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 [145] - CAR T cell therapy and the tumor microenvironment: Current challenges and opportunities - L. Fonkoua, S. Kenderian et al
June 14, 2022 20:00 - 41 minutes - 75.5 MBChimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable outcomes in individuals with hematological malignancies, but its success has been hindered by barriers intrinsic to the tumor microenvironment (TME), particularly for solid tumors, where it has yet to make its mark. In this article, we provide an updated review and future perspectives on features of the TME that represent barriers to CART cell therapy efficacy, including competition for metabolic fuels, physical barri...
PubReading [144] - What machine learning can do for developmental biology - P. Villoutreix
June 13, 2022 20:00 - 33 minutes - 62 MBDevelopmental biology has grown into a data intensive science with the development of high-throughput imaging and multi-omics approaches. Machine learning is a versatile set of techniques that can help make sense of these large datasets with minimal human intervention, through tasks such as image segmentation, super- resolution microscopy and cell clustering. In this Spotlight, I introduce the key concepts, advantages and limitations of machine learning, and discuss how these methods are bei...
PubReading [143] - Homology directed correction, a new pathway model for point mutation repair catalyzed by CRISPR‐Cas - B. Sansbury, E. Kmiec et al
June 10, 2022 20:00 - 27 minutes - 51.1 MBGene correction is often referred to as the gold standard for precise gene editing and while CRISPR‐ Cas systems continue to expand the toolbox for clinically relevant genetic repair, mechanistic hurdles still hinder widespread implementation. One of the most prominent challenges to precise CRISPR‐ directed point mutation repair centers on the prevalence of on‐site mutagenesis, wherein insertions and deletions appear at the targeted site following correction. Here, we introduce a pathway mod...
PubReading [142] - Artificial nucleic acid backbones and their applications in therapeutics, synthetic biology and biotechnology - S. Epple, A. El-Sagheer and T. Brown
June 09, 2022 20:00 - 13 minutes - 24 MBThe modification of DNA or RNA backbones is an emerging technology for therapeutic oligonucleotides, synthetic biology and biotechnology. Despite a plethora of reported arti- ficial backbones, their vast potential is not fully utilised. Limited synthetic accessibility remains a major bottleneck for the wider application of backbone-modified oligonucleo- tides. Thus, a variety of readily accessible artificial backbones and robust methods for their introduction into oligonucleotides are urgent...
PubReading [141] - Single-molecule fluorescence detection of a tricyclic nucleoside analogue - G. Samaan, B. Purse et al
June 08, 2022 20:00 - 21 minutes - 40.1 MBFluorescent nucleobase surrogates capable of Watson–Crick hydrogen bonding are essential probes of nucleic acid structure and dynamics, but their limited brightness and short absorption and emission wavelengths have rendered them unsuitable for single-molecule detection. Aiming to improve on these properties, we designed a new tricyclic pyrimidine nucleoside analogue with a push–pull conjugated system and synthesized it in seven sequential steps. The resulting C-linked 8-(diethylamino)benzo[...
PubReading [140] - Peptide Nucleic Acid-Based Biosensors for Cancer Diagnosis - R. D’Agata, M. Giuffrida and G. Spoto
June 07, 2022 20:00 - 40 minutes - 74.9 MBThe monitoring of DNA and RNA biomarkers freely circulating in the blood constitutes the basis of innovative cancer detection methods based on liquid biopsy. Such methods are expected to provide new opportunities for a better understanding of cancer disease at the molecular level, thus contributing to improved patient outcomes. Advanced biosensors can advance possibilities for cancer-related nucleic acid biomarkers detection. In this context, peptide nucleic acids (PNAs) play an important ro...
PubReading [139] - Harnessing DNA as a Designable Scaffold for Asymmetric Catalysis: Recent Advances and Future Perspectives - JJ. Yum, H. Sugiyama and S. Park
June 06, 2022 20:00 - 56 minutes - 103 MBSince the first report of DNAzyme by in vitro selection in 1994, catalytic DNA has investigated extensively, and their application has expanded continually in virtue of rapid advances in molecular biology and biotechnology. Nowadays, DNA is in the second prime time by way of DNA-based hybrid catalysts and DNA metalloenzymes in which helical chirality of DNA serves to asymmetric catalysis. DNA-based hybrid catalysts are attractive system to respond the demand of the times to pursuit green and...
PubReading [138] - Improving CRISPR–Cas specificity with chemical modifications in single-guide RNAs - D. Ryan, D. Dellinger et al
June 03, 2022 20:00 - 34 minutes - 63.5 MBCRISPR systems have emerged as transformative tools for altering genomes in living cells with un- precedented ease, inspiring keen interest in increasing their specificity for perfectly matched targets. We have developed a novel approach for improving specificity by incorporating chemical modifications in guide RNAs (gRNAs) at specific sites in their DNA recognition sequence (‘guide sequence’) and systematically evaluating their on-target and off-target activities in biochemical DNA cleavage...
PubReading [137] - Double-headed nucleic acids condense the molecular information of DNA to half the number of nucleotides -K. Beck, P. Nielsen et al
June 02, 2022 20:00 - 19 minutes - 35.5 MBNucleotide monomers that hold two nucleobases each, i.e. double- headed nucleotides, have been shown to form two sets of functional Watson–Crick base pairs when incorporated into dsDNA, and they hereby behave as dinucleotides. To form the basis for fully modified double-headed nucleic acids (DhNA), we have prepared three new DhNA monomers and can now demonstrate that the molecular information of 10 Watson–Crick base pairs can be condensed to highly stable 5-mer DhNA duplexes. DOI: 10.1039/d...
PubReading [136] - A prebiotically plausible scenario of an RNA–peptide world - F. Müller, C. Chan, T. Carell
June 01, 2022 20:00 - 24 minutes - 45.3 MBThe RNA world concept1 is one of the most fundamental pillars of the origin of life theory. It predicts that life evolved from increasingly complex self-replicating RNA molecules. The question of how this RNA world then advanced to the next stage, in which proteins became the catalysts of life and RNA reduced its function predominantly to information storage, is one of the most mysterious chicken-and-egg conundrums in evolution. Here we show that non-canonical RNA bases, which are found toda...
PubReading [135] - Structural basis for broad anti-phage immunity by DISARM - J. Bravo, D. Taylor et al
May 31, 2022 20:00 - 42 minutes - 78.4 MBIn the evolutionary arms race against phage, bacteria have assembled a diverse arsenal of antiviral immune strategies. While the recently discovered DISARM (Defense Island System Associated with Restriction-Modification) systems can provide protection against a wide range of phage, the molecular mechanisms that underpin broad antiviral targeting but avoiding autoimmunity remain enigmatic. Here, we report cryo-EM structures of the core DISARM complex, DrmAB, both alone and in complex with an ...
PubReading [134] - Tethering Carbohydrates to the Vinyliminium Ligand of Antiproliferative Organometallic Diiron Complexes - S. Schoch, M. Dalla Pozza, G. Gasser, F. Marchetti et al
May 30, 2022 20:00 - 32 minutes - 58.8 MBFour propargyl O-glycosides derivatized with mannose, glucose, and fructose moieties were synthesized and then incorporated within a diiron structure as part of a vinyliminium ligand. Hence, six glycoconjugated diiron complexes, [2−5]CF3SO3 (see Scheme 1) and the nonglycosylated analogues [6a−b]CF3SO3, were obtained in high yields and unambiguously characterized by elemental analysis, mass spectrometry, and IR and multinuclear NMR spectroscopies. All compounds exhibited a significant stabili...
PubReading [133] - Life in the light: nucleic acid photoproperties as a legacy of chemical evolution - A. Beckstead, B. Kohler
May 26, 2022 20:00 - 53 minutes - 98.8 MBPhotophysical investigations of the canonical nucleobases that make up DNA and RNA during the past 15 years have revealed that excited states formed by the absorption of UV radiation decay with subpicosecond lifetimes (i.e., o1012 s). Ultrashort lifetimes are a general property of absorbing sunscreen molecules, suggesting that the nucleobases are molecular survivors of a harsh UV environment. Encoding the genome using photostable building blocks is an elegant solution to the threat of photo...
PubReading [132] - Unnatural bases for recognition of noncoding nucleic acid interfaces - S. Miao, D. Bong et al
May 25, 2022 20:00 - 59 minutes - 109 MBThe notion of using synthetic heterocycles instead of the native bases to interface with DNA and RNA has been explored for nearly 60 years. Unnatural bases compatible with the DNA/RNA coding interface have the potential to expand the genetic code and co-opt the machinery of biology to access new macromolecular function; accordingly, this body of research is core to synthetic biology. While much of the literature on artificial bases focuses on code expansion, there is a significant and grow- ...
PubReading [131] - Microneedling for Hair Loss - A. Gupta, M. Bamimore et al.
May 24, 2022 20:00 - 27 minutes - 51.2 MBThere are limited studies that investigate microneedling as a monotherapy for hair loss since majority of the trials combine it with other therapies such as topical minoxidil or platelet-rich plasma. While preliminary results look promising, further investigation of microneedling as a monotherapy in larger, randomized controlled trials will help determine its safety and efficacy, and place in treating Androgenic Alopecia. - DOI: 10.1111/jocd.14525 - 2021
PubReading [130] - Computational analysis of next generation sequencing data and its applications in clinical oncology - R. Wadapurkar and Renu Vyas
May 23, 2022 20:00 - 47 minutes - 86.1 MBNext generation sequencing (NGS) has made great strides in sequencing technology as it enables sequencing of genes in a high throughput manner with low cost. Various NGS platforms such as Illumina, Roche, ABI/SOLiD are used for wet-lab analysis of NGS data and computational tools such as BWA, Bowtie, Galaxy, SanGeniX are used for dry-lab analysis of NGS data. One of the important aspects of NGS data is its usage in early disease diagnosis especially in cancer which was earlier not possible w...
PubReading [129] - Beginner’s guide to mass spectrometry–based proteomics - A. Sinha and M. Mann
May 20, 2022 20:00 - 23 minutes - 43.4 MBMass spectrometry (MS)-based proteomics is the most comprehensive approach for the quantitative profiling of proteins, their interactions and modifications. It is a challenging topic as a firm grasp requires expertise in biochemistry for sample preparation, analytical chemistry for instrumentation and computational biology for data analysis. In this short guide, we highlight the various components of a mass spectrometer, the sample preparation process for conversion of proteins into peptides...
PubReading [128] - Best practices for variant calling in clinical sequencing - D. Koboldt
May 19, 2022 20:00 - 42 minutes - 77.1 MBNext-generation sequencing technologies have enabled a dramatic expansion of clinical genetic testing both for inherited conditions and diseases such as cancer. Accurate variant calling in NGS data is a critical step upon which virtually all downstream analysis and interpretation processes rely. Just as NGS technologies have evolved considerably over the past 10 years, so too have the software tools and approaches for detecting sequence variants in clinical samples. In this review, I discuss...
PubReading [127] - Insufficient Evidence for ‘‘Autism-Specific’’ Genes - S. Myers, D. Ledbetter
May 18, 2022 20:00 - 42 minutes - 77.3 MBDespite evidence that deleterious variants in the same genes are implicated across multiple neurodevelopmental and neuropsychiatric disorders, there has been considerable interest in identifying genes that, when mutated, confer risk that is largely specific for autism spectrum disorder (ASD). Here, we review the findings and limitations of recent efforts to identify relatively ‘‘autism-specific’’ genes, efforts which focus on rare variants of large effect size that are thought to account for...
PubReading [126] - Split light up aptamers as a probing tool for nucleic acids - Y. Gerasimovaa, D Nedorezovab and D. Kolpashchikov
May 17, 2022 20:00 - 27 minutes - 50 MBAptamers that bind non-fluorescent dyes and increase their fluorescence can be converted to fluorescent sensors. Here, we discuss and provide guidance for the design of split (binary) light up aptameric sensors (SLAS) for nucleic acid analysis. SLAS consist of two RNA or DNA strands and a fluorogenic organic dye added as a buffer component. The two strands hybridize to the analyzed DNA or RNA sequence and form a dye-binding pocket, followed by dye binding, and increase in its fluorescence. S...
PubReading [125] - How cryo-electron microscopy and X-ray crystallography complement each other - H. Wang, and J. Wang
May 16, 2022 20:00 - 30 minutes - 56.5 MBWith the ability to resolve structures of macromolecules at atomic resolution, X-ray crystallography has been the most powerful tool in modern structural biology. At the same time, recent technical improvements have triggered a resolution revolution in the single-particle cryo-EM method. While the two methods are different in many respects, from sample preparation to structure determination, they both have the power to solve macromolecular structures at atomic resolution. It is important to ...
PubReading [124] - A biomedical open knowledge network harnesses the power of AI to understand deep human biology - S. Baranzini, S. Huang et al
May 13, 2022 20:00 - 28 minutes - 52.3 MBKnowledge representation and reasoning (KR&R) has been successfully imple- mented in many fields to enable computers to solve complex problems with AI methods. However, its application to biomedicine has been lagging in part due to the daunting complexity of molecular and cellular pathways that govern human physiology and pathology. In this article, we describe concrete uses of Scalable PrecisiOn Medicine Knowledge Engine (SPOKE), an open knowledge network that connects curated information f...
PubReading [123] - Next-Generation Sequencing Technologies - R. McCombie, J. McPherson, and E. Mardis
May 12, 2022 20:00 - 39 minutes - 71.6 MBAlthough DNA and RNA sequencing has a history spanning five decades, large-scale massively parallel sequencing, or next-generation sequencing (NGS), has only been commercially available for about 10 years. Nonetheless, the meteoric increase in sequencing throughput with NGS has dramatically changed our understanding of our genome and our- selves. Sequencing the first human genome as a haploid reference took nearly 10 years but now a full diploid human genome sequence can be accomplished in j...
PubReading [122] - Systematic benchmarking of tools for CpG methylation detection from nanopore sequencing - Z. Yuen, E. Eyras et al
May 11, 2022 20:00 - 36 minutes - 67.2 MBDNA methylation plays a fundamental role in the control of gene expression and genome integrity. Although there are multiple tools that enable its detection from Nanopore sequencing, their accuracy remains largely unknown. Here, we present a systematic benchmarking of tools for the detection of CpG methylation from Nanopore sequencing using individual reads, control mixtures of methylated and unmethylated reads, and bisulfite sequencing. We found that tools have a tradeoff between false posi...
PubReading [121] - Cone-shaped HIV-1 capsids are transported through intact nuclear pores - V. Zila, M. Beck et al
May 10, 2022 20:00 - 48 minutes - 89.6 MBHuman immunodeficiency virus (HIV-1) remains a major health threat. Viral capsid uncoating and nuclear import of the viral genome are critical for productive infection. The size of the HIV-1 capsid is generally believed to exceed the diameter of the nuclear pore complex (NPC), indicating that capsid uncoating has to occur prior to nuclear import. Here, we combined correlative light and electron microscopy with subtomogram averaging to capture the structural status of reverse transcription-co...
PubReading [120] - Modern epigenetics methods in biological research - Yuanyuan Li
May 09, 2022 20:00 - 59 minutes - 108 MBThe definition of epigenetics refers that molecular modifications on DNA that can regulate gene activity are independent of DNA sequence and mitotically stable. Notably, epigenetics studies have grown exponentially in the past few years. Recent progresses that lead to exciting discoveries and groundbreaking nature of this area demand thorough methodologies and advanced technologies to move epigenetics to the forefront of molecular biology. The most recognized epigenetic regulations are DNA m...
PubReading [119] - CAR T‐cell therapy: Full speed ahead - D. Sermer and R. Brentjens
May 06, 2022 20:00 - 27 minutes - 50.3 MBChimeric antigen receptor (CAR) T‐cell therapy has dramatically shifted the landscape of treatment for lymphoid malignancies, especially diffuse large B‐cell lymphoma (DLBCL) and acute lymphoblastic leukemia (ALL). However, there continue to be significant limitations of this therapy, such as incomplete or nonsustained responses and severe toxicities in a subset of patients. Furthermore, expanding the role of CAR T‐cell therapy to new disease types is an important next step. In this review, ...
PubReading [118] - Robust transcriptome-wide discovery of RNA-binding protein binding sites with enhanced CLIP (eCLIP) - E. Van Nostrand, G. Yeo et al
May 05, 2022 20:00 - 37 minutes - 68.4 MBAs RNA-binding proteins (RBPs) play essential roles in cellular physiology by interacting with target RNA molecules, binding site identification by UV crosslinking and immunoprecipitation (CLIP) of ribonucleoprotein complexes is critical to understanding RBP function. However, current CLIP protocols are technically demanding and yield low-complexity libraries with high experimental failure rates. We have developed an enhanced CLIP (eCLIP) protocol that decreases requisite amplification by ∼1...
PubReading [117] - Real-time Voltammetric Anion Sensing Under Flow - S. Patrick, J. Davis
May 04, 2022 20:00 - 24 minutes - 45.5 MBThe development of real-life applicable ion sensors, in particular those capable of repeat use and long-term monitoring, remains a formidable challenge. Herein, we demonstrate, in a proof-of-concept, the real-time voltammet- ric sensing of anions under continuous flow in a 3D-printed microfluidic system. Electro-active anion receptive halogen bonding (XB) and hydrogen bonding (HB) ferrocene-isophtha- lamide-(iodo)triazole films were employed as exemplary sensory interfaces. Upon exposure to ...
PubReading [116] - Improved protein structure prediction using potentials from deep learning - A. Senior, D. Hassabis et al.
May 03, 2022 20:00 - 21 minutes - 39.9 MBProtein structure prediction can be used to determine the three-dimensional shape of a protein from its amino acid sequence1. This problem is of fundamental importance as the structure of a protein largely determines its function2; however, protein structures can be difficult to determine experimentally. Considerable progress has recently been made by leveraging genetic information. It is possible to infer which amino acid residues are in contact by analysing covariation in homologous sequen...
PubReading [115] - The Current Revolution in Cryo-EM - E. Egelman
May 02, 2022 20:00 - 23 minutes - 42.1 MBStructural biology is the study of the molecular architecture of proteins and nucleic acids, which are the basis for all life forms. Knowledge of these structures alone is not enough to understand their functions, but it has become clear that a detailed mechanistic picture of function is not possible without structural information. Studying structure can reveal how molecules have evolved, and this type of insight would otherwise be lost by looking at only the molecule’s sequence. - .doi.org/...
PubReading [114] - Oncogene-induced DNA damage: cyclic AMP steps into the ring - J. Fagin and J. Petrini
April 29, 2022 20:00 - 15 minutes - 28.3 MBGrowth hormone–secreting (GH-secreting) pituitary tumors are driven by oncogenes that induce cAMP signaling. In this issue of the JCI, Ben-Shlomo et al. performed a whole-exome study of pituitary adenomas. GH-secreting tumors had a high frequency of whole chromosome or chromosome arm copy number alterations and were associated with an increase in the tumor protein p53 and the cyclin-dependent kinase inhibitor p21WAF1/CIP1, which are findings consistent with induction of a response to DNA dam...
PubReading [113] - Highly accurate protein structure prediction with AlphaFold - J. Jumper, P. Kohli, D. Hassabis et al
April 28, 2022 20:00 - 31 minutes - 58.3 MBProteins are essential to life, and understanding their structure can facilitate a mechanistic understanding of their function. Through an enormous experimental effort, the structures of around 100,000 unique proteins have been determined5, but this represents a small fraction of the billions of known protein sequences. Structural coverage is bottlenecked by the months to years of painstaking effort required to determine a single protein structure. Accurate computational approaches are neede...
PubReading [112] - Automated Tools to Advance High-Resolution Imaging in Liquid - G. Jonaid, D. Kelly
April 27, 2022 20:00 - 35 minutes - 64.9 MBLiquid-electron microscopy (EM), the room-temperature correlate to cryo-EM, is a rapidly growing field providing high-resolution insights of macromolecules in solution. Here, we describe how liquid-EM experiments can incorporate automated tools to propel the field to new heights. We demonstrate fresh workflows for specimen preparation, data collection, and computing processes to assess biological structures in liquid. Adeno-associated virus (AAV) and the SARS-CoV-2 nucleocapsid (N) were used...
PubReading [111] - Chemical reprogramming of human somatic cells to pluripotent stem cells - J. Guang, H. Dang et al
April 26, 2022 20:00 - 34 minutes - 62.8 MBCellular reprogramming can manipulate the identity of cells to generate the desired cell types1–3. The use of cell intrinsic components, including oocyte cytoplasm and transcription factors, can enforce somatic cell reprogramming to pluripotent stem cells4–7. By contrast, chemical stimulation by exposure to small molecules offers an alternative approach that can manipulate cell fate in a simple and highly controllable manner8–10. However, human somatic cells are refractory to chemical stimul...
PubReading [110] - Hallmarks of Cancer: New Dimensions - Douglas Hanahan
April 25, 2022 20:00 - 1 hour - 156 MBThe hallmarks of cancer conceptualization is a heuristic tool for distilling the vast complexity of cancer phenotypes and genotypes into a provisional set of underlying principles. As knowledge of cancer mechanisms has progressed, other facets of the disease have emerged as potential refinements. Herein, the prospect is raised that phenotypic plasticity and disrupted differentiation is a discrete hallmark capability, and that nonmutational epigenetic reprogram- ming and polymorphic microbiom...
PubReading [109] - Novel therapeutic targets for cancer metastasis - K. Stoletov, P. Beatty and J. Lewis
April 22, 2022 20:00 - 59 minutes - 109 MBThe development of metastatic disease is a complex interplay of genetic and epigenetic factors from the host and cancer cells acting in a patient-specific manner. Inhibiting key driver traits of metastasis should yield survival benefit at any stage of the disease, and we look forward to the next generation of personalized medicines for cancer therapy that target cancer cell motility for increased therapeutic efficacy. - doi.org/10.1080/14737140.2020.1718496 - 2020
PubReading [108] - Untapped Neuroimaging Tools for Neuro-Oncology: Connectomics and Spatial Transcriptomics - J. Germann, A. Boutet et al
April 21, 2022 20:00 - 25 minutes - 46.3 MBBrain imaging, specifically magnetic resonance imaging (MRI), plays a key role in the clinical and research aspects of neuro-oncology. Novel neuroimaging techniques enable the transformation of a brain MRI into a so-called average brain. This allows projects using already acquired brain MRIs to perform group analyses and draw conclusions. Once the data are in this average brain, several types of analyses can be performed. For example, determining the most vulnerable locations for certain tum...
PubReading [107] - Genome editing for Duchenne muscular dystrophy: a glimpse of the future? - C. Kupatt, M. Walter et al
April 20, 2022 20:00 - 34 minutes - 63.5 MBMutations in Dystrophin, one of the largest proteins in the mammalian body, are causative for a severe form of muscle disease, Duchenne Muscular Dystrophy (DMD), affecting not only skeletal muscle, but also the heart. In particular, exons 45–52 constitute a hotspot for DMD mutations. A variety of molecular therapies have been developed, comprising vectors encoding micro-and minidystrophins as well as utrophin, a protein with partially overlapping functions. With the advent of the CRISPR-Cas9...
PubReading [106] - The Ultimate (Mis)match: When DNA Meets RNA - B. Palancade and R. Rothstein
April 19, 2022 20:00 - 1 hour - 113 MBRNA-containing structures, including ribonucleotide insertions, DNA:RNA hybrids and R-loops, have recently emerged as critical players in the maintenance of genome integrity. Strikingly, different enzymatic activities classically involved in genome maintenance contribute to their generation, their processing into genotoxic or repair intermediates, or their removal. Here we review how this substrate promiscuity can account for the detrimental and beneficial impacts of RNA insertions during ge...
PubReading [104] - Structural principles of CRISPR-Cas enzymes used in nucleic acid detection - A. Dasa, H. Li et al
April 15, 2022 20:00 - 29 minutes - 53.3 MBClustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-based technology has revolutionized the field of biomedicine with broad applications in genome editing, therapeutics and diagnostics. While a majority of applications involve the RNA-guided site-specific DNA or RNA cleavage by CRISPR enzymes, recent successes in nucleic acid detection rely on their collateral and non-specific cleavage activated by viral DNA or RNA. Ranging in enzyme composition, the mechanism for distinguishin...
PubReading [103] - IceBreaker: Software for high-resolution single-particle cryo-EM with non-uniform ice - M. Olek, P. Zhang et al
April 14, 2022 20:00 - 33 minutes - 62 MBDespite the abundance of available software tools, optimal particle selection is still a vital issue in single-particle cryoelectron microscopy (cryo-EM). Regardless of the method used, most pickers struggle when ice thickness varies on a micrograph. IceBreaker allows users to estimate the relative ice gradient and flatten it by equalizing the local contrast. It allows the differentiation of particles from the background and improves overall particle picking performance. Furthermore, we intr...
PubReading [102] - Brain charts for the human lifespan - R. Bethlehem, J. Seidlitz, A. Alexander-Bloch et al
April 13, 2022 20:00 - 33 minutes - 61.4 MBOver the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data (http://www.brainchart.io/). With the...
PubReading [101] - Glycemic control in the critically ill: Less is more - G. Alhatemi, B. Seyoum et al
April 12, 2022 20:00 - 34 minutes - 64.1 MBHyperglycemia is associated with poor clinical outcomes in critically ill patients. Initial clinical trials of intensive insulin therapy targeting blood glucose levels of 80 to 110 mg/dL showed improved outcomes, but subsequent trials found no benefits and even increased harm with this approach. Emerging literature has evaluated other glycemic indices including time-in-target blood glucose range, glycemic variability, and stress hyperglycemia ratio. These indices, while well described in obs...
PubReading [100] - The complete sequence of a human genome - S. Nurk, S. Koren, A. Rhie, A. Phillips et al
April 11, 2022 20:00 - 49 minutes - 90.1 MBSince its initial release in 2000, the human reference genome has covered only the euchromatic fraction of the genome, leaving important heterochromatic regions unfinished. Addressing the remaining 8% of the genome, the Telomere-to-Telomere (T2T) Consortium presents a complete 3.055 billion–base pair sequence of a human genome, T2T-CHM13, that includes gapless assemblies for all chromosomes except Y, corrects errors in the prior references, and introduces nearly 200 million base pairs of seq...
PubReading [99] - MicroED: conception, practice and future opportunities - M. Clabbers, A. Shiriaevaa and T. Gonen
April 03, 2022 20:00 - 43 minutes - 80.2 MBThis article documents a keynote seminar presented at the IUCr Congress in Prague, 2021. The cryo-EM method microcrystal electron diffraction is described and put in the context of macromolecular electron crystallography from its origins in 2D crystals of membrane proteins to today’s application to 3D crystals a millionth the size of that needed for X-ray crystallography. Milestones in method development and applications are described with an outlook to the future. - doi.org/10.1107/S2052252...
PubReading [89] - Immunotherapy and prevention of pancreatic cancer - A. Morrison, K. Byrne and R. Vonderheide
April 01, 2022 20:00 - 42 minutes - 78.7 MBPancreatic cancer is the third leading cause of cancer mortality in the United States, recently surpassing breast cancer. A key component of pancreatic cancer’s lethality is its acquired immune privilege, which is driven by an immunosuppressive microenvironment, poor T-cell infiltration, and a low mutational burden. Although immunotherapies such as checkpoint blockade or engineered T cells have yet to demonstrate efficacy, a growing body of evidence suggests that orthogonal combinations of t...
PubReading [97] - Ultra-High Dose Rate (FLASH) Radiotherapy: Silver Bullet or Fool’s Gold? - J. Wilson, K. Petersson et al.
March 31, 2022 20:00 - 1 hour - 113 MBRadiotherapy is a cornerstone of both curative and palliative cancer care. However, radiotherapy is severely limited by radiation-induced toxicities. If these toxicities could be reduced, a greater dose of radiation could be given therefore facilitating a better tumor response. Initial pre-clinical studies have shown that irradiation at dose rates far exceeding those currently used in clinical contexts reduce radiation-induced toxicities whilst maintaining an equivalent tumor response. This ...
PubReading [96] - Highly accurate protein structure prediction for the human proteome - K. Tunyasuvunakool, D. Hassabis et al.
March 30, 2022 20:00 - 30 minutes - 55.9 MBProtein structures can provide invaluable information, both for reasoning about biological processes and for enabling interventions such as structure-based drug development or targeted mutagenesis. After decades of effort, 17% of the total residues in human protein sequences are covered by an experimentally determined structure1. Here we markedly expand the structural coverage of the proteome by applying the state-of-the-art machine learning method, AlphaFold2, at a scale that covers almost ...
PubReading [95] - A safe lithium mimetic for bipolar disorder - N. Singh, G. Churchill et al.
March 29, 2022 20:00 - 23 minutes - 42.3 MBLithium is the most effective mood stabilizer for the treatment of bipolar disorder, but it is toxic at only twice the therapeutic dosage and has many undesirable side effects. It is likely that a small molecule could be found with lithium-like efficacy but without toxicity through target-based drug discovery; however, therapeutic target of lithium remains equivocal. Inositol monophosphatase is a possible target but no bioavailable inhibitors exist. Here we report that the antioxidant ebsele...