Comprehensive encoding of conformational and compositional protein structural ensembles through the mmCIF data structure.

In the folded state, biomolecules exchange between multiple conformational states crucial for their function. However, most structural models derived from experiments and computational predictions only encode a single state. To represent biomolecules accurately, we must move towards modeling and predicting structural ensembles. Information about structural ensembles exists within experimental data from X-ray crystallography and cryo-electron microscopy. Although new tools are available to detect conformational and compositional heterogeneity within these ensembles, the legacy PDB data structure does not robustly encapsulate this complexity. We propose modifications to the macromolecular crystallographic information file (mmCIF) to improve the representation and interrelation of conformational and compositional heterogeneity. These modifications will enable the capture of macromolecular ensembles in a human and machine-interpretable way, potentially catalyzing breakthroughs for ensemble-function predictions, analogous to the achievements of AlphaFold with single-structure prediction.

What are the different biomolecules involved in the selective recovery of REEs from mining wastewater using FeNPs synthesized from two plant extracts?

Extracting rare earth elements (REEs) from wastewater is crucial for saving the environment, sustainable use of natural resources and economic growth. Reported here is a simple, low cost and one-step synthesis of Fe nanoparticles (FeNPs) based on two plant extracts having the ability to recover REEs. The synthesis of FeNPs using Excoecaria cochinchinensis leaves extract (Ec-FeNPs) exhibited high selectivity for heavy rare earth due to unique biomolecules, achieving separation coefficients (Kd) of 3.16 × 103-4.04 × 106 mL/g and recovery efficiencies ranging from 71.7 to 100 %. Conversely, the synthesis of FeNPs using Pinus massoniana lamb extract (PML-FeNPs) revealed poorer REE recovery efficiencies of 7.2-86.7 %. To understand the differences between Ec-FeNPs and PML-FeNPs in terms of selectivity and efficiency, LC-QTOF-MS served to analyze the biomolecules differences of two plant extracts. In addition, various types of characterization were carried out to identify the different functional groups encapsulated on the surface of FeNPs. These results reveal the source of the difference in the selectivity of Ec-FeNPs and PML-FeNPs for REEs. Furthermore, during DFT calculations, it was found that biomolecules with varying affinities for the surface of FeNPs interact with each other, leading to the formation of structures that exhibit high reactivity towards REEs. Finally, incorporating Spearman correlation analysis demonstrates that the selective removal efficiency of REEs was closely linked to surface complexation, ion exchange, and electrostatic adsorption. Consequently, this work strongly highlights the potential for the practical application of novel adsorbents in this field.

Peptide Nucleic Acids: From Origami to Editing.

Peptide nucleic acids (PNAs) combine the programmability of native nucleic acids with the robustness and ease of synthesis of a peptide backbone. These designer biomolecules have demonstrated tremendous utility across a broad range of applications, from the formation of bespoke biosupramolecular architectures to biosensing and gene regulation. Herein, we explore some of the key developments in the application of PNA in chemical biology and biotechnology in the last 5 years and present anticipated key areas of future development.

Superlarge, Rigidified DNA Tetrahedron with a Y-Shaped Backbone for Organizing Biomolecules Spatially and Maintaining Their Full Bioactivity.

A major impediment to the clinical translation of DNA tiling nanostructures is a technical bottleneck for the programmable assembly of DNA architectures with well-defined local geometry due to the inability to achieve both sufficient structural rigidity and a large framework. In this work, a Y-backbone was inserted into each face to construct a superlarge, sufficiently rigidified tetrahedral DNA nanostructure (called RDT) with extremely high efficiency. In RDT, the spatial size increased by 6.86-fold, and the structural rigidity was enhanced at least 4-fold, contributing to an ∼350-fold improvement in the resistance to nucleolytic degradation even without a protective coating. RDT can be mounted onto an artificial lipid-bilayer membrane with molecular-level precision and well-defined spatial orientation that can be validated using the fluorescence resonance energy transfer (FRET) assay. The spatial orientation of Y-shaped backbone-rigidified RDT is unachievable for conventional DNA polyhedrons and ensures a high level of precision in the geometric positioning of diverse biomolecules with an approximately homogeneous environment. In tests of RDT, surface-confined horseradish peroxidase (HRP) exhibited nearly 100% catalytic activity and targeting aptamer-immobilized gold nanoparticles showed 5.3-fold enhanced cellular internalization. Significantly, RDT exhibited a 27.5-fold enhanced structural stability in a bodily environment and did not induce detectable systemic toxicity.

Germination and biological adaptation approaches as salt-stress tolerance process in selected paddy cultivars under salinity stress.

Cultivating productive paddy crops on salty soil to maximise production is a challenging approach to meeting the world's growing food demand. Thus, determining salinity tolerance rates in specific paddy cultivars is urgently needed. In this study, the salt tolerance traits of selected paddy cultivars, ADT45 and ADT39, were investigated by analysing germination, metabolites (pigments and biomolecules), and enzymatic (Superoxide dismutase (SOD), Catalase (CAT), and Peroxidase (POD) adaptation strategies as salt-stress tolerance mechanisms. This study found that salinity-induced reactive oxygen species (ROS) were efficiently detoxified by the antioxidant enzymes Superoxide dismutase (SOD), Catalase (CAT), and Peroxidase (POD) in ADT45 paddy varieties, followed by ADT39. Salinity stress had a significant impact on pigments and essential biomolecules in ADT45 and ADT39 paddy cultivars, including total chlorophyll, anthocyanin, carotenoids, ascorbic acid, hydrogen peroxide (H2O2), malondialdehyde, and proline. ADT45 demonstrated a significant relationship between H2O2 and antioxidant enzyme levels, followed by ADT39 paddy but not IR64. Morphological, physiological, and biochemical analyses revealed that ADT45, followed by ADT39, is a potential salt-tolerant rice cultivar.

Atg45 is an autophagy receptor for glycogen, a non-preferred cargo of bulk autophagy in yeast.

The mechanisms governing autophagy of proteins and organelles have been well studied, but how other cytoplasmic components such as RNA and polysaccharides are degraded remains largely unknown. In this study, we examine autophagy of glycogen, a storage form of glucose. We find that cells accumulate glycogen in the cytoplasm during nitrogen starvation and that this carbohydrate is rarely observed within autophagosomes and autophagic bodies. However, sequestration of glycogen by autophagy is observed following prolonged nitrogen starvation. We identify a yet-uncharacterized open reading frame, Yil024c (herein Atg45), as encoding a cytosolic receptor protein that mediates autophagy of glycogen (glycophagy). Furthermore, we show that, during sporulation, Atg45 is highly expressed and is associated with an increase in glycophagy. Our results suggest that cells regulate glycophagic activity by controlling the expression level of Atg45.

The dynamic duo: cryo-EM teams up with machine learning to visualize biomolecules in motion.

Cryo-EM has been a key technique in our understanding of biomolecular structures. Now, machine learning techniques are being used to put these structures in motion, revealing dynamic interactions and processes happening on a molecular and cellular level.[Formula: see text].

Applications of Raman spectroscopy in ocular biofluid detection.

Ophthalmic and many systemic diseases may damage the eyes, resulting in changes in the composition and content of biomolecules in ocular biofluids such as aqueous humor and tear. Therefore, the biomolecules in biofluids are potential biomarkers to reveal pathological processes and diagnose diseases. Raman spectroscopy is a non-invasive, label-free, and cost-effective technique to provide chemical bond information of biomolecules and shows great potential in the detection of ocular biofluids. This review demonstrates the applications of Raman spectroscopy technology in detecting biochemical components in aqueous humor and tear, then summarizes the current problems encountered for clinical applications of Raman spectroscopy and looks forward to possible approaches to overcome technical bottlenecks. This work may provide a reference for wider applications of Raman spectroscopy in biofluid detection and inspire new ideas for the diagnosis of diseases using ocular biofluids.

Cell-penetrating peptides for sustainable agriculture.

Cell-penetrating peptides (CPPs) are short (typically 5-30 amino acids), cationic, amphipathic, or hydrophobic peptides that facilitate the cellular uptake of diverse cargo molecules by eukaryotic cells via direct translocation or endocytosis across the plasma membrane. CPPs can deliver a variety of bioactive cargos, including proteins, peptides, nucleic acids, and small molecules into the cell. Once inside, the delivered cargo may function in the cytosol, nucleus, or other subcellular compartments. Numerous CPPs have been used for studies and drug delivery in mammalian systems. Although CPPs have many potential uses in plant research and agriculture, the application of CPPs in plants remains limited. Here we review the structures and mechanisms of CPPs and highlight their potential applications for sustainable agriculture.

Studying Structure and Functions of Nucleosomes with Atomic Force Microscopy.

Chromatin is an epigenetic platform for implementation of DNA-dependent processes. Nucleosome, as a basic level of chromatin compaction, largely determines its properties and structure. In the study of nucleosomes structure and functions physicochemical tools are actively used, such as magnetic and optical "tweezers", "DNA curtains", nuclear magnetic resonance, X-ray crystallography, and cryogenic electron microscopy, as well as optical methods based on Förster resonance energy transfer. Despite the fact that these approaches make it possible to determine a wide range of structural and functional characteristics of chromatin and nucleosomes with high spatial and time resolution, atomic force microscopy (AFM) complements the capabilities of these methods. The results of structural studies of nucleosome focusing on the AFM method development are presented in this review. The possibilities of AFM are considered in the context of application of other physicochemical approaches.

Use of natural peptide TP4 as a food preservative prevents contamination by fungal pathogens.

Molecules of natural origin often possess useful biological activities. For instance, the natural peptide Tilapia Piscidin 4 (TP4) exhibits potent antimicrobial activity against a broad spectrum of pathogens. In this study, we explored the potential application of TP4 as a food preservative, asking whether it can prevent spoilage due to microbial contamination. A preliminary in silico analysis indicated that TP4 should interact strongly with fungal cell membrane components. Hence, we tested the activity of TP4 toward Candida albicans within fruit juice and found that the addition of TP4 could abolish fungal growth. We further determined that the peptide acts via a membranolytic mechanism and displays concentration-dependent killing efficiency. In addition, we showed that TP4 inhibited growth of Rhizopus oryzae in whole fruit (tomato) samples. Based on these findings, we conclude that TP4 should be further evaluated as a potentially safe and green solution to prevent food spoilage.

Macromolecule-Nanoparticle-Based Hybrid Materials for Biosensor Applications.

Biosensors function as sophisticated devices, converting biochemical reactions into electrical signals. Contemporary emphasis on developing biosensor devices with refined sensitivity and selectivity is critical due to their extensive functional capabilities. However, a significant challenge lies in the binding affinity of biosensors to biomolecules, requiring adept conversion and amplification of interactions into various signal modalities like electrical, optical, gravimetric, and electrochemical outputs. Overcoming challenges associated with sensitivity, detection limits, response time, reproducibility, and stability is essential for efficient biosensor creation. The central aspect of the fabrication of any biosensor is focused towards forming an effective interface between the analyte electrode which significantly influences the overall biosensor quality. Polymers and macromolecular systems are favored for their distinct properties and versatile applications. Enhancing the properties and conductivity of these systems can be achieved through incorporating nanoparticles or carbonaceous moieties. Hybrid composite materials, possessing a unique combination of attributes like advanced sensitivity, selectivity, thermal stability, mechanical flexibility, biocompatibility, and tunable electrical properties, emerge as promising candidates for biosensor applications. In addition, this approach enhances the electrochemical response, signal amplification, and stability of fabricated biosensors, contributing to their effectiveness. This review predominantly explores recent advancements in utilizing macrocyclic and macromolecular conjugated systems, such as phthalocyanines, porphyrins, polymers, etc. and their hybrids, with a specific focus on signal amplification in biosensors. It comprehensively covers synthetic strategies, properties, working mechanisms, and the potential of these systems for detecting biomolecules like glucose, hydrogen peroxide, uric acid, ascorbic acid, dopamine, cholesterol, amino acids, and cancer cells. Furthermore, this review delves into the progress made, elucidating the mechanisms responsible for signal amplification. The Conclusion addresses the challenges and future directions of macromolecule-based hybrids in biosensor applications, providing a concise overview of this evolving field. The narrative emphasizes the importance of biosensor technology advancement, illustrating the role of smart design and material enhancement in improving performance across various domains.

Status of Fishery Discards and By-Products in Greece and Potential Valorization Scenarios towards a National Exploitation Master Plan.

The valorization of aquaculture/fishery processing by-products, as well as unavoidable/unwanted catches and discards in Greece, is currently an underutilized activity despite the fact that there are several best practices in Northern Europe and overseas. One of the main challenges is to determine whether the available quantities for processing are sufficient to warrant the valorization of discards and fish side streams. This is the first attempt to systematically record and analyze the available quantities of fish by-products and discards in Greece spatially and temporally in an effort to create a national exploitation Master Plan for the valorization of this unavoidable and unwanted biomass. A thorough survey conducted within the VIOAXIOPIO project unveiled a substantial biomass of around 19,000 tonnes annually that could be harnessed for valorization. Furthermore, the production of various High-Added-Value Biomolecules (HAVBs) was investigated and experimental trials were conducted to assess the potential yields, with the collected data used to formulate four valorization scenarios.

Dry molten globule conformational state of CYP11A1 (SCC) regulates the first step of steroidogenesis in the mitochondrial matrix.

Multiple metabolic events occur in mitochondria. Mitochondrial protein translocation from the cytoplasm across compartments depends on the amino acid sequence within the precursor. At the mitochondria associated-ER membrane, misfolding of a mitochondrial targeted protein prior to import ablates metabolism. CYP11A1, cytochrome P450 cholesterol side chain cleavage enzyme (SCC), is imported from the cytoplasm to mitochondrial matrix catalyzing cholesterol to pregnenolone, an essential step for metabolic processes and mammalian survival. Multiple steps regulate the availability of an actively folded SCC; however, the mechanism is unknown. We identified that a dry molten globule state of SCC exists in the matrix by capturing intermediate protein folding steps dictated by its C-terminus. The intermediate dry molten globule state in the mitochondrial matrix of living cells is stable with a limited network of interaction and is inactive. The dry molten globule is activated with hydrogen ions availability, triggering cleavage of cholesterol sidechain, and initiating steroidogenesis.

The impact of biomolecule interactions on the cytotoxic effects of rhenium(I) tricarbonyl complexes.

Rhenium complexes show great promise as anticancer drug candidates. Specifically, compounds with a Re(CO)3(NN)(py)+ core in their architecture have shown cytotoxicity equal to or greater than that of well-established anticancer drugs based on platinum or organic molecules. This study aimed to evaluate how the strength of the interaction between rhenium(I) tricarbonyl complexes fac-[Re(CO)3(NN)(py)]+, NN = 1,10-phenanthroline (phen), dipyrido[3,2-f:2',3'-h]quinoxaline (dpq) or dipyrido[3,2-a:2'3'-c]phenazine (dppz) and biomolecules (protein, lipid and DNA) impacted the corresponding cytotoxic effect in cells. Results showed that fac-[Re(CO)3(dppz)(py)]+ has higher Log Po/w and binding constant (Kb) with biomolecules (protein, lipid and DNA) compared to complexes of fac-[Re(CO)3(phen)(py)]+ and fac-[Re(CO)3(dpq)(py)]+. As consequence, fac-[Re(CO)3(dppz)(py)]+ exhibited the highest cytotoxicity (IC50 = 8.5 µM for HeLa cells) for fac-[Re(CO)3(dppz)(py)]+ among the studied compounds (IC50 > 15 µM). This highest cytotoxicity of fac-[Re(CO)3(dppz)(py)]+ are probably related to its lipophilicity, higher permeation of the lipid bilayers of cells, and a more potent interaction of the dppz ligand with biomolecules (protein and DNA). Our findings open novel avenues for rational drug design and highlight the importance of considering the chemical structures of rhenium complexes that strongly interact with biomolecules (proteins, lipids, and DNA).

A comprehensive review and advanced biomolecule-based therapies for osteoporosis.

BACKGROUND: The prevalence of osteoporosis (OP) on a global scale is significantly elevated that causes life threatening issues. The potential of groundbreaking biomolecular therapeutics in the field of OP is highly encouraging. The administration of biomolecular agents has the potential to mitigate the process of bone demineralization while concurrently augmenting the regenerative capacity of bone tissue, thereby facilitating a personalized therapeutic approach. Biomolecules-based therapies showed promising results in term of bone mass protection and restoration in OP. AIM OF REVIEW: We summarized the recent biomolecular therapies with notable progress in clinical, demonstrating the potential to transform illness management. These treatments frequently utilize different biomolecule based strategies. Biomolecular therapeutics has a targeted character, which results in heightened specificity and less off-target effects, ultimately leading to increased patient outcomes. These aspects have the capacity to greatly enhance the management of OP, thus resulting in a major enhancement in the quality of life encountered by individuals affected by this condition.

Inhibitors of amyloid fibril formation.

Many diseases are caused by misfolded and denatured proteins, leading to neurodegenerative diseases. In recent decades researchers have developed a variety of compounds, including polymeric inhibitors and natural compounds, antibodies, and chaperones, to inhibit protein aggregation, decrease the toxic effects of amyloid fibrils, and facilitate refolding proteins. The causes and mechanisms of amyloid formation are still unclear, and there are no effective treatments for Amyloid diseases. This section describes research and achievements in the field of inhibiting amyloid accumulation and also discusses the importance of various strategies in facilitating the removal of aggregates species (refolding) in the treatment of neurological diseases such as chemical methods like as, small molecules, metal chelators, polymeric inhibitors, and nanomaterials, as well as the use of biomolecules (peptide and, protein, nucleic acid, and saccharide) as amyloid inhibitors, are also highlighted.

Development and Characterization of Gelatin-Based Hydrogels Containing Triblock Copolymer and Phytic Acid.

In recent research, significant interest has been directed towards gelatin-based hydrogels due to their affordable price, extensive availability, and biocompatibility, making them promising candidates for various biomedical applications. The development and characterization of novel hydrogels formed from varying ratios of gelatin, triblock copolymer Pluronic F-127, and phytic acid have been presented. Swelling properties were examined at different pH levels. The morphology of hydrogels and their thermal properties were analyzed using scanning electron microscopy (SEM), thermogravimetric analysis (TG), and differential scanning calorimetry (DSC). Fourier-transform infrared (FTIR) analysis of the hydrogels was also performed. The introduction of phytic acid in the hydrogel plays a crucial role in enhancing the intermolecular interactions within gelatin-based hydrogels, contributing to a more stable, elastic, and robust network structure.

YAP condensates are highly organized hubs.

YAP/TEAD signaling is essential for organismal development, cell proliferation, and cancer progression. As a transcriptional coactivator, how YAP activates its downstream target genes is incompletely understood. YAP forms biomolecular condensates in response to hyperosmotic stress, concentrating transcription-related factors to activate downstream target genes. However, whether YAP forms condensates under other signals, how YAP condensates organize and function, and how YAP condensates activate transcription in general are unknown. Here, we report that endogenous YAP forms sub-micron scale condensates in response to Hippo pathway regulation and actin cytoskeletal tension. YAP condensates are stabilized by the transcription factor TEAD1, and recruit BRD4, a coactivator that is enriched at active enhancers. Using single-particle tracking, we found that YAP condensates slowed YAP diffusion within condensate boundaries, a possible mechanism for promoting YAP target search. These results reveal that YAP condensate formation is a highly regulated process that is critical for YAP/TEAD target gene expression.