bluuebunny/crossref_metadata_2025_split huggingface dataset:
SIRT6-dependent cysteine monoubiquitination in the PRE-SET domain of Suv39h1 regulates the NF-κB pathway
Authors: Santos-Barriopedro Irene , Bosch-Presegué Laia , Marazuela-Duque Anna , de la Torre Carolina , Colomer Carlota , Vazquez Berta N. , Fuhrmann Thomas , Martínez-Pastor Bárbara , Lu Wenfu , Braun Thomas , Bober Eva , Jenuwein Thomas , Serrano Lourdes , Esteller Manel , Chen Zhenbang , Barceló-Batllori Silvia , Mostoslavsky Raúl , Espinosa Lluis , Vaquero Alejandro 
Published: January 2018

AbstractSirtuins are NAD+-dependent deacetylases that facilitate cellular stress response. They include SirT6, which protects genome stability and regulates metabolic homeostasis through gene silencing, and whose loss induces an accelerated aging phenotype directly linked to hyperactivation of the NF-κB pathway. Here we show that SirT6 binds to the H3K9me3-specific histone methyltransferase Suv39h1 and induces monoubiquitination of conserved cysteines in the PRE-SET domain of Suv39h1. Following activation of NF-κB signaling Suv39h1 is released from the IκBα locus, subsequently repressing the NF-κB pathway. We propose that SirT6 attenuates the NF-κB pathway through IκBα upregulation via cysteine monoubiquitination and chromatin eviction of Suv39h1. We suggest a mechanism based on SirT6-mediated enhancement of a negative feedback loop that restricts the NF-κB pathway.
Versatile and on-demand biologics co-production in yeast
Authors: Cao Jicong , Perez-Pinera Pablo , Lowenhaupt Ky , Wu Ming-Ru , Purcell Oliver , de la Fuente-Nunez Cesar , Lu Timothy K. 
Published: January 2018

AbstractCurrent limitations to on-demand drug manufacturing can be addressed by technologies that streamline manufacturing processes. Combining the production of two or more drugs into a single batch could not only be useful for research, clinical studies, and urgent therapies but also effective when combination therapies are needed or where resources are scarce. Here we propose strategies to concurrently produce multiple biologics from yeast in single batches by multiplexing strain development, cell culture, separation, and purification. We demonstrate proof-of-concept for three biologics co-production strategies: (i) inducible expression of multiple biologics and control over the ratio between biologic drugs produced together; (ii) consolidated bioprocessing; and (iii) co-expression and co-purification of a mixture of two monoclonal antibodies. We then use these basic strategies to produce drug mixtures as well as to separate drugs. These strategies offer a diverse array of options for on-demand, flexible, low-cost, and decentralized biomanufacturing applications without the need for specialized equipment.
HoxC5 and miR-615-3p target newly evolved genomic regions to repress hTERT and inhibit tumorigenesis
Authors: Yan TingDong , Ooi Wen Fong , Qamra Aditi , Cheung Alice , Ma DongLiang , Sundaram Gopinath Meenakshi , Xu Chang , Xing Manjie , Poon LaiFong , Wang Jing , Loh Yan Ping , Ho Jess Hui Jie , Ng Joscelyn Jun Quan , Ramlee Muhammad Khairul , Aswad Luay , Rozen Steve G. , Ghosh Sujoy , Bard Frederic A. , Sampath Prabha , Tergaonkar Vinay , Davies James O. J. , Hughes Jim R. , Goh Eyleen , Bi Xuezhi , Fullwood Melissa Jane , Tan Patrick , Li Shang 
Published: January 2018

AbstractThe repression of telomerase activity during cellular differentiation promotes replicative aging and functions as a physiological barrier for tumorigenesis in long-lived mammals, including humans. However, the underlying mechanisms remain largely unclear. Here we describe how miR-615-3p represses hTERT expression. mir-615-3p is located in an intron of the HOXC5 gene, a member of the highly conserved homeobox family of transcription factors controlling embryogenesis and development. Unexpectedly, we found that HoxC5 also represses hTERT expression by disrupting the long-range interaction between hTERT promoter and its distal enhancer. The 3′UTR of hTERT and its upstream enhancer region are well conserved in long-lived primates. Both mir-615-3p and HOXC5 are activated upon differentiation, which constitute a feed-forward loop that coordinates transcriptional and post-transcriptional repression of hTERT during cellular differentiation. Deregulation of HOXC5 and mir-615-3p expression may contribute to the activation of hTERT in human cancers.
A proline deletion in IFNAR1 impairs IFN-signaling and underlies increased resistance to tuberculosis in humans
Authors: Zhang Guoliang , deWeerd Nicole A. , Stifter Sebastian A. , Liu Lei , Zhou Boping , Wang Wenfei , Zhou Yiping , Ying Binwu , Hu Xuejiao , Matthews Antony Y. , Ellis Magda , Triccas James A. , Hertzog Paul J. , Britton Warwick J. , Chen Xinchun , Feng Carl G. 
Published: January 2018

AbstractType I interferons (IFN), best known for their anti-viral functions, have been shown to impair host resistance to intracellular bacteria in mice. However, the precise role of type I IFN signaling in bacterial infection in humans is unclear. Here, we show that genetic variation in the human IFNAR1 gene is associated with decreased susceptibility to tuberculosis and an increased risk of viral hepatitis in Chinese populations. Receptor mutagenesis and cell signaling studies establish that the IFNAR1 mutation corresponding to a proline deletion in the hinge region of the membrane-proximal domain of IFNAR1 decreases the binding affinity of IFNAR1 to IFN-β, impeding type I IFN signaling. Our findings suggest that IFNAR1 signaling underlies an increased risk of tuberculosis in humans and reveals a function for the IFNAR1 inter-domain region in cytokine–cytokine receptor interaction and signal transduction.
Interneuron-specific signaling evokes distinctive somatostatin-mediated responses in adult cortical astrocytes
Authors: Mariotti Letizia , Losi Gabriele , Lia Annamaria , Melone Marcello , Chiavegato Angela , Gómez-Gonzalo Marta , Sessolo Michele , Bovetti Serena , Forli Angelo , Zonta Micaela , Requie Linda Maria , Marcon Iacopo , Pugliese Arianna , Viollet Cécile , Bettler Bernhard , Fellin Tommaso , Conti Fiorenzo , Carmignoto Giorgio 
Published: January 2018

AbstractThe signaling diversity of GABAergic interneurons to post-synaptic neurons is crucial to generate the functional heterogeneity that characterizes brain circuits. Whether this diversity applies to other brain cells, such as the glial cells astrocytes, remains unexplored. Using optogenetics and two-photon functional imaging in the adult mouse neocortex, we here reveal that parvalbumin- and somatostatin-expressing interneurons, two key interneuron classes in the brain, differentially signal to astrocytes inducing weak and robust GABAB receptor-mediated Ca2+ elevations, respectively. Furthermore, the astrocyte response depresses upon parvalbumin interneuron repetitive stimulations and potentiates upon somatostatin interneuron repetitive stimulations, revealing a distinguished astrocyte plasticity. Remarkably, the potentiated response crucially depends on the neuropeptide somatostatin, released by somatostatin interneurons, which activates somatostatin receptors at astrocytic processes. Our study unveils, in the living brain, a hitherto unidentified signaling specificity between interneuron subtypes and astrocytes opening a new perspective into the role of astrocytes as non-neuronal components of inhibitory circuits.
Carotenoid metabolism strengthens the link between feather coloration and individual quality
Authors: Weaver Ryan J. , Santos Eduardo S. A. , Tucker Anna M. , Wilson Alan E. , Hill Geoffrey E. 
Published: January 2018

AbstractThirty years of research has made carotenoid coloration a textbook example of an honest signal of individual quality, but tests of this idea are surprisingly inconsistent. Here, to investigate sources of this heterogeneity, we perform meta-analyses of published studies on the relationship between carotenoid-based feather coloration and measures of individual quality. To create color displays, animals use either carotenoids unchanged from dietary components or carotenoids that they biochemically convert before deposition. We hypothesize that converted carotenoids better reflect individual quality because of the physiological links between cellular function and carotenoid metabolism. We show that feather coloration is an honest signal of some, but not all, measures of quality. Where these relationships exist, we show that converted, but not dietary, carotenoid coloration drives the relationship. Our results have broad implications for understanding the evolutionary role of carotenoid coloration and the physiological mechanisms that maintain signal honesty of animal ornamental traits.
Disclosing the double mutualist role of birds on Galápagos
Authors: Olesen Jens M. , Damgaard Christian F. , Fuster Francisco , Heleno Ruben H. , Nogales Manuel , Rumeu Beatriz , Trøjelsgaard Kristian , Vargas Pablo , Traveset Anna 
Published: January 2018

AbstractLife on oceanic islands deviate in many ways from that on the mainland. Their biodiversity is relatively poor and some groups are well-represented, others not, especially not insects. A scarcity of insects forces birds to explore alternative food, such as nectar and fruit. In this way, island birds may pollinate and disperse seed to an extent unseen on any mainland; they may even first consume floral resources of a plant species and then later harvest the fruit of the same species. Through this biotic reuse, they may act as double mutualists. The latter have never been studied at the level of the network, because they are traditionally considered rare. We sampled pollination and seed-dispersal interactions on Galápagos and constructed a plant-bird mutualism network of 108 plant (12% being double mutualists) and 21 bird species (48% being double mutualists), and their 479 interactions, being either single (95%) or double mutualisms (5%). Double mutualists constitute the core in the pollination-dispersal network, coupling the two link types together. They may also initiate positive feedbacks (more pollination leading to more dispersal), which theoretically are known to be unstable. Thus, double mutualisms may be a necessary, but risky prerequisite to the survival of island biodiversity.
In situ immune response and mechanisms of cell damage in central nervous system of fatal cases microcephaly by Zika virus
Authors: Azevedo Raimunda S. S. , de Sousa Jorge R. , Araujo Marialva T. F. , Martins Filho Arnaldo J. , de Alcantara Bianca N. , Araujo Fernanda M. C. , Queiroz Maria G. L. , Cruz Ana C. R. , Vasconcelos Beatriz H. Baldez , Chiang Jannifer O. , Martins Lívia C. , Casseb Livia M. N. , da Silva Eliana V. , Carvalho Valéria L. , Vasconcelos Barbara C. Baldez , Rodrigues Sueli G. , Oliveira Consuelo S. , Quaresma Juarez A. S. , Vasconcelos Pedro F. C. 
Published: January 2018

AbstractZika virus (ZIKV) has recently caused a pandemic disease, and many cases of ZIKV infection in pregnant women resulted in abortion, stillbirth, deaths and congenital defects including microcephaly, which now has been proposed as ZIKV congenital syndrome. This study aimed to investigate the in situ immune response profile and mechanisms of neuronal cell damage in fatal Zika microcephaly cases. Brain tissue samples were collected from 15 cases, including 10 microcephalic ZIKV-positive neonates with fatal outcome and five neonatal control flavivirus-negative neonates that died due to other causes, but with preserved central nervous system (CNS) architecture. In microcephaly cases, the histopathological features of the tissue samples were characterized in three CNS areas (meninges, perivascular space, and parenchyma). The changes found were mainly calcification, necrosis, neuronophagy, gliosis, microglial nodules, and inflammatory infiltration of mononuclear cells. The in situ immune response against ZIKV in the CNS of newborns is complex. Despite the predominant expression of Th2 cytokines, other cytokines such as Th1, Th17, Treg, Th9, and Th22 are involved to a lesser extent, but are still likely to participate in the immunopathogenic mechanisms of neural disease in fatal cases of microcephaly caused by ZIKV.
LSD1 activation promotes inducible EMT programs and modulates the tumour microenvironment in breast cancer
Authors: Boulding T. , McCuaig R. D. , Tan A. , Hardy K. , Wu F. , Dunn J. , Kalimutho M. , Sutton C. R. , Forwood J. K. , Bert A. G. , Goodall G. J. , Malik L. , Yip D. , Dahlstrom J. E. , Zafar A. , Khanna K. K. , Rao S. 
Published: January 2018

AbstractComplex regulatory networks control epithelial-to-mesenchymal transition (EMT) but the underlying epigenetic control is poorly understood. Lysine-specific demethylase 1 (LSD1) is a key histone demethylase that alters the epigenetic landscape. Here we explored the role of LSD1 in global epigenetic regulation of EMT, cancer stem cells (CSCs), the tumour microenvironment, and therapeutic resistance in breast cancer. LSD1 induced pan-genomic gene expression in networks implicated in EMT and selectively elicits gene expression programs in CSCs whilst repressing non-CSC programs. LSD1 phosphorylation at serine-111 (LSD1-s111p) by chromatin anchored protein kinase C-theta (PKC-θ), is critical for its demethylase and EMT promoting activity and LSD1-s111p is enriched in chemoresistant cells in vivo. LSD1 couples to PKC-θ on the mesenchymal gene epigenetic template promotes LSD1-mediated gene induction. In vivo, chemotherapy reduced tumour volume, and when combined with an LSD1 inhibitor, abrogated the mesenchymal signature and promoted an innate, M1 macrophage-like tumouricidal immune response. Circulating tumour cells (CTCs) from metastatic breast cancer (MBC) patients were enriched with LSD1 and pharmacological blockade of LSD1 suppressed the mesenchymal and stem-like signature in these patient-derived CTCs. Overall, LSD1 inhibition may serve as a promising epigenetic adjuvant therapy to subvert its pleiotropic roles in breast cancer progression and treatment resistance.
Gadoterate meglumine decreases ADC values of breast lesions depending on the b value combination
Authors: Arponen Otso , Sudah Mazen , Sutela Anna , Taina Mikko , Masarwah Amro , Liimatainen Timo , Vanninen Ritva 
Published: January 2018

AbstractTo retrospectively evaluated the influence of administration of the gadolinium based intravenous contrast agent (G-CA) on apparent diffusion coefficient (ADC) values in ADC maps generated using multiple b value combinations. A total of 106 women underwent bilateral 3.0 T breast MRI. As an internal validation, diffusion-weighted imaging (b values of 0, 200, 400, 600, 800 s/mm2) was performed before and after the G-CA (gadoterate meglumine (0.2 ml/kg, 3 ml/s)). Whole lesion and fibroglandular tissue (FGT) covering region-of-interests (ROIs) were drawn on the b = 800 s/mm2 images; ROIs were then propagated to multiple retrospectively generated ADC maps. Twenty-seven patients (mean age 55.8 ± 10.8 years) with 32 mass-like enhancing breast lesions including 25 (78.1 %) histopathologically malignant lesions were enrolled. Lesion ADC values were statistically significantly higher in pre-G-CA than post-G-CA ADC maps (ADC0,200,400,600,800: 1.05 ± 0.35 × 10−3 mm2/s vs. 1.02 ± 0.36 × 10−3 mm2/s (P < 0.05); ADC0,200,400: 1.25 ± 0.42 × 10−3 mm2/s vs. 1.20 ± 0.35 × 10−3 mm2/s (P < 0.05)). ADC values between pre- and post-contrast maps were not statistically different when the maps were generated using other b value combinations. Contrast agent administration did not affect the FGT ADC values. G-CA statistically significantly reduced the ADC values of breast lesions on ADC maps generated using the clinically widely utilized b values.
Low-dimensional organization of angular momentum during walking on a narrow beam
Authors: Chiovetto Enrico , Huber Meghan E. , Sternad Dagmar , Giese Martin A. 
Published: January 2018

AbstractWalking on a beam is a challenging motor skill that requires the regulation of upright balance and stability. The difficulty in beam walking results from the reduced base of support compared to that afforded by flat ground. One strategy to maintain stability and hence avoid falling off the beam is to rotate the limb segments to control the body’s angular momentum. The aim of this study was to examine the coordination of the angular momentum variations during beam walking. We recorded movement kinematics of participants walking on a narrow beam and computed the angular momentum contributions of the body segments with respect to three different axes. Results showed that, despite considerable variability in the movement kinematics, the angular momentum was characterized by a low-dimensional organization based on a small number of segmental coordination patterns. When the angular momentum was computed with respect to the beam axis, the largest fraction of its variation was accounted for by the trunk segment. This simple organization was robust and invariant across all participants. These findings support the hypothesis that control strategies for complex balancing tasks might be easier to understand by investigating angular momentum instead of the segmental kinematics.
An assay for the identification of Plasmodium simium infection for diagnosis of zoonotic malaria in the Brazilian Atlantic Forest
Authors: de Alvarenga Denise Anete Madureira , Culleton Richard , de Pina-Costa Anielle , Rodrigues Danielle Fonseca , Bianco Cesare , Silva Sidnei , Nunes Ana Júlia Dutra , de Souza Julio César , Hirano Zelinda Maria Braga , Moreira Sílvia Bahadian , Pissinatti Alcides , de Abreu Filipe Vieira Santos , Lisboa Areas André Luiz , Lourenço-de-Oliveira Ricardo , Zalis Mariano Gustavo , Ferreira-da-Cruz Maria de Fátima , Brasil Patricia , Daniel-Ribeiro Cláudio Tadeu , de Brito Cristiana Ferreira Alves 
Published: January 2018

AbstractZoonotic malaria poses a unique problem for malaria control. Autochthonous cases of human malaria in the Atlantic Forest have recently been attributed to Plasmodium simium, a parasite that commonly infects non-human primates in this Brazilian biome. However, due to its close similarity at both the morphological and molecular level to Plasmodium vivax, the diagnosis of P. simium in this region remains problematic. Therefore, a diagnostic assay able to accurately identify P. simium is important for malaria surveillance. Based on mitochondrial genome sequences, primers were designed to amplify a region containing a SNP specific to P. simium. This region can then be digested with the restriction enzyme HpyCH4III, which results in digestion of P. simium sequences, but not of any other malaria parasite. Fifty-two human and monkey blood samples from different regions and infected with different Plasmodium species were used to validate this protocol. This easy and inexpensive tool can be used for the diagnosis of P. simium in non-human primates and human infections from the Atlantic Forest region to monitor zoonotic malaria transmission in Brazil.
Spontaneous and training-induced cortical plasticity in MD patients: Hints from lateral masking
Authors: Maniglia Marcello , Soler Vincent , Cottereau Benoit , Trotter Yves 
Published: January 2018

AbstractMacular degeneration (MD) affects central vision and represents the leading cause of visual diseases in elderly population worldwide. As a consequence of central vision loss, MD patients develop a preferred retinal locus (PRL), an eccentric fixation point that replaces the fovea. Here, our aim was to determine whether and to what extent spontaneous plasticity takes place in the cortical regions formerly responding to central vision and whether a visual training based on perceptual learning (PL) can boost this plasticity within the PRL area. Spontaneous and PL-induced cortical plasticity were characterized by using lateral masking, a contrast sensitivity modulation induced by collinear flankers. This configuration is known to be sensitive to neural plasticity and underlies several rehabilitation trainings. Results in a group of 4 MD patients showed that collinear facilitation was similar to what observed in age- and eccentricity-matched controls. However, MD patients exhibited significantly reduced collinear inhibition, a sign of neural plasticity, consistent with the hypothesis of partial cortical reorganization. Three AMD patients from the same group showed a further reduction of inhibition after training, but not controls. This result suggests that PL might further boost neural plasticity, opening promising perspectives for the development of rehabilitation protocols for MD patients.
Closed-loop control of trunk posture improves locomotion through the regulation of leg proprioceptive feedback after spinal cord injury
Authors: Moraud Eduardo Martin , von Zitzewitz Joachim , Miehlbradt Jenifer , Wurth Sophie , Formento Emanuele , DiGiovanna Jack , Capogrosso Marco , Courtine Grégoire , Micera Silvestro 
Published: January 2018

AbstractAfter spinal cord injury (SCI), sensory feedback circuits critically contribute to leg motor execution. Compelled by the importance to engage these circuits during gait rehabilitation, assistive robotics and training protocols have primarily focused on guiding leg movements to reinforce sensory feedback. Despite the importance of trunk postural dynamics on gait and balance, trunk assistance has comparatively received little attention. Typically, trunk movements are either constrained within bodyweight support systems, or manually adjusted by therapists. Here, we show that real-time control of trunk posture re-established dynamic balance amongst bilateral proprioceptive feedback circuits, and thereby restored left-right symmetry, loading and stepping consistency in rats with severe SCI. We developed a robotic system that adjusts mediolateral trunk posture during locomotion. This system uncovered robust relationships between trunk orientation and the modulation of bilateral leg kinematics and muscle activity. Computer simulations suggested that these modulations emerged from corrections in the balance between flexor- and extensor-related proprioceptive feedback. We leveraged this knowledge to engineer control policies that regulate trunk orientation and postural sway in real-time. This dynamical postural interface immediately improved stepping quality in all rats regardless of broad differences in deficits. These results emphasize the importance of trunk regulation to optimize performance during rehabilitation.
(Pro)renin receptor is involved in mesangial fibrosis and matrix expansion
Authors: Narumi Kaori , Sato Emiko , Hirose Takuo , Yamamoto Tae , Nakamichi Takashi , Miyazaki Mariko , Sato Hiroshi , Ito Sadayoshi 
Published: January 2018

Abstract(Pro)renin receptor [(P)RR] is expressed in the kidney and is involved in renal injury. Although (P)RR is activated by indoxyl sulfate (IS) and may be related to renal injury, the details remain unclear. We used mouse mesangial cell line SV40 MES13 to investigate the association of (P)RR with mesangial fibrosis or expansion. Furthermore, we examined the correlation between serum soluble (P)RR [s(P)RR] and various laboratory data including serum IS, a uremic toxin that induces renal fibrosis through (P)RR, and pathological indices in chronic kidney disease and particularly in IgA nephropathy patients. In vitro study using SV40 MES13 cells revealed that (P)RR expression significantly increased in the presence of IS. IS stimulated the fibrotic factors’ expression, which was significantly suppressed by (P)RR knockdown. Moreover, it significantly increased the expression of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 via the ERK1/2 pathway. In addition, the s(P)RR level significantly correlated with serum IS and mesangial injury markers in our patients. Our results suggest that (P)RR is associated with mesangial fibrosis and matrix expansion through the IS-(P)RR-ERK1/2 pathway. Clinically, s(P)RR may be a biomarker of mesangial fibrosis and matrix expansion.