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https://www.readbyqxmd.com/read/28431230/structural-basis-for-guide-rna-processing-and-seed-dependent-dna-targeting-by-crispr-cas12a
#1
Daan C Swarts, John van der Oost, Martin Jinek
The CRISPR-associated protein Cas12a (Cpf1), which has been repurposed for genome editing, possesses two distinct nuclease activities: endoribonuclease activity for processing its own guide RNAs and RNA-guided DNase activity for target DNA cleavage. To elucidate the molecular basis of both activities, we determined crystal structures of Francisella novicida Cas12a bound to guide RNA and in complex with an R-loop formed by a non-cleavable guide RNA precursor and a full-length target DNA. Corroborated by biochemical experiments, these structures reveal the mechanisms of guide RNA processing and pre-ordering of the seed sequence in the guide RNA that primes Cas12a for target DNA binding...
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28429714/pif1-family-dna-helicases-suppress-r-loop-mediated-genome-instability-at-trna-genes
#2
Phong Lan Thao Tran, Thomas J Pohl, Chi-Fu Chen, Angela Chan, Sebastian Pott, Virginia A Zakian
Saccharomyces cerevisiae encodes two Pif1 family DNA helicases, Pif1 and Rrm3. Rrm3 promotes DNA replication past stable protein complexes at tRNA genes (tDNAs). We identify a new role for the Pif1 helicase: promotion of replication and suppression of DNA damage at tDNAs. Pif1 binds multiple tDNAs, and this binding is higher in rrm3Δ cells. Accumulation of replication intermediates and DNA damage at tDNAs is higher in pif1Δ rrm3Δ than in rrm3Δ cells. DNA damage at tDNAs in the absence of these helicases is suppressed by destabilizing R-loops while Pif1 and Rrm3 binding to tDNAs is increased upon R-loop stabilization...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28429172/a-new-species-of-haematoloechus-looss-1899-digenea-plagiorchioidea-haematoloechidae-a-parasite-of-rana-psilonota-webb-and-r-zweifeli-hillis-frost-webb-anura-ranidae-in-mexico
#3
Virginia León-Règagnon, Ángeles R Romero-Mayén
During an inventory of the helminths of amphibians in Mexico, specimens of an undescribed species of Haematoloechus Looss, 1899 (Digenea: Haematoloechidae) were collected from the lungs of frogs of the "tarahumarae" group in western México. Haematoloechus longicollum n. sp. differs from other known species of Haematoloechus by the combination of the following characters: body elongate and slender in the preovarian region and broad and blunt in the postovarian region, ovary separated from the ventral sucker more than twice the ovary length, oral sucker to pharynx length ratio 1:0...
April 20, 2017: Systematic Parasitology
https://www.readbyqxmd.com/read/28427352/point-of-sampling-detection-of-zika-virus-within-a-multiplexed-kit-capable-of-detecting-dengue-and-chikungunya
#4
Ozlem Yaren, Barry W Alto, Priyanka V Gangodkar, Shatakshi R Ranade, Kunal N Patil, Kevin M Bradley, Zunyi Yang, Nikhil Phadke, Steven A Benner
BACKGROUND: Zika, dengue, and chikungunya are three mosquito-borne viruses having overlapping transmission vectors. They cause diseases having similar symptoms in human patients, but requiring different immediate management steps. Therefore, rapid (< one hour) discrimination of these three viruses in patient samples and trapped mosquitoes is needed. The need for speed precludes any assay that requires complex up-front sample preparation, such as extraction of nucleic acids from the sample...
April 20, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28426557/loop-ileostomy-vs-total-colectomy-as-surgical-treatment-for-clostridium-difficile-associated-disease-an-eastern-association-for-the-surgery-of-trauma-multicenter-trial
#5
Paula Ferrada, Rachael Callcut, Martin D Zielinski, Brandon Bruns, Daniel Dante Yeh, Tanya L Zakrison, Jonathan P Meizoso, Babak Sarani, Richard D Catalano, Peter Kim, Valerie Plant, Amelia Pasley, Linda A Dultz, Asad J Choudhry, Elliott R Haut
OBJECTIVES: The mortality of patients with Clostridum Dificile Associated Disease (CDAD) requiring surgery continues to be very high. Loop ileostomy (LI) was introduced as an alternative procedure to total colectomy (TC) for CDAD by a single center study. To date, no reproducible results have been published. The objective of this study is to compare these two procedures in a multicentric approach to help the surgeon decide what procedure is best suited for the patient in need. METHODS: This was a retrospective multicenter study conducted under the sponsorship of the Eastern Association for the Surgery of Trauma (EAST)...
April 20, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28425683/preservation-of-duodenal-passage-as-a-determinant-of-short-and-long-term-quality-of-life-in-gastric-cancer-patients-after-total-gastrectomy
#6
Tomasz Olesiński, Marek Szpakowski, Piotr Saramak, Andrzej Rutkowski, Krzysztof Jeziorski
BACKGROUND: The aim of this prospective study was to compare subjective and objective quality of life (QoL) of gastric cancer patients after total gastrectomy with and without preservation of the duodenal passage during short- and long-term follow-up. METHODS: The study included 68 patients, among them 37 (54%) persons subjected to total gastrectomy with Roux-Y reconstruction (R-Y group) and 31 (46%) individuals in whom gastrectomy was followed by formation of Henley-Longmire loop (H-L group)...
April 19, 2017: Minerva Chirurgica
https://www.readbyqxmd.com/read/28425625/a-missense-mutation-in-damage-specific-dna-binding-protein-2-is-a-genetic-risk-factor-for-limbal-squamous-cell-carcinoma-in-horses
#7
Rebecca R Bellone, Jiayin Liu, Jessica L Petersen, Maura Mack, Moriel Singer-Berk, Cord Drögemüller, Julia Malvick, Barbara Wallner, Gottfried Brem, M Cecilia Penedo, Mary Lassaline
Squamous cell carcinoma (SCC) is the most common cancer of the equine eye, frequently originating at the limbus, with the potential to invade the cornea, cause visual impairment, and result in loss of the eye. Several breeds of horses have a high occurrence of limbal SCC implicating a genetic basis for limbal SCC predisposition. Pedigree analysis in the Haflinger breed supports a simple recessive mode of inheritance and a genome wide association study (N=23) identified a 1.5 Mb locus on ECA12 significantly associated with limbal SCC (Pcorrected = 0...
April 20, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28424523/cohesin-is-positioned-in-mammalian-genomes-by-transcription-ctcf-and-wapl
#8
Georg A Busslinger, Roman R Stocsits, Petra van der Lelij, Elin Axelsson, Antonio Tedeschi, Niels Galjart, Jan-Michael Peters
Mammalian genomes are spatially organized by CCCTC-binding factor (CTCF) and cohesin into chromatin loops and topologically associated domains, which have important roles in gene regulation and recombination. By binding to specific sequences, CTCF defines contact points for cohesin-mediated long-range chromosomal cis-interactions. Cohesin is also present at these sites, but has been proposed to be loaded onto DNA elsewhere and to extrude chromatin loops until it encounters CTCF bound to DNA. How cohesin is recruited to CTCF sites, according to this or other models, is unknown...
April 19, 2017: Nature
https://www.readbyqxmd.com/read/28420362/clinical-hemispheric-and-autonomic-changes-associated-with-use-of-closed-loop-allostatic-neurotechnology-by-a-case-series-of-individuals-with-self-reported-symptoms-of-post-traumatic-stress
#9
Charles H Tegeler, Jared F Cook, Catherine L Tegeler, Joshua R Hirsch, Hossam A Shaltout, Sean L Simpson, Brian C Fidali, Lee Gerdes, Sung W Lee
BACKGROUND: The objective of this pilot study was to explore the use of a closed-loop, allostatic, acoustic stimulation neurotechnology for individuals with self-reported symptoms of post-traumatic stress, as a potential means to impact symptomatology, temporal lobe high frequency asymmetry, heart rate variability (HRV), and baroreflex sensitivity (BRS). METHODS: From a cohort of individuals participating in a naturalistic study to evaluate use of allostatic neurotechnology for diverse clinical conditions, a subset was identified who reported high scores on the Posttraumatic Stress Disorder Checklist (PCL)...
April 19, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/28418376/a-circrna-from-sepallata3-regulates-splicing-of-its-cognate-mrna-through-r-loop-formation
#10
Vanessa M Conn, Véronique Hugouvieux, Aditya Nayak, Stephanie A Conos, Giovanna Capovilla, Gökhan Cildir, Agnès Jourdain, Vinay Tergaonkar, Markus Schmid, Chloe Zubieta, Simon J Conn
Circular RNAs (circRNAs) are a diverse and abundant class of hyper-stable, non-canonical RNAs that arise through a form of alternative splicing (AS) called back-splicing. These single-stranded, covalently-closed circRNA molecules have been identified in all eukaryotic kingdoms of life(1), yet their functions have remained elusive. Here, we report that circRNAs can be used as bona fide biomarkers of functional, exon-skipped AS variants in Arabidopsis, including in the homeotic MADS-box transcription factor family...
April 18, 2017: Nature Plants
https://www.readbyqxmd.com/read/28412545/dna-topoisomerase-1-prevents-r-loop-accumulation-to-modulate-auxin-regulated-root-development-in-rice
#11
Sarfraz Shafiq, Chunli Chen, Jing Yang, Lingling Cheng, Fei Ma, Emilie Widemann, Qianwen Sun
R-loop structures (RNA:DNA hybrids) have important functions in many biological processes, including transcriptional regulation and genome instability among diverse organisms. DNA Topoisomerase 1 (TOP1), an essential manipulator of DNA topology during RNA transcription and DNA replication processes, can prevent R-loop accumulation by removing the positive and negative DNA supercoiling that is made by RNA polymerases during transcription. TOP1 is required for plant development, but little is known about its function in preventing co-transcriptional R-loops in different plant biological processes...
April 12, 2017: Molecular Plant
https://www.readbyqxmd.com/read/28409399/pro-apoptotic-signaling-induced-by-retinoic-acid-and-dsrna-is-under-the-control-of-interferon-regulatory-factor-3-in-breast-cancer-cells
#12
Ana R Bernardo, José M Cosgaya, Ana Aranda, Ana M Jiménez-Lara
Breast cancer is one of the most lethal malignancies for women. Retinoic acid (RA) and double-stranded RNA (dsRNA) are considered signaling molecules with potential anticancer activity. RA, co-administered with the dsRNA mimic polyinosinic-polycytidylic acid (poly(I:C)), synergizes to induce a TRAIL (Tumor-Necrosis-Factor Related Apoptosis-Inducing Ligand)- dependent apoptotic program in breast cancer cells. Here, we report that RA/poly(I:C) co-treatment, synergically, induce the activation of Interferon Regulatory Factor-3 (IRF3) in breast cancer cells...
April 13, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28408437/the-myc-mrna-3-utr-couples-rna-polymerase-ii-function-to-glutamine-and-ribonucleotide-levels
#13
Francesca R Dejure, Nadine Royla, Steffi Herold, Jacqueline Kalb, Susanne Walz, Carsten P Ade, Guido Mastrobuoni, Jens T Vanselow, Andreas Schlosser, Elmar Wolf, Stefan Kempa, Martin Eilers
Deregulated expression of MYC enhances glutamine utilization and renders cell survival dependent on glutamine, inducing "glutamine addiction". Surprisingly, colon cancer cells that express high levels of MYC due to WNT pathway mutations are not glutamine-addicted but undergo a reversible cell cycle arrest upon glutamine deprivation. We show here that glutamine deprivation suppresses translation of endogenous MYC via the 3'-UTR of the MYC mRNA, enabling escape from apoptosis. This regulation is mediated by glutamine-dependent changes in adenosine-nucleotide levels...
April 13, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28408397/the-il-31-il-31-receptor-axis-general-features-and-role-in-tumor-microenvironment
#14
REVIEW
Elisa Ferretti, Anna Corcione, Vito Pistoia
IL-31 is a recently identified cytokine with a well-defined role in the pathogenesis of pruritus. IL-31, whose production is induced by IL-4 and IL-33, binds a heterodimeric receptor (R) composed of the exclusive IL-31RA chain and the shared oncostatin M R. Signaling through the IL-31R involves the MAPK, PI3K/AKT and Jak/STAT pathways. Different variants and isoforms of IL-31RA with different signaling activities have been identified. IL-31 is produced predominantly by circulating Th2 lymphocytes and skin-homing CLA(+)CD45RO(+) T cells...
April 13, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28408237/habituation-and-adaptation-to-odors-in-humans
#15
REVIEW
R Pellegrino, C Sinding, R A de Wijk, T Hummel
Habituation, or decreased behavioral response, to odors is created by repeated exposure and several detailed characteristics, whereas adaptation relates to the neural processes that constitute this decrease in a behavioral response. As with all senses, the olfactory system continually encounters an enormous variety of odorants which is why mechanisms must exist to segment them and respond to changes. Although most olfactory habitation studies have focused on animal models, this non-systematic review provides an overview of olfactory habituation and adaptation in humans, and techniques that have been used to measure them...
April 10, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28406751/repetitive-dna-loci-and-their-modulation-by-the-non-canonical-nucleic-acid-structures-r-loops-and-g-quadruplexes
#16
Amanda C Hall, Lauren A Ostrowski, Violena Pietrobon, Karim Mekhail
Cells have evolved intricate mechanisms to maintain genome stability despite allowing mutational changes to drive evolutionary adaptation. Repetitive DNA sequences, which represent the bulk of most genomes, are a major threat to genome stability often driving chromosome rearrangements and disease. The major source of repetitive DNA sequences and thus the most vulnerable constituents of the genome are the rDNA (rDNA) repeats, telomeres, and transposable elements. Maintaining the stability of these loci is critical to overall cellular fitness and lifespan...
March 4, 2017: Nucleus
https://www.readbyqxmd.com/read/28405673/gly74ser-mutation-in-protein-c-causes-thrombosis-due-to-a-defect-in-protein-s-dependent-anticoagulant-function
#17
Changming Chen, Likui Yang, Bruno O Villoutreix, Xuefeng Wang, Qiulan Ding, Alireza R Rezaie
Protein C is a vitamin K-dependent serine protease zymogen in plasma which upon activation by thrombin in complex with thrombomodulin (TM) down-regulates the clotting cascade by a feedback loop inhibition mechanism. Activated protein C (APC) exerts its anticoagulant function through protein S-dependent degradation of factors Va and VIIIa. We recently identified a venous thrombosis patient whose plasma level of protein C antigen is normal, but its anticoagulant activity is only 34 % of the normal level. Genetic analysis revealed that the proband and her younger brother carry a novel heterozygous mutation c...
April 13, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28402681/characterization-of-oligonucleotide-aptamers-targeting-the-5-utr-from-dengue-virus
#18
Elismar Jn Cnossen, Amanda G Silva, Karina Marangoni, Rívia Ar Arruda, Evellyn G Souza, Fabiana Aa Santos, Patrícia T Fujimura, Jonny Yokosawa, Luiz R Goulart, Adriana F Neves
AIM: The dengue virus is responsible for a high worldwide incidence of infections, aggravated by late diagnosis, and often confused with other tropical diseases. Results/methodology: Oligonucleotide aptamers binding to the 5'-UTR from dengue virus selected after eight rounds by systematic evolution of ligands by exponential enrichment technology were analyzed by dot-blot assay and in silico prediction of secondary structures, demonstrating the presence of stem-loops that may have the potential for interaction with the viral genome, which can lead to loss of their original conformation...
April 12, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28402411/impact-of-acute-hypertension-transients-on-diastolic-function-in-patients-with-heart-failure-with-preserved-ejection-fraction
#19
Candelas Pérez Del Villar, Konstantinos Savvatis, Begoña López, Mario Kasner, Pablo Martinez-Legazpi, Raquel Yotti, Arantxa González, Javier Díez, Francisco Fernández-Avilés, Carsten Tschöpe, Javier Bermejo
Aim: To address the mechanisms responsible for the increase in LV filling pressures induced by acute hypertension transients in patients with heart failure with preserved ejection fraction (HFpEF). Methods and results: Multiple-beat pressure-volume loops were recorded during inferior vena cava occlusion in 39 HFpEF patients and 20 controls during handgrip and atrial pacing. We measured the contribution of relaxation, elastic recoil, and stiffness to instantaneous diastolic pressure using a novel processing method...
April 11, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28400788/the-lin28-let-7-pathway-in-cancer
#20
REVIEW
Julien Balzeau, Miriam R Menezes, Siyu Cao, John P Hagan
Among all tumor suppressor microRNAs, reduced let-7 expression occurs most frequently in cancer and typically correlates with poor prognosis. Activation of either LIN28A or LIN28B, two highly related RNA binding proteins (RBPs) and proto-oncogenes, is responsible for the global post-transcriptional downregulation of the let-7 microRNA family observed in many cancers. Specifically, LIN28A binds the terminal loop of precursor let-7 and recruits the Terminal Uridylyl Transferase (TUTase) ZCCHC11 that polyuridylates pre-let-7, thereby blocking microRNA biogenesis and tumor suppressor function...
2017: Frontiers in Genetics
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