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https://www.readbyqxmd.com/read/29165552/what-happened-to-the-igf-binding-proteins
#1
Leon A Bach
Insulin-like growth factor binding proteins (IGFBPs) 1-6 are high affinity regulators of IGF activity. They generally inhibit IGF actions by preventing binding to the IGF-I receptor but may also enhance their actions under some conditions. Post-translational modifications such as glycosylation and phosphorylation modulate IGFBP properties, and IGFBP proteolysis results in IGF release. IGFBPs have more recently been shown to have IGF-independent actions. A number of mechanisms are involved, including modulation of other growth factor pathways, nuclear localization and transcriptional regulation, interaction with the sphingolipid pathway, and binding to non-IGF biomolecules in the extracellular space and matrix, on the cell surface and intracellularly...
November 20, 2017: Endocrinology
https://www.readbyqxmd.com/read/29163363/human-prolactin-point-mutations-and-their-projected-effect-on-vasoinhibin-generation-and-vasoinhibin-related-diseases
#2
Jakob Triebel, Christin J Friedrich, Andreas Leuchs, Gonzalo Martínez de la Escalera, Carmen Clapp, Thomas Bertsch
Background: A dysregulation of the generation of vasoinhibin hormones by proteolytic cleavage of prolactin (PRL) has been brought into context with diabetic retinopathy, retinopathy of prematurity, preeclampsia, pregnancy-induced hypertension, and peripartum cardiomyopathy. Factors governing vasoinhibin generation are incompletely characterized, and the composition of vasoinhibin isoforms in human tissues or compartments, such as the circulation, is unknown. The aim of this study was to determine the possible contribution of PRL point mutations to the generation of vasoinhibins as well as to project their role in vasoinhibin-related diseases...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29161859/theoretical-investigation-on-models-of-circadian-rhythms-based-on-dimerization-and-proteolysis-of-per-and-tim
#3
Jifa Jiang, Qiang Liu, Lei Niu
Circadian rhythms of physiology and behavior are widespread\break mechanisms in many organisms. The internal biological rhythms are driven by molecular clocks, which oscillate with a period nearly but not exactly 24 hours. Many classic models of circadian rhythms are based on a time-delayed negative feedback, suggested by the protein products inhibiting transcription of their own genes. In 1999, based on stabilization of PER upon dimerization, Tyson et al. [J. J. Tyson, C. I. Hong, C. D. Thron, B. Novak, Biophys...
October 2017: Mathematical Biosciences and Engineering: MBE
https://www.readbyqxmd.com/read/29161009/a-sensitive-microbead-based-organic-media-assisted-method-for-proteomics-sample-preparation-from-dilute-and-denaturing-solutions
#4
Masato Taoka, Michihiko Fujii, Masahiro Tsuchiya, Takamasa Uekita, Tohru Ichimura
We developed a robust and sensitive sample preparation method for proteomics termed microbead-based and organic-media-assisted proteolysis strategy (BOPs). BOPs combine two advantages of current techniques, (1) unbiased binding of reversed-phase polymeric microbeads to any type of protein and (2) enhanced trypsin digestion efficiency in CH3CN-aqueous solvent systems, into a single-tube workflow. Compared with conventional techniques, this method effectively concentrates proteins and improves proteolytic digestion, and can be used with submicromolar protein samples in dilute and/or denaturing solutions such as 70 % formic acid, 8 M urea, or 7 M guanidine hydrochloride without any sample pretreatment...
November 21, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29159880/swim-bladder-mycosis-in-pretty-tetra-hemigrammus-pulcher-caused-by-exophiala-pisciphila-and-phaeophleospora-hymenocallidicola-and-experimental-verification-of-pathogenicity
#5
J Řehulka, A Kubátová, V Hubka
Spontaneous invasive and chronic disseminated mycosis affected Hemigrammus pulcher kept in a public aquarium, and infection was manifested by inappetence, exophthalmia, erratic swimming, eroded scales, anaemia of the gills and abdominal distension. Internally, there was a grossly swollen swim bladder with a thickened wall filled with a dark mass. The body cavities contained a clear, light amber fluid and a swollen intestine which was full of a watery fluid containing small gas bubbles. Histopathology revealed a granulomatous inflammatory response with fungal hyphae in the lumen and wall of the swim bladder, hepatopancreas, spleen and kidneys with signs of nephrohydrosis...
November 21, 2017: Journal of Fish Diseases
https://www.readbyqxmd.com/read/29157946/endolysosomal-protease-susceptibility-of-amb-a-1-as-a-determinant-of-allergenicity
#6
Martin Wolf, Lorenz Aglas, Teresa E Twaroch, Markus Steiner, Sara Huber, Michael Hauser, Maria A Parigiani, Heidi Hofer, Christof Ebner, Barbara Bohle, Peter Briza, Angela Neubauer, Frank Stolz, Michael Wallner, Fatima Ferreira
In the absence of extrinsic adjuvants, purified Amb a 1 induced a strong Th2-polarized immune response in mice. This high allergenic activity seems to be linked to the allergen's susceptibility to endolysosomal proteolysis.
November 17, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29157202/target-proteins-reprogrammed-by-as-and-as%C3%A2-%C3%A2-si-treatments-in-solanum-lycopersicum-l-fruit
#7
Marta Marmiroli, Francesca Mussi, Davide Imperiale, Nelson Marmiroli
BACKGROUND: Arsenic is an important contaminant of many arable soils worldwide, while silicon, one of the most abundant elements in the earth's crust, interacts with As in the context of plant metabolism. As toxicity results largely from its stimulation of reactive oxygen species, and it is believed that Si can mitigate this process through reduction of the level of oxidative stress. Experiments targeting the proteomic impact of exposure to As and Si have to date largely focused on analyses of root, shoot and seed of a range of mainly non-solanaceous species, thus it remains unclear whether oxidative stress is the most important manifestation of As toxicity in Solanum lycopersicum fruit which during ripening go through drastic physiological and molecular readjustments...
November 21, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/29156207/intracellular-protein-degradation-from-a-vague-idea-thru-the-lysosome-and-the-ubiquitin-proteasome-system-and-onto-human-diseases-and-drug-targeting
#8
REVIEW
Aaron Ciechanover
Between the 1950s and 1980s, scientists were focusing mostly on how the genetic code is transcribed to RNA and translated to proteins, but how proteins are degraded has remained a neglected research area. With the discovery of the lysosome by Christian de Duve it was assumed that cellular proteins are degraded within this organelle. Yet, several independent lines of experimental evidence strongly suggested that intracellular proteolysis is largely non-lysosomal, but the mechanisms involved remained obscure...
December 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29155817/analysis-of-the-interactome-of-schistosoma-mansoni-histone-deacetylase-8
#9
Stéphanie Caby, Lucile Pagliazzo, Julien Lancelot, Jean-Michel Saliou, Nicolas Bertheaume, Raymond J Pierce, Emmanuel Roger
BACKGROUND: Histone deacetylase 8 from Schistosoma mansoni (SmHDAC8) is essential to parasite growth and development within the mammalian host and is under investigation as a target for the development of selective inhibitors as novel schistosomicidal drugs. Although some protein substrates and protein partners of human HDAC8 have been characterized, notably indicating a role in the function of the cohesin complex, nothing is known of the partners and biological function of SmHDAC8. METHODOLOGY/PRINCIPAL FINDINGS: We therefore employed two strategies to characterize the SmHDAC8 interactome...
November 20, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29155321/clp-protease-and-or-directly-control-the-proteostasis-of-phytoene-synthase-the-crucial-enzyme-for-carotenoid-biosynthesis-in-arabidopsis
#10
Ralf Welsch, Xiangjun Zhou, Hui Yuan, Daniel Álvarez, Tianhu Sun, Dennis Schlossarek, Yong Yang, Guoxin Shen, Hong Zhang, Manuel Rodriguez-Concepcion, Theodore W Thannhauser, Li Li
Phytoene synthase (PSY) is the crucial plastidial enzyme in the carotenoid biosynthetic pathway. However, its post-translational regulation remains elusive. Likewise, Clp protease constitutes a central part of the plastid protease networks, but its substrates for degradation are not well known. In this study, we report that PSY is a substrate of the Clp protease. PSY was uncovered to physically interact with various Clp protease subunits (i.e. ClpS1, ClpC1, and ClpD). High levels of PSY and several other carotenogenic enzymes over-accumulate in the clpc1, clpp4 and clpr1-2 mutants...
November 16, 2017: Molecular Plant
https://www.readbyqxmd.com/read/29154460/elevated-co2-increases-r-gene-dependent-resistance-of-medicago-truncatula-against-the-pea-aphid-by-up-regulating-a-heat-shock-gene
#11
Yucheng Sun, Huijuan Guo, Erliang Yuan, Feng Ge
Resistance against pathogens and herbivorous insects in many plant results from the expression of resistance (R) genes. Few reports, however, have considered the effects of elevated CO2 on R gene-based resistance in plants. The current study determined the responses of two near isogenic Medicago truncatula genotypes (Jester has an R gene and A17 does not) to the pea aphid and elevated CO2 in open-top chambers in the field. Aphid abundance, mean relative growth rate and feeding efficiency were increased by elevated CO2 on A17 plants but were reduced on Jester plants...
November 20, 2017: New Phytologist
https://www.readbyqxmd.com/read/29153610/tdp-43-proteolysis-is-associated-with-astrocyte-reactivity-after-traumatic-brain-injury-in-rodents
#12
Chih-Yuan Huang, Yi-Che Lee, Ping-Chia Li, Po-Chou Liliang, Kang Lu, Kuo-Wei Wang, Li-Ching Chang, Li-Yen Shiu, Ming-Feng Chen, Yuan-Ting Sun, Hao-Kuang Wang
The aggregation and deposition of transactivation response DNA-binding protein 43 (TDP-43) in neurons and astrocytes is characteristic in a number of neurodegenerative diseases including Alzheimer's disease, frontotemporal lobar degeneration, and amyotrophic lateral sclerosis. Nevertheless, the exact role of TDP-43 in astrocytes is unknown. Recently, TDP-43 was identified in neurons but not astrocytes after traumatic brain injury (TBI) in humans. In the present study, we evaluated TDP-43 expression and proteolysis in astrocytes in a rat model of TBI...
December 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29152137/emodin-and-rhein-decrease-levels-of-hypoxia-inducible-factor-1%C3%AE-in-human-pancreatic-cancer-cells-and-attenuate-cancer-cachexia-in-athymic-mice-carrying-these-cells
#13
Lijuan Hu, Rui Cui, Hongyi Liu, Feng Wang
The transcription factor hypoxia-inducible factor-1 (HIF-1) consists of oxygen-sensitive HIF-1α and constitutive HIF-1β. HIF-1α is undetectable in normal cells, but cancer cells frequently express HIF-1α to support their growth, angiogenesis, and high glycolysis (also known as the Warburg effect). The Warburg effect in cancer cells increases energy expenditure and thus participates in cancer-induced metabolic disorder, cancer cachexia. In the present study, we investigated whether two components of Rheum palmatum, emodin and rhein, inhibited HIF-1α expression in human pancreatic cancer cells and whether the inhibiting effect, if any, attenuated cancer cachexia...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151899/globular-domain-structure-and-function-of-restriction-like-endonuclease-lines-similarities-to-eukaryotic-splicing-factor-prp8
#14
M Murshida Mahbub, Saiful M Chowdhury, Shawn M Christensen
Background: R2 elements are a clade of early branching Long Interspersed Elements (LINEs). LINEs are retrotransposable elements whose replication can have profound effects on the genomes in which they reside. No crystal or EM structures exist for the reverse transcriptase (RT) and linker regions of LINEs. Results: Using limited proteolysis as a probe for globular domain structure, we show that the protein encoded by the Bombyx mori R2 element has two major globular domains: (1) a small globular domain consisting of the N-terminal zinc finger and Myb motifs, and (2) a large globular domain consisting of the RT, linker, and type II restriction-like endonuclease (RLE)...
2017: Mobile DNA
https://www.readbyqxmd.com/read/29149593/notch2-hajdu-cheney-mutations-escape-scf-fbw7-dependent-proteolysis-to-promote-osteoporosis
#15
Hidefumi Fukushima, Kouhei Shimizu, Asami Watahiki, Seira Hoshikawa, Tomoki Kosho, Daiju Oba, Seiji Sakano, Makiko Arakaki, Aya Yamada, Katsuyuki Nagashima, Koji Okabe, Satoshi Fukumoto, Eijiro Jimi, Anna Bigas, Keiichi I Nakayama, Keiko Nakayama, Yoko Aoki, Wenyi Wei, Hiroyuki Inuzuka
Hajdu-Cheney syndrome (HCS), a rare autosomal disorder caused by heterozygous mutations in NOTCH2, is clinically characterized by acro-osteolysis, severe osteoporosis, short stature, neurological symptoms, cardiovascular defects, and polycystic kidneys. Recent studies identified that aberrant NOTCH2 signaling and consequent osteoclast hyperactivity are closely associated with the bone-related disorder pathogenesis, but the exact molecular mechanisms remain unclear. Here, we demonstrate that sustained osteoclast activity is largely due to accumulation of NOTCH2 carrying a truncated C terminus that escapes FBW7-mediated ubiquitination and degradation...
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29149532/exploitation-of-micrornas-by-japanese-encephalitis-virus-in-human-microglial-cells
#16
Meghana Rastogi, Neha Srivastava, Sunit K Singh
JEV infection in CNS leads to the JE neuroinflammation. Children and old age individual have been reported to be more prone to JEV infection. MicroRNAs are endogenous, small non-coding RNAs, which regulate the gene expression. These are ∼22 nucleotide long, conserved RNA sequence that binds at the 3'UTR of a target mRNA and regulate the post-transcriptional gene expression. The role of microRNAs has been reported in several diseases like cancer, viral infection, neuro-degeneration, diabetes etc. In the present study, the human microglial cells were infected with JEV (JaOAr strain)...
November 17, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/29148177/high-concentrations-of-gtp-induce-conformational-changes-in-the-essential-bacterial-gtpase-enga-and-enhance-its-binding-to-the-ribosome
#17
Catarina da Silveira Tomé, Anne-Emmanuelle Foucher, Jean-Michel Jault, Dominique Housset
EngA is a conserved bacterial GTPase involved in ribosome biogenesis. While essential in bacteria, EngA does not have any human ortholog and can thus be an interesting target for new antibacterial compounds. EngA is the only known GTPase bearing two G-domains, making unique its catalytic cycle and the induced modulation of its conformation and interaction with the ribosome. We have investigated nucleotide-induced conformational changes in EngA in order to unveil their role in ribosome binding. SAXS and limited proteolysis were used to probe EngA conformational changes, and revealed a change in protein structure and a distinct rate of proteolysis induced by GTP...
November 17, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29147091/evaluation-of-the-digestibility-of-korean-hanwoo-beef-cuts-using-the-in-vitro-physicochemical-upper-gastrointestinal-system
#18
Ji-Hye Jeon, Michelle Yoo, Tae-Hwan Jung, Woo-Min Jeon, Kyoung-Sik Han
The aim of this study was to investigate the digestibility of different Korean Hanwoo beef cuts using an in vitro digestion model, in vitro physicochemical upper gastrointestinal system (IPUGS). The four most commonly consumed cuts - tenderloin, sirloin, brisket and flank, and bottom round - were chosen for this study. Beef samples (75 g) were cooked and ingested into IPUGS, which was composed of mouth, esophagus, and stomach, thereby simulating the digestion conditions of humans. Digested samples were collected every 15 min for 4 h of simulation and their pH monitored...
2017: Korean Journal for Food Science of Animal Resources
https://www.readbyqxmd.com/read/29146341/oxidation-and-nitrosation-of-meat-proteins-under-gastro-intestinal-conditions-consequences-in-terms-of-nutritional-and-health-values-of-meat
#19
Diane de La Pomélie, Véronique Santé-Lhoutellier, Thierry Sayd, Philippe Gatellier
The chemical changes (oxidation/nitrosation) of meat proteins during digestion lead to a decrease in their nutritional value. Moreover, oxidized and nitrosated amino acids are suspected to promote various human pathologies. To investigate the mechanisms and the kinetics of these endogenous protein modifications, we used a dynamic artificial digestive system (DIDGI®) that mimics the physicochemical conditions of digestion. The combined effect of meat cooking and endogenous addition of ascorbate and nitrite was evaluated on protein oxidation (by measuring carbonyl groups), protein nitrosation (by measuring nitrosamines), and proteolysis...
March 15, 2018: Food Chemistry
https://www.readbyqxmd.com/read/29145514/why-patients-with-thbd-c-1611c-a-p-cys537x-nonsense-mutation-have-high-levels-of-soluble-thrombomodulin
#20
Yohann Jourdy, Nathalie Enjolras, Sandra Le Quellec, Jean Claude Bordet, Claude Négrier, Christine Vinciguerra, Yesim Dargaud
BACKGROUND: Recently our group has described a new autosomal dominant bleeding disorder characterized by very high plasma levels of soluble thrombomodulin (TM). The THBD c.1611C>A (p.Cys537X) mutation in heterozygous state was found in the propositus. This mutation leads to the synthesis of a truncated TM which has lost the last three amino-acids of the transmembrane domain and the cytoplasmic tail. OBJECTIVE: We investigated the mechanism responsible for TM shedding in endothelial cells with THBD c...
2017: PloS One
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