, networks generated with this tool usually create large modules with a large set of functional annotations hard to decipher. We have developed TGCN, a new method to create Targeted Gene Co-expression Networks. This method identifies the transcripts that best predict the trait of interest based on gene expression using a refinement of the LASSO regression. Then, it builds the co-expression modules around those transcripts. Algorithm properties were characterized using the expression of 13 brain regions from the Genotype-Tissue Expression project. When comparing our method with WGCNA, TGCN networks lead to more precise modules that have more specific and yet rich biological meaning. Then, we illustrate its applicability by creating an APP-TGCN on The Religious Orders Study and Memory and Aging Project dataset, aiming to identify the molecular pathways specifically associated with APP role in Alzheimer’s disease. Main biological findings were further validated in two independent cohorts. In conclusion, we provide a new framework that serves to create targeted networks that are smaller, biologically relevant and useful in high throughput hypothesis driven research. The TGCN R package is available on Github: https://github.com/aliciagp/TGCN.

Introduction to the Special Issue ‘Umwelt Theory and Phenomenology’

This introduction to the special issue “Umwelt Theory and Phenomenology” is composed of a brief theoretical introduction to phenomenology seen as a key attitude of philosophical research, an investigation of the possibilities offered by a combined application of phenomenology and biosemiotics, and an overview of the articles that are included in the special issue. The theoretical introduction stresses the possibility of distinguishing, within phenomenology, between approaches centred on the object (in other terms, the phenomenon), and subject-centred approaches which have emerged in the wake of Kantian transcendental idealism. The connection with biosemiotics is explored for both kinds of approaches, showing how Uexküll, and many other scholars after him, have used phenomenological tools and perspectives in the study of biological meaning and meaning-making processes. For each article in the collection, the overview of the articles indicates one or two points that we believe are of the greatest interest for the reader.

Strain variation in the Candida albicans iron limitation response.

Iron acquisition is critical for pathogens to proliferate during invasive infection, and the human fungal pathogen Candida albicans is no exception. The iron regulatory network, established in reference strain SC5314 and derivatives, includes the central player Sef1, a transcription factor that activates iron acquisition genes in response to iron limitation. Here, we explored potential variation in this network among five diverse C. albicans strains through mutant analysis, Nanostring gene expression profiling, and, for two strains, RNA-Seq. Our findings highlight four features that may inform future studies of natural variation and iron acquisition in this species. (i) Conformity: In all strains, major iron acquisition genes are upregulated during iron limitation, and a sef1Δ/Δ mutation impairs that response and growth during iron limitation. (ii) Response variation: Some aspects of the iron limitation response vary among strains, notably the activation of hypha-associated genes. As this gene set is tied to tissue damage and virulence, variation may impact the progression of infection. (iii) Genotype-phenotype variation: The impact of a sef1Δ/Δ mutation on cell wall integrity varies, and for the two strains examined the phenotype correlated with sef1Δ/Δ impact on several cell wall integrity genes. (iv) Phenotype discovery: DNA repair genes were induced modestly by iron limitation in sef1Δ/Δ mutants, with fold changes we would usually ignore. However, the response occurred in both strains tested and was reminiscent of a much stronger response described in Cryptococcus neoformans, a suggestion that it may have biological meaning. In fact, we observed that the iron limitation of a sef1Δ/Δ mutant caused recessive phenotypes to emerge at two heterozygous loci. Overall, our results show that a network that is critical for pathogen proliferation presents variation outside of its core functions.IMPORTANCEA key virulence factor of Candida albicans is the ability to maintain iron homeostasis in the host where iron is scarce. We focused on a central iron regulator, SEF1. We found that iron regulator Sef1 is required for growth, cell wall integrity, and genome integrity during iron limitation. The novel aspect of this work is the characterization of strain variation in a circuit that is required for survival in the host and the connection of iron acquisition to genome integrity in C. albicans.

Biological samples for examination: concepts, conditions, sampling tactics

During the commission of crimes, traces of biological origin are left on the objects of the environment, tools, clothing, and the body of the participants. To conduct an identification study, an expert needs to compare the traces of the crime with biological samples of the person being tested. Criteria for determining biological samples are proposed. The biological criterion means that the samples reflect the internal and external properties of a person as a biological organism. The informational criterion is that the samples meet certain requirements: undoubted origin, required quantity, proper quality, compatibility with traces of crime. The identification criterion establishes that the human properties reflected by the samples are individual, stable, cannot be deliberately altered by a person and are suitable for identification. The procedural criterion means that biological samples must be collected in a lawful manner. Based on these criteria, biological samples for examination include: body parts; secretions as products of human activity; imprints of the skin relief of the human body. The mandatory participants in the collection of biological samples as a procedural action are: persons from whom biological samples are collected; officials who conduct the collection of samples and are responsible for its legality and validity; a specialist or expert; witnesses; employees of the relevant law enforcement agencies (in the case of compulsory collection of biological samples). Optional participants are a defence counsel, legal representative, representative, lawyer, doctor at their request. During the compulsory collection of biological samples, in order to ensure the legality, objectivity, reliability of the objects of expert research, preservation of health and observance of human rights, it is necessary to comply with legal, ethical, medical and forensic conditions. The author proposes a general algorithm for the tactics of obtaining biological samples for examination at the stage of pre-trial investigation, which includes the preparatory, working and final stages.

The Progress of Ganoderma Lucidum Cultivation by Utilizing Agricultural and Forestry Wastes

Agricultural and forestry waste is one of the important and abundant biomass resources in China, and it is of great significance to realise the resource utilisation of agricultural and forestry waste through green and low-carbon biological means, which is conducive to achieving the goal of “carbon neutrality” and promoting the sustainable development of the agricultural and forestry industry. Ganoderma lucidum is rich in various active ingredients and has high medicinal value, so the artificial cultivation of Ganoderma lucidum and product research and development have received extensive attention worldwide. With the expansion of Ganoderma lucidum artificial cultivation industry, the use of agricultural and forestry wastes as a substitute material for Ganoderma lucidum cultivation is a hot research topic nowadays. This paper reviews the research results and application cases of various agricultural & forestry waste conversion using in the field of Ganoderma lucidum substitution cultivation and discusses the development potential and advantages of Ganoderma lucidum cultivation and combined cultivation mode of agriculture and forestry. By analyzing the research results on the resource utilization of agroforestry wastes in Ganoderma lucidum cultivation, we focused on the effects of culture media R&D protocols with different culture substrates, and its effect on the growth efficiency, yield and nutrient composition of Ganoderma lucidum. This provides reference for the high-value utilisation of agricultural and forestry wastes and the development of artificial Ganoderma lucidum cultivation industry, as well as the enhancement of carbon sinks in agricultural and forestry ecosystems.

Diurnal-Rhythmic Relationships between Physiological Parameters and Photosynthesis- and Antioxidant-Enzyme Genes Expression in the Raphidophyte Chattonella marina Complex.

Diurnal rhythms in physiological functions contribute to homeostasis in many organisms. Although relationships between molecular biology and diurnal rhythms have been well studied in model organisms like higher plants, those in harmful algal bloom species are poorly understood. Here we measured several physiological parameters and the expression patterns of photosynthesis-related and antioxidant-enzyme genes in the Chattonella marina complex to understand the biological meaning of diurnal rhythm. Under a light-dark cycle, Fv/Fm and expression of psbA, psbD, and 2-Cys prx showed significant increases in the light and decreases during the dark. These rhythms remained even under continuous dark conditions. DCMU suppressed the induction of psbA, psbD, and 2-Cys prx expression under both light regimes. Oxidative stress levels and H2O2 scavenging activities were relatively stable, and there was no significant correlation between H2O2 scavenging activities and antioxidant-enzyme gene expression. These results indicate that the Chattonella marina complex has developed mechanisms for efficient photosynthetic energy production in the light. Our results showed that this species has a diurnal rhythm and a biological clock. These phenomena are thought to contribute to the efficiency of physiological activities centered on photosynthesis and cell growth related to the diurnal vertical movement of this species.

Modelling pH Dynamics, SCOBY Biomass Formation, and Acetic Acid Production of Kombucha Fermentation Using Black, Green, and Oolong Teas

Kombucha is a traditional, fermented beverage made with an essential biomaterial known as SCOBY (symbiotic culture of bacteria and yeast). Three different tea types, namely black, green, and oolong, were compared in kombucha fermentation in terms of pH dynamics, the formation of SCOBY biomass, and the production of acetic acid. The rational, exponential, and polynomial models described pH dynamics with good fit, R2 > 0.98. The formation of SCOBY biomass and the production of acetic acid were modelled using sigmoidal functions, with three-parameter logistic and Gompertz models and four-parameter Boltzmann and Richards models. The F-test indicated that the three-parameter models were statistically adequate; thus, the Gompertz model was modified to present the biological meaning of the parameters. The SCOBY biomass formation rates ranged from 7.323 to 9.980 g/L-day, and the acetic acid production rates ranged from 0.047 to 0.049% acid (wt/vol)/day, with the highest values from the non-conventional substrate, oolong tea. The correlations between pH and SCOBY biomass or acetic acid using polynomial models enable the prediction of product formation in kombucha processing.

Numerical threshold stability of a nonlinear age-structured reaction diffusion heroin transmission model

This paper deals with the numerical threshold stability of a nonlinear age-space structured heroin transmission model. A semi-discrete system is established by spatially domain discretization of the original nonlinear age-space structured model. A threshold value is proposed in stability analysis of the semi-discrete system and named as a numerical basic reproduction number. Besides the role it plays in numerical threshold stability analysis, the numerical basic reproduction number can preserve qualitative properties of the exact basic reproduction number and converge to the latter while stepsizes vanish. A fully discrete system is established via a time discretization of the semi-discrete system, in which an implicit-explicit technique is implemented to ensure the preservation of the biological meanings (such as positivity) without CFL restriction. Some numerical experiments are exhibited in the end to confirm the conclusions and explore the final state.

A novel optimal control strategy for nutrient–phytoplankton–zooplankton model with viral infection in plankton

This paper presents a mathematical model that explores the intricate dynamics between nutrients, phytoplankton, and zooplankton populations, incorporating viral infection phenomena in the frame of the Caputo fractional derivative. The conceptual properties such as the existence, uniqueness, and stability of multiple equilibria are analyzed under specific conditions. We have defined some threshold parameters whose biological meaning helps in strengthening the stability conditions. Furthermore, an optimal control strategy is proposed for the suggested model and the impacts of the optimal control strategy on both commensurate and non-commensurate systems are investigated. A dynamic framework is developed to investigate the optimal use of resources, stock sustainability, and resource benefits. The control variables considered are concerned with the infection of the susceptible phytoplankton and the nutrient consumption of infected phytoplankton. Pontryagin’s maximum principle is employed to determine the best control strategy. Using the Adam-Bashforth-Moulton predictor–corrector method we have performed the numerical simulation that provides the justification of the theoretical findings.

Economic effectiveness of the use of biological means of apple tree protection against diseases

Economic effectiveness of the use of biological means of apple tree protection against diseases

Stability and Bifurcation Analysis in a Discrete Predator–Prey System of Leslie Type with Radio-Dependent Simplified Holling Type IV Functional Response

In this paper, we use a semi-discretization method to consider the predator–prey model of Leslie type with ratio-dependent simplified Holling type IV functional response. First, we discuss the existence and stability of the positive fixed point in total parameter space. Subsequently, through using the central manifold theorem and bifurcation theory, we obtain sufficient conditions for the flip bifurcation and Neimark–Sacker bifurcation of this system to occur. Finally, the numerical simulations illustrate the existence of Neimark–Sacker bifurcation and obtain some new dynamical phenomena of the system—the existence of a limit cycle. Corresponding biological meanings are also formulated.

The role and mechanism of circadian clock gene BMAL1 in the proliferation and metastasis of nasopharyngeal carcinoma by inhibition TGF-β1/Smads pathway.

6027 Background: To explore the molecular mechanism of biological clock gene BMAL1 inhibiting the proliferation and metastasis of nasopharyngeal carcinoma(NPC). Methods: 1. IHC detected the expression of BMAL1 in 41 cases of nasopharyngeal chronic inflammatory tissue and 71 cases of NPCtissue. PCR and Western blot measured the expression levels of BMAL1 in NP69 in NPC cells and human immortalized nasopharyngeal epithelial cells, respectively. 2. To detect the effect of BMAL1 on the proliferation capacity of NPCcells in vitro and in vivo; Scratch healing and Transwell invasion migration experiments detected the effect of BMAL1 on the invasion and migration ability of NPCcells in vitro. Fluorescence in vivo imaging and HE staining to determine the transfer of nude mouse tail intravenous injection model. PCR and Western blot detect the effect of BMAL1 on the expression of EMT-related markers at the transcriptional and protein levels in NPC cells. 3. A series of molecular biological means such as bioinformatics technology, ChIP experiment, double luciferase reporter gene experiment, immunofluorescence colocalization experiment and Co-IP were used to verify its mechanism. Results: 1. The expression of BMAL1 in NPCtissues and cells is reduced. The expression of BMAL1 in NPC tissues was associated with the M stage of nasopharyngeal carcinoma patients (p=0.006). 2. Overexpression of BMAL1 can inhibit the proliferation, invasion and migration ability of nasopharyngeal cancer cells, while knocking down BMAL1 is the opposite. Overexpression of BMAL1 inhibits EMT of NPCcells. 3. There are 5 BMAL1 binding sites in the TGF-β1promoter region, and BMAL1 can directly bind to the TGF-β1promoter region, which can inhibit the transcriptional activity of TGF-β1. Overexpression of BMAL1 inhibits TGF-β1/Smads pathway activity. Under the induction of recombinant human TGF-β1, the proliferation ability of NPC cells was enhanced, the activity of TGF-β1/Smads signaling pathway was enhanced, and nasopharyngeal cancer cells underwent EMT, and cell invasion and migration capacity increased. After overexpression of BMAL1, TGF-β1 no longer promotes TGF-β1/Smads signaling pathway activity, EMT is inhibited, and cell invasion and migration ability is weakened. BMAL1 combined with TGF-β1 has certain diagnostic value in predicting whether nasopharyngeal carcinoma metastasis. Conclusions: BMAL1 expression is downregulated in nasopharyngeal carcinoma, and its expression level is related to the development and metastasis of nasopharyngeal carcinoma. BMAL1 can inhibit the proliferation, epithelial-mesenchymal transformation and invasion and metastasis ability of NPC cells, and its mechanism is related to the inhibition of TGF-β1/Smads signaling pathway activity. It is speculated that it may become a new prognostic marker and therapeutic target for nasopharyngeal carcinoma.

Biotechnological achievements in combating pest insects

Climate change, global food security and environmental sustainability have become major challenges over the past decades. The race against the clock, in which humanity finds itself due to the irreversible nature of global warming and the increasing impact of harmful organisms on agricultural crops, which considerably reduce food security and food safety, determines the need to develop and apply biotechnological, ecologically harmless means of maintaining the dynamic balance between phytosanitary agents and useful natural entities. This paper discusses the results recorded in the application of biotechnological methods of production and application of biological means aimed at reducing the impact of harmful insect populations through the application of entomopathogenic microorganisms and genetic methods of combat through sterilization, the cultivation of same-sex and conditionally sterile specimens, the application of technologies genome editing, which changes their genetic background.