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DoD2006, an updated version of Database of Databases is an online resource maintained collectively by ProGene Biosciences and Department of Inorganic and Analytical Chemistry, Andhra University. It links to all molecular biology databases that appeared in Nucleic Acids Research 2006 database issue. DoD2006 includes 873 databases, of which, 858 are derived from Nucleic Acids Research database issue and 15 are collected from In Silico Biology, Bioinformation journals and Google Scholar search. Each database has a search option, keyword help and a brief description with direct link to the database home page. The database is freely available online at http://www.progenebio.in/DoD/index.htm.
We recently developed 'cellular' reagents-lyophilized bacteria overexpressing proteins of interest-that can replace commercial pure enzymes in typical diagnostic and molecular biology reactions. To make cellular reagent technology widely accessible and amenable to local production with minimal instrumentation, we now report a significantly simplified method for preparing cellular reagents that requires only a common bacterial incubator to grow and subsequently dry enzyme-expressing bacteria at 37°C with the aid of inexpensive chemical desiccants. We demonstrate application of such dried cellular reagents in common molecular and synthetic biology processes, such as PCR, qPCR, reverse transcription, isothermal amplification, and Golden Gate DNA assembly, in building easy-to-use testing kits, and in rapid reagent production for meeting extraordinary diagnostic demands such as those being faced in the ongoing SARS-CoV-2 pandemic. Furthermore, we demonstrate feasibility of local production by successfully implementing this minimized procedure and preparing cellular reagents in several countries, including the United Kingdom, Cameroon, and Ghana. Our results demonstrate possibilities for readily scalable local and distributed reagent production, and further instantiate the opportunities available via synthetic biology in general.
The use of molecular biology tools in the field of bioadhesion is still in its infancy. For new research groups who are considering taking a molecular approach, the techniques presented here are essential to unravelling the sequence of a gene, its expression and its biological function. Here we provide an outline for addressing adhesion-related genes in diverse organisms. We show how to gradually narrow down the number of candidate transcripts that are involved in adhesion by (1) generating a transcriptome and a differentially expressed cDNA list enriched for adhesion-related transcripts, (2) setting up a BLAST search facility, (3) perform an in situ hybridization screen, and (4) functional analyses of selected genes by using RNA interference knock-down. Furthermore, latest developments in genome-editing are presented as new tools to study gene function. By using this iterative multi-technologies approach, the identification, isolation, expression and function of adhesion-related genes can be studied in most organisms. These tools will improve our understanding of the diversity of molecules used for adhesion in different organisms and these findings will help to develop innovative bio-inspired adhesives.
The Nucleic Acids Research online Molecular Biology Database Collection is a public repository that lists more than 1000 databases described in this and previous Nucleic Acids Research annual database issues, as well as a selection of molecular biology databases described in other journals. All databases included in this Collection are freely available to the public. The 2008 update includes 1078 databases, 110 more than the previous one. The links to more than 80 databases have been updated and 25 obsolete databases have been removed from the list. The complete database list and summaries are available online at the Nucleic Acids Research web site, http://nar.oxfordjournals.org/.
The Nucleic Acids Research Molecular Biology Database Collection is a public online resource that lists the databases described in this and previous issues of Nucleic Acids Research together with other databases of value to the biologist and available throughout the world. All databases included in this Collection are freely available to the public. The 2005 update includes 719 databases, 171 more than the 2004 one. The databases are organized in a hierarchical classification that simplifies the process of finding the right database for any given task. The growing number of databases related to immunology, plant and organelle research have been accommodated by separating them into three new categories. The database summaries provide brief descriptions of the databases, contact details, appropriate references and acknowledgements. The online summaries also serve as a venue for the maintainers of each database to introduce database updates and other improvements in the scope and tools. These updates are particularly important for those databases that have not been described in print in the recent past. The database list and summaries are available online at the Nucleic Acids Research web site, http://nar.oupjournals.org/.
CellPAINT is an interactive digital tool that allows non-expert users to create illustrations of the molecular structure of cells and viruses. We present a new release with several key enhancements, including the ability to generate custom ingredients from structure information in the Protein Data Bank, and interaction, grouping, and locking functions that streamline the creation of assemblies and illustration of large, complex scenes. An example of CellPAINT as a tool for hypothesis generation in the interpretation of cryoelectron tomograms is presented. CellPAINT is freely available at http://ccsb.scripps.edu/cellpaint.
Herbal medicine is one of the forms of traditional medical practice. Traditional Chinese medicine (TCM) and traditional Vietnamese medicine (TVM) are well-known for their long-standing tradition of herbal medicine. Secreted by many species of blister beetle, most notably by the 'Spanish fly' (Lytta vesicatoria), cantharidin inhibits protein phosphatases 1 and 2A (PP1, PP2A). Blister beetle has been used in Asian traditional medicine to treat Molluscum contagiosum virus (MCV) infections and associated warts, and is now also used for cancer treatment. A combination of both genomic and postgenomic techniques was used in our studies to identify candidate genes affecting sensitivity or resistance to cantharidin. Cantharidin was not found to be related to multidrug resistance phenotype, suggesting its potential usefulness for the treatment of refractory tumors. Oxidative stress response genes diminish the activity of cantharidin by inducing DNA strand breaks which may be subject to base excision repair and induce apoptosis in a p53- and Bcl2-dependent manner. Cantharidin is one of many natural products used in traditional Chinese medicine and traditional Vietnamese medicine for cancer treatment. Combined methods of pharmaceutical biology and molecular biology can help elucidate modes of action of these natural products.
Soft tissue sarcomas (STS) are a set of very heterogeneous tumors with numerous histological categories. The development of the molecular biology allowed identifying recurring molecular anomalies in certain subgroups of sarcomas, being able to represent diagnostic, prognosis and therapeutic tools. The molecular classification of STS includes until today 5 main groups of abnormalities: sarcomas with "simple genomic profile" showing reciprocal (1) chromosomal translocations, (2) activating mutation, (3) inhibitive mutation or (4) simple amplification; (5) sarcomas with "complex genomic profile" can include several tens of molecular abnormalities. The development of new-targeted therapies is based on the identification of a target, specific of a tumors subgroup and involved in carcinogenesis mechanisms and/or tumoral growth. Then, the aim of clinical research is to establish the proof of the concept through clinical trials, demonstrating the benefit brought to the patient and ending in the marketing of the drug. This proof of the concept was clearly established for imatinib, sunitinib and regorafenib in gastrointestinal stromal tumors, for imatinib in dermatofibrosarcoma protuberans and pigmented vilo-nodular synovitis, for denosumab in giant cell tumors of the bone, ending in the authorization to use these new therapies in these indications. It is in progress and promising for anti-IGF-1R in Ewing sarcomas, for crizotinib in myofibroblastic inflammatory tumors, for mTOR inhibitor in PEComas... The role of molecular abnormalities identified in the mechanisms of tumoral progress for sarcomas and their potential therapeutic impact will be detailed.
Peritoneal metastases are a common form of tumor cell dissemination in gastrointestinal malignancies. Peritoneal metastatic disease (PMD) is associated with severe morbidity and resistance to currently employed therapies. Given the distinct route of dissemination compared with distant organ metastases, and the unique microenvironment of the peritoneal cavity, specific tumor cell characteristics are needed for the development of PMD. In this review, we provide an overview of the known histopathological, genomic, and transcriptomic features of PMD. We find that cancers representing the mesenchymal subtype are strongly associated with PMD in various malignancies. Furthermore, we discuss the peritoneal niche in which the metastatic cancer cells reside, including the critical role of the peritoneal immune system. Altogether, we show that PMD should be regarded as a distinct disease entity, that requires tailored treatment strategies.
The NAR Molecular Biology Database Collection is a public online resource that contains links to all databases described in this issue of Nucleic Acids Research. In addition, this collection lists databases that have been featured in previous issues of NAR, as well as selected other databases that are freely available to the public and may be useful to the molecular biologist. The 2006 update includes 858 databases, 139 more than the previous one. The databases come with brief summaries, many of which have been updated recently. Each database is assigned a stable accession number that does not change if the database moves to a new location and its URL, authors' names or the contact person address are updated. The complete database list and summaries are available online at the Nucleic Acids Research website http://nar.oxfordjournals.org/.
The NAR online Molecular Biology Database Collection is a public resource that contains links to the databases described in this issue of Nucleic Acids Research, previous NAR database issues, as well as a selection of other molecular biology databases that are freely available on the web and might be useful to the molecular biologist. The 2007 update includes 968 databases, 110 more than the previous one. Many databases that have been described in earlier issues of NAR come with updated summaries, which reflect recent progress and, in some instances, an expanded scope of these databases. The complete database list and summaries are available online on the Nucleic Acids Research web site http://nar.oxfordjournals.org/.
The classical action of androgen receptor (AR) is to regulate gene transcriptional processes via AR nuclear translocation, response element binding and recruitment of, or crosstalk with, transcription factors. AR also utilises non-classical, non-genomic mechanisms of signal transduction. These precede gene transcription or protein synthesis, and involve steroid-induced modulation of cytoplasmic or cell membrane-bound regulatory proteins. Despite many decades of investigation, the role of AR in gene regulation of cells and tissues remains only partially characterised. AR exerts most of its effects in sex hormone-dependent tissues of the body, but the receptor is also expressed in many tissues not previously thought to be androgen sensitive. Thus it is likely that a complex, more over-arching, role for AR exists. Each AR domain co-ordinates a multitude of individual and vital roles via a diverse array of interacting partner molecules that are necessary for cellular and tissue development and maintenance. Aberrant AR activity, promoted by mutations or binding partner misregulation, can present as many clinical manifestations including androgen insensitivity syndrome and prostate cancer. In the case of malignant prostate cancer, treatment generally revolves around androgen deprivation therapies designed to interfere with AR action and the androgen signalling axis. Androgen therapies for prostate cancer often fail, highlighting a real need for increased research into AR function.
This review provides insights at the molecular level into the current and old methods for treating meniscal injuries. Meniscal injuries have been found to have a substantial impact on the progression of osteoarthritis. In line with the "save the meniscus" approach, meniscectomy is considered a last-resort treatment. Nevertheless, it is important to note that mechanical repair alone may not achieve the complete restoration of the meniscus. A deep understanding of the healing pathways could lead to future improvements in meniscal healing. The inclusion of cytokines and chemokines has the potential to facilitate the process of tear repair or impede the inflammatory catabolic cascade. MicroRNA (miRNA) could serve as a potential biomarker for meniscal degeneration, and RNA injections might promote collagen and growth factor production. The critical aspect of the healing process is angiogenesis within the inner zone of the meniscus. The use of collagen scaffolds and the implantation of autologous meniscus fragments have been successfully integrated into clinical settings. These findings are encouraging and underscore the need for well-designed clinical trials to explore the most effective factors that can enhance the process of meniscal repair.
Toll-like receptors (TLRs) are pivotal biomolecules in the immune system. Today, we are all aware of the importance of TLRs in bridging innate and adaptive immune system to each other. The TLRs are activated through binding to damage/danger-associated molecular patterns (DAMPs), microbial/microbe-associated molecular patterns (MAMPs), pathogen-associated molecular patterns (PAMPs), and xenobiotic-associated molecular patterns (XAMPs). The immunogenetic molecules of TLRs have their own functions, structures, coreceptors, and ligands which make them unique. These properties of TLRs give us an opportunity to find out how we can employ this knowledge for ligand-drug discovery strategies to control TLRs functions and contribution, signaling pathways, and indirect activities. Hence, the authors of this paper have a deep observation on the molecular and structural biology of human TLRs (hTLRs).
The integration of cellular and molecular structural data is key to understanding the function of macromolecular assemblies and complexes in their in vivo context. Here we report on the outcomes of a workshop that discussed how to integrate structural data from a range of public archives. The workshop identified two main priorities: the development of tools and file formats to support segmentation (that is, the decomposition of a three-dimensional volume into regions that can be associated with defined objects), and the development of tools to support the annotation of biological structures.
Metastatic urothelial cancer (UC) is associated with poor prognosis. In the first-line setting, platinum-based chemotherapy is the standard of care but resistance rapidly occurs. With no validated treatment proven to increase survival after platinum failure, there is an urgent unmet medical need to develop new and efficacious cytotoxic agents. A better understanding of the molecular signaling pathways regulating UC has led to the development of new and innovative therapeutic strategies. Despite this, many recent drugs show only modest activity as single agents, and combining them with standard chemotherapy does not seem to enhance efficacy. Ongoing research is producing, however, a generation of new drugs that are showing promising results in clinical trials. This paper aims to review the most important mechanisms in bladder cancer tumorigenesis and describe the new therapeutic options currently undergoing evaluation in clinical trials.
Uveal melanoma (UM) is the most common intraocular malignancy in adults. So far, no systemic therapy or standard treatment exists to reduce the risk of metastasis and improve overall survival of patients. With the increased knowledge regarding the molecular pathways that underlie the oncogenesis of UM, it is expected that novel therapeutic approaches will be available to conquer this disease. This review provides a summary of the current knowledge of, and progress made in understanding, the pathogenesis, genetic mutations, epigenetics, and immunology of UM. With the advent of the omics era, multi-dimensional big data are publicly available, providing an innovation platform to develop effective targeted and personalized therapeutics for UM patients. Indeed, recently, a great number of therapies have been reported specifically for UM caused by oncogenic mutations, as well as other etiologies. In this review, special attention is directed to advancements in targeted therapies. In particular, we discuss the possibilities of targeting: GNAQ/GNA11, PLCβ, and CYSLTR2 mutants; regulators of G-protein signaling; the secondary messenger adenosine diphosphate (ADP)-ribosylation factor 6 (ARF6); downstream pathways, such as those involving mitogen-activated protein kinase/MEK/extracellular signal-related kinase, protein kinase C (PKC), phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (mTOR), Trio/Rho/Rac/Yes-associated protein, and inactivated BAP1; and immune-checkpoint proteins cytotoxic T-lymphocyte antigen 4 and programmed cell-death protein 1/programmed cell-death ligand 1. Furthermore, we conducted a survey of completed and ongoing clinical trials applying targeted and immune therapies for UM. Although drug combination therapy based on the signaling pathways involved in UM has made great progress, targeted therapy is still an unmet medical need.
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