bluuebunny/crossref_metadata_2025_split huggingface dataset:
Postnatal development of GABAergic interneurons and perineuronal nets in mouse temporal cortex subregions
Authors: Ueno Hiroshi , Suemitsu Shunsuke , Murakami Shinji , Kitamura Naoya , Wani Kenta , Okamoto Motoi , Aoki Shozo , Ishihara Takeshi 
Published: August 2017

AbstractIn human neuropsychiatric disorders, there are functional and anatomical abnormalities of GABAergic interneurons in each temporal cortex subregion. Furthermore, accumulation of amyloid‐β is observed in the temporal cortex in the early stages of Alzheimer's disease. Each subregion of the temporal cortex has an important role in coordinating the input and output of the hippocampus. When subregions of the temporal cortex are impaired, memory and learning ability decrease. GABAergic interneurons control excitatory neurons, forming the cortico‐cortical and cortico‐hippocampal networks. However, in temporal cortex subregions, details of the distribution and developmental processes of GABAergic interneurons and perineuronal nets (PNNs) have not been elucidated. Here we examined the development of GABAergic interneurons and PNNs in mouse temporal cortex subregions. Results indicate that temporal cortex GABAergic interneurons have developmental stages different to those of the primary sensory cortex. In addition, the density of PNNs in the temporal cortex is lower than that in the sensory cortex. Furthermore, we found that the Wisteria floribunda agglutinin‐reactive extracellular matrix molecule is present in the upper level of layer 1 of the temporal cortex. These results support the idea that mouse temporal cortex subregions develop differently from other cortical regions and have region‐specific characteristics after maturation. The present study results suggested that the structure of the temporal cortex is significantly different from the sensory cortex and that temporal cortex may be highly vulnerable to neuropsychiatric and neurodegenerative disorders.
Cerebral Manifestations of Mitochondrial Disorders
Authors: Finsterer Josef , Carvalho Elmano Henrique Torres de 
Published: August 2017

ABSTRACTThis review aims at summarizing and discussing previous and recent findings concerning the cerebral manifestations of mitochondrial disorders (MIDs). MIDs frequently present as mitochondrial multiorgan disorder syndrome (MIMODS) either already at onset or later in the course. After the muscle, the brain is the organ second most frequently affected in MIMODS. Cerebral manifestations of MIDs are variable and may present with or without a lesion on imaging or functional studies, but there can be imaging/functional lesions without clinical manifestations. The most well-known cerebral manifestations of MIDs include stroke-like episodes, epilepsy, headache, ataxia, movement disorders, hypopituitarism, muscle weakness, psychiatric abnormalities, nystagmus, white and gray matter lesions, atrophy, basal ganglia calcification, and hypometabolism on 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron-emission tomography. For most MIDs, only symptomatic therapy is currently available. Symptomatic treatment should be supplemented by vitamins, cofactors, and antioxidants. In conclusion, cerebral manifestations of MIDs need to be recognized and appropriately managed because they strongly determine the outcome of MID patients.
On “personal protective deities” (’go ba'i lha) and the Old Tibetan verb ’go
Authors: Dotson Brandon 
Published: August 2017

AbstractThe ’go ba'i lha – usually translated with “personal protective deities” – are often approached as an integral part of Tibetan popular or folk religion. Typically five in number, these gods are said to be born with an individual, to reside in his or her body, and to protect various facets of his or her existence. As for the etymology of ’go ba'i lha, while “protective deities” is the dominant translation, it remains a highly communicative and contextual gloss of ’go, whose attested meanings do not include “to protect”. The present contribution offers a new analysis of the verb ’go based on attestations in Old Tibetan texts from Dunhuang from the ninth and tenth centuries. In doing so, the article not only proposes a new etymology of ’go ba'i lha, but also touches on the changing relationship between Tibetans and their gods over time.
CRIMINALIZATION WITHOUT PUNISHMENT
Authors: Edwards James 
Published: August 2017

ABSTRACTWhat is the relationship between a theory of permissible criminalization and a theory of permissible state punishment? One answer runs as follows: to identify the conditions under which it is permissible to criminalize, we must first identify the conditions under which it is permissible for the state to punish. The latter set of conditions doubles as part of the former set. Call this the punishment thesis. It is a thesis with some prominent advocates, but explicit defenses are hard to find. In this paper, I ask how such a defense might proceed. Section I clarifies the punishment thesis itself. Sections II–IV consider a number of arguments in its favor. My contention is that none of these arguments succeeds. Unless a better argument can be found, we should reject the punishment thesis.
Three-Dimensional Nanoscale Mapping of State-of-the-Art Field-Effect Transistors (FinFETs)
Authors: Parikh Pritesh , Senowitz Corey , Lyons Don , Martin Isabelle , Prosa Ty J. , DiBattista Michael , Devaraj Arun , Meng Y. Shirley 
Published: August 2017

AbstractThe semiconductor industry has seen tremendous progress over the last few decades with continuous reduction in transistor size to improve device performance. Miniaturization of devices has led to changes in the dopants and dielectric layers incorporated. As the gradual shift from two-dimensional metal-oxide semiconductor field-effect transistor to three-dimensional (3D) field-effect transistors (finFETs) occurred, it has become imperative to understand compositional variability with nanoscale spatial resolution. Compositional changes can affect device performance primarily through fluctuations in threshold voltage and channel current density. Traditional techniques such as scanning electron microscope and focused ion beam no longer provide the required resolution to probe the physical structure and chemical composition of individual fins. Hence advanced multimodal characterization approaches are required to better understand electronic devices. Herein, we report the study of 14 nm commercial finFETs using atom probe tomography (APT) and scanning transmission electron microscopy–energy-dispersive X-ray spectroscopy (STEM-EDS). Complimentary compositional maps were obtained using both techniques with analysis of the gate dielectrics and silicon fin. APT additionally provided 3D information and allowed analysis of the distribution of low atomic number dopant elements (e.g., boron), which are elusive when using STEM-EDS.
Dispositional Properties of Metaphor
Authors: Fetterman Adam K. , Meier Brian P. , Robinson Michael D. 
Published: August 2017

Abstract. Metaphors often characterize prosocial actions and people as sweet. Three studies sought to explore whether conceptual metaphors of this type can provide insights into the prosocial trait of agreeableness and into daily life prosociality. Study 1 (n = 698) examined relationships between agreeableness and food taste preferences. Studies 2 (n = 66) and 3 (n = 132) utilized daily diary protocols. In Study 1, more agreeable people liked sweet foods to a greater extent. In Study 2, greater sweet food preferences predicted a stronger positive relationship between daily prosocial behaviors and positive affect, a pattern consistent with prosocial motivation. Finally, Study 3 found that daily prosocial feelings and behaviors varied positively with sweet food consumption in a manner that could not be ascribed to positive affect or self-control. Altogether, the findings encourage further efforts to extend conceptual metaphor theory to the domain of personality processes, in part by building on balance-related ideas.
Silencing FLI or targeting CD13/ANPEP lead to dephosphorylation of EPHA2, a mediator of BRAF inhibitor resistance, and induce growth arrest or apoptosis in melanoma cells
Authors: Azimi Alireza , Tuominen Rainer , Costa Svedman Fernanda , Caramuta Stefano , Pernemalm Maria , Frostvik Stolt Marianne , Kanter Lena , Kharaziha Pedram , Lehtiö Janne , Hertzman Johansson Carolina , Höiom Veronica , Hansson Johan , Egyhazi Brage Suzanne 
Published: August 2017

AbstractA majority of patients with BRAF-mutated metastatic melanoma respond to therapy with BRAF inhibitors (BRAFi), but relapses are common owing to acquired resistance. To unravel BRAFi resistance mechanisms we have performed gene expression and mass spectrometry based proteome profiling of the sensitive parental A375 BRAF V600E-mutated human melanoma cell line and of daughter cell lines with induced BRAFi resistance. Increased expression of two novel resistance candidates, aminopeptidase-N (CD13/ANPEP) and ETS transcription factor FLI1 was observed in the BRAFi-resistant daughter cell lines. In addition, increased levels of the previously reported resistance mediators, receptor tyrosine kinase ephrine receptor A2 (EPHA2) and the hepatocyte growth factor receptor MET were also identified. The expression of these proteins was assessed in matched tumor samples from melanoma patients obtained before BRAFi and after disease progression. MET was overexpressed in all progression samples while the expression of the other candidates varied between the individual patients. Targeting CD13/ANPEP by a blocking antibody induced apoptosis in both parental A375- and BRAFi-resistant daughter cells as well as in melanoma cells with intrinsic BRAFi resistance and led to dephosphorylation of EPHA2 on S897, previously demonstrated to cause inhibition of the migratory capacity. AKT and RSK, both reported to induce EPHA2 S897 phosphorylation, were also dephosphorylated after inhibition of CD13/ANPEP. FLI1 silencing also caused decreases in EPHA2 S897 phosphorylation and in total MET protein expression. In addition, silencing of FLI1 sensitized the resistant cells to BRAFi. Furthermore, we show that BRAFi in combination with the multi kinase inhibitor dasatinib can abrogate BRAFi resistance and decrease both EPHA2 S897 phosphorylation and total FLI1 protein expression. This is the first report presenting CD13/ANPEP and FLI1 as important mediators of resistance to BRAF inhibition with potential as drug targets in BRAFi refractory melanoma.
HSPB1 facilitates ERK-mediated phosphorylation and degradation of BIM to attenuate endoplasmic reticulum stress-induced apoptosis
Authors: Kennedy Donna , Mnich Katarzyna , Oommen Deepu , Chakravarthy Reka , Almeida-Souza Leonardo , Krols Michiel , Saveljeva Svetlana , Doyle Karen , Gupta Sanjeev , Timmerman Vincent , Janssens Sophie , Gorman Adrienne M , Samali Afshin 
Published: August 2017

AbstractBIM, a pro-apoptotic BH3-only protein, is a key regulator of the intrinsic (or mitochondrial) apoptosis pathway. Here, we show that BIM induction by endoplasmic reticulum (ER) stress is suppressed in rat PC12 cells overexpressing heat shock protein B1 (HSPB1 or HSP27) and that this is due to enhanced proteasomal degradation of BIM. HSPB1 and BIM form a complex that immunoprecipitates with p-ERK1/2. We found that HSPB1-mediated proteasomal degradation of BIM is dependent on MEK-ERK signaling. Other studies have shown that several missense mutations in HSPB1 cause the peripheral neuropathy, Charcot-Marie-Tooth (CMT) disease, which is associated with nerve degeneration. Here we show that cells overexpressing CMT-related HSPB1 mutants exhibited increased susceptibility to ER stress-induced cell death and high levels of BIM. These findings identify a novel function for HSPB1 as a negative regulator of BIM protein stability leading to protection against ER stress-induced apoptosis, a function that is absent in CMT-associated HSPB1 mutants.
Dual role of DR5 in death and survival signaling leads to TRAIL resistance in cancer cells
Authors: Shlyakhtina Yelyzaveta , Pavet Valeria , Gronemeyer Hinrich 
Published: August 2017

AbstractBesides its tumor-selective apoptotic activity, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) promotes pro-survival, proliferative or migratory signaling (NF-κB, PI3K/Akt, MAPK and JNK; referred to as 'non-apoptotic' cascades). Indeed, apoptosis and non-apoptotic signaling can be activated in clonal populations of cancer cells in response to treatment and, as a result, only a part of the initial cellular population dies while a fraction survives and develops resistance to TRAIL-induced apoptosis (referred to as 'fractional survival'). Notably, the molecular characterization of the protein platforms streaming into tumoricidalversustumor-promoting cascades that control fractional survival remained elusive. Here we demonstrate that, in the context of DR4–DR5–DcR2 hetero-oligomeric complexes, a single death receptor (DR5) suffices to assemble composite plasma membrane-proximal pro-apoptotic/pro-survival platforms that propagate TRAIL signaling to both death and survival pathways in clonal populations of cancer cells. Moreover, we show that while all members of TRAIL-induced complexes support survival, none of them acted exclusively pro-apoptotic. Indeed, key apoptotic proteins as FADD and procaspase-8 were also involved in transducing non-apoptotic signaling in response to this cytokine. Collectively, this study reveals the Janus faces of DR5, and the contributions of other death complex components in fractional survival that foster the generation of resistance. Our data highlight a new level of complexity in TRAIL signaling and point to an improved therapeutic rationale in view of hitherto disappointing results.
Tunneling anisotropic magnetoresistance driven by magnetic phase transition
Authors: Chen X. Z. , Feng J. F. , Wang Z. C. , Zhang J. , Zhong X. Y. , Song C. , Jin L. , Zhang B. , Li F. , Jiang M. , Tan Y. Z. , Zhou X. J. , Shi G. Y. , Zhou X. F. , Han X. D. , Mao S. C. , Chen Y. H. , Han X. F. , Pan F. 
Published: August 2017

AbstractThe independent control of two magnetic electrodes and spin-coherent transport in magnetic tunnel junctions are strictly required for tunneling magnetoresistance, while junctions with only one ferromagnetic electrode exhibit tunneling anisotropic magnetoresistance dependent on the anisotropic density of states with no room temperature performance so far. Here, we report an alternative approach to obtaining tunneling anisotropic magnetoresistance in α′-FeRh-based junctions driven by the magnetic phase transition of α′-FeRh and resultantly large variation of the density of states in the vicinity of MgO tunneling barrier, referred to as phase transition tunneling anisotropic magnetoresistance. The junctions with only one α′-FeRh magnetic electrode show a magnetoresistance ratio up to 20% at room temperature. Both the polarity and magnitude of the phase transition tunneling anisotropic magnetoresistance can be modulated by interfacial engineering at the α′-FeRh/MgO interface. Besides the fundamental significance, our finding might add a different dimension to magnetic random access memory and antiferromagnet spintronics.
Community-like genome in single cells of the sulfur bacterium Achromatium oxaliferum
Authors: Ionescu Danny , Bizic-Ionescu Mina , De Maio Nicola , Cypionka Heribert , Grossart Hans-Peter 
Published: August 2017

AbstractPolyploid bacteria are common, but the genetic and functional diversity resulting from polyploidy is unknown. Here we use single-cell genomics, metagenomics, single-cell amplicon sequencing, and fluorescence in situ hybridization, to show that individual cells of Achromatium oxaliferum, the world’s biggest known freshwater bacterium, harbor genetic diversity typical of whole bacterial communities. The cells contain tens of transposable elements, which likely cause the unprecedented diversity that we observe in the sequence and synteny of genes. Given the high within-cell diversity of the usually conserved 16S ribosomal RNA gene, we suggest that gene conversion occurs in multiple, separated genomic hotspots. The ribosomal RNA distribution inside the cells hints to spatially differential gene expression. We also suggest that intracellular gene transfer may lead to extensive gene reshuffling and increased diversity.
Silicon quantum processor with robust long-distance qubit couplings
Authors: Tosi Guilherme , Mohiyaddin Fahd A. , Schmitt Vivien , Tenberg Stefanie , Rahman Rajib , Klimeck Gerhard , Morello Andrea 
Published: August 2017

AbstractPractical quantum computers require a large network of highly coherent qubits, interconnected in a design robust against errors. Donor spins in silicon provide state-of-the-art coherence and quantum gate fidelities, in a platform adapted from industrial semiconductor processing. Here we present a scalable design for a silicon quantum processor that does not require precise donor placement and leaves ample space for the routing of interconnects and readout devices. We introduce the flip-flop qubit, a combination of the electron-nuclear spin states of a phosphorus donor that can be controlled by microwave electric fields. Two-qubit gates exploit a second-order electric dipole-dipole interaction, allowing selective coupling beyond the nearest-neighbor, at separations of hundreds of nanometers, while microwave resonators can extend the entanglement to macroscopic distances. We predict gate fidelities within fault-tolerance thresholds using realistic noise models. This design provides a realizable blueprint for scalable spin-based quantum computers in silicon.
HSP90 inhibition enhances cancer immunotherapy by upregulating interferon response genes
Authors: Mbofung Rina M. , McKenzie Jodi A. , Malu Shruti , Zhang Min , Peng Weiyi , Liu Chengwen , Kuiatse Isere , Tieu Trang , Williams Leila , Devi Seram , Ashkin Emily , Xu Chunyu , Huang Lu , Zhang Minying , Talukder Amjad H. , Tripathi Satyendra C. , Khong Hiep , Satani Nikunj , Muller Florian L. , Roszik Jason , Heffernan Timothy , Allison James P. , Lizee Gregory , Hanash Sam M. , Proia David , Amaria Rodabe , Davis R. Eric , Hwu Patrick 
Published: August 2017

AbstractT-cell-based immunotherapies are promising treatments for cancer patients. Although durable responses can be achieved in some patients, many patients fail to respond to these therapies, underscoring the need for improvement with combination therapies. From a screen of 850 bioactive compounds, we identify HSP90 inhibitors as candidates for combination with immunotherapy. We show that inhibition of HSP90 with ganetespib enhances T-cell-mediated killing of patient-derived human melanoma cells by their autologous T cells in vitro and potentiates responses to anti-CTLA4 and anti-PD1 therapy in vivo. Mechanistic studies reveal that HSP90 inhibition results in upregulation of interferon response genes, which are essential for the enhanced killing of ganetespib treated melanoma cells by T cells. Taken together, these findings provide evidence that HSP90 inhibition can potentiate T-cell-mediated anti-tumor immune responses, and rationale to explore the combination of immunotherapy and HSP90 inhibitors.
Multivariate discovery and replication of five novel loci associated with Immunoglobulin G N-glycosylation
Authors: Shen Xia , Klarić Lucija , Sharapov Sodbo , Mangino Massimo , Ning Zheng , Wu Di , Trbojević-Akmačić Irena , Pučić-Baković Maja , Rudan Igor , Polašek Ozren , Hayward Caroline , Spector Timothy D. , Wilson James F. , Lauc Gordan , Aulchenko Yurii S. 
Published: August 2017

AbstractJoint modeling of a number of phenotypes using multivariate methods has often been neglected in genome-wide association studies and if used, replication has not been sought. Modern omics technologies allow characterization of functional phenomena using a large number of related phenotype measures, which can benefit from such joint analysis. Here, we report a multivariate genome-wide association studies of 23 immunoglobulin G (IgG) N-glycosylation phenotypes. In the discovery cohort, our multi-phenotype method uncovers ten genome-wide significant loci, of which five are novel (IGH, ELL2, HLA-B-C, AZI1, FUT6-FUT3). We convincingly replicate all novel loci via multivariate tests. We show that IgG N-glycosylation loci are strongly enriched for genes expressed in the immune system, in particular antibody-producing cells and B lymphocytes. We empirically demonstrate the efficacy of multivariate methods to discover novel, reproducible pleiotropic effects.
Promoting Drp1-mediated mitochondrial fission in midlife prolongs healthy lifespan of Drosophila melanogaster
Authors: Rana Anil , Oliveira Matheus P. , Khamoui Andy V. , Aparicio Ricardo , Rera Michael , Rossiter Harry B. , Walker David W. 
Published: August 2017

AbstractThe accumulation of dysfunctional mitochondria has been implicated in aging, but a deeper understanding of mitochondrial dynamics and mitophagy during aging is missing. Here, we show that upregulating Drp1—a Dynamin-related protein that promotes mitochondrial fission—in midlife, prolongs Drosophila lifespan and healthspan. We find that short-term induction of Drp1, in midlife, is sufficient to improve organismal health and prolong lifespan, and observe a midlife shift toward a more elongated mitochondrial morphology, which is linked to the accumulation of dysfunctional mitochondria in aged flight muscle. Promoting Drp1-mediated mitochondrial fission, in midlife, facilitates mitophagy and improves both mitochondrial respiratory function and proteostasis in aged flies. Finally, we show that autophagy is required for the anti-aging effects of midlife Drp1-mediated mitochondrial fission. Our findings indicate that interventions that promote mitochondrial fission could delay the onset of pathology and mortality in mammals when applied in midlife.
An in-silico approach to predict and exploit synthetic lethality in cancer metabolism
Authors: Apaolaza Iñigo , San José-Eneriz Edurne , Tobalina Luis , Miranda Estíbaliz , Garate Leire , Agirre Xabier , Prósper Felipe , Planes Francisco J. 
Published: August 2017

AbstractSynthetic lethality is a promising concept in cancer research, potentially opening new possibilities for the development of more effective and selective treatments. Here, we present a computational method to predict and exploit synthetic lethality in cancer metabolism. Our approach relies on the concept of genetic minimal cut sets and gene expression data, demonstrating a superior performance to previous approaches predicting metabolic vulnerabilities in cancer. Our genetic minimal cut set computational framework is applied to evaluate the lethality of ribonucleotide reductase catalytic subunit M1 (RRM1) inhibition in multiple myeloma. We present a computational and experimental study of the effect of RRM1 inhibition in four multiple myeloma cell lines. In addition, using publicly available genome-scale loss-of-function screens, a possible mechanism by which the inhibition of RRM1 is effective in cancer is established. Overall, our approach shows promising results and lays the foundation to build a novel family of algorithms to target metabolism in cancer.