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Marine-derived Bioactive Compounds: A Promising Frontier against Multidrug-resistant Microbial Infections.

The global escalation of Multidrug-Resistant (MDR) bacterial infections poses a serious and growing threat to public health, contributing to increased morbidity, mortality, and substantial economic burden worldwide. The widespread and often indiscriminate use of antibiotics in clinical and agricultural settings has accelerated the emergence of resistance, significantly diminishing the efficacy of conventional antimicrobial therapies. This pressing challenge necessitates the exploration of alternative sources for novel antibiotics. Marine ecosystems-renowned for their immense biodiversity and ecological complexity-have gained attention as a rich and largely untapped reservoir of bioactive natural products with potent antimicrobial activity. Marine organisms, such as sponges, tunicates, algae, and bacteria and fungi derived from marine sources, produce structurally diverse and pharmacologically active metabolites, including peptides, polyketides, alkaloids, terpenoids, sterols, lactones, and halogenated compounds. Many of these marine-derived molecules possess unique chemical scaffolds and novel mechanisms of action, offering the potential to circumvent existing resistance pathways. Some compounds have shown promising activity against MDR pathogens, including Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii. However, challenges such as low natural abundance, difficulty in cultivation, and structural complexity have limited their clinical translation. Recent advancements in marine biotechnology, genomics, metagenomics, and synthetic biology have opened new avenues for the discovery, biosynthesis, and structural optimization of these compounds. These innovative approaches not only facilitate sustainable production but also enhance the pharmacological properties.

Humans

Conformational and structural modulation of the NH2-terminal regions of fibrinogen and fibrin associated with plasmin cleavage.

Conformational and structural modulations of the NH2-terminal region of fibrinogen and fibrin associated with plasmin cleavage have been examined utilizing specific antibody probes. The E region derived from the NH2-terminal aspects of fibrinogen undergoes complex structural and conformational changes throughout the cleavage process as indicated by differences in the quantitative and qualitative expression of antigenic determinants by the E region of each isolated cleavage fragment. When the range of antigenic determinants recognized by the antibody probe is limited to a specific molecular marker on the gamma chain within the E region, fg-E-neo, evidence for a systematic and progressive modulation of this site during plasmin cleavage is observed. Fg-E-neo undergoes progressive exposure as the cleavage of fibrinogen proceeds from X to Y to D:E complex. Separation of the D:E complex into its constituent, D and E fragments, is associated with further exposure of fg-E-neo determinants. The sequential cleavage of fibrin by plasmin also leads to progressive exposure of the fg-E-neo site; however, comparison of corresponding fragments derived from fibrinogen and fibrin reveals significant differences in the character of fg-E-neo expression. Immunochemical differences between fibrin and fibrinogen E fragments are not abolished by further exposure of the fragments to plasmin, are apparently not due to the presence or absence of fibrinopeptides, and are maintained following denaturation and renaturation of the fragments. These results suggest that the differential expression of fg-E-neo by the E fragments may be primarily dependent upon differences in amino acid compositions of the fragments.

Antigen-Antibody Reactions

Chemistry of heparitin sulfate and heparin from normal tissues and from patients with Hunter syndrome.

Some structural features of heparitin sulfate excreted by patients with Hunter syndrome are described. It is shown, with the aid of heparitinases and heparinase from Flavobacterium heparinum, that the Hunter heparitin sulfate is a very complex structure composed of nine different disaccharide units containing regions akin to normal heparitin sulfate and regions akin the heparin. Two-thirds of the iduronic acid residues of Hunter heparitin sulfate are devoid of sulfate, contrasting with heparin in which most of the iduronic acid residues are sulfated. The isolation and characterization of the non-reducing ends of heparin and of the heparitin sulfates is also described. Based on these results the specificity of the heparinase and heparitinases as well as the biosynthesis of iduronic acid-containing heparin-like compounds is discussed.

Chemical Phenomena

The structure and formation of the egg-shell of Syphacia obvelata Rudolphi (Nematoda: Oxyurida).

The egg of Syphacia obvelata is a flattened elipsoid. The egg-shell consists of 5 layers: external uterine layer, internal uterine layer, vitelline layer, chitinous layer and lipid layer. An operculum is present at one pole of the egg. The opercular groove consists of a break in the uterine layers and the modification of the chitinous layer by the deposition of lipoprotein material. On the curved side of the egg the uterine layers are modified to form alternate ridges and depressions. Discrete spaces are present in the internal uterine layer between the ridges. These are open to the exterior via pores in the external uterine layer. The structure of the uterine layers is quite different on the flattened side of the egg. The morphology of the reproductive system and the formation of the egg-shell is described. It is suggested that the complex structure of the uterine layers of oxyurids forms by a self-assembly process.

Animals

Putative rhamnogalacturonan-II glycosyltransferase identified through callus gene editing which bypasses embryo lethality.

Rhamnogalacturonan II (RG-II) is a structurally complex and conserved domain of the pectin present in the primary cell walls of vascular plants. Borate cross-linking of RG-II is required for plants to grow and develop normally. Mutations that alter RG-II structure also affect cross-linking and are lethal or severely impair growth. Thus, few genes involved in RG-II synthesis have been identified. Here, we developed a method to generate viable loss-of-function Arabidopsis (Arabidopsis thaliana) mutants in callus tissue via CRISPR/Cas9-mediated gene editing. We combined this with a candidate gene approach to characterize the male gametophyte defective 2 (MGP2) gene that encodes a putative family GT29 glycosyltransferase. Plants homozygous for this mutation do not survive. We showed that in the callus mutant cell walls, RG-II does not cross-link normally because it lacks 3-deoxy-D-manno-octulosonic acid (Kdo) and thus cannot form the α-L-Rhap-(1→5)-α-D-kdop-(1→sidechain). We suggest that MGP2 encodes an inverting RG-II CMP-β-Kdo transferase (RCKT1). Our discovery provides further insight into the role of sidechains in RG-II dimerization. Our method also provides a viable strategy for further identifying proteins involved in the biosynthesis of RG-II.

Arabidopsis

Renal neoplastic response to leukosis virus strains BAI A (avian myeloblastosis virus) and MC29.

Previous reports described the induction of avian renal neoplasms by leukosis virus strains BAI A [avian myeloblastosis virus (AMV)] and MC29, and illustrated morphological characteristics of the tumors. Continued studies in this work confirm evidence of the origin of the tumors from embryonal cells residual in the posthatched chick. The work further emphasizes differences in histopathology of the neoplasms caused by the two viruses and reveals differences in the histopathogenesis of the respective growths. Embryonal rests may consist of two types of cells, those of epithelial characteristics and a second element of differentiation between nephroblastema (mesenchyme) and epithelium and designated here as nephromesoblastoma. Infection by AMV induces tumors of epithelial characteristics and, in addition, derivatives of nephromesoblastoma consisting of cartilage, bone, areas of keratinization, and sarcoma. Keratinized structures in the nephroblastoma originate from nephromesoblastoma. In contrast, MC29 virus induces only epithelial growths representing principally aberrant and malformed glomerular and tubular structures with occasional cartilage derived from epithelial cells. MC29 tumors are completely lacking in nephromesoblastoma tissue and contain no bone, sarcoma, or keratinized formations. In MC29 tumors, occasional cartilage was derived from epithelium. Tumors caused by AMV exhibit the complex structure of nephroblastoma with all of the features of the growth in humans (Wilms' tumor). The neoplasms induced by both AMV and MC29 exhibit marked aberration, distortion, and malformation in the differentiation of the cells growing out from the embryonal rests representing rare manifestations of cell genetic influence inherent in the primordial growth of nephroblastema. The results thus illustrate fundamental differences in cellular composition and capacity to respond to etiologically different leukosis viruses.

Adenocarcinoma

The genetic system of kinetoplasts in trypanosomatides.

In the present report, the genetic system of Crithidia oncopelti kinetoplast is used as a model for investigation of kinetoplast DNA (kDNA) structure, its transcription, protein synthesizing apparatus of the kinetoplast and the protein synthesis controlled genetically by kDNA. It was shown that kDNA of C. oncopelti can be isolated from cells or from kinetoplast fraction in the form of a network complex structure consisting of a lot of circular molecules. These minicircles have a contour length of about 0.83 micronm and molecular weight of 1.6 X 10(6). The kDNA was demonstrated to be of higher AT content type than nuclear DNA. Besides, kDNA is characterized by a lesser degree of clustering of pyrimidines as compared with the nuclear one. The isolated kinetoplasts of C. oncopelti were shown to exhibit activity of DNA dependent RNA polymerase. The effect of some antibiotics and intercalating substances on RNA synthesis in kinetoplasts and mitochondria appears to be identical. Kinetoplasts of C. oncopelti have their own protein synthesizing system, whose components (ribosomes, rRNA, proteins, factors of incorporation) differ from those of the cytoplasm. Inhibition of translation by some antibiotics and of transcription by acriflavin allowed the suggestion that several proteins of kinetoplast ribosomes may be synthesized within this organoid. It was shown then that kDNA may be involved in the formation of the protein synthesizing apparatus in the kinetoplast.

Animals

Ultrastructure of the collagen fibril. I. Some features of the structure of the collagen fibril.

In the human ovary, thyroid gland and in the rat tail tendon the plasma membrane of fibroblasts may "disappear" or "dissolve", leading to a direct contact of the cytoplasm with extracellular space. Extracellular filaments and collagen fibrils may grow directly out of the cytoplasm and from extracellular vesicles and cellular remnants. The filaments are complex structures composed of 3 to 5 subfilaments. Adjacent collagen fibrils are connected with interfibrillar bridges. In the rat tail tendon 2 different types and opposite orientated fibrils are found. After enzymatic treatment it becomes clear that the collagen fibril has a tridimensional organization and is composed of filaments and amorphous cementing matrix. The matrix is easily affected by various enzymes and washed away, revealing thus the inner spiral structure of the fibril.

Adolescent

Is the cytoskeleton-plasma membrane complex involved in lens protein biosynthesis?

Calf lens fiber cells contain a population of polyribosomes that direct, at least in vitro, the synthesis of a specific plasma membrane protein MP26. This protein may serve as a marker in terminal differentiation, since it is absent in the lens epithelium but appears in lens fiber plasma membranes. The MP26 manufacturing polyribosomes are found to be associated with a structural complex in which also the cytoskeleton and plasma membranes participate. They can be released from the complex by treatment with DNAse I. This result presumably reflects the involvement of actin in the linkage of the MP26 synthesizing polyribosomes to the cytoskeleton-membrane complex.

Animals

Microanatomy of the human amniotic membranes. A light microscopic, transmission, and scanning electron microscopic study.

The human amnion was examined by means of light microscopy and scanning and transmission electron microscopy. The surface shows apart from microvilli a particular structure, called "blebs"; the intercellular junction is formed by desmosomes and a labyrinthine channel system, and at the base pedicels extend into the basement membrane. Cell shedding uncovers the basement membrane which seems to play a primordial role in preserving the intact amniotic cavity. These data underline the complex structure and the multiple role the amnion performs during gestation.

Amnion

[Chromatin fibril. Structure and relationship to the nuclear membrane].

Literature for the recent years on chromatin fibrilla structure is reviewed in the work. Ultrastructural and molecular organization of the elementary chromatin subunits--nucleosomes, discovered in 1974 is discussed and their relation to other discrete chromatin particles is analyzed. The author represents his own data on electron microscopic studies of the cell nucleus after certain experimental effect demonstrating a complex structure of chromatin particles. The scheme of chromatin fibrilla structure is given; morphologic and functional aspects of its connection with the nuclear membrane are considered.

Animals

From glycosylation to inflammation: insights from NMR-Derived GlycA and GlycB.

Post-translational modifications (PTMs) play a crucial role in increasing proteomic diversity. N-linked glycosylation acts as a key regulatory layer that influences protein stability, trafficking, circulation, and immune responses. Unlike conventional inflammatory biomarkers that measure individual proteins, nuclear magnetic resonance (NMR) spectroscopy identifies the combined signals GlycA and GlycB from glycoproteins, offering an overall view of systemic glycoprotein changes. These signals represent the N-glycosylation patterns of several abundant acute-phase proteins (APPs), giving detailed molecular insights. This review offers a detailed assessment of GlycA and GlycB as mechanistically grounded indicators of liver glycoprotein remodeling and systemic inflammation. GlycA mainly indicates the levels and structural complexity of N-acetylglucosamine (GlcNAc) and N-acetylgalactosamine (GalNAc) residues linked to acute-phase glycoproteins and glycan branching. In contrast, GlycB reflects changes in terminal sialylation, which influences glycoprotein half-life, immune recognition via lectins, and inflammatory signaling. Collectively, these biomarkers combine measurements of hepatic APP production with variations in glycan structure, offering mechanistically anchored reporters of hepatic glycoprotein remodeling. We explore the enzymatic pathways responsible for N-glycan branching, fucosylation, and sialylation, as well as the roles of major APP scaffolds in the GlycA and GlycB resonances. We also highlight the emerging clinical significance of these signals across infectious, autoimmune, cardiovascular, metabolic, neurodegenerative, and cancer-related diseases. Rather than serving simply as markers of inflammation, GlycA and GlycB provide mechanistically interpretable readouts of cytokine-driven hepatic glycoprotein remodeling and systemic immune activation, supporting their application in disease risk stratification, longitudinal monitoring, therapeutic response assessment, and precision medicine.

GlycA

Structure of the D-mannan and D-arabino-D-galactan in Crithidia fasciculata: changes in proportion with age of culture.

Cells of the insect flagellate Crithidia fasciculata contained mannan and arabinogalactan components, whose porportion varied with culture age, the former predominating during early stages, and the latter during the later stages of exponential growth and the deceleration phase. The mannan was a beta-D-(1 leads to 2)-linked D-mannopyranan. The arabinogalactan had a complex structure containing, in part, a beta-D-(1 leads to 3)-linked galactopyranose main-chain substituted in the 2 positions by single-unit D-arabinopyranose side-chains and with some unsubstituted units.

Animals

CS Ratio is an immune-related prognostic biomarker for cervical cancer.

BACKGROUND: The tumor microenvironment (TME) plays a crucial role in cancer progression but its complex structure significant variability among patients present considerable challenges for research. Recent studies have demonstrated that macrophage polarization states defined by the expression levels of CXCL9 SPP1 (CS Ratio) are more prognostically relevant than traditional M1/M2 markers. The CS polarization state reflects a highly coordinated network of pro-tumor anti-tumor variables offering a simplified yet effective immune response indicator for the complex TME. The CS Ratio has been shown to correlate with the abundance of anti-tumor immune cells the gene expression programs of tumor-infiltrating cells responses to immunotherapy. Cervical cancer, one of the most common gynecological malignancies, still faces limited therapeutic options. CXCL9, a member of the CXC chemokine family, plays a critical role in immune regulation, inflammation, tumor growth, angiogenesis, and metastasis. Similarly, SPP1, a cytokine, influences immune-related pathways by regulating molecules such as interferon-&#x3b3; and interleukin-12. However, no studies have systematically investigated the role of the CS Ratio in cervical cancer or its relationship with immunotherapy characteristics. Research in this area could provide critical insights into the role and clinical potential of the CS Ratio in cervical cancer and related tumors. METHODS: The expression ratio of CXCL9 to SPP1 was analyzed in cervical cancer patients using data from the Gene Expression Omnibus (GEO) database, which revealed significant differences. Data for cervical cancer patients were obtained from The Cancer Genome Atlas (TCGA) database. The optimal cutoff value for the CS Ratio was determined using the maxstat package in R, and Kaplan-Meier (KM) survival curves were constructed. Patients were categorized into High and Low groups based on the median CS Ratio. Immune scores were analyzed, and immune cell infiltration was assessed using CIBERSORT. Differences in the CS Ratio were evaluated across patients with varying pathological T stages and FIGO stages. Additionally, receiver operating characteristic (ROC) analysis was performed using the pROC package in R to calculate the area under the curve (AUC). Univariate and multivariate Cox regression analyses were performed to evaluate the potential of the CS Ratio as an independent prognostic factor in cervical cancer. A Cox regression-based nomogram integrating four key features was subsequently developed for the TCGA-CESC cohort. Nomogram performance was assessed using calibration curves and ROC analysis. RESULTS: The CS Ratio was significantly lower in cervical cancer patients compared to normal controls (P < 0.05). KM survival curves indicated that patients in the CS High group exhibited better prognoses. Immune score analysis revealed significantly higher immune scores (P < 0.05) and lower tumor purity (P < 0.05)in the CS High group compared to the Low group. CIBERSORT analysis revealed significantly higher proportions of CD8+ T cells (P < 0.05) and M1 macrophages (P < 0.05), and a significantly lower proportion of M2 macrophages (P < 0.05), in the CS High group compared to the Low group. The CS Ratio significantly decreased with advancing FIGO stage (P < 0.05). Both univariate (P < 0.05) and multivariate Cox regression analyses (P < 0.05) confirmed the CS Ratio as an independent prognostic factor. ROC analysis demonstrated that the CS Ratio had higher AUC values for predicting 1-year (AUC=0.69), 3-year (AUC=0.66), and 5-year OS (AUC=0.68) than CXCL9 or SPP1 alone. The Cox regression-based nomogram integrating four key features demonstrated predictive capability for 1-, 3-, and 5-year OS in CESC patients (Concordance Index = 0.751; 95% CI: 0.678-0.824; p = 1.50&#xcd;10-11). Significant survival differences were observed between the high-risk and low-risk groups based on the nomogram score. ROC analysis yielded high AUC values for survival prediction: 0.85 (95% CI: 0.94-0.75) at 1-year, 0.74 (95% CI:0.84-0.64) at 3-year, and 0.72 (95% CI:0.84-0.61) at 5-year. CONCLUSION: The CS Ratio may serve as a more effective prognostic biomarker for cervical cancer patients.

CXCL9

PangyPlot: multi-scale interactive visualization of pangenome variation graphs.

SUMMARY: Pangenome variation graphs integrate multiple samples into a unified representation, mitigating the reference bias inherent to linear genomes. However, these graphs can be large and structurally complex. Existing visualization tools are each confined to a fixed scale of resolution, requiring researchers to switch between multiple tools to examine variation at different levels of detail. PangyPlot is an interactive pangenome browser designed for multi-scale exploration of reference variation graphs from full chromosome to nucleotide-level sequence segments. PangyPlot anchors navigation to linear reference coordinates, organizes variation into hierarchical bubble structures, and uses a force-directed layout engine for automatic node arrangement. AVAILABILITY AND IMPLEMENTATION: An instance preloaded with data is available at https://pangyplot.research.sickkids.ca. Source code and documentation are openly available at https://github.com/strug-hub/pangyplot under the MIT License.

Software

[Characteristics of phages of spore-forming bacteria isolated from the soil].

Phages lyzing spore forming bacteria were isolated from soil, and their biological properties and fine structure were studied. The spectrum of lytic activity was determined as well as parameters of the intracellular phage growth. The burst size of the phage varies from 8 to 725 particles per infected cell, the latent period lasts 25-100 min for various phages. According to the data of electron microscopy, the phages are divided into three morphological groups. The phages Tg7, AR13 and BPP10 have a complex structure.

Bacillus subtilis

Quantitative comparison of the amygdala in insectivores and primates.

Comparative architectonic studies have resulted in a classification of the amygdaloid complex which differs somewhat from the commonly used classification (first proposed by Humphrey, 1936) by separating the cortical amygdaloid nucleus from the centromedial group and assigning it to the basolateral group, which then forms a cortico-basolateral group. The size changes of these groups and of the nucleus of the lateral olfactory tract (belonging to the centromedial group) and the large-celled part of the basal nucleus (belonging to the corticobasolateral group) have been investigated in representatives of an ascending primate scale. In all structural complexes investigated so far, the small-celled part of the cortico-basolateral group is the most progressive. In descending order of progression there follow: the corticobasolateral group as a whole, the amygdala as a whole, and the large-celled basal nucleus. No clear changes were found in the centromedial group as a whole, whereas the size of the nucleus of the lateral olfactory tract, which represents a small component of this latter group, shows a strong reduction. These differences in the developmental trends point to increasing or decreasing capacities of the functional (limbic and olfactory) systems, to which these structures are related.

Amygdala

Integrating structure and experimental data annotations with computational modeling framework for predicting micro-nanoplastics toxicities.

The wide use of plastic materials leads to increased emissions of micro-nanoplastics (MNPs) into the environment, raising significant concerns about their impact on human health. Traditional experimental approaches for assessing MNPs toxicity are costly, time-consuming, and there are no experimental protocols that are universally acceptable. Computational modeling using machine learning (ML) approaches provides an efficient alternative to MNP toxicity assessment. However, most modeling studies of MNPs are limited due to the lack of high-quality data and there are few previous modeling studies considering complex structures of MNPs for model training. To address this challenge, we constructed three MNP datasets with popular toxicity endpoints from various resources and used nanostructure annotation techniques to create virtual MNPs (vMNPs) for all MNP structures. The MNP structures were digitalized from annotated vMNPs, and geometrical descriptors were calculated using the Delaunay Tessellation approach. Moreover, important experimental information, such as concentrations and cell lines, were transformed into extra training variables. Partial least squares regression (PLSR) models were built using both experimental and geometrical descriptors and validated through a leave-one-out cross validation procedure. The resulting models showed reasonable performance in predicting toxicity potentials of MNPs for the three endpoints in the present datasets. Moreover, an additional library of vMNPs with their predicted properties and bioactivities was constructed, directing further research of new MNPs. This study provides three novel ML models for MNPs by integrating geometrical and experimental descriptors, which have the potential to assess new MNPs for their toxicity. The modeling strategy developed in this study can be easily expanded to model other MNP toxicity endpoints and create promising new models for MNP toxicity assessments.

Data annotation