Rice grassy stunt virus (RGSV) a member of Tenuivirus family, is very potent and destructive which effects rice crop in many countries, particularly China. Non coding RNAs have important functions in development and epigenetic regulation of gene expression in numerous organsisms. There is three type of small non coding RNAs have been found in eukaryotes, which are small interferring RNAs (siRNAs), microRNAs (miRNAs) and piwi interacting RNAs (piRNAs). Small RNAs (sRNAs) origination is from the infecting virus which is known as virus-derived small interfering RNAs (vsiRNAs), has responsibility for RNA silencing in plants. Virus-induced gene silencing (VIGS) is mainly dependent on RNA silencing (RNAi). Interestingly, RNA silencing happens in plants during viral infections. RNAi technique showed significant results in Nephotettix cincticeps. RNAi technique demonstrated the gene silencing of planthopper Nilaparvata lugens. The proteins P5, pcf4, Dnj, psn5, and pn6 act as potential movement proteins and serve as silencing suppressors for RGSV. VsiRNAs originate from dsRNA molecules which require Dicer-like (DCL) proteins, RNA dependent RNA polymerase (RdRP) proteins, and Argonaute (AGO) proteins. RdRP uses ssRNA for perfect RNA amplification process and can also be used for DCL dependent secondary vsiRNA formation. VSRs interfere with the movement of signals during silencing mechanism. Moreover, intercellular movement of viruses is facilitated by virus-encoded movement protein. RNAi is found in many eukaryotes which are related to transcriptional or post-transcriptional regulation by gene suppression. Transcription is bidirectional in ssDNA viruses which are originated from dsRNA molecules. In this review, we highlighted the biology of Rice grassy stunt virus and its insect vector and its silencing suppressors. This work will be helpful for plant virologists to understand the whole biogenesis mechanism for rice viruses especially RGSV.

The development of saltiness enhancement peptides is important in reducing salt intake and promoting dietary health. Our study aimed to analyze and identify straw mushroom enzymatic peptides with salty taste enhancing effects. The taste-related peptides within the straw mush-room extract were isolated via ultrafiltration and identified using UPLC-Q-TOF-MS/MS. Sub-sequent, E-tongue and sensory analyses unveiled that the ultrafiltration fraction (500-2000 Da) of straw mushroom peptides exhibited a saltiness enhancement effect. The UPLC-Q-TOF-MS/MS analysis identified 220 peptides within the ultrafiltration fractions (500-2000 Da), which were then assessed for their interaction with the T1R1/T1R3 receptor. The investigation underscored the significant involvement of Asp223, Gln243, Leu232, Asp251, and Pro254 in the binding of peptides from triple enzymatically hydrolyzed straw mushrooms to T1R1/T1R3. Based on the binding energy and active site analysis, three peptides were selected for synthesis: DFNALPFK (-9.2 kcal/mol), YNEDNGIVK (-8.8 kcal/mol), and VPGGQEIKDR (-8.9 kcal/mol). Notably, 3.2 mmol of VPGGQEIKDR enhanced a 0.05% NaCl solution to the saltiness level of a 0.15% NaCl solution. Also, 0.8 mmol of YNEDNGIVK elevated a 0.05% NaCl solution to the saltiness of a 0.1% NaCl solution.

Diabetic retinopathy (DR), a prevalent complication of diabetes mellitus affecting a significant portion of the global population, has long been viewed primarily as a microvascular disorder. However, emerging evidence suggests that it should be redefined as a neurovascular disease with multifaceted pathogenesis rooted in oxidative stress and advanced glycation end products. The transforming growth factor-β (TGF-β) signaling family has emerged as a major contributor to DR pathogenesis due to its pivotal role in retinal vascular homeostasis, endothelial cell barrier function, and pericyte differentiation. However, the precise roles of TGF-β signaling in DR remain incompletely understood, with conflicting reports on its impact in different stages of the disease. Additionally, the BMP subfamily within the TGF-β superfamily introduces further complexity, with BMPs exhibiting both pro- and anti-angiogenic properties. Furthermore, TGF-β signaling extends beyond the vascular realm, encompassing immune regulation, neuronal survival, and maintenance. The intricate interactions between TGF-β and reactive oxygen species (ROS), non-coding RNAs, and inflammatory mediators have been implicated in the pathogenesis of DR. This review delves into the complex web of signaling pathways orchestrated by the TGF-β superfamily and their involvement in DR. A comprehensive understanding of these pathways may hold the key to developing targeted therapies to halt or mitigate the progression of DR and its devastating consequences.

The formation and functioning of membrane-less organelles (MLOs) is one of the main driving forces in the molecular life of the cell. These processes are based on the separation of biopolymers into phases regulated by multiple specific and nonspecific inter- and intramolecular interactions. Among the realm of MLOs, a special place is taken by the promyelocytic leukemia nuclear bodies (PML-NBs or PML bodies), which are the intranuclear compartments involved in the regulation of cellular metabolism, transcription, maintenance of genome stability, response to viral infection, apoptosis, and tumor suppression. According to the accepted models, specific interactions, such as SUMO/SIM, formation of disulfide bonds, etc., play a decisive role in the biogenesis of PML bodies. In this work, a number of bioinformatics approaches were used to study proteins found in the proteome of PML-bodies for their tendency to spontaneous liquid-liquid phase separation (LLPS), which is usually caused by weak nonspecific interactions. 205 proteins found in PML bodies have been identified. It has been suggested that UBC9, P53, HIPK2, and SUMO1 can be considered as the scaffold proteins of PML bodies. It was shown that more than half of the proteins in the analyzed proteome are capable of spontaneous LLPS, with 85% of the analyzed proteins being intrinsically disordered proteins (IDPs), and remaining 15% being proteins with intrinsically disordered protein regions (IDPRs). About 44% of all proteins analyzed in this study contain SUMO binding sites and can potentially be SOMYylated. These data suggest that weak nonspecific interactions play a significantly larger role in the formation and biogenesis of PML bodies than previously expected.

Active research of metal-containing compounds and enzymes as effective antifungal agents is currently noted. The interest in metals is due to the wide variety of ligands that can be used for metals, including chemically synthesized and naturally obtained variants as a result of the so-called "green synthesis". The main mechanism of antifungal action of metals is the triggering of generation and accumulation of reactive oxygen species (ROS). Further action of ROS on various biomolecules is nonspecific. This review highlights various hydrolytic enzymes (glucanases and proteases) that affect the structural elements of fungal cells (cell walls, membranes), fungal quorum sensing molecules, fungal own protective agents (mycotoxins and antibiotics), proteins responsible for the adhesion and formation of stable highly concentrated populations in the form of biofilms. A wide range of the substrates for enzymes allows the use of various mechanisms of their antifungal actions. The prospects of combining two different types of antifungal agents (metals and enzymes) for mycelial fungi and yeast cells are discussed in this review. Special attention is paid to the possible influence of metals on activity of the enzymes and the possible effects of proteins on antifungal activity of metal-containing compounds.

Insulin-like growth factor binding proteins (IGFBPs) are critical modulators of the metabolism. In adults, IGFBPs are associated with obesity and insulin resistance but the association of IGFBPs with metabolic homeostasis in children and adolescents is not fully characterized. In this study we investigated the association of plasma IGFBPs (IGFBP-1, 3 and 7) with weight status, central adiposity and cardiovascular disease markers Hs-CRP and Ox-LDL. A total of 420 adolescents (age 11-14 years) were randomly recruited from public middle schools in Kuwait. IGFBPs were measured using bead-based multiplexing while Hs-CRP and Ox-LDL were measured using ELISA. IGFBP-1 levels were significantly lower in obese and overweight participants compared to normal weight children. Only IGFBP-1 was negatively associated with waist circumference to height (WC/Ht) ratio. IGFBP-1 was negatively correlated with Hs-CRP while IGFBP-3 and IGFBP-7 were negatively correlated with Ox-LDL. These data demonstrate a robust negative association of IGFBP-1, but not IGFBP-3 or -7, with overweight and obesity, and the inflammation marker Hs-CRP. Central adiposity (WC/Ht ratio) was a stronger predictor of IGFBP-1 than BMI-for-age z-score. IGFBP-1 could thus be used as a sensitive predictive diagnostic tool for obesity and its subsequent effects in screening and monitoring of obesity-related metabolic complications in adolescents.

The global increase in population has placed significant pressure on food security, leading to the emergence of aquaculture as a vital source of aquatic foods. However, rising costs and the limited availability of fishmeal in aquafeeds have spurred the search for alternative protein sources. While plant-based ingredients have been integrated into commercial aquafeeds, they come with challenges, including low protein content, palatability issues, and the presence of antinutritional factors. In this context, fish silage, derived from fish waste and discarded fish, stands out as a promising alternative technology due to its cost-effectiveness and sustainability attributes. The production of fish silage involves the addition of organic/inorganic acids or lactic acid bacteria to homogenized fish waste. This process yields a valuable mixture rich in peptides, free amino acids, and partially hydrolyzed proteins, offering significant nutritional benefits for animal diets. Beyond its nutritional advantages, fish silage contributes to environmental sustainability by reducing the impact of waste disposal and enhancing the value of fish waste. The objective of this review is to promote sustainable practices in the aquaculture industry in response to the increasing demand for high-quality feed nutrients. To achieve this, it includes an analysis of research results related to silage technology, an appraisal of the advantages and disadvantages of using fish silage as a feed additive, and a focus on emerging trends in this field.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the disease COVID-19 has wreaked havoc on the health and economy of humanity. In addition, the disease is observed in domestic and wild animals. The disease has impacted directly and indirectly every corner of the planet. Currently, there are no vaccines and effective therapies for COVID-19. SARS-CoV-2 is an enveloped virus with a single-stranded RNA genome of 29.8 kb. More than two-thirds of the genome comprises Orf1ab encoding 16 non-structural proteins (nsps) followed by mRNAs encoding structural proteins, spike (S), envelop (E), membrane (M), and nucleocapsid (N). These genes are interspaced with several accessory genes (open reading frames [Orf] 3a, 3b, 6, 7a, 7b, 8, 9b, 9c and 10). The functions of these proteins are of particular interest for understanding the pathogenesis of SARS-CoV-2. Several of the nsps (nsp3, nsp4, nsp6) and Orf3a are transmembrane proteins involved in regulating the host immunity, modifying host cell organelles for viral replication and escape and hence considered drug targets. In this paper we report mapping the transmembrane structure of the non-structural proteins of SARS-CoV-2.

In the mid-1950s, Bert L. Vallee and his colleague Marvin Margoshes discovered a molecule known today as metallothionein (MT). Meanwhile MTs have been shown to be common in many biological organisms. Despite their prevalence, however, it remains unclear to date what exactly MTs do and how they contribute to the biological function of an organism or organ. Honoring Dr. Vallee’s sometimes innovative approach to research, this contribution sets out to show how philosophy of science can help us gain a clearer picture of biochemical research. We shall look into both the discovery of as well as recent research on Dr. Vallee’s beloved family of MT proteins to illustrate (i) how exploratory and upward-looking research play important roles in biochemical discoveries although they do not fit the paradigmatic approach of decomposition and struc-ture-function mapping. Besides, we shall suggest (ii) that while other biochemical molecules ex-hibit a clearly identifiable function, other research hypotheses might be worthy of pursuit in the case of MTs.

The inhibition of heat shock protein 90 (Hsp90) a molecular chaperone for multiple oncogenic client proteins is considered as a promising approach to overcome radioresistance. Since most Hsp90 inhibitors activate HSF-1 that induces the transcription of cytoprotective and tumor-promoting stress proteins such as Hsp70 and Hsp27, a combined approach consisting of HSF-1 knockdown (k.d.) and Hsp90 inhibition was investigated. A specific HSF-1 k.d. was achieved in H1339 lung cancer cells using RNAi-Ready pSIRENRetroQ vectors with puromycin resistance. The Hsp90 inhibitor NVP-AUY922 was evaluated at low concentrations - ranging from 1-10nM - in control and HSF-1 k.d. cells. Protein expression (i.e., Hsp27/Hsp70, HSF-1, pHSF-1) and transcriptional activity was assessed by Western blot analysis and luciferase assays and radiosensitivity was measured by proliferation, apoptosis (Annexin V, active caspase 3), clonogenic cell survival, alkaline comet, γH2AX, 53BP1 and Rad51 foci assays. The k.d. of HSF-1 resulted in a significant reduction of basal and NVP-AUY922-induced Hsp70/Hsp27 expression levels. A combined approach consisting of HSF-1 k.d. and low concentrations of the Hsp90 inhibitor NVP-AUY922 potentiates radiosensitization which involves an impaired homologous recombination mediated by Rad51. Our findings are key for clinical applications of Hsp90 inhibitors with respect to adverse hepatotoxic effects.

The castor plant (Ricinus communis L.) has been known since time immemorial in traditional medicine in the pharmacopeia of Mediterranean and eastern ancient cultures. Moreover, it is still used in folk medicine worldwide. Castor bean has been mainly recommended as anti-inflammatory, anthelmintic, anti-bacterial, laxative, abortifacient, for wounds, ulcers, and many other indications. Many cases of human intoxication occurred accidentally or voluntarily with the ingestion of castor seeds or derivatives. Ricinus toxicity depends on several molecules, among them the most important is ricin, a protein belonging to the family of ribosome-inactivating proteins. Ricin is the most studied of this category of proteins and it is also known to the general public, having been used for biocrimes in several cases. Here, the main steps of ricin research are reported with particular regards to its enzymatic activity, structure and cytotoxicity. Moreover, we discuss ricin toxicity for animals and humans, as well as the relation amongst bioterrorism and ricin and its impact on environmental toxicity. Ricin has also been of great utility to develop a number of immunotoxins specific for the elimination of unwanted cells, mainly cancer cells; some of these immunotoxins gave promising results also in clinical trials.

Zn is an essential element for children related to optimal growth, development and nutritional metabolism. We measured Zn bioaccesibility (Zn-BA) levels of foods by Inductively coupled plasma mass spectrometry (ICP-MS) after in vitro digestion-fermentation method from children with gluten related disorders (GRD-CH), obesity (OB-CH) and allergy/intolerance to cow’s milk proteins (AICM-CH). Zn-BA levels in sick children (34.7 ± 28.8, 29.6 ± 30.1 and 26.7 ± 30.4%, respectively) were significantly lower (p < 0.05) than in healthy norm-weight children (HE-CH). For AICM-CH, Zn-BA in animal foods was significantly lower than in plant foods, and in both plant and animal foods from sick and healthy children (p < 0.05). In foods of animal origin in sick and healthy children, Zn-BA in foods heated in liquid media (frying and boiling) was significantly higher than in foods heated by hot air (roasting and grilling). In conclusion, in children the studied diseases diminished the Zn-BA, probably by the alteration of the gut microbiota which could negatively affect their appropriate long-term development. In AICM-CH, the allergy to cow's milk proteins could induce intestinal dysbiosis and inflammatory processes, leading to allergies to other animal food proteins, and to a more pronounced decrease of Zn-BA.

(1) Background: Artificial Intelligence (AI) models have shown potential in various educational contexts. However, their utility in explaining complex biological phenomena, such as Intrinsically Disordered Proteins (IDPs), requires further exploration. This study empirically evaluated the performance of various Large Language Models (LLMs) in the educational domain of IDPs. (2) Methods: Four LLMs, GPT-3.5, GPT-4, GPT-4 with Browsing, and Google Bard (PaLM 2), were assessed using a set of IDP-related questions. An expert evaluated their responses across five categories: accuracy, relevance, depth of understanding, clarity, and overall quality. Descriptive statistics, ANOVA, and Tukey's honesty significant difference tests were utilized for analysis. (3) Results: The GPT-4 model consistently outperformed the others across all evaluation categories. Although GPT-4 and GPT-3.5 were not statistically significantly different in performance (p>0.05), GPT-4 was preferred as the best response in 13 out of 15 instances. The AI models with browsing capabilities, GPT-4 with Browsing and Google Bard (PaLM 2) displayed lower performance metrics across the board with statistically significant differences (p<0.0001). (4) Conclusion: Our findings underscore the potential of AI models, particularly LLMs such as GPT-4, in enhancing scientific education, especially in complex domains such as IDPs. Continued innovation and collaboration among AI developers, educators, and researchers are essential to fully harness the potential of AI for enriching scientific education.

Antibody-mediated targeting is an efficient strategy to enhance the specificity and selectivity of polymer nanomedicines towards the target site, typically a tumor. However, direct covalent coupling of an antibody with a polymer usually results in a partial damage of the antibody binding site accompanied with a compromised biological activity. Here, an original solution based on well-defined non-covalent interactions between tris-nitrilotriacetic acid (trisNTA) and hexahistidine (His-tag) groups, purposefully introduced to the structure of each macromolecule, is described. Specifically, trisNTA groups were attached along the chains of a hydrophilic statistical copolymer based on N-(2-hydroxypropyl)methacrylamide (HPMA), and at the end or along the chains of thermo-responsive di-block copolymers based on N-isopropylmethacrylamide (NIPMAM) and HPMA; His-tag was incorporated to the structure of a recombinant single chain fragment of an anti-GD2 monoclonal antibody (scFv-GD2). Static and dynamic light scattering analyses confirmed that mixing of polymer with scFv-GD2 led to the formation of polymer/scFv-GD2 complexes; those prepared from thermo-responsive polymers formed stable micelles at 37 °C. Flow cytometry and fluorescence microscopy clearly demonstrated antigen-specific binding of the prepared complexes to GD2 positive murine T-cell lymphoma cells EL-4 and human neuroblastoma cells UKF-NB3, while no interaction with GD2 negative murine fibroblast cells NIH-3T3 was observed. These non-covalent polymer protein complexes represent a new generation of highly specific actively targeted polymer therapeutics or diagnostics.

Jingmen viruses are newly described segmented flavi-like viruses that have a worldwide distribution in ticks and have been associated with febrile illnesses in humans. Computational analyses were used to predict that Jingmen flavi-like virus glycoproteins have structural features of class II viral fusion proteins, including an ectodomain consisting of beta-sheets and short alpha-helices, a fusion peptide with interfacial hydrophobicity and a three domain architecture. Jingmen flavi-like virus glycoproteins have a sequence enriched in serine, threonine and proline at the amino terminus, which is a feature of mucin-like domains. Several of the serines and threonines are predicted be modified by the addition of O-linked glycans. Some of the glycoproteins are predicted to have an additional mucin-like domain located prior to the transmembrane anchor, whereas others are predicted to have a stem consisting of two alpha-helices. The flavivirus envelope protein and Jingmen flavi-virus glycoproteins may have diverged from a common class II precursor glycoprotein with a mucin-like domain or domains acquired after divergence.

To examine the role of RNA silencing in defense against viroid, a Dicer-like 2 and 4 (DCL2&4)—double knockdown transgenic tomato line 72E was created. The expression of endogenous DCL2 and DCL4 in line 72E decreased to about a half of the empty cassette line EC. When challenged with potato spindle tuber viroid (PSTVd), 72E allowed significantly higher level of PSTVd accumulation early in infection and showed lethal systemic necrosis. The size distribution of PSTVd-derived small RNA was significantly changed: the numbers of 21 and 22 nucleotides (nt) species in line 72E was approximately 66.7% and 5% of those in line EC, respectively. Conversely, the numbers of 24-nt species increased by 1100%. Furthermore, expression of miR398a-3p and miR398 increased 770–868% in the PSTVd-infected 72E, compared to the PSTVd-infected EC. In parallel, superoxide dismutase (SOD1) in PSTVd-infected 72E showed higher expression levels. In concert with miR398a-3p, SOD1 controls detoxification of reactive oxygen species (ROS) generated in cells. Since high levels of ROS production and its scavenging activity were observed in PSTVd-infected 72E, the lack of full-activity of DCLs was thought to have made the plant incapable to control excessive ROS production and thus resulted in to develop lethal systemic necrosis.

African swine fever (ASF) is a lethal disease in pigs that has grave socio-economic implications worldwide. For the development of vaccines against African swine fever virus (ASFV), immunogenic antigens that generate protective immune responses need to be identified. There are over 150 viral proteins - many of which are uncharacterized – and humoral immunity to ASFV has not been closely examined. To profile antigen specific antibody responses, we developed luciferase-linked antibody capture assays (LACAs) for a panel of ASFV capsid proteins and screened sera from inbred and outbred animals that were previously immunized with low virulent ASFV before challenge with virulent ASFV. Antibodies to B646L/p72, D117L/p17, M1249L and E120R/p14.5 were detected in this study; however, we were unable to detect B438L specific antibodies. Although OURT88/1 induced viremia was observed in the presence of anti-B646L/p72 antibodies as well as B602L antibodies they were associated with recovery from lethal disease in inbred and outbred animals. However, these antibodies did not correlate with protection against Georgia 2007/1 infection. Antibody responses against M1249L and E120R/p14.5 were observed in animals with reduced clinical signs and viremia. Here we present LACAs as a tool for targeted profiling of antigen specific antibody responses to inform vaccine development.

Ribosomes are macromolecular complexes important to protein translation, and thus, essential to life. Comprising an ensemble of ribosomal proteins and RNA molecules, ribosomes are conserved in structure and function across all domains of life, but recent structural studies have revealed differentiated structures of ribosomes from bacterial, archaea and eukaryotes. Additionally, unique ribosomal protein mass fingerprints have been found for individual species; thereby, indicating that ribosomes are differentiated in structure amongst different species. Given that structure defines function, differentiated function likely exists amongst ribosomes of different species, which could manifest as differences in translation efficiency that could impact on cell growth rate. But ribosomal proteins also hold phylogenetic significance in informing the evolutionary trajectory of each species. Such ribosomal proteins are thus not highly conserved and offers sufficient sequence space for the evolution of differentiated structure and function in different species. Using ribosomal proteins that hold phylogenetic significance as templates, this study sought to understand the mutational and conformational limits that define functional ribosomes. Specifically, ribosomal proteins in Bacillus subtilis that hold phylogenetic cues would be mutated through error-prone polymerase chain reaction to generate variants that are subsequently transformed into Escherichia coli. To help assess the functional properties of the heterologous ribosomal proteins, endogenous ribosomal protein genes would be inactivated by multiplex CRISPR interference. Since variants in ribosomal proteins would likely impact on ribosome function and translation efficiency, live/dead screening on LB agar would be effective as a preliminary screen for functional mutants. These mutants would subsequently be inoculated into liquid LB medium in 96 well plates to quantify relative growth rates between different strains harbouring different heterologous variants of ribosomal proteins. Plasmids containing different ribosomal protein mutants would be extracted from each functional strain and subjected to Sanger sequencing for determining the specific mutations involved. Collection of such mutations would provide a comprehensive mutational map that define the limits of ribosomal protein sequence space important to ribosome function. Furthermore, biochemical isolation of ribosomal proteins and their structural characterization by X-ray crystallography or cryo-electron microscopy would further illuminate the structural significance of each mutation on ribosome structure and function; thereby, elucidating the structural tolerance space for functional ribosomes. Overall, generating a diverse pool of mutant ribosomal proteins in viability assays followed by sequencing and structural characterization would help define the mutational and conformational limits of a functional and efficient ribosome.

The bipolar mitotic spindle drives accurate chromosome segregation by capturing the kinetochore and pulling each set of sister chromatids to the opposite poles. In this review, we describe recent findings on the multiple pathways leading to bipolar spindle formation in fission yeast and discuss these results from a broader perspective. Roles of four mitotic kinesins (Kinesin-5, Kinesin-6, Kinesin-12 and Kinesin-14) in spindle assembly are depicted, and how a group of microtubule-associated proteins, sister chromatid cohesion and the kinetochore collaborates with these motors is shown. We have paid special attention to the molecular pathways that render otherwise essential Kinesin-5 to become non-essential: how cells build bipolar mitotic spindles without the need for Kinesin-5 and where the alternate forces come from are considered. We highlight the force balance for bipolar spindle assembly and explain how outward and inward forces are generated by various ways, in which the proper fine-tuning of microtubule dynamics plays a crucial role. Overall, these new pathways have illuminated remarkable plasticity and adaptability of spindle mechanics. Kinesin molecules are regarded as prospective targets for cancer chemotherapy and many specific inhibitors have been developed. However, several hurdles have arisen against their clinical implementation. This review provides insight into possible strategies to overcome these challenges.

Background: Recent developments in our understanding of the interactions between long non-coding RNA (lncRNA) and cellular components have improved treatment approaches for various human diseases including cancer, vascular diseases, and neurological diseases. Although investigation of specific lncRNAs revealed their role in the metabolism of cellular RNA, our understanding of their contribution to post-transcriptional regulation is relatively limited. In this study, we explore the role of lncRNAs in modulating alternative splicing and their impact on downstream protein-RNA interaction networks. Results: Analysis of alternative splicing events across 39 lncRNA wildtype and knockout RNA-sequencing datasets from three human cell lines: HeLa (Cervical Cancer), K562 (Myeloid Leukemia), and U87 (Glioblastoma), resulted in high confidence (fdr < 0.01) identification of 4432 skipped exon events and 2474 retained intron events, implicating 759 genes to be impacted at post-transcriptional level due to the loss of lncRNAs. We observed that a majority of the alternatively spliced genes in a lncRNA knockout were specific to the cell type, in agreement with the finding that genes affected by alternative splicing also displayed enriched functions in a cell type specific manner. To understand the mechanism behind this cell-type specific alternative splicing patterns, we analyzed RNA binding protein (RBP)-RNA interaction profiles across the spliced regions. Conclusions: Despite limited RBP binding data across cell lines, alternatively spliced events detected in lncRNA perturbation experiments were associated with RBPs binding in proximal intron-exon junctions, in a cell type specific manner. The cellular functions affected by alternative splicing were also affected in a cell type specific manner. Based on the RBP binding profiles in HeLa and K562 cells, we hypothesize that several lncRNAs are likely to exhibit a sponge effect in disease contexts, resulting in the functional disruption of RBPs due to altered titration of the RBPs from their target loci. We propose that such lncRNA sponges can extensively rewire the post-transcriptional gene regulatory networks by altering the protein-RNA interaction landscape in a cell-type specific manner.

This is a brief critique of the functions—particularly olfactory functions—specified for the “Chemosensory Protein” (CSPs) molecule family. On the basis of these proteins’ presence in the sensory antennal lymph of locusts, odor chemosensory ligand binding functions have been hypothesized. According to this hypothesis, the entire protein molecule superfamily is referred to as “CSPs”. However, new information and developments in the field of CSP molecular research, such as the expression of CSP genes in the gut, brain, fat body, epidermis, and pheromone gland, as well as gene expression profiling from most early developmental stages—that is, CSP expression well in advance of the appearance of chemical sense nerve cells—strongly suggest that the protein molecule has other roles that are unrelated to chemosensing. Moreover, CSPs are found in bacterial microbial prokaryote organisms in addition to insects. Thus, we examine the molecule’s name, definition, RNA editing, protein structure, lipid binding properties, DNA interaction, and evolutionary characteristics in brief before referring to this protein family as “Chemosensory Proteins”. This article tries to compel and discuss the most recent information as a way to rename this protein family. Because of its highly conserved molecular distinctive feature (four adjacent cysteines), we propose renaming “CSPs” as “4CSPs” (4 Cysteines Soluble Proteins).

Viruses rely on host cells to replicate their genomes and assemble new viral particles. Thus, they have evolved intricate mechanisms to exploit host factors. Host cells, in turn, have developed strategies to inhibit viruses, resulting in a nuanced interplay of co-evolution between virus and host. This dynamic often involves competition for resources crucial for both host cell survival and virus replication. Iron and iron-containing cofactors, including iron-sulfur clusters, are known to be a heavily battled resource during bacterial infections where control over iron can tug the war in favor of the pathogen or the host. It is logical to assume that viruses also engage in this competition. Surprisingly, our knowledge about how viruses utilize iron (Fe) and iron-sulfur (FeS) clusters remains limited. The handful of reviews on this topic primarily emphasize the significance of iron in supporting the host immune response against viral infections. The aim of this review, however, is to organize our current understanding of how viral proteins utilize FeS clusters, to give perspectives on what questions to ask next and to propose important avenues for future investigations.

Background: Macrophage inflammatory protein-1 alpha (MIP-1α) and C-reactive protein (CRP) are pro-inflammatory biomarkers that quantify clinical and subclinical inflammation in cardiac ischemia in cardiac inflammation and disease. Adiponectin is an anti-inflammatory marker associated with good health. The susceptibility of periodontitis patients to cardiovascular events needs to be evaluated. Objective: This study aims to assess the levels of biomarkers in periodontitis patients with and without acute myocardial infarction (AMI) compared to controls. Material and methods: Pro-inflammatory and anti-inflammatory analytes were examined by collecting unstimulated saliva from three groups (n = 20/each): healthy individuals, individuals with stage III periodontitis, and post-myocardial infarction patients with stage III periodontitis. The samples were collected within 48 hours of AMI. Results: Adiponectin levels were significantly lower in patients with periodontitis with and without AMI compared to controls, while CRP and MIP-1α were significantly higher in patients with periodontitis with and without AMI compared to controls. The highest titers for MIP-1α and CRP were detected among patients with periodontitis with and AMI. Conclusion: Our study provides evidence of the association between periodontitis and salivary analytes that occur in tandem with cardiovascular disease. The lower levels of Adiponectin and higher levels of CRP and MIP-1α in patients with periodontitis indicate that this condition is a potential risk factor for cardiovascular disease. The findings emphasize the importance of early detection and intervention for periodontitis patients to prevent cardiovascular events.

The author's method of oligomer sums for analysis of oligomer compositions of eukaryotic and prokaryotic genomes is described. The use of this method revealed the existence of general rules for cooperative oligomeric organization of a wide list of genomes. These rules are called hyperbolic because they are associated with hyperbolic sequences including the harmonic progression 1, 1/2, 1/3, .., 1/n. These rules are demonstrated by examples of quantitative analysis of many genomes from the human genome to the genomes of archaea and bacteria. The hyperbolic (harmonic) rules, speaking about the existence of algebraic invariants in full genomic sequences, are considered as candidates for the role of universal rules for the cooperative organization of genomes. The described phenomenological results were obtained as consequences of the previously published author's quantum-information model of long DNA sequences. The oligomer sums method was also applied to the analysis of long genes and viruses including the COVID-19 virus; this revealed, in characteristics of many of them, the phenomenon of such rhythmically repeating deviations from model hyperbolic sequences, which are associated with DNA triplets. In addition, an application of the oligomer sums method are shown to the analysis of the following long sequences: 1) amino acid sequences in long proteins like the protein Titin; 2) phonetic sequences of long Russan literary texts (for checking of thoughts of many authors that phonetic organization of human languages is deeply connected with the genetic language). The topics of the algebraic harmony in living bodies and of the quantum-information approach in biology are discussed.

The coronavirus 2019 (COVID-19) pandemic was caused by a positive sense single-stranded RNA (ssRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, other human coronaviruses (hCoVs) exist, of which Middle East Respiratory Syndrome (MERS) and SARS-CoV (SARS) showed higher mortality rates without causing a pandemic. As of December 2022, SARS-CoV-2 has resulted in over 6.6 million deaths worldwide through an array of acute to chronic pathologies. Historical pandemics include smallpox and influenza with efficacious therapeutics utilized to reduce overall disease burden. Therefore, immune system process analysis is required to compare innate and adaptive immune system interactions. Lymphatic system organs include bone marrow and thymus using a network of nodes throughout which white blood cells traverse glycolipid membranes utilizing cytokines and chemokine gradients that affect cell development, differentiation, proliferation, and migration processes as well as genetic factors affecting cell receptor expression. Innate processes involve antigen-presenting cells and B lymphocyte cellular responses to pathogens relevant to other viral and bacterial infections but also in oncogenic diseases. Such processes utilize cluster of differentiation (CD) marker expression, major histocompatibility complexes (MHC), pleiotropic interleukins (IL) and chemokines. The adaptive immune system consists of Natural Killer (NK) and T cells. Other viruses are also contributory to cancer including human papillomavirus (cervical carcinoma ), Epstein-Barr virus (EBV) ( lymphoma), hepatitis B and C (hepatocellular carcinoma) and human T cell leukemia virus-1 (adult T-cell leukemia). Bacterial infections also increase the risk of developing cancer( e.g. H. pylori). Therefore, as the above factors can cause both morbidity and mortality along-side being transmitted within clinical and community settings, it is appropriate to now examine advances in single cell sequencing, FACS analysis and many other laboratory techniques that allow insights into discoveries of newer cell types. These developments offer improved clarity and understanding that over-lap with known autoimmune conditions that could be affected by innate B cell or T cell responses to SARS-CoV-2 infection. Thus, this review quantifies and outlines the nature of specific receptors and proteins relevant to clinical laboratories and medical research by documenting both innate and adaptive immune system cells within current coronavirus immunology case study data and other pathologies to date.

We apply principles of Gibbs phase plane chemistry to and across the entire ocean-atmospheric interface. Surface tension increments support a two dimensional, tangential pressure well known to determine rates of bulk gas, bubble, salt, spray and momentum transfer plus both sensible and latent heat fluxes. Hence it is worth asking whether tension mapping follows from current understanding of two dimensional composition. A history is provided dating back centuries and demonstrating that detrital organic macromolecules are central; subtle surfactant functional variation creates a microforcing field which dissipates turbulent energy at the sub-meter scale. Since we have just distributed major biopolymeric classes emitted as primary organic aerosol, further climate links can be established by considering full planar thermochemistry. Organic microlayer behaviors are reviewed with attention to confined, analog phase transitions among two dimensional “solid, liquid, (and) gaseous” states serving as elasticity indicators. We also discuss surfactant properties of general marine dissolved organic carbon, demonstrating that only proteins and lipids are capable of occupying significant local micro-area. The literature often suggests albumin and stearic acid as best proxies, and so we distribute their concentrations through multilevel global ecodynamic simulations. Consensus distributions are obtained in order to control adsorptive equilibria. Working from conservation of planar free energy, a parametric equation of state is devised relating excess coverage to the surface pressure-modulus. Constant settings for the proxy pair are drawn from laboratory study, and they successfully reproduce frequencies for surfactant solid-to-gas occurrence in ambient compression experiments. Functionally resolved organic measurements are rare and so we group them into super-ecological province tables showing that our bulk concentration estimates are reasonable. Outputs are then fed into a coverage-tension-elasticity code. Resulting contours traverse the critical range for piston velocity, bubble-spray and damping effects on either a regional or seasonal basis. There is also a possibility for widespread microlayer crystallization in polar seas. The concepts are a direct extension of our organic aerosol work, and the two approaches could be inserted into Earth System Models in tandem. Uncertainties in the logic are enumerated and include kinetic and thermochemical factors at multiple scales. But the problems are reducible through molecular modeling coupled to renewed laboratory and field study. Connections to marine colloids-gels, microlayer iron chelation, and linings of the ice channel network are discussed additionally.

The cell stress response is an essential system present in every cell for responding and adapting to extracellular environmental stimulations. A major program for stress response is the heat shock factor (HSF)–heat shock protein (HSP) system that maintains proteostasis in cells and promotes cancer progression. However, less is known about how the cell stress response is regulated by alternative transcription factors. Here, we show that the SCAN domain-containing transcription factors (SCAN-TFs) are involved in repressing the stress response in cancer. SCAND1 and SCAND2 are SCAN-TFs that can hetero-oligomerize with SCAN-zinc finger transcription factors, such as MZF1(ZSCAN6), for accessing DNA and transcriptionally co-repressing target genes. We found that heat stress induced the expression of both SCAND1 and MZF1(ZSCAN6) bound to HSP90 gene promoter regions in prostate cancer cells. SCAND1 and MZF1 blocked the heat shock responsiveness of HSP90 in prostate cancer cells. Gene expression of SCAND2, SCAND1 and MZF1 was negatively correlated with HSP90 expression in patients-derived prostate adenocarcinoma. MZF1 and SCAND2 were more highly expressed in paired normal tissues than in tumor tissues in several cancer types. High expression of SCAND2, SCAND1 and MZF1 correlated with enhanced prognoses of pancreatic cancer and head and neck cancers. Additionally, high expression of SCAND2 was correlated with better prognoses of lung adenocarcinoma and sarcoma. In contrast, high expression of HSP90AA1 correlated with poorer prognoses in several cancer types. These data suggest that the stress-inducible SCAN-TFs can function as a feedback system, suppressing excessive stress response and inhibiting cancers.

The current SARS-CoV-2 pandemic is still threatening humankind. Despite first successes in vaccine development and approval, no antiviral treatment is available for COVID-19 patients. The success is further tarnished by the emergence and spreading of mutation variants of SARS-CoV-2, for which some vaccines are not effective anymore. This highlights the urgent need for antiviral therapies even more. This article describes how the Genome-Scale Metabolic Model (GEM) of the host-virus interaction of human alveolar macrophages and SARS-CoV-2 was refined by incorporating the latest information about the virus’s structural proteins and the mutant variants B.1.1.7 and B.1.351. We confirmed the initially identified guanylate kinase as a potential antiviral target with this refined model and identified further potential targets from the purine and pyrimidine metabolism. The model was further extended by incorporating the virus’ lipid requirements. This opened new perspectives for potential antiviral targets in the altered lipid metabolism. Especially the phosphatidylcholine biosynthesis seems to play a pivotal role in viral replication. The guanylate kinase is even a robust target in all investigated mutation variants currently spreading worldwide. These new insights can guide laboratory experiments for the validation of identified potential antiviral targets. Only the combination of vaccines and antiviral therapies will effectively defeat this ongoing pandemic.

At the molecular level, aging is often accompanied by dysfunction of stress-induced membrane-less organelles (MLOs) and changes in their material state. In this work, we analyzed the proteins included in the proteome of stress granules (SGs) and P-bodies for their tendency to transform the material state of these MLOs. Particular attention was paid to proteins whose gene expression changes during replicative aging. It was shown that the proteome of the studied MLOs practically does not differ in the analyzed characteristics and consists of completely or partially intrinsically disordered proteins, 30 - 40% of which are potentially capable of liquid-liquid phase separation (LLPS). At the same time, the proportion of proteins capable of spontaneous LLPS is relatively small, which indicates the leading role of nucleic acids in the biogenesis of these membrane-less organelles. Proteins whose gene expression changes during the transition of human cells to a senescent state make up about 20% of the studied proteomes. There is a statistically significant increase in the number of positively charged proteins in both datasets studied compared to the complete proteomes of these organelles. An increase in the relative content of DNA-, but not RNA-binding proteins, was also found in the stress-granules dataset with senescence-related processes. Among SG proteins potentially involved in senescent processes, there is an increase in the abundance of potentially amyloidogenic proteins compared to the whole proteome. The hnRPDL protein has the highest degree of disorder and highest propensity for LLPS among such proteins, which allows us to consider it as “potentially dangerous.” Proteins common to SGs and P bodies, potentially involved in processes associated with senescence, form clusters of interacting proteins. The largest cluster is represented by RNA-binding proteins involved in RNA processing and translation regulation. These data indicate that SG proteins, but not proteins of P-bodies, are more likely to transform the material state of MLOs. Furthermore, these MLOs can participate in processes associated with aging in a coordinated manner.

There are no theorems (proven theories) in the biological sciences. We propose that the 3 31 nt minihelix tRNA evolution theorem be universally accepted as one. The 3 31 nt minihelix theorem completely describes evolution of type I and type II tRNAs from ordered precursors (RNA repeats and inverted repeats). Despite diversification of tRNAome sequences, statistical tests overwhelmingly support the theorem. Furthermore, the theorem relates the dominant pathway for the origin of life on Earth, specifically, how tRNAomes and the genetic code may have coevolved. Alternate models for tRNA evolution (i.e., 2 minihelix, convergent and accretion models) are falsified. In the context of the pre-life world, tRNA was a molecule that via mutation could modify anticodon sequences and teach itself to code. We relate the clearest history to date of the chemical evolution of life on Earth. From analysis of tRNA evolution, ribozyme-mediated RNA ligation was a primary driving force in evolution of complexity during the pre-life to life transition on Earth.

Transition between the unfolded and native states of the ordered globular proteins is accompanied by accumulation of several intermediates, such as pre-molten globule, wet molten globule, and dry molten globule. Structurally equivalent conformations can serve as native functional states of intrinsically disordered proteins. This overview captures the characteristics and importance of these molten globules in both structured and intrinsically disordered proteins. It also discusses examples of engineered molten globules. The formation of these intermediates under the conditions of macromolecular crowding and their interactions with nanomaterials are also reviewed.

Both SARS-CoV-2 (COVID-19) and SARS coronaviruses (CoVs) are members of the subgenus Sarbecovirus. To understand the origin of SARS-CoV-2, protein sequences from sarbecoviruses were analyzed to identify highly-specific molecular markers consisting of conserved inserts or deletions (termed CSIs) in the spike (S) and nucleocapsid (N) proteins that are specific for either particular clusters/lineages of these viruses or are commonly shared by specific lineages. Three novel CSIs in the N-terminal domain of the spike protein S1-subunit (S1-NTD) are uniquely shared by the SARS-CoV-2, BatCoV-RaTG13 and most pangolin CoVs, distinguishing this cluster of viruses (SARS-CoV-2r) from all others. In the same positions, where these CSIs are found, related CSIs are also present in two other sarbecoviruses (viz. CoVZXC21 and CoVZC45 forming CoVZC cluster), which form an out group of the SARS-CoV-2r cluster. These three CSIs are not found in the SARS-CoVs. However, both SARS and SARS-CoV-2r CoVs contain two large CSIs in the C-terminal domain of S1 (S1-CTD), which binds the human ACE-2 receptor, that are absent in the CoVZC cluster of CoVs. These results indicate that while the S1-NTD of the SARS-CoV-2r viruses possesses the sequence characteristics of the CoVZC cluster of CoVs, their S1-CTD resembles the SARS viruses. Thus, the spike protein of SARS-CoV-2r viruses has likely originated from a recombination event between the S1-NTD of the CoVZC viruses and the S1-CTD of SARS viruses. This inference is also supported by the amino acid sequence similarity of the S1-NTD and S1-CTD from SARS-CoV-2 compared to the CoVZC and SARS CoVs. We also present evidence that one of the pangolin-CoV_MP789, whose receptor-binding domain is most similar to the SARS-CoV-2, is also derived by a recent recombination between the S1-NTD of the CoVZC CoVs and the S1-CTD of a SARS-CoV-2 related virus. Several other identified CSIs are specific for others clusters of sarbecoviruses including a clade consisting of bat SARS-CoVs (BM48-31/BGR/2008 and SARS_BtKY72). Structural mappings studies show that the identified CSIs are located within surface-exposed loops and form distinct patches on the surface of the spike protein. These surface loops/patches are predicted to interact with other host components and play important role in the biology/pathology of SARS-CoV-2 virus. Lastly, the CSIs specific for the SARS-CoV-2r clade provide novel means for development of new diagnostic and therapeutic targets for these viruses.