PubReading
346 episodes - English - Latest episode: 10 months ago -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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Episodes
PubReading [194] - Biological functions of therapy-induced senescence in cancer - E. Fitsiou, A. Soto-Gamez and M. Demaria
October 07, 2022 05:00 - 43 minutes - 60.4 MBTherapy-induced cellular senescence is a state of stable growth arrest induced by common cancer treatments such as chemotherapy and radiation. In an oncogenic context, therapy-induced senescence can have different consequences. By blocking cellular proliferation and by facilitating immune cell infiltration, it functions as tumor suppressive mechanism. By fueling the proliferation of bystander cells and facilitating metastasis, it acts as a tumor promoting factor. This dual role is mainly att...
PubReading [193] - A crystallization apparatus for temperature-controlled flow-cell dialysis with real-time visualization - N. Junius, M. Budayova-Spano et al.
October 06, 2022 20:00 - 31 minutes - 42.9 MBMany instrumentation developments in crystallization have concentrated on massive parallelization assays and reduction of sample volume per experiment to find initial crystallization conditions. Yet improving the size and diffraction quality of the crystals for diffraction studies often requires decoupling of crystal nucleation and growth. This in turn requires the control of variables such as precipitant and protein concentration, equilibration rate, and temperature, which are all difficult...
PubReading [192] - Optimizing data collection for structure determination - A. GonzaÂlez
October 05, 2022 20:00 - 35 minutes - 48.1 MBThe ultimate purpose of diffraction data collection is to produce a data set which will result in the required structural information about the molecule of interest. This usually entails collecting a complete and accurate set of re ̄ection intensities to as high a resolution as possible. In practice, the characteristics of the crystal and properties of the X-ray source can be limiting factors to the data-set quality that can be achieved and a careful strategy has to be used to extract the ma...
PubReading [191] - Review on mechanistic strategy of gene therapy in the treatment of disease - S. Alnasser
October 04, 2022 20:00 - 35 minutes - 48.7 MBGene therapy has become a revolution and its breakthrough is a corner stone in modern science. This treatment has rising advantages with limited negative aspects. Gene therapy is a therapeutic method in which, transfer of DNA to an individual to manipulate a defective gene is performed and to mitigate a disease which is not responding to pharmacological therapy. The gene therapy strategies are divided into two main categories such as direct in-vivo gene delivery of manipulated viral vector v...
PubReading [190] - Contextualizing the Impostor “Syndrome” - S. Feenstra, J. Jordan et al.
October 03, 2022 20:00 - 18 minutes - 25.9 MBThe impostor “syndrome” refers to the notion that some individuals feel as if they ended up in esteemed roles and positions not because of their competencies, but because of some oversight or stroke of luck. Such individuals therefore feel like frauds or “impostors.” Despite the fact that impostor feelings are often linked to marginalized groups in society, to date, research predominantly approaches this phenomenon as an issue of the individual: pointing toward individuals for the roots and ...
PubReading [189] - Clinical Experience With Gene Therapy in Older Patients With Spinal Muscular Atrophy - S. Metesanz, E. Kichula et al.
September 30, 2022 20:00 - 18 minutes - 25.9 MBOnasemnogene abeparvovec was recently approved for the treatment of spinal muscular atrophy (SMA) in children younger than two years; however, clinical trials were primarily completed in children younger than seven months, so practical experience dosing older children began in summer 2019. Here, we look at the safety and efficacy of onasemnogene in seven infants older than seven months who were treated at our center. Overall, onasemnogene appears to be efficacious in children older than seve...
PubReading [188] - m1A and m6A modifications function cooperatively to facilitate rapid mRNA degradation - S. Ho Boo, H. Ha, Y. Ki Kim
September 29, 2022 12:54 - 36 minutes - 49.9 MBN6-Methyladenosine (m6A), the most abundant internal mRNA modification, affects multiple steps in gene expression. Mechanistically, the binding of YTHDF2 to m6A on mRNAs elicits rapid mRNA degradation by recruiting several RNA degrading enzymes. Here, we show that N1-methyladenosine (m1A), another type of RNA modification, accelerates rapid m6A RNA degradation. We identify HRSP12 as an RNA-binding protein that recognizes m1A. The binding of HRSP12 to m1A promotes efficient interaction of YTH...
PubReading [188] - m1A and m6A modifications function cooperatively to facilitate rapid mRNA degradation - S. Ho Boo, H. Ha, Y. Kim
September 28, 2022 20:00 - 36 minutes - 49.9 MBN6-Methyladenosine (m6A), the most abundant internal mRNA modification, affects multiple steps in gene expression. Mechanistically, the binding of YTHDF2 to m6A on mRNAs elicits rapid mRNA degradation by recruiting several RNA degrading enzymes. Here, we show that N1-methyladenosine (m1A), another type of RNA modification, accelerates rapid m6A RNA degradation. We identify HRSP12 as an RNA-binding protein that recognizes m1A. The binding of HRSP12 to m1A promotes efficient interaction of YTH...
PubReading [187] - T-cell invigoration to tumour burden ratio associated with anti-PD-1 response - A. Huang, J. Wherry et al
September 27, 2022 20:00 - 27 minutes - 37.3 MBDespite the success of monotherapies based on blockade of programmed cell death 1 (PD-1) in human melanoma, most patients do not experience durable clinical benefit. Pre-existing T-cell infiltration and/or the presence of PD-L1 in tumours may be used as indicators of clinical response; however, blood-based profiling to understand the mechanisms of PD-1 blockade has not been widely explored. Here we use immune profiling of peripheral blood from patients with stage IV melanoma before and after...
PubReading [186] - Copper(II) and silver(I)‐1,10‐phenanthroline‐5,6‐dione complexes interact with double‐stranded DNA: further evidence of their apparent multi‐modal activity towards Pseudomonas aeruginosa - A. Galdino, A. los Santos et al.
September 26, 2022 20:00 - 32 minutes - 44.2 MBTackling microbial resistance requires continuous efforts for the development of new molecules with novel mechanisms of action and potent antimicrobial activity. Our group has previously identified metal-based compounds, [Ag(1,10-phenan- throline-5,6-dione)2]ClO4 (Ag-phendione) and [Cu(1,10-phenanthroline-5,6-dione)3](ClO4)2.4H2O (Cu-phendione), with efficient antimicrobial action against multidrug-resistant species. Herein, we investigated the ability of Ag-phendione and Cu-phendione to bin...
PubReading [185] - A methodology and an instrument for the temperature-controlled optimization of crystal growth - M. Budayova-Spano, S. Cusak et al
September 23, 2022 20:00 - 32 minutes - 44.4 MBA method and a device for the promotion of crystal growth by keeping the crystallization solution metastable during the growth process are described. This is achieved by controlled temperature variation of the crystallization solution using parameters determined in situ during the growth process. The technique finds application in the growth of large high-quality crystals for neutron crystallography. Thus, it has been applied to grow large crystals of several proteins of interest such as hum...
PubReading [184] - Biophysical Techniques in Structural Biology - C. Dobson
September 22, 2022 20:00 - 30 minutes - 42.4 MBOver the past six decades, steadily increasing progress in the application of the principles and techniques of the physical sciences to the study of biological systems has led to remarkable insights into the molecular basis of life. Of particular significance has been the way in which the determination of the structures and dynamical properties of proteins and nucleic acids has so often led directly to a profound understanding of the nature and mechanism of their functional roles. The increa...
PubReading [183] - From structure to function: Route to understanding lncRNA mechanism - J. Graf and M. Kretz
September 21, 2022 20:00 - 44 minutes - 61.1 MBRNAs have emerged as a major target for diagnostics and therapeutics approaches. Regulatory nonprotein-coding RNAs (ncRNAs) in particular display remarkable ver- satility. They can fold into complex structures and interact with proteins, DNA, and other RNAs, thus modulating activity, localization, or interactome of multi-protein complexes. Thus, ncRNAs confer regulatory plasticity and represent a new layer of reg- ulatory control. Interestingly, long noncoding RNAs (lncRNAs) tend to acquire ...
PubReading [182] - Three's a crowd – stabilisation, structure, and applications of DNA triplexes - M. Dalla Pozza, A. Abdullrahman, C. Cardin, G. Gasser and J. Hall
September 20, 2022 20:00 - 1 hour - 137 MBDNA is a strikingly flexible molecule and can form a variety of secondary structures, including the triple helix, which is the subject of this review. The DNA triplex may be formed naturally, during homologous recombination, or can be formed by the introduction of a synthetic triplex forming oligonucleotide (TFO) to a DNA duplex. As the TFO will bind to the duplex with sequence specificity, there is significant interest in developing TFOs with potential therapeutic applications, including us...
PubReading [181] - Degraders: The Ultimate Weapon Against Amplified Driver Kinases in Cancer - P. Torres-Ayuso and J. Brognard
September 19, 2022 20:00 - 37 minutes - 69 MBAmplification of pro-oncogenic kinases is a common genetic alteration driving tumorigenic phenotypes. Cancer cells rely on the amplified kinases to sustain cell proliferation, survival, and growth, presenting an opportunity to develop therapies targeting the amplified kinases. Utilizing small molecule catalytic inhibitors as therapies to target amplified kinases is plagued by de novo resistance driven by increased expression of the target, and amplified kinases can drive tumorigenic phenotyp...
PubReading [180] - Glioblastoma hijacks neuronal mechanisms for brain invasion - V. Venkataramani, F. Winkler et al.
September 16, 2022 20:00 - 43 minutes - 80.1 MBGlioblastomas are incurable tumors infiltrating the brain. A subpopulation of glioblastoma cells forms a functional and therapy-resistant tumor cell network interconnected by tumor microtubes (TMs). Other sub-populations appear unconnected, and their biological role remains unclear. Here, we demonstrate that whole-brain colonization is fueled by glioblastoma cells that lack connections with other tumor cells and astrocytes yet receive synaptic input from neurons. This subpopulation correspon...
PubReading [179] - Metallodrugs: Mechanisms of Action, Molecular Targets and Biological Activity - G. Ferrano and A. Merlino
September 15, 2022 20:00 - 13 minutes - 25.2 MBThe research interest in the field of inorganic medicinal chemistry had a large increase after the serendipitous discovery of the cytotoxic activity of cisplatin by Rosenberg at the end of 1960s. Since then, cisplatin has entered clinical practice and become one of the most common treatments for solid tumors. Unfortunately, the use of cisplatin and its derivatives is associated with undesired side effects, such as general toxicity and intrinsic and acquired drug-resistance. For these reasons...
PubReading [178] - Mass spectrometry techniques for imaging and detection of metallodrugs - S. Theiner, G. Koellensperger et al.
September 14, 2022 20:00 - 41 minutes - 76.6 MBUndoubtedly, metallomic approaches based on mass spectrometry have evolved into essential tools supporting the drug development of novel metal-based anticancer drugs. This article will comment on the state-of-the-art instrumentation and highlight some of the recent analytical advances beyond routine, especially focusing on the latest developments in inductively coupled plasma-mass spectrometry (ICP-MS). Mass spectrometry-based bioimaging and single-cell methods will be presented, paving the ...
PubReading [177] - Systematic Review of miRNA as Biomarkers in Alzheimer’s Disease - S. Swarbrick, N. Wragg, S. Ghosh and A. Stolzing
September 13, 2022 20:00 - 30 minutes - 56.7 MBCurrently there are 850,000 people with Alzheimer’s disease in the UK, with an estimated rise to 1.1 million by 2025. Alzheimer’s disease is characterised by the accumulation of amyloid-beta plaques and hyperphosphorylated tau in the brain causing a progressive decline in cognitive impairment. Small non-coding microRNA (miRNA) sequences have been found to be deregulated in the peripheral blood of Alzheimer patients. A systematic review was conducted to extract all miRNA found to be significa...
PubReading [176] - miRNA Targeting: Growing beyond the Seed - L. Chipman and A. Pasquinelli
September 12, 2022 20:00 - 23 minutes - 43.1 MBmiRNAs are small RNAs that guide Argonaute proteins to specific target mRNAs to repress their translation and stability. Canonically, miRNA targeting is reliant on base pairing of the seed region, nucleotides 2–7, of the miRNA to sites in mRNA 30 untranslated regions. Recently, the 30 half of the miRNA has gained attention for newly appreciated roles in regulating target specificity and regulation. In addition, the extent of pairing to the miRNA 30 end can influence the stability of the miRN...
PubReading [175] - Solution Oligonucleotide APIs: Regulatory Considerations - C. Wetter. J. Tom et al.
September 09, 2022 20:00 - 20 minutes - 37.1 MBManufacture of oligonucleotide active pharmaceutical ingredients (APIs) typically consists of solid-phase synthesis, deprotection and cleavage, purification and filtration, and isolation from aqueous solutions through lyophilization. In the first step of drug product manufacture, the API is dissolved in water again and excipients are added. While isolation of oligonucleotide APIs can be meaningful in many cases, there may be cases where keeping the API in solution provides benefit, and multi...
PubReading [174] - All-atom simulations to studying metallodrugs/target interactions - P. Janos, A. Spinello and A. Magistrato
September 08, 2022 20:00 - 21 minutes - 39.1 MBMetallodrugs are extensively used to treat and diagnose distinct disease types. The unique physical-chemical properties of metal ions offer tantalizing opportunities to tailor effective scaffolds for selectively targeting specific biomolecules. Modern experimental techniques have collected a large body of structural data concerning the interactions of metallodrugs with their biomolecular targets, although being unable to exhaustively assess the molecular basis of their mechanism of action. I...
PubReading [173] - CAR T cell immunotherapy for human cancer - C. June, M. Milone et al.
September 07, 2022 20:00 - 34 minutes - 63.2 MBAdoptive T cell transfer (ACT) is a new area of transfusion medicine involving the infusion of lymphocytes to mediate antitumor, antiviral, or anti-inflammatory effects. The field has rapidly advanced from a promising form of immuno-oncology in preclinical models to the recent commercial approvals of chimeric antigen receptor (CAR) T cells to treat leukemia and lymphoma. This Review describes opportunities and challenges for entering mainstream oncology that presently face the CAR T field, w...
PubReading [172] - Delivery of oligonucleotide-based therapeutics: challenges and opportunities - S. Hammond, V. Arechavala-Gomeza et.
September 06, 2022 20:00 - 1 hour - 142 MBNucleic acid-based therapeutics that regulate gene expression have been developed towards clinical use at a steady pace for several decades, but in recent years the field has been accelerating. To date, there are 11 marketed products based on antisense oligonucleotides, aptamers and small interfering RNAs, and many others are in the pipeline for both academia and industry. A major technology trigger for this development has been progress in oligonucleotide chemistry to improve the drug prope...
PubReading [171] - Dual action of ketamine confines addiction liability - L. Simmler, C. Lüscher et al.
September 05, 2022 20:00 - 23 minutes - 43.3 MBKetamine is used clinically as an anaesthetic and a fast-acting antidepressant, and recreationally for its dissociative properties, raising concerns of addiction as a possible side effect. Addictive drugs such as cocaine increase the levels of dopamine in the nucleus accumbens. This facilitates synaptic plasticity in the mesolimbic system, which causes behavioural adaptations and eventually drives the transition to compulsion1–4. The addiction liability of ketamine is a matter of much debate...
PubReading [170] - Accelerating reaction generality and mechanistic insight through additive mapping - C. Kullmer, D. MacMillan et al
September 02, 2022 20:00 - 27 minutes - 50.9 MBReaction generality is crucial in determining the overall impact and usefulness of synthetic methods. Typical generalization protocols require a priori mechanistic understanding and suffer when applied to complex, less understood systems. We developed an additive mapping approach that rapidly expands the utility of synthetic methods while generating concurrent mechanistic insight. Validation of this approach on the metallaphotoredox decarboxylative arylation resulted in the discovery of a ph...
PubReading [169] - The Epigenetic Basis of Hematopoietic Stem Cell Aging - A. Kramer and G. Challen
September 01, 2022 20:00 - 37 minutes - 69.4 MBHighly proliferative tissues such as the gut, skin and bone marrow lose millions of cells each day to normal attrition and challenge from different biological adversities. To achieve a lifespan beyond the longevity of individual cell types, tissue-specific stem cells sustain these tissues throughout the life of a human. For example, the lifespan of erythrocytes is about 100 days and adults make about two million new erythrocytes every second. A small pool of hematopoietic stem cells (HSCs) i...
PubReading [168] - Advances of epigenetic editing - R. Gjaltema and M. Rots
July 29, 2022 20:00 - 23 minutes - 43.7 MBEpigenetic editing refers to the locus-specific targeting of epigenetic enzymes to rewrite the local epigenetic landscape of an endogenous genomic site, often with the aim of transcriptional reprogramming. Implementing clustered regularly interspaced short palindromic repeat–dCas9 greatly accelerated the advancement of epigenetic editing, yielding preclinical therapeutic successes using a variety of epigenetic enzymes. Here, we review the current applications of these epigenetic editing tool...
PubReading [167] - Molecular Biology and Evolution of Cancer: From Discovery to Action - J. Somarelli, J. Townsend et al
July 28, 2022 20:00 - 27 minutes - 49.4 MBCancer progression is an evolutionary process. During this process, evolving cancer cell populations encounter restrictive ecological niches within the body, such as the primary tumor, circulatory system, and diverse metastatic sites. Efforts to prevent or delay cancer evolution—and progression—require a deep understanding of the underlying molecular evolutionary processes. Herein we discuss a suite of concepts and tools from evolutionary and ecological theory that can inform cancer biology ...
PubReading [166] - Understanding the fate of DNA nanostructures inside the cell - C. Green, D. Mathur and I. Medinitz
July 27, 2022 20:00 - 37 minutes - 67.8 MBStructural DNA nanotechnology is poised to transform targeted therapeutic and theranostic delivery agents. Some of the most promising biomedical applications of DNA nanostructures include carriers for biosensing, imaging, and drug delivery. Additionally, the unique ability to precisely position inorganic and organic molecules on DNA-based substrates enables the spatially optimized high density interfacing of ligands with cell membrane receptors. To realize clinically viable biomedical produc...
PubReading [165] - Macrocyclic Metal Complex−DNA Conjugates for Electrochemical Sensing of Single Nucleobase Changes in DNA - J. Duprey, J. Tucker et al
July 26, 2022 20:00 - 17 minutes - 31.7 MBThe direct incorporation of macrocyclic cyclidene complexes into DNA via automated synthesis results in a new family of metal-functionalized DNA derivatives that readily demonstrate their utility through the ability of one redox-active copper(II)-containing strand to distinguish electrochemically between all four canonical DNA nucleobases at a single site within a target sequence of DNA. DOI: 10.1021/jacs.5b11319 - 2015
PubReading [164] - DNA Nanostructures for Targeted Antimicrobial Delivery - I. Mela, C. Kaminiski et al
July 25, 2022 20:00 - 19 minutes - 36.3 MBWe report the use of DNA origami nanostructures, functionalized with aptamers, as a vehicle for delivering the antibacterial enzyme lysozyme in a specific and efficient manner. We test the system against Gram-positive (Bacillus subtilis) and Gram-negative (Escherichia coli) targets. We use direct stochastic optical reconstruction microscopy (dSTORM) and atomic force microscopy (AFM) to characterize the DNA origami nanostructures and structured illumination microscopy (SIM) to assess the bind...
PubReading [163] - Synthetic protein-conductive membrane nanopores built with DNA - T. Diederichs, R. Tampé, S. Howorka et al.
July 08, 2022 20:00 - 36 minutes - 66.8 MBNanopores are key in portable sequencing and research given their ability to transport elongated DNA or small bioactive molecules through narrow transmembrane channels. Transport of folded proteins could lead to similar scientific and technological benefits. Yet this has not been realised due to the shortage of wide and structurally defined natural pores. Here we report that a synthetic nanopore designed via DNA nanotechnology can accommodate folded proteins. Transport of fluorescent protein...
PubReading [162] - The second decade of synthetic biology: 2010–2020 - F. Meng and T. Ellis
July 07, 2022 20:00 - 16 minutes - 30.2 MBSynthetic biology is among the most hyped research topics this century, and in 2010 it entered its teenage years. But rather than these being a problematic time, we’ve seen synthetic biology blossom and deliver many new technologies and landmark achievements. doi.org/10.1038/s41467-020-19092-2 - 2020
PubReading [161] - Even Cancer Cells Watch Their Cholesterol! - R. Riscal, N. Skuli and C. Simon
July 06, 2022 20:00 - 55 minutes - 102 MBDeregulated cell proliferation is an established feature of cancer, and altered tumor metabolism has witnessed renewed interest over the past decade, including the study of how cancer cells rewire metabolic pathways to renew energy sources and ‘‘building blocks’’ that sustain cell division. Microenvironmental oxygen, glucose, and glutamine are regarded as principal nutrients fueling tumor growth. However, hostile tumor microenvironments render O2/nutrient supplies chronically insufficient fo...
PubReading [160] - Sequence-Selective Minor Groove Recognition of a DNA Duplex Containing Synthetic Genetic Components - G. Padroni, G. Burley et al.
July 05, 2022 20:00 - 31 minutes - 57.6 MBThe structural basis of minor groove recognition of a DNA duplex containing synthetic genetic information by hairpin pyrrole- imidazole polyamides is described. Hairpin polyamides induce a higher melting stabilization of a DNA duplex containing the unnatural P·Z base- pair when an imidazole unit is aligned with a P nucleotide. An NMR structural study showed that the incorporation of two isolated P·Z pairs enlarges the minor groove and slightly narrows the major groove at the site of this syn...
PubReading [159] - Designing Hydrogels for On-Demand Therapy - N. Oliva, N. Artzi et al.
July 04, 2022 20:00 - 35 minutes - 65.7 MBSystemic administration of therapeutic agents has been the preferred approach to treat most pathological conditions, in particular for cancer therapy. This treatment modality is associated with side effects, off-target accumulation, toxicity, and rapid renal and hepatic clearance. Multiple efforts have focused on incorporating targeting moieties into systemic therapeutic vehicles to enhance retention and minimize clearance and side effects. However, only a small percentage of the nanoparticl...
PubReading [158] - Junctions in DNA: underexplored targets for therapeutic intervention - E. Ivens, M. Cominetti and M. Searcey
July 01, 2022 20:00 - 29 minutes - 53.5 MBDNA has been a key target for cancer therapy, with a range of compounds able to bind and either impair its processing or induce damage. Targeting DNA with small molecules in a truly sequence specific way, to impair gene specific processes, remains out of reach. The ability of DNA to assume different structures from the classical double helix allows access to more specific ligand binding modes and, potentially, to new avenues of treatment. In this review, we illustrate the small molecules tha...
PubReading [157] - Cell-SELEX Technology - S. Ohuchi
June 30, 2022 20:00 - 29 minutes - 53.5 MBAptamers are molecules identified from large combinatorial nucleic acid libraries by their high affinity to target molecules. Due to a variety of desired properties, aptamers are attractive alternatives to antibodies in molecular biology and medical applications. Aptamers are identified through an iterative selection–amplification process known as systematic evolution of ligands by exponential enrichment (SELEX). Although SELEX is typically carried out using purified target molecules, whole ...
PubReading [156] - Direct Nanopore Sequencing of Individual Full Length tRNA Strands - N. Thomas, R. Abu-Shumays et al
June 29, 2022 20:00 - 31 minutes - 58.3 MBWe describe a method for direct tRNA sequencing using the Oxford Nanopore MinION. The principal technical advance is custom adapters that facilitate end-to-end sequencing of individual transfer RNA (tRNA) molecules at subnanometer precision. A second advance is a nanopore sequencing pipeline optimized for tRNA. We tested this method using purified E. coli tRNAfMet, tRNALys, and tRNAPhe samples. 76–92% of individual aligned tRNA sequence reads were full length. As a proof of concept, we showe...
PubReading [155] - The central role of DNA damage in the ageing process - B. Schumacher, J. Pothof, Vijg and Hoeijmakers
June 28, 2022 20:00 - 51 minutes - 94.5 MBAgeing is a complex, multifaceted process leading to widespread functional decline that affects every organ and tissue, but it remains unknown whether ageing has a unifying causal mechanism or is grounded in multiple sources. Phenotypically, the ageing process is associated with a wide variety of features at the molecular, cellular and physiological level—for example, genomic and epigenomic alterations, loss of proteostasis, declining overall cellular and subcellular function and deregulatio...
PubReading [154] - Mitochondria‐ER Tethering in Neurodegenerative Diseases - R. Raeisossadati, M. Ferrari
June 27, 2022 20:00 - 47 minutes - 86.1 MBOrganelles juxtaposition has been detected for decades, although only recently gained importance due to a pivotal role in the regulation of cellular processes dependent on membrane contact sites. Endoplasmic reticulum (ER) and mitochondria interaction is a prime example of organelles contact sites. Mitochondria-associated membranes (MAM) are proposed to harbor ER-mitochondria tether complexes, mainly when these organelles are less than 30 nm apart. Dysfunctions of proteins located at the MAM...
PubReading [153] - The DNA methyltransferase family: a versatile toolkit for epigenetic regulation - Frank Lyko
June 24, 2022 20:00 - 52 minutes - 95.4 MBThe DNA methyltransferase (DNMT) family comprises a conserved set of DNA-modifying enzymes that have a central role in epigenetic gene regulation. Recent studies have shown that the functions of the canonical DNMT enzymes — DNMT1, DNMT3A and DNMT3B — go beyond their traditional roles of establishing and maintaining DNA methylation patterns. This Review analyses how molecular interactions and changes in gene copy numbers modulate the activity of DNMTs in diverse gene regulatory functions, inc...
PubReading [152] - Teaching photosensitizers a new trick: red light-triggered G-quadruplex alkylation by ligand co-localization - E. Cadoni, A. Madder et al
June 23, 2022 20:00 - 17 minutes - 31.8 MBWe propose a bimolecular approach for G-quadruplex alkylation, using a pro-reactive furan-containing ligand, activated by red-light irradiation of a proximate G4-binding photosensitizer. G4- over dsDNA alkylation can be achieved selectively and proves high-yielding at low ligand excess. HPLC and modelling studies allowed identifying potential residues involved in the alkylation. DOI: 10.1039/d0cc06030e - 2021
PubReading [151] - Chirality transmission in macromolecular domains - S. Pandey, C. Lou, H.Mao et al
June 22, 2022 20:00 - 36 minutes - 67.4 MBChiral communications exist in secondary structures of foldamers and copolymers via a network of noncovalent interactions within effective intermolecular force (IMF) range. It is not known whether long-range chiral communication exists between macromolecular tertiary structures such as peptide coiled-coils beyond the IMF distance. Harnessing the high sensitivity of single-molecule force spectroscopy, we investigate the chiral interaction between covalently linked DNA duplexes and peptide coi...
PubReading [150] - 1‐Deazaguanosine-Modified RNA: The Missing Piece for Functional RNA Atomic Mutagenesis - R. Bereiter, R. Micura et al
June 21, 2022 20:00 - 32 minutes - 59.3 MBAtomic mutagenesis is the key to advance our understanding of RNA recognition and RNA catalysis. To this end, deazanucleosides are utilized to evaluate the participation of specific atoms in these processes. One of the remaining challenges is access to RNA-containing 1-deazaguanosine (c1G). Here, we present the synthesis of this nucleoside and its phosphoramidite, allowing first time access to c1G-modified RNA. Thermodynamic analyses revealed the base pairing parameters for c1G-modified RNA....
PubReading [149] - Therapeutic design of peptide modulators of protein-protein interactions in membranes - T. Stone and C. Deber
June 20, 2022 20:00 - 47 minutes - 87.3 MBMembrane proteins play the central roles in a variety of cellular processes, ranging from nutrient uptake and signalling, to cell-cell communication. Their biological functions are directly related to how they fold and assemble; defects often lead to disease. Protein–protein interactions (PPIs) within the membrane are therefore of great interest as therapeutic targets. Here we review the progress in the application of membrane–insertable peptides for the disruption or stabilization of membra...
PubReading [148] - The current landscape of nucleic acid therapeutics - J. Kulkarni, R. van der Meel et al.
June 17, 2022 20:00 - 1 hour - 64.4 MBThe increasing number of approved nucleic acid therapeutics demonstrates the potential to treat diseases by targeting their genetic blueprints in vivo. Conventional treatments generally induce therapeutic effects that are transient because they target proteins rather than underlying causes. In contrast, nucleic acid therapeutics can achieve long-lasting or even curative effects via gene inhibition, addition, replacement or editing. Their clinical translation, however, depends on delivery tec...
PubReading [147] - Furan-containing polymeric Materials: Harnessing the Diels-Alder chemistry for biomedical applications - T. Gevrek and A. Sanyal
June 16, 2022 20:00 - 53 minutes - 97.9 MBPolymeric materials that can be readily modified with (bio)molecules of interest to render them suitable for intended applications are in demand for use in various areas of biomedical and materials science. Among various clickable reactive groups that can be incorporated into polymeric materials as handles for functionalization, ready availability, efficient reactivity under relatively mild conditions, as well as selectivity to specific functional groups makes the furan moiety an attractive ...
PubReading [146] - Pyrene-modified PNAs: Stacking interactions and selective excimer emission in PNA2DNA triplexes - A. Manicardi, L. Guidi, A. Ghidini and R. Corradini
June 15, 2022 20:00 - 24 minutes - 45.1 MBPyrene derivatives can be incorporated into nucleic acid analogs in order to obtain switchable probes or supramolecular architectures. In this paper, peptide nucleic acids (PNAs) containing 1 to 3 1-pyreneacetic acid units (PNA1–6) with a sequence with prevalence of pyrimidine bases, complementary to cystic fibrosis W1282X point mutation were synthesized. These compounds showed sequence-selective switch-on of pyrene excimer emission in the presence of target DNA, due to PNA2DNA triplex forma...