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https://www.readbyqxmd.com/read/29781240/predominant-nonproductive-substrate-binding-by-fungal-cellobiohydrolase-i-and-implications-for-activity-improvement
#1
Mikhail L Rabinovich, Maria S Melnik, Mikhail L Herner, Yakov V Voznyi, Lilia G Vasilchenko
Enzymatic conversion of the most abundant renewable source of organic compounds, cellulose to fermentable sugars is attractive for production of green fuels and chemicals. The major component of industrial enzyme systems, cellobiohydrolase I from Hypocrea jecorina (Trichoderma reesei) (HjCel7A) processively splits disaccharide units from the reducing ends of tightly packed cellulose chains. HjCel7A consists of a catalytic domain (CD) and a carbohydrate-binding module (CBM) separated by a linker peptide. A tunnel-shaped substrate-binding site in the CD includes 9 subsites for β-D-glucose units, 7 of which (-7 to -1) precede the catalytic center...
May 21, 2018: Biotechnology Journal
https://www.readbyqxmd.com/read/29773329/mutation-screening-of-the-tia1-gene-in-chinese-patients-with-amyotrophic-lateral-sclerosis-frontotemporal-dementia
#2
XiaoJing Gu, YongPing Chen, QianQian Wei, Bei Cao, RuWei Ou, XiaoQin Yuan, YanBin Hou, LingYu Zhang, Hui Liu, XuePing Chen, Hui-Fang Shang
Mutations in the low-complexity domain (LCD) of T-cell intracellular antigen-1 (TIA1) have been reported to be associated with amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) in the Caucasian population. In the present study, we aimed to screen mutations in the LCD (exon 11-13) of TIA1 and determine the mutation frequency in Chinese ALS/FTD patients. A total of 740 ALS patients, including 721 sporadic ALS (sALS), 19 familial ALS, 24 FTD patients, and 501 healthy controls, were directly sequenced...
April 24, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29771110/low-fouling-protein-detection-in-complex-biological-media-supported-by-a-designed-multifunctional-peptide
#3
Nianzu Liu, Ni Hui, Jason J Davis, Xiliang Luo
The construction of sensitive and selective biosensors capable of detecting specific targets in complex biological samples remains a challenge highly relevant to a range of sensor/diagnostic applications. Herein, we have utilized a multifunctional peptide to present an interface that supports the very specific recruitment of targets from serum. The novel peptide sequence designed contains an anchoring domain (CPPPP-), an antifouling domain (-NQNQNQNQDHWRGWVA) and a human immunoglobulin G (IgG) recognition domain (-HWRGWVA), and the whole peptide was designed to be antifouling...
May 17, 2018: ACS Sensors
https://www.readbyqxmd.com/read/29768021/diminished-heart-rate-complexity-in-adolescent-girls-a-sign-of-vulnerability-to-anxiety-disorders
#4
Aina Fiol-Veny, Alejandro De la Torre-Luque, Maria Balle, Xavier Bornas
BACKGROUND AND OBJECTIVES: Diminished heart rate variability has been found to be associated with high anxiety symptomatology. Since adolescence is the period of onset for many anxiety disorders, this study aimed to determine sex- and anxiety-related differences in heart rate variability and complexity in adolescents. METHODS: We created four groups according to sex and anxiety symptomatology: high-anxiety girls (n = 24) and boys (n = 25), and low-anxiety girls (n = 22) and boys (n = 24) and recorded their cardiac function while they performed regular school activities...
May 15, 2018: Anxiety, Stress, and Coping
https://www.readbyqxmd.com/read/29767241/transcriptome-sequencing-analysis-reveals-the-effect-of-combinative-treatment-with-low%C3%A2-intensity-pulsed-ultrasound-and-magnesium-ions-on-hfob1-19-human-osteoblast-cells
#5
Haiyue Zu, Xueting Yi, Dewei Zhao
Biodegradable magnesium (Mg) materials are considered ideal as osteosynthesis implants. However, clinical application has proven complex. This is primarily associated with the issue of reducing the extent of implant degradation to a range acceptable for the human body, while simultaneously enhancing osteogenesis or osteoinduction. In the present study, a combination of Mg ions and low‑intensity pulsed ultrasound (LIPUS) treatment was applied in hFOB 1.19 human osteoblast cells as a potential strategy to resolve this issue...
May 11, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29766737/identification-of-small-molecule-egfr-allosteric-inhibitors-by-high-throughput-docking
#6
Fabiana Caporuscio, Annachiara Tinivella, Valentina Restelli, Marta S Semrau, Luca Pinzi, Paola Storici, Massimo Broggini, Giulio Rastelli
AIM: The EGFR inhibitors represent the first-line treatment of non-small-cell lung cancer. However, the emergence of resistance urgently requires the development of new inhibitors targeting drug-resistant mutants. METHODOLOGY: A recently released structure of an EGFR kinase domain in complex with an allosteric inhibitor and a mutant protein model derived from it were used to set up a low-cost high-throughput docking protocol for the fast identification of EGFR allosteric inhibitors...
May 16, 2018: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29756604/alkaloids-nitric-oxide-and-nitrite-reductases-evolutionary-coupling-as-key-regulators-of-cellular-bioenergetics-with-special-relevance-to-the-human-microbiome
#7
George B Stefano, Richard M Kream
Typical alkaloids expressed by prokaryotic and eukaryotic cells are small heterocyclic compounds containing weakly basic nitrogen groups that are critically important for mediating essential biological activities. The prototype opiate alkaloid morphine represents a low molecular mass heterocyclic compound that has been evolutionarily fashioned from a relatively restricted role as a secreted antimicrobial phytoalexin into a broad spectrum regulatory molecule. As an essential corollary, positive evolutionary pressure has driven the development of a cognate 6-transmembrane helical (TMH) domain μ3 opiate receptor that is exclusively responsive to morphine and related opiate alkaloids...
May 14, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29755654/mycn-acts-as-a-direct-co-regulator-of-p53-in-mycn-amplified-neuroblastoma
#8
Saurabh Agarwal, Giorgio Milazzo, Kimal Rajapakshe, Ronald Bernardi, Zaowen Chen, Eveline Barberi, Jan Koster, Giovanni Perini, Cristian Coarfa, Jason M Shohet
The MYC oncogenes and p53 have opposing yet interrelated roles in normal development and tumorigenesis. How MYCN expression alters the biology and clinical responsiveness of pediatric neuroblastoma remains poorly defined. Neuroblastoma is p53 wild type at diagnosis and repression of p53 signaling is required for tumorigenesis. Here, we tested the hypothesis that MYCN amplification alters p53 transcriptional activity in neuroblastoma. Interestingly, we found that MYCN directly binds to the tetrameric form of p53 at its C-terminal domain, and this interaction is independent of MYCN/MAX heterodimer formation...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29755516/synaptic-paths-to-neurodegeneration-the-emerging-role-of-tdp-43-and-fus-in-synaptic-functions
#9
REVIEW
Shuo-Chien Ling
TAR DNA-binding protein-43 KDa (TDP-43) and fused in sarcoma (FUS) as the defining pathological hallmarks for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), coupled with ALS-FTD-causing mutations in both genes, indicate that their dysfunctions damage the motor system and cognition. On the molecular level, TDP-43 and FUS participate in the biogenesis and metabolism of coding and noncoding RNAs as well as in the transport and translation of mRNAs as part of cytoplasmic mRNA-ribonucleoprotein (mRNP) granules...
2018: Neural Plasticity
https://www.readbyqxmd.com/read/29751623/a-bds-interference-suppression-technique-based-on-linear-phase-adaptive-iir-notch-filters
#10
Hongbo Zhao, Yinan Hu, Hua Sun, Wenquan Feng
The continuous wave interferences (CWIs) and the narrow-band interferences (NBIs) have significantly impacted the acquisition, tracking and positioning accuracy of Beidou Navigation Satellite System (BDS) receivers. As an interference suppression technology with a simple structure and low hardware cost, the adaptive infinite-duration impulse response (IIR) notch filter has been widely employed in the receivers to mitigate the CWIs and the NBIs. However, the nonlinear phase characteristics introduced by the IIR notch filters into the navigation receivers, may cause the distortion of navigation signals...
May 11, 2018: Sensors
https://www.readbyqxmd.com/read/29741930/highly-sensitive-index-of-cardiac-autonomic-control-based-on-time-varying-respiration-derived-from-ecg
#11
Pierre Gilfriche, Laurent M Arsac, Yannick Daviaux, Jaime Diaz-Pineda, Brice Miard, Olivier Morellec, Jean-Marc André
Frequency-domain indices of Heart Rate Variability (HRV) have been used as a marker of sympathovagal balance. However, they have been shown to be degraded by inter-individual or task-dependent variability, and especially breathing frequency. The study introduces a new method for analyzing respiratory (vagally) mediated Heart Rate Variability, to better assess subtle variations in sympathovagal balance, using ECG information. We evaluated the sensitivity of our new method comparatively to classic HRV analyses with cognitive workload...
May 9, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29740297/a-multitude-of-neural-representations-behind-multisensory-social-norm-processing
#12
Felipe Pegado, Michelle H A Hendriks, Steffie Amelynck, Nicky Daniels, Jessica Bulthé, Haemy Lee Masson, Bart Boets, Hans Op de Beeck
Humans show a unique capacity to process complex information from multiple sources. Social perception in natural environment provides a good example of such capacity as it typically requires the integration of information from different sensory systems, and also from different levels of sensory processing. Here, instead of studying one isolate system and level of representation, we focused upon a neuroimaging paradigm which allows to capture multiple brain representations simultaneously, i.e., low and high-level processing in two different sensory systems, as well as abstract cognitive processing of congruency...
2018: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/29739825/safety-ii-behavior-in-a-pediatric-intensive-care-unit
#13
Jenna Merandi, Kathryn Vannatta, J Terrance Davis, Richard E McClead, Richard Brilli, Thomas Bartman
: media-1vid110.1542/5763093009001PEDS-VA_2018-0018 Video Abstract BACKGROUND AND OBJECTIVE: Safety I error elimination concepts are focused on retrospectively investigating what went wrong and redesigning system processes and individual behaviors to prevent similar future occurrences. The Safety II approach recognizes complex systems and unpredictable circumstances, mandating flexibility and resilience within systems and among individuals to avoid errors. We hypothesized that in our high-complexity and high-risk PICU, Safety II concepts contribute to its remarkably low adverse drug event rate...
May 8, 2018: Pediatrics
https://www.readbyqxmd.com/read/29737567/impact-of-a-non-synonymous-q281r-polymorphism-on-structure-of-human-lipoprotein-associated-phospholipase-a-2-lp-pla-2
#14
Arun B Gurung, Atanu Bhattacharjee
Non-synonymous single nucleotide polymorphisms (nsSNPs) are genetic variations at single base resulting in an amino acid change which have been associated with various complex human diseases. The human Lipoprotein-associated phospholipase A2 (Lp-PLA2 ) gene harbours a rare Q281R polymorphism which was previously reported to cause loss of enzymatic function. Lp-PLA2 is an important enzyme which catalyzes the hydrolysis of polar phospholipids releasing pro-atherogenic and pro-inflammatory mediators involved in the pathogenesis of atherosclerosis...
May 8, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29725819/senataxin-mutations-elicit-motor-neuron-degeneration-phenotypes-and-yield-tdp-43-mislocalization-in-als4-mice-and-human-patients
#15
Craig L Bennett, Somasish G Dastidar, Shuo-Chien Ling, Bilal Malik, Travis Ashe, Mandheer Wadhwa, Derek B Miller, Changwoo Lee, Matthew B Mitchell, Michael A van Es, Christopher Grunseich, Yingzhang Chen, Bryce L Sopher, Linda Greensmith, Don W Cleveland, Albert R La Spada
Amyotrophic lateral sclerosis type 4 (ALS4) is a rare, early-onset, autosomal dominant form of ALS, characterized by slow disease progression and sparing of respiratory musculature. Dominant, gain-of-function mutations in the senataxin gene (SETX) cause ALS4, but the mechanistic basis for motor neuron toxicity is unknown. SETX is a RNA-binding protein with a highly conserved helicase domain, but does not possess a low-complexity domain, making it unique among ALS-linked disease proteins. We derived ALS4 mouse models by expressing two different senataxin gene mutations (R2136H and L389S) via transgenesis and knock-in gene targeting...
May 3, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29725305/development-of-a-high-throughput-flow-cytometry-assay-to-monitor-defective-trafficking-and-rescue-of-long-qt2-mutant-herg-channels
#16
Scott A Kanner, Ananya Jain, Henry M Colecraft
Long QT Syndrome (LQTS) is an acquired or inherited disorder characterized by prolonged QT interval, exertion-triggered arrhythmias, and sudden cardiac death. One of the most prevalent hereditary LQTS subtypes, LQT2, results from loss-of-function mutations in the hERG channel, which conducts I Kr , the rapid component of the delayed rectifier K+ current, critical for cardiac repolarization. The majority of LQT2 mutations result in Class 2 deficits characterized by impaired maturation and trafficking of hERG channels...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29723523/the-physiological-and-pathological-biophysics-of-phase-separation-and-gelation-of-rna-binding-proteins-in-amyotrophic-lateral-sclerosis-and-fronto-temporal-lobar-degeneration
#17
Peter St George-Hyslop, Julie Qiaojin Lin, Akinori Miyashita, Emma C Phillips, Seema Qamar, Suzanne J Randle, GuoZhen Wang
Many RNA binding proteins, including FUS, contain moderately repetitive, low complexity, intrinsically disordered domains. These sequence motifs have recently been found to underpin reversible liquid: liquid phase separation and gelation of these proteins, permitting them to reversibly transition from a monodispersed state to liquid droplet- or hydrogel-like states. This function allows the proteins to serve as scaffolds for the formation of reversible membraneless intracellular organelles such as nucleoli, stress granules and neuronal transport granules...
April 30, 2018: Brain Research
https://www.readbyqxmd.com/read/29718136/molecular-insights-to-withaferin-a-induced-senescence-bioinformatics-and-experimental-evidence-to-the-role-of-nf-kappa-b-and-carf
#18
Priyanshu Bhargava, Vidhi Malik, Ye Liu, Jihoon Ryu, Sunil C Kaul, Durai Sundar, Renu Wadhwa
Withaferin-A (Wi-A) has been shown to possess anticancer activity. Molecular mechanism(s) of its action have not been fully resolved. We recruited low dose of Wi-A that caused slow growth arrest in cancer cells, and was relatively safe for normal cells. Consistently, we detected nuclear translocation of NFκB and activation of p38MAPK selectively in cancer cells. Bioinformatics analyses revealed that Wi-A did not disrupt IKK/IKKβ-Nemo complex that regulates NFκB activity. However, it caused moderate change in the conformation of IKKβ-Nemo interacting domain...
April 28, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29717015/regulation-of-flagellum-biosynthesis-in-response-to-cell-envelope-stress-in-salmonella-enterica-serovar-typhimurium
#19
Imke Spöring, Sebastian Felgner, Matthias Preuße, Denitsa Eckweiler, Manfred Rohde, Susanne Häussler, Siegfried Weiss, Marc Erhardt
Flagellum-driven motility of Salmonella enterica serovar Typhimurium facilitates host colonization. However, the large extracellular flagellum is also a prime target for the immune system. As consequence, expression of flagella is bistable within a population of Salmonella , resulting in flagellated and nonflagellated subpopulations. This allows the bacteria to maximize fitness in hostile environments. The degenerate EAL domain protein RflP (formerly YdiV) is responsible for the bistable expression of flagella by directing the flagellar master regulatory complex FlhD4 C2 with respect to proteolytic degradation...
May 1, 2018: MBio
https://www.readbyqxmd.com/read/29714690/multivalency-regulates-activity-in-an-intrinsically-disordered-transcription-factor
#20
Sarah A Clark, Janette B Myers, Ashleigh King, Radovan Fiala, Jiri Novacek, F Grant Pearce, Jörg Heierhorst, Steve L Reichow, Elisar J Barbar
The transcription factor ASCIZ (ATMIN, ZNF822) has an unusually high number of recognition motifs for the product of its main target gene, the hub protein LC8 (DYNLL1). Using a combination of biophysical methods, structural analysis by NMR and electron microscopy, and cellular transcription assays, we developed a model that proposes a concerted role of intrinsic disorder and multiple LC8 binding events in regulating LC8 transcription. We demonstrate that the long intrinsically disordered C-terminal domain of ASCIZ binds LC8 to form a dynamic ensemble of complexes with a gradient of transcriptional activity that is inversely proportional to LC8 occupancy...
May 1, 2018: ELife
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