Biological Modifiers Research Articles

Of Context, Quality, and Complexity: Fine-combing Tumor Mutation Burden in Immunotherapy Treated Cancers.

Tumor mutational burden (TMB) is considered a prototypic feature of tumor foreignness and has been established as a tumor-agnostic FDA-approved biomarker at a threshold of 10 mut/Mb for immune checkpoint inhibitors (ICI). Despite its clinical utility as a companion diagnostic for ICI across cancers, high TMB does not consistently predict response due to technical and biological limitations. Tumor heterogeneity and purity, blood vs. tissue sampling, variation in next generation sequencing and algorithmic evaluation attenuate the predictive value of TMB. In addition to technical standardization and moving beyond TMB as a numeric or binarized value, it is of paramount importance to consider the underlying biology and differential contribution of mutation subsets to tumor foreignness and immunogenicity. The importance of consideration of mutations within the overall TMB that are unlikely to be immunoedited together with the density of immunogenic "quality" mutation-associated neoantigens introduce the concept of biological calibration of TMB that may enhance its clinical utility. Mutagenic processes such as microsatellite instability and ultra-mutation and cancer lineage-dependent co-mutation patterns also represent biological modifiers that enable the interpretation of the overall TMB in different contexts. In this perspective, we dissect TMB on a biological and technical level followed by a critical assessment of the predictive role of TMB in capturing ICI response in the setting of clinical trials across human cancers. Standardization of technical methodologies together with the interpretation of TMB on the basis of the tumor genomic landscape represent key steps towards maximizing the predictive value of TMB for cancer immunotherapy.

Colchicine Colchicine-Induced Phenotypic Alterations in Dendrobium 'Transient White Rika' and 'Florenza': Valuable Material for Genetics-Based Learning Modules

This study investigates the phenotypic alterations in Dendrobium 'Transient White Rika' (RKA) and 'Florenza' (FLO) orchids resulting from colchicine-induced polyploidy during in vitro cultivation. Colchicine, a known mitotic inhibitor, was applied at varying concentrations (0 ppm, 4000 ppm, 5000 ppm, 6000 ppm) to induce chromosome doubling and assess its impact on the vegetative and generative phases of the orchids. A factorial Randomized Block Design (RBD) was employed to analyze the effects of these treatments. The study revealed significant variations in leaf length and color, particularly at higher colchicine concentrations. Morphological changes were most pronounced at 6000 ppm, where the leaf length decreased, and flower morphology exhibited unique features compared to the control. The study also observed a reduction in stomatal density as colchicine concentration increased, correlating with an enlargement of leaf epidermal cells. These findings indicate that colchicine treatment can effectively induce phenotypic changes in Dendrobium orchids, contributing to the development of hybrids with superior ornamental qualities. However, the study also notes that the response to colchicine is variable, with certain parameters like the number of new shoots and leaf width not showing significant changes. The results underscore the potential of colchicine-induced polyploidy in orchid breeding, though further research is necessary to optimize treatment protocols and ensure the stability and viability of the resulting hybrids. These findings may serve as valuable material for genetics-based learning modules in biology.

Diversity of The Insect Visitors Species on Lily-Leaf Acriopsis Acriopsis liliifolia (J. Koenig) Ormerod in Ayunan Langit, Kalurahan Purwosari, Girimulyo, Kulon Progo

Besides being a microhabitat for insects, Acriopsis liliifolia orchid's economic value can be increased through cultivation techniques, but it is constrained because A. liliifolia flowers can't self-pollinate. Based on their flower structure, insects have the potential to become their pollinator. Insect visitors of A. liliifolia must be identified to know their species diversity and roles during visiting orchids. The research was conducted in Ayunan Langit, Sabrangkidul, Kalurahan Purwosari, Girimulyo, Kulon Progo from September to October 2023. Insect collection was done manually by brush and then put in a flask bottle containing 5 mL of 70% alcohol. The collected specimens were then carried out to the Entomology Laboratory, Faculty of Biology, Gadjah Mada University, and identified based on morphology characters. The results showed that there was one member of Cicadellidae and 14 species of insect visitors to the A. liliifolia. The majority of insect visitors acted as herbivores (73.33%), 20% as carnivores, and the rest is unknown. It is predicted that the Braunsapis genus is a pollinator because it has a tonguelike maxilla and labium used to suck nectar. In this study, we conclude that the diversity of insect visitor species in A. liliifolia is moderate (H’= 1.95) and Braunsapis has potential as a pollinators

Based on disulfidptosis, unveiling the prognostic and immunological signatures of Asian hepatocellular carcinoma and identifying the potential therapeutic target ZNF337-AS1

BackgroundDisulfidptosis is a newly discovered programmed cell death pathway that may be connected to tumorigenesis and development, showing promise as a novel treatment strategy for cancer. This study aims to construct a prognostic model of disulfidptosis-related Long non-coding RNAs (DRLRs) within the Asian HCC population and to investigate the impact of DRLRs on HCC.MethodsUtilising a combination of univariate Cox, Lasso-Cox, and multivariate Cox analyses, five pivotal DRLRs (AC099850.3, ZNF337-AS1, LINC01138, AL031985.3, AC131009.1) were identified, forming a robust prognostic signature. Subsequent validations included Receiver Operating Characteristic (ROC) and Concordance Index analyses, alongside Principal Component Analysis. Comprehensive bioinformatics analysis was performed on the hub DRLRs, followed by experimental validation using quantitative real-time polymerase chain reaction and cellular functional assays.ResultsThe risk score independently predicted prognosis, outperforming traditional clinical-pathological factors across varying ages, tumour stages, and pathological classifications in the cohort. A nomogram integrating these variables demonstrated capability in forecasting survival. Multivariate analysis confirmed that the risk score and AJCC TNM staging are independent prognostic factors for predicting overall survival (OS) in Asian HCC patients (both P < 0.001). The prognostic model’s ROC area under the ROC values for 1-, 3-, and 5-year predictions were 0.837, 0.794, and 0.783, respectively, indicating its strong diagnostic and prognostic value. Pathway and immune landscape analyses elucidated the biological underpinnings and immune modulations associated with the high-risk group. Immune landscape analysis indicated that both immunescore (P < 0.001) and estimatescore (P < 0.05) were significantly decreased in the high-risk group, with both specific and non-specific immune responses being significantly suppressed, while the tumour immune dysfunction and exclusion score was notably increased (P < 0.001). Tumour mutational burden (TMB) analysis revealed a significantly higher TMB in the high-risk group (P = 0.033) and shorter OS for HCC patients in the high TMB subgroup (P = 0.002). Notably, Potential chemotherapeutic agents (PFI3, 5-Fluorouracil, BPD-00008900, GDC0810, and AZ6102) were identified for high-risk group. Experimental validations through quantitative PCR and in vitro assays confirmed the deregulation of these DRLRs in HCC, with functional studies highlighting the potential of ZNF337-AS1 silencing in curtailing tumour invasiveness.ConclusionOur investigations validate a DRLR-based risk scoring model as an effective prognostic tool for Asian HCC. This model not only enhances understanding of disulfidptosis’s role in HCC but also facilitates personalised treatment strategies, potentially improving patient outcomes.

Integrated transcriptome and metabolome analysis revealed hub genes and metabolites associated with subzero temperature tolerance following cold acclimation in rapeseed (Brassica rapa L.).

Integrated transcriptome and metabolome analysis revealed hub genes and metabolites associated with subzero temperature tolerance following cold acclimation in rapeseed (Brassica rapa L.).

Integrative approaches for predicting protein network perturbations through machine learning and structural characterization.

Integrative approaches for predicting protein network perturbations through machine learning and structural characterization.

How Does Sharing Data from Research Institutions on Global Biodiversity Information Facility Enhance Its Scientific Value?

For decades, thousands of scientific institutions worldwide have been digitizing collections documenting biodiversity. The advantages and benefits of this process are widely described. In this study, we test the hypothesis that digital data from local scientific institutions gain additional value once shared through the Global Biodiversity Information Facility (GBIF). We have closely examined the fate of over 2.2 million digital records deposited at the Faculty of Biology, Adam Mickiewicz University in Poznań, Poland (FBAMU), which have been available to the global community for over three years. The effectiveness of this effort is measured by the number of downloads (approximately 123,000), the number of records downloaded (45 billion), and most importantly, the number of scientific publications utilizing these data (an average of 3 publications per week). These publications appear both in the most prestigious scientific journals and regional sources. The thematic scope of papers utilizing FBAMU data shared through GBIF is very broad, covering 12 research areas, including fundamental biological fields (morphology, taxonomy and systematics, phylogeny and evolution, paleobiology, ecology, biogeography, biodiversity conservation, and biodiversity informatics), closely related applied research (agriculture and human health), and climate science and linguistic phylogeny. The most frequent uses of GBIF/FBAMU data have been in studies on processes and phenomena such as biodiversity loss, biological invasions, biogeographical patterns, changes in species ranges, climatic niche dynamics, interactions between organisms, and mechanisms of evolution.

Biological modulatorns with Bacillus licheniformis and Bacillus subtilis in compost barn

Numerous products are launched annually in Brazil and worldwide, marketed as biological modulators aimed at reducing disease spread by influencing the microorganisms present in animal production. These products are often promoted based on observational data from producers and sellers, which should not imply causal relationships. In this sense, this study evaluated a modulator containing Bacillus licheniformis and Bacillus subtilis through experimental methodology at the Instituto Federal Farroupilha - Campus Frederico Westphalen. Twelve plots (50cm x 40cm x 10cm) were prepared with wood shavings at a stocking rate of one cow per 10 m². Every day for 90 days, 40g of bovine feces were added to each plot, an amount proportional to the daily production of 32 kg of feces. Treatments included: T0 (Control, no modulator), T50 (5 ml/animal/week; 0.01875 ml/plot), and T100 (10 ml/animal/week; 0.0375 ml/plot). pH and temperature evaluations were conducted after 15 and 30 days. At 30 days, 20 g of substrate were analyzed for microbiological parameters, and colorimetric evaluations were performed. At the trial's end, total coliforms (TC) and E. coli were quantified using the Colilert method. Results showed no significant differences in pH (7) or temperature (21°C) across treatments. Minor colorimetric changes occurred in T50. While TC was higher in T50 and lower in T100 compared to the control, no statistical differences were observed. E. coli levels were lowest in T50 but not significantly different from the control. Further studies are recommended to assess the effects of longer exposure periods.

General education biology labs: a Delphi study of student learning outcomes

Introductory biology courses at most colleges and universities have two components: a lecture and a lab. However, for students who are not majoring in biology and taking the introductory course as part of their general education requirements, the distinct role of the lab has not been clearly articulated. We performed an online modified-Delphi study of student learning outcomes (SLOs) for non-majors biology. We engaged 73 biology faculty experts from institutions across the US in four iterative rounds to identify, rate, discuss, and re-rate ten SLOs for non-majors biology labs on the dimensions of importance, feasibility, and distribution of responsibility between lab and lecture. On average, the panel achieved consensus around eight SLOs as “important.” All of the SLOs were rated as “feasible” under optimal teaching and learning contexts, but the panelists noted that current institutional constraints render some as less feasible. Our analysis suggests that labs share many SLOs with lectures, but there are also some SLOs that are unique to the lab. Our study provides recommendations for coordinated strategies and efforts between lecture and lab activities to promote more rigorous learning and better attainment of those outcomes.

Identification of disease-specific pathways and modifiers in phospholamban R14del cardiomyopathy: rationale, design and baseline characteristics of DECIPHER-PLN cohort.

Phospholamban (PLN) p.Arg14del (R14del, R14∆/+) is the most commonly identified pathogenic variant that causes cardiomyopathy in the Netherlands. Many disease characteristics are still unclear, including the phenotypic triggers, disease progression and disease-specific biomarkers. We aim to gain abetter understanding of the R14∆/+ pathophysiology by establishing acohort across the R14∆/+ disease spectrum. The Disease spECifIc PatHways and modifiERs in PhosphoLambaN r14del cardiomyopathy (DECIPHER-PLN) cohort includes 101 participants, categorised as unaffected R14∆/+ (n = 21), early affected R14∆/+ (n = 42), end-stage R14∆/+ (n = 28) and heart failure (HF) of another aetiology (n = 10). R14∆/+ category was based on left ventricular ejection fraction, HF symptoms, electrocardiogram (ECG) and N‑terminal pro-brain natriuretic peptide concentrations. Of the 91included R14∆/+ carriers, 46 (51%) were female, with amean age of 55years (standard deviation: 14). Low-voltage ECG older age, arrhythmias, and conduction and repolarisation abnormalities were common in (early) affected R14∆/+ carriers. Serum and plasma were collected from all participants. Induced pluripotent stem cells were generated from fibroblasts of end-stage R14∆/+ patients and unaffected R14∆/+ family members (n = 4) and differentiated into cardiomyocytes. Explanted heart tissue was obtained from R14∆/+ patients undergoing cardiac surgery and patients with other HF aetiologies as control. Abnormal PLN protein localisation was confirmed in R14∆/+ carriers. DECIPHER-PLN comprises R14∆/+ carriers across the disease and non-disease spectrum and can be used to identify disease-specific biological pathways and modifiers that play arole in R14∆/+ cardiomyopathy. Using amulti-omics approach and in vitro disease modelling, we aim to identify novel biomarkers and improve our understanding of R14∆/+ pathophysiology. Material is available upon request.

Comprehensive characterization of fatty acid oxidation in triple-negative breast cancer: Focus on biological roles and drug modulation.

Comprehensive characterization of fatty acid oxidation in triple-negative breast cancer: Focus on biological roles and drug modulation.

How do Early-career Biology Faculty Develop Pedagogical Content Knowledge? Exploring Variation and Longitudinal Development.

Active-learning instructors are more effective when they use pedagogical content knowledge (PCK) to anticipate, interpret, and respond to student thinking. PCK is topic-specific and includes knowledge of student thinking (e.g., common difficulties) and knowledge of instructional strategies (e.g., effective learning tasks). Currently, we know little about how instructors develop PCK. We documented how 11 early-career undergraduate life science instructors developed PCK over multiple semesters by eliciting knowledge as instructors planned, implemented, and reflected on instruction. Qualitative content analysis indicated that instructors' PCK about student thinking was not necessarily grounded in evidence from students and their PCK about instructional strategies varied in whether and how it considered student thinking. We adapted a rubric to test hypotheses about PCK development trajectories. Participants' PCK about student thinking tended to become more grounded in evidence from students and their PCK about instructional strategies tended to focus more on student thinking over time. However, teaching experience did not necessarily lead to PCK development. Case study analysis revealed that pedagogical knowledge and specific practices supported PCK development. We propose a hypothetical model to explain how teaching knowledge and practices support PCK development. We also suggest reflections and actions for instructors who want to develop their PCK.

Microbiome-Based Therapeutics for Salt-Sensitive Hypertension: A Scoping Review.

The purpose of this scoping review was to provide a comprehensive understanding of the current knowledge concerning the gut microbiome and SCFAs as emerging treatments for salt-sensitive hypertension. Relevant animal and human studies were identified via PubMed through August 2024. Twenty-four human (n = 9) and animal (n = 15) trials were included. Most human studies were observational (n = 6), aiming to compare gut microbiota differences between hypertensive and normotensive individuals. Three human studies evaluated microbiome-based interventions either via a sodium-restricted diet (n = 2) or prebiotic supplementation (n = 1). Fifteen animal trials involving either mice or rats were identified, all of which were interventional. These included dietary changes (n = 9), probiotic treatments (n = 1), postbiotic primarily bacterial metabolites (n = 4), and live biotherapeutic products (n = 4). All interventions were effective in decreasing blood pressure. Microbiome-based therapies as biologic modifiers for salt-sensitive hypertension are emerging. Substantial knowledge gaps remain, warranting further research to fully explore this promising therapeutic avenue.

Patient-centered brain transcriptomic and multimodal imaging determinants of clinical progression, physical activity, and treatment needs in Parkinson’s disease

We continue to lack a clear understanding on how the biological and clinical complexity of Parkinson’s disease emerges from molecular to macroscopic brain interactions. Here, we use personalized multiscale spatiotemporal computational brain models to characterize for the first time the synergistic links between genes, several multimodal neuroimaging-derived biological factors, clinical profiles, and therapeutic needs in PD. We identified genes modulating PD-caused brain reorganization in dopamine transporter level, neuronal activity integrity, microstructure, dendrite density and tissue atrophy. Inter-individual heterogeneity in the identified gene-mediated biological mechanisms was associated with five distinct configurations of PD motor and non-motor symptoms. Notably, the protein-protein interaction networks underlying both brain phenotypic and symptom configurations in PD revealed distinct hub genes including MYC, CCNA2, CCDK1, SRC, STAT3 and PSMD4. We also studied the biological mechanisms associated with physical activities performance, observing that leisure and work activities are strongly related to neurotypical cholesterol homeostasis and inflammatory response processes, respectively. Finally, patient-tailored in silico gene perturbations revealed a set of putative disease-modifying drugs with potential to effectively treat PD across different biological levels, most of which are associated with dopamine reuptake and anti-inflammation. Our study constitutes the first self-contained multiscale spatiotemporal computational approach providing comprehensive insights into the complex multifactorial pathogenesis of PD, unraveling key biological modulators of physical and clinical deterioration, and serving as a blueprint for optimum drug selection at personalized level.

ANTIFUNGAL EFFECT AND PHYTOCHEMICAL ANALYSIS OF SOLANUM MACROCARPON LIN. LEAF EXTRACT IN SOUTHEAST NIGERIA

The study investigated the antifungal activities and phytochemical composition of Solanum macrocarpon Lin. Leaf extract. The research was carried out at the Microbiology Laboratory, Department of Microbiology, Faculty of Biological Sciences, Imo State University, Owerri, Nigeria. The phytochemical revealed that alkaloid, phenol, saponin, flavonoid and tannin were present while steroid and terpenoid were absent. Quantitatively, flavonoid, constitutes the highest substance at 9.44% while phenol was lowest with 0.145. Antifungal investigation reveals that aqueous and ethanol extract of Solanum macrocarpon Lin was able to exhibit strong inhibitory activity against fungal isolates. (Aspergillus niger, Fusarium oxysporum, Geotrichum candidum and Botrodipodia theobromae tested). Ethanol extract showed higher inhibitory effect than aqueous extract. In aqueous extract the inhibitory effect is independent of the extract concentration. For 0.5ml aqueous, Fusarium oxysporum had 2.3cm mycelium growth while it was 2.93cm in 1ml. Botrodipodia theobromae had 3.95cm mycelium growth in 0.5ml but 2.75cm in 1ml. The ethanol extract inhibition increases with increase in concentration. In Geotrichum candidum at 0.5ml, mycelium growth was 1.60cm but 1.02cm in 1ml. The antifungal activity of these extract is possibly linked to the presence of flavonoids, saponins and tannins. Further analysis should be carried out to determine the precise active bioactive compounds from Solanum macrocarpon L. that could inhibit fungi growth.

Abstracts fook of the Scientific Session of the Faculty of Biology (SSFB), New Trends in Biology: from Molecules to Complex Systems, 4th edition, October 25th - 26th, 2024

Abstracts of the scientific works that have been presented at the Scientific Session of the Faculty of Biology (SSFB), New Trends in Biology: from Molecules to Complex Systems, 4th edition, October 25-26, 2024, Iasi, Romania

Faculty perceptions of a professional development program for developing CUREs and promoting inclusive and equitable teaching.

The Diffusion of Innovations (DOI) model can be used to explore how faculty prioritize learning about and adopting new pedagogical approaches. Here, we use the DOI framework to contextualize biology faculty perceptions of a professional development (PD) program designed to help them create a full semester course-based undergraduate research experience (CURE) class at a large, public comprehensive university. PD sessions included exploring self-reflexive identity while fostering inclusive classroom spaces through understanding and interrupting implicit bias and microaggressions. This qualitative study sought to determine 11 biology faculty members' beliefs about the influence of their year-long PD on their CURE development and teaching practices. Findings suggest that faculty were motivated to teach CUREs for a variety of reasons. A common incentive was integrating research into a CURE to bring their passion into their classroom and to engage more students in research. This may be particularly important at institutions where faculty have a heavy teaching load. Faculty also reported modifying their teaching in their CUREs and other courses to be more inclusive and equitable. The importance of peer interactions in the PD was emphasized repeatedly as faculty learned from experts, the literature, and faculty who had already developed a CURE. Our results illustrate that a community of practice structure can enhance the learning aspect of the community, helping faculty consider their implementation of inclusive, equitable, and high-impact practices as an ongoing educational process for themselves and emphasizing the importance of reflection and iteration in a DOI framework.

Tregs levels and phenotype modifications during Amyotrophic Lateral Sclerosis course.

T regulatory cells (Tregs) inversely correlate with disease progression in Amyotrophic Lateral Sclerosis (ALS) and fast-progressing ALS patients have been reported to exhibit dysfunctional, as well as reduced, levels of Tregs. This study aimed to evaluate the longitudinal changes in Tregs among ALS patients, considering potential clinical and biological modifiers of their percentages and concentrations. Additionally, we explored whether measures of ALS progression, such as the decline over time in the revised ALS Functional Rating Scale (ALSFRS-r) or forced vital capacity (FVC) correlated Treg levels and whether Treg phenotype varied during the course of ALS. Total Tregs (detected by CD3, CD4, FoxP3, CD25, and CD127) were quantified at five time points over 54 weeks in 21 patients in the placebo arm of the RAP-ALS trial; next they were characterized for the expression of surface markers including CD38, CD39, CXCR3, and PD1. Repeated measures mixed models were used to analyze the longitudinal course of Tregs, considering potential associations with other clinical and laboratory characteristics. Correlations between ALSFRS-r or FVC and Tregs over time were similarly investigated. Our study showed that Treg levels did not change significantly on average during the observation period in our ALS cohort. However, PD1+Tregs decreased and CD39+Tregs increased over time. Male sex and cholesterol levels were associated with increasing Tregs (%) over time, while monocytes positively affected Treg concentrations. Treg concentrations showed a modesty association with FVC decline but were not associated with ALSFRS-r decline. Treg levels remained stable during the ALS observation period and were not significantly associated with ALSFRS-r variations, suggesting that Treg numbers alone may have limited utility as a pharmaco-dynamic biomarker for ALS trials. However the observed changes in Treg phenotypes, such as the decrease in PD1+Tregs, indicate that phenotypic variations may warrant further investigation for their potential role in ALS progression and therapeutic targeting.

Exploration and morphological characterization of Trichoderma spp from organic waste at TPST Rempoah-Baturraden, Banyumas Regency

Members of the Trichoderma genera are able to adapt to various habitats including organic waste, with a fairly high population density. This study aimed to determine the differences in the morphological characteristics of Trichoderma spp isolated from the Rempoah Integrated Waste Processing Facility (TPST), Baturraden District, Banyumas Regency. The experiment was conducted at the Mycology and Phytopathology Laboratory, Faculty of Biology, Jenderal Soedirman University. The results of the exploration of the Trichoderma genera obtained three isolates. The characteristics observed were macroscopic characteristics including the colour and shape of the colonies, and microscopic characteristics including the shape of conidiophores, phialides, and conidia. The results showed that the three Trichoderma isolates from Rempoah TPST had different morphological characteristics. The species of Trichoderma spp obtained were T. koningii, T. asperellum, and T. harzianum.

Graph-Theoretical Prediction and Analysis of Biologically Relevant Substructures in an Open and Closed Conformation of Respiratory Complex I.

Protein complexes are functional modules within the hierarchy of the cellular organization. Large protein complexes often consist of smaller functional modules, which are biologically relevant substructures with specific functions. The first protein complex of the respiratory chain, complex I, consists of functional modules for the electron transfer from NADH to quinone and the translocation of protons across the inner mitochondrial membrane. Complex I is well-characterized and biological modules have been experimentally assigned. Nevertheless, there is an ongoing discussion about the coupling of the electron transfer and the proton translocation, and about the proton translocation pathways.We modelled a mammalian complex I in open and closed conformations as complex graphs, with vertices representing protein chains and edges representing chain-chain contacts. Using a graph-theoretical method, we computed the structural modules of complex I, which indicated functional, biological substructures. We described characteristic structural features of complex I and observed a rearrangement of the structural modules. The changes in the structural modules indicated the formation of a functional module in the membrane arm of complex I during the conformational change.