bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engram-specific transcriptome profiling of contextual memory consolidation
Authors: Rao-Ruiz Priyanka , Couey Jonathan J. , Marcelo Ivo M. , Bouwkamp Christian G. , Slump Denise E. , Matos Mariana R. , van der Loo Rolinka J. , Martins Gabriela J. , van den Hout Mirjam , van IJcken Wilfred F. , Costa Rui M. , van den Oever Michel C. , Kushner Steven A. 
Published: May 2019

AbstractSparse populations of neurons in the dentate gyrus (DG) of the hippocampus are causally implicated in the encoding of contextual fear memories. However, engram-specific molecular mechanisms underlying memory consolidation remain largely unknown. Here we perform unbiased RNA sequencing of DG engram neurons 24 h after contextual fear conditioning to identify transcriptome changes specific to memory consolidation. DG engram neurons exhibit a highly distinct pattern of gene expression, in which CREB-dependent transcription features prominently (P = 6.2 × 10−13), including Atf3 (P = 2.4 × 10−41), Penk (P = 1.3 × 10−15), and Kcnq3 (P = 3.1 × 10−12). Moreover, we validate the functional relevance of the RNAseq findings by establishing the causal requirement of intact CREB function specifically within the DG engram during memory consolidation, and identify a novel group of CREB target genes involved in the encoding of long-term memory.
The computational landscape of general physical theories
Authors: Barrett Jonathan , de Beaudrap Niel , Hoban Matty J. , Lee Ciarán M. 
Published: May 2019

AbstractThere is good evidence that quantum computers are more powerful than classical computers, and that various simple modifications of quantum theory yield computational power that is dramatically greater still. However, these modifications also violate fundamental physical principles. This raises the question of whether there exists a physical theory, allowing computation more powerful than quantum, but which still respects those fundamental physical principles. Prior work by two of us introduced this question within a suitable framework for theories that make good operational sense, and showed that in any theory satisfying tomographic locality, the class of problems that can be solved efficiently is contained in the complexity class AWPP. Here, we show that this bound is tight, in the sense that there exists a theory, satisfying tomographic locality, as well as a basic principle of causality, which can efficiently decide everything in AWPP. Hence this theory can efficiently simulate any computation in this framework, including quantum computation.
A gapmer antisense oligonucleotide targeting SRRM4 is a novel therapeutic medicine for lung cancer
Authors: Shimojo Masahito , Kasahara Yuuya , Inoue Masaki , Tsunoda Shin-ichi , Shudo Yoshie , Kurata Takayasu , Obika Satoshi 
Published: May 2019

AbstractSmall cell lung cancer (SCLC) is the most aggressive neuroendocrine phenotype of the deadliest human lung cancers. However the therapeutic landscape for SCLC has not changed in over 30 years. Effective treatment and prognosis are needed to combat this aggressive cancer. Herein we report that Ser/Arg repetitive matrix 4 (SRRM4), a splicing activator, is abnormally expressed at high levels in SCLC and thus is a potential therapeutic target. We screened an effective gapmer antisense oligonucleotide (gASO) targeting SRRM4 in vitro which led to cell death of SCLC. Our gASO, which is stabilized by containing artificial nucleotides, effectively represses SRRM4 mRNA. We found that our gASO repressed SRRM4 synthesis leading to a dramatic tumor reduction in a lung cancer mouse model. We also analyzed miRNA microarray and found that the miR-4516 is abnormally increased in exosomes in the blood of SCLC patients. Treating with gASO suppressed tumors in the SCLC model mouse concurrently reduced plasma miR-4516. In conclusion this study reports that administration of an SRRM4-targeted gASO coupled with a novel miRNA diagnostic methodology represents a potential breakthrough in the therapeutic treatment of high mortality SCLC.
Classification of arm swing as a clinical marker of advancing spinal deformity among community-dwelling female volunteers 60 years or older
Authors: Kobayashi Tetsuya , Jimbo Shizuo , Senoo Issei , Shimizu Mutsuya , Ito Hiroshi , Hisashi Chiba P. T. 
Published: May 2019

AbstractThe clinical characteristics of adult spinal deformity (ASD) include worsening of deformity during gait, which leads to unstable posture and propensity to fall. The purpose of this study was to classify arm swing and to analyse its clinical implications. Clinical and radiographic evaluations were performed with 168 community-dwelling female volunteers recruited from a population register in Hokkaido, Japan, with a mean age of 67.3 ± 4.7 years, and arm swing was classified into four groups according to maximum forward and backward arm swing distance: (1) predominantly forward swing with forward swing always larger than backward swing (FS, n = 138), (2) equal or equivocal swing (ES, n = 8), (3) predominantly backward swing with backward swing always larger than forward swing (BS, n = 20), and (4) thigh-hand type without arm swing with their hands placed on thighs (TH, n = 2). BS and FS showed significant differences in radiographic lumbar lordosis (BS 19.4 ± 18.1° vs. FS 40.6 ± 14.5°, P < 0.01 ANOVA), pelvic tilt (BS 40.0 ± 7.3° vs. FS 22.9 ± 8.9°, p < 0.01), number of vertebral fractures (BS 1.2 ± 1.4 vs. FS 0.3 ± 0.6, p < 0.01), and trunk extensor muscle strength (BS 374.9 ± 134.8 N vs. FS 478.1 ± 172.6 N, p < 0.05). Arm swing correlated with severity of radiographic ASD, osteoporotic changes, and back muscle weakness. The number of ASD patients, which includes patients with de novo/idiopathic scoliosis, degenerative/osteoporotic kyphosis, and other neuromuscular deformities, has been increasing, and further study should clarify the importance of dynamic evaluation of ASD among elderly patients.
Amido-bridged nucleic acid (AmNA)-modified antisense oligonucleotides targeting α-synuclein as a novel therapy for Parkinson’s disease
Authors: Uehara Takuya , Choong Chi-Jing , Nakamori Masayuki , Hayakawa Hideki , Nishiyama Kumiko , Kasahara Yuuya , Baba Kousuke , Nagata Tetsuya , Yokota Takanori , Tsuda Hiroshi , Obika Satoshi , Mochizuki Hideki 
Published: May 2019

AbstractParkinson’s disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons in the substantia nigra. A characteristic pathological feature of PD is cytoplasmic accumulation of α-synuclein (SNCA) protein. Multiplication of theSNCAgene in familial PD and pathological accumulation of SNCA protein during progression of sporadic PD suggest that increased SNCA protein levels increase the risk of PD. Thus, reducing SNCA expression levels could delay PD onset or modify the disease course. For efficient knock down, we designed and synthesized an amido-bridged nucleic acids (AmNA)-modified antisense oligonucleotide (ASO) that targeted SNCA with improved stability and cellular uptakein vivo. AmNA-ASO efficiently downregulated SNCA at both the mRNA and protein levelin vitroandin vivo. Notably, AmNA-ASO was efficiently delivered into the mouse brain by intracerebroventricular injection without the aid of additional chemicals. Furthermore, administration of AmNA-ASO ameliorated neurological defects in PD model mice expressing human wild type SNCA. Taken together, these findings suggest that AmNA-ASO is a promising therapeutic strategy for SNCA-associated pathology in PD.
Posterior cingulate cortex can be a regulatory modulator of the default mode network in task-negative state
Authors: Wang Regina W. Y. , Chang Wei-Li , Chuang Shang-Wen , Liu I-Ning 
Published: May 2019

AbstractIn recent years, the regulation of brain networks and interactions between different brain regions have become important issues in neuroscience. Effective connectivity can be employed to understand the modulatory mechanisms of brain networks. Previous studies have used the task-positive mode to examine effective connectivity between brain regions and very few studies have considered the task-negative mode to explore effective connectivity using electroencephalography (EEG). In the present study, high-density EEG experiments were conducted in 85 participants to measure EEG effective connectivity in relevant default mode network (DMN) brain regions (i.e., the medial prefrontal cortex [mPFC], posterior cingulate cortex [PCC], precuneus, and right frontal and left occipital regions) to observe the effects of different task-negative modes (eyes-open/eyes-closed state) and personality traits (introversion/extroversion). The results showed that in the eyes-closed state, the PCC had significantly increased effective connectivity and played a prominent role as a regulatory modulator of outflow to other regions mediated by alpha rhythms. The mPFC was a regulatory modulator of outflow in the eyes-open state mediated by delta rhythms. The introvert group showed stronger co-modulations in the relevant DMN regions than the extrovert group.
Increased response to sequential infections of honeybee, Apis mellifera scutellata, colonies by socially parasitic Cape honeybee, A. m. capensis, workers
Authors: Neumann Peter , Pirk Christian W. W. 
Published: May 2019

AbstractCape honeybee, Apis mellifera capensis, workers can be social parasites and host colonies can defend themselves by rejection of such workers. Using the pseudo-clonal obligate parasitic lineage of A. m. capensis and wild-type A. m. capensis workers, which are facultative parasites, we show that host colonies significantly increase their defence behaviour towards social parasites upon secondary exposure. Most obligate and facultative social parasites were rejected before they could even produce significant amounts of the queen-like mandibular gland pheromone secretion or activate their ovaries. This suggests that other signals, like cuticular hydrocarbons, could be used by host colonies to identify potential invaders. Honeybee colonies seem to be able to utilise these potential cues, learn from their initial exposure to hive intruders and enable them to improve their defensive behaviour during subsequent infestations, resulting in increased removal rates of parasites.
Multiplexed temporally focused light shaping through a gradient index lens for precise in-depth optogenetic photostimulation
Authors: Accanto Nicolò , Chen I-Wen , Ronzitti Emiliano , Molinier Clément , Tourain Christophe , Papagiakoumou Eirini , Emiliani Valentina 
Published: May 2019

AbstractIn the past 10 years, the use of light has become irreplaceable for the optogenetic study and control of neurons and neural circuits. Optical techniques are however limited by scattering and can only see through a depth of few hundreds µm in living tissues. GRIN lens based micro-endoscopes represent a powerful solution to reach deeper regions. In this work we demonstrate that cutting edge optical methods for the precise photostimulation of multiple neurons in three dimensions can be performed through a GRIN lens. By spatio-temporally shaping a laser beam in the two-photon regime we project several tens of spatially confined targets in a volume of at least 100 × 150 × 300 µm3. We then apply such approach to the optogenetic stimulation of multiple neurons simultaneously in vivo in mice. Our work paves the way for an all-optical investigation of neural circuits in previously inaccessible brain areas.
A low-carbohydrate ketogenic diet promotes ganglioside synthesis via the transcriptional regulation of ganglioside metabolism-related genes
Authors: Okuda Tetsuya 
Published: May 2019

AbstractLow-carbohydrate ketogenic diets (LCKDs) are used for treating obesity and epilepsy; however, the molecular mechanism of LCKDs in tissues has not been fully investigated. In this study, novel LCKD-associated molecular targets were explored using gene expression profiling in the liver of mice fed a LCKD. The result showed that the LCKD promoted the expression of glycosyltransferase genes involved in ganglioside synthesis and suppressed the expression of Gm2a, the gene encoding GM2 ganglioside activator protein, a lysosomal protein indispensable for ganglioside degradation. These changes were correlated with increased ganglioside content in the liver and serum. As gangliosides are mainly expressed in central nervous tissues, we also analyzed LCKD effect on cerebral cortex. Although ganglioside levels were unchanged in mice on the LCKD, Gm2a expression was significantly down-regulated. Further analyses suggested that the LCKD altered the expression levels of gangliosides in a limited area of central nervous system tissues susceptible to Gm2a.
Symbiotic N fixation is sufficient to support net aboveground biomass accumulation in a humid tropical forest
Authors: Brookshire E. N. J. , Wurzburger Nina , Currey Bryce , Menge Duncan N. L. , Oatham Michael P. , Roberts Carlton 
Published: May 2019

AbstractSymbiotic nitrogen (N) fixation has been shown to support carbon storage in young regenerating tropical forests, but N-fixing trees can also be strong competitors with non-fixing trees, making it unclear which mechanism drives long term patterns in biomass accretion. Many tropical forests have excess N, but factors such as rising atmospheric CO2or selective cutting practices might induce additional N demand. Here we combine decades of stem inventory data,in-situmeasures of symbiotic N fixation, and simulations of N demand to evaluate demographic and biogeochemical controls on biomass dynamics in legume-rich lowland forests of Trinidad. We document sustained net biomass accumulation and high rates of N fixation in these forests, regardless of the timing of selective timber harvests, including an old growth stand. The biomass accumulation was explained by growth of non-fixing trees, not N-fixing trees, but the total amount of symbiotic N fixation was sufficient to account for most of net above ground N demands, suggesting that N-fixers could contribute to the long-term C sink in these forests via fertilizing non-fixers.
A quantitative analysis of the contribution of melanopsin to brightness perception
Authors: Yamakawa Masahiko , Tsujimura Sei-ichi , Okajima Katsunori 
Published: May 2019

AbstractIn the retina, intrinsically photosensitive retinal ganglion cells (ipRGCs) which express photopigment melanopsin have been identified as photoreceptors which differ from cones and rods. It has been established that such melanopsin-expressing RGCs are involved in the circadian photo-entrainment and pupillary light reflexes. An additional projection from ipRGCs to the lateral geniculate nucleus has been identified, which indicates the association of ipRGCs with visual perception induced by the image-forming pathway. Reportedly, ipRGCs modulate brightness perception but quantitative analysis of brightness perception involving melanopsin and cones-based signals has not been elucidated. We conducted brightness perception experiments that involved melanopsin using a novel projector with six primary colors and formulated the results for melanopsin and cone stimuli. The white visual stimuli (5 degrees in size) that we used had a single xy-chromaticity values but melanopsin stimuli were modulated by designing different spectral distributions. Perceived brightness was measured using a magnitude estimation method at several luminance levels in the near periphery (7 degrees). Additionally, pupil diameter was measured for estimating the intensity of visual stimuli on the retina. The results showed that the perceived brightness of a white visual stimulus with different spectral distributions can be described by a summation of the nearly linear melanopsin response and the non-linear cone response with weighted coefficients, and the contribution ratio of melanopsin in brightness perception increased to 50% and more with increasing visual stimulus. These suggest that melanopsin signals play a crucial role in the estimation of the absolute intensity of the light environment by obtaining absolute brightness information even when cones are adapted by light.
Ontogenetic changes in the body plan of the sauropodomorph dinosaur Mussaurus patagonicus reveal shifts of locomotor stance during growth
Authors: Otero Alejandro , Cuff Andrew R. , Allen Vivian , Sumner-Rooney Lauren , Pol Diego , Hutchinson John R. 
Published: May 2019

AbstractOntogenetic information is crucial to understand life histories and represents a true challenge in dinosaurs due to the scarcity of growth series available. Mussaurus patagonicus was a sauropodomorph dinosaur close to the origin of Sauropoda known from hatchling, juvenile and mature specimens, providing a sufficiently complete ontogenetic series to reconstruct general patterns of ontogeny. Here, in order to quantify how body shape and its relationship with locomotor stance (quadruped/biped) changed in ontogeny, hatchling, juvenile (~1 year old) and adult (8+ years old) individuals were studied using digital models. Our results show that Mussaurus rapidly grew from about 60 g at hatching to ~7 kg at one year old, reaching >1000 kg at adulthood. During this time, the body’s centre of mass moved from a position in the mid-thorax to a more caudal position nearer to the pelvis. We infer that these changes of body shape and centre of mass reflect a shift from quadrupedalism to bipedalism occurred early in ontogeny in Mussaurus. Our study indicates that relative development of the tail and neck was more influential in determining the locomotor stance in Sauropodomorpha during ontogeny, challenging previous studies, which have emphasized the influence of hindlimb vs. forelimb lengths on sauropodomorph stance.
A comprehensive metabolomics investigation of hippocampus, serum, and feces affected by chronic fluoxetine treatment using the chronic unpredictable mild stress mouse model of depression
Authors: Zhao Jing , Jung Yang-Hee , Jin Yan , Kang Seulgi , Jang Choon-Gon , Lee Jeongmi 
Published: May 2019

AbstractA metabolomic investigation of depression and chronic fluoxetine treatment was conducted using a chronic unpredictable mild stress model with C57BL/6N mice. Establishment of the depressive model was confirmed by body weight measurement and behavior tests including the forced swim test and the tail suspension test. Behavioral despair by depression was reversed by four week-treatment with fluoxetine. Hippocampus, serum, and feces samples collected from four groups (control + saline, control + fluoxetine, model + saline, and model + fluoxetine) were subjected to metabolomic profiling based on ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. Alterations in the metabolic patterns were evident in all sample types. The antidepressant effects of fluoxetine appeared to involve various metabolic pathways including energy metabolism, neurotransmitter synthesis, tryptophan metabolism, fatty acid metabolism, lipid metabolism, and bile acid metabolism. Predictive marker candidates of depression were identified, including β-citryl-L-glutamic acid (BCG) and docosahexaenoic acid (DHA) in serum and chenodeoxycholic acid and oleamide in feces. This study suggests that treatment effects of fluoxetine might be differentiated by altered levels of tyramine and BCG in serum, and that DHA is a potential serum marker for depression with positive association with hippocampal DHA. Collectively, our comprehensive study provides insights into the biochemical perturbations involved in depression and the antidepressant effects of fluoxetine.
Role of pannexin-1 in the cellular uptake, release and hydrolysis of anandamide by T84 colon cancer cells
Authors: Alhouayek Mireille , Sorti René , Gilthorpe Jonathan D. , Fowler Christopher J. 
Published: May 2019

AbstractThe large pore ion channel pannexin-1 (Panx1) has been reported to play a role in the cellular uptake and release of anandamide (AEA) in the hippocampus. It is not known whether this is a general mechanism or limited to the hippocampus. We have investigated this pharmacologically using T84 colon cancer cells. The cells expressed Panx1 at the mRNA level, and released ATP in a manner that could be reduced by treatment with the Panx1 inhibitors carbenoxolone and mefloquine and the Panx1 substrate SR101. However, no significant effects of these compounds upon the uptake or hydrolysis of exogenously applied AEA was seen. Uptake by T84 cells of the other main endocannabinoid 2-arachidonoylglycerol and the AEA homologue palmitoylethanolamide was similarly not affected by carbenoxolone or mefloquine. Total release of tritium from [3H]AEA-prelabelled T84 cells over 10 min was increased, rather than inhibited by carbenoxolone and mefloquine. Finally, AEA uptake by PC3 prostate cancer and SH-SY5Y neuroblastoma cells, which express functional Panx1 channels, was not inhibited by carbenoxolone. Thus, in contrast to the hippocampus, Panx1 does not appear to play a role in AEA uptake and release from the cells studied under the conditions used.
Covalent-bonding-induced strong phonon scattering in the atomically thin WSe2 layer
Authors: Choi Young-Gwan , Jeong Do-Gyeom , Ju H. I. , Roh C. J. , Kim Geonhwa , Mun Bongjin Simon , Kim Tae Yun , Kim Sang-Woo , Lee J. S. 
Published: May 2019

AbstractIn nano-device applications using two-dimensional (2D) van der Waals materials, a heat dissipation through nano-scale interfaces can be a critical issue for optimizing device performances. By using a time-domain thermoreflectance measurement technique, we examine a cross-plane thermal transport through mono-layered (n = 1) and bi-layered (n = 2) WSe2 flakes which are sandwiched by top metal layers of Al, Au, and Ti and the bottom Al2O3 substrate. In these nanoscale structures with hetero- and homo-junctions, we observe that the thermal boundary resistance (TBR) is significantly enhanced as the number of WSe2 layers increases. In particular, as the metal is changed from Al, to Au, and to Ti, we find an interesting trend of TBR depending on the WSe2 thickness; when referenced to TBR for a system without WSe2, TBR for n = 1 decreases, but that for n = 2 increases. This result clearly demonstrates that the stronger bonding for Ti leads to a better thermal conduction between the metal and the WSe2 layer, but in return gives rise to a large mismatch in the phonon density of states between the first and second WSe2 layers so that the WSe2-WSe2 interface becomes a major thermal resistance for n = 2. By using photoemission spectroscopy and optical second harmonic generation technique, we confirm that the metallization induces a change in the valence state of W-ions, and also recovers a non-centrosymmetry for the bi-layered WSe2.