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https://www.readbyqxmd.com/read/29161709/impact-of-local-and-systemic-factors-on-kidney-dysfunction-in-bardet-biedl-syndrome
#1
Miriam Zacchia, Giovanna Capolongo, Francesco Trepiccione, Vincent Marion
Bardet Biedl syndrome (BBS) is a rare inherited syndromic condition characterized by renal and extra-renal disorders. Renal defect, at either structural or functional level, is one of the cardinal clinical features, and is a major cause of morbidity. However, the pathogenic mechanism underlying its dysfunction remains largely unknown, and to date only symptomatic treatment with no specific therapy is available for these patients. Elucidating aberrant cellular and/or systemic processes that impact kidney function is therefore a prerequisite to develop targeted innovative therapeutic strategies for the BBS patients...
November 21, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29161362/the-hierarchical-organization-of-the-default-dorsal-attention-and-salience-networks-in-adolescents-and-young-adults
#2
Yuan Zhou, Karl J Friston, Peter Zeidman, Jie Chen, Shu Li, Adeel Razi
An important characteristic of spontaneous brain activity is the anticorrelation between the core default network (cDN) and the dorsal attention network (DAN) and the salience network (SN). This anticorrelation may constitute a key aspect of functional anatomy and is implicated in several brain disorders. We used dynamic causal modeling to assess the hypothesis that a causal hierarchy underlies this anticorrelation structure, using resting-state fMRI of healthy adolescent and young adults (N = 404). Our analysis revealed an asymmetric effective connectivity, such that the regions in the SN and DAN exerted an inhibitory influence on the cDN regions; whereas the cDN exerted an excitatory influence on the SN and DAN regions...
November 17, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29157493/atomic-resolution-conformational-dynamics-of-intrinsically-disordered-proteins-from-nmr-spin-relaxation
#3
REVIEW
Nicola Salvi, Anton Abyzov, Martin Blackledge
Nuclear magnetic resonance (NMR) spectroscopy is one of the most powerful experimental approaches for investigating the conformational behaviour of intrinsically disordered proteins (IDPs). IDPs represent a significant fraction of all proteomes, and, despite their importance for understanding fundamental biological processes, the molecular basis of their activity still remains largely unknown. The functional mechanisms exploited by IDPs in their interactions with other biomolecules are defined by their intrinsic dynamic modes and associated timescales, justifying the considerable interest over recent years in the development of technologies adapted to measure and describe this behaviour...
November 2017: Progress in Nuclear Magnetic Resonance Spectroscopy
https://www.readbyqxmd.com/read/29156593/site-directed-mutagenesis-of-the-fibronectin-domains-in-insulin-receptor-related-receptor
#4
Igor E Deyev, Natalia A Chachina, Egor S Zhevlenev, Alexander G Petrenko
The orphan insulin receptor-related receptor (IRR), in contrast to its close homologs, the insulin receptor (IR) and insulin-like growth factor receptor (IGF-IR) can be activated by mildly alkaline extracellular medium. We have previously demonstrated that IRR activation is defined by its extracellular region, involves multiple domains, and shows positive cooperativity with two synergistic sites. By the analyses of point mutants and chimeras of IRR with IR in, we now address the role of the fibronectin type III (FnIII) repeats in the IRR pH-sensing...
November 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29155043/stk33-is-required-for-spermatid-differentiation-and-male-fertility-in-mice
#5
Leila R Martins, Raffaela K Bung, Stefan Koch, Karsten Richter, Laura Schwarzmüller, Dorothee Terhardt, Bahtiyar Kurtulmus, Christof Niehrs, Arefeh Rouhi, Ingrid Lohmann, Gislene Pereira, Stefan Fröhling, Hanno Glimm, Claudia Scholl
Spermiogenesis is the final phase during sperm cell development in which round spermatids undergo dramatic morphological changes to generate spermatozoa. Here we report that the serine/threonine kinase Stk33 is essential for the differentiation of round spermatids into functional sperm cells and male fertility. Constitutive Stk33 deletion in mice results in severely malformed and immotile spermatozoa that are particularly characterized by disordered structural tail elements. Stk33 expression first appears in primary spermatocytes, and targeted deletion of Stk33 in these cells recapitulates the defects observed in constitutive knockout mice, confirming a germ cell-intrinsic function...
November 16, 2017: Developmental Biology
https://www.readbyqxmd.com/read/29154992/structural-and-biophysical-characterization-of-rv3716c-a-hypothetical-protein-from-mycobacterium-tuberculosis
#6
A Gopalan, G Deka, M Prabhavathi, H S Savithri, M R N Murthy, A Raja
Latent tuberculosis (TB) is the main hurdle in reaching the goal of "Stop TB 2050". Tuberculin skin and Interferon-gamma release assay tests used currently for the diagnosis of TB infection cannot distinguish between active disease and latent tuberculosis infection (LTBI) and hence new and sensitive protein markers need to be identified for the diagnosis. A protein Rv3716c from Mycobacterium tuberculosis (MtbRv3716c) has been identified as a potential surrogate marker for the diagnosis of LTBI. Here, we present characterization of MtbRv3716c (∼13 kDa) using both biophysical and X-Ray crystallographic methods...
November 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29152585/total-lipopolysaccharide-from-the-human-gut-microbiome-silences-toll-like-receptor-signaling
#7
Eva d'Hennezel, Sahar Abubucker, Leon O Murphy, Thomas W Cullen
Cohabitation of microbial communities with the host enables the formation of a symbiotic relationship that maintains homeostasis in the gut and beyond. One prevailing model suggests that this relationship relies on the capacity of host cells and tissues to remain tolerant to the strong immune stimulation generated by the microbiota such as the activation of Toll-like receptor 4 (TLR4) pathways by lipopolysaccharide (LPS). Indeed, gut microbial LPS is thought to be one of the most potent activators of innate immune signaling and an important mediator of the microbiome's influence on host physiology...
November 2017: MSystems
https://www.readbyqxmd.com/read/29151218/structures-of-dynamic-protein-complexes-hybrid-techniques-to-study-map-kinase-complexes-and-the-escrt-system
#8
Wolfgang Peti, Rebecca Page, Evzen Boura, Bartosz Różycki
The integration of complementary molecular methods (including X-ray crystallography, NMR spectroscopy, small angle X-ray/neutron scattering, and computational techniques) is frequently required to obtain a comprehensive understanding of dynamic macromolecular complexes. In particular, these techniques are critical for studying intrinsically disordered protein regions (IDRs) or intrinsically disordered proteins (IDPs) that are part of large protein:protein complexes. Here, we explain how to prepare IDP samples suitable for study using NMR spectroscopy, and describe a novel SAXS modeling method (ensemble refinement of SAXS; EROS) that integrates the results from complementary methods, including crystal structures and NMR chemical shift perturbations, among others, to accurately model SAXS data and describe ensemble structures of dynamic macromolecular complexes...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29150311/functional-connectivity-of-the-vigilant-attention-network-in-children-and-adolescents-with-attention-deficit-hyperactivity-disorder
#9
Florian D Zepf, Sarah Bubenzer-Busch, Kevin C Runions, Pradeep Rao, Janice W Y Wong, Simone Mahfouda, Hugo A E Morandini, Richard M Stewart, Julia K Moore, Caroline S Biskup, Simon B Eickhoff, Gereon R Fink, Robert Langner
The ability to maintain attention to simple tasks (i.e., vigilant attention, VA) is often impaired in attention-deficit/hyperactivity disorder (ADHD), but the underlying pathophysiological mechanisms at the brain network level are not clear yet. We therefore investigated ADHD-related differences in resting-state functional connectivity within a meta-analytically defined brain network of 14 distinct regions subserving VA (comprising 91 connections in total), as well as the association of connectivity with markers of behavioural dysfunction in 17 children (age range: 9-14 years) with a diagnosis of ADHD and 21 age-matched neurotypical controls...
November 14, 2017: Brain and Cognition
https://www.readbyqxmd.com/read/29149602/specification-of-physiologic-and-disease-states-by-distinct-proteins-and-protein-conformations
#10
REVIEW
Daniel F Jarosz, Vikram Khurana
Protein conformational states-from intrinsically disordered ensembles to amyloids that underlie the self-templating, infectious properties of prion-like proteins-have attracted much attention. Here, we highlight the diversity, including differences in biophysical properties, that drive distinct biological functions and pathologies among self-templating proteins. Advances in chemical genomics, gene editing, and model systems now permit deconstruction of the complex interplay between these protein states and the host factors that react to them...
November 16, 2017: Cell
https://www.readbyqxmd.com/read/29145487/defining-external-factors-that-determine-neuronal-survival-apoptosis-and-necrosis-during-excitotoxic-injury-using-a-high-content-screening-imaging-platform
#11
Ujval Anilkumar, Petronela Weisova, Jasmin Schmid, Tytus Bernas, Heinrich J Huber, Heiko Düssmann, Niamh M C Connolly, Jochen H M Prehn
Cell death induced by excessive glutamate receptor overactivation, excitotoxicity, has been implicated in several acute and chronic neurological disorders. While numerous studies have demonstrated the contribution of biochemically and genetically activated cell death pathways in excitotoxic injury, the factors mediating passive, excitotoxic necrosis are less thoroughly investigated. To address this question, we developed a high content screening (HCS) based assay to collect high volumes of quantitative cellular imaging data and elucidated the effects of intrinsic and external factors on excitotoxic necrosis and apoptosis...
2017: PloS One
https://www.readbyqxmd.com/read/29141966/nutritional-factors-affecting-adult-neurogenesis-and-cognitive-function
#12
REVIEW
Shibu M Poulose, Marshall G Miller, Tammy Scott, Barbara Shukitt-Hale
Adult neurogenesis, a complex process by which stem cells in the hippocampal brain region differentiate and proliferate into new neurons and other resident brain cells, is known to be affected by many intrinsic and extrinsic factors, including diet. Neurogenesis plays a critical role in neural plasticity, brain homeostasis, and maintenance in the central nervous system and is a crucial factor in preserving the cognitive function and repair of damaged brain cells affected by aging and brain disorders. Intrinsic factors such as aging, neuroinflammation, oxidative stress, and brain injury, as well as lifestyle factors such as high-fat and high-sugar diets and alcohol and opioid addiction, negatively affect adult neurogenesis...
November 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/29141068/new-insight-into-the-pathophysiology-of-hair-loss-trigger-a-paradigm-shift-in-the-treatment-approach
#13
Neil S Sadick, Valerie D Callender, Leon H Kircik, Sophia Kogan
<p>Hair loss affects millions of men and women of all ages and ethnicities, impacting appearance, social interactions, and psycho-emotional well-being. Although a number of options are available, they are limited, carry a potential risk of side effects, and none have proven to be comprehensive for treatment of hair loss. Across the spectrum of hair loss disorders, there has long been a segmentation into distinct mechanisms, driving the main trend in current therapeutics to focus on targeting single molecules or pathways...
November 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/29141024/quantifying-indices-of-short-and-long-range-white-matter-connectivity-at-each-cortical-vertex
#14
Maria Carmela Padula, Marie Schaer, Elisa Scariati, A Kadir Mutlu, Daniela Zöller, Maude Schneider, Stephan Eliez
Several neurodevelopmental diseases are characterized by impairments in cortical morphology along with altered white matter connectivity. However, the relationship between these two measures is not yet clear. In this study, we propose a novel methodology to compute and display metrics of white matter connectivity at each cortical point. After co-registering the extremities of the tractography streamlines with the cortical surface, we computed two measures of connectivity at each cortical vertex: the mean tracts' length, and the proportion of short- and long-range connections...
2017: PloS One
https://www.readbyqxmd.com/read/29140585/timap-the-versatile-protein-phosphatase-1-regulator-in-endothelial-cells
#15
REVIEW
Anita Boratkó, Csilla Csortos
Transforming growth factor (TGF)-β inhibited membrane associated protein, TIMAP, is the member of the myosin phosphatase targeting protein (MYPT) family of protein phosphatase 1 (PP1) regulatory subunits. The N-terminal part of TIMAP has a typical MYPT family structure with a sequence element called MyPhone (myosin phosphatase N-terminal element), a putative bipartite nuclear localization signal, a PP1 catalytic subunit binding motif, and five ankyrin repeats. The C-terminal half of TIMAP is intrinsically disordered, but ends with a functional CAAX box for lipid modification which allows localization of TIMAP at the plasma membrane...
November 15, 2017: IUBMB Life
https://www.readbyqxmd.com/read/29140480/the-intrinsically-disordered-n-terminal-arm-of-the-brome-mosaic-virus-coat-protein-specifically-recognizes-the-rna-motif-that-directs-the-initiation-of-viral-rna-replication
#16
Alexander Jacobs, Haley Hoover, Edward Smith, David E Clemmer, Chul-Hyun Kim, C Cheng Kao
In the brome mosaic virus (BMV) virion, the coat protein (CP) selectively contacts the RNA motifs that regulate translation and RNA replication (Hoover et al., 2016. J. Virol. 90, 7748). We hypothesize that the unstructured N-terminal arm (NTA) of the BMV CP can specifically recognize RNA motifs. Using ion mobility spectrometry-mass spectrometry, we demonstrate that peptides containing the NTA of the CP were found to preferentially bind to an RNA hairpin motif that directs the initiation of BMV RNA synthesis...
November 11, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29138501/targeting-sxip-eb1-interaction-an-integrated-approach-to-the-discovery-of-small-molecule-modulators-of-dynamic-binding-sites
#17
T B Almeida, A J Carnell, I L Barsukov, N G Berry
End binding protein 1 (EB1) is a key element in the complex network of protein-protein interactions at microtubule (MT) growing ends, which has a fundamental role in MT polymerisation. EB1 is an important protein target as it is involved in regulating MT dynamic behaviour, and has been associated with several disease states, such as cancer and neuronal diseases. Diverse EB1 binding partners are recognised through a conserved four amino acid motif, (serine-X-isoleucine-proline) which exists within an intrinsically disordered region...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138428/structural-disorder-and-induced-folding-within-two-cereal-aba-stress-and-ripening-asr-proteins
#18
Karama Hamdi, Edoardo Salladini, Darragh P O'Brien, Sébastien Brier, Alexandre Chenal, Ines Yacoubi, Sonia Longhi
Abscisic acid (ABA), stress and ripening (ASR) proteins are plant-specific proteins involved in plant response to multiple abiotic stresses. We previously isolated the ASR genes and cDNAs from durum wheat (TtASR1) and barley (HvASR1). Here, we show that HvASR1 and TtASR1 are consistently predicted to be disordered and further confirm this experimentally. Addition of glycerol, which mimics dehydration, triggers a gain of structure in both proteins. Limited proteolysis showed that they are highly sensitive to protease degradation...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29136219/mobidb-3-0-more-annotations-for-intrinsic-disorder-conformational-diversity-and-interactions-in-proteins
#19
Damiano Piovesan, Francesco Tabaro, Lisanna Paladin, Marco Necci, Ivan Micetic, Carlo Camilloni, Norman Davey, Zsuzsanna Dosztányi, Bálint Mészáros, Alexander M Monzon, Gustavo Parisi, Eva Schad, Pietro Sormanni, Peter Tompa, Michele Vendruscolo, Wim F Vranken, Silvio C E Tosatto
The MobiDB (URL: mobidb.bio.unipd.it) database of protein disorder and mobility annotations has been significantly updated and upgraded since its last major renewal in 2014. Several curated datasets for intrinsic disorder and folding upon binding have been integrated from specialized databases. The indirect evidence has also been expanded to better capture information available in the PDB, such as high temperature residues in X-ray structures and overall conformational diversity. Novel nuclear magnetic resonance chemical shift data provides an additional experimental information layer on conformational dynamics...
November 10, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29133811/site-specific-phosphorylation-regulates-the-structure-and-function-of-an-intrinsically-disordered-domain-of-the-glucocorticoid-receptor
#20
Shagufta H Khan, William A McLaughlin, Raj Kumar
Intrinsically disordered (ID) regions of the transcription factor proteins have much larger frequency of phosphorylation sites than ordered regions, suggesting an important role in their regulatory capacity. Consistent with this phenomenon, most of the functionally known phosphorylation sites in the steroid receptor family of transcription factors are located in the ID N-terminal domain that contains a powerful activation function (AF1) region. In this study, we determined the structural and functional consequences of functionally known phosphorylation residues (Ser203, 211, and 226) located in the human glucocorticoid receptor's (GR's) ID AF1 domain...
November 13, 2017: Scientific Reports
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