Explore the vast range of titles available.

\"One of Literary Hub's Most Anticipated Books of 2024. Exploring the most transformative breakthroughs in biology since the discovery of the double helix, a Nobel Prize-winning scientist unveils the RNA age. For over half a century, DNA has dominated science and the popular imagination as the \"secret of life.\" But over the last several decades, a quiet revolution has taken place. In a series of breathtaking discoveries, the biochemist Thomas R. Cech and a diverse cast of brilliant scientists have revealed that RNA--long overlooked as the passive servant of DNA--sits at the center of biology's greatest mysteries: How did life begin? What makes us human? Why do we get sick and grow old? In The Catalyst, Cech finally brings together years of research to demonstrate that RNA is the true key to understanding life on Earth, from its very origins to our future in the twenty-first century. A gripping journey of discovery, The Catalyst moves from the early experiments that first hinted at RNA's spectacular powers, to Cech's own paradigm-shifting finding that it can catalyze cellular reactions, to the cutting-edge biotechnologies poised to reshape our health. We learn how RNA--once thought merely to transmit DNA's genetic instructions to the cell's protein-making machinery--may have jump-started life itself, and how, at the same time, it can cut our individual lives short through viral diseases and cancer. We see how RNA is implicated in the aging process and explore the darker depths of the supposed fountain of youth, telomerase. And we catch a thrilling glimpse into how RNA-powered therapies--from CRISPR, the revolutionary tool that uses RNA to rewrite the code of life, to the groundbreaking mRNA vaccines that have saved millions during the pandemic, and more--may enable us to improve and even extend life beyond nature's current limits. Written by one of our foremost scientists, The Catalyst is a must-read guide to the present and future of biology and medicine\"-- Provided by publisher.

This study reports on 382 COVID-19 patients having undergone allogeneic ( n  = 236) or autologous ( n  = 146) hematopoietic cell transplantation (HCT) reported to the European Society for Blood and Marrow Transplantation (EBMT) or to the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH). The median age was 54.1 years (1.0–80.3) for allogeneic, and 60.6 years (7.7–81.6) for autologous HCT patients. The median time from HCT to COVID-19 was 15.8 months (0.2–292.7) in allogeneic and 24.6 months (−0.9 to 350.3) in autologous recipients. 83.5% developed lower respiratory tract disease and 22.5% were admitted to an ICU. Overall survival at 6 weeks from diagnosis was 77.9% and 72.1% in allogeneic and autologous recipients, respectively. Children had a survival of 93.4%. In multivariate analysis, older age ( p  = 0.02), need for ICU ( p  < 0.0001) and moderate/high immunodeficiency index ( p  = 0.04) increased the risk while better performance status ( p  = 0.001) decreased the risk for mortality. Other factors such as underlying diagnosis, time from HCT, GVHD, or ongoing immunosuppression did not significantly impact overall survival. We conclude that HCT patients are at high risk of developing LRTD, require admission to ICU, and have increased mortality in COVID-19.

\"Breakthrough chronicles the life, hard work, and accomplishments of Katalin Karikó, one of the pioneering mRNA researchers whose work led to COVID-19 vaccines, depicting her as an inspirational figure for readers interested in science\"-- Provided by publisher.

Introduction: P. candolleana Wight et Arn. Is a traditional Chinese herbal medicine used by the Gelao nationality in southwest China, has been historically applied to treat various gastrointestinal disorders. Despite its traditional usage, scientific evidence elucidating its efficacy and mechanisms in treating ulcerative colitis (UC) remains sparse. This study aimed to determine the quality and chemical composition of Pimpinella candolleana and to identify its potential therapeutic targets and mechanisms in acetic acid-induced ulcerative colitis (UC) rats through integrated approaches. Methods: Morphological and microscopic characteristics, thin layer chromatography (TLC) identification, and quantitative analysis of P. candolleana were performed. UPLC-Q-TOF-MS, network pharmacology, and molecular docking were used to identify its chemical composition and predict its related targets in UC. Furthermore, a rat model was established to evaluate the therapeutic effect and potential mechanism of P. candolleana on UC. Results: Microscopic identification revealed irregular and radial arrangement of the xylem in P. candolleana , with a light green cross-section and large medullary cells. UPLC-Q-TOF-MS analysis detected and analyzed 570 metabolites, including flavonoids, coumarins, and terpenoids. Network pharmacology identified 12 effective components and 176 target genes, with 96 common targets for P. candolleana -UC, including quercetin, luteolin, and nobiletin as key anti-inflammatory components. GO and KEGG revealed the potential involvement of their targets in RELA, JUN, TNF, IKBKB, PTGS2, and CHUK, with action pathways such as PI3K-Akt, TNF, IL-17, and apoptosis. Molecular docking demonstrated strong affinity and binding between these key components (quercetin, luteolin, and nobiletin) and the key targets of the pathway, including JUN and TNF. Treatment with P. candolleana improved body weight loss, the disease activity index, and colonic histological damage in UC rats. Pimpinella candolleana also modulated the levels of IL-2 and IL-6 in UC rats, reduced the expression of pro-inflammatory cytokines such as IL-6, MAPK8, TNF-α, CHUK, and IKBKB mRNA, and decreased the expression of TNF, IKBKB, JUN, and CHUK proteins in the colon of UC rats, thereby reducing inflammation and alleviating UC symptoms. Conclusion: P. candolleana exerts its protective effect on UC by reducing the expression of proinflammatory cytokines and inhibiting inflammation, providing scientific evidence for its traditional use in treating gastrointestinal diseases. This study highlights the potential of P. candolleana as a natural therapeutic agent for UC and contributes to the development of novel medicines for UC treatment.

This review summarizes the current knowledge on the contribution of metals to the development of oxidative stress in fish. Metals are important inducers of oxidative stress in aquatic organisms, promoting formation of reactive oxygen species through two mechanisms. Redox active metals generate reactive oxygen species through redox cycling, while metals without redox potential impair antioxidant defences, especially that of thiol-containing antioxidants and enzymes. Elevated levels of reactive oxygen species lead to oxidative damage including lipid peroxidation, protein and DNA oxidation, and enzyme inactivation. Antioxidant defences include the enzyme system and low molecular weight antioxidants. Metal-binding proteins, such as ferritin, ceruloplasmin and metallothioneins, have special functions in the detoxification of toxic metals and also play a role in the metabolism and homeostasis of essential metals. Recent studies of metallothioneins as biomarkers indicate that quantitative analysis of mRNA expression of metallothionein genes can be appropriate in cases with elevated levels of metals and no evidence of oxidative damage in fish tissue. Components of the antioxidant defence are used as biochemical markers of oxidative stress. These markers may be manifested differently in the field than in results found in laboratory studies. A complex approach should be taken in field studies of metal contamination of the aquatic environment.

Many examples of extreme virus resistance and posttranscriptional gene silencing of endogenous or reporter genes have been described in transgenic plants containing sense or antisense transgenes. In these cases of either cosuppression or antisense suppression, there appears to be induction of a surveillance system within the plant that specifically degrades both the transgene and target RNAs. We show that transforming plants with virus or reporter gene constructs that produce RNAs capable of duplex formation confer virus immunity or gene silencing on the plants. This was accomplished by using transcripts from one sense gene and one antisense gene colocated in the plant genome, a single transcript that has self-complementarity, or sense and antisense transcripts from genes brought together by crossing. A model is presented that is consistent with our data and those of other workers, describing the processes of induction and execution of posttranscriptional gene silencing.

Double-stranded RNA (dsRNA) recently has been shown to give rise to genetic interference in Caenorhabditis elegans and also is likely to be the basis for phenotypic cosuppression in plants in certain instances. While constructing a plasmid vector for transfection of trypanosome cells, we serendipitously discovered that in vivo expression of dsRNA of the alpha-tubulin mRNA 5' untranslated region (5' UTR) led to multinucleated cells with striking morphological alterations and a specific block of cytokinesis. Transfection of synthetic alpha-tubulin 5' UTR dsRNA, but not of either strand individually, caused the same phenotype. On dsRNA transfection, tubulin mRNA, but not the corresponding pre-mRNA, was rapidly and specifically degraded, leading to a deficit of alpha-tubulin synthesis. The transfected cells were no longer capable of carrying out cytokinesis and eventually died. Analysis of cytoskeletal structures from these trypanosomes revealed defects in the microtubules of the flagellar axoneme and of the flagellar attachment zone, a complex cortical structure that we propose is essential for establishing the path of the cleavage furrow at cytokinesis. Last, dsRNA-mediated mRNA degradation is not restricted to alpha-tubulin mRNA but can be applied to other cellular mRNAs, thus establishing a powerful tool to genetically manipulate these important protozoan parasites

mRNA vaccine pioneers uncover tangled history of discoveries, sparking new era of revolutionary cures. Unaware of the impending pandemic, visionary scientists sought gene therapy methods for cancer, HIV, and other deadly diseases. Their groundbreaking work on messenger RNA (mRNA) technology, now crowned by the 2023 Nobel Prize in Medicine, is sparking a new era of revolutionary cures.

Gene silencing is an important but little understood regulatory mechanism in plants. Here we report that a viral sequence, initially identified as a mediator of synergistic viral disease, acts to suppress the establishment of both transgene-induced and virus-induced posttranscriptional gene silencing. The viral suppressor of silencing comprises the 5′-proximal region of the tobacco etch potyviral genomic RNA encoding P1, helper component-proteinase (HC-Pro) and a small part of P3, and is termed the P1/HC-Pro sequence. A reversal of silencing assay was used to assess the effect of the P1/HC-Pro sequence on transgenic tobacco plants (line T4) that are posttranscriptionally silenced for the uidA reporter gene. Silencing was lifted in offspring of T4 crosses with four independent transgenic lines expressing P1/HC-Pro, but not in offspring of control crosses. Viral vectors were used to assess the effect of P1/HC-Pro expression on virus-induced gene silencing (VIGS). The ability of a potato virus X vector expressing green fluorescent protein to induce silencing of a green fluorescent protein transgene was eliminated or greatly reduced when P1/HC-Pro was expressed from the same vector or from coinfecting potato virus X vectors. Expression of the HC-Pro coding sequence alone was sufficient to suppress virus-induced gene silencing, and the HC-Pro protein product was required for the suppression. This discovery points to the role of gene silencing as a natural antiviral defense system in plants and offers different approaches to elucidate the molecular basis of gene silencing.

Taking the extraction amount of rutin as the index, the extraction process of rutin from Ilex asprella (Hook. et Arn.) Champ. ex Benth. using the ultrasonic-assisted deep eutectic solvent method was optimized through response surface method. The effects of various factors, including the types of deep eutectic solvent, molar ratio of the solvent, water content, liquid-solid ratio, the temperature, power and time of ultrasound on the extraction amount of rutin were investigated. In accordance with the result of univariate experiments, the extraction process was optimized through employing the Box-Behnken response surface design method. A three-factor, three-level experimental model was established with the liquid-solid ratio, water content and ultrasonic time as variables. The findings indicated that the optimal technological conditions were as stated below: the molar ratio of lactic acid to choline chloride at 1:1, the ultrasonic extraction temperature at 40 °C, the ultrasonic extraction time at 31 min, the water content at 28%, and the liquid-solid ratio at 20:1 mL/g. Under optimal conditions, the validation experimental result revealed that the extraction amount of rutin was 86.553 ± 1.35 µg/g, with an absolute error of less than 0.6% in comparison with the predicted value of the model. The use of deep eutectic solvents for the extraction of rutin and the application of response surface method for optimizing the extraction process of rutin from Ilex asprella (Hook. et Arn.) Champ. ex Benth. were demonstrated. The present study provided a reference for the comprehensive utilization of Ilex asprella (Hook. et Arn.) Champ. ex Benth. .