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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 [294] - Violation of DNA neighbor exclusion principle in RNA recognition - M. Yousuf, K. Kim et al.

February 24, 2023 12:00 - 27 minutes - 25.1 MB

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...

PubReading [293] - The Nuclear Factor Kappa B (NF-kB) signaling in cancer development and immune diseases - M. Zinatizadeh, S. Miri et al.

February 23, 2023 13:00 - 36 minutes - 33.7 MB

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 p...

PubReading [292] - Acquisition of Dynamic Function in Human Stem Cell-Derived b Cells - L. Velazco-Cruz, J. Millman et al.

February 22, 2023 14:00 - 36 minutes - 33.5 MB

Recent advances in human pluripotent stem cell (hPSC) differentiation protocols have generated insulin-producing cells resembling pancreatic b cells. While these stem cell-derived b (SC-b) cells are capable of undergoing glucose-stimulated insulin secretion (GSIS), insulin secretion per cell remains low compared with islets and cells lack dynamic insulin release. Herein, we report a differentiation strategy focused on modulating transforming growth factor b (TGF-b) signaling, controlling cel...

PubReading [291] - Tumour Cell Secretome in Chemoresistance and Tumour Recurrence - E. Madden, A. Samali et al.

February 21, 2023 13:00 - 40 minutes - 37.1 MB

Chemoresistance is a major factor driving tumour relapse and the high rates of cancer-related deaths. Understanding how cancer cells overcome chemotherapy-induced cell death is critical in promoting patient survival. One emerging mechanism of chemoresistance is the tumour cell secretome (TCS), an array of protumorigenic factors released by tumour cells. Chemotherapy exposure can also alter the composition of the TCS, known as therapy-induced TCS, and can promote tumour relapse and the format...

PubReading [290] - Placebo Controls- Now??? - A. Caplan

February 20, 2023 13:00 - 9 minutes - 8.25 MB

In this era of a pandemic, why do we need the placebo controls for regulatory agency or Food and Drug Administration (FDA)-approved clinical trials aimed at COVID-19 patients? The answer is always that we have to establish a ruler with a baseline onto which efficacy measurements can be statistically judged. https://doi.org/10.1007/s00005-021-00612-x - 2021

PubReading [289] - The importance of loop length on the stability of i-motif structures - S. Gurung, C. Schwarz, J. Hall, C. Cardin and J. Brazier

February 17, 2023 12:00 - 14 minutes - 13.4 MB

Using UV and srCD spectroscopy it is found that loop length within the i-motif structure is important for both thermal and pH stability, but in contrast to previous statements, it is the shorter loops that exhibit the highest stability. DOI: 10.1039/c4cc07279k - 2015

PubReading [288] - Structural and functional diversity calls for a new classification of ABC transporters - C. Thomas, J. Zimmer and R. Tampe

February 16, 2023 13:00 - 12 minutes - 11.3 MB

Members of the ATP-binding cassette (ABC) transporter superfamily translocate a broad spectrum of chemically diverse substrates. While their eponymous ATP-binding cassette in the nucleotide-binding domains (NBDs) is highly conserved, their transmembrane domains (TMDs) forming the translocation pathway exhibit distinct folds and topologies, suggesting that during evolution the ancient motor domains were combined with different transmembrane mechanical systems to orchestrate a variety of cellu...

PubReading [287] - On the Origin of the Term ‘‘Stem Cell’’ - M. Ramalho-Santos and H. Willenbring

February 15, 2023 13:00 - 14 minutes - 12.9 MB

Stem cells have fascinated both biologists and clinicians for over a century. Here, we discuss the origin of the term ‘‘stem cell,’’ which can be traced back to the late 19th century. The term stem cell originated in the context of two major embryological questions of that time: the continuity of the germ-plasm and the origin of the hematopoietic system. Theodor Boveri and Valentin Hacker used the term stem cell to describe cells committed to give rise to the germline. In parallel, Artur Pap...

PubReading [286] - Cancer occurrence in Turner syndrome and the effect of sex hormone substitution therapy - M. Viuff, C. Gravholt et al.

February 14, 2023 13:00 - 27 minutes - 25.1 MB

Although the overall risk of cancer is not increased in Turner syndrome, the pattern of cancer occurrence differs from the general population. We aim to describe the cancer morbidity pattern in Turner syndrome and evaluate the effect of long-term hormone replacement therapy (HRT). Design: Nationwide epidemiological study. The lack of one X chromosome might play a role in skin neoplasms, CNS tumors, colon and rectal cancers. The risk of breast cancer is lower than in the general population. L...

PubReading [285] - Promoting Scientist–Advocate Collaborations in Cancer Research- Why and How - J. Salamone, A. Shajahan-Haq et al.

February 13, 2023 11:00 - 26 minutes - 24.7 MB

Advocates bring unique and important viewpoints to the cancer research process, ensuring that scientific and medical advances are patient-centered and relevant. In this article, we discuss the benefits of engaging advocates in cancer research and underscore ways in which both the scientific and patient communities can facilitate this mutually beneficial collaboration. We discuss how to establish and nurture successful scientist-advocate relationships throughout the research process. We revie...

PubReading [284] - A brief history of nearly EV-erything – The rise and rise of extracellular vesicles - Y. Couch, D. Carter et al.

February 10, 2023 12:00 - 35 minutes - 32.6 MB

Extracellular vesicles (EVs) are small cargo-bearing vesicles released by cells into the extracellular space. The field of EVs has grown exponentially over the past two decades; this growth follows the realisation that EVs are not simply a waste disposal system as had originally been suggested by some, but also a complex cell-to-cell communication mechanism. Indeed, EVs have been shown to transfer functional cargo between cells and can influence several biological processes. These small biol...

PubReading [283] - PARP1 Gene Knockout Suppresses Expression of DNA Base Excision Repair Genes - A. Zakharenkoa, O. Lavrik et al.

February 09, 2023 13:00 - 17 minutes - 16.2 MB

The effect of PARP1 knockout in HEK293 cells on the gene expression of DNA base excision repair (BER) proteins was studied. It was shown that the expression of all differentially expressed genes (DEGs) of BER was reduced by knockout. The expression of the DNA glycosylase gene NEIL1, which is considered to be one of the common “hubs” for binding BER proteins, has changed the most. The expression of genes of auxiliary subunits of DNA polymerases δ and ε is also significantly reduced. The PARP1...

PubReading [282] - Modified RNA triplexes- Thermodynamics, structure and biological potential - M. Szabat, E. Kierzek & R. Kierzek

February 08, 2023 13:00 - 28 minutes - 25.8 MB

The occurrence of triplexes in vivo has been well documented and is determined by the presence of long homopurine-homopyrimidine tracts. The formation of these structures is the result of conformational changes that occur in the duplex, which allow the binding of a third strand within the major groove of the helix. Formation of these noncanonical forms by introducing synthetic triplex-forming oligonucleotides (TFOs) into the cell may have applications in molecular biology, diagnostics and th...

PubReading [281] - Light-Responsive Dynamic DNA-Origami-Based Plasmonic Assemblies - J. Ryssy, A. Kuzyk et al.

February 07, 2023 13:00 - 16 minutes - 15.2 MB

DNA nanotechnology offers a versatile toolbox for precise spatial and temporal manipulation of matter on the nanoscale. However, rendering DNA-based systems responsive to light has remained challenging. Herein, we describe the remote manipulation of native (non-photoresponsive) chiral plasmonic molecules (CPMs) using light. Our strategy is based on the use of a photoresponsive medium comprising a merocyanine-based photoacid. Upon exposure to visible light, the medium decreases its pH, induci...

PubReading [280] - Ethics assessment in research proposals adopting CRISPR technology - F. Hirsch, R. Iphofen, Z. Koporc

February 06, 2023 12:00 - 25 minutes - 23.6 MB

The rapid and exponential growth of genome editing has posed many challenges for bioethics. This article briefly explains the nature of the technique and the particularly rapid development of Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) technology. The international and, specifically, European-level systems for assessing the ethical issues consequent on these developments are outlined and discussed. The challenges posed by cases in China are summarized to raise concerns ...

PubReading [279] - Facts and Hopes in Immunotherapy for Early-Stage Triple-Negative Breast Cancer - I. Nederlof, L. Voorwerk & M. Kok

February 03, 2023 13:00 - 50 minutes - 46.6 MB

A substantial fraction of early-stage triple-negative breast cancer (eTNBC) is characterized by high levels of stromal tumor-infiltrating lymphocytes (sTIL) and has a good prognosis even without systemic treatment, highlighting the importance of an endogenous anticancer immune response. Still, a considerable proportion of patients with eTNBC need some “therapeutical push” to kick-start this immune response. Exploiting this immune response with immune-checkpoint inhibition (ICI), in combinati...

PubReading [278] - Light-Enhanced Cytotoxicity of Doxorubicin by Photoactivation - G. Greco, M. Calvaresi et al.

February 02, 2023 13:00 - 22 minutes - 20.3 MB

The combination of photodynamic therapy with chemotherapy (photochemotherapy, PCT) can lead to additive or synergistic antitumor effects. Usually, two different molecules, a photosensitizer (PS) and a chemotherapeutic drug are used in PCT. Doxorubicin is one of the most successful chemotherapy drugs. Despite its high efficacy, two factors limit its clinical use: severe side effects and the development of chemoresistance. Doxorubicin is a chromophore, able to absorb light in the visible range...

PubReading [277] - Direct targeting of amplified gene loci for proapoptotic anticancer therapy - M. Tiwari, F. Rogers at al..

February 01, 2023 13:00 - 33 minutes - 30.9 MB

Gene amplification drives oncogenesis in a broad spectrum of cancers. A number of drugs have been developed to inhibit the protein products of amplified driver genes, but their clinical efficacy is often hampered by drug resistance. Here, we introduce a therapeutic strategy for targeting cancer-associated gene amplifications by activating the DNA damage response with triplex-forming oligonucleotides (TFOs), which drive the induction of apoptosis in tumors, whereas cells without amplification...

PubReading [276] - Impact of 3D cell culture on bone regeneration potential of mesenchymal stromal cells - M. Bicer, G. Cottrell and D. Widera

January 31, 2023 13:00 - 45 minutes - 42.1 MB

As populations age across the world, osteoporosis and osteoporosis-related fractures are becoming the most prevalent degenerative bone diseases. More than 75 million patients suffer from osteoporosis in the USA, the EU and Japan. Furthermore, it is anticipated that the number of patients affected by osteoporosis will increase by a third by 2050. Although conventional therapies including bisphosphonates, calcitonin and oestrogen-like drugs can be used to treat degenerative diseases of the bon...

PubReading [275] - The biospheric emergency calls for scientists to change tactics - F. Racimo, J. Halder et al.

January 30, 2023 12:01 - 38 minutes - 35.5 MB

Our current economic and political structures have an increasingly devastating impact on the Earth's climate and ecosystems: we are facing a biospheric emergency, with catastrophic consequences for both humans and the natural world on which we depend. Life scientists - including biologists, medical scientists, psychologists and public health experts - have had a crucial role in documenting the impacts of this emergency, but they have failed to drive governments to take action in order to pre...

PubReading [274] - The eukaryotic replisome tolerates leading-strand base damage by replicase switching - T. Guilliam & J. Yeeles

January 27, 2023 12:00 - 42 minutes - 39 MB

The high-fidelity replicative DNA polymerases, Pol e and Pol d, are generally thought to be poorly equipped to replicate damaged DNA. Direct and complete replication of a damaged template therefore typically requires the activity of low-fidelity translesion synthesis (TLS) polymerases. Here we show that a yeast replisome, reconstituted with purified proteins, is inherently tolerant of the common oxidative lesion thymine glycol (Tg). Surprisingly, leading-strand Tg was bypassed efficiently in...

PubReading [273] - RNA targeting unleashes indiscriminate nuclease activity of CRISPR–Cas12a2 - J. Bravo, D. Taylor et al.

January 26, 2023 12:00 - 26 minutes - 24 MB

Cas12a2 is a CRISPR-associated nuclease that performs RNA-guided, sequence- nonspecific degradation of single-stranded RNA, single-stranded DNA and double- stranded DNA following recognition of a complementary RNA target, culminating in abortive infection1. Here we report structures of Cas12a2 in binary, ternary and quaternary complexes to reveal a complete activation pathway. Our structures reveal that Cas12a2 is autoinhibited until binding a cognate RNA target, which exposes the RuvC activ...

PubReading [272] - Frailty biomarkers under the perspective of geroscience- A narrative review - R. Dos Santos Aguiar Gonçalves, P. de Souto Barreto

January 25, 2023 12:00 - 42 minutes - 38.9 MB

Cellular and molecular aging biomarkers might contribute to identify at-risk individuals for frailty before overt clinical manifestations appear. Although studies on the associations of aging biomarkers and frailty exist, no investigation has gathered this information using a structured framework for identifying aging biomarkers; as a result, the evidence on frailty and aging biomarkers is diffuse and incomplete. Therefore, this narrative review aimed to gather information on the association...

PubReading [271] - Mass-resolved electronic circular dichroism ion spectroscopy - S. Daly, F. Rosu, V. Gabelica

January 24, 2023 12:00 - 19 minutes - 18.1 MB

DNA and proteins are chiral: Their three-dimensional structures cannot be superimposed with their mirror images. Circular dichroism spectroscopy is widely used to characterize chiral compounds, but data interpretation is difficult in the case of mixtures. We recorded the electronic circular dichroism spectra of DNA helices separated in a mass spectrometer. We studied guanine-rich strands having various secondary structures, electrosprayed them as negative ions, irradiated them with an ultrav...

PubReading [270] - Why do researchers decide to publish in questionable journals? A review of the literature - T. Frandsen

January 23, 2023 13:00 - 23 minutes - 21.5 MB

Peer review is a cornerstone of scientific publication, and consequently, predatory journals are feared to be a threat to the credibility of science as they perform no or low-quality peer review. The question of why researchers decide to publish in a questionable journal remains relatively unexplored. This paper provides an overview of the existing literature on why researchers decide to publish papers in questionable journals, specifically whether or not they search for a low-barrier way to...

PubReading [269] - Rapid and reversible optogenetic silencing of synaptic transmission by clustering of synaptic vesicles - D. Vettkötter, A. Gottschalk et al.

January 20, 2023 12:00 - 47 minutes - 43.2 MB

Acutely silencing specific neurons informs about their functional roles in circuits and behavior. Existing optogenetic silencers include ion pumps, channels, metabotropic receptors, and tools that damage the neurotransmitter-release machinery. While the former hyperpolarize the cell, alter ionic gradients or cellular biochemistry, the latter allow only slow recovery, requiring de novo synthesis. Thus, tools combining fast activation and reversibility are needed. Here, we use light-evoked hom...

PubReading [268] - Inheritance of paternal DNA damage by histone-mediated repair restriction - S. Wang, D. Meyer & B. Schumacher

January 19, 2023 12:00 - 41 minutes - 37.6 MB

How paternal exposure to ionizing radiation affects genetic inheritance and disease risk in the offspring has been a long-standing question in radiation biology. In humans, nearly 80% of transmitted mutations arise in the paternal germline1, but the transgenerational effects of ionizing radiation exposure has remained controversial and the mechanisms are unknown. Here we show that in sex-separated Caenorhabditis elegans strains, paternal, but not maternal, exposure to ionizing radiation lead...

PubReading [267] - Circular dichroism and its uses in biomolecular research - A Review - Sangeeta and Anu Radha Pathania

January 18, 2023 12:00 - 33 minutes - 30.7 MB

The higher-order structure of proteins as well as their thermal stability can be determined using the circular dichroism (CD). CD is a common approach for swiftly assessing binding, secondary structure, and folding properties of proteins. In a nutshell, circular dichroism is an absorption spectroscopy technique that employs circularly polarized light to explore structural properties of optically active chiral compounds. Biological molecules, as well as their interactions with metals and othe...

PubReading [266] - High-pressure crystallography shows noble gas intervention into protein-lipid interaction and suggests a model for anaesthetic action - I. Melnikov, V. Gordeliy, A. Popov et al.

January 17, 2023 13:00 - 28 minutes - 25.9 MB

In this work we examine how small hydrophobic molecules such as inert gases interact with membrane proteins (MPs) at a molecular level. High pressure atmospheres of argon and krypton were used to produce noble gas derivatives of crystals of three well studied MPs (two different proton pumps and a sodium light-driven ion pump). The structures obtained using X-ray crystallography showed that the vast majority of argon and krypton binding sites were located on the outer hydrophobic surface of t...

PubReading [265] - The art of writing literature review- What do we know and what do we need T to know? - J. Paula & A. Criado

January 16, 2023 13:00 - 44 minutes - 41.1 MB

A literature review article provides a comprehensive overview of literature related to a theme/theory/method and synthesizes prior studies to strengthen the foundation of knowledge. In the growing International Business (IB) research field, systematic literature reviews have great value, yet there are not many reviews published describing how researchers can design and develop classic review articles. In explaining the purpose, methodology, and structure of a systematic review, we provide gu...

PubReading [264] - Role of astrocytes in rhythmic motor activity - A. Montalant, E. Carlsen, JF Perrier

January 13, 2023 13:00 - 21 minutes - 19.8 MB

Rhythmic motor activities such as breathing, locomotion, tremor, or mastication are organized by groups of interconnected neurons. Most synapses in the central nervous system are in close apposition with processes belonging to astrocytes. Neurotransmitters released from neurons bind to receptors expressed by astrocytes, activating a signaling pathway that leads to an increase in calcium concentration and the release of gliotransmitters that eventually modulate synaptic transmission. It is th...

PubReading [263] - Molecular mechanism of light-driven sodium pumping - K. Kovalev, V. Gordeliy et al.

January 12, 2023 13:00 - 41 minutes - 37.9 MB

The light-driven sodium-pumping rhodopsin KR2 from Krokinobacter eikastus is the only non- proton cation active transporter with demonstrated potential for optogenetics. However, the existing structural data on KR2 correspond exclusively to its ground state, and show no sodium inside the protein, which hampers the understanding of sodium-pumping mechanism. Here we present crystal structure of the O-intermediate of the physiologically relevant pentameric form of KR2 at the resolution of 2.1 Å...

PubReading [262] - Lipids mediate supramolecular outer membrane protein assembly in bacteria - M. Webby, C. Kleanthous et al.

January 11, 2023 13:00 - 41 minutes - 38.3 MB

Beta Barrel outer membrane proteins (OMPs) cluster into supramolecular assemblies that give function to the outer membrane (OM) of Gram-negative bacteria. How such assemblies form is unknown. Here, through photoactivatable cross-linking into the Escherichia coli OM, coupled with simulations, and biochemical and biophysical analysis, we uncover the basis for OMP clustering in vivo. OMPs are typically surrounded by an annular shell of asymmetric lipids that mediate higher-order complexes with ...

PubReading [261] - Correlated Motions in Structural Biology - D. Xu, S. Meisburger, and N. Ando

January 10, 2023 13:00 - 40 minutes - 37.2 MB

Correlated motions in proteins arising from the collective movements of residues have long been proposed to be fundamentally important to key properties of proteins, from allostery and catalysis to evolvability. Recent breakthroughs in structural biology have made it possible to capture proteins undergoing complex conformational changes, yet intrinsic correlated motions within a conformation remain one of the least understood facets of protein structure. For many decades, the analysis of tot...

PubReading [260] - Towards a framework for embedding doctorateness in research proposals - E. Sanganyado, W. Nunu and S. Sanganyado

January 09, 2023 12:00 - 24 minutes - 22.5 MB

Doctorate graduates are expected to contribute original knowledge and possess advanced skills essential for addressing complex problems. Embedding doctorateness in doctorate programmes could help ensure that the productivity of doctoral research is explicitly demonstrated. Doctorateness represents independent scholarship, the transition from knowledge consumption to knowledge creation, original scholarly contribution, and research integrity. A research proposal is the backbone of a doctoral ...

PubReading [259] - Patient-Derived Organoids for Precision Cancer Immunotherapy - M. Groenholm, V. Cerullo et al.

January 06, 2023 13:00 - 45 minutes - 41.6 MB

Cancer immunotherapy has revolutionized the way tumors are treated. Nevertheless, efficient and robust testing platforms are still missing, including clinically relevant human ex vivo tumor assays that allow pretreatment testing of cancer therapies and selection of the most efficient and safe therapy for a specific patient. In the case of immunotherapy, this testing platform would require not only cancer cells, but also the tumor micro-environment, including immune cells. Here, we discuss th...

PubReading [258] - Visualization of macromolecular structures - S. O’Donoghue, A. Olson et al.

January 05, 2023 12:00 - 45 minutes - 41.6 MB

Structural biology is rapidly accumulating a wealth of detailed information about protein function, binding sites, RNA, large assemblies and molecular motions. These data are increasingly of interest to a broader community of life scientists, not just structural experts. Visualization is a primary means for accessing and using these data, yet visualization is also a stumbling block that prevents many life scientists from benefiting from three-dimensional structural data. In this review, we f...

PubReading [257] - AlphaFill- enriching AlphaFold models with ligands and cofactors - M. Hekkelman, A. Perrakis et al.

January 04, 2023 13:00 - 32 minutes - 30.2 MB

Artificial intelligence-based protein structure prediction approaches have had a transformative effect on biomolecular sciences. The predicted protein models in the AlphaFold protein structure database, however, all lack coordinates for small molecules, essential for molecular structure or function: hemoglobin lacks bound heme; zinc-finger motifs lack zinc ions essential for structural integrity and metalloproteases lack metal ions needed for catalysis. Ligands important for biological funct...

PubReading [256] - A Phenotypic Approach for the Identification of New Molecules for Targeted Protein Degradation Applications - P. Stacey, M. Muelbaier et al.

January 03, 2023 13:01 - 30 minutes - 28.2 MB

Targeted protein degradation is an emerging new strategy for the modulation of intracellular protein levels with applications in chemical biology and drug discovery. One approach to enable this strategy is to redirect the ubiquitin–proteasome system to mark and degrade target proteins of interest (POIs) through the use of proteolysis targeting chimeras (PROTACs). Although great progress has been made in enabling PROTACs as a platform, there are still a limited number of E3 ligases that have ...

PubReading [255] - Doing better- eleven ways to improve the integration of sex and gender in health research proposals - R. Mason

January 02, 2023 12:00 - 14 minutes - 12.9 MB

Health researchers are often challenged on how to integrate a sex and gender lens into their work. Reviews completed across a range of health research studies show there are several commonly overlooked opportunities to do better in this regard. Nine ways to improve the integration of a sex and gender lens in health research proposals have been identified. https://doi.org/10.1186/s41073-020-00102-2 - 2020

PubReading [254] - DNA polymerase Epsilon and Delta exonuclease domain mutations in endometrial cancer - D. Church, I. Tomlinson

December 30, 2022 13:00 - 32 minutes - 30.1 MB

Accurate duplication of DNA prior to cell division is essential to suppress mutagenesis and tumour development. The high fidelity of eukaryotic DNA replication is due to a combination of accurate incorporation of nucleotides into the nascent DNA strand by DNA polymerases, the recognition and removal of mispaired nucleotides (proofreading) by the exonuclease activity of DNA polymerases Delta and Epsilon, and post-replication surveillance and repair of newly synthesized DNA by the mismatch rep...

PubReading [253] - Automated data collection for macromolecular crystallography - G. Winter & K. McAuley

December 28, 2022 19:06 - 49 minutes - 45.8 MB

An overview, together with some practical advice, is presented of the current status of the automation of macromolecular crystallography (MX) data collection, with a focus on MX beamlines at Diamond Light Source, UK. doi:10.1016/j.ymeth.2011.06.010 - 2011

PubReading [252] - Epigenetic Heterogeneity in Friedreich Ataxia Underlies Variable FXN Reactivation - L. Rodden, S. Bidichandani et al.

December 28, 2022 12:00 - 28 minutes - 25.7 MB

Friedreich ataxia (FRDA) is typically caused by homozygosity for an expanded GAA triplet-repeat in intron 1 of the FXN gene. The expanded repeat induces repressive histone changes and DNA hypermethylation, which result in epigenetic silencing and FXN transcriptional deficiency. A class I histone deacetylase inhibitor (HDACi-109) reactivates the silenced FXN gene, although with considerable inter-individual variability, which remains etiologically unexplained. Because HDAC inhibitors work by ...

PubReading [251] - Directed DNA Metallization - G. Burley, T. Carell et al.

December 27, 2022 12:00 - 10 minutes - 9.86 MB

DNA is an outstanding material for the preparation of nano- and microscale assemblies, which are believed to have potential for the construction of nanoelectronic devices. DNA metallization procedures were developed in order to increase the conductivity of subsequent DNA nanostructures, thereby enabling their use as molecular wires. 10.1021/ja055517v - 2006

PubReading [250] - Promoting Scientist–Advocate Collaborations in Cancer Research- Why and How -

December 26, 2022 12:00 - 26 minutes - 24.7 MB

Advocates bring unique and important viewpoints to the cancer research process, ensuring that scientific and medical advances are patient-centered and relevant. In this article, we discuss the benefits of engaging advocates in cancer research and underscore ways in which both the scientific and patient communities can facilitate this mutually beneficial collaboration. We discuss how to establish and nurture successful scientist–advocate relationships throughout the research process. We revie...

PubReading [249] - A flow platform for degradation-free CuAAC bioconjugation - M. Hatit, A. Watson et al.

December 23, 2022 12:00 - 17 minutes - 16.4 MB

The Cu-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is a cornerstone method for the ligation of biomolecules. However, undesired Cu-mediated oxidation and Cu- contamination in bioconjugates limits biomedical utility. Here, we report a generic CuAAC flow platform for the rapid, robust, and broad-spectrum formation of discrete triazole bio-conjugates. This process leverages an engineering problem to chemical advantage: solvent-mediated Cu pipe erosion generates ppm levels of Cu in sit...

PubReading [248] - Third Generation Sequencing of Epigenetic DNA - B. Searle, M. Müller, T. Carell and A. Kellett

December 22, 2022 12:00 - 58 minutes - 53.8 MB

The discovery of epigenetic bases has revolutionised the understanding of disease and development. Among the most studied epigenetic marks are cytosines covalently modified at the 5 position. In order to gain insight into their biological significance, the ability to determine their spatiotemporal distribution within the genome is essential. Techniques for sequencing on ‘Next Generation’ platforms often involve harsh chemical treatments leading to sample degradation. Third generation sequenc...

PubReading [247] - The frequency of Ras mutations in cancer - I. Prior, F. Hood and J. Hartley

December 21, 2022 13:00 - 29 minutes - 41.2 MB

Ras is frequently mutated in cancer; however, there is a lack of consensus in the literature regarding the cancer mutation frequency of Ras, with quoted values varying from 10–30%. This variability is at least in part due to the selective aggregation of data from different databases and the dominant influence of particular cancer types and particular Ras isoforms within these datasets. In order to provide a more definitive figure for Ras mutation frequency in cancer, we cross-referenced the ...

PubReading [246] - Mechanistic insights into mRNA 3'-end processing - A. Kumar, M. Jinek et al.

December 20, 2022 13:00 - 28 minutes - 39.3 MB

The polyadenosine (poly(A)) tail found on the 3'-end of almost all eukaryotic mRNAs is important for mRNA stability and regulation of translation. mRNA 3'-end processing occurs co-transcriptionally and involves more than 20 proteins to specifically recognize the polyadenylation site, cleave the pre-mRNA, add a poly(A) tail, and trigger transcription termination. The polyadenylation site (PAS) defines the end of the 30-untranslated region (3'-UTR) and, therefore, selection of the cleavage sit...

PubReading [245] - The biospheric emergency calls for scientists to change tactics - F. Racimo, J. Halder et al.

December 19, 2022 12:00 - 38 minutes - 53.3 MB

Our current economic and political structures have an increasingly devastating impact on the Earth’s climate and ecosystems: we are facing a biospheric emergency, with catastrophic consequences for both humans and the natural world on which we depend. Life scientists – including biologists, medical scientists, psychologists and public health experts – have had a crucial role in documenting the impacts of this emergency, but they have failed to drive governments to take action in order to pre...