Researchers would love if they can expand time to fit in that publication, article, or review of their topic of interest; if that were true, however, there is no end to bottomless scrolling and missing the important details. PubReading would read out the abstract, results, and discussions to allow hassle-free information and a chance to create connections with like-minded individuals.
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- PubReading [317] - Nucleic acid sensing via electrochemical oligonucleotide-templated reactions - P. Gillespie, D. O’Har et al.Short single-stranded nucleic acids as found in a variety of bodily fluids have recently emerged as minimally invasive biomarkers for a broad range of pathologies, most notably cancer. Because of their small size, low natural abundance and high sequence homology between family members they are challenging to detect using standard technologies suitable for use at the point-of-care. Herein we report the design, engineering and testing of a novel sensing strategy: electrochemically active molecular probes based on peptide nucleic acid (PNA) scaffolds for the detection of single-stranded oligonucleotides, in particular microRNAs (or miRs). As a proof-of- principle, a wide range of probes were designed and tested to detect miR-141, a known diagnostic biomarker for prostate cancer. Optimal quantitative sensing of miR-141 was achieved via the first example of an electro-chemical oligonucleotide-templated reaction (EOTR), whereby two PNA probes - functionalized with an aniline and a 1,4-catechol respectively - preferentially react with each other upon simultaneous hybridization to the same RNA target strand, serving here as a template. Quantitative, electrochemical detection of the product of this bio-orthogonal reaction showed direct correlation between adduct formation and miR-141 concentration. Coupling the specificity of OTR with the speed and sensitivity of electrochemical sensing delivers EOTRs as a promising new technique for fast, low-cost, quantitative and sequence-specific detection of short nucleic acids from liquid biopsies. https://doi.org/10.1016/j.bios.2020.112891 - 20200 comments0
- PubReading [316] - A brief history of human disease genetics - M. Claussnitzer, M. McCarthy et al.A primary goal of human genetics is to identify DNA sequence variants that influence biomedical traits, particularly those related to the onset and progression of human disease. Over the past 25 years, progress in realizing this objective has been transformed by advances in technology, foundational genomic resources and analytical tools, and by access to vast amounts of genotype and phenotype data. Genetic discoveries have substantially improved our understanding of the mechanisms responsible for many rare and common diseases and driven development of novel preventative and therapeutic strategies. Medical innovation will increasingly focus on delivering care tailored to individual patterns of genetic predisposition. https://doi.org/10.1038/s41586-019-1879-7 - 20200 comments0
- PubReading Mar 27 · 10m PubReading [315] - Technology transfer programme for influenza vaccines – Lessons from the past to inform the future - C. Chadwick, E. Sparrow et al.In 2006, to address the global inequitable access to influenza vaccines in the event of an influenza pandemic, WHO, with support of donors and partners, embarked on an ambitious project, the Technology Transfer Initiative (TTI), to facilitate influenza vaccine production capacity-building in low- and middle-income countries (LMICs). This commentary briefly summarizes the high-level lessons learned, key challenges encountered, and critical components needed for success. https://doi.org/10.1016/j.vaccine.2022.06.057 - 20220 comments0
- PubReading [314]- MicroRNAs, damage levels, and DNA damage response control - H. Visser and A. ThomasDNA damage–inducible miRNA s are likely to be functional in the DNA damage response. This response can elicit damage resolution and cell survival or apoptosis. The current, albeit incomplete, picture suggests that miRNAs can affect cell fate via modulation of key response proteins, but the question is, who’s in charge? https://doi.org/10.1016/j.tig.2021.06.018 - 20210 comments0
- PubReading [313] - Physical activity, exercise, and chronic diseases- A brief review - E. Anderson, J. L. DurstineChronic diseases are the leading cause of death worldwide with increasing prevalence in all age groups, genders, and ethnicities. Most chronic disease deaths occur in middle-to low-income countries but are also a significant health problem in developed nations. Multiple chronic diseases now affect children and adolescents as well as adults. Being physically inactive is associated with increased chronic disease risk. Global societies are being negatively impacted by the increasing prevalence of chronic disease which is directly related to rising healthcare expenditures, workforce complications regarding attendance and productivity, military personnel recruitment, and academic success. However, increased physical activity (PA) and exercise are associated with reduced chronic disease risk. Most physiologic systems in the body benefit positively from PA and exercise by primary disease prevention and secondary disease prevention/treatment. The purpose of this brief review is to describe the sig- nificant global problem of chronic diseases for adults and children, and how PA and exercise can provide a non-invasive means for added prevention and treatment. https://doi.org/10.1016/j.smhs.2019.08.006 - 20190 comments0
- PubReading [312] - Identification of endocrine disrupting chemicals acting on human aromatase - R. Baravalle, G. Gilardi et al.Human aromatase is the cytochrome P450 catalysing the conversion of androgens into estrogens playing a key role in the endocrine system. Due to this role, it is likely to be a target of the so-called endocrine disrupting chemicals, a series of compounds able to interfere with the hormone system with toxic effects. If on one side the toxicity of some compounds such as bisphenol A is well known, on the other side the toxic concentrations of such compounds as well as the effect of the many other molecules that are in contact with us in everyday life still need a deep investigation. The availability of biological assays able to detect the interaction of chemicals with key molecular targets of the endocrine system represents a possible solution to identify potential endocrine disrupting chemicals.Here the so-called alkali assay previously developed in our laboratory is applied to test the effect of different compounds on the activity of human aromatase. The assay is based on the detection of the alkali product that forms upon strong alkali treatment of the NADP + released upon enzyme turnover. Here it is applied on human aromatase and validated using anastrozole and sildenafil as known aromatase inhibitors. Out of the small library of compounds tested, resveratrol and ketoconazole resulted to inhibit aromatase activity, while bisphenol A and nicotine were found to exert an inhibitory effect at relatively high concentrations (100 μM), and other molecules such as lindane and four plasticizers did not show any significant effect. These data are confirmed by quantification of the product estrone in the same reaction mixtures through ELISA.Overall, the results show that the alkali assay is suitable to screen for molecules that interfere with aromatase activity. As a consequence it can also be applied to other molecular targets of EDCs that use NAD(P)H for catalysis in a high throughput format for the fast screening of many different compounds as endocrine disrupting chemicals. http://dx.doi.org/10.1016/j.bbapap.2017.05.013 - 20170 comments0
- PubReading [311] - Chemical biology of non-canonical structures of nucleic acids for therapeutic applications - H. Tateishi-Karimata and N. SugimotoDNA forms not only the canonical duplex structure but also non-canonical structures. Most potential sequences that induce the formation of non-canonical structures are present in disease-related genes. Interestingly, biological reactions are inhibited or dysregulated by non-canonical structure formation in disease-related genes. To control biological reactions, methods for inducing the formation of non- canonical structures have been developed using small molecules and oligonucleotides. In this feature article, we review biological reactions such as replication, transcription, and reverse transcription controlled by non-canonical DNA structures formed by disease-related genes. Furthermore, we discuss recent studies aimed at developing methods for regulating these biological reactions using drugs targeting the DNA structure. DOI: 10.1039/c9cc09771f - 20200 comments0
- PubReading [310] - How to Write the Methods Section of a Research Paper - R. KalletThe methods section of a research paper provides the information by which a study’s validity is judged. Therefore, it requires a clear and precise description of how an experiment was done, and the rationale for why specific experimental procedures were chosen. The methods section should describe what was done to answer the research question, describe how it was done, justify the experimental design, and explain how the results were analyzed. Scientific writing is direct and orderly. Therefore, the methods section structure should: describe the materials used in the study, explain how the materials were prepared for the study, describe the research protocol, explain how measurements were made and what calculations were performed, and state which statistical tests were done to analyze the data. Once all elements of the methods section are written, subsequent drafts should focus on how to present those elements as clearly and logically as possibly. The description of preparations, measurements, and the protocol should be organized chronologically. For clarity, when a large amount of detail must be presented, information should be presented in sub-sections according to topic. Material in each section should be organized by topic from most to least important. 49 (10) 1229-1232; - 20040 comments0
- PubReading Mar 17 · 24m PubReading [309] - What We Talk About When We Talk About “Junk DNA” - N. Fagundes, A. Zani et al.“ Junk DNA ” is a popular yet controversial concept that states that organisms carry in their genomes DNA that has no positive impact on their fitness. Nonetheless, biochemical functions have been identified for an increasing fraction of DNA elements traditionally seen as “Junk DNA”. These findings have been interpreted as fundamentally undermining the “Junk DNA” concept. Here, we reinforce previous arguments that this interpretation relies on an inadequate concept of biological function that does not consider the selected effect of a given genomic structure, which is central to the “Junk DNA” concept. Next, we suggest that another (though ignored) confounding factor is that the discussion about biological functions includes two different dimensions: a horizontal, ecological dimension that reflects how a given genomic element affects fitness in a specific time, and a vertical, temporal dimension that reflects how a given genomic element persisted along time. We suggest that “Junk DNA” should be used exclusively relative to the horizontal dimension, while for the vertical dimension, we propose a new term, “Spam DNA”, that reflects the fact that a given genomic element may persist in the genome even if not selected for on their origin. Importantly, these concepts are complementary. An element can be both “ Spam DNA ” and “Junk DNA”, and “Spam DNA” can also be recruited to perform evolved biological functions, as illustrated in processes of exaptation or constructive neutral evolution. https://doi.org/10.1093/gbe/evac055 - 20220 comments0
- PubReading [308] - Deep learning in cancer pathology- a new generation of clinical biomarkers - A. Echle, J. Kather et al.Clinical workflows in oncology rely on predictive and prognostic molecular biomarkers. However, the growing number of these complex biomarkers tends to increase the cost and time for decision-making in routine daily oncology practice; furthermore, biomarkers often require tumour tissue on top of routine diagnostic material. Nevertheless, routinely available tumour tissue contains an abundance of clinically relevant information that is currently not fully exploited. Advances in deep learning (DL), an artificial intelligence (AI) technology, have enabled the extraction of previously hidden information directly from routine histology images of cancer, providing potentially clinically useful information. Here, we outline emerging concepts of how DL can extract biomarkers directly from histology images and summarise studies of basic and advanced image analysis for cancer histology. Basic image analysis tasks include detection, grading and subtyping of tumour tissue in histology images; they are aimed at automating pathology workflows and consequently do not immediately translate into clinical decisions. Exceeding such basic approaches, DL has also been used for advanced image analysis tasks, which have the potential of directly affecting clinical decision -making processes. These advanced approaches include inference of molecular features, prediction of survival and end-to-end prediction of therapy response. Predictions made by such DL systems could simplify and enrich clinical decision-making, but require rigorous external validation in clinical settings. https://doi.org/10.1038/s41416-020-01122-x - 20200 comments0
- PubReading [307] - Comparison of X-ray and NMR Structures- Is There a Systematic Difference in Residue Contacts between X-ray- and NMR-Resolved Protein Structures? - S. Garbuzynskiy, O. Galzitskaya et al.We have compared structures of 78 proteins determined by both NMR and X-ray methods. It is shown that X-ray and NMR structures of the same protein have more differences than various X-ray structures obtained for the protein, and even more than various NMR structures of the protein. X-ray and NMR structures of 18 of these 78 proteins have obvious large-scale structural differences that seem to reflect a difference of crystal and solution structures. The other 60 pairs of structures have only small-scale differences comparable with differences between various X-ray or various NMR structures of a protein; we have analyzed these structures more attentively. One of the main differences between NMR and X-ray structures concerns the number of contacts per residue: NMR structures presented in PDB have more contacts than X-ray structures at distances below 3.0 Å and 4.5– 6.5 Å, and fewer contacts at distances of 3.0 – 4.5 Å and 6.5–8.0 Å; this difference in the number of contacts is greater for internal residues than for external ones, and it is larger for -containing proteins than for all proteins. Another significant difference is that the main-chain hydrogen bonds identified in X-ray and NMR structures often differ. Their correlation is 69% only. However, analogous difference is found for refined and rerefined NMR structures, allowing us to suggest that the observed difference in interresidue contacts of X-ray and NMR structures of the same proteins is due mainly to a difference in mathematical treatment of experimental results. DOI: 10.1002/prot.20491 - 20050 comments0
- PubReading [306] - A Brief History of IL-9 - R. Goswami and M. KaplanIL-9 was first described in the late 1980s as a member of a growing number of cytokines that had pleiotropic functions in the immune system. Although many biological functions have been attributed to IL-9, it remains an understudied cytokine. A resurgence of interest in IL-9 has been spurred by recent work demonstrating a role for IL-9 in regulating inflammatory immunity and defining the transcription factors that activate the Il9 gene in cells that most efficiently produce IL-9. In this review, we summarize the characterization of IL-9 biological activities, highlight roles for the cytokine that are clearly defined, and outline questions regarding IL-9 functions that still require further exploration. www.jimmunol.org/cgi/doi/10.4049/jimmunol.1003049 - 20110 comments0
- PubReading [305] - The sciences of science communication - B. FischhoffThe May 2012 Sackler Colloquium on “The Science of Science Communication ” brought together scientists with research to communicate and scientists whose research could facilitate that communication. The latter include decision scientists who can identify the scientific results that an audience needs to know, from among all of the scientific results that it would be nice to know; behavioral scientists who can design ways to convey those results and then evaluate the success of those attempts; and social scientists who can create the channels needed for trustworthy communications. This overview offers an introduction to these communication sciences and their roles in science-based communication programs.0 comments0
- PubReading [304] - What are Biomarkers? - K. Strimbu and J. TavelThis article provides working definitions and a conceptual framework to understand the roles of biomarkers in clinical research. The definitions of the terms discussed in this article—medical signs, symptoms, biomarkers, surrogate endpoints, clinical endpoints, validation—are still under discussion, as are their relationships to each other, but broad consensus has developed in the past decade and a half about the necessity of distinguishing between, in particular, surrogate and clinical endpoints. doi:10.1097/COH.0b013e32833ed177. - 20100 comments0
- PubReading Mar 9 · 41m PubReading [303] - The Epigenomics of Cancer - P. Jones and S. BaylinAberrant gene function and altered patterns of gene expression are key features of cancer. Growing evidence shows that acquired epigenetic abnormalities participate with genetic alterations to cause this dysregulation. Here, we review recent advances in understanding how epigenetic alterations participate in the earliest stages of neoplasia, including stem/ precursor cell contributions, and discuss the growing implications of these advances for strategies to control cancer. DOI 10.1016/j.cell.2007.01.029 -20070 comments0
- PubReading [302] - The evolution, evolvability and engineering of gene regulatory DNA - E. Vaishnav, A. Regev et al.Mutations in non-coding regulatory DNA sequences can alter gene expression, organismal phenotype and fitness1–3. Constructing complete fitness landscapes, in which DNA sequences are mapped to fitness, is a long-standing goal in biology, but has remained elusive because it is challenging to generalize reliably to vast sequence spaces4–6. Here we build sequence-to-expression models that capture fitness landscapes and use them to decipher principles of regulatory evolution. Using millions of randomly sampled promoter DNA sequences and their measured expression levels in the yeast Saccharomyces cerevisiae, we learn deep neural network models that generalize with excellent prediction performance, and enable sequence design for expression engineering. Using our models, we study expression divergence under genetic drift and strong-selection weak-mutation regimes to find that regulatory evolution is rapid and subject to diminishing returns epistasis; that conflicting expression objectives in different environments constrain expression adaptation; and that stabilizing selection on gene expression leads to the moderation of regulatory complexity. We present an approach for using such models to detect signatures of selection on expression from natural variation in regulatory sequences and use it to discover an instance of convergent regulatory evolution. We assess mutational robustness, finding that regulatory mutation effect sizes follow a power law, characterize regulatory evolvability, visualize promoter fitness landscapes, discover evolvability archetypes and illustrate the mutational robustness of natural regulatory sequence populations. Our work provides a general framework for designing regulatory sequences and addressing fundamental questions in regulatory evolution. https://doi.org/10.1038/s41586-022-04506-6 - 20220 comments0
- PubReading [301] - Cancer Progress and Priorities- Lung Cancer - M. Schabath and M. CoteIn the United States, lung cancer is the second most common diagnosed cancer and the leading cause of cancer-related death. Although tobacco smoking is the major risk factor accounting for 80% to 90% of all lung cancer diagnoses, there are numerous other risk factors that have been identified as casually associated with lung cancer etiology. However, there are few causally linked risk factors for lung cancer diagnosed among never smokers, which, if considered a unique reportable category, is the 11th most common cancer and the 7th leading cause of cancer-related death. Lung cancer survival has only marginally improved over the last several decades, but the availability of screening and early detection by low-dose CT and advances in targeted treatments and immunotherapy will likely decrease mortality rates and improve patient survival outcomes in the near future. doi: 10.1158/1055-9965.EPI-19-0221 - 20190 comments0
- PubReading [300] - Randomisation in clinical trials - E. Beller, V. Gebski & A. KeechRandomisation is the process of assigning clinical trial participants to treatment groups. Randomisation gives each participant a known (usually equal) chance of being assigned to any of the groups. Successful randomisation requires that group assignment cannot be predicted in advance. DOI: 10.5694/j.1326-5377.2002.tb04955.x - 20020 comments0
- PubReading [299] - The Formation and Displacement of Ordered DNA Triplexes in Self- Assembled Three-Dimensional DNA Crystals - Y. Zhao, R. Sha et al.Reconfigurable structures engineered through DNA hybridization and self-assembly offer both structural and dynamic applications in nanotechnology. Here, we have demonstrated that strand displacement of triplex-forming oligonucleotides (TFOs) can be translated to a robust macroscopic DNA crystal by coloring the crystals with covalently attached fluorescent dyes. We show that three different types of triplex strand displacement are feasible within the DNA crystals and the bound TFOs can be removed and/or replaced by (a) changing the pH from 5 to 7, (b) the addition of the Watson–Crick complement to a TFO containing a short toehold, and (c) the addition of a longer TFO that uses the duplex edge as a toehold. We have also proved by X-ray diffraction that the structure of the crystals remains as designed in the presence of the TFOs. https://doi.org/10.1021/jacs.2c12667 - 20230 comments0
- PubReading [298] - Simultaneous sequencing of genetic and epigenetic bases in DNA - J. Füllgrabe, S. Balasubramanian et al.DNA comprises molecular information stored in genetic and epigenetic bases, both of which are vital to our understanding of biology. Most DNA sequencing approaches address either genetics or epigenetics and thus capture incomplete information. Methods widely used to detect epigenetic DNA bases fail to capture common C-to-T mutations or distinguish 5-methylcytosine from 5-hydroxymethylcytosine. We present a single base-resolution sequencing methodology that sequences complete genetics and the two most common cytosine modifications in a single workflow. DNA is copied and bases are enzymatically converted. Coupled decoding of bases across the original and copy strand provides a phased digital readout. Methods are demonstrated on human genomic DNA and cell-free DNA from a blood sample of a patient with cancer. The approach is accurate, requires low DNA input and has a simple workflow and analysis pipeline. Simultaneous, phased reading of genetic and epigenetic bases provides a more complete picture of the information stored in genomes and has applications throughout biomedicine. https://doi.org/10.1038/s41587-022-01652-0 - 20220 comments0
- PubReading Mar 1 · 34m PubReading [297] - Modulation of the helical properties of DNA- next-to-nearest neighbour effects and beyond - A. Balaceanu, M. OrozcoWe used extensive molecular dynamics simulations to study the structural and dynamic properties of the central d(TpA) step in the highly polymorphic d(CpTpApG) tetranucleotide. Contrary to the assumption of the dinucleotide model and its nearest neighbours (tetranucleotide-model), the properties of the central d(TpA) step change quite significantly dependent on the next-to-nearest (hexanucleotide) sequence context and in a few cases are modulated by even remote neighbours (beyond next-to-nearest from the central TpA). Our results highlight the existence of previously undescribed dynamical mechanisms for the transmission of structural information into the DNA and demonstrate the existence of certain sequences with special physical properties that can impact on the global DNA structure and dynamics.0 comments0
- PubReading [296] - Telomerase structural biology comes of age - Y. He & J. FeignTelomerase is an RNA–protein complex comprising telomerase reverse transcriptase, a non-coding telomerase RNA, and proteins involved in biogenesis, assembly, localization, or recruitment. Telomerase synthesizes the telomeric DNA at the 30-ends of linear chromosomes. During the past decade, structural studies have defined the architecture of Tetrahymena and human telomerase as well as protein and RNA domain structures, but high-resolution details of interactions remained largely elusive. In the past two years, several sub-4 Å cryo-electron microscopy structures of telomerase were published, including Tetrahymena telomerase at different steps of telomere repeat addition and human telomerase with telomere shelterin proteins that recruit telomerase to telomeres. These and other recent structural studies have expanded our understanding of telomerase assembly, mechanism, recruitment, and mutations leading to disease. https://doi.org/10.1016/j.sbi.2022.102446 - 20220 comments0
- PubReading [295] - Decentralized Clinical Trials The Future of Medical Product Development? - G. Van Norman,The Covid-19 pandemic disrupted many clinical trials that were potentially bringing new therapeutics to market—an additional untallied cost of the pandemic in lives and quality of life owing to delays in releasing potentially beneficial therapeutics to patients in need. A separate side effect of the pandemic has been swift adoption of virtual interactions between physicians and patients to provide continuity of care while maintaining social distancing. This comes at a time of rapid advancement of technology permitting those interactions, such as enhanced internet connectivity, electronic health records, real-time video conferencing, smartphone health applications, and remotely connectable health monitoring devices that are becoming both more accurate, practical, and affordable. Interest in decentralized clinical trials (DCTs) that use “virtual elements” like these has grown in parallel with acceptance of “ virtual medicine,” accelerating shifts in clinical trial design that many feel are long overdue. https://doi.org/10.1016/j.jacbts.2021.01.011 - 20210 comments0
- PubReading [294] - Violation of DNA neighbor exclusion principle in RNA recognition - M. Yousuf, K. Kim et al.DNA intercalation has been very useful for engineering DNA-based functional materials. It is generally expected that the intercalation phenomenon in RNA would be similar to that in DNA. Here we note that the neighbor-exclusion principle is violated in RNA by naphthalene-based cationic probes, in contrast to the fact that it is usually valid in DNA. All the intercalation structures are responsible for the fluorescence, where small naphthalene moieties are intercalated in between bases via p–p interactions. The structure is aided by hydrogen bonds between the cationic moieties and the ribose-phosphate backbone, which results in specific selectivity for RNA over DNA. This experimentally observed mechanism is supported by computationally reproducing the fluorescence and CD data. MD simulations confirm the unfolding of RNA due to the intercalation of probes. Elucidation of the mechanism of selective sensing for RNA over DNA would be highly beneficial for dynamical observation of RNA which is essential for studying its biological roles. DOI: 10.1039/c5sc03740a - 20160 comments0
- PubReading [293] - The Nuclear Factor Kappa B (NF-kB) signaling in cancer development and immune diseases - M. Zinatizadeh, S. Miri et al.The nuclear factor kappa B (NF-kB) family of transcription factors plays an essential role as stressors in the cellular environment, and controls the expression of important regulatory genes such as immunity, inflammation, death, and cell proliferation. NF-kB protein is located in the cytoplasm, and can be activated by various cellular stimuli. There are two pathways for NF-kB activation, as the canonical and non-canonical pathways, which require complex molecular interactions with adapter proteins and phosphorylation and ubiquitinase enzymes. Accordingly, this increases NF-kB translocation in the nucleus and regulates gene expression. In this study, the concepts that emerge in different cellular systems allow the design of NF-kB function in humans. This would not only allow the development for rare diseases associated with NF-kB, but would also be used as a source of useful information to eliminate widespread consequences such as cancer or inflammatory/immune diseases. https://doi.org/10.1016/j.gendis.2020.06.005 - 20200 comments0
![PubReading [317] - Nucleic acid sensing via electrochemical oligonucleotide-templated reactions - P. Gillespie, D. O’Har et al.](https://podvine.com/cdn-cgi/image/width=175/https://media.rss.com/pub-reading/20220604_120651_b1eb6c62ae4201ef92e04bdcecbaf143.jpg "PubReading [317] - Nucleic acid sensing via electrochemical oligonucleotide-templated reactions - P. Gillespie, D. O’Har et al.")
![PubReading [316] - A brief history of human disease genetics - M. Claussnitzer, M. McCarthy et al.](https://podvine.com/cdn-cgi/image/width=175/https://images.podvine.com/2bbf5fb8b7f06f82cbc8eaf5fc6f7c7d1287fa8a.jpeg "PubReading [316] - A brief history of human disease genetics - M. Claussnitzer, M. McCarthy et al.")
Podcast hosts
- AhmadAbdullrahm..
@AhmadAbdullrahm..
© Mando Mourad 2021
