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The COVID-19 pandemic has highlighted the urgent need for rapid and accurate diagnostic methods for various infectious diseases, including SARS-CoV-2. Traditional RT-PCR methods, while highly sensitive and specific, require complex equipment and skilled personnel. In response, we developed an integrated RT-LAMP-MS assay, which combines rapid reverse transcription loop-mediated isothermal amplification (RT-LAMP) with microscanning (MS) technology for detecting SARS-CoV-2. The assay uses magnesium pyrophosphate formed during LAMP amplification as a visual marker, allowing direct observation via microscopy without the need for additional chemical indicators or probes. For the SARS-CoV-2/IC RT-LAMP-MS assay, the sample-LAMP reagent mixture was added to a microchip with SARS-CoV-2 primers and internal controls, then incubated at 62 °C for 30 min in a heat block, followed by amplification analysis using a microscanner. In clinical tests, the RT-LAMP-MS assay showed 99% sensitivity and 100% specificity, which is identical to the RT-LAMP results and comparable to the commercial AllplexTM SARS-CoV-2 assay results. Additionally, the limit of detection (LOD) was determined to be 10−1 PFU mL−1 (dynamic range: 103~10−1 PFU mL−1). The assay delivers results in 30 min, uses low-cost equipment, and demonstrates 100% reproducibility in repeated tests, making it suitable for point-of-care use in resource-limited settings. [ABSTRACT FROM AUTHOR]

Comparative sociogenomics has the potential to provide important insights into how social behaviour evolved. We examined brain gene expression profiles of the primitively eusocial wasp Polistes metricus and compared the results with a growing base of brain gene expression information for the advanced eusocial honeybee, Apis mellifera. We studied four female wasp groups that show variation in foraging/provisioning behaviour and reproductive status, using our newly developed microarray representing approximately 3248 P. metricus genes based on sequences generated from high-throughput pyrosequencing. We found differences in the expression of approximately 389 genes across the four groups. Pathways known from Drosophila melanogaster to be related to lipid metabolism, heat and stress response, and various forms of solitary behaviour were associated with behavioural differences among wasps. Forty-five per cent of differentially expressed transcripts showed significant associations with foraging/provisioning status, and 14 per cent with reproductive status. By comparing these two gene lists with lists of genes previously shown to be differentially expressed in association with honeybee division of labour, we found a significant overlap of genes associated with foraging/provisioning, but not reproduction, across the two species. These results suggest common molecular roots for foraging division of labour in two independently evolved social insect species and the possibility of more lineage-specific roots of reproductive behaviour. We explore the implications of these findings for the idea that there is a conserved ‘genetic toolkit’ for division of labour across multiple lineages. [ABSTRACT FROM AUTHOR]

Noroviruses are a primary cause of gastroenteritis and foodborne illness with cases that affect millions of people worldwide each year. Inexpensive tests for norovirus that do not require sophisticated laboratory equipment are important tools for ensuring that patients receive timely treatment and for containing outbreaks. Herein, we demonstrate a low-cost colorimetric assay that detects norovirus from clinical samples by combining paper-based cell-free transcription-translation systems, isothermal amplification and virus enrichment by synbodies. Using isothermal amplification and cell-free RNA sensing with toehold switches, we demonstrate that the assay enables detection of norovirus GII.4 Sydney from stool down to concentrations of 270 aM in reactions that can be directly read by eye. Furthermore, norovirus-binding synbodies and magnetic beads are used to concentrate the virus and provide a 1000-fold increase in assay sensitivity extending its detection limit to 270 zM. These results demonstrate the utility of paper-based cell-free diagnostic systems for identification of foodborne pathogens and provide a versatile diagnostic assay that can be applied to the concentration, amplification and detection of a broad range of infectious agents. [ABSTRACT FROM AUTHOR]

Abstract: Many studies link pulp and paper mill effluent (PPME) exposure to adverse effects in fish populations present in the mill receiving environments. These impacts are often characteristic of endocrine disruption and may include impaired reproduction, development and survival. While these physiological endpoints are well-characterized, the molecular mechanisms causing them are not yet understood. To investigate changes in gene transcription induced by exposure to a PPME at several stages of treatment, male and female fathead minnows (FHMs) were exposed for 6days to 25% (v/v) secondary (biologically) treated kraft effluent (TK) or 100% (v/v) combined mill outfall (CMO) from a mill producing both kraft pulp and newsprint. The gene expression changes in the livers of these fish were analyzed using a 22K oligonucleotide microarray. Exposure to TK or CMO resulted in significant changes in the expression levels of 105 and 238 targets in male FHMs and 296 and 133 targets in females, respectively. Targets were then functionally analyzed using gene ontology tools to identify the biological processes in fish hepatocytes that were affected by exposure to PPME after its secondary treatment. Proteolysis was affected in female FHMs exposed to both TK and CMO. In male FHMs, no processes were affected by TK exposure, while sterol, isoprenoid, steroid and cholesterol biosynthesis and electron transport were up-regulated by CMO exposure. The results presented in this study indicate that short-term exposure to PPMEs affects the expression of reproduction-related genes in the livers of both male and female FHMs, and that secondary treatment of PPMEs may not neutralize all of their metabolic effects in fish. Gene ontology analysis of microarray data may enable identification of biological processes altered by toxicant exposure and thus provide an additional tool for monitoring the impact of PPMEs on fish populations. [Copyright &y& Elsevier]

Termites are highly eusocial insects that thrive on recalcitrant materials like wood and soil and thus play important roles in global carbon recycling and also in damaging wooden structures. Termites, such as Reticulitermes flavipes ( Rhinotermitidae), owe their success to their ability to extract nutrients from lignocellulose (a major component of wood) with the help of gut-dwelling symbionts. With the aim to gain new insights into this enzymatic process we provided R. flavipes with a complex lignocellulose (wood) or pure cellulose (paper) diet and followed the resulting differential gene expression on a custom oligonucleotide-microarray platform. We identified a set of expressed sequence tags ( ESTs ) with differential abundance between the two diet treatments and demonstrated the source (host/symbiont) of these genes, providing novel information on termite nutritional symbiosis. Our results reveal: (1) the majority of responsive wood- and paper-abundant ESTs are from host and symbionts, respectively; (2) distinct pathways are associated with lignocellulose and cellulose feeding in both host and symbionts; and (3) sets of diet-responsive ESTs encode putative digestive and wood-related detoxification enzymes. Thus, this study illuminates the dynamics of termite nutritional symbiosis and reveals a pool of genes as potential targets for termite control and functional studies of termite-symbiont interactions. [ABSTRACT FROM AUTHOR]

Intensive scientific research devoted in the recent years to understand the molecular mechanisms or neurodegeneration in spinocerebellar ataxias (SCAs) are identifying new pathways and targets providing new insights and a better understanding of the molecular pathogenesis in these diseases. In this consensus manuscript, the authors discuss their current views on the identified molecular processes causing or modulating the neurodegenerative phenotype in spinocerebellar ataxias with the common opinion of translating the new knowledge acquired into candidate targets for therapy. The following topics are discussed: transcription dysregulation, protein aggregation, autophagy, ion channels, the role of mitochondria, RNA toxicity, modulators of neurodegeneration and current therapeutic approaches. Overall point of consensus includes the common vision of neurodegeneration in SCAs as a multifactorial, progressive and reversible process, at least in early stages. Specific points of consensus include the role of the dysregulation of protein folding, transcription, bioenergetics, calcium handling and eventual cell death with apoptotic features of neurons during SCA disease progression. Unresolved questions include how the dysregulation of these pathways triggers the onset of symptoms and mediates disease progression since this understanding may allow effective treatments of SCAs within the window of reversibility to prevent early neuronal damage. Common opinions also include the need for clinical detection of early neuronal dysfunction, for more basic research to decipher the early neurodegenerative process in SCAs in order to give rise to new concepts for treatment strategies and for the translation of the results to preclinical studies and, thereafter, in clinical practice. [ABSTRACT FROM AUTHOR]

Plant transcription factors (TFs) are integral proteins associated with gene transcription. That ability arises after TFs bind to specific DNA sequences, such as promoters, responding positively or negatively to a multitude of endogenous and exogenous factors or stressors. For this reason, in plants, the vast majority of TFs are associated with growth, development, and responses to biotic and abiotic stresses. As is commonly known, the genes coding for TFs are written in uppercase italics, whereas the resulting proteins are written in lowercase, such as OsWRKY28 and OsWRKY28, respectively for a member of the WRKY TF family in rice (Oryza sativa L.). However, despite the existence of some conventions for the nomenclature of TFs, some deviation from these norms has been observed in the literature. Several cases are highlighted, primarily related to NAC TFs. These cases emphasize the need for stricter quality control of literature pertaining to the nomenclature of plant TFs. [ABSTRACT FROM AUTHOR]

Point-of-care (POC) diagnostics have emerged as a crucial technology for emerging pathogen detections to enable rapid and on-site detection of infectious diseases. However, current POC devices often suffer from limited sensitivity with poor reliability to provide quantitative readouts. In this paper, we present a self-powered digital loop-mediated isothermal amplification (dLAMP) microfluidic chip (SP-dChip) for the rapid and quantitative detection of nucleic acids. The SP-dChip utilizes a vacuum lung design to passively digitize samples into individual nanoliter wells for high-throughput analysis. The superior digitization scheme is further combined with reverse transcription loop-mediated isothermal amplification (RT-LAMP) to demonstrate dLAMP detection of Zika virus (ZIKV). Firstly, the LAMP assay is loaded into the chip and passively digitized into individual wells. Mineral oil is then pipetted through the chip to differentiate each well as an individual reactor. The chip did not require any external pumping or power input for rapid and reliable results to detect ZIKA RNA as low as 100 copies per μL within one hour. As such, this SP-dChip offers a new class of solutions for truly affordable, portable, and quantitative POC detections for emerging viruses. [ABSTRACT FROM AUTHOR]

Colorectal cancer is a malignant tumor with high morbidity and mortality worldwide. Histone lactylation, a new protein post-translational modification, can be used as a potential biomarker for the diagnosis and treatment of colorectal cancer by regulating the structure of chromatin and gene transcription. This paper focuses on the role and mechanism of histone lactylation modification in the development of colorectal cancer. Additionally, the latest research progress and clinical experimental results are presented. This paper further shows that histone lactylation manipulates gene expression by affecting nuclear transcription factors and other epigenetic modifications involved in various life processes and subsequently regulates cell physiological function, revealing its regulatory mechanism and the functions of related enzymes. The relationships between histone lactylation and energy metabolic pathways such as glycolysis and oxidative phosphorylation are discussed in detail. The final part of this paper illustrates the important role of this modification in terms of the occurrence and development of colorectal cancer, cell metabolic reprogramming, and epigenetic regulation, supporting the clinical application of the use of histone lactylation as a biomarker. [ABSTRACT FROM AUTHOR]

This document is a retraction notice from the journal Oncology Letters regarding a paper titled "miR-148a-3p suppresses epithelial ovarian cancer progression primarily by targeting c-Met." The retraction was prompted by a concerned reader who noticed that data in Figure 2C had already appeared in a different article by different authors. Since the contentious data had been submitted for publication prior to its submission to Oncology Letters, the editor decided to retract the paper. The authors were asked for an explanation but did not respond. The retraction notice apologizes for any inconvenience caused. [Extracted from the article]

Background: The ability of lignocellulose degradation for filamentous fungi is always attributed to their efficient CAZymes system with broader applications in bioenergy development. ADP-ribosylation factor GTPase-activating proteins (Arf-GAPs), pivotal in fungal morphogenesis, lack comprehensive studies on their regulatory mechanisms in lignocellulose utilization. Results: Here, the orthologs (TgGlo3 and TgGcs1) of Arf-GAPs in S. cerevisiae were characterized in Trichoderma guizhouense NJAU4742. The results indicated that overexpression of Tggcs1 (OE-Tggcs1) enhanced the lignocellulose utilization, whereas increased expression of Tgglo3 (OE-Tgglo3) elicited antithetical responses. On the fourth day of fermentation with rice straw as the sole carbon source, the activities of endoglucanase, cellobiohydrolase, xylanase, and filter paper of the wild-type strain (WT) reached 8.20 U mL−1, 4.42 U mL−1, 14.10 U mL−1, and 3.56 U mL−1, respectively. Compared to WT, the four enzymes activities of OE-Tggcs1 increased by 7.93%, 6.11%, 9.08%, and 12.92%, respectively, while those decreased to varying degrees of OE-Tgglo3. During the nutritional growth, OE-Tgglo3 resulted in the hyphal morphology characterized by sparsity and constriction, while OE-Tggcs1 led to a notable increase in vacuole volume. In addition, OE-Tggcs1 exhibited higher transport efficiencies for glucose and cellobiose thereby sustaining robust cellular metabolic rates. Further investigations revealed that Tgglo3 and Tggcs1 differentially regulated the transcription level of a dynamin-like GTPase gene (Tggtp), eliciting distinct redox states and apoptotic reaction, thus orchestrating the cellular response to lignocellulose utilization. Conclusions: Overall, these findings underscored the significance of TgArf-GAPs as pivotal regulators in lignocellulose utilization and provided initial insights into their differential modulation of downstream targets. [ABSTRACT FROM AUTHOR]

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After an RNA polymerase reaches a terminator, instead of dissociating from the template, it may diffuse along the DNA and recommence RNA synthesis from the previous or a different promoter. Magnetic tweezers were used to monitor such secondary transcription and determine the effects of low forces assisting or opposing translocation, protein roadblocks, and transcription factors. Remarkably, up to 50% of Escherichia coli (E. coli) RNA polymerases diffused along the DNA after termination. Force biased the direction of diffusion (sliding) and the velocity increased rapidly with force up to 0.7 pN and much more slowly thereafter. Sigma factor 70 (σ70) likely remained associated with the DNA promoting sliding and enabling re-initiation from promoters in either orientation. However, deletions of the α-C-terminal domains severely limited the ability of RNAP to turn around between successive rounds of transcription. The addition of elongation factor NusG, which competes with σ70 for binding to RNAP, limited additional rounds of transcription. Surprisingly, sliding RNA polymerases blocked by a DNA-bound lac repressor could slowly re-initiate transcription and were not affected by NusG, suggesting a σ-independent pathway. Low forces effectively biased promoter selection suggesting a prominent role for topological entanglements that affect RNA polymerase translocation. Tiny forces cause E. coli RNA polymerase to slide along DNA after transcription termination at up to 700 bp/s. In this paper, the authors use magnetic tweezers to show that sliding complexes containing complete alpha C-terminal domains repeat transcription from protein roadblocks sites and promoters in either orientation. [ABSTRACT FROM AUTHOR]

The analysis of transcriptional activity of the bacteriophage T5 hol/endo operon conducted in the paper revealed a strong constitutive promoter recognized by E. coli RNA polymerase and a transcription initiation point of the operon. It was also shown that the only translational start codon for holin was a non-canonical TTG. Translation initiation regions (TIRs) of both genes of the operon (hol and endo) were further analyzed using chimeric constructs, in which parts of the hol/endo regulatory regions were fused with the gene of a reporter protein (EGFP). It was found that TIR of hol was 20 times less effective than that of endo. As it turned out, the level of EGFP production was influenced by the composition of the constructs and the type of the hol start codon. Apparently, the translational suppression of holin's accumulation and posttranslational activation of endolysin by Ca2+ are the main factors ensuring the proper timing of the host cell lysis by bacteriophage T5. The approach based on the use of chimeric constructs proposed in the paper can be recommended for studying other native or artificial operons of any complexity: analyzing the impacts of separate DNA regions, as well as their coupled effect, on the processes of transcription and translation of recombinant protein(s). [ABSTRACT FROM AUTHOR]

Introduction: Bacteria frequently encounter nutrient limitation in nature. The ability of living in this nutrient shortage environment is vital for bacteria to preserve their population and important for some pathogenic bacteria to cause infectious diseases. Usually, we study how bacteria survive after nutrient depletion, a total starvation condition when bacteria almost cease growth and try to survive. However, nutrient limitation may not always lead to total starvation. Methods: Bacterial adaptation to nutrient shortage was studied by determining bacterial growth curves, intracellular pH, intracellular amino acid contents, gene transcription, protein expression, enzyme activity, and translation and replication activities. Results: No exogenous supply of methionine results in growth attenuation of Streptococcus pneumoniae, a human pathogen. In this paper, we refer to this inhibited growth state between ceased growth under total starvation and fullspeed growth with full nutrients as semi-starvation. Similar to total starvation, methionine semi-starvation also leads to intracellular acidification. Surprisingly, it is intracellular acidification but not insufficient methionine synthesis that causes growth attenuation under methionine semi-starvation. With excessive glutamine supply in the medium, intracellular methionine level was not changed, while bacterial intracellular pH was elevated to ~ 7.6 (the optimal intracellular pH for pneumococcal growth) by glutamine deamination, and bacterial growth under semi-starvation was restored fully. Our data suggest that intracellular acidification decreases translation level and glutamine supply increases intracellular pH to restore translation level, thus restoring bacterial growth. Discussion: This growth with intracellular pH adjustment by glutamine is a novel strategy we found for bacterial adaptation to nutrient shortage, which may provide new drug targets to inhibit growth of pathogenic bacteria under semi-starvation. [ABSTRACT FROM AUTHOR]

Background: Plasmodium vivax is the main causative agent of malaria in Panama. However, the prevalence of asymptomatic infections in the different endemic regions remains unknown. Understanding the epidemiological behavior of asymptomatic infections is essential for the elimination of malaria. This study aimed to determine the prevalence of asymptomatic malarial infections in one of the main endemic regions of Panama using multiplex real-time reverse transcription RT-MqPCR. Methods: A cross-sectional study was conducted in three communities in the Guna Yala Comarca. A total of 551 thick blood smears and their respective samples on filter paper were collected from volunteers of different ages and sexes from June 20 to 25, 2016. Infections by the Plasmodium spp. were diagnosed using microscopy and RT-MqPCR. All statistical analyses were performed using the R software. Results: The average prevalence of asymptomatic infections by P. vivax in the three communities detected by RT-MqPCR was 9.3%, with Ukupa having the highest prevalence (13.4%), followed by Aidirgandi (11.1%) and Irgandi (3.3%). A total of 74 samples were diagnosed as asymptomatic infections using RT-MqPCR. Light microscopy (LM) detected that 17.6% (13/74) of the asymptomatic samples and 82.4% (61/74) were diagnosed as false negatives. A 100% correlation was observed between samples diagnosed using LM and RT-MqPCR. A total of 52.7% (39/74) of the asymptomatic patients were female and 85.1% (63/74) were registered between the ages of 1 and 21 years. Factors associated with asymptomatic infection were community (aOR = 0.38 (95% CI 0.17–0.83), p < 0.001) and age aOR = 0.98 (95% CI 0.97–1.00), p < 0.05); F = 5.38; p < 0.05). Conclusions: This study provides novel evidence of the considerable prevalence of asymptomatic P. vivax infections in the endemic region of Kuna Yala, representing a new challenge that requires immediate attention from the National Malaria Program. The results of this study provide essential information for the health authorities responsible for developing new policies. Furthermore, it will allow program administrators to reorient and design effective malaria control strategies that consider asymptomatic infections as a fundamental part of malaria control and move towards fulfilling their commitment to eliminate it. [ABSTRACT FROM AUTHOR]

T cell exhaustion occurs mostly in chronic infections, cancers and autoimmune diseases. Continuous antigenic stimulation leads to the generation of exhausted T cells, which is characterized by progressive loss of effector function, continuous high expression of inhibitory receptors, transcription and epigenetic changes, and metabolic disorders. The in-depth study of the specific mechanism of T cell exhaustion is providing new ideas for the immunotherapy of chronic infection, lung cancer and chronic airway inflammatory disease in respiratory diseases. This paper discussed the influencing factors and characteristics of T cell exhaustion and reviewed the current research status of T cell exhaustion and respiratory diseases. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a complex disease that develops through a sequence of molecular events that are still poorly defined. This process is driven by a multitude of context-dependent genes that play different roles based on their environment. The complexity and multi-faceted nature of these genes make it difficult to study the genetic basis of IBD. The goal of this article is to review the key genes in the pathophysiology of IBD and highlight new technology that can be used in further research. This paper examines Nanostring RNA probe technology, which uses tissue analyzed without the use of enzymes, transcription, or amplification. Nanostring offers several panels of genes to test, including an inflammation panel of 234 genes. This article analyzes this panel and reviews the literature for each gene's effect in IBD for use as a framework to review the pathophysiology of the disease. The panel was narrowed to 26 genes with significant evidence of mechanistic potential in IBD, which were then categorized into specific areas of pathogenesis. These include gut barrier breakdown, inappropriate recognition of commensal bacteria, immune cell activation, proinflammatory cytokine release, and subsequent impairment of the anti-inflammatory response. The eventual goal of this paper is the creation of a customized panel of IBD genes that can be used to better understand the genetic mechanism of IBD and aid in the development of future therapies in IBD. [ABSTRACT FROM AUTHOR]

The Epstein-Barr virus (EBV) is frequently found in endomyocardial biopsies (EMBs) from patients with heart failure, but the detection of EBV-specific DNA has not been associated with progressive hemodynamic deterioration. In this paper, we investigate the use of targeted next-generation sequencing (NGS) to detect EBV transcripts and their correlation with myocardial inflammation in EBV-positive patients with heart failure with reduced ejection fraction (HFrEF). Forty-four HFrEF patients with positive EBV DNA detection and varying degrees of myocardial inflammation were selected. EBV-specific transcripts from EMBs were enriched using a custom hybridization capture-based workflow and, subsequently, sequenced by NGS. The short-read sequencing revealed the presence of EBV-specific transcripts in 17 patients, of which 11 had only latent EBV genes and 6 presented with lytic transcription. The immunohistochemical staining for CD3+ T lymphocytes showed a significant increase in the degree of myocardial inflammation in the presence of EBV lytic transcripts, suggesting a possible influence on the clinical course. These results imply the important role of EBV lytic transcripts in the pathogenesis of inflammatory heart disease and emphasize the applicability of targeted NGS in EMB diagnostics as a basis for specific treatment. [ABSTRACT FROM AUTHOR]

Cellular senescence is closely related to DNA damage, proteasome inactivity, histone loss, epigenetic alterations, and tumorigenesis. The mammalian proteasome activator PA200 (also referred to as PSME4) or its yeast ortholog Blm10 promotes the acetylation-dependent degradation of the core histones during transcription, DNA repair, and spermatogenesis. According to recent studies, PA200 plays an important role in senescence, probably because of its role in promoting the degradation of the core histones. Loss of PA200 or Blm10 is a major cause of the decrease in proteasome activity during senescence. In this paper, recent research progress on the association of PA200 with cellular senescence is summarized, and the potential of PA200 to serve as a therapeutic target in age-related diseases is discussed. [ABSTRACT FROM AUTHOR]

Protein-DNA complex interactivity plays a crucial role in biological activities such as gene expression, modification, replication and transcription. Understanding the physiological significance of protein-DNA binding interfacial hot spots, as well as the development of computational biology, depends on the precise identification of these regions. In this paper, a hot spot prediction method called EC-PDH is proposed. First, we extracted features of these hot spots' solid solvent-accessible surface area (ASA) and secondary structure, and then the mean, variance, energy and autocorrelation function values of the first three intrinsic modal components (IMFs) of these conventional features were extracted as new features via the empirical modal decomposition algorithm (EMD). A total of 218 dimensional features were obtained. For feature selection, we used the maximum correlation minimum redundancy sequence forward selection method (mRMR-SFS) to obtain an optimal 11-dimensional-feature subset. To address the issue of data imbalance, we used the SMOTE-Tomek algorithm to balance positive and negative samples and finally used cat gradient boosting (CatBoost) to construct our hot spot prediction model for protein-DNA binding interfaces. Our method performs well on the test set, with AUC, MCC and F1 score values of 0.847, 0.543 and 0.772, respectively. After a comparative evaluation, EC-PDH outperforms the existing state-of-the-art methods in identifying hot spots. [ABSTRACT FROM AUTHOR]

Lists forthcoming papers on biochemistry, compiled as of April 1992. 'The Effect of Polylysine on Casein-kinase-2 Activity is Influenced by Both the Structure of the Protein/Peptide Substrates and the Subunit Composition of the Enzyme,' by F. Meggio, B. Boldyreff and O. Marin; 'Increased Steady-State Levels of Several Mitochondrial and Nuclear Gene Transcripts in Rat Hepatoma With a Low Content of Mitochondria,' by K. Luctakova and S. Kuzela; 'Phycobilisome Structure in the Cyanobacteria Mastiglocladus laminosus and Anabaena Sp. PCC 7120,' by M. Glauser and D.A. Bryant.

The article announces that Vanessa Ferreira Merino is honored with the Paper of the Year 2005 Award by the Editors of Biological Chemistry and the German Society for Biochemistry and Molecular Biology for her paper on "Molecular structure and transcriptional regulation by nuclear factor-κB of the mouse kinin B1 receptor gene," that was published in June 2005 issue of Biological Chemistry. A brief profile of Vanessa with a discussion on her paper is provided.

Reports that Rui Monteiro's paper "Spatio-temporal Activation of Smad1 and Smad5 in Vivo: Monitoring Transcriptional Activity of Smad Proteins" received the award for the Best Paper published in 2004 in the "Journal of Cell Science". Profile of Monteiro; Prize; Insights about his research article.

Vascular endothelial cell functions affect lower extremity arteriosclerosis obliterans (LEASO), while alpha-2-macroglobulin (A2M) and CCCTC-binding factor (CTCF) are closely related to the function of such cells. This paper aims to identify the influences of CTCF on vascular endothelial cells in LEASO by regulating A2M. A rat model of LEASO was established to measure intima-media ratio, blood lipid, and inflammatory factor levels. By constructing LEASO cell models, cell viability and apoptosis were assayed, while autophagy-related proteins, CTCF and A2M levels in femoral artery tissues and HUVECs were determined. The transcriptional regulation of CTCF on A2M was verified. In LEASO rat models, femoral artery lumen was narrowed and endothelial cells were disordered; levels of total cholesterol, IL-1, and TNF-a enhanced, and HDL-C decreased, with strong expression of A2M and low expression of CTCF. The viability of ox-LDL-treated HUVECs was decreased, together with higher apoptosis, lower LC3II/I expression, and higher p62 expression, which were reversed by sh-A2M transfection. Overexpression of CTCF inhibited A2M transcription, promoted the viability and autophagy of HUVECs, and decreased apoptosis. Collectively, CTCF improves the function of vascular endothelial cells in LEASO by inhibiting A2M transcription. [ABSTRACT FROM AUTHOR]

Transcription factors (TFs) are proteins essential for regulating genetic transcriptions by binding to transcription factor binding sites (TFBSs) in DNA sequences. Accurate predictions of TFBSs can contribute to the design and construction of metabolic regulatory systems based on TFs. Although various deep-learning algorithms have been developed for predicting TFBSs, the prediction performance needs to be improved. This paper proposes a bidirectional encoder representations from transformers (BERT)-based model, called BERT-TFBS, to predict TFBSs solely based on DNA sequences. The model consists of a pre-trained BERT module (DNABERT-2), a convolutional neural network (CNN) module, a convolutional block attention module (CBAM) and an output module. The BERT-TFBS model utilizes the pre-trained DNABERT-2 module to acquire the complex long-term dependencies in DNA sequences through a transfer learning approach, and applies the CNN module and the CBAM to extract high-order local features. The proposed model is trained and tested based on 165 ENCODE ChIP-seq datasets. We conducted experiments with model variants, cross-cell-line validations and comparisons with other models. The experimental results demonstrate the effectiveness and generalization capability of BERT-TFBS in predicting TFBSs, and they show that the proposed model outperforms other deep-learning models. The source code for BERT-TFBS is available at https://github.com/ZX1998-12/BERT-TFBS. [ABSTRACT FROM AUTHOR]

The "warts and all" transcriptions of two early Olive Schreiner draft manuscripts of parts of what was later published as From Man to Man are examined in detail. They are analysed by treating them as avant-textes and using a genetic criticism approach. Doing so, different aspects of her writing practices come into view around the distinction she made between her "ordinary writing", which encompassed "in the moment" additions, deletions, and amendments, and what she described as "overworking", the after the event activities usually termed editing. Although coexisting on the manuscript pages, these are shown to be distinct sets of practices exerting different pressures. Some problems of emplotment and narrative continuity arose through attempting to combine both, so she contemplated having recourse to an earlier version of the manuscript, with hints in letters raising the possibility that this had a different narrative structure. [ABSTRACT FROM AUTHOR]

The article presents information about the upcoming papers related to biochemistry that will appear in the 1987 issue of the journal "European Journal of Biochemistry." Some of the papers are "Influence of Different S'-Flanking Sequences of tRNA Genes on Their in Vivo Transcription Efficiencies in Saccharomyces Cerevisiae," by researchers T. Dingermann, K. Nerke and R. Marschatek, "Transcription Factois Mediate rRNA Synthesis During Myogenesis," by researchers P. Zahradka and B. H. Sells, "Influence of the Piotonation Degree on the Self-Association Properties of Adenosine 5'-Triphosphate (ATP)," by researchers R. Tribolet and H. Sigel.

This study examines the transcriptional response of human epidermal keratinocytes (HEK) to sulfur mustard (HD) in order to gain a better understanding of the intracellular events that result in cytotoxicity. Differential display polymerase chain reaction technology was used to examine the relative transcriptional activity of healthy cells to those exposed to subvesicating or vesicating concentrations of HD for 4 h. Approximately 2% of the HEK transcriptome had altered expression. Sixty of the most prominently altered transcripts were characterized. Important upregulated genes include NADH dehydrogenase III, GADD45 and ubiquitin. Key downregulated genes include type I keratin 14, α-enolase and caltractin. Many of the identified transcripts protein products presently do not have an assigned function and eleven transcripts were unidentifiable. These transcriptional alterations provide one of the first molecular insights into the intracellular events induced by HD. Published in 2003 by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Resource-limited regions face a greater burden of infectious diseases due to limited access to molecular tests, complicating timely diagnosis and management. Current molecular point-of-care tests (POCTs) either come with high costs or lack adequate sensitivity and specificity. To facilitate better prevention and control of infectious diseases in underserved areas, we seek to address the need for molecular POCTs that better align with the World Health Organization (WHO)'s ASSURED criteria—Affordable, Sensitive, Specific, User-friendly, Rapid and robust, Equipment-free, and Deliverable to end users. Methods: A novel molecular POCT, Pasteur Pipette-assisted isothermal probe amplification (pp-IPA), was developed for malaria detection. Without any microfluidics, this method captures Plasmodium 18S rRNA in a modified Pasteur pipette using tailed genus-specific probes. After washing, the bound tailed probes are ligated to form a template for subsequent novel isothermal probe amplification using a pair of generic primers, bypassing nucleic acid extraction and reverse transcription. The method was assessed using cultured Plasmodium and compared with real-time quantitative reverse transcription PCR (RT-qPCR) or reverse transcription loop-mediated isothermal amplification (RT-LAMP) in clinical blood samples. Results: The entire assay is completed in 60–80 min with minimal hands-on time, using only a Pasteur pipette and a water bath. The pp-IPA's analytical sensitivity is 1.28 × 10–4 parasites/μl, with 100% specificity against various blood-borne pathogens causing malaria-like symptoms. Additionally, pp-IPA needs only liquid-transfer skill for operation and the cost is around USD 0.25 per test, making it at least 300 times lower than mainstream POCT platforms. Conclusions: Designed to improve the accessibility of molecular detection in resource-limited settings, pp-IPA's simplicity, affordability, high sensitivity/specificity, and minimal equipment requirements make it a promising point-of-care pathogen identification tool in resource-constrained regions. [ABSTRACT FROM AUTHOR]

Droplet digital polymerase chain reaction (ddPCR) stands out as a highly sensitive diagnostic technique that is gaining traction in infectious disease diagnostics due to its ability to quantitate very low numbers of viral gene copies. By partitioning the sample into thousands of droplets, ddPCR enables precise and absolute quantification without relying on a standard curve. However, current ddPCR systems often exhibit relatively low levels of integration, and the analytical process remains dependent on elaborate workflows for up-front sample preparation. Here, we introduce a fully-integrated system seamlessly combining viral lysis, RNA extraction, emulsification, reverse transcription (RT) ddPCR, and fluorescence readout in a sample-to-answer format. The system comprises a disposable microfluidic cartridge housing buffers and reagents required for the assay, and a centrifugal platform that allows for pneumatic actuation of liquids during rotation, enabling automation of the workflow. Highly monodisperse droplets (∼50 μm in diameter) are produced using centrifugal step emulsification and automatically transferred to an integrated heating module for target amplification. The platform is equipped with a miniature fluorescence imaging system enabling on-chip read-out of droplets after RT-ddPCR. We demonstrate sample-to-answer detection of SARS-CoV-2 N and E genes, along with RNase P endogenous reference, using hydrolysis probes and multiplexed amplification within single droplets for concentrations as low as 0.1 copy per μL. We also tested 14 nasopharyngeal swab specimens from patients and were able to distinguish positive and negative SARS-CoV-2 samples with 100% accuracy, surpassing results obtained by conventional real-time amplification. [ABSTRACT FROM AUTHOR]

A novel Gd-MOF based on tetrafluoro-terephthalic acid has been synthesized and its structure has been solved using X-ray single crystal diffraction data. The compound, with the formula [Gd2(F4BDC)3·H2O]·DMF, is isostructural with other Ln-MOFs based on the same ligand and has been recently reported. Its crystals were also reduced to nanometer size by employing acetic acid or cetyltrimethylammonium bromide (CTAB) as a modulator. The relaxometric properties of the nanoparticles were evaluated in solution by measuring 1H T1 and T2 as a function of the applied magnetic field and temperature. The biocompatibility of Gd-MOFs was evaluated on murine microglial BV-2 and human glioblastoma U251 cell lines. In both cell lines, Gd-MOFs do not modify the cell cycle profile or the activation levels of ERK1/2 and Akt, which are protein-serine/threonine kinases that participate in many signal transduction pathways. These pathways are fundamental in the regulation of a large variety of processes such as cell migration, cell cycle progression, differentiation, cell survival, metabolism, transcription, tumour progression and others. These data indicate that Gd-MOF nanoparticles exhibit high biocompatibility, making them potentially valuable for diagnostic and biomedical applications. [ABSTRACT FROM AUTHOR]

Loop-mediated isothermal amplification (LAMP) of genetic materials has emerged as a powerful molecular biology technique with great potential to be a standard point-of-care (POC) technique. This method has found several applications, but it still presents challenges for its direct on-site application, particularly in terms of integrated reaction and detection systems and the risk of carryover contamination. In this work, we propose an innovative solution – an electrochemical microcentrifuge tube cap (ElectrochemCap) based on a screen-printed electrode, a 3D printed adapter and an adhesive layer – which integrates the amplification reaction and its subsequent electrochemical detection in a single device. The design, fabrication, and electrochemical characterization of the ElectrochemCap are reported here, demonstrating its suitability for LAMP detection. Rapidly emerging technologies, such as 3D printing or xurography, are the basis of a prototype that has been validated for the detection of SARS-CoV-2 using reverse transcription LAMP (RT-LAMP), achieving results comparable to those obtained by gold-standard RT-qPCR. Moreover, we have explored the versatility of the ElectrochemCap presenting several additional designs (for containers with different volumes, shapes and materials, as well as multiplexed approaches), expanding its potential applications. Overall, the ElectrochemCap represents an affordable, versatile, and marketable innovation for integrated quantitative electrochemical detection, with enormous possibilities in bioelectroanalytical procedures and portable laboratory setups. [ABSTRACT FROM AUTHOR]

This correction notice addresses a formatting error in Figure 3 of the published paper titled "HSV-1 ICP22 Is a Selective Viral Repressor of Cellular RNA Polymerase II-Mediated Transcription Elongation." The authors provide a revised version of Figure 3, which includes a graph showing the interaction between ICP22 and the FACT complex. The authors assure readers that the scientific conclusions of the paper remain unaffected. The original publication has been updated accordingly. [Extracted from the article]

Background: We currently have the ability to quantify transcript abundance of messenger RNA (mRNA), genome-wide, using microarray technologies. Analyzing genotype, phenotype and expression data from 20 pedigrees, the members of our Genetic Analysis Workshop (GAW) 19 gene expression group published 9 papers, tackling some timely and important problems and questions. To study the complexity and interrelationships of genetics and gene expression, we used established statistical tools, developed newer statistical tools, and developed and applied extensions to these tools. Methods: To study gene expression correlations in the pedigree members (without incorporating genotype or trait data into the analysis), 2 papers used principal components analysis, weighted gene coexpression network analysis, meta-analyses, gene enrichment analyses, and linear mixed models. To explore the relationship between genetics and gene expression, 2 papers studied expression quantitative trait locus allelic heterogeneity through conditional association analyses, and epistasis through interaction analyses. A third paper assessed the feasibility of applying allele-specific binding to filter potential regulatory single-nucleotide polymorphisms (SNPs). Analytic approaches included linear mixed models based on measured genotypes in pedigrees, permutation tests, and covariance kernels. To incorporate both genotype and phenotype data with gene expression, 4 groups employed linear mixed models, nonparametric weighted U statistics, structural equation modeling, Bayesian unified frameworks, and multiple regression. Results and discussion: Regarding the analysis of pedigree data, we found that gene expression is familial, indicating that at least 1 factor for pedigree membership or multiple factors for the degree of relationship should be included in analyses, and we developed a method to adjust for familiality prior to conducting weighted co-expression gene network analysis. For SNP association and conditional analyses, we found FaST-LMM (Factored Spectrally Transformed Linear Mixed Model) and SOLAR-MGA (Sequential Oligogenic Linkage Analysis Routines -Major Gene Analysis) have similar type 1 and type 2 errors and can be used almost interchangeably. To improve the power and precision of association tests, prior knowledge of DNase-I hypersensitivity sites or other relevant biological annotations can be incorporated into the analyses. On a biological level, eQTL (expression quantitative trait loci) are genetically complex, exhibiting both allelic heterogeneity and epistasis. Including both genotype and phenotype data together with measurements of gene expression was found to be generally advantageous in terms of generating improved levels of significance and in providing more interpretable biological models. Conclusions: Pedigrees can be used to conduct analyses of and enhance gene expression studies. [ABSTRACT FROM AUTHOR]

Changes in the abundance of certain bacterial species within the colorectal microbiota correlate with colorectal cancer (CRC) development. While carcinogenic mechanisms of single pathogenic bacteria have been characterized in vitro, limited tools are available to investigate interactions between pathogenic bacteria and both commensal microbiota and colonocytes in a physiologically relevant tumor microenvironment. To address this, we developed a microfluidic device that can be used to co-culture colonocyte spheroids and colorectal microbiota. The device was used to explore the effect of Fusobacterium nucleatum, an opportunistic pathogen associated with colorectal cancer development in humans, on colonocyte gene expression and microbiota composition. F. nucleatum altered the transcription of genes involved in cytokine production, epithelial-to-mesenchymal transition, and proliferation in colonocytes in a contact-independent manner; however, most of these effects were significantly diminished by the presence of commensal microbiota. Interestingly, F. nucleatum significantly altered the abundance of multiple bacterial clades associated with mucosal immune responses and cancer development in the colon. Our results highlight the importance of evaluating the potential carcinogenic activity of pathogens in the context of a commensal microbiota, and the potential to discover novel inter-species microbial interactions in the CRC microenvironment. [ABSTRACT FROM AUTHOR]

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DNA gyrase, a ubiquitous bacterial enzyme, is a type IIA topoisomerase formed by heterotetramerisation of 2 GyrA subunits and 2 GyrB subunits, to form the active complex. DNA gyrase can loop DNA around the C-terminal domains (CTDs) of GyrA and pass one DNA duplex through a transient double-strand break (DSB) established in another duplex. This results in the conversion from a positive (+1) to a negative (-1) supercoil, thereby introducing negative supercoiling into the bacterial genome by steps of 2, an activity essential for DNA replication and transcription. The strong protein interface in the GyrA dimer must be broken to allow passage of the transported DNA segment and it is generally assumed that the interface is usually stable and only opens when DNA is transported, to prevent the introduction of deleterious DSBs in the genome. In this paper, we show that DNA gyrase can exchange its DNA-cleaving interfaces between two active heterotetramers. This so-called interface 'swapping' (IS) can occur within a few minutes in solution. We also show that bending of DNA by gyrase is essential for cleavage but not for DNA binding per se and favors IS. Interface swapping is also favored by DNA wrapping and an excess of GyrB. We suggest that proximity, promoted by GyrB oligomerization and binding and wrapping along a length of DNA, between two heterotetramers favors rapid interface swapping. This swapping does not require ATP, occurs in the presence of fluoroquinolones, and raises the possibility of non-homologous recombination solely through gyrase activity. The ability of gyrase to undergo interface swapping explains how gyrase heterodimers, containing a single active-site tyrosine, can carry out double-strand passage reactions and therefore suggests an alternative explanation to the recently proposed 'swivelling' mechanism for DNA gyrase (Gubaev et al., 2016). [ABSTRACT FROM AUTHOR]

Transcription is extremely important for cellular processes but can be hindered by RNA polymerase II (RNAPII) pausing and stalling. Cockayne syndrome protein B (CSB) promotes the progression of paused RNAPII or initiates transcription-coupled nucleotide excision repair (TC-NER) to remove stalled RNAPII. However, the specific mechanism by which CSB initiates TC-NER upon damage remains unclear. In this study, we identified the indispensable role of the ARK2N-CK2 complex in the CSB-mediated initiation of TC-NER. The ARK2N-CK2 complex is recruited to damage sites through CSB and then phosphorylates CSB. Phosphorylation of CSB enhances its binding to stalled RNAPII, prolonging the association of CSB with chromatin and promoting CSA-mediated ubiquitination of stalled RNAPII. Consistent with this finding, Ark2n-/-mice exhibit a phenotype resembling Cockayne syndrome. These findings shed light on the pivotal role of the ARK2N-CK2 complex in governing the fate of RNAPII through CSB, bridging a critical gap necessary for initiating TC-NER. [ABSTRACT FROM AUTHOR]

Mammalian DNA folds into 3D structures that facilitate and regulate genetic processes such as transcription, DNA repair, and epigenetics. Several insights derive from chromosome capture methods, such as Hi-C, which allow researchers to construct contact maps depicting 3D interactions among all DNA segment pairs. These maps show a complex cross-scale organization spanning megabase-pair compartments to short-ranged DNA loops. To better understand the organizing principles, several groups analyzed Hi-C data assuming a Russian-doll-like nested hierarchy where DNA regions of similar sizes merge into larger and larger structures. Apart from being a simple and appealing description, this model explains, e.g., the omnipresent chequerboard pattern seen in Hi-C maps, known as A/B compartments, and foreshadows the co-localization of some functionally similar DNA regions. However, while successful, this model is incompatible with the two competing mechanisms that seem to shape a significant part of the chromosomes' 3D organization: loop extrusion and phase separation. This paper aims to map out the chromosome's actual folding hierarchy from empirical data. To this end, we take advantage of Hi-C experiments and treat the measured DNA-DNA interactions as a weighted network. From such a network, we extract 3D communities using the generalized Louvain algorithm. This algorithm has a resolution parameter that allows us to scan seamlessly through the community size spectrum, from A/B compartments to topologically associated domains (TADs). By constructing a hierarchical tree connecting these communities, we find that chromosomes are more complex than a perfect hierarchy. Analyzing how communities nest relative to a simple folding model, we found that chromosomes exhibit a significant portion of nested and non-nested community pairs alongside considerable randomness. In addition, by examining nesting and chromatin types, we discovered that nested parts are often associated with active chromatin. These results highlight that cross-scale relationships will be essential components in models aiming to reach a deep understanding of the causal mechanisms of chromosome folding. Author summary: The 3D organization of mammalian DNA affects genetic processes, such as transcription, DNA repair, and epigenetics. To unravel the complexity of the 3D structure, researchers developed numerous experimental methods, the most advanced being Hi-C. This method enables scientists to create "contact maps" illustrating the 3D interactions among all pairs of DNA segments across the genome. These maps unveiled a multi-scale organization, ranging from megabase-pair compartments to short-range DNA loops. Common explanations for this organization rest on nested hierarchies, where DNA regions of similar sizes coalesce into larger structures. However, such a model is incompatible with competing molecular mechanisms, primarily loop extrusion and phase separation, that shape the chromosomes' 3D organization at different scales. Our study aims to map out the actual chromosome folding relationships using Hi-C data sets. Treating the data as a weighted network of DNA-DNA interactions, we identified 3D communities across different network scales using the Generalized Louvain method, a standard community detection algorithm. By building a tree linking these communities, we discovered that chromosome organization is more intricate than a perfect hierarchy suggests. Instead, we found that chromosomes exhibit a mix of nested and non-nested community pairs alongside considerable randomness. The nested parts often associate with active chromatin. These results highlight that cross-scale relationships are critical for understanding the causal mechanisms of chromosome folding. [ABSTRACT FROM AUTHOR]

Vitamins, exogenous organic compounds that play a vital role in metabolic reactions, and fundamental powerful antioxidants with a crucial role in the genetic transcription process, are considered essential nutritional factors. Folic acid (FA), also known as folate, or Vitamin B9, plays an indispensable role in various intracellular reactions, being the main pawn, with a strong impact on medical and dental science. The aim of this paper mainly focuses on presenting the latest and most advanced aspects related to the following topics: (1) the resonance that FA, and more specifically FA deficiency, has at the level of the oral cavity; (2) the elements involved in the molecular landscape, which reflect the interaction and the possible mechanisms of action, through which FA influences oral health; and (3) the particular processes by which FA deficiency causes certain clinical conditions. Moreover, we aim to draw the attention and trigger the curiosity of health professionals on the need to know the specific host–environment interactions, particularly the linkage between individual genotype and phenotypic variability, which in the future could represent the basis of novel and effective treatment methods. From this perspective, we begin by providing an overview of the general radar echo of the human body induced by FA deficiency, before focusing on the genetic strategic substrate and biochemical processes involved in the molecular mechanisms through which FA acts at the cellular level. Finally, we reflect on the resulting conclusions: (1) the complex interrelationships between different types of cytokines (CKs) and abnormal folate metabolism are involved in the occurrence of neural tube defects (NTDs) and orofacial clefts (OFCs); (2) increased oxidative stress, endothelial dysfunction, and genomic instability, induced by folate deficiency, have a major impact on periodontal health; and (3) glutamate carboxypeptidase II, GCP2 1561C>T allelic variant, constitutes the main pawn, which specifically influences the bioavailability of natural folates and FA, as the main actors, with essential roles in oral health. [ABSTRACT FROM AUTHOR]

• Extracting complex feature information of TIS using multiple encodings. • Capturing hierarchical relationships between features using capsule network. • Improvements are made to the capsule network to enhance performance. • The proposed model improves the prediction performance compared to other models. Genes are the basic units of protein synthesis in organisms, and accurately identifying the translation initiation site (TIS) of genes is crucial for understanding the regulation, transcription, and translation processes of genes. However, the existing models cannot adequately extract the feature information in TIS sequences, and they also inadequately capture the complex hierarchical relationships among features. Therefore, a novel predictor named CapsNet-TIS is proposed in this paper. CapsNet-TIS first fully extracts the TIS sequence information using four encoding methods, including One-hot encoding, physical structure property (PSP) encoding, nucleotide chemical property (NCP) encoding, and nucleotide density (ND) encoding. Next, multi-scale convolutional neural networks are used to perform feature fusion of the encoded features to enhance the comprehensiveness of the feature representation. Finally, the fused features are classified using capsule network as the main network of the classification model to capture the complex hierarchical relationships among the features. Moreover, we improve the capsule network by introducing residual block, channel attention, and BiLSTM to enhance the model's feature extraction and sequence data modeling capabilities. In this paper, the performance of CapsNet-TIS is evaluated using TIS datasets from four species: human, mouse, bovine, and fruit fly, and the effectiveness of each part is demonstrated by performing ablation experiments. By comparing the experimental results with models proposed by other researchers, the results demonstrate the superior performance of CapsNet-TIS. [ABSTRACT FROM AUTHOR]