bluuebunny/crossref_metadata_2025_split huggingface dataset:
Late Cretaceous Temperature Evolution of the Southern High Latitudes: A TEX86 Perspective
Authors: O'Connor Lauren K. , Robinson Stuart A. , Naafs B. David A. , Jenkyns Hugh C. , Henson Sam , Clarke Madeleine , Pancost Richard D. 
Published: February 2019

AbstractThe Late Cretaceous was a greenhouse world, characterized by elevated temperatures and high atmospheric pCO2. Even in the context of an extreme greenhouse climate, existing planktic foraminiferal δ18O data from the Falkland Plateau (paleolatitude of ~55°S) suggest anomalous warmth, with sea‐surface temperatures (SSTs) >30 °C for much of the Late Cretaceous, followed by sudden cooling in the Campanian. Over the last two decades, there has been discussion as to whether these high δ18O‐based SSTs reflect a genuine temperature signal and, if so, whether there was a local temperature anomaly in the South Atlantic or whether the data are representative of zonal paleotemperatures at 55°S. To provide new insights into the degree of ocean warming in the southern high latitudes during the Late Cretaceous (Cenomanian to Campanian), new SST records from the Falkland and Kerguelen Plateaus are presented here using the organic geochemical paleothermometer TetraEther indeX of 86 carbon atoms (TEX86). Overall, the TEX86 data support the δ18O data, indicating extreme and widespread warmth in the middle to high southern latitudes in the Late Cretaceous, with SSTs from 27 to 37 °C. Crucially, the TEX86 data show slow, steady cooling from the Turonian to the Campanian and suggest that temperature gradients during the Campanian did not become as steep as suggested by some planktic foraminiferal data.
Investigation of the impact of total sleep deprivation at home on the number of intrusive memories to an analogue trauma
Authors: Porcheret Kate , van Heugten–van der Kloet Dalena , Goodwin Guy M. , Foster Russell G. , Wulff Katharina , Holmes Emily A. 
Published: February 2019

AbstractSleep enhances the consolidation of memory; however, this property of sleep may be detrimental in situations where memories of an event can lead to psychopathology, such as following a traumatic event. Intrusive memories of trauma are emotional memories that spring to mind involuntarily and are a core feature of post-traumatic stress disorder. Total sleep deprivation in a hospital setting on the first night after an analogue trauma (a trauma film) led to fewer intrusive memories compared to sleep as usual in one study. The current study aimed to test an extension of these findings: sleep deprivation under more naturalistic conditions—at home. Polysomnographic recordings show inconsistent sleep deprivation was achieved at home. Fewer intrusive memories were reported on day 1 after the trauma film in the sleep-deprived condition. On day 2 the opposite was found: more intrusive memories in the sleep-deprived condition. However, no significant differences were found with the removal of two participants with extreme values and no difference was found in the total number of intrusive memories reported in the week following the trauma film. Voluntary memory of the trauma film was found to be slightly impaired in the sleep deprivation condition. In conclusion, compared to our eariler findings using total sleep deprivation in a hospital setting, in the current study the use of inconsistent sleep deprivation at home does not replicate the pattern of results on reducing the number of intrusive memories. Considering the conditions under which sleep deprivation (naturalistic versus hospital) was achieved requires further examination.
Tissue-infiltrating immune cells as prognostic markers in oral squamous cell carcinoma: a systematic review and meta-analysis
Authors: Hadler-Olsen Elin , Wirsing Anna Maria 
Published: February 2019

AbstractBackgroundVarious immune cells have been suggested as prognostic markers for cancer patients. In this article, we present a systematic review and meta-analysis of studies assessing the prognostic value of tissue-infiltrating immune cells in oral cancer and discuss the reporting quality of these studies.MethodsWe performed a systematic literature search and included studies using immunohistochemistry and survival analysis to assess the prognostic value of tumour-infiltrating T cells, B cells, macrophages, dendritic cells, mast cells and natural killer cells in oral cancer. We performed meta-analysis of studies providing necessary statistical data and investigated the studies’ adherence to the REporting recommendations for tumour MARKer prognostic studies (REMARK) guidelines.ResultsOf the 1960 articles identified, 33 were eligible for this systematic review and 8 were included in the meta-analysis. CD163+ M2 macrophages and CD57+ natural killer cells were the most promising predictors of survival in oral cancer patients. Many studies lacked important information on their design and conduct.ConclusionDeficiencies in the reporting of study design and conduct make it difficult to draw reliable conclusions about the suggested markers. The prognostic value of CD163+ M2 macrophages and CD57+ natural killer cells should be validated in large, standardised studies.
AKT-dependent and -independent pathways mediate PTEN deletion-induced CNS axon regeneration
Authors: Huang Haoliang , Miao Linqing , Yang Liu , Liang Feisi , Wang Qizhao , Zhuang Pei , Sun Yang , Hu Yang 
Published: February 2019

AbstractPhosphatase and tensin homolog (PTEN) acts as a brake for the phosphatidylinositol 3-kinase–AKT–mTOR complex 1 (mTORC1) pathway, the deletion of which promotes potent central nervous system (CNS) axon regeneration. Previously, we demonstrated that AKT activation is sufficient to promote CNS axon regeneration to a lesser extent than PTEN deletion. It is still questionable whether AKT is entirely responsible for the regenerative effect of PTEN deletion on CNS axons. Here, we show that blocking AKT or its downstream effectors, mTORC1 and GSK3β, significantly reduces PTEN deletion-induced mouse optic nerve regeneration, indicating the necessary role of AKT-dependent signaling. However, AKT is only marginally activated in PTEN-null mice due to mTORC1-mediated feedback inhibition. That combining PTEN deletion with AKT overexpression or GSK3β deletion achieves significantly more potent axonal regeneration suggests an AKT-independent pathway for axon regeneration. Elucidating the AKT-independent pathway is required to develop effective strategies for CNS axon regeneration.
Organoids as a new model for improving regenerative medicine and cancer personalized therapy in renal diseases
Authors: Grassi Ludovica , Alfonsi Romina , Francescangeli Federica , Signore Michele , De Angelis Maria Laura , Addario Antonio , Costantini Manuela , Flex Elisabetta , Ciolfi Andrea , Pizzi Simone , Bruselles Alessandro , Pallocca Matteo , Simone Giuseppe , Haoui Mustapha , Falchi Mario , Milella Michele , Sentinelli Steno , Di Matteo Paola , Stellacci Emilia , Gallucci Michele , Muto Giovanni , Tartaglia Marco , De Maria Ruggero , Bonci Désirée 
Published: February 2019

AbstractThe pressure towards innovation and creation of new model systems in regenerative medicine and cancer research has fostered the development of novel potential therapeutic applications. Kidney injuries provoke a high request of organ transplants making it the most demanding system in the field of regenerative medicine. Furthermore, renal cancer frequently threaten patients’ life and aggressive forms still remain difficult to treat. Ethical issues related to the use of embryonic stem cells, has fueled research on adult, patient-specific pluripotent stem cells as a model for discovery and therapeutic development, but to date, normal and cancerous renal experimental models are lacking. Several research groups are focusing on the development of organoid cultures. Since organoids mimic the original tissue architecture in vitro, they represent an excellent model for tissue engineering studies and cancer therapy testing. We established normal and tumor renal cell carcinoma organoids previously maintained in a heterogeneous multi-clone stem cell-like enriching medium. Starting from adult normal kidney specimens, we were able to isolate and propagate organoid 3D-structures composed of both differentiated and undifferentiated cells while expressing nephron specific markers. Furthermore, we were capable to establish organoids derived from cancer tissues although with a success rate inferior to that of their normal counterpart. Cancer cultures displayed epithelial and mesenchymal phenotype while retaining tumor specific markers. Of note, tumor organoids recapitulated neoplastic masses when orthotopically injected into immunocompromised mice. Our data suggest an innovative approach of long-term establishment of normal- and cancer-derived renal organoids obtained from cultures of fleshly dissociated adult tissues. Our results pave the way to organ replacement pioneering strategies as well as to new models for studying drug-induced nephrotoxicity and renal diseases. Along similar lines, deriving organoids from renal cancer patients opens unprecedented opportunities for generation of preclinical models aimed at improving therapeutic treatments.
The intracellular domain of β-dystroglycan mediates the nucleolar stress response by suppressing UBF transcriptional activity
Authors: Azuara-Medina Paulina Margarita , Sandoval-Duarte Ariana María , Morales-Lázaro Sara L. , Modragón-González Ricardo , Vélez-Aguilera Griselda , Gómez-López Juan de Dios , Jiménez-Gutiérrez Guadalupe Elizabeth , Tiburcio-Félix Reynaldo , Martínez-Vieyra Ivette , Suárez-Sánchez Rocío , Längst Gernot , Magaña Jonathan Javier , Winder Steve J. , Ortega Arturo , Ramos Perlingeiro Rita de Cassia , Jacobs Laura A. , Cisneros Bulmaro 
Published: February 2019

Abstractβ-dystroglycan (β-DG) is a key component of multiprotein complexes in the plasma membrane and nuclear envelope. In addition, β-DG undergoes two successive proteolytic cleavages that result in the liberation of its intracellular domain (ICD) into the cytosol and nucleus. However, stimuli-inducing ICD cleavage and the physiological relevance of this proteolytic fragment are largely unknown. In this study we show for the first time that β-DG ICD is targeted to the nucleolus where it interacts with the nuclear proteins B23 and UBF (central factor of Pol I-mediated rRNA gene transcription) and binds to rDNA promoter regions. Interestingly DG silencing results in reduced B23 and UBF levels and aberrant nucleolar morphology. Furthermore, β-DG ICD cleavage is induced by different nucleolar stressors, including oxidative stress, acidosis, and UV irradiation, which implies its participation in the response to nucleolar stress. Consistent with this idea, overexpression of β-DG elicited mislocalization and decreased levels of UBF and suppression of rRNA expression, which in turn provoked altered ribosome profiling and decreased cell growth. Collectively our data reveal that β-DG ICD acts as negative regulator of rDNA transcription by impeding the transcriptional activity of UBF, as a part of the protective mechanism activated in response to nucleolar stress.
A novel variant in FN1 in a family with fibronectin glomerulopathy
Authors: Aslam Nabeel , Singh Anshika , Cortese Cherise , Riegert-Johnson Douglas L. 
Published: February 2019

AbstractGlomerulopathy with fibronectin deposits (GFND) is a rare glomerular disorder. We report a 28-year-old male diagnosed with GFND by mass spectrometry on kidney biopsy tissue. Whole-exome sequencing (WES) identified that a previously undescribed FN1 gene mutation (c.3051G > T, p.W1017C) was likely responsible for this patient’s fibronectin glomerulopathy. We discuss the implications of this novel variant of FN1 and the importance of WES to identify a mutation in a gene of interest.
Secreted metalloproteases ADAMTS9 and ADAMTS20 have a non-canonical role in ciliary vesicle growth during ciliogenesis
Authors: Nandadasa Sumeda , Kraft Caroline M. , Wang Lauren W. , O’Donnell Anna , Patel Rushabh , Gee Heon Yung , Grobe Kay , Cox Timothy C. , Hildebrandt Friedhelm , Apte Suneel S. 
Published: February 2019

AbstractAlthough hundreds of cytosolic or transmembrane molecules form the primary cilium, few secreted molecules are known to contribute to ciliogenesis. Here, homologous secreted metalloproteases ADAMTS9 and ADAMTS20 are identified as ciliogenesis regulators that act intracellularly. Secreted and furin-processed ADAMTS9 bound heparan sulfate and was internalized by LRP1, LRP2 and clathrin-mediated endocytosis to be gathered in Rab11 vesicles with a unique periciliary localization defined by super-resolution microscopy. CRISPR-Cas9 inactivation of ADAMTS9 impaired ciliogenesis in RPE-1 cells, which was restored by catalytically active ADAMTS9 or ADAMTS20 acting in trans, but not by their proteolytically inactive mutants. Their mutagenesis in mice impaired neural and yolk sac ciliogenesis, leading to morphogenetic anomalies resulting from impaired hedgehog signaling, which is transduced by primary cilia. In addition to their cognate extracellular proteolytic activity, ADAMTS9 and ADAMTS20 thus have an additional proteolytic role intracellularly, revealing an unexpected regulatory dimension in ciliogenesis.
Subnanometer cobalt oxide clusters as selective low temperature oxidative dehydrogenation catalysts
Authors: Lee Sungsik , Halder Avik , Ferguson Glen A. , Seifert Sönke , Winans Randall E. , Teschner Detre , Schlögl Robert , Papaefthimiou Vasiliki , Greeley Jeffrey , Curtiss Larry A. , Vajda Stefan 
Published: February 2019

AbstractThe discovery of more efficient, economical, and selective catalysts for oxidative dehydrogenation is of immense economic importance. However, the temperatures required for this reaction are typically high, often exceeding 400 °C. Herein, we report the discovery of subnanometer sized cobalt oxide clusters for oxidative dehydrogenation of cyclohexane that are active at lower temperatures than reported catalysts, while they can also eliminate the combustion channel. These results found for the two cluster sizes suggest other subnanometer size (CoO)xclusters will also be active at low temperatures. The high activity of the cobalt clusters can be understood on the basis of density functional studies that reveal highly active under-coordinated cobalt atoms in the clusters and show that the oxidized nature of the clusters substantially decreases the binding energy of the cyclohexene species which desorb from the cluster at low temperature.
An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics
Authors: Angelidis Ilias , Simon Lukas M. , Fernandez Isis E. , Strunz Maximilian , Mayr Christoph H. , Greiffo Flavia R. , Tsitsiridis George , Ansari Meshal , Graf Elisabeth , Strom Tim-Matthias , Nagendran Monica , Desai Tushar , Eickelberg Oliver , Mann Matthias , Theis Fabian J. , Schiller Herbert B. 
Published: February 2019

AbstractAging promotes lung function decline and susceptibility to chronic lung diseases, which are the third leading cause of death worldwide. Here, we use single cell transcriptomics and mass spectrometry-based proteomics to quantify changes in cellular activity states across 30 cell types and chart the lung proteome of young and old mice. We show that aging leads to increased transcriptional noise, indicating deregulated epigenetic control. We observe cell type-specific effects of aging, uncovering increased cholesterol biosynthesis in type-2 pneumocytes and lipofibroblasts and altered relative frequency of airway epithelial cells as hallmarks of lung aging. Proteomic profiling reveals extracellular matrix remodeling in old mice, including increased collagen IV and XVI and decreased Fraser syndrome complex proteins and collagen XIV. Computational integration of the aging proteome with the single cell transcriptomes predicts the cellular source of regulated proteins and creates an unbiased reference map of the aging lung.
Enantioselective Rhodium-Catalyzed Cycloisomerization of 1,6-Allenynes to access 5/6-Fused Bicycle[4.3.0]nonadienes
Authors: Deng Xu , Shi Li-Yang , Lan Jialing , Guan Yu-Qing , Zhang Xiaoyong , Lv Hui , Chung Lung Wa , Zhang Xumu 
Published: February 2019

AbstractTransition-metal-catalyzed cycloisomerization of 1,n-allenynes represents a powerful synthetic tool to rapidly assemble complex polycyclic skeletons from simple linear substrates. Nevertheless, there are no reports of the asymmetric version of these reactions. Moreover, most of these reactions proceed through a 6-endo-dig cyclization pathway, which preferentially delivers the distal product (via 5/5 rhodacyclic intermediate) rather than the proximal one (via 6/5 rhodacyclic intermediate). Herein, we report an enantioselective rhodium(I)-catalyzed cycloisomerization of 1,6-allenynes to provide the proximal product 5/6-fused bicycle[4.3.0]nonadienes in good yields and with excellent enantioselectivities. Remarkably, this chemistry works perfectly for 1,6-allenynes having a cyclic substituent within the allene component, thereby affording synthetically formidable tricyclic products with excellent enantioselectivities. Moreover, extensive DFT calculations suggest an uncommon pathway involving 5-exo-dig cycloisomerization, ring-expansion, rate-determining alkene isomerization involving Csp3-H activation, C-C activation of the cyclobutene moiety and finally reductive elimination. Deuterium labeling experiments support the rate-determining step involving the C–H bond activation in this transformation.
Omegasome-proximal PtdIns(4,5)P2 couples F-actin mediated mitoaggregate disassembly with autophagosome formation during mitophagy
Authors: Hsieh Cheng-Wei , Yang Wei Yuan 
Published: February 2019

AbstractCells govern their homeostasis through autophagy by sequestering substrates, ranging from proteins to aggregates and organelles, into autophagosomes for lysosomal degradation. In these processes cells need to coordinate between substrate remodeling and autophagosome formation for efficient engulfment. We found that in Parkin-mediated mitophagy, mitochondria to be turned over first become grape-like mitoaggregates, followed by their disassembly into smaller pieces via the actinomyosin system. At the disassembly step, we observed spatially-associated, synchronous formation of circular F-actin and BATS-labeled autophagy initiation sites near mitochondria, suggesting coordination between substrate downsizing and autophagosome formation during mitophagy. Interestingly, PtdIns(4,5)P2, instead of PtdIns(3)P, regulates this mitophagy-associated formation of circular F-actin and BATS-sites. Selective depletion of PtdIns(4,5)P2near omegasomes, the endoplasmic reticulum (ER) subdomains involved in autophagosome formation, impaired mitoaggregate disassembly. Our findings demonstrate the presence of a pool of PtdIns(4,5)P2adjacent to omegasomes, and that they coordinate mitoaggregate disassembly with autophagy initiation during Parkin-mediated mitophagy.
Epigenetic clock analysis of blood samples from Japanese schizophrenia patients
Authors: Okazaki Satoshi , Otsuka Ikuo , Numata Shusuke , Horai Tadasu , Mouri Kentaro , Boku Shuken , Ohmori Tetsuro , Sora Ichiro , Hishimoto Akitoyo 
Published: February 2019

AbstractThe accelerated aging hypothesis of schizophrenia (SCZ) has been proposed. DNA methylation profiles were developed for determining “epigenetic age.” Here, we assessed intrinsic and extrinsic epigenetic age acceleration (IEAA and EEAA, respectively) in SCZ. We examined two independent cohorts of Japanese ancestry. The first cohort consisted of 80 patients with SCZ under long-term or repeated hospitalization and 40 controls, with the economical DNA pooling technique. The second cohort consisted of 24 medication-free patients with SCZ and 23 controls. Blood of SCZ subjects exhibited decreased EEAA in the first cohort (p = 0.0162), but not in the second cohort. IEAA did not differ in either cohort. We performed replication analyses using publicly available datasets from European ancestry (three blood and one brain datasets). One blood dataset showed increased EEAA in SCZ (p = 0.0228). Overall, our results provide evidence for decreased EEAA in SCZ associated with hospitalization in the Japanese population.
Multiple mutations in the nicotinic acetylcholine receptor Ccα6 gene associated with resistance to spinosad in medfly
Authors: Ureña Enric , Guillem-Amat Ana , Couso-Ferrer Francisco , Beroiz Beatriz , Perera Nathalia , López-Errasquín Elena , Castañera Pedro , Ortego Félix , Hernández-Crespo Pedro 
Published: February 2019

AbstractSpinosad is an insecticide widely used for the control of insect pest species, including Mediterranean fruit fly, Ceratitis capitata. Its target site is the α6 subunit of the nicotinic acetylcholine receptors, and different mutations in this subunit confer resistance to spinosad in diverse insect species. The insect α6 gene contains 12 exons, with mutually exclusive versions of exons 3 (3a, 3b) and 8 (8a, 8b, 8c). We report here the selection of a medfly strain highly resistant to spinosad, JW-100 s, and we identify three recessive Ccα6 mutant alleles in the JW-100 s population: (i) Ccα63aQ68* containing a point mutation that generates a premature stop codon on exon 3a (3aQ68*); (ii) Ccα63aAG>AT containing a point mutation in the 5′ splicing site of exon 3a (3aAG > AT); and (iii) Ccα63aQ68*-K352* that contains the mutation 3aQ68* and another point mutation on exon 10 (K352*). Though our analysis of the susceptibility to spinosad in field populations indicates that resistance has not yet evolved, a better understanding of the mechanism of action of spinosad is essential to implement sustainable management practices to avoid the development of resistance in field populations.
Fabrication of transition metal dichalcogenides quantum dots based on femtosecond laser ablation
Authors: Xu Yanmin , Yan Lihe , Li Xiaoyu , Xu Huanhuan 
Published: February 2019

AbstractAs heavy metal-free quantum dots, transition metal dichalcogenides (TMDs) and boron nitride (BN) quantum dots (QDs) have aroused great interest due to features such as good thermal conductivity, chemical stability, and unique optical properties. Although TMDs have been synthesized using different methods, most of these methods require time-consuming or complex steps, limiting the applications of TMDs. We propose a fast and simple method for the synthesis of high-quality molybdenum disulfide (MoS2) QDs and tungsten disulfide (WS2) QDs based on femtosecond laser ablation and sonication-assisted liquid exfoliation. The prepared MoS2 QDs and WS2 QDs were characterized by transmission electron microscopy, atomic force microscopy, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy. The resulting products possessed few-layered thickness with an average size of 3.7 nm and 2.1 nm. Due to the abundance of functional groups on their surface, the MoS2 QDs and WS2 QDs showed bright blue-green luminescence under UV irradiation. Our method offers a facile and novel synthetic strategy for TMDs QDs and other two-dimensional nanomaterial quantum dots, such as boron nitride quantum dots (BNQDs).