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https://www.readbyqxmd.com/read/28424241/microbiota-induced-antibodies-are-essential-for-host-inflammatory-responsiveness-to-sterile-and-infectious-stimuli
#1
Daniel Cisalpino, Caio T Fagundes, Camila B Brito, Fernando R Ascenção, Celso M Queiroz-Junior, Angélica T Vieira, Lirlândia P Sousa, Flávio A Amaral, Leda Q Vieira, Jacques R Nicoli, Mauro M Teixeira, Danielle G Souza
The indigenous intestinal microbiota is frequently considered an additional major organ of the human body and exerts profound immunomodulating activities. Germ-free (GF) mice display a significantly different inflammatory responsiveness pattern compared with conventional (CV) mice, and this was dubbed a "hyporesponsive phenotype." Taking into account that the deposition of immune complexes is a major event in acute inflammation and that GF mice have a distinct Ig repertoire and B cell activity, we aimed to evaluate whether this altered Ig repertoire interferes with the inflammatory responsiveness of GF mice...
April 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28423502/acute-lymphoblastic-leukemia-cells-are-sensitive-to-disturbances-in-protein-homeostasis-induced-by-proteasome-deubiquitinase-inhibition
#2
Magdalena Mazurkiewicz, Ellin-Kristina Hillert, Xin Wang, Paola Pellegrini, Maria Hägg Olofsson, Karthik Selvaraju, Padraig D'Arcy, Stig Linder
The non-genotoxic nature of proteasome inhibition makes it an attractive therapeutic option for the treatment of pediatric malignancies. We recently described the small molecule VLX1570 as an inhibitor of proteasome deubiquitinase (DUB) activity that induces proteotoxic stress and apoptosis in cancer cells. Here we show that acute lymphoblastic leukemia (ALL) cells are highly sensitive to treatment with VLX1570, resulting in the accumulation of polyubiquitinated proteasome substrates and loss of cell viability...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416749/acute-lymphoblastic-leukemia-cells-are-sensitive-to-disturbances-in-protein-homeostasis-induced-by-proteasome-deubiquitinase-inhibition
#3
Magdalena Mazurkiewicz, Ellin-Kristina Hillert, Xin Wang, Paola Pellegrini, Maria Hägg Olofsson, Karthik Selvaraju, Padraig D'Arcy, Stig Linder
The non-genotoxic nature of proteasome inhibition makes it an attractive therapeutic option for the treatment of pediatric malignancies. We recently described the small molecule VLX1570 as an inhibitor of proteasome deubiquitinase (DUB) activity that induces proteotoxic stress and apoptosis in cancer cells. Here we show that acute lymphoblastic leukemia (ALL) cells are highly sensitive to treatment with VLX1570, resulting in the accumulation of polyubiquitinated proteasome substrates and loss of cell viability...
February 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410891/advancing-our-understanding-of-ubiquitination-using-the-ub-toolkit
#4
REVIEW
Katharina F Witting, Monique P C Mulder, Huib Ovaa
Post-translational protein modification by ubiquitin (Ub) and ubiquitin-like modifiers (Ubl) is orchestrated by the sequential action of ubiquitin activating, conjugating, and ligating enzymes to regulate a vast array of fundamental biological processes. Unsurprisingly, the dysregulation of the intricate interplay between ubiquitination and deubiquitination gives rise to numerous pathologies, most notably cancer and neurodegenerative diseases. While activity-based probes (ABPs) and assay reagents have been extensively developed and applied for deubiquitinating enzymes (DUBs), similar tools for the ubiquitin cascade have only recently emerged...
April 11, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28399284/olfactory-ionotropic-receptors-in-mosquito-aedes-albopictus-diptera-culicidae
#5
Qian Chen, Yahui Man, Jianyong Li, Di Pei, Wenjian Wu
Ionotropic glutamate receptors (iGluRs) are a conserved family of ligand-gated ion channels that primarily function to mediate neuronal communication at synapses. A variant subfamily of iGluRs, the ionotropic receptors (IRs), was recently identified in insects and proved with the function in odorant recognition. Ionotropic receptors participate in a distinct olfactory signaling pathway that is independent of olfactory receptors activity. In the present study, we identify 102 putative IR genes, dubbed as AalbIr genes, in mosquito Aedes albopictus (Skuse) by in silico comparative sequence analysis...
March 28, 2017: Journal of Medical Entomology
https://www.readbyqxmd.com/read/28396573/synapses-in-the-spotlight-with-synthetic%C3%A2-optogenetics
#6
REVIEW
Shai Berlin, Ehud Y Isacoff
Membrane receptors and ion channels respond to various stimuli and relay that information across the plasma membrane by triggering specific and timed processes. These include activation of second messengers, allowing ion permeation, and changing cellular excitability, to name a few. Gaining control over equivalent processes is essential to understand neuronal physiology and pathophysiology. Recently, new optical techniques have emerged proffering new remote means to control various functions of defined neuronal populations by light, dubbed optogenetics...
April 10, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28394268/fusing-bluetooth-beacon-data-with-wi-fi-radiomaps-for-improved-indoor-localization
#7
Loizos Kanaris, Akis Kokkinis, Antonio Liotta, Stavros Stavrou
Indoor user localization and tracking are instrumental to a broad range of services and applications in the Internet of Things (IoT) and particularly in Body Sensor Networks (BSN) and Ambient Assisted Living (AAL) scenarios. Due to the widespread availability of IEEE 802.11, many localization platforms have been proposed, based on the Wi-Fi Received Signal Strength (RSS) indicator, using algorithms such as K-Nearest Neighbour (KNN), Maximum A Posteriori (MAP) and Minimum Mean Square Error (MMSE). In this paper, we introduce a hybrid method that combines the simplicity (and low cost) of Bluetooth Low Energy (BLE) and the popular 802...
April 10, 2017: Sensors
https://www.readbyqxmd.com/read/28393942/spin-filtering-with-poly-t-wrapped-single-wall-carbon-nanotubes
#8
Kazi M Alam, Sandipan Pramanik
Spin filtering is an essential operation in spintronics that allows the creation and detection of spin polarized carriers. Transition metal ferromagnets are used as spin filters in most cases, though their spin filtering efficiency is only around ∼50%, thereby limiting the efficiency of spintronic devices. Recently, chiral systems such as DNA have been shown to exhibit efficient spin filtering, a phenomenon often dubbed as "chirality induced spin selectivity" (CISS). In this work, we consider single wall carbon nanotubes helically wrapped with single stranded poly-T DNA...
April 20, 2017: Nanoscale
https://www.readbyqxmd.com/read/28393213/micrornas-driving-invasion-and-metastasis-in-ovarian-cancer-opportunities-for-translational-medicine-review
#9
Carlos Palma Flores, Raúl García-Vázquez, Dolores Gallardo Rincón, Erika Ruiz-García, Horacio Astudillo de la Vega, Laurence A Marchat, Yarely M Salinas Vera, César López-Camarillo
Epithelial ovarian cancer is the fifth most frequent cause of cancer death in women. In spite of the advantages in early detection and treatment options, overall survival rates have improved only slightly in the last decades. Therefore, alternative therapeutic approaches need to overcome resistance and improve the patient survival and outcome. MicroRNAs are evolutionary conserved small non-coding RNAs that function as negative regulators of gene expression by inhibiting translation or inducing degradation of messenger RNAs...
May 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28388882/an-abdominal-ectopic-pregnancy-following-a-frozen-thawed-art-cycle-a-case-report-and-review-of-the-literature
#10
Atsushi Yanaihara, Shirei Ohgi, Kenichirou Motomura, Yuko Hagiwara, Tae Mogami, Keisuke Saito, Takumi Yanaihara
BACKGROUND: Ectopic pregnancy (EP) occurs in 1% of pregnancies and is reported to be more common in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) pregnancies. An abdominal ectopic pregnancy (AEP) is a rare form of EP, and there are few reports of an AEP after IVF/ICSI. In this case report, a rare case of AEP after frozen-thawed cycle of ICSI is presented. CASE PRESENTATION: After a frozen-thawed cycle of ICSI, the beta-human chorionic gonadotropin (HCG) level at 4 weeks 0 days of gestation was 3...
April 7, 2017: BMC Pregnancy and Childbirth
https://www.readbyqxmd.com/read/28386537/revealing-a-novel-otubain-like-enzyme-from-leishmania-infantum-with-deubiquitinating-activity-toward-k48-linked-substrate
#11
Clênia S Azevedo, Bruna C Guido, Jhonata L Pereira, Diego O Nolasco, Rafael Corrêa, Kelly G Magalhães, Flávia N Motta, Jaime M Santana, Philippe Grellier, Izabela M D Bastos
Deubiquitinating enzymes (DUBs) play an important role in regulating a variety of eukaryotic processes. In this context, exploring the role of deubiquitination in Leishmania infantum could be a promising alternative to search new therapeutic targets for leishmaniasis. Here we present the first characterization of a DUB from L. infantum, otubain (OtuLi), and its localization within parasite. The recombinant OtuLi (rOtuLi) showed improved activity on lysine 48 (K48)-linked over K63-linked tetra-ubiquitin (Ub) and site-directed mutations on amino acids close to the catalytic site (F82) or involved in Ub interaction (L265 and F182) caused structural changes as shown by molecular dynamics, resulting in a reduction or loss of enzyme activity, respectively...
2017: Frontiers in Chemistry
https://www.readbyqxmd.com/read/28382714/enzyme-reversal-to-explore-the-function-of-yeast-e3-ubiquitin-ligases
#12
Chris MacDonald, Stanley Winistorfer, R Marshall Pope, Michael E Wright, Robert C Piper
The covalent attachment of ubiquitin onto proteins can elicit a variety of downstream consequences. Attachment is mediated by a large array of E3 ubiquitin ligases, each thought be subject to regulatory control and to have a specific repertoire of substrates. Assessing the biological roles of ligases, and in particular, identifying their biologically relevant substrates has been a persistent yet challenging question. In this study we describe tools that may help achieve both of these goals. We describe a strategy whereby the activity of a ubiquitin ligase has been enzymatically reversed, accomplished by fusing it to a catalytic domain of an exogenous deubiquitinating enzyme...
April 6, 2017: Traffic
https://www.readbyqxmd.com/read/28376984/insulin-almost-a-century-of-lifesaving
#13
(no author information available yet)
The identification and purification of insulin in 1922 changed life for individuals with type 1 diabetes mellitus (T1DM). Its discovery was, to a certain extent, serendipitous. Although medical researchers suspected that some type of hormone was responsible for carbohydrate metabolism, by the end of the 19th century they had made little progress. When World War I broke out, efforts stalled. A somewhat cantankerous group of Canadian researchers led by Frederick Grant Banting, a surgeon, are credited with insulin's discovery...
April 1, 2017: Consultant Pharmacist: the Journal of the American Society of Consultant Pharmacists
https://www.readbyqxmd.com/read/28375142/crystal-structure-and-rna-binding-properties-of-an-hfq-homolog-from-the-deep-branching-aquificae-conservation-of-the-lateral-rna-binding-mode
#14
Kimberly A Stanek, Jennifer Patterson-West, Peter S Randolph, Cameron Mura
The host factor Hfq, as the bacterial branch of the Sm family, is an RNA-binding protein involved in the post-transcriptional regulation of mRNA expression and turnover. Hfq facilitates pairing between small regulatory RNAs (sRNAs) and their corresponding mRNA targets by binding both RNAs and bringing them into close proximity. Hfq homologs self-assemble into homo-hexameric rings with at least two distinct surfaces that bind RNA. Recently, another binding site, dubbed the `lateral rim', has been implicated in sRNA·mRNA annealing; the RNA-binding properties of this site appear to be rather subtle, and its degree of evolutionary conservation is unknown...
April 1, 2017: Acta Crystallographica. Section D, Structural Biology
https://www.readbyqxmd.com/read/28368852/biomedical-applications-of-nanodiamond-review
#15
Kostiantyn Turcheniuk, Vadym Mochalin
The interest to applications of nanodiamond in biology and medicine is on the rise over the recent years. This is due to the unique combination of properties that nanodiamond provides. Small size (~ 5 nm), low cost, scalable production, negligible toxicity, chemical inertness of diamond core and rich chemistry of nanodiamond surface, as well as bright and robust fluorescence resistant to photobleaching are the distinct parameters that render nanodiamond superior to any other nanomaterial when it comes to biomedical applications...
April 3, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28363837/when-math-operations-have-visuospatial-meanings-versus-purely-symbolic-definitions-which-solving-stages-and-brain-regions-are-affected
#16
Aryn A Pyke, Jon M Fincham, John R Anderson
How does processing differ during purely symbolic problem solving versus when mathematical operations can be mentally associated with meaningful (here, visuospatial) referents? Learners were trained on novel math operations (↓, ↑), that were defined strictly symbolically or in terms of a visuospatial interpretation (operands mapped to dimensions of shaded areas, answer = total area). During testing (scanner session), no visuospatial representations were displayed. However, we expected visuospatially-trained learners to form mental visuospatial representations for problems, and exhibit distinct activations...
March 28, 2017: NeuroImage
https://www.readbyqxmd.com/read/28363724/hidden-targets-of-ubiquitin-proteasome-system-to-prevent-diabetic-nephropathy
#17
REVIEW
Santosh Kumar Goru, Almesh Kadakol, Anil Bhanudas Gaikwad
Diabetic nephropathy (DN) is the major cause of end stage renal failure. Although, several therapeutic targets have emerged to prevent the progression of DN, the number of people with DN still continues to rise worldwide, suggesting an urgent need of novel targets to prevent DN completely. Currently, the role of ubiquitin proteasome system (UPS) has been highlighted in the pathogenesis and progression of various diseases like obesity, insulin resistance, atherosclerosis, cancers, neurodegerative disorders and including secondary complications of diabetes...
March 29, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28362430/cyld-a20-and-otulin-deubiquitinases-in-nf-%C3%AE%C2%BAb-signaling-and-cell-death-so-similar-yet-so-different
#18
REVIEW
Marie Lork, Kelly Verhelst, Rudi Beyaert
Polyubiquitination of proteins has a pivotal role in the regulation of numerous cellular functions such as protein degradation, DNA repair and cell signaling. As deregulation of these processes can result in pathological conditions such as inflammatory diseases, neurodegeneration or cancer, tight regulation of the ubiquitin system is of tremendous importance. Ubiquitination by E3 ubiquitin ligases can be counteracted by the activity of several deubiquitinating enzymes (DUBs). CYLD, A20 and OTULIN have been implicated as key DUBs in the negative regulation of NF-κB transcription factor-mediated gene expression upon stimulation of cytokine receptors, antigen receptors and pattern recognition receptors, by removing distinct types of polyubiquitin chains from specific NF-κB signaling proteins...
March 31, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28355105/josd1-negatively-regulates-type-i-interferon-antiviral-activity-by-deubiquitinating-and-stabilizing-socs1
#19
Xiaofang Wang, Liting Zhang, Yunli Zhang, Peng Zhao, Liping Qian, Yukang Yuan, Jin Liu, Qiao Cheng, Wenqian Xu, Yibo Zuo, Tingting Guo, Zhengyuan Yu, Hui Zheng
The Josephin domain-containing (JOSD) protein 1 (JOSD1) is recognized as one member of deubiquitinases (DUBs) due to its catalytic "Josephin" domain. However, the in vivo deubiquitinating activity of JOSD1 remains unidentified, and the biological functions of JOSD1 are largely unknown. In this study, we report that JOSD1 plays an important role in regulating type-I interferon (IFN-I)-mediated antiviral activity. JOSD1 physically interacts with SOCS1, which is an essential negative regulator of many cytokines signaling, and enhances SOCS1 stability by deubiquitinating K48-linked polyubiquitination of SOCS1...
March 29, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28343629/biallelic-variants-in-otud6b-cause-an-intellectual-disability-syndrome-associated-with-seizures-and-dysmorphic-features
#20
Teresa Santiago-Sim, Lindsay C Burrage, Frédéric Ebstein, Mari J Tokita, Marcus Miller, Weimin Bi, Alicia A Braxton, Jill A Rosenfeld, Maher Shahrour, Andrea Lehmann, Benjamin Cogné, Sébastien Küry, Thomas Besnard, Bertrand Isidor, Stéphane Bézieau, Isabelle Hazart, Honey Nagakura, LaDonna L Immken, Rebecca O Littlejohn, Elizabeth Roeder, Bulent Kara, Katia Hardies, Sarah Weckhuysen, Patrick May, Johannes R Lemke, Orly Elpeleg, Bassam Abu-Libdeh, Kiely N James, Jennifer L Silhavy, Mahmoud Y Issa, Maha S Zaki, Joseph G Gleeson, John R Seavitt, Mary E Dickinson, M Cecilia Ljungberg, Sara Wells, Sara J Johnson, Lydia Teboul, Christine M Eng, Yaping Yang, Peter-Michael Kloetzel, Jason D Heaney, Magdalena A Walkiewicz
Ubiquitination is a posttranslational modification that regulates many cellular processes including protein degradation, intracellular trafficking, cell signaling, and protein-protein interactions. Deubiquitinating enzymes (DUBs), which reverse the process of ubiquitination, are important regulators of the ubiquitin system. OTUD6B encodes a member of the ovarian tumor domain (OTU)-containing subfamily of deubiquitinating enzymes. Herein, we report biallelic pathogenic variants in OTUD6B in 12 individuals from 6 independent families with an intellectual disability syndrome associated with seizures and dysmorphic features...
April 6, 2017: American Journal of Human Genetics
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