A journey of a thousand miles begins with one small step
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PROVIDER: S-EPMC10839723 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-EPMC9350584 | biostudies-literature
Project description:This article discusses the recently published EMPA-REG OUTCOME trial, which assessed cardiovascular outcomes with empagliflozin therapy in persons with type 2 diabetes mellitus and coexisting cardiovascular disease. The article describes the background and challenges of modern cardiovascular outcome trials, points out the strengths of the EMPA-REG OUTCOME study, and places the results in perspective. It highlights the significant impact that these results will have on cardiovascular preventive pharmacotherapy, and on future drug development in diabetes. At the same time, it reminds readers of the limitations of the results, and lists the questions raised by, or left unanswered by, the trial.
| S-EPMC4674475 | biostudies-literature
Project description:We explore humans' rule-based category learning using analytic approaches that highlight their psychological transitions during learning. These approaches confirm that humans show qualitatively sudden psychological transitions during rule learning. These transitions contribute to the theoretical literature contrasting single vs. multiple category-learning systems, because they seem to reveal a distinctive learning process of explicit rule discovery. A complete psychology of categorization must describe this learning process, too. Yet extensive formal-modeling analyses confirm that a wide range of current (gradient-descent) models cannot reproduce these transitions, including influential rule-based models (e.g., COVIS) and exemplar models (e.g., ALCOVE). It is an important theoretical conclusion that existing models cannot explain humans' rule-based category learning. The problem these models have is the incremental algorithm by which learning is simulated. Humans descend no gradient in rule-based tasks. Very different formal-modeling systems will be required to explain humans' psychology in these tasks. An important next step will be to build a new generation of models that can do so.
| S-EPMC4558046 | biostudies-literature
Project description:Animal cloning has been popularized for more than two decades, since the birth of Dolly the Sheep 25 years ago in 1996. There has been an apparent waning of interest in cloning, evident by a reduced number of reports. Over 1500 dogs, representing approximately 20% of the American Kennel Club's recognized breeds, have now been cloned, making the dog (Canis familiaris) one of the most successfully cloned mammals. Dogs have a unique relationship with humans, dating to prehistory, and a high degree of genome homology to humans. A number of phenotypic variations, rarely recorded in natural reproduction have been observed in in these more than 1000 clones. These observations differ between donors and their clones, and between clones from the same donor, indicating a non-genetic effect. These differences cannot be fully explained by current understandings but point to epigenetic and cellular reprograming effects of somatic cell nuclear transfer. Notably, some phenotypic variations have been reversed through further cloning. Here we summarize these observations and elaborate on the cloning procedure.
| S-EPMC9249891 | biostudies-literature
Project description:Motivation:Intron length distribution (ILD) is a specific feature of a genome that exhibits extensive species-specific variation. Whereas ILD contributes to up to 30% of the total information content for intron recognition in some species, rendering it an important component of computational gene prediction, very few studies have been conducted to quantitatively characterize ILDs of various species. Results:We developed a set of computer programs (fitild, compild, etc.) to build statistical models of ILDs and compare them with one another. Each ILD of more than 1000 genomes was fitted with fitild to a statistical model consisting of one, two, or three components of Frechet distributions. Several measures of distances between ILDs were calculated by compild. A theoretical model was presented to better understand the origin of the observed shape of an ILD. Availability and implementation:The C++ source codes are available at https://github.com/ogotoh/fitild.git/. Supplementary information:Supplementary data are available at Bioinformatics online.
| S-EPMC6157073 | biostudies-literature
Project description:In the last decade, it has become evident that RNA is frequently found in DNA. It is now well established that single embedded ribonucleoside monophosphates (rNMPs) are primarily introduced by DNA polymerases and that longer stretches of RNA can anneal to DNA, generating RNA:DNA hybrids. Among them, the most studied are R-loops, peculiar three-stranded nucleic acid structures formed upon the re-hybridization of a transcript to its template DNA. In addition, polyribonucleotide chains are synthesized to allow DNA replication priming, double-strand breaks repair, and may as well result from the direct incorporation of consecutive rNMPs by DNA polymerases. The bright side of RNA into DNA is that it contributes to regulating different physiological functions. The dark side, however, is that persistent RNA compromises genome integrity and genome stability. For these reasons, the characterization of all these structures has been under growing investigation. In this review, we discussed the origin of single and multiple ribonucleotides in the genome and in the DNA of organelles, focusing on situations where the aberrant processing of RNA:DNA hybrids may result in multiple rNMPs embedded in DNA. We concluded by providing an overview of the currently available strategies to study the presence of single and multiple ribonucleotides in DNA in vivo.
| S-EPMC7084774 | biostudies-literature
Project description: Not available
| S-EPMC7364739 | biostudies-literature
Project description:Amino acid-based hydrogels have received widespread attention because of their wide range of sources, biodegradability, and biocompatibility. Despite considerable progress, the development of such hydrogels has been limited by critical problems such as bacterial infection and complex preparation. Herein, by using the non-toxic gluconolactone (GDL) to adjust the pH of the solution to induce the rapid self-assembly of N-[(benzyloxy)carbonyl]-L-tryptophan (ZW) to form a three-dimensional (3D) gel network, we developed a stable and effective self-assembled small-molecule hydrogel. Characterization assays and molecular dynamics studies indicate that π-π stacking and hydrogen bonding are the main drivers of self-assembly between ZW molecules. In vitro experiments further confirmed this material's sustained release properties, low cytotoxicity, and excellent antibacterial activity, particularly against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. This study provides a different and innovative perspective for the further development of antibacterial materials based on amino acid derivatives.
| S-EPMC10141015 | biostudies-literature
Project description:Genome driven precision oncology has transformed the landscape of multiple cancers. However, access barriers exist. A recent study exemplified a direct-to-patient outreach program via social media through the implementation of a global program that offered free tumor genomic testing with a focus on rare cancers. See related article by Doe-Tetteh et al., p. 2445.
| S-EPMC10330328 | biostudies-literature
Project description:Bacteria are indispensable for the study of fundamental molecular biology processes due to their relatively simple gene and genome architecture. The ability to engineer bacterial chromosomes is quintessential for understanding gene functions. Here we demonstrate the engineering of the small-ribosomal subunit (16S) RNA of Mycoplasma mycoides, by combining the CRISPR/Cas9 system and the yeast recombination machinery. We cloned the entire genome of M. mycoides in yeast and used constitutively expressed Cas9 together with in vitro transcribed guide-RNAs to introduce engineered 16S rRNA genes. By testing the function of the engineered 16S rRNA genes through genome transplantation, we observed surprising resilience of this gene to addition of genetic elements or helix substitutions with phylogenetically-distant bacteria. While this system could be further used to study the function of the 16S rRNA, one could envision the "simple" M. mycoides genome being used in this setting to study other genetic structures and functions to answer fundamental questions of life.
| S-EPMC4973257 | biostudies-literature