bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinctive Seafloor Fabric Produced Near Western Versus Eastern Ridge‐Transform Intersections of the Northern Mid‐Atlantic Ridge: Possible Influence of Ridge Migration
Authors: Cormier Marie‐Helene , Sloan Heather
Published: February 2019

Multibeam bathymetry compiled along fracture zones of the northern Atlantic reveals a striking morphological asymmetry. Seafloor fabric produced at western ridge‐transform intersections (RTIs) tends to consist of linear ridges, small in amplitude, and regularly spaced, and oceanic core complexes (OCCs) occur infrequently. In contrast, seafloor fabric produced at eastern RTIs is more irregular and blocky and displays characteristics usually associated with melt‐poor accretion: These include more than double the occurrence of OCCs as well as greater seafloor depths, even where seafloor is younger than that on the opposite side of the fracture zone. We propose that this asymmetry is a consequence of the westward migration of the Mid‐Atlantic Ridge. Such migration is expected to result in an enhanced melt supply at leading (western) RTIs compared to trailing (eastern) RTIs. The morphological asymmetry is observed for ridge offsets of ~40 to ~200 km, a range that may be related to the width of melting regimes that supply ridge segments. At slow spreading ridges, contrasting melt supplies across fracture zones may therefore be best expressed in the distinct seafloor fabrics preserved beyond the dynamically maintained relief of the axial rift valley and walls rather than in the contrasting axial depths documented for faster spreading ridges. Although OCCs appear to form preferentially at spreading rates lower than 30 mm/year, their common occurrence along the northern Mid‐Atlantic Ridge may also reflect the significantly higher rates at which it is migrating compared to the southern Mid‐Atlantic Ridge.
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

The 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

Sleep 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

Background

Various 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.

Methods

We 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.

Results

Of 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.

Conclusion

Deficiencies 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

Phosphatase 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

The 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

β-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

Glomerulopathy 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

Although 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

The 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

Aging 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

Transition-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

Cells 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

The 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

Spinosad 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

As 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).
A novel ABA functional analogue B2 enhances drought tolerance in wheat
Authors: Zhou Yuyi , He Rui , Guo Yuling , Liu Keke , Huang Guanmin , Peng Chuanxi , Liu Yiguo , Zhang Mingcai , Li Zhaohu , Duan Liusheng
Published: February 2019

Drought stress negatively affects wheat growth and yield. Application of drought agent is an effective way to improve crop drought tolerance, therefore increasing crop yield. Based on the structure of abscisic acid (ABA), Pyrabactin and coronatine (COR), we designed the target compound B2. To investigate the function of B2 in alleviating drought stress on wheat, the drought-resistant variety ND212 and drought-sensitive variety LX99 were used under hydroponic conditions. The results showed that B2 had a similar function with ABA, especially 0.01 μmol·L−1 B2. Under drought stress conditions, 0.01 μmol·L−1 B2 increased the water content of wheat, enhanced the osmotic adjustment ability of leaves, and reduced the toxicity of reactive oxygen species on cells. What’s more, 0.01 μmol·L−1 B2 improved the expression level of ABA-responsive genes TaSnRK2.4 and TaMYB3R1. It also improved the expression level of drought-responsive genes TaSRHP and TaERF3. Taken together, B2 enhanced drought tolerance in wheat by activating ABA signaling pathway.
Long fragments achieve lower base quality in Illumina paired-end sequencing
Authors: Tan Ge , Opitz Lennart , Schlapbach Ralph , Rehrauer Hubert
Published: February 2019

Illumina’s technology provides high quality reads of DNA fragments with error rates below 1/1000 per base. Sequencing runs typically generate millions of reads in which the vast majority of the reads has an average error rate below 1/1000. However, some paired-end sequencing data show the presence of a subpopulation of reads where the second read (R2) has lower average qualities. We show that the fragment length is a major driver of increased error rates in the R2 reads. Fragments above 500 nt tend to yield lower base qualities and higher error rates than shorter fragments. We use publicly available Illumina data to demonstrate that the fragment length dependency of the R2 read qualities exists in various library protocols, in different labs and using different sequencer models. Our finding extends the understanding of the Illumina read quality and has implications on error models for Illumina reads. It also sheds a light on the importance of controlling the fragment size during library preparation.
Towards Improving Embryo Prioritization: Parallel Next Generation Sequencing of DNA and RNA from a Single Trophectoderm Biopsy
Authors: Fuchs Weizman Noga , Wyse Brandon A. , Antes Ran , Ibarrientos Zenon , Sangaralingam Mugundhine , Motamedi Gelareh , Kuznyetsov Valeriy , Madjunkova Svetlana , Librach Clifford L.
Published: February 2019

Improved embryo prioritization is crucial in optimizing the results in assisted reproduction, especially in light of increasing utilization of elective single embryo transfers. Embryo prioritization is currently based on morphological criteria and in some cases incorporates preimplantation genetic testing for aneuploidy (PGT-A). Recent technological advances have enabled parallel genomic and transcriptomic assessment of a single cell. Adding transcriptomic analysis to PGT-A holds promise for better understanding early embryonic development and implantation, and for enhancing available embryo prioritization tools. Our aim was to develop a platform for parallel genomic and transcriptomic sequencing of a single trophectoderm (TE) biopsy, that could later be correlated with clinical outcomes. Twenty-five embryos donated for research were utilized; eight for initial development and optimization of our method, and seventeen to demonstrate clinical safety and reproducibility of this method. Our method achieved 100% concordance for ploidy status with that achieved by the classic PGT-A. All sequencing data exceeded quality control metrics. Transcriptomic sequencing data was sufficient for performing differential expression (DE) analysis. All biopsies expressed specific TE markers, further validating the accuracy of our method. Using PCA, samples clustered in euploid and aneuploid aggregates, highlighting the importance of controlling for ploidy in every transcriptomic assessment.
Non-Markovianity of qubit evolution under the action of spin environment
Authors: Chakraborty Sagnik , Mallick Arindam , Mandal Dipanjan , Goyal Sandeep K. , Ghosh Sibasish
Published: February 2019

The question, whether an open system dynamics is Markovian or non-Markovian can be answered by studying the direction of the information flow in the dynamics. In Markovian dynamics, information must always flow from the system to the environment. If the environment is interacting with only one of the subsystems of a bipartite system, the dynamics of the entanglement in the bipartite system can be used to identify the direction of information flow. Here we study the dynamics of a two-level system interacting with an environment, which is also a heat bath, and consists of a large number of two-level quantum systems. Our model can be seen as a close approximation to the ‘spin bath’ model at low temperatures. We analyze the Markovian nature of the dynamics, as we change the coupling between the system and the environment. We find the Kraus operators of the dynamics for certain classes of couplings. We show that any form of time-independent or time-polynomial coupling gives rise to non-Markovianity. Also, we witness non-Markovianity for certain parameter values of time-exponential coupling. Moreover, we study the transition from non-Markovian to Markovian dynamics as we change the value of coupling strength.
Leptin receptor deficiency induces early, transient and hyperglycaemia-independent blood-brain barrier dysfunction
Authors: Corem Noa , Anzi Shira , Gelb Sivan , Ben-Zvi Ayal
Published: February 2019

Diabetes mellitus (DM) significantly increases susceptibility to central nervous system (CNS) pathologies, including stroke, vascular dementia, cognitive deficits and Alzheimer’s disease. Previous studies (mostly using the streptozotocin model) suggested that blood-brain barrier (BBB) disruption is involved in these conditions. Here, we examined the integrity of brain capillaries and BBB permeability in Leprdb/db obesity-related diabetic mice. Surprisingly, significant BBB leakage was observed only in young mice at the pre-hyperglycemic stage. Thorough examination of barrier permeability at later diabetic stages showed no evidence for significant BBB leakage during the hyperglycemic state. Electron microscopy imaging of mice with short-term hyperglycaemia supported normal BBB permeability but indicated other stress-related changes in capillary ultrastructure, such as mitochondrial degeneration. Based on our study with this mouse genetic model of obesity-related DM, we suggest that previously reported hyperglycaemia-induced BBB leakage is most likely not the underlying mechanism of DM-related CNS pathologies. Finally we propose that BBB hyper-permeability might be an early and transient phenomenon while stress-related endothelial pathologies do correlate with a short-term diabetic state.
Multi-parameters of Magnetic Resonance Imaging to Estimate Ischemia-Reperfusion Injury after Stroke in Hyperglycemic Rats
Authors: Huang Wei-yuan , Wu Gang , Guo Shan-xi , Geng Dao-ying , Li Jian-jun , Yang Kai
Published: February 2019

The aim of the study is to verify the effect of hyperglycemia on ischemia-reperfusion injury and to explore the feasibility of noninvasive observation of ischemic-reperfusion injury in hyperglycemic ischemic stroke by MRI technique. According to the duration of ischemia and blood glucose levels, 40 rats were divided into hyperglycemic ischemic 2-hr (H-I2h), hyperglycemic ischemic 6-hr (H-I6h), non- hyperglycemic ischemic 2-hr (NH-I2h), and non- hyperglycemic ischemic 6-hr (NH-I6h) groups. T2W imaging, DW imaging, T2 mapping, T2* mapping, DCE, and T1 mapping after enhancement sequences were acquired before reperfusion and approximately 3-hr after reperfusion. ADC, T1, T2, T2*, and Ktrans values of ischemic lesion were obtained in different groups. After reperfusion, the variation of ADC values showed no significant difference between groups with diabetes and groups without diabetes and between different recanalization time-points (2-hr vs 6-hr). After reperfusion, T2, T2*, and Ktrans values increased in different degrees in all four groups. Only the T1 value decreased in all groups. The change of all parameters in groups with hyperglycemia was more obvious than that in groups without hyperglycemia and was more obvious in groups with H-I6h versus those with H-I2h. This study confirms that hyperglycemia aggravates ischemia-reperfusion injury and may be an important risk factor for the prognosis of ischemic stroke. The Ktrans values should be noninvasive imaging indicators to monitor blood brain barrier permeability and ischemic-reperfusion injury in ischemic stroke.
Dynamic generation of multi-qubit entanglement in the ultrastrong-coupling regime
Authors: Liu Xin , Liao Qinghong , Fang Guangyu , Liu Shutian
Published: February 2019

We propose a dynamic evolution protocol for generating multi-qubit GHZ states in the ultrastrong-coupling regime of circuit QED. By varying the time length of sequences, the protocol works for any coupling strength g/ωr ≥ 0.25. The time for generating the GHZ states in our protocol can be in the subnanoseconds. By taking into account realistic parameters of circuit QED, the degeneracy of fidelity due to decoherence can be as low as 0.02%.
Insulin secretory granules labelled with phogrin-fluorescent proteins show alterations in size, mobility and responsiveness to glucose stimulation in living β-cells
Authors: Ferri Gianmarco , Digiacomo Luca , Lavagnino Zeno , Occhipinti Margherita , Bugliani Marco , Cappello Valentina , Caracciolo Giulio , Marchetti Piero , Piston David W. , Cardarelli Francesco
Published: February 2019

The intracellular life of insulin secretory granules (ISGs) from biogenesis to secretion depends on their structural (e.g. size) and dynamic (e.g. diffusivity, mode of motion) properties. Thus, it would be useful to have rapid and robust measurements of such parameters in living β-cells. To provide such measurements, we have developed a fast spatiotemporal fluctuation spectroscopy. We calculate an imaging-derived Mean Squared Displacement (iMSD), which simultaneously provides the size, average diffusivity, and anomalous coefficient of ISGs, without the need to extract individual trajectories. Clustering of structural and dynamic quantities in a multidimensional parametric space defines the ISGs’ properties for different conditions. First, we create a reference using INS-1E cells expressing proinsulin fused to a fluorescent protein (FP) under basal culture conditions and validate our analysis by testing well-established stimuli, such as glucose intake, cytoskeleton disruption, or cholesterol overload. After, we investigate the effect of FP-tagged ISG protein markers on the structural and dynamic properties of the granule. While iMSD analysis produces similar results for most of the lumenal markers, the transmembrane marker phogrin-FP shows a clearly altered result. Phogrin overexpression induces a substantial granule enlargement and higher mobility, together with a partial de-polymerization of the actin cytoskeleton, and reduced cell responsiveness to glucose stimulation. Our data suggest a more careful interpretation of many previous ISG-based reports in living β-cells. The presented data pave the way to high-throughput cell-based screening of ISG structure and dynamics under various physiological and pathological conditions.
Investigating causality in the association between vitamin D status and self-reported tiredness
Authors: Havdahl Alexandra , Mitchell Ruth , Paternoster Lavinia , Davey Smith George
Published: February 2019

Self-reported tiredness or low energy, often referred to as fatigue, has been linked to low levels of circulating 25-hydroxyvitamin D (25OHD), a biomarker of vitamin D status. Although it is uncertain if the association is causal, fatigue is a common indication for testing, and correcting, low 25OHD-levels. We used two-sample Mendelian randomization to test for genetic evidence of a causal association between low 25OHD-levels and fatigue. Genetic-25OHD associations were estimated from the largest genome-wide association study of vitamin D to date, and genetic-fatigue associations were estimated in 327,478 individuals of European descent in UK Biobank, of whom 19,526 (5.96%) reported fatigue (tiredness or low energy nearly every day over the past two weeks). Using seven genome-wide significant 25OHD-reducing genetic variants, there was little evidence for a causal effect of 25OHD on fatigue [odds ratio for fatigue was 1.05 with 95% confidence interval (CI) of 0.87–1.27 per unit decrease in log-transformed 25OHD (1.02 with 95% CI of 0.99-1.06 per 1-SD decrease in log-transformed 25OHD)]. There was also little evidence of association between any individual 25OHD-reducing variant and fatigue. Our results suggest that a clinically relevant protective effect of 25OHD-levels on fatigue is unlikely. Therefore, vitamin D supplementation of the general population to raise 25OHD-levels is not likely to be useful in preventing fatigue.
TSA restores hair follicle-inductive capacity of skin-derived precursors
Authors: Guo Ling , Wang Xiaoxiao , Yuan Jifan , Zhu Meishu , Fu Xiaobing , Xu Ren-He , Wu Chuanyue , Wu Yaojiong
Published: February 2019

The genesis of the hair follicle relies on signals derived from mesenchymal cells in the dermis during skin morphogenesis and regeneration. Multipotent skin-derived precursors (SKPs), which exhibit long term proliferation potential when being cultured in spheroids, have been shown to induce hair genesis and hair follicle regeneration in mice, implying a therapeutic potential of SKPs in hair follicle regeneration and bioengineering. However, the hair-inductive property of SKPs declines progressively upon ex vivo culture expansion, suggesting that the expressions of the genes responsible for hair induction are epigenetically unstable. In this study, we found that TSA markedly alleviated culture expansion induced SKP senescence, increased the expression and activity of alkaline phosphatase (AP) in the cells and importantly restored the hair inductive capacity of SKPs. TSA increased the acetylation level of histone H3, including the K19/14 sites in the promoter regions of bone morphogenetic proteins (BMPs) genes, which were associated with elevated gene expression and BMP signaling activity, suggesting a potential attribution of BMP pathway in TSA induced recovery of the hair inductive capacity of SKPs.
Flat-band localization and self-collimation of light in photonic crystals
Authors: Myoung Nojoon , Park Hee Chul , Ramachandran Ajith , Lidorikis Elefterios , Ryu Jung-Wan
Published: February 2019

We investigate the optical properties of a photonic crystal (PC) composed of a quasi-one-dimensional flat-band lattice array through finite-difference time-domain simulations. The photonic bands contain flat bands (FBs) at specific frequencies, which correspond to compact localized states as a consequence of destructive interference. The FBs are shown to be nondispersive along the Г → X line, prohibiting optical transmission with incident light in x direction. On the other hand, the photonic band for the FB frequency is found to be dispersive along the Г → Y line, resulting in nonzero optical transmission. Such anisotropic optical response of the PC due to the FB localization of light in a single direction only results in a self-collimation of light propagation throughout the PC at the FB frequency.
Alteration of specific cytokine expression patterns in patients with breast cancer
Authors: Kawaguchi Kosuke , Sakurai Masashi , Yamamoto Yasuko , Suzuki Eiji , Tsuda Moe , Kataoka Tatsuki R. , Hirata Masahiro , Nishie Mariko , Nojiri Takashi , Kumazoe Motofumi , Saito Kuniaki , Toi Masakazu
Published: February 2019

Systemic inflammation has been associated with aggressive tumor growth, invasion, and metastasis. Here we performed a comprehensive analysis of 26 kinds of inflammatory cytokine expression patterns among 185 patients with breast cancer and 54 healthy volunteers followed by chemometric analysis. We identified the specific cytokine expression patterns of breast cancer patients compared to healthy volunteers with (1) VEGF, IL-9, GM-CSF, IL-13, IL-4, and IFNγ, (2) IL-8, IL-10, IL-12, IL-5, IL-7, IL-1α, GCSF, IL-1β, and TNFα and (3) IL-2, Eotaxin, MIP1β, MIP1α, IL-17, and bFGF. Among the patients with breast cancer, we identified the specific cytokine signature of metastatic patients compared to non-metastatic patients. We also established a mathematical model for distinguishing patients with breast cancer from healthy volunteers and metastatic patients from non-metastatic patients. This cytokine network analysis could provide new insights into early intervention and effective therapeutic strategy for patients with breast cancer.
Nuclear import of Xenopus egg extract components into cultured cells for reprogramming purposes: a case study on goldfish fin cells
Authors: Chênais Nathalie , Lorca Thierry , Morin Nathalie , Guillet Brigitte , Rime Hélène , Le Bail Pierre-Yves , Labbé Catherine
Published: February 2019

Reprogramming of cultured cells using Xenopus egg extract involves controlling four major steps: plasma membrane permeabilization, egg factors import into the nucleus, membrane resealing, and cell proliferation. Using propidium iodide to assess plasma membrane permeability, we established that 90% of the cultured fin cells were permeabilized by digitonin without any cell losses. We showed that egg extract at metaphase II stage was essential to maintain nuclear import function in the permeabilized cells, as assessed with a fusion GFP protein carrying the nuclear import signal NLS. Moreover, the Xenopus-egg-specific Lamin B3 was detected in 87% of the cell nuclei, suggesting that other egg extract reprogramming factors of similar size could successfully enter the nucleus. Lamin B3 labelling was maintained in most cells recovered 24 h after membrane resealing with calcium, and cells successfully resumed cell cycle in culture. In contrast, permeabilized cells that were not treated with egg extract failed to proliferate in culture and died, implying that egg extract provided factor essential to the survival of those cells. To conclude, fish fin cells were successfully primed for treatment with reprogramming factors, and egg extract was shown to play a major role in their survival and recovery after permeabilization.
Unprecedented Microbial Conversion of Biliverdin into Bilirubin-10-sulfonate
Authors: Shiels Ryan G. , Vidimce Josif , Pearson Andrew G. , Matthews Ben , Wagner Karl-Heinz , Battle Andrew R. , Sakellaris Harry , Bulmer Andrew C.
Published: February 2019

Biliverdin (BV) possesses antioxidant and anti-inflammatory properties, with previous reports identifying protection against oxidant and inflammatory injury in animal models. Recent reports indicate that intra-duodenal administration of BV results in the formation of an uncharacterised metabolite, which is potently absorbed into the blood and excreted into the bile. This compound may be responsible for protection against inflammatory responses. This study aimed to identify novel, enterally-derived BV metabolites and determine the source of their metabolic transformation. Rat duodena and bacterial cultures of Citrobacter youngae were treated with BV and subsequently analysed via high performance liquid chromatography/high resolution tandem mass spectrometry to identify and characterise metabolites of BV. A highly abundant metabolite was detected in duodenal wash and bacterial culture supernatants with a 663.215 m/z (3 ppm mass accuracy) and a composition of C33N4O9H36S, which conformed to the predicted structure of bilirubin-10-sulfonate (BRS) and possessed a λmax of 440 nm. Bilirubin-10-sulfonate was then synthesized for comparative LCMS/MS analysis and matched with that of the biologically formed BV metabolite. This report confirms the formation of a previously undocumented metabolite of BV in mammals, indicating that a new metabolic pathway likely exists for BV metabolism requiring enteric bacteria, Citrobacter youngae. These data may have important implications with regard to understanding and harnessing the therapeutic efficacy of oral BV administration.
High-throughput LPS profiling as a tool for revealing of bacteriophage infection strategies
Authors: Kulikov Eugene E. , Golomidova Alla K. , Prokhorov Nikolai S. , Ivanov Pavel A. , Letarov Andrey V.
Published: February 2019

O-antigens of Gram-negative bacteria modulate the interactions of bacterial cells with diverse external factors, including the components of the immune system and bacteriophages. Some phages need to acquire specific adhesins to overcome the O-antigen layer. For other phages, O-antigen is required for phage infection. In this case, interaction of phage receptor binding proteins coupled with enzymatic degradation or modification of the O-antigen is followed by phage infection. Identification of the strategies used by newly isolated phages may be of importance in their consideration for various applications. Here we describe an approach based on screening for host LPS alterations caused by selection by bacteriophages. We describe an optimized LPS profiling procedure that is simple, rapid and suitable for mass screening of mutants. We demonstrate that the phage infection strategies identified using a set of engineeredE. coli4 s mutants with impaired or altered LPS synthesis are in good agreement with the results of simpler tests based on LPS profiling of phage-resistant spontaneous mutants.
Isopycnal mixing of interhemispheric intermediate waters by subthermocline eddies east of the Philippines
Authors: Nan Feng , Yu Fei , Ren Qiang , Wei Chuanjie , Liu Yansong , Sun Shuhui
Published: February 2019

Both sporadic observations and modelling studies suggest that subthermocline eddies (SEs) exist east of the Philippines, where interhemispheric waters meet. However, effects of SEs on water mass mixing have never been observed. Here, using data from mooring and buoy deployed in the frontal region of the interhemispheric water masses, we show for the first time that the SEs act as an “underwater mixer” of intermediate waters from north and south Pacific oceans. The SEs have typical swirl speeds of 0.1~0.4 m s−1 between 200 and 800 m depth with a dominant period of ~90 days. Variation in intermediate water salinity also had a period of ~90 days, lagging eddy speed by ~8 days. Horizontal eddy diffusivity representative of eddy mixing rate was quantified using a mixing-length framework. Horizontal eddy diffusivity had both surface and subthermocline maxima. The vertically varying eddy diffusivity can be used to improve parameterization of eddy stirring in the tropical Pacific by coarse-resolution ocean climate models. The effect of the SEs on mixing of intermediate water masses seems not resolved by available eddy-resolving ocean models typically used for this region.