The eukaryotic ribosome: current status and challenges.
Ontology highlight
ABSTRACT:
SUBMITTER: Dinman JD
PROVIDER: S-EPMC2673243 | biostudies-literature | 2009 May
REPOSITORIES: biostudies-literature
Publications
The eukaryotic ribosome: current status and challenges.
The Journal of biological chemistry 20081231 18
Despite having been identified first, their greater degree of complexity has resulted in our understanding of eukaryotic ribosomes lagging behind that of their bacterial and archaeal counterparts. A much more complicated biogenesis program results in ribosomes that are structurally, biochemically, and functionally more complex. However, recent advances in molecular genetics and structural biology are helping to reveal the intricacies of the eukaryotic ribosome and to address many longstanding qu ...[more]
Similar Datasets
Project description:AimMaternal vaccination is a promising strategy for protecting pregnant women and newborns against severe infections. This review aims to describe the current status and challenges associated with maternal vaccination against seasonal influenza, tetanus-diphtheria-pertussis (Tdap/DTaP), and novel coronavirus disease of 2019 (COVID-19) in Japan and other countries, mainly the United States and the United Kingdom.MethodsA literature search was conducted in PubMed and other public websites (e.g., Centers for Disease Control and Prevention) to obtain information on maternal vaccination.ResultsInactivated vaccines are recommended for pregnant women by gynecologic societies in Japan, the United States, and the United Kingdom. Among pregnant Japanese women, the influenza and COVID-19 (two doses) vaccine coverage rates were 27.0%-53.5% (six studies) and 73.6% (one study), respectively; there are no studies on maternal vaccination with DTaP. Concerns regarding vaccine safety are a major barrier to maternal vaccination across countries. Maternal vaccination is effective in preventing severe disease in pregnant women and protecting infants aged <6 months, is generally safe, and does not increase the risk of adverse maternal and fetal outcomes. Providing accurate information regarding vaccination through healthcare providers and the government and government funding for vaccines may help improve maternal vaccination rates in Japan.ConclusionCurrent coverage for maternal vaccination is still low globally mainly because of vaccine hesitancy among pregnant women. The government, drug-regulatory authorities, and healthcare professionals must educate pregnant women about the effectiveness and safety of maternal vaccines and encourage vaccination when the benefits outweigh the risks.
| S-EPMC10100318 | biostudies-literature
Project description:Boron neutron capture therapy (BNCT) is a re-emerging therapy with the ability to selectively kill tumor cells. After the boron delivery agents enter the tumor tissue and enrich the tumor cells, the thermal neutrons trigger the fission of the boron atoms, leading to the release of boron atoms and then leading to the release of the α particles (4He) and recoil lithium particles (7Li), along with the production of large amounts of energy in the narrow region. With the advantages of targeted therapy and low toxicity, BNCT has become a unique method in the field of radiotherapy. Since the beginning of the last century, BNCT has been emerging worldwide and gradually developed into a technology for the treatment of glioblastoma multiforme, head and neck cancer, malignant melanoma, and other cancers. At present, how to develop and innovate more efficient boron delivery agents and establish a more accurate boron-dose measurement system have become the problem faced by the development of BNCT. We discuss the use of boron delivery agents over the past several decades and the corresponding clinical trials and preclinical outcomes. Furthermore, the discussion brings recommendations on the future of boron delivery agents and this therapy.
| S-EPMC9009440 | biostudies-literature
Project description:Biosimilar products are already approved and marketed in several countries. The Food and Drug Administration has approved ten different biosimilars, and the European Medicines Agency has approved 40. Even though this scenario has provided important experience with biosimilar products, there are still challenges and unanswered questions. Up to now, a good amount of knowledge has been gathered in order to support the importance of the totality of evidence and the construction of a biosimilarity exercise for regulatory approval. In addition, the extrapolation of indications has been proved viable when a careful analysis is performed. The models for clinical trials and the use of the most sensible populations have been extensively discussed, and there is apparent homogeneity in manufacturer choices for study designs. However, some challenges remain. The lack of regulatory harmony, especially concerning naming, the marketed intended copies, the interchangeability, and the biosimilars in orphan diseases are some of those and are the focus of discussion in this review.
| S-EPMC6172013 | biostudies-other
Project description:BackgroundRibosome biogenesis is a central process in every growing cell. In eukaryotes, it requires more than 250 non-ribosomal assembly factors, most of which are essential. Despite this large repertoire of potential targets, only very few chemical inhibitors of ribosome biogenesis are known so far. Such inhibitors are valuable tools to study this highly dynamic process and elucidate mechanistic details of individual maturation steps. Moreover, ribosome biogenesis is of particular importance for fast proliferating cells, suggesting its inhibition could be a valid strategy for treatment of tumors or infections.ResultsWe systematically screened ~ 1000 substances for inhibitory effects on ribosome biogenesis using a microscopy-based screen scoring ribosomal subunit export defects. We identified 128 compounds inhibiting maturation of either the small or the large ribosomal subunit or both. Northern blot analysis demonstrates that these inhibitors cause a broad spectrum of different rRNA processing defects.ConclusionsOur findings show that the individual inhibitors affect a wide range of different maturation steps within the ribosome biogenesis pathway. Our results provide for the first time a comprehensive set of inhibitors to study ribosome biogenesis by chemical inhibition of individual maturation steps and establish the process as promising druggable pathway for chemical intervention.
| S-EPMC6558755 | biostudies-literature
Project description:The recently emerged Zika virus (ZIKV) spread to the Americas, causing a spectrum of congenital diseases including microcephaly in newborn and Guillain-Barré syndrome (GBS) in adults. The unprecedented nature of the epidemic and serious diseases associated with the viral infections prompted the global research community to understand the immunopathogenic mechanisms of the virus and rapidly develop safe and efficacious vaccines. This has led to a number of ZIKV vaccine candidates that have shown significant promise in human clinical trials. These candidates include nucleic acid vaccines, inactivated vaccines, viral-vectored vaccines, and attenuated vaccines. Additionally, a number of vaccine candidates have been shown to protect animals in preclinical studies. However, as the epidemic has waned in the last three years, further development of the most promising vaccine candidates faces challenges in clinical efficacy trials, which is needed before a vaccine is brought to licensure. It is important that a coalition of government funding agencies and private sector companies is established to move forward with a safe and effective vaccine ready for deployment when the next ZIKV epidemic occurs.
| S-EPMC7349928 | biostudies-literature
Project description:Current staging systems of cancer are mainly based on the anatomical extent of disease. They need refinement by biological parameters to improve stratification of patients for tumor therapy or surveillance strategies. Thanks to developments in genomic, transcriptomic, and big-data technologies, we are now able to explore molecular characteristics of tumors in detail and determine their clinical relevance. This has led to numerous prognostic and predictive gene expression signatures that have the potential to establish a classification of tumor subgroups by biological determinants. However, only a few gene signatures have reached the stage of clinical implementation so far. In this review article, we summarize the current status, and present and future challenges of prognostic gene signatures in three relevant cancer entities: breast cancer, colorectal cancer, and hepatocellular carcinoma.
| S-EPMC8000474 | biostudies-literature
Project description:Studies on host genomics have revealed the existence of identifiable HIV-1 specific protective factors among infected individuals who remain naturally resistant viraemia controllers with little or no evidence of virus replication. These factors are broadly grouped into those that are immune associated (MHC, chemokines, cytokines, CTLs and others), linked to viral entry (chemokine co-receptors and ligands), act as post-entry restriction elements (TRIM5a, APOBEC3) and those associated with viral replication (cytokines and others). These features have been identified through multiple experimental approaches ranging from candidate gene approaches, genome wide association studies (GWAS), expression analysis in conjunction with functional assays in humans to primate based models. Several studies have highlighted the individual and population level gross differences both in the viral clade sequences as well as host determined genetic associations. This review collates current information on studies involving major histocompatibility complex (MHC) as well as non MHC genes in the context of HIV-1 infection and AIDS involving varied ethnic groups. Special focus of the review is on the genetic studies carried out on the Indian population. Further challenges with regard to therapeutic interventions based on current knowledge have been discussed along with discussion on documented cases of stem cell therapy and very early highly active antiretroviral therapy (HAART) interventions.
| S-EPMC3928698 | biostudies-literature
Project description:Glioblastoma (GBM), also known as grade IV astrocytoma, is the most common and deadly type of central nervous system malignancy in adults. Despite significant breakthroughs in current GBM treatments such as surgery, radiotherapy, and chemotherapy, the prognosis for late-stage glioblastoma remains bleak due to tumor recurrence following surgical resection. The poor prognosis highlights the evident and pressing need for more efficient and targeted treatment. Vaccination has successfully treated patients with advanced colorectal and lung cancer. Therefore, the potential value of using tumor vaccines in treating glioblastoma is increasingly discussed as a monotherapy or in combination with other cellular immunotherapies. Cancer vaccination includes both passive administration of monoclonal antibodies and active vaccination procedures to activate, boost, or bias antitumor immunity against cancer cells. This article focuses on active immunotherapy with peptide, genetic (DNA, mRNA), and cell-based vaccines in treating GBM and reviews the various treatment approaches currently being tested. Although the ease of synthesis, relative safety, and ability to elicit tumor-specific immune responses have made these vaccines an invaluable tool for cancer treatment, more extensive cohort studies and better guidelines are needed to improve the efficacy of these vaccines in anti-GBM therapy.
| S-EPMC10155120 | biostudies-literature
Project description:Toxoplasma gondii causes fatal and debilitating brain and eye diseases. Medicines that are currently used to treat toxoplasmosis commonly have toxic side effects and require prolonged courses that range from weeks to more than a year. The need for long treatment durations and the risk of relapsing disease are in part due to the lack of efficacy against T. gondii tissue cysts. The challenges for developing a more effective treatment for toxoplasmosis include decreasing toxicity, achieving therapeutic concentrations in the brain and eye, shortening duration, eliminating tissue cysts from the host, safety in pregnancy, and creating a formulation that is inexpensive and practical for use in resource-poor areas of the world. Over the last decade, significant progress has been made in identifying and developing new compounds for the treatment of toxoplasmosis. Unlike clinically used medicines that were repurposed for toxoplasmosis, these compounds have been optimized for efficacy against toxoplasmosis during preclinical development. Medicines with enhanced efficacy as well as features that address the unique aspects of toxoplasmosis have the potential to greatly improve toxoplasmosis therapy. This review discusses the facets of toxoplasmosis that are pertinent to drug design and the advances, challenges, and current status of preclinical drug research for toxoplasmosis.
| S-EPMC5279849 | biostudies-literature
Project description:The association between thyroid hormone status and plasma levels of low-density lipoprotein cholesterol has raised the awareness for the development of thyroid hormone mimetics as lipid-lowering agents. The discovery of the two main types of thyroid hormone receptors (? and ?) as well as the development of novel combinatorial chemistry providing organ specificity has drastically improved the selectivity of these compounds. In the past decades, several thyroid hormone mimetics have been investigated with the purpose of lowering low-density lipoprotein cholesterol levels. However, until now, none of the thyromimetics reached the stage of completing a phase III clinical trial without deleterious side effects. Here, we review the currently available literature on thyromimetics investigated for the treatment of dyslipidemia, their rise, their downfall and the challenges for the development of novel agents.
| S-EPMC4757599 | biostudies-literature