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Science Signaling

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https://www.readbyqxmd.com/read/28720718/phosphorylation-of-amyloid-precursor-protein-by-mutant-lrrk2-promotes-aicd-activity-and-neurotoxicity-in-parkinson-s-disease
#1
Zhong-Can Chen, Wei Zhang, Ling-Ling Chua, Chou Chai, Rong Li, Lin Lin, Zhen Cao, Dario C Angeles, Lawrence W Stanton, Jian-He Peng, Zhi-Dong Zhou, Kah-Leong Lim, Li Zeng, Eng-King Tan
Mutations in LRRK2, which encodes leucine-rich repeat kinase 2, are the most common genetic cause of familial and sporadic Parkinson's disease (PD), a degenerative disease of the central nervous system that causes impaired motor function and, in advanced stages, dementia. Dementia is a common symptom of another neurodegenerative disease, Alzheimer's disease, and research suggests that there may be pathophysiological and genetic links between the two diseases. Aggregates of β amyloid [a protein produced through cleavage of amyloid precursor protein (APP)] are seen in both diseases and in PD patients carrying G2019S-mutant LRRK2...
July 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28720717/sting-is-an-essential-mediator-of-the-ku70-mediated-production-of-ifn-%C3%AE-1-in-response-to-exogenous-dna
#2
Hongyan Sui, Ming Zhou, Hiromi Imamichi, Xiaoli Jiao, Brad T Sherman, H Clifford Lane, Tomozumi Imamichi
We previously identified Ku70, a subunit of a DNA repair protein complex, as a cytosolic DNA sensor that induces the production of interferon-λ1 (IFN-λ1) by human primary cells and cell lines. IFN-λ1 is a type III IFN and has similar antiviral activity to that of the type I IFNs (IFN-α and IFN-β). We observed that human embryonic kidney (HEK) 293T cells, which are deficient in the innate immune adaptor protein STING (stimulator of IFN genes), did not produce IFN-λ1 in response to DNA unless they were reconstituted with STING...
July 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28720716/pi3k%C3%AE-activity-in-leukocytes-promotes-adipose-tissue-inflammation-and-early-onset-insulin-resistance-during-obesity
#3
Ludovic Breasson, Barbara Becattini, Claudia Sardi, Angela Molinaro, Fabio Zani, Romina Marone, Fabrizio Botindari, Mélanie Bousquenaud, Curzio Ruegg, Matthias P Wymann, Giovanni Solinas
The phosphoinositide 3-kinase γ (PI3Kγ) plays a major role in leukocyte recruitment during acute inflammation and has been proposed to inhibit classical macrophage activation by driving immunosuppressive gene expression. PI3Kγ plays an important role in diet-induced obesity and insulin resistance. In seeking to determine the underlying molecular mechanisms, we showed that PI3Kγ action in high-fat diet-induced inflammation and insulin resistance depended largely on its role in the control of adiposity, which was due to PI3Kγ activity in a nonhematopoietic cell type...
July 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28698220/activation-of-camkiv-by-soluble-amyloid-%C3%AE-1-42-impedes-trafficking-of-axonal-vesicles-and-impairs-activity-dependent-synaptogenesis
#4
Daehun Park, Myeongsu Na, Jung Ah Kim, Unghwi Lee, Eunji Cho, Mirye Jang, Sunghoe Chang
The prefibrillar form of soluble amyloid-β (sAβ1-42) impairs synaptic function and is associated with the early phase of Alzheimer's disease (AD). We investigated how sAβ1-42 led to presynaptic defects using a quantum dot-based, single particle-tracking method to monitor synaptic vesicle (SV) trafficking along axons. We found that sAβ1-42 prevented new synapse formation induced by chemical long-term potentiation (cLTP). In cultured rat hippocampal neurons, nanomolar amounts of sAβ1-42 impaired Ca(2+) clearance from presynaptic terminals and increased the basal Ca(2+) concentration...
July 11, 2017: Science Signaling
https://www.readbyqxmd.com/read/28698219/the-transcription-factor-c-ebp%C3%AE-in-the-dorsal-root-ganglion-contributes-to-peripheral-nerve-trauma-induced-nociceptive-hypersensitivity
#5
Zhisong Li, Yuanyuan Mao, Lingli Liang, Shaogen Wu, Jingjing Yuan, Kai Mo, Weihua Cai, Qingxiang Mao, Jing Cao, Alex Bekker, Wei Zhang, Yuan-Xiang Tao
Changes in gene transcription in the dorsal root ganglion (DRG) after nerve trauma contribute to the genesis of neuropathic pain. We report that peripheral nerve trauma caused by chronic constriction injury (CCI) increased the abundance of the transcription factor C/EBPβ (CCAAT/enhancer binding protein β) in the DRG. Blocking this increase mitigated the development and maintenance of CCI-induced mechanical, thermal, and cold pain hypersensitivities without affecting basal responses to acute pain and locomotor activity...
July 11, 2017: Science Signaling
https://www.readbyqxmd.com/read/28698218/heart-failure-inhibitor
#6
John F Foley
Targeting a G protein-coupled receptor in cardiomyocytes offers protection in a mouse model of cardiac failure.
July 11, 2017: Science Signaling
https://www.readbyqxmd.com/read/28698217/new-connections-amyloid-%C3%AE-calcium-and-the-synapse
#7
Leslie K Ferrarelli
Insight into how amyloid-β impairs synaptic function reveals potential therapeutic targets for patients with Alzheimer's disease.
July 11, 2017: Science Signaling
https://www.readbyqxmd.com/read/28698216/paper-of-note-in-science-translational-medicine9-397
#8
Leslie K Ferrarelli
This week's article describes how chemotherapy unintentionally enhances the dissemination of cancer cells into the circulation.
July 11, 2017: Science Signaling
https://www.readbyqxmd.com/read/28698215/paper-of-note-in-science357-6346
#9
Annalisa M VanHook
This week's article offers a possible explanation for how Zika virus causes microcephaly.
July 11, 2017: Science Signaling
https://www.readbyqxmd.com/read/28698214/papers-of-note-in-nature547-7661
#10
Annalisa M VanHook
This week's articles highlight progress in predicting T cell receptor specificity; an evolutionarily ancient form of antiviral defense; a mechanism of chemotherapy-induced cell death; metabolic rewiring in cancer cells; and structural insights into activation of a GPCR and of a mechanosensitive ion channel.
July 11, 2017: Science Signaling
https://www.readbyqxmd.com/read/28698213/gene-expression-profiles-of-brain-endothelial-cells-during-embryonic-development-at-bulk-and-single-cell-levels
#11
Mike Hupe, Minerva Xueting Li, Susanne Kneitz, Daria Davydova, Chika Yokota, Julianna Kele-Olovsson, Belma Hot, Jan M Stenman, Manfred Gessler
The blood-brain barrier is a dynamic interface that separates the brain from the circulatory system, and it is formed by highly specialized endothelial cells. To explore the molecular mechanisms defining the unique nature of vascular development and differentiation in the brain, we generated high-resolution gene expression profiles of mouse embryonic brain endothelial cells using translating ribosome affinity purification and single-cell RNA sequencing. We compared the brain vascular translatome with the vascular translatomes of other organs and analyzed the vascular translatomes of the brain at different time points during embryonic development...
July 11, 2017: Science Signaling
https://www.readbyqxmd.com/read/28698212/erratum-for-the-research-article-agrobacterium-counteracts-host-induced-degradation-of-its-effector-f-box-protein-by-s-magori-and-v-citovsky
#12
(no author information available yet)
No abstract text is available yet for this article.
July 11, 2017: Science Signaling
https://www.readbyqxmd.com/read/28676491/a-perspective-on-akt-25-plus-years-after-its-discovery
#13
REVIEW
Maria D Paraskevopoulou, Philip N Tsichlis
Since its discovery more than 25 years ago, the kinase AKT has become a central figure in cell signaling. We highlight some of the landmark findings in those 25 years that contributed to our understanding of the regulation and function of AKT in directing cellular processes and behavior. Future progress toward fully understanding the roles of AKT in cell, tissue, and organismal biology will depend on technological innovations and the combination of in-depth reductionist analyses with systems-based strategies...
July 4, 2017: Science Signaling
https://www.readbyqxmd.com/read/28676490/tgf-%C3%AE-promotes-pi3k-akt-signaling-and-prostate-cancer-cell-migration-through-the-traf6-mediated-ubiquitylation-of-p85%C3%AE
#14
Anahita Hamidi, Jie Song, Noopur Thakur, Susumu Itoh, Anders Marcusson, Anders Bergh, Carl-Henrik Heldin, Maréne Landström
Transforming growth factor-β (TGF-β) is a pluripotent cytokine that regulates cell fate and plasticity in normal tissues and tumors. The multifunctional cellular responses evoked by TGF-β are mediated by the canonical SMAD pathway and by noncanonical pathways, including mitogen-activated protein kinase (MAPK) pathways and the phosphatidylinositol 3'-kinase (PI3K)-protein kinase B (AKT) pathway. We found that TGF-β activated PI3K in a manner dependent on the activity of the E3 ubiquitin ligase tumor necrosis factor receptor-associated factor 6 (TRAF6)...
July 4, 2017: Science Signaling
https://www.readbyqxmd.com/read/28676489/voltage-dependent-ca-2-entry-into-smooth-muscle-during-contraction-promotes-endothelium-mediated-feedback-vasodilation-in-arterioles
#15
Christopher J Garland, Pooneh Bagher, Chloe Powell, Xi Ye, Hamish A L Lemmey, Lyudmyla Borysova, Kim A Dora
Vascular smooth muscle contraction is suppressed by feedback dilation mediated by the endothelium. In skeletal muscle arterioles, this feedback can be activated by Ca(2+) signals passing from smooth muscle through gap junctions to endothelial cells, which protrude through holes in the internal elastic lamina to make contact with vascular smooth muscle cells. Although hypothetically either Ca(2+) or inositol trisphosphate (IP3) may provide the intercellular signal, it is generally thought that IP3 diffusion is responsible...
July 4, 2017: Science Signaling
https://www.readbyqxmd.com/read/28676488/papers-of-note-in-science-immunology2-12
#16
John F Foley
This month's articles show how Plasmodium by-products cause bone loss and how citrullination of an NF-κB subunit enhances inflammatory responses.
July 4, 2017: Science Signaling
https://www.readbyqxmd.com/read/28676487/papers-of-note-in-nature546-7660
#17
Annalisa M VanHook
This week's articles highlight a mechanism by which melanoma cells prepare the metastatic niche, intestinal defense against rotavirus, and immune tolerance in the human fetus.
July 4, 2017: Science Signaling
https://www.readbyqxmd.com/read/28676486/papers-of-note-in-science356-6345
#18
Annalisa M VanHook
This week's articles address the release of volatile organic compounds from plant cells, a gene regulatory network that ensures proper neural patterning despite variability in morphogen gradients, and a role for adenosine signaling in the plasticity of an auditory circuit.
July 4, 2017: Science Signaling
https://www.readbyqxmd.com/read/28676485/papers-of-note-in-science-translational-medicine9-396
#19
Leslie K Ferrarelli
This week's articles describe ways to potentially treat lymphoma and fatty liver-associated fibrosis.
July 4, 2017: Science Signaling
https://www.readbyqxmd.com/read/28676484/a-therapy-for-fxs
#20
Leslie K Ferrarelli
The antidiabetic drug metformin might be repurposed to treat patients with fragile X syndrome.
July 4, 2017: Science Signaling
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