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https://www.readbyqxmd.com/read/29351669/how-pairwise-coevolutionary-models-capture-the-collective-residue-variability-in-proteins
#1
Matteo Figliuzzi, Pierre Barrat-Charlaix, Martin Weigt
Global coevolutionary models of homologous protein families, as constructed by direct coupling analysis (DCA), have recently gained popularity in particular due to their capacity to accurately predict residueresidue contacts from sequence information alone, and thereby to facilitate tertiary and quaternary protein structure prediction. More recently, they have also been used to predict fitness effects of aminoacid substitutions in proteins, and to predict evolutionary conserved protein-protein interactions...
January 17, 2018: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/29351565/sumo-targeting-of-a-stress-tolerant-ulp1-sumo-protease
#2
Jennifer Peek, Catherine Harvey, Dreux Gray, Danny Rosenberg, Likhitha Kolla, Reuben Levy-Myers, Rui Yin, Jonathan L McMurry, Oliver Kerscher
SUMO proteases of the SENP/Ulp family are master regulators of both sumoylation and desumoylation and regulate SUMO homeostasis in eukaryotic cells. SUMO conjugates rapidly increase in response to cellular stress, including nutrient starvation, hypoxia, osmotic stress, DNA damage, heat shock, and other proteotoxic stressors. Nevertheless, little is known about the regulation and targeting of SUMO proteases during stress. To this end we have undertaken a detailed comparison of the SUMO-binding activity of the budding yeast protein Ulp1 (ScUlp1) and its ortholog in the thermotolerant yeast Kluyveromyces marxianus, KmUlp1...
2018: PloS One
https://www.readbyqxmd.com/read/29351497/screen-targeting-lung-and-prostate-cancer-oncogene-identifies-novel-inhibitors-of-rgs17-and-problematic-chemical-substructures
#3
Christopher R Bodle, Josephine H Schamp, Joseph B O'Brien, Michael P Hayes, Meng Wu, Jonathan A Doorn, David L Roman
Regulator of G protein signaling (RGS) proteins temporally regulate heterotrimeric G protein signaling cascades elicited by G protein-coupled receptor activation and thus are essential for cell homeostasis. The dysregulation of RGS protein expression has been linked to several pathologies, spurring discovery efforts to identify small-molecule inhibitors of these proteins. Presented here are the results of a high-throughput screening (HTS) campaign targeting RGS17, an RGS protein reported to be inappropriately upregulated in several cancers...
January 1, 2018: SLAS Discovery
https://www.readbyqxmd.com/read/29351356/epha2-ephrin-a1-mediate-corneal-epithelial-cell-compartmentalization-via-adam10-regulation-of-egfr-signaling
#4
Nihal Kaplan, Rosa Ventrella, Han Peng, Sonali Pal-Ghosh, Constadina Arvanitis, Joshua Z Rappoport, Brian J Mitchell, Mary Ann Stepp, Robert M Lavker, Spiro Getsios
Purpose: Progenitor cells of the limbal epithelium reside in a discrete area peripheral to the more differentiated corneal epithelium and maintain tissue homeostasis. What regulates the limbal-corneal epithelial boundary is a major unanswered question. Ephrin-A1 ligand is enriched in the limbal epithelium, whereas EphA2 receptor is concentrated in the corneal epithelium. This reciprocal pattern led us to assess the role of ephrin-A1 and EphA2 in limbal-corneal epithelial boundary organization...
January 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29351342/a-homozygous-missense-variant-in-vwa2-encoding-an-interactor-of-the-fraser-complex-in-a-patient-with-vesicoureteral-reflux
#5
Amelie T van der Ven, Birgit Kobbe, Stefan Kohl, Shirlee Shril, Hans-Martin Pogoda, Thomas Imhof, Hadas Ityel, Asaf Vivante, Jing Chen, Daw-Yang Hwang, Dervla M Connaughton, Nina Mann, Eugen Widmeier, Mary Taglienti, Johanna Magdalena Schmidt, Makiko Nakayama, Prabha Senguttuvan, Selvin Kumar, Velibor Tasic, Elijah O Kehinde, Shrikant M Mane, Richard P Lifton, Neveen Soliman, Weining Lu, Stuart B Bauer, Matthias Hammerschmidt, Raimund Wagener, Friedhelm Hildebrandt
Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause (40-50%) of chronic kidney disease (CKD) in children. About 40 monogenic causes of CAKUT have so far been discovered. To date less than 20% of CAKUT cases can be explained by mutations in these 40 genes. To identify additional monogenic causes of CAKUT, we performed whole exome sequencing (WES) and homozygosity mapping (HM) in a patient with CAKUT from Indian origin and consanguineous descent. We identified a homozygous missense mutation (c...
2018: PloS One
https://www.readbyqxmd.com/read/29351335/the-effects-of-an-acute-exercise-bout-on-gh-and-igf-1-in-prediabetic-and-healthy-african-americans-a-pilot-study-investigating-gene-expression
#6
Nathaniel T Berry, Monica Hubal, Laurie Wideman
The incidence of pre-diabetes (PD) and Type-2 Diabetes Mellitus (T2D) is a worldwide epidemic. African American (AA) individuals are disproportionately more likely to become diabetic than other ethnic groups. Over the long-term, metabolic complications related to diabetes result in significant alterations in growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Considering the limited exercise-related studies in the area of gene expression changes with disease progression, the objective of this study was to examine differences in exercise-induced gene expression related to the GH and IGF-1 pathways in peripheral blood mononuclear cells (PBMCs) of healthy (CON) and PD AA individuals...
2018: PloS One
https://www.readbyqxmd.com/read/29351266/from-extraction-of-local-structures-of-protein-energy-landscapes-to-improved-decoy-selection-in-template-free-protein-structure-prediction
#7
Nasrin Akhter, Amarda Shehu
Due to the essential role that the three-dimensional conformation of a protein plays in regulating interactions with molecular partners, wet and dry laboratories seek biologically-active conformations of a protein to decode its function. Computational approaches are gaining prominence due to the labor and cost demands of wet laboratory investigations. Template-free methods can now compute thousands of conformations known as decoys, but selecting native conformations from the generated decoys remains challenging...
January 19, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29351238/telomeres-implications-for-cancer-development
#8
REVIEW
Aina Bernal, Laura Tusell
Telomeres facilitate the protection of natural ends of chromosomes from constitutive exposure to the DNA damage response (DDR). This is most likely achieved by a lariat structure that hides the linear telomeric DNA through protein-protein and protein-DNA interactions. The telomere shortening associated with DNA replication in the absence of a compensatory mechanism culminates in unmasked telomeres. Then, the subsequent activation of the DDR will define the fate of cells according to the functionality of cell cycle checkpoints...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29351211/wide-field-fluorescence-microscopy-of-real-time-bioconjugation-sensing
#9
Marcin Szalkowski, Karolina Sulowska, Justyna Grzelak, Joanna Niedziółka-Jönsson, Ewa Roźniecka, Dorota Kowalska, Sebastian Maćkowski
We apply wide-field fluorescence microscopy to measure real-time attachment of photosynthetic proteins to plasmonically active silver nanowires. The observation of this effect is enabled, on the one hand, by sensitive detection of fluorescence and, on the other hand, by plasmonic enhancement of protein fluorescence. We examined two sample configurations with substrates being a bare glass coverslip and a coverslip functionalized with a monolayer of streptavidin. The different preparation of the substrate changes the observed behavior as far as attachment of the protein is concerned as well as its subsequent photobleaching...
January 19, 2018: Sensors
https://www.readbyqxmd.com/read/29351144/cardiac-dysfunction-in-critical-illness
#10
Allison Dalton, Sajid Shahul
PURPOSE OF REVIEW: Sepsis and septic shock are prevalent conditions that are likely to increase in prevalence in the future. Given the high mortality and morbidity associated with sepsis and sepsis-induced cardiac dysfunction, we must continue to make advances in knowledge of the complex physiologic interactions and how we may target specific mediators for potential therapeutic options in the future. RECENT FINDINGS: Multiple biomarkers have been discovered, which when assayed in sepsis-induced cardiomyopathy predict morbidity and mortality...
January 17, 2018: Current Opinion in Anaesthesiology
https://www.readbyqxmd.com/read/29351143/nutrition-in-the-icu-new-trends-versus-old-fashioned-standard-enteral-feeding
#11
Kristine W A C Koekkoek, Arthur R H van Zanten
PURPOSE OF REVIEW: The narrative review aims to summarize the relevant studies from the last 2 years and provide contextual information to understand findings. RECENT FINDINGS: Recent ICU studies have provided insight in the pathophysiology and time course of catabolism, anabolic resistance, and metabolic and endocrine derangements interacting with the provision of calories and proteins.Early provision of high protein intake and caloric overfeeding may confer harm...
January 18, 2018: Current Opinion in Anaesthesiology
https://www.readbyqxmd.com/read/29351065/measurement-of-binding-strength-between-prey-proteins-interacting-with-toxoplasma-gondii-sag1-and-sag2-using-isothermal-titration-calorimetry-itc
#12
Meng-Yee Lai, Yee-Ling Lau
Following the outcome from a previously performed yeast two-hybrid experiment, the binding strength between T. gondii SAG1 and SAG2 and their respective prey proteins were further confirmed in this study. The sag1, sag2 and their prey genes were amplified and cloned into a pGEMT vector. To express the recombinant proteins, the fragments were then subcloned into a pRSETA vector and transformed into E. coli BL21 (DE3) cells. The recombinant proteins were expressed optimally at 37°C and 1mM of IPTG. The 6X His-tag fusion proteins were purified, dialyzed and concentrated...
March 26, 2018: Acta Parasitologica
https://www.readbyqxmd.com/read/29350922/computing-curvature-sensitivity-of-biomolecules-in-membranes-by-simulated-buckling
#13
Federico Elias-Wolff, Martin Lindén, Alexander P Lyubartsev, Erik G Brandt
Membrane curvature sensing, where the binding free energies of membrane-associated molecules depend on the local membrane curvature, is a key factor to modulate and maintain the shape and organization of cell membranes. However, the microscopic mechanisms are not well understood, partly due to absence of efficient simulation methods. Here, we describe a method to compute the curvature dependence of the binding free energy of a membrane-associated probe molecule that interacts with a buckled membrane, which has been created by lateral compression of a flat bilayer patch...
January 19, 2018: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/29350881/interferon-induced-protein-35-ifi35-inhibits-endothelial-cell-proliferation-migration-and-re-endothelialization-of-injured-arteries-by-inhibiting-the-nuclear-factor-kappa-b-nf-kb-pathway
#14
Dongdong Jian, Weina Wang, Xinmiao Zhou, Zhen Jia, Jing Wang, Mei Yang, Wenting Zhao, Zhen Jiang, Xiaotong Hu, Jianhua Zhu
AIM: Endothelial recovery, or re-endothelialization, plays an important role in intimal hyperplasia and atherosclerosis after endothelial injury. Studying the mechanisms of re-endothelialization and strategies to promote efficient endothelial recovery are still needed. Interferon-induced protein 35 (IFI35) is an IFN-γ-induced protein that plays important roles in the anti-virus-related immune-inflammatory response. In this study, we tested whether overexpression IFI35 affects the proliferation and migration of endothelial cells (ECs) and re-endothelialization...
January 19, 2018: Acta Physiologica
https://www.readbyqxmd.com/read/29350745/tio2-nanoparticles-can-selectively-bind-cxcl8-impacting-on-neutrophil-chemotaxis
#15
J Batt, M Milward, I Chapple, M Grant, H Roberts, O Addison
The interaction between TiO2 nanoparticles (NPs) and inflammatory cytokines, including CXCL8, a clinically relevant pro-inflammatory chemokine was investigated. TiO2 is present in tissues adjacent to failing implanted Ti (titanium) devices. TiO2 NPs were shown to bind to CXCL8 in vitro, causing perturbation of quantification of CXCL8 by ELISA, in both simple and complex protein panels, in a dose-dependent manner. Binding between TiO2 NPs and CXCL8 was demonstrated by protein gel electrophoresis. TiO2 NPs were also shown to inactivate the chemoattractant property of CXCL8 in a dose-dependent manner, suggesting that the binding between TiO2 NPs and CXCL8 is likely to be clinically relevant...
January 19, 2018: European Cells & Materials
https://www.readbyqxmd.com/read/29350282/neutrophil-chemotaxis
#16
REVIEW
Björn Petri, Maria-Jesús Sanz
Neutrophils are the primary cells recruited to inflamed sites during an innate immune response to tissue damage and/or infection. They are finely sensitive to inciting stimuli to reach in great numbers and within minutes areas of inflammation and tissue insult. For this effective response, they can detect extracellular chemical gradients and move towards higher concentrations, the so-called chemotaxis process or guided cell migration. This directed neutrophil recruitment is orchestrated by chemoattractants, a chemically diverse group of molecular guidance cues (e...
January 19, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29350244/autophagy-related-atg-11-atg9-and-the-phosphatidylinositol-3-kinase-control-atg2-mediated-formation-of-autophagosomes-in-arabidopsis
#17
Sangwoo Kang, Kwang Deok Shin, Jeong Hun Kim, Taijoon Chung
Using quantitative assays for autophagy, we analyzed 4 classes of atg mutants, discovered new atg2 phenotypes and ATG gene interactions, and proposed a model of autophagosome formation in plants. Plant and other eukaryotic cells use autophagy to target cytoplasmic constituents for degradation in the vacuole. Autophagy is regulated and executed by a conserved set of proteins called autophagy-related (ATG). In Arabidopsis, several groups of ATG proteins have been characterized using genetic approaches. However, the genetic interactions between ATG genes have not been established and the relationship between different ATG groups in plants remains unclear...
January 19, 2018: Plant Cell Reports
https://www.readbyqxmd.com/read/29349926/extracellular-vesicles-from-early-stage-p-falciparum-infected-red-blood-cells-contain-pfemp1-and-induce-transcriptional-changes-in-human-monocytes
#18
Natália G Sampaio, Samantha Emery, Alexandra Garnham, Qiao Y Tan, Xavier Sisquella, Matthew A Pimentel, Neta Regev-Rudzki, Louis Schofield, Emily M Eriksson
Pathogens can release extracellular vesicles (EVs) for cell-cell communication and host modulation. EVs from Plasmodium falciparum, the deadliest malaria parasite species, can transfer drug resistance genes between parasites. EVs from late-stage parasite-infected RBC (iRBC-EVs) are immunostimulatory and affect endothelial cell permeability, but little is known about EVs from early-stage iRBC. We detected the parasite virulence factor PfEMP1, which is responsible for iRBC adherence and a major contributor to disease severity, in EVs only up to 12 hours-post RBC invasion...
January 18, 2018: Cellular Microbiology
https://www.readbyqxmd.com/read/29349888/distal-amyloid-%C3%AE-protein-fragments-template-amyloid-assembly
#19
Thanh D Do, Smriti Sangwan, Natália E C de Almeida, Alexandre I Ilitchev, Maxwell Giammona, Michael R Sawaya, Steven K Buratto, David S Eisenberg, Michael T Bowers
Amyloid formation is associated with devastating diseases such as Alzheimer's, Parkinson's and Type-2 diabetes. The large amyloid deposits found in patients suffering from these diseases have remained difficult to probe by structural means. Recent NMR models also predict heterotypic interactions from distinct peptide fragments but limited evidence of heterotypic packed sheets is observed in solution. Here we characterize two segments of the protein amyloid β (Aβ) known to form fibrils in Alzheimer's disease patients...
January 19, 2018: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29349763/immune-checkpoint-blockade-for-breast-cancer
#20
April Swoboda, Rita Nanda
An effective antitumor immune response requires interaction between cells of the adaptive and innate immune system. Three key elements are required: generation of activated tumor-directed T cells, infiltration of activated T cells into the tumor microenvironment, and killing of tumor cells by activated T cells. Tumor immune evasion can occur as a result of the disruption of each of these three key T cell activities, resulting in three distinct cancer-immune phenotypes. The immune inflamed phenotype, characterized by the presence of a robust tumor immune infiltrate, suggests impaired activated T cell killing of tumor cells related to the presence of inhibitory factors...
2018: Cancer Treatment and Research
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