bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delta-9-tetrahydrocannabinol increases striatal glutamate levels in healthy individuals: implications for psychosis
Authors: Colizzi Marco , Weltens Nathalie , McGuire Philip , Lythgoe David , Williams Steve , Van Oudenhove Lukas , Bhattacharyya Sagnik 
Published: February 2019

AbstractThe neurobiological mechanisms underlying the association between cannabis use and acute or long-lasting psychosis are not completely understood. While some evidence suggests altered striatal dopamine may underlie the association, direct evidence that cannabis use affects either acute or chronic striatal dopamine is inconclusive. In contrast, pre-clinical research suggests that cannabis may affect dopamine via modulation of glutamate signaling. A double-blind, randomized, placebo-controlled, crossover design was used to investigate whether altered striatal glutamate, as measured using proton magnetic resonance spectroscopy, underlies the acute psychotomimetic effects of intravenously administered delta-9-tetrahydrocannabinol (Δ9-THC; 1.19 mg/2 ml), the key psychoactive ingredient in cannabis, in a set of 16 healthy participants (7 males) with modest previous cannabis exposure. Compared to placebo, acute administration of Δ9-THC significantly increased Glutamate (Glu) + Glutamine (Gln) metabolites (Glx) in the left caudate head (P = 0.027). Furthermore, compared to individuals who were not sensitive to the psychotomimetic effects of Δ9-THC, individuals who developed transient psychotic-like symptoms (~70% of the sample) had significantly lower baseline Glx (placebo; P 7= 0.023) and a 2.27-times higher increase following Δ9-THC administration. Lower baseline Glx values (r = −0.55; P = 0.026) and higher previous cannabis exposure (r = 0.52; P = 0.040) were associated with a higher Δ9-THC-induced Glx increase. These results suggest that an increase in striatal glutamate levels may underlie acute cannabis-induced psychosis while lower baseline levels may be a marker of greater sensitivity to its acute psychotomimetic effects and may have important public health implications.
Smac mimetic suppresses tunicamycin-induced apoptosis via resolution of ER stress
Authors: Abhari Behnaz Ahangarian , McCarthy Nicole , Le Berre Marie , Kilcoyne Michelle , Joshi Lokesh , Agostinis Patrizia , Fulda Simone 
Published: February 2019

AbstractSince Inhibitor of Apoptosis (IAP) proteins have been implicated in cellular adaptation to endoplasmic reticulum (ER) stress, we investigated the regulation of ER stress-induced apoptosis by small-molecule second mitochondria-derived activator of caspase (Smac) mimetics that antagonize IAP proteins. Here, we discover that Smac mimetic suppresses tunicamycin (TM)-induced apoptosis via resolution of the unfolded protein response (UPR) and ER stress. Smac mimetics such as BV6 selectively inhibit apoptosis triggered by pharmacological or genetic inhibition of protein N-glycosylation using TM or knockdown of DPAGT1, the enzyme that catalyzes the first step of protein N-glycosylation. In contrast, BV6 does not rescue cell death induced by other typical ER stressors (i.e., thapsigargin (TG), dithiothreitol, brefeldin A, bortezomib, or 2-deoxyglucose). The protection from TM-triggered apoptosis is found for structurally different Smac mimetics and for genetic knockdown of cellular IAP (cIAP) proteins in several cancer types, underlining the broader relevance. Interestingly, lectin microarray profiling reveals that BV6 counteracts TM-imposed inhibition of protein glycosylation. BV6 consistently abolishes TM-stimulated accumulation of ER stress markers such as glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) and reduces protein kinase RNA-like ER kinase (PERK) phosphorylation and X box-binding protein 1 (XBP1) splicing upon TM treatment. BV6-stimulated activation of nuclear factor-κB (NF-κB) contributes to the resolution of ER stress, since NF-κB inhibition by overexpression of dominant-negative IκBα superrepressor counteracts the suppression of TM-stimulated transcriptional activation of CHOP and GRP78 by BV6. Thus, our study is the first to show that Smac mimetic protects from TM-triggered apoptosis by resolving the UPR and ER stress. This provides new insights into the regulation of cellular stress responses by Smac mimetics.
MiR-451a suppressing BAP31 can inhibit proliferation and increase apoptosis through inducing ER stress in colorectal cancer
Authors: Xu Ke , Han Bin , Bai Yang , Ma Xiu-Ying , Ji Zhen-Ni , Xiong Yao , Miao Shi-Kun , Zhang Yuan-Yuan , Zhou Li-Ming 
Published: February 2019

AbstractThe global morbidity and mortality of colorectal cancer (CRC) are ranked the third among gastrointestinal tumors in the world. MiR-451a is associated with several types of cancer, including CRC. However, the roles and mechanisms of miR-451a in CRC have not been elucidated. BAP31 is a predicted target gene of miR-451a in our suppression subtractive hybridization library. Its relationship with miR-451a and function in CRC are unclear. We hypothesized that miR-451a could induce apoptosis through suppressing BAP31 in CRC. Immunohistochemistry and real-time PCR were used to measure BAP31 expressions in CRC tissues and pericarcinous tissues from 57 CRC patients and CRC cell lines. Dual-luciferase reporter assay was used to detect the binding of miR-451a to BAP31. The expression of BAP31 protein in CRC tissues was significantly higher than that in pericarcinous tissues, which was correlated with distant metastasis and advanced clinical stages of CRC patients. The expression of BAP31 was higher in HCT116, HT29, SW620, and DLD cells than that in the normal colonic epithelial cell line NCM460. The expression of BAP31 was absolutely down-regulated when over-expressing miR-451a in HCT116 and SW620 cells compared with control cells. Mir-451a inhibited the expression of BAP31 by binding to its 5’-UTR. Over-expressing miR-451a or silencing BAP31 suppressed the proliferation and apoptosis of CRC cells by increasing the expressions of endoplasmic reticulum stress (ERS)-associated proteins, including GRP78/BIP, BAX, and PERK/elF2α/ATF4/CHOP, which resulted in increased ERS, cytoplasmic calcium ion flowing, and apoptosis of CRC cells. These changes resulting from over-expressing miR-451a were reversed by over-expressing BAP31 with mutated miR-451a-binding sites. Over-expressing miR-451a or silencing BAP31 inhibited tumor growth by inducing ERS. The present study demonstrated that miR-451a can inhibit proliferation and increase apoptosis through inducing ERS by binding to the 5’-UTR of BAP31 in CRC.
Recessive mutations in muscle-specific isoforms of FXR1 cause congenital multi-minicore myopathy
Authors: Estañ María Cristina , Fernández-Núñez Elisa , Zaki Maha S. , Esteban María Isabel , Donkervoort Sandra , Hawkins Cynthia , Caparros-Martin José A. , Saade Dimah , Hu Ying , Bolduc Véronique , Chao Katherine Ru-Yui , Nevado Julián , Lamuedra Ana , Largo Raquel , Herrero-Beaumont Gabriel , Regadera Javier , Hernandez-Chico Concepción , Tizzano Eduardo F. , Martinez-Glez Victor , Carvajal Jaime J. , Zong Ruiting , Nelson David L. , Otaify Ghada A. , Temtamy Samia , Aglan Mona , Issa Mahmoud , Bönnemann Carsten G. , Lapunzina Pablo , Yoon Grace , Ruiz-Perez Victor L. 
Published: February 2019

AbstractFXR1 is an alternatively spliced gene that encodes RNA binding proteins (FXR1P) involved in muscle development. In contrast to other tissues, cardiac and skeletal muscle express two FXR1P isoforms that incorporate an additional exon-15. We report that recessive mutations in this particular exon of FXR1 cause congenital multi-minicore myopathy in humans and mice. Additionally, we show that while Myf5-dependent depletion of all FXR1P isoforms is neonatal lethal, mice carrying mutations in exon-15 display non-lethal myopathies which vary in severity depending on the specific effect of each mutation on the protein.
Evidence of cooperative effect on the enhanced superconducting transition temperature at the FeSe/SrTiO3 interface
Authors: Song Q. , Yu T. L. , Lou X. , Xie B. P. , Xu H. C. , Wen C. H. P. , Yao Q. , Zhang S. Y. , Zhu X. T. , Guo J. D. , Peng R. , Feng D. L. 
Published: February 2019

AbstractAt the interface between monolayer FeSe films and SrTiO3 substrates the superconducting transition temperature (Tc) is unexpectedly high, triggering a surge of excitement. The mechanism for the Tc enhancement has been the central question, as it may present a new strategy for seeking out higher Tc materials. To reveal this enigmatic mechanism, by combining advances in high quality interface growth, 16O $$\leftrightarrow$$
↔
18O isotope substitution, and extensive data from angle resolved photoemission spectroscopy, we provide striking evidence that the high Tc in FeSe/SrTiO3 is the cooperative effect of the intrinsic pairing mechanism in the FeSe and interactions between the FeSe electrons and SrTiO3 phonons. Furthermore, our results point to the promising prospect that similar cooperation between different Cooper pairing channels may be a general framework to understand and design high-temperature superconductors.
A functional subset of CD8+ T cells during chronic exhaustion is defined by SIRPα expression
Authors: Myers Lara M. , Tal Michal Caspi , Torrez Dulgeroff Laughing Bear , Carmody Aaron B. , Messer Ronald J. , Gulati Gunsagar , Yiu Ying Ying , Staron Matthew M. , Angel Cesar Lopez , Sinha Rahul , Markovic Maxim , Pham Edward A. , Fram Benjamin , Ahmed Aijaz , Newman Aaron M. , Glenn Jeffrey S. , Davis Mark M. , Kaech Susan M. , Weissman Irving L. , Hasenkrug Kim J. 
Published: February 2019

AbstractProlonged exposure of CD8+T cells to antigenic stimulation, as in chronic viral infections, leads to a state of diminished function termed exhaustion. We now demonstrate that even during exhaustion there is a subset of functional CD8+T cells defined by surface expression of SIRPα, a protein not previously reported on lymphocytes. On SIRPα+CD8+T cells, expression of co-inhibitory receptors is counterbalanced by expression of co-stimulatory receptors and it is only SIRPα+cells that actively proliferate, transcribe IFNγ and show cytolytic activity. Furthermore, target cells that express the ligand for SIRPα, CD47, are more susceptible to CD8+T cell-killing in vivo. SIRPα+CD8+T cells are evident in mice infected with Friend retrovirus, LCMV Clone 13, and in patients with chronic HCV infections. Furthermore, therapeutic blockade of PD-L1 to reinvigorate CD8+T cells during chronic infection expands the cytotoxic subset of SIRPα+CD8+T cells.
Multimaterial actinic spatial control 3D and 4D printing
Authors: Schwartz J. J. , Boydston A. J. 
Published: February 2019

AbstractProduction of objects with varied mechanical properties is challenging for current manufacturing methods. Additive manufacturing could make these multimaterial objects possible, but methods able to achieve multimaterial control along all three axes of printing are limited. Here we report a multi-wavelength method of vat photopolymerization that provides chemoselective wavelength-control over material composition utilizing multimaterial actinic spatial control (MASC) during additive manufacturing. The multicomponent photoresins include acrylate- and epoxide-based monomers with corresponding radical and cationic initiators. Under long wavelength (visible) irradiation, preferential curing of acrylate components is observed. Under short wavelength (UV) irradiation, a combination of acrylate and epoxide components are incorporated. This enables production of multimaterial parts containing stiff epoxide networks contrasted against soft hydrogels and organogels. Variation in MASC formulation drastically changes the mechanical properties of printed samples. Samples printed using different MASC formulations have spatially-controlled chemical heterogeneity, mechanical anisotropy, and spatially-controlled swelling that facilitates 4D printing.
Copy-choice recombination during mitochondrial L-strand synthesis causes DNA deletions
Authors: Persson Örjan , Muthukumar Yazh , Basu Swaraj , Jenninger Louise , Uhler Jay P. , Berglund Anna-Karin , McFarland Robert , Taylor Robert W. , Gustafsson Claes M. , Larsson Erik , Falkenberg Maria 
Published: February 2019

AbstractMitochondrial DNA (mtDNA) deletions are associated with mitochondrial disease, and also accumulate during normal human ageing. The mechanisms underlying mtDNA deletions remain unknown although several models have been proposed. Here we use deep sequencing to characterize abundant mtDNA deletions in patients with mutations in mitochondrial DNA replication factors, and show that these have distinct directionality and repeat characteristics. Furthermore, we recreate the deletion formation process in vitro using only purified mitochondrial proteins and defined DNA templates. Based on our in vivo and in vitro findings, we conclude that mtDNA deletion formation involves copy-choice recombination during replication of the mtDNA light strand.
The Tec kinase ITK is essential for ILC2 survival and epithelial integrity in the intestine
Authors: Cho Hyoung-Soo , Reboldi Andrea , Hall Jason A. , Berg Leslie J. 
Published: February 2019

AbstractInnate lymphoid cells (ILC) are lymphocytes that lack an antigen-specific receptor and are preferentially localized in non-lymphoid tissues, such as mucosal barriers. In these locations ILC respond to tissue perturbations by producing factors that promote tissue repair and improve barrier integrity. We show that mice lacking the Tec kinase ITK have impaired intestinal tissue integrity, and a reduced ability to restore homeostasis after tissue damage. This defect is associated with a substantial loss of Type 2 ILC (ILC2) in the intestinal lamina propria. Adoptive transfer of bone marrow ILC2 precursors confirms a cell-intrinsic role for ITK. Intestinal ILC2 numbers in Itk-/- mice are restored by the administration of IL-2 complexes, also leading to improved intestinal tissue damage repair. Reduced Bcl-2 expression in intestinal Itk-/- ILC2 is also restored to WT levels after IL-2 complex treatment, indicating a tissue-specific role for ITK in ILC2 survival in the intestine.
Tear resistance of soft collagenous tissues
Authors: Bircher Kevin , Zündel Manuel , Pensalfini Marco , Ehret Alexander E. , Mazza Edoardo 
Published: February 2019

AbstractFracture toughness characterizes the ability of a material to maintain a certain level of strength despite the presence of a macroscopic crack. Understanding this tolerance for defects in soft collagenous tissues (SCT) has high relevance for assessing the risks of fracture after cutting, perforation or suturing. Here we investigate the peculiar toughening mechanisms of SCT through dedicated experiments and multi-scale simulations, showing that classical concepts of fracture mechanics are inadequate to quantify and explain the high defect tolerance of these materials. Our results demonstrate that SCT strength is only modestly reduced by defects as large as several millimeters. This defect tolerance is achieved despite a very narrow process zone at the crack tip and even for a network of brittle fibrils. The fracture mechanics concept of tearing energy fails in predicting failure at such defects, and its magnitude is shown to depend on the chemical potential of the liquid environment.
The rise and fall of cooperation through reputation and group polarization
Authors: Gross Jörg , De Dreu Carsten K. W. 
Published: February 2019

AbstractHumans exhibit a remarkable capacity for cooperation among genetically unrelated individuals. Yet, human cooperation is neither universal, nor stable. Instead, cooperation is often bounded to members of particular groups, and such groups endogenously form or break apart. Cooperation networks are parochial and under constant reconfiguration. Here, we demonstrate how parochial cooperation networks endogenously emerge as a consequence of simple reputation heuristics people may use when deciding to cooperate or defect. These reputation heuristics, such as “a friend of a friend is a friend” and “the enemy of a friend is an enemy” further lead to the dynamic formation and fission of cooperative groups, accompanied by a dynamic rise and fall of cooperation among agents. The ability of humans to safeguard kin-independent cooperation through gossip and reputation may be, accordingly, closely interlinked with the formation of group-bounded cooperation networks that are under constant reconfiguration, ultimately preventing global and stable cooperation.
Lack of androgen receptor SUMOylation results in male infertility due to epididymal dysfunction
Authors: Zhang Fu-Ping , Malinen Marjo , Mehmood Arfa , Lehtiniemi Tiina , Jääskeläinen Tiina , Niskanen Einari A. , Korhonen Hanna , Laiho Asta , Elo Laura L. , Ohlsson Claes , Kotaja Noora , Poutanen Matti , Sipilä Petra , Palvimo Jorma J. 
Published: February 2019

AbstractAndrogen receptor (AR) is regulated by SUMOylation at its transactivation domain. In vitro, the SUMOylation is linked to transcriptional repression and/or target gene-selective regulation. Here, we generated a mouse model (ArKI) in which the conserved SUMO acceptor lysines of AR are permanently abolished (ArK381R, K500R). ArKI males develop normally, without apparent defects in their systemic androgen action in reproductive tissues. However, the ArKI males are infertile. Their spermatogenesis appears unaffected, but their epididymal sperm maturation is defective, shown by severely compromised motility and fertilization capacity of the sperm. Fittingly, their epididymal AR chromatin-binding and gene expression associated with sperm maturation and function are misregulated. AR is SUMOylated in the wild-type epididymis but not in the testis, which could explain the tissue-specific response to the lack of AR SUMOylation. Our studies thus indicate that epididymal AR SUMOylation is essential for the post-testicular sperm maturation and normal reproductive capability of male mice.
Multi-cohort study identifies social determinants of systemic inflammation over the life course
Authors: Berger Eloïse , Castagné Raphaële , Chadeau-Hyam Marc , Bochud Murielle , d’Errico Angelo , Gandini Martina , Karimi Maryam , Kivimäki Mika , Krogh Vittorio , Marmot Michael , Panico Salvatore , Preisig Martin , Ricceri Fulvio , Sacerdote Carlotta , Steptoe Andrew , Stringhini Silvia , Tumino Rosario , Vineis Paolo , Delpierre Cyrille , Kelly-Irving Michelle 
Published: February 2019

AbstractChronic inflammation has been proposed as having a prominent role in the construction of social inequalities in health. Disentangling the effects of early life and adulthood social disadvantage on inflammation is key in elucidating biological mechanisms underlying socioeconomic disparities. Here we explore the relationship between socioeconomic position (SEP) across the life course and inflammation (as measured by CRP levels) in up to 23,008 participants from six European cohort studies from three countries conducted between 1958 and 2013. We find a consistent inverse association between SEP and CRP across cohorts, where participants with a less advantaged SEP have higher levels of inflammation. Educational attainment is most strongly related to inflammation, after adjusting for health behaviours, body mass index and later-in-life SEP. These findings suggest socioeconomic disadvantage in young adulthood is independently associated with later life inflammation calling for further studies of the pathways operating through educational processes.
Single gametophyte sequencing reveals that crossover events differ between sexes in maize
Authors: Luo Cheng , Li Xiang , Zhang Qinghua , Yan Jianbing 
Published: February 2019

AbstractMeiotic crossover (CO) plays a key role in producing gametophytes and generating genetic variation. The patterns of CO production differ inter- and intra-species, as well as between sexes. However, sex-specific patterns of CO production have not been accurately profiled independently of genetic backgrounds in maize. Here, we develop a method to isolate single female gametophyte for genomes sequencing in maize. We show that more COs are observed in male (19.3 per microspore) than in female (12.4 per embryo sac). Based on Beam-Film model, the more designated class I and II COs are identified in male than in female. In addition, CO maturation inefficiency (CMI) is detected in some genetic backgrounds, suggesting that maize may be an ideal model for dissecting CMI. This research provides insights toward understanding the molecular mechanism of CO production between sexes and may help to improve maize breeding efficiency through paternal selection.
A method using electroporation for the protein delivery of Cre recombinase into cultured Arabidopsis cells with an intact cell wall
Authors: Furuhata Yuichi , Sakai Ayako , Murakami Tomi , Morikawa Mone , Nakamura Chikashi , Yoshizumi Takeshi , Fujikura Ushio , Nishida Keiji , Kato Yoshio 
Published: February 2019

AbstractGenome engineering in plants is highly dependent on the availability of effective molecular techniques. Despite vast quantities of research, genome engineering in plants is still limited in terms of gene delivery, which requires the use of infectious bacteria or harsh conditions owing to the difficulty delivering biomaterial into plant cells through the cell wall. Here, we describe a method that uses electroporation-mediated protein delivery into culturedArabidopsis thalianacells possessing an intact cell wall, and demonstrate Cre-mediated site-specific recombination. By optimizing conditions for the electric pulse, protein concentration, and electroporation buffer, we were able to achieve efficient and less-toxic protein delivery intoArabidopsis thalianacells with 83% efficiency despite the cell wall. To the best of our knowledge, this is the first report demonstrating the electroporation-mediated protein delivery of Cre recombinase to achieve nucleic acid-free genome engineering in plant cells possessing an intact cell wall.
Impact of the Atlantic Multidecadal Oscillation on the Pacific North Equatorial Current bifurcation
Authors: Wu Chau-Ron , Lin Yong-Fu , Qiu Bo 
Published: February 2019

AbstractVariability in surface currents is mainly induced by the time-varying wind forcing. Recent studies have revealed robust pronounced changes in the atmospheric circulation over the Pacific came with the Pacific Decadal Oscillation (PDO). However, the PDO is a climate index based on sea surface temperature (SST) variations, and may not be appropriately considered as a climate forcing. Here, we suggest the Atlantic SST variability is the ultimate forcing leading to changes in the atmospheric circulation and surface winds over the North Pacific. Anomalous warm North Atlantic and cold South Atlantic leads to weak Hadley cell in the Northern Hemisphere, resulting in a northward displacement of the ITCZ as well as a positive wind stress curl anomaly in the Pacific subtropical region, which would reduce the North Pacific subtropical gyre (NPSG). Associated with reduced sea surface height in the subtropics by the weakened NPSG, the North Equatorial Current (NEC) is weakened based on geostrophy. Changes in basin-scale winds further result in the southward migration of the tropical gyre and consequential downstream ocean circulation.