Biological Modification Research Articles

Biological modification of coastal pH depends on community composition and time.

Biological processes play important roles in determining how global changes manifest at local scales. Primary producers can absorb increased CO2 via daytime photosynthesis, modifying pH in aquatic ecosystems. Yet producers and consumers also increase CO2 via respiration. It is unclear whether biological modification of pH differs across the year, and, if so, what biotic and abiotic drivers underlie temporal differences. We addressed these questions using the intensive study of tide pool ecosystems in Alaska, USA, including quarterly surveys of 34 pools over 1 year and monthly surveys of five pools from spring to fall in a second year. We measured physical conditions, community composition, and changes in pH and dissolved oxygen during the day and night. We detected strong temporal patterns in pH dynamics. Our measurements indicate that pH modification varies spatially (between tide pools) and temporally (across months). This variation in pH dynamics mirrored changes in dissolved oxygen and was associated with community composition, including both relative abundance and diversity of benthic producers and consumers, whose role differed across the year, particularly at night. These results highlight the importance of the time of year when considering the ways that community composition influences pH conditions in aquatic ecosystems.

Advances of Modified Lignin as Substitute to Develop Lignin-Based Phenol-Formaldehyde Resin Adhesives.

Traditionally, phenols used to prepare phenol-formaldehyde (PF) resin adhesives are obtained from phenolic compounds and various chemicals, which are extracted from petroleum-based raw materials. Lignin, a sustainable phenolic macromolecule in the cell wall of biomass with an aromatic ring and a phenolic hydroxyl group similar to those of phenol, can be an ideal substitute for phenol in PF resin adhesives. However, only a few lignin-based adhesives are produced on a large scale in industry, mainly because of the low activity of lignin. Preparing lignin-based PF resin adhesives with exceptional achievements by modifying lignin instead of phenol is an efficient method to improve the economic benefits and protect the environment. In this review, the latest progress in the preparation of PF resin adhesives via lignin modification, including chemical, physical, and biological modifications, is discussed. In addition, the advantages and disadvantages of different lignin modification methods for adhesives are compared and discussed, and future research directions for the synthesis of lignin-based PF resin adhesives are proposed.

Serotonin transporter (5-HTT) gene network moderates the impact of prenatal maternal adversity on orbitofrontal cortical thickness in middle childhood.

In utero, the developing brain is highly susceptible to the environment. For example, adverse maternal experiences during the prenatal period are associated with outcomes such as altered neurodevelopment and emotion dysregulation. Yet, the underlying biological mechanisms remain unclear. Here, we investigate whether the function of a network of genes co-expressed with the serotonin transporter in the amygdala moderates the impact of prenatal maternal adversity on the structure of the orbitofrontal cortex (OFC) in middle childhood and/or the degree of temperamental inhibition exhibited in toddlerhood. T1-weighted structural MRI scans were acquired from children aged 6-12 years. A cumulative maternal adversity score was used to conceptualize prenatal adversity and a co-expression based polygenic risk score (ePRS) was generated. Behavioural inhibition at 18 months was assessed using the Early Childhood Behaviour Questionnaire (ECBQ). Our results indicate that in the presence of a low functioning serotonin transporter gene network in the amygdala, higher levels of prenatal adversity are associated with greater right OFC thickness at 6-12 years old. The interaction also predicts temperamental inhibition at 18 months. Ultimately, we identified important biological processes and structural modifications that may underlie the link between early adversity and future deviations in cognitive, behavioural, and emotional development.

Vital roles of m5C RNA modification in cancer and immune cell biology.

RNA modification plays an important role in epigenetics at the posttranscriptional level, and 5-methylcytosine (m5C) has attracted increasing attention in recent years due to the improvement in RNA m5C site detection methods. By influencing transcription, transportation and translation, m5C modification of mRNA, tRNA, rRNA, lncRNA and other RNAs has been proven to affect gene expression and metabolism and is associated with a wide range of diseases, including malignant cancers. RNA m5C modifications also substantially impact the tumor microenvironment (TME) by targeting different groups of immune cells, including B cells, T cells, macrophages, granulocytes, NK cells, dendritic cells and mast cells. Alterations in immune cell expression, infiltration and activation are highly linked to tumor malignancy and patient prognosis. This review provides a novel and holistic examination of m5C-mediated cancer development by examining the exact mechanisms underlying the oncogenicity of m5C RNA modification and summarizing the biological effects of m5C RNA modification on tumor cells as well as immune cells. Understanding methylation-related tumorigenesis can provide useful insights for the diagnosis as well as the treatment of cancer.

Extraction, Modification and Biomedical Application of Agarose Hydrogels: A Review

Numerous compounds present in the ocean are contributing to the development of the biomedical field. Agarose, a polysaccharide derived from marine red algae, plays a vital role in biomedical applications because of its reversible temperature-sensitive gelling behavior, excellent mechanical properties, and high biological activity. Natural agarose hydrogel has a single structural composition that prevents it from adapting to complex biological environments. Therefore, agarose can be developed into different forms through physical, biological, and chemical modifications, enabling it to perform optimally in different environments. Agarose biomaterials are being increasingly used for isolation, purification, drug delivery, and tissue engineering, but most are still far from clinical approval. This review classifies and discusses the preparation, modification, and biomedical applications of agarose, focusing on its applications in isolation and purification, wound dressings, drug delivery, tissue engineering, and 3D printing. In addition, it attempts to address the opportunities and challenges associated with the future development of agarose-based biomaterials in the biomedical field. It should help to rationalize the selection of the most suitable functionalized agarose hydrogels for specific applications in the biomedical industry.

Enhanced Chemiluminescence under the Nanoconfinement of Covalent-Organic Frameworks and Its Application in Sensitive Detection of Cancer Biomarkers.

Chemiluminescence (CL) with intensive emission has been pursued for decades. It is still challenging to find a new mechanism to enhance CL. In this work, confinement-enhanced CL was developed for the first time by the coembedding of N-(aminobutyl)-N-(ethylisoluminol) (ABEI) and Co2+ into gold nanoparticle-modified covalent-organic frameworks (COFs). For the consideration of improving the hydrophilicity of COFs and facilitating subsequent biological modification, gold nanoparticles were first reduced on the COF surface (Au-COF) in situ without other reducing reagents. By virtue of the abundant imine bond and π backbones, ABEI and Co2+ were embedded in Au-COF synergistically through π-π stacking and coordination. The confinement of ABEI and Co2+ into Au-COF brought an over 20-fold enhancement of CL intensity compared to that of adding them to a liquid phase, which benefitted from the three aspects of the confinement effect, including the molecular enrichment effect, the physical constraint effect, and the molecular preorganization effect. As proof of concept, a lipid-protein dual-recognition sandwich strategy based on this CL-functionalized COF was developed for the detection of breast cancer cell line-derived extracellular vesicles (EVs) with four orders of magnitude improvement in the detection limit compared to ELISA. The successful distinction of human epidermal growth factor receptor 2 (HER2)-positive patients from HER2-negative patients indicated the great application potential of the proposed bioassay in HER2-positive breast cancer diagnosis. This work proposed a novel enhancement mechanism for CL based on crystalline porous materials, which provides a new perspective for the development of CL-functionalized materials for biosensors and bioassays.

A multi-method approach for the investigation of termite mound structures (Kalahari Basin, Botswana)

Fungus-growing termites (FGT) are important agents in subtropical and semiarid ecosystems for the biological and geological modifications they bring through the construction of their mounds. In order to survive and thrive, the mounds are designed to host the Termitomyces fungus in pre-set conditions of humidity and temperature. The interior structure of FGT mounds has only been scarcely studied in the scientific literature, making knowledge about mound morphology and development incomplete. In this study, a relic FGT mound in northern Botswana was analyzed using a combination of electrical resistivity tomography (ERT), particle size distribution (PSD), X-ray computed microtomography (X-ray micro-CT), and soil micromorphology methods. Specifically, we set out to investigate (i) whether changes in the measured soil resistivities reflect expected changes between the various functional compartments of the mound; (ii) what changes in soil texture and structure are associated with the resistivity variations; and (iii) whether this information can be used to better understand the mound compartments and their development. Our results suggest that ERT may eventually provide an attractive and efficient method to investigate the interior structure of FGT mounds that is non-destructive. The use of ERT does not require to remove the epigeal of the mound. The modifications brought by FGT to the texture and structure of the soil, respective to the function of each mound compartment, can increase resistivity of up to three orders of magnitude. Further, the work presented in this paper helps to (i) identify processes involved in the sediment transfer between the mound and its surroundings, (ii) increases the understanding of mound morphology, and (iii) show that fungus-growing termitaria affect durably savanna landscape. Finally, this study demonstrates that ERT is a pertinent non-destructive method to investigate mound structure.

The human malaria parasite Plasmodium falciparum can sense environmental changes and respond by antigenic switching

The primary antigenic and virulence determinant of the human malaria parasite Plasmodium falciparum is a variant surface protein called PfEMP1. Different forms of PfEMP1 are encoded by a multicopy gene family called var, and switching between active genes enables the parasites to evade the antibody response of their human hosts. var gene switching is key for the maintenance of chronic infections; however, what controls switching is unknown, although it has been suggested to occur at a constant frequency with little or no environmental influence. var gene transcription is controlled epigenetically through the activity of histone methyltransferases (HMTs). Studies in model systems have shown that metabolism and epigenetic control of gene expression are linked through the availability of intracellular S-adenosylmethionine (SAM), the principal methyl donor in biological methylation modifications, which can fluctuate based on nutrient availability. To determine whether environmental conditions and changes in metabolism can influence var gene expression, P. falciparum was cultured in media with altered concentrations of nutrients involved in SAM metabolism. We found that conditions that influence lipid metabolism induce var gene switching, indicating that parasites can respond to changes in their environment by altering var gene expression patterns. Genetic modifications that directly modified expression of the enzymes that control SAM levels similarly led to profound changes in var gene expression, confirming that changes in SAM availability modulate var gene switching. These observations directly challenge the paradigm that antigenic variation in P. falciparum follows an intrinsic, programed switching rate, which operates independently of any external stimuli.

MSFragger-Labile: A Flexible Method to Improve Labile PTM Analysis in Proteomics

Posttranslational modifications of proteins play essential roles in defining and regulating the functions of the proteins they decorate, making identification of these modifications critical to understanding biology and disease. Methods for enriching and analyzing a wide variety of biological and chemical modifications of proteins have been developed using mass spectrometry-based proteomics, largely relying on traditional database search methods to identify the resulting mass spectra of modified peptides. These database search methods treat modifications as static attachments of a mass to particular position in the peptide sequence, but many modifications undergo fragmentation in tandem mass spectrometry experiments alongside, or instead of, the peptide backbone. While this fragmentation can confound traditional search methods, it also offers unique opportunities for improved searches that incorporate modification-specific fragment ions. Here, we present a new labile mode in the MSFragger search engine that provides the flexibility to tailor modification-centric searches to the fragmentation observed. We show that labile mode can dramatically improve spectrum identification rates of phosphopeptides, RNA-crosslinked peptides, and ADP-ribosylated peptides. Each of these modifications presents distinct fragmentation characteristics, showcasing the flexibility of MSFragger labile mode to improve search for a wide variety of biological and chemical modifications.

Marine-Derived Lead Fascaplysin: Pharmacological Activity, Total Synthesis, and Structural Modification.

Fascaplysin is a planar structure pentacyclic alkaloid isolated from sponges, which can effectively induce the apoptosis of cancer cells. In addition, fascaplysin has diverse biological activities, such as antibacterial, anti-tumor, anti-plasmodium, etc. Unfortunately, the planar structure of fascaplysin can be inserted into DNA and such interaction also limits the further application of fascaplysin, necessitating its structural modification. In this review, the biological activity, total synthesis and structural modification of fascaplysin will be summarized, which will provide useful information for pharmaceutical researchers interested in the exploration of marine alkaloids and for the betterment of fascaplysin in particular.

Sleep Deprivation and Insomnia in Adolescence: Implications for Mental Health.

Sleep changes significantly throughout the human lifespan. Physiological modifications in sleep regulation, in common with many mammals (especially in the circadian rhythms), predispose adolescents to sleep loss until early adulthood. Adolescents are one-sixth of all human beings and are at high risk for mental diseases (particularly mood disorders) and self-injury. This has been attributed to the incredible number of changes occurring in a limited time window that encompasses rapid biological and psychosocial modifications, which predispose teens to at-risk behaviors. Adolescents' sleep patterns have been investigated as a biunivocal cause for potential damaging conditions, in which insufficient sleep may be both a cause and a consequence of mental health problems. The recent COVID-19 pandemic in particular has made a detrimental contribution to many adolescents' mental health and sleep quality. In this review, we aim to summarize the knowledge in the field and to explore implications for adolescents' (and future adults') mental and physical health, as well as to outline potential strategies of prevention.

The Potential Use of Exosomes in Anti-Cancer Effect Induced by Polarized Macrophages.

The rapid development of aberrant cells outgrowing their normal bounds, which can subsequently infect other body parts and spread to other organs-a process known as metastasis-is one of the significant characteristics of cancer. The main reason why cancer patients die is because of widespread metastases. This abnormal cell proliferation varies in cancers of over a hundred types, and their response to treatment can vary substantially. Several anti-cancer drugs have been discovered to treat various tumors, yet they still have harmful side-effects. Finding novel, highly efficient targeted therapies based on modifications in the molecular biology of tumor cells is essential to reduce the indiscriminate destruction of healthy cells. Exosomes, an extracellular vesicle, are promising as a drug carrier for cancer therapy due to their good tolerance in the body. In addition, the tumor microenvironment is a potential target to regulate in cancer treatment. Therefore, macrophages are polarized toward M1 and M2 phenotypes, which are involved in cancer proliferation and are malignant. It is evident from recent studies that controlled macrophage polarization might contribute to cancer treatment, by the direct way of using miRNA. This review provides an insight into the potential use of exosomes to develop an 'indirect', more natural, and harmless cancer treatment through regulating macrophage polarization.

Searching and Evaluating Publications and Preprints Using Europe PMC

In the field of life sciences there is a growing need for literature analysis tools that help scientists tackle information overload. Europe PubMed Central (Europe PMC), a partner of PubMed Central (PMC; National Library of Medicine, 2022), is an open access database of over 41 million life science publications and preprints, enriched with supporting data, reviews, protocols, and other relevant resources. Europe PMC is a trusted repository of choice for many life science funders (Europe PMC, 2022a), offering a suite of innovative search tools that allow users to search and evaluate the literature, including finding highly cited articles, preprints with community peer reviews, or papers referencing a proteomics dataset in the figure legend. In addition, Europe PMC utilizes text-mining to help researchers identify key terms and find data and evidence in the literature. First-time users often do not utilize the wealth of tools Europe PMC offers and can feel overwhelmed about how to perform the most effective search. This protocol, describing how to search and evaluate publications and preprints using Europe PMC, demonstrates how to carry out more efficient and effective literature searches using the tools provided by Europe PMC. This includes discovering the latest findings on a research topic, following research from a specific author, journal, or preprint server, exploring literature on a new method, expanding your reading list with relevant articles, as well as accessing and evaluating publications and preprints of interest. © 2023 EMBL-EBI. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Finding articles and preprints on a topic of interest Basic Protocol 2: Accessing an article Basic Protocol 3: Browsing the article Basic Protocol 4: Evaluating the article Basic Protocol 5: Refining search results Basic Protocol 6: Finding research by author Basic Protocol 7: Finding a specific article Basic Protocol 8: Finding information about a methodology Basic Protocol 9: Finding evidence of biological interactions, relations, and modifications Basic Protocol 10: Finding data behind a publication Basic Protocol 11: Expanding a reading list and building a bibliography Basic Protocol 12: Staying on top of the current literature.

Update on Lean Body Mass Diagnostic Assessment in Critical Illness.

Acute critical illnesses can alter vital functions with profound biological, biochemical, metabolic, and functional modifications. Despite etiology, patient's nutritional status is pivotal to guide metabolic support. The assessment of nutritional status remains complex and not completely elucidated. Loss of lean body mass is a clear marker of malnutrition; however, the question of how to investigate it still remains unanswered. Several tools have been implemented to measure lean body mass, including a computed tomography scan, ultrasound, and bioelectrical impedance analysis, although such methods unfortunately require validation. A lack of uniform bedside measurement tools could impact the nutrition outcome. Metabolic assessment, nutritional status, and nutritional risk have a pivotal role in critical care. Therefore, knowledge about the methods used to assess lean body mass in critical illnesses is increasingly required. The aim of the present review is to update the scientific evidence regarding lean body mass diagnostic assessment in critical illness to provide the diagnostic key points for metabolic and nutritional support.

Proteomic Analysis of Female Synovial Fluid to Identify Novel Biomarkers for Osteoarthritis.

Osteoarthritis (OA) is a highly prevalent degenerative joint condition that disproportionately affects females. The pathophysiology of the disease is not well understood, which makes diagnosis and treatment difficult. Given the physical connection of synovial fluid (SF) with articular tissues, the SF's composition can reflect relevant biological modifications, and has therefore been a focus of research. Previously, we demonstrated that extracellular vesicles isolated from the synovial fluid of OA patients carry different cargo (protein and miRNA) in a sex-specific manner. Given the increased prevalence and severity of OA in females, this study aims to identify differential protein content within the synovial fluid of female OA and non-osteoarthritic (non-OA) patients. We found that several proteins were differentially expressed in osteoarthritic females compared with age-matched controls. Presenilin, Coagulation Factor X, Lysine-Specific Demethylase 2B, Tenascin C, Leucine-Rich Repeat-Containing Protein 17 fragments, and T-Complex Protein 1 were negatively regulated in the OA group, with PGD Synthase, Tubulointerstitial Nephritis Antigen, and Nuclear Receptor Binding SET Domain Protein 1 positively regulated in the OA group. Database for Annotation, Visualization, and Integrated Discovery (DAVID) and QuickGO analyses established these proteins as significantly involved in many biological, cellular, and molecular processes. In conclusion, the protein content of female synovial fluid is altered in OA patients, which is likely to provide insights into gender-specific pathophysiology.

Engineered Cancer Cells as Signal Probes for Fluorescence-Assisted Digital Counting Analysis.

Fluorescence-assisted digital counting analysis allowed sensitive quantification of targets by measuring individual fluorescent labels. However, traditional fluorescent labels suffered from low brightness, small size, and sophisticated preparation procedures. Herein, engineering fluorescent dye-stained cancer cells with magnetic nanoparticles were proposed to construct single-cell probes for fluorescence-assisted digital counting analysis by quantifying the target-dependent binding or cleaving events. Various engineering strategies of cancer cells including biological recognition and chemical modification were developed for rationally designing single-cell probes. Introduction of suitable recognition elements into single-cell probes allowed digital quantification of each target-dependent event via counting the colored single-cell probes in the representative image taken using a confocal microscope. The reliability of the proposed digital counting strategy was corroborated by traditional optical microscopy- and flow cytometry-dependent counting technologies. The advantages of single-cell probes, including high brightness, big size, ease of preparation, and magnetic separation, contributed to the sensitive and selective analysis of targets of interest. As proof-to-concept assays, indirect analysis of exonuclease III (Exo III) activity, as well as direct quantitation of cancer cells, were investigated, and the potential in biological sample analysis was also assessed. This sensing strategy will open a new avenue for the development of biosensors.

Understanding the Epitranscriptome for Avant-Garde Brain Tumour Diagnostics.

RNA modifications are diverse, dynamic, and reversible transcript alterations rapidly gaining attention due to their newly defined RNA regulatory roles in cellular pathways and pathogenic mechanisms. The exciting emerging field of 'epitranscriptomics' is predominantly centred on studying the most abundant mRNA modification, N6-methyladenine (m6A). The m6A mark, similar to many other RNA modifications, is strictly regulated by so-called 'writer', 'reader', and 'eraser' protein species. The abundance of genes coding for the expression of these regulator proteins and m6A levels shows great potential as diagnostic and predictive tools across several cancer fields. This review explores our current understanding of RNA modifications in glioma biology and the potential of epitranscriptomics to develop new diagnostic and predictive classification tools that can stratify these highly complex and heterogeneous brain tumours.

Differential Protein Citrullination in Human ER- and ER+ Tumor and Adjacent Healthy Breast Tissue.

Post-translational modification of arginine to citrulline is catalyzed by members of the peptidylarginine deiminase (PAD) family. Dysregulation of this catalysis is a significant driver of the pathogenesis of numerous inflammatory diseases, including cancer. However, dysregulation of PAD activity has not been examined in breast cancer with respect to hormone receptor status. In this study, we measured PAD enzyme levels using Western blotting and investigated protein citrullination using a mass spectrometry-based proteomics approach in primary estrogen receptor negative (ER-) or positive (ER+) breast tumor and matched adjacent normal tissue. Our findings reveal 72 and 41 citrullinated proteins in ER- tumor and adjacent healthy tissue, respectively, where 20 of these proteins are common between the two groups. We detected 64 and 49 citrullinated proteins in ER+ tumor and adjacent healthy tissue, respectively, where 32 proteins are common. Interestingly, upon comparison of ER- and ER+ tumor tissue, only 32 citrullinated proteins are shared between the two and the rest are unique to the tumor's receptor status. Using the STRING database for protein-protein interaction network analysis, these proteins are involved in protein-folding events (i.e., heat shock proteins) in ER- samples and blood-clotting events (i.e., fibulin) in ER+ samples. Constituents of the extracellular matrix structure (i.e., collagen and fibrinogen) were found in both. Herein, we establish evidence that supports the role of this unique post-translational modification in breast cancer biology. Finally, to aid drug discovery against citrullination, we developed a liquid chromatography-ultraviolet method to measure PAD enzymatic activity and optimized glucagon-like peptide II to quantitatively measure the ability of PADs to citrullinate its substrate.

Highly Sensitive Magnetoelastic Biosensor for Alpha2-Macroglobulin Detection Based on MnFe2O4@chitosan/MWCNTs/PDMS Composite

The need for Alpha2-Macroglobulin (α2-M) detection has increased because it plays an important role in the diagnosis of diabetic nephropathy (DN). However, few sensors can realize the high-sensitive detection for α2-M with characteristics of being fast, flexible, wearable and portable. Herein, a biosensor based on a MnFe2O4@chitosan/MWCNTs/PDMS composite film was developed for α2-M detection. Due to the excellent magnetoelastic effect of MnFe2O4 nanoparticles, the stress signal of the biosensor surface induced by the specific antibody-antigen binding was transformed into the electrical and magnetic signal. Chitosan-coated MnFe2O4 particles were used to provide biological modification sites for the α2-M antibody, which simplified the conventional biological functionalization modification process. The MnFe2O4@chitosan particles were successfully prepared by a chemical coprecipitation method and the property was studied by TEM, FT-IR and XRD. MWCNTs were employed to enhance electrical conductivity and the sensitivity of the biosensor. The detection limit (LOD) was reduced to 0.1299 ng·mL-1 in the linear range from 10 ng∙mL-1 to 100 µg·mL-1, which was significantly lower than the limit of health diagnostics. The biosensor is fabricated by a simple method, with advantages of being rapid and highly-sensitive, and having selective detection of α2-M, which provides a novel method for the early diagnosis of DN, and it has potential in the point of care (PoC) field.

Post-COVID-19 syndrome: Insights into a novel post-infectious systemic disorder

Coronavirus disease 2019 (COVID-19) is currently considered a complex systemic infectious and inflammatory disease, determined by the infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and the cause of one of the most important epidemiological phenomena in the last century - the COVID-19 pandemic. This infectious-inflammatory disease may generate a wide range of clinical manifestations and biological modifications, explained by the ubiquitous nature of the SARS-CoV-2 receptors, represented by the angiotensin-converting enzyme-2 (ACE-2), and by the host's violent immune and proinflammatory reaction to the viral infection. These manifestations include immunological disturbances, which, according to certain clinical findings, may persist post-infection, in the form of a presumed systemic inflammatory entity, defined by several clinical concepts with a common pathological significance: post-COVID-19 multisystem (or systemic) inflammatory syndrome, post-COVID syndrome or long-COVID. Although the pathophysiological mechanisms of the post-COVID-19 syndrome are elusive at the present moment, there are currently several studies that describe a systemic inflammatory or autoimmune phenomenon following the remission of the COVID-19 infection in some patients, which suggests the existence of molecular and cellular immune abnormalities, most probably due to the host's initial violent immune response to the viral infection, in the form of three overlapping entities: secondary hemophagocytic lymph histiocytosis (HLH), macrophage activation syndrome (MAS) and cytokine release syndrome (CRS). Thus, this is reminiscent of different classic autoimmune diseases, in which various infections are risk factors in developing the autoimmune process.