Oligomers of amyloid β42 (Aβ42) rather than fibrils, drive the pathogenesis of Alzheimer’s disease (AD). In particular, toxic oligomeric species called protofibrils (PFs) have attracted significant attention. Herein, we report RNA aptamers with higher affinity toward PFs derived from a toxic Aβ42 dimer than toward fibrils produced from wild-type Aβ42 or from a toxic, conformationally constrained Aβ42 variant, E22P-Aβ42. We obtained these RNA aptamers by using the pre-incubated dimer model of E22P-Aβ42,...
07:30
The voltage-gated potassium channel Kv1.5 plays important roles in atrial repolarization and regulation of vascular tone. In the present study, we investigated the effects of mechanical stretch on Kv1.5 channels. We induced mechanical stretch by centrifuging or culturing Kv1.5-expressing HEK 293 cells and neonatal rat ventricular myocytes in low osmolarity (LO) medium, and then recorded Kv1.5 current (IKv1.5) in a normal, isotonic solution. We observed that mechanical stretch increased IKv1.5, and...
00:30
The interplay between the transforming growth factor β (TGF-β) signaling proteins, SMAD family member 2 (SMAD2) and SMAD3, and the TGF-β inhibiting SMAD, SMAD7, seems to play a vital role in proper pancreatic endocrine development, and also in normal β cell function in adult pancreatic islets. Here, we generated conditional SMAD7 knockout mice by crossing insulin1Cre mice with SMAD7fx/fx mice. We also created a β cell-specific SMAD7 overexpressing mouse line by crossing insulin1Dre mice with HPRT-SMAD7/RosaGFP...
Mon Mar 02, 2020 23:30
The linear ubiquitin assembly complex (LUBAC) is an essential component of the innate and adaptive immune system. Modification of cellular substrates with linear polyubiquitin chains is a key regulatory step in signal transduction that impacts cell death and inflammatory signaling downstream of various innate immunity receptors. Loss of function mutations in the LUBAC components HOIP and HOIL-1 yields a systemic autoinflammatory disease in humans, while their genetic ablation is embryonically lethal...
Mon Mar 02, 2020 21:30
Heterotrimeric G proteins are the core upstream elements that transduce and amplify the cellular signals from G protein-coupled receptors (GPCRs) to intracellular effectors. GPCRs are the largest family of membrane proteins encoded in the human genome and are the targets of about one third of prescription medicines. However, to date, no single therapeutic agent exerts its effects via perturbing heterotrimeric G protein function, despite a plethora of evidence linking G protein malfunction to human...
Mon Mar 02, 2020 15:30
Specificity protein 1 (Sp1) is an important transcription factor implicated in numerous cellular processes. However, whether Sp1 is involved in the regulation of RNA polymerase Ⅲ (Pol Ⅲ)-directed gene transcription in human cells remains unknown. Here, we first show that filamin A (FLNA) represses Sp1 expression as well as expression of TFIIB-related factor 1 (BRF1) and general transcription factor Ⅲ C subunit 2(GTF3C2) in HeLa, 293T and SaOS2 cells lines stably expressing FLNA-silencing shRNAs....
Sun Mar 01, 2020 23:30
Nitrate is one of the major inorganic nitrogen sources for microbes. Many bacterial and archaeal lineages have the capacity to express assimilatory nitrate reductase (NAS), which catalyzes the rate-limiting reduction of nitrate to nitrite. Although a nitrate assimilatory pathway in mycobacteria has been proposed and validated physiologically and genetically, the putative NAS enzyme has yet to be identified. Here, we report the characterization of a novel NAS encoded by Mycolicibacterium smegmatis...
Sat Feb 29, 2020 01:38
P-glycoprotein (P-gp; also known as MDR1 or ABCB1) is an ATP-driven multidrug transporter that extrudes various hydrophobic toxic compounds to the extracellular space. P-gp consists of two transmembrane domains (TMDs) that form the substrate translocation pathway and two nucleotide-binding domains (NBDs) that bind and hydrolyze ATP. At least two P-gp states are required for transport. In the inward-facing (pre-drug transport) conformation, the two NBDs are separated, and the two TMDs are open to...
Fri Feb 28, 2020 22:30
A disintegrin and metalloprotease 10 (ADAM10) is a transmembrane protein essential for embryonic development, and its dysregulation underlies disorders such as cancer, Alzheimer’s disease and inflammation. ADAM10 is a “molecular scissor” that proteolytically cleaves the extracellular region from >100 substrates, including Notch, amyloid precursor protein, cadherins, growth factors, and chemokines. ADAM10 has been recently proposed to function as six distinct scissors with different substrates,...
Fri Feb 28, 2020 21:30
Motor protein-based active transport is essential for mRNA localization and local translation in animal cells, yet how mRNA granules interact with motor proteins remains poorly understood. Using an unbiased yeast-two-hybrid screen for interactions between murine RNA binding proteins (RBPs) and motor proteins, here we identified protein interaction with APP tail 1 (PAT1) as a potential direct adapter between zipcode binding protein 1 (ZBP1, a β-actin RBP) and the Kinesin-I motor complex. The amino...
Fri Feb 28, 2020 19:31
The WW domain is a modular protein structure that recognizes the proline-rich Pro–Pro-x-Tyr (PPxY) motif contained in specific target proteins. The compact modular nature of the WW domain makes it ideal for mediating interactions between proteins in complex networks and signaling pathways of the cell (e.g. the Hippo pathway). As a result, WW domains play key roles in a plethora of both normal and disease processes. Intriguingly, RNA and DNA viruses have evolved strategies to hijack cellular WW domain–containing...
Fri Feb 28, 2020 19:31
Group A flavin-dependent monooxygenases catalyze the cleavage of the oxygen-oxygen bond of dioxygen, followed by the incorporation of one oxygen atom into the substrate molecule with the aid of NADPH and FAD. These flavoenzymes play an important role in many biological processes, and their most distinct structural feature is the choreographed motions of flavin, which typically adopts two distinct conformations (OUT and IN) to fulfill its function. Notably, these enzymes seem to have evolved a delicate...
Fri Feb 28, 2020 17:31
Chronic wasting disease (CWD) is caused by an unknown spectrum of prions and has become enzootic in populations of cervid species that express PrPC molecules varying in amino acid composition. These PrPC polymorphisms can affect prion transmission, disease progression, neuropathology, and emergence of new prion strains, but the mechanistic steps in prion evolution are not understood. Here, using conformation-dependent immunoassay (CDI), conformation stability assay (CSA) and protein misfolding cyclic...
Fri Feb 28, 2020 17:31
Leucine-rich repeat kinase 2 (LRRK2) encodes a complex protein that includes both kinase and GTPase domains. Genome-wide association studies have identified dominant LRRK2 alleles that predispose their carriers to late-onset idiotypic Parkinson’s disease (PD) and also to autoimmune disorders such as Crohn’s disease. Considerable evidence indicates that PD initiation and progression involve the activation of innate immune functions in microglia, which are brain-resident macrophages. Here, we asked...
Fri Feb 28, 2020 17:31
Microtubules are cytoskeletal structures critical for mitosis, cell motility, and protein and organelle transport, and are a validated target for anticancer drugs. However, how tubulins are regulated and recruited to support these distinct cellular processes is incompletely understood. Post-translational modifications of tubulins are proposed to regulate microtubule functions and dynamics. Although many of these modifications have been investigated, only one prior study reports on tubulin methylation...
Fri Feb 28, 2020 16:30
Thyroid, Ahead of Print.
Mon Mar 02, 2020 10:00
Thyroid, Ahead of Print.
Mon Mar 02, 2020 10:00
The Journal of Alternative and Complementary Medicine, Ahead of Print.
Mon Mar 02, 2020 10:00
The Journal of Alternative and Complementary Medicine, Ahead of Print.
Fri Feb 28, 2020 10:00
The Journal of Alternative and Complementary Medicine, Ahead of Print.
Fri Feb 28, 2020 10:00
Abstract Cellular adaptation to various types of stress requires a complex network of steps that altogether lead to reconstitution of redox balance, degradation of damaged macromolecules and restoration of cellular metabolism. Advances in our understanding of the interplay between cellular signalling and signal translation paint a complex picture of multi-layered paths of regulation. In this review we explore the link between cellular adaptation to metabolic and oxidative stresses...
02:00
In the original publication of this manuscript [1], Fig. 2 contains incorrect labels and feedback loops. The revised version of Fig. 2 is shown below.
02:00
Abstract Background FK506-binding protein 9 (FKBP9) is amplified in high-grade gliomas (HGGs). However, the roles and mechanism(s) of FKBP9 in glioma are unknown. Methods The expression of FKBP9 in clinical glioma tissues was detected by immunohistochemistry (IHC). The correlation between FKBP9 expression levels and the clinical prognosis of...
Fri Feb 28, 2020 02:00
Abstract Introduction We used data from MOBI-Kids, a 14-country international collaborative case–control study of brain tumors (BTs), to study clinical characteristics of the tumors in older children (10 years or older), adolescents and young adults (up to the age of 24). Methods Information from clinical records was obtained for 899 BT cases, including...
02:00
Abstract Introduction Opening of the blood–brain barrier (BBB) by pulsed low intensity ultrasound has been developed during the last decade and is now recognized as a safe technique to transiently and repeatedly open the BBB. This non- or minimally invasive technique allows for a targeted and uniform dispersal of a wide range of therapeutic substances throughout the brain, including immune cells and antibodies. ...
Fri Feb 28, 2020 02:00
German chemical giant BASF has steadily been saturating the 3D printing industry with its presence. The latest partnership established by the world’s largest chemical company is with machine tool manufacturer Cincinnati Incorporated (CI). The two inked a distribution deal in which CI will supply ABS, carbon fiber PET and recycled PET materials from BASF 3D Printing Solutions (B3DPS) for use with its Small Area Additive Manufacturing (SAAM HT) 3D printer. The SAAM HT 3D printer from CI. Image courtesy...
04:25
Today Max and I speak with Xometry’s Greg Paulson again. This time we talk about scale in 3D printing. With manufacturing and real production seen as the new 3D printing frontier, companies are gearing up for products, services and the ever-popular “end to end solutions.” But, can we really do scale in 3D printing? And also should we want to do millions of low-cost parts? Or should we focus on scale but in limited verticals and applications? Can you do low cost and high-value parts at the same time?...
Mon Mar 02, 2020 16:53
In a previous post on the subject, we revisited 3D-printed sex toys. The topic was such a titillating one a few years ago that it was covered on a broad range of mainstream media outlets and the SEO-friendly term “3D-printed sex toy” brought to the fore the concept of customized devices for sexual pleasure that one could print at home. Though it seemed, for a time, that everyone would soon be fabricating sex toys on their personal 3D printers, the idea didn’t quite pan out. This was probably due...
Mon Mar 02, 2020 16:15
Researchers from Iran and the UK are taking on central topics in digital fabrication, delving deeper into parameters, properties, and composites, with their findings outlined in the recently published ‘The Synergic Effects of FDM 3D Printing Parameters on Mechanical Behaviors of Bronze Poly Lactic Acid Composites.’ The authors use optimization in this study to find out more about the effects of printing on a bronze PLA composite. Popular due to its plant-based origins and biodegradable and biocompatible...
Mon Mar 02, 2020 10:56
Aluna Everitt recently submitted her thesis, ‘Digital Fabrication Approaches for the Design and Development of Shape-Changing Displays,’ to the Faculty of Science and Technology at Lancaster University. To achieve better success with deformable surfaces, Everitt explores the uses of 3D printing and laser cutting. As technology continues to progress worldwide, shape-changing displays are just one element that make users lives easier with features like tangible interaction, enhancing applications...
Mon Mar 02, 2020 10:52
Researchers from Canada and China have created a new technique for improving 3D printing, outlined in the recently published ‘Topology Optimization for Multipatch Fused Deposition Modeling 3D Printing.’ The authors point out that as digital fabrication progresses further, new design rules are emerging, as well as constraints. These are related to supports and post-processing, size limitations, directional material properties, cellular structure, topology design, and more. Constrictions caused by...
Mon Mar 02, 2020 10:35
Janne Kyttanen is truly a 3D printing pioneer having spearheaded product design and consumer, industrial design, furniture, clothing, and other products with 3D printing. Roles at Materialise and 3D Systems as well as his own startups have prepared him to become the world’s unlikeliest VC. We spoke to him previously on investing in 3D printing, creativity in 3D printing and interviewed him during an entertaining podcast. With a designer heart and mind, he is now trying to design 3D printing businesses...
Mon Mar 02, 2020 10:34
MIT scientists are researching new ways to improve automated systems, outlining their findings in the recently published ‘Scalable and Probabilistically Complete Planning for Robotic Spatial Extrusion.’ Exploring new ways to integrate robotics into production, the authors have created a new concept for robotic spatial extrusion, accompanied by complete planning algorithms. Focusing on an alternative to the traditional 3D printing layering method, the researchers sought to overcome current challenges...
Sun Mar 01, 2020 10:52
It’s necessary to perform studies on medical devices, 3D printed or otherwise, to make sure they’re working the way they’re supposed to be. Some examples we’ve heard about include: a Virginia Tech researcher used sensors to compile data about how well 3D printed amniotic band prosthetics were performing, researchers from TU Delft evaluated the level of functionality for a 3D printed hand prosthetic, and a team from the University of Nebraska at Omaha (UNO) investigated how a 3D printed partial finger...
Sat Feb 29, 2020 11:17
In today’s 3D Printing News Briefs, AMUG has announced the recipients of its two scholarships, Ultimaker is marking a milestone with a new online marketplace and new Cura features, and a company has created a revolutionary 3D printed helmet to help children with flat head syndrome. AMUG Announces Scholarship Recipients The Additive Manufacturing Users Group (AMUG) just announced the two recipients of its annual scholarships, who will now be recognized at the AMUG Conference in Chicago next month....
Fri Feb 28, 2020 18:08
“Here’s lookin’ at you, kid.” “Hasta la vista, baby.” “Life is like a box of chocolates.” “Game over, man, game over!” These are all memorable lines from iconic films, though some people may not recognize the last one. This is a line from one of my absolute favorite movies, the 1986 Aliens, and was uttered by Private Hudson, played by Bill Paxton, after (most of) the group narrowly escapes with their lives from a close encounter with the film’s titular creatures. (Image: IMDB) Needless to say,...
Fri Feb 28, 2020 10:35
Chinese researchers are experimenting with materials for bioprinting, outlining their findings in the recently published ‘Dual-Enzyme Crosslinking and Post-polymerization for Printing of Polysaccharide-Polymer Hydrogel.’ Tissue engineering, while yielding many successful and astounding efforts in research labs today—from the creation of a variety of hydrogels to scaffolds, to kidney organoids—is a complex area requiring much trial and error as cells can be considerably (and understandably) difficult...
Fri Feb 28, 2020 09:06
Pediatric Allergy, Immunology, and Pulmonology, Ahead of Print.
Mon Mar 02, 2020 10:00
Pediatric Allergy, Immunology, and Pulmonology, Ahead of Print.
Fri Feb 28, 2020 10:00
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