bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetotelluric Constraints on the Temperature, Composition, Partial Melt Content, and Viscosity of the Upper Mantle Beneath Svalbard
Authors: Selway Kate , Smirnov Maxim Yu , Beka Thomas , O'Donnell J. P. , Minakov Alexander , Senger Kim , Faleide Jan Inge , Kalscheuer Thomas
Published: April 2020

Long‐period magnetotelluric (MT) data can be used to interpret upper mantle temperature, hydrogen content, and the presence of partial melt, all of which strongly influence mantle viscosity. We have collected the first long‐period MT data in Svalbard and have combined them with preexisting broadband MT data to produce a model of the electrical resistivity of Svalbard's upper mantle. Asthenospheric resistivities are low compared to stable continental settings but more comparable to young oceanic asthenosphere, suggesting that the physical state of Svalbard's upper mantle is controlled by its proximity to the Mid‐Atlantic Ridge. Interpretation of the MT model using a petrologically constrained genetic algorithm approach shows that partial melt is present in the uppermost asthenosphere beneath Svalbard. This is the first direct evidence of partial melt in Svalbard's asthenosphere from deep geophysical soundings. Viscosities calculated from the geophysical data show a low viscosity layer (~1018 Pa s) coincident with the partial melt layer, underlain by a higher viscosity layer (~1020 Pa s) extending to the transition zone. Viscosities calculated from glacial isostatic adjustment (GIA) data in Svalbard show a considerable range due mainly to uncertainties in past ice sheet models. Improved constraints on Svalbard's mantle viscosity from geophysical data may help to improve these GIA models.
3‐D Magnetotelluric Imaging of the Easternmost Kunlun Fault: Insights Into Strain Partitioning and the Seismotectonics of the Jiuzhaigou Ms7.0 Earthquake
Authors: Sun Xiangyu , Zhan Yan , Unsworth Martyn , Egbert Gary , Zhang Huiping , Chen Xiaobin , Zhao Guoze , Sun Jianbao , Zhao Lingqiang , Cui Tengfa , Liu Zhongyin , Han Jing
Published: April 2020

We present a three‐dimensional electrical resistivity model of the crust and upper mantle beneath the easternmost Kunlun fault (EKLf), obtained by three‐dimensional inversion of magnetotelluric (MT) data. The crust of the Songpan‐Ganzi block is characterized by high resistivity from the surface to a depth of around 20 km, and by low resistivity in the mid‐lower crust in the depth range 20–40 km. The eastern edge of the high conductivity layer is coincident with the EKLf and the Huya fault. The electrical resistivity structure provides new insights into both (1) the generation of recent M > 6 earthquakes and (2) strain partitioning on this segment of the EKLf. Our model reveals that the Huya fault is the main branch of the EKLf in the region. Together with the EKLf, the Huya fault defines the boundary between the Songpan‐Ganzi and Bikou blocks. The mid‐lower crust of the Songpan‐Ganzi block in this region has a low resistivity that likely represents a mechanically weak layer. The 2017 Jiuzhaigou Ms7.0 earthquake and other recent M > 6 earthquakes may have been controlled by the change in viscosity in the mid‐lower crust that occurs across this boundary. The high conductivity may be acting as either (1) a channel of lower crustal flow, or (2) as a weak layer that decouples the upper and lower crust. The fact that the high conductivity layer does not extend along the north side of the Sichuan Basin questions the idea that crustal flow occurs in this area.
Analysis of Location Errors of the U.S. National Lightning Detection Network Using Lightning Strikes to Towers
Authors: Zhu Yanan , Lyu Weitao , Cramer John , Rakov Vladimir , Bitzer Phillip , Ding Ziqin
Published: April 2020

The location accuracy of the U.S. National Lightning Detection Network (NLDN) has been evaluated using as ground‐truth rocket‐triggered lightning data or video records but only at a few specific locations. In this study, by using the NLDN data for the events attributable to lightning strikes to towers, the location error of the NLDN across the entire contiguous United States was evaluated for the first time. We found that, on average, the NLDN median location error reduced from 198 to 84 m after the 2013 NLDN upgrade. The location error at the periphery of the network is significantly larger than that in its interior. In the coastal regions, there is directional location bias toward the water. Simulation results suggest that the bias is related to the lengthening of field waveform front due to electromagnetic wave propagation over lossy ground coupled with the asymmetrical sensor configuration relative to the strike point (lack of offshore sensors).
Activation of STAT3 is a key event in TLR4 signaling-mediated melanoma progression
Authors: Fu Xiu-Qiong , Liu Bin , Wang Ya-Ping , Li Jun-Kui , Zhu Pei-Li , Li Ting , Tse Kai-Wing , Chou Ji-Yao , Yin Cheng-Le , Bai Jing-Xuan , Liu Yu-Xi , Chen Ying-Jie , Yu Zhi-Ling
Published: April 2020

Malignant melanoma is aggressive and has a high mortality rate. Toll-like receptor 4 (TLR4) has been linked to melanoma growth, angiogenesis and metastasis. However, signal transduction mediated by TLR4 for driving melanoma progression is not fully understood. Signal transducer and activator of transcription 3 (STAT3) has been identified as a major oncogene in melanoma progression. We found: that TLR4 expression positively correlates with activation/phosphorylation of STAT3 in human melanoma samples; that TLR4 ligands activate STAT3 through MYD88 and TRIF in melanoma cells; and that intratumoral activation of TLR4 increases STAT3 activation in the tumor and promotes tumor growth, angiogenesis, epithelial–mesenchymal transition (EMT) and the formation of an immunosuppressive tumor microenvironment in mice. Further, we found that the effects mediated by activating TLR4 are weakened by suppressing STAT3 function with a dominant negative STAT3 variant in melanoma. Collectively, our work identifies STAT3 activation as a key event in TLR4 signaling-mediated melanoma progression, shedding new light on the pathophysiology of melanoma.
Kinesin-7 CENP-E regulates chromosome alignment and genome stability of spermatogenic cells
Authors: She Zhen-Yu , Yu Kai-Wei , Zhong Ning , Xiao Yu , Wei Ya-Lan , Lin Yang , Li Yue-Ling , Lu Ming-Hui
Published: April 2020

Kinesin-7 CENP-E is an essential kinetochore motor required for chromosome alignment and congression. However, the specific functions of CENP-E in the spermatogenic cells during spermatogenesis remain unknown. In this study, we find that CENP-E proteins are expressed in the spermatogonia, spermatocytes, and the elongating spermatids. CENP-E inhibition by specific inhibitor GSK923295 results in the disruption of spermatogenesis and cell cycle arrest of spermatogenic cells. Both spermatogonia and spermatocytes are arrested in metaphase and several chromosomes are not aligned at the equatorial plate. We find that CENP-E inhibition leads to chromosome misalignment, the spindle disorganization, and the formation of the aneuploidy cells. Furthermore, the inhibition of CENP-E results in the defects in the formation of spermatids, including the sperm head condensation and the sperm tail formation. We have revealed that kinesin-7 CENP-E is essential for chromosome alignment and genome stability of the spermatogenic cells.
Genetic characterization of a unique neuroendocrine transdifferentiation prostate circulating tumor cell-derived eXplant model
Authors: Faugeroux Vincent , Pailler Emma , Oulhen Marianne , Deas Olivier , Brulle-Soumare Laura , Hervieu Céline , Marty Virginie , Alexandrova Kamelia , Andree Kiki C. , Stoecklein Nikolas H. , Tramalloni Dominique , Cairo Stefano , NgoCamus Maud , Nicotra Claudio , Terstappen Leon W. M. M. , Manaresi Nicolo , Lapierre Valérie , Fizazi Karim , Scoazec Jean-Yves , Loriot Yohann , Judde Jean-Gabriel , Farace Françoise
Published: April 2020

Transformation of castration-resistant prostate cancer (CRPC) into an aggressive neuroendocrine disease (CRPC-NE) represents a major clinical challenge and experimental models are lacking. A CTC-derived eXplant (CDX) and a CDX-derived cell line are established using circulating tumor cells (CTCs) obtained by diagnostic leukapheresis from a CRPC patient resistant to enzalutamide. The CDX and the derived-cell line conserve 16% of primary tumor (PT) and 56% of CTC mutations, as well as 83% of PT copy-number aberrations including clonal TMPRSS2-ERG fusion and NKX3.1 loss. Both harbor an androgen receptor-null neuroendocrine phenotype, TP53, PTEN and RB1 loss. While PTEN and RB1 loss are acquired in CTCs, evolutionary analysis suggest that a PT subclone harboring TP53 loss is the driver of the metastatic event leading to the CDX. This CDX model provides insights on the sequential acquisition of key drivers of neuroendocrine transdifferentiation and offers a unique tool for effective drug screening in CRPC-NE management.
Cryo-EM structures reveal intricate Fe-S cluster arrangement and charging in Rhodobacter capsulatus formate dehydrogenase
Authors: Radon Christin , Mittelstädt Gerd , Duffus Benjamin R. , Bürger Jörg , Hartmann Tobias , Mielke Thorsten , Teutloff Christian , Leimkühler Silke , Wendler Petra
Published: April 2020

Metal-containing formate dehydrogenases (FDH) catalyse the reversible oxidation of formate to carbon dioxide at their molybdenum or tungsten active site. They display a diverse subunit and cofactor composition, but structural information on these enzymes is limited. Here we report the cryo-electron microscopic structures of the soluble Rhodobacter capsulatus FDH (RcFDH) as isolated and in the presence of reduced nicotinamide adenine dinucleotide (NADH). RcFDH assembles into a 360 kDa dimer of heterotetramers revealing a putative interconnection of electron pathway chains. In the presence of NADH, the RcFDH structure shows charging of cofactors, indicative of an increased electron load.
The endoplasmic reticulum stress-autophagy pathway controls hypothalamic development and energy balance regulation in leptin-deficient neonates
Authors: Park Soyoung , Aintablian Aleek , Coupe Berengere , Bouret Sebastien G.
Published: April 2020

Obesity is associated with the activation of cellular responses, such as endoplasmic reticulum (ER) stress. Here, we show that leptin-deficient ob/ob mice display elevated hypothalamic ER stress as early as postnatal day 10, i.e., prior to the development of obesity in this mouse model. Neonatal treatment of ob/ob mice with the ER stress-relieving drug tauroursodeoxycholic acid (TUDCA) causes long-term amelioration of body weight, food intake, glucose homeostasis, and pro-opiomelanocortin (POMC) projections. Cells exposed to ER stress often activate autophagy. Accordingly, we report that in vitro induction of ER stress and neonatal leptin deficiency in vivo activate hypothalamic autophagy-related genes. Furthermore, genetic deletion of autophagy in pro-opiomelanocortin neurons of ob/ob mice worsens their glucose homeostasis, adiposity, hyperphagia, and POMC neuronal projections, all of which are ameliorated with neonatal TUDCA treatment. Together, our data highlight the importance of early life ER stress-autophagy pathway in influencing hypothalamic circuits and metabolic regulation.
Structural basis of astrocytic Ca2+ signals at tripartite synapses
Authors: Arizono Misa , Inavalli V. V. G. Krishna , Panatier Aude , Pfeiffer Thomas , Angibaud Julie , Levet Florian , Ter Veer Mirelle J. T. , Stobart Jillian , Bellocchio Luigi , Mikoshiba Katsuhiko , Marsicano Giovanni , Weber Bruno , Oliet Stéphane H. R. , Nägerl U. Valentin
Published: April 2020

Astrocytic Ca2+ signals can be fast and local, supporting the idea that astrocytes have the ability to regulate single synapses. However, the anatomical basis of such specific signaling remains unclear, owing to difficulties in resolving the spongiform domain of astrocytes where most tripartite synapses are located. Using 3D-STED microscopy in living organotypic brain slices, we imaged the spongiform domain of astrocytes and observed a reticular meshwork of nodes and shafts that often formed loop-like structures. These anatomical features were also observed in acute hippocampal slices and in barrel cortex in vivo. The majority of dendritic spines were contacted by nodes and their sizes were correlated. FRAP experiments and Ca2+ imaging showed that nodes were biochemical compartments and Ca2+ microdomains. Mapping astrocytic Ca2+ signals onto STED images of nodes and dendritic spines showed they were associated with individual synapses. Here, we report on the nanoscale organization of astrocytes, identifying nodes as a functional astrocytic component of tripartite synapses that may enable synapse-specific communication between neurons and astrocytes.
Impact of visual callosal pathway is dependent upon ipsilateral thalamus
Authors: Ramachandra Vishnudev , Pawlak Verena , Wallace Damian J. , Kerr Jason N. D.
Published: April 2020

The visual callosal pathway, which reciprocally connects the primary visual cortices, is thought to play a pivotal role in cortical binocular processing. In rodents, the functional role of this pathway is largely unknown. Here, we measure visual cortex spiking responses to visual stimulation using population calcium imaging and functionally isolate visual pathways originating from either eye. We show that callosal pathway inhibition significantly reduced spiking responses in binocular and monocular neurons and abolished spiking in many cases. However, once isolated by blocking ipsilateral visual thalamus, callosal pathway activation alone is not sufficient to drive evoked cortical responses. We show that the visual callosal pathway relays activity from both eyes via both ipsilateral and contralateral visual pathways to monocular and binocular neurons and works in concert with ipsilateral thalamus in generating stimulus evoked activity. This shows a much greater role of the rodent callosal pathway in cortical processing than previously thought.
Hepatic saturated fatty acid fraction is associated with de novo lipogenesis and hepatic insulin resistance
Authors: Roumans Kay H. M. , Lindeboom Lucas , Veeraiah Pandichelvam , Remie Carlijn M. E. , Phielix Esther , Havekes Bas , Bruls Yvonne M. H. , Brouwers Martijn C. G. J. , Ståhlman Marcus , Alssema Marjan , Peters Harry P. F. , de Mutsert Renée , Staels Bart , Taskinen Marja-Riitta , Borén Jan , Schrauwen Patrick , Schrauwen-Hinderling Vera B.
Published: April 2020

Hepatic steatosis is associated with poor cardiometabolic health, with de novo lipogenesis (DNL) contributing to hepatic steatosis and subsequent insulin resistance. Hepatic saturated fatty acids (SFA) may be a marker of DNL and are suggested to be most detrimental in contributing to insulin resistance. Here, we show in a cross-sectional study design (ClinicalTrials.gov ID: NCT03211299) that we are able to distinguish the fractions of hepatic SFA, mono- and polyunsaturated fatty acids in healthy and metabolically compromised volunteers using proton magnetic resonance spectroscopy (1H-MRS). DNL is positively associated with SFA fraction and is elevated in patients with non-alcoholic fatty liver and type 2 diabetes. Intriguingly, SFA fraction shows a strong, negative correlation with hepatic insulin sensitivity. Our results show that the hepatic lipid composition, as determined by our 1H-MRS methodology, is a measure of DNL and suggest that specifically the SFA fraction may hamper hepatic insulin sensitivity.
Synthesis and evaluation of designed PKC modulators for enhanced cancer immunotherapy
Authors: Hardman Clayton , Ho Stephen , Shimizu Akira , Luu-Nguyen Quang , Sloane Jack L. , Soliman Mohamed S. A. , Marsden Matthew D. , Zack Jerome A. , Wender Paul A.
Published: April 2020

Bryostatin 1 is a marine natural product under investigation for HIV/AIDS eradication, the treatment of neurological disorders, and enhanced CAR T/NK cell immunotherapy. Despite its promising activity, bryostatin 1 is neither evolved nor optimized for the treatment of human disease. Here we report the design, synthesis, and biological evaluation of several close-in analogs of bryostatin 1. Using a function-oriented synthesis approach, we synthesize a series of bryostatin analogs designed to maintain affinity for bryostatin’s target protein kinase C (PKC) while enabling exploration of their divergent biological functions. Our late-stage diversification strategy provides efficient access to a library of bryostatin analogs, which per our design retain affinity for PKC but exhibit variable PKC translocation kinetics. We further demonstrate that select analogs potently increase cell surface expression of CD22, a promising CAR T cell target for the treatment of leukemias, highlighting the clinical potential of bryostatin analogs for enhancing targeted immunotherapies.
Fasting inhibits aerobic glycolysis and proliferation in colorectal cancer via the Fdft1-mediated AKT/mTOR/HIF1α pathway suppression
Authors: Weng Mei-lin , Chen Wan-kun , Chen Xiang-yuan , Lu Hong , Sun Zhi-rong , Yu Qi , Sun Peng-fei , Xu Ya-jun , Zhu Min-min , Jiang Nan , Zhang Jin , Zhang Jian-ping , Song Yuan-lin , Ma Duan , Zhang Xiao-ping , Miao Chang-hong
Published: April 2020

Evidence suggests that fasting exerts extensive antitumor effects in various cancers, including colorectal cancer (CRC). However, the mechanism behind this response is unclear. We investigate the effect of fasting on glucose metabolism and malignancy in CRC. We find that fasting upregulates the expression of a cholesterogenic gene, Farnesyl-Diphosphate Farnesyltransferase 1 (FDFT1), during the inhibition of CRC cell aerobic glycolysis and proliferation. In addition, the downregulation of FDFT1 is correlated with malignant progression and poor prognosis in CRC. Moreover, FDFT1 acts as a critical tumor suppressor in CRC. Mechanistically, FDFT1 performs its tumor-inhibitory function by negatively regulating AKT/mTOR/HIF1α signaling. Furthermore, mTOR inhibitor can synergize with fasting in inhibiting the proliferation of CRC. These results indicate that FDFT1 is a key downstream target of the fasting response and may be involved in CRC cell glucose metabolism. Our results suggest therapeutic implications in CRC and potential crosstalk between a cholesterogenic gene and glycolysis.
Physical drivers of the summer 2019 North Pacific marine heatwave
Authors: Amaya Dillon J. , Miller Arthur J. , Xie Shang-Ping , Kosaka Yu
Published: April 2020

Summer 2019 observations show a rapid resurgence of the Blob-like warm sea surface temperature (SST) anomalies that produced devastating marine impacts in the Northeast Pacific during winter 2013/2014. Unlike the original Blob, Blob 2.0 peaked in the summer, a season when little is known about the physical drivers of such events. We show that Blob 2.0 primarily results from a prolonged weakening of the North Pacific High-Pressure System. This reduces surface winds and decreases evaporative cooling and wind-driven upper ocean mixing. Warmer ocean conditions then reduce low-cloud fraction, reinforcing the marine heatwave through a positive low-cloud feedback. Using an atmospheric model forced with observed SSTs, we also find that remote SST forcing from the central equatorial and, surprisingly, the subtropical North Pacific Ocean contribute to the weakened North Pacific High. Our multi-faceted analysis sheds light on the physical drivers governing the intensity and longevity of summertime North Pacific marine heatwaves.
Overcoming the exciton binding energy in two-dimensional perovskite nanoplatelets by attachment of conjugated organic chromophores
Authors: Gélvez-Rueda María C. , Fridriksson Magnus B. , Dubey Rajeev K. , Jager Wolter F. , van der Stam Ward , Grozema Ferdinand C.
Published: April 2020

In this work we demonstrate a novel approach to achieve efficient charge separation in dimensionally and dielectrically confined two-dimensional perovskite materials. Two-dimensional perovskites generally exhibit large exciton binding energies that limit their application in optoelectronic devices that require charge separation such as solar cells, photo-detectors and in photo-catalysis. Here, we show that by incorporating a strongly electron accepting moiety, perylene diimide organic chromophores, on the surface of the two-dimensional perovskite nanoplatelets it is possible to achieve efficient formation of mobile free charge carriers. These free charge carriers are generated with ten times higher yield and lifetimes of tens of microseconds, which is two orders of magnitude longer than without the peryline diimide acceptor. This opens a novel synergistic approach, where the inorganic perovskite layers are combined with functional organic chromophores in the same material to tune the properties for specific applications.
Author Correction: Human FCHO1 deficiency reveals role for clathrin-mediated endocytosis in development and function of T cells
Authors: Łyszkiewicz Marcin , Ziętara Natalia , Frey Laura , Pannicke Ulrich , Stern Marcel , Liu Yanshan , Fan Yanxin , Puchałka Jacek , Hollizeck Sebastian , Somekh Ido , Rohlfs Meino , Yilmaz Tuğba , Ünal Ekrem , Karakukcu Musa , Patiroğlu Türkan , Kellerer Christina , Karasu Ebru , Sykora Karl-Walter , Lev Atar , Simon Amos , Somech Raz , Roesler Joachim , Hoenig Manfred , Keppler Oliver T. , Schwarz Klaus , Klein Christoph
Published: April 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Publisher Correction: Increasing ambient temperature progressively disassembles Arabidopsis phytochrome B from individual photobodies with distinct thermostabilities
Authors: Hahm Joseph , Kim Keunhwa , Qiu Yongjian , Chen Meng
Published: April 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Deeply conserved synteny resolves early events in vertebrate evolution
Authors: Simakov Oleg , Marlétaz Ferdinand , Yue Jia-Xing , O’Connell Brendan , Jenkins Jerry , Brandt Alexander , Calef Robert , Tung Che-Huang , Huang Tzu-Kai , Schmutz Jeremy , Satoh Nori , Yu Jr-Kai , Putnam Nicholas H. , Green Richard E. , Rokhsar Daniel S.
Published: April 2020

Although it is widely believed that early vertebrate evolution was shaped by ancient whole-genome duplications, the number, timing and mechanism of these events remain elusive. Here, we infer the history of vertebrates through genomic comparisons with a new chromosome-scale sequence of the invertebrate chordate amphioxus. We show how the karyotypes of amphioxus and diverse vertebrates are derived from 17 ancestral chordate linkage groups (and 19 ancestral bilaterian groups) by fusion, rearrangement and duplication. We resolve two distinct ancient duplications based on patterns of chromosomal conserved synteny. All extant vertebrates share the first duplication, which occurred in the mid/late Cambrian by autotetraploidization (that is, direct genome doubling). In contrast, the second duplication is found only in jawed vertebrates and occurred in the mid–late Ordovician by allotetraploidization (that is, genome duplication following interspecific hybridization) from two now-extinct progenitors. This complex genomic history parallels the diversification of vertebrate lineages in the fossil record.
Imaging-assisted hydrogel formation for single cell isolation
Authors: Oldenhof Sander , Mytnyk Serhii , Arranja Alexandra , de Puit Marcel , van Esch Jan H.
Published: April 2020

We report a flexible single-cell isolation method by imaging-assisted hydrogel formation. Our approach consists of imaging-aided selective capture of cells of interest by encasing them into a polymeric hydrogel, followed by removal of unwanted cells and subsequent release of isolated cells by enzymatic hydrogel degradation, thus offering an opportunity for further analysis or cultivation of selected cells. We achieved high sorting efficiency and observed excellent viability rates (>98%) for NIH/3T3 fibroblasts and A549 carcinoma cells isolated using this procedure. The method presented here offers a mask-free, cost-efficient and easy-to-use alternative to many currently existing surface-based cell-sorting techniques, and has the potential to impact the field of cell culturing and isolation, e.g. single cell genomics and proteomics, investigation of cellular heterogeneity and isolation of best performing mutants for developing new cell lines.
The effect of Palm Oil Mill Effluent Final Discharge on the Characteristics of Pennisetum purpureum
Authors: Osman Nurul Atiqah , Ujang Farhana Aziz , Roslan Ahmad Muhaimin , Ibrahim Mohamad Faizal , Hassan Mohd Ali
Published: April 2020

Phytoremediation is one of the environmental-friendly and cost-effective systems for the treatment of wastewater, including industrial wastewater such as palm oil mill effluent final discharge (POME FD). However, the effects of the wastewater on the phytoremediator plants, in term of growth performance, lignocellulosic composition, and the presence of nutrients and heavy metals in the plants are not yet well studied. In the present work, we demonstrated that POME FD increased the growth of P. purpureum. The height increment of P. purpureum supplied with POME FD (treatment) was 61.72% as compared to those supplied with rain water (control) which was 14.42%. For lignocellulosic composition, the cellulose percentages were 38.77 ± 0.29% (treatment) and 34.16 ± 1.01% (control), and the difference was significant. These results indicated that POME FD could be a source of plant nutrients, which P. purpureum can absorb for growth. It was also found that the heavy metals (Al, As, Cd, Co, Cr, Ni and Pb) inside the plant were below the standard limit of the World Health Organization (WHO). Since POME FD was shown to have no adverse effects on P. purpureum, further research regarding the potential application of P. purpureum following phytoremediation of POME FD such as biofuel production is warranted to evaluate its potential use to fit into the waste-to-wealth agenda.
Combination of Simultaneous Artificial Sensory Percepts to Identify Prosthetic Hand Postures: A Case Study
Authors: Segil Jacob L. , Cuberovic Ivana , Graczyk Emily L. , Weir Richard F. ff. , Tyler Dustin
Published: April 2020

Multiple sources of sensory information are combined to develop hand posture percepts in the intact system, but the combination of multiple artificial somatosensory percepts by human prosthesis users has not been studied. Here, we report on a case study in which a person with transradial amputation identified prosthetic hand postures using artificial somatosensory feedback. He successfully combined five artificial somatosensory percepts to achieve above-chance performance of 95.0% and 75.7% in identifying four and seven postures, respectively. We studied how artificial somatosensation and the extant hand representation are combined in the decision-making process by providing two mappings between the prosthetic sensor and the location of the sensory percept: (1) congruent, and (2) incongruent. The participant’s ability to combine and engage with the sensory feedback significantly differed between the two conditions. The participant was only able to successfully generalize prior knowledge to novel postures in the congruent mapping. Further, he learned postures more accurately and quickly in the congruent mapping. Finally, he developed an understanding of the relationships between postures in the congruent mapping instead of simply memorizing each individual posture. These experimental results are corroborated by a Bayesian decision-making model which tracked the participant’s learning.
RAC1-Dependent ORAI1 Translocation to the Leading Edge Supports Lamellipodia Formation and Directional Persistence
Authors: Lopez-Guerrero Aida M. , Espinosa-Bermejo Noelia , Sanchez-Lopez Irene , Macartney Thomas , Pascual-Caro Carlos , Orantos-Aguilera Yolanda , Rodriguez-Ruiz Lola , Perez-Oliva Ana B. , Mulero Victoriano , Pozo-Guisado Eulalia , Martin-Romero Francisco Javier
Published: April 2020

Tumor invasion requires efficient cell migration, which is achieved by the generation of persistent and polarized lamellipodia. The generation of lamellipodia is supported by actin dynamics at the leading edge where a complex of proteins known as the WAVE regulatory complex (WRC) promotes the required assembly of actin filaments to push the front of the cell ahead. By using an U2OS osteosarcoma cell line with high metastatic potential, proven by a xenotransplant in zebrafish larvae, we have studied the role of the plasma membrane Ca2+ channel ORAI1 in this process. We have found that epidermal growth factor (EGF) triggered an enrichment of ORAI1 at the leading edge, where colocalized with cortactin (CTTN) and other members of the WRC, such as CYFIP1 and ARP2/3. ORAI1-CTTN co-precipitation was sensitive to the inhibition of the small GTPase RAC1, an upstream activator of the WRC. RAC1 potentiated ORAI1 translocation to the leading edge, increasing the availability of surface ORAI1 and increasing the plasma membrane ruffling. The role of ORAI1 at the leading edge was studied in genetically engineered U2OS cells lacking ORAI1 expression that helped us to prove the key role of this Ca2+ channel on lamellipodia formation, lamellipodial persistence, and cell directness, which are required for tumor cell invasiveness in vivo.
Prion protein N1 cleavage peptides stimulate microglial interaction with surrounding cells
Authors: Carroll J. A. , Groveman B. R. , Williams K. , Moore R. , Race B. , Haigh C. L.
Published: April 2020

Microglia act as the protective immune cell of the brain. By surveying the tissue to identify and rectify problems, they function to maintain the health of brain cells. The prion protein N-terminal cleavage fragment, N1, has demonstrated neuroprotective activities in vitro and in vivo. This study aimed to elucidate whether N1 could modulate microglial function and, if so, determine the consequences for the surrounding tissue. Using a mixed neuronal lineage and microglia co-culture system, we showed that N1 stimulation changed overall morphology and metabolism, suggesting enhanced cellular viability. Furthermore, N1 induced an increase in Cxcl10 secretion in the co-cultures. Recombinant Cxcl10, administered exogenously, mediated the changes in the mixed neuronal lineage culture morphology and metabolism in the absence of microglia, but no effect of Cxcl10 was observed on microglia cultured on their own. Direct cell-to-cell contact was required for N1 to influence microglia in the co-cultures, and this was linked with restructuring of microglial membrane composition to include a higher GM1 content at interaction sites with surrounding cells. Our findings show that N1 can play a regulatory role in microglial function in the context of an inter-connected network of cells by changing both cellular interaction sites and cytokine secretion.
Resistance training preserves high-intensity interval training induced improvements in skeletal muscle capillarization of healthy old men: a randomized controlled trial
Authors: Leuchtmann Aurel B. , Mueller Sandro Manuel , Aguayo David , Petersen Jens A. , Ligon-Auer Maria , Flück Martin , Jung Hans H. , Toigo Marco
Published: April 2020

Skeletal muscle capillarization is a determining factor in gas and metabolite exchange, while its impairments may contribute to the development of sarcopenia. Studies on the potential of resistance training (RT) to induce angiogenesis in older muscles have been inconclusive, and effects of sequential endurance training (ET) and RT on capillarization are unknown. Healthy older men (66.5 ± 3.8 years) were engaged in either 12 weeks of habitual course observation (HC) followed by 12 weeks of RT (n = 8), or 12 weeks of high-intensity interval training (HIIT) followed by 12 weeks of RT (n = 9). At baseline, following 12 and 24 weeks, m. vastus lateralis biopsies were obtained. (Immuno-)histochemistry was used to assess indices of muscle fiber capillarization, muscle fiber morphology and succinate dehydrogenase (SDH) activity. Single periods of RT and HIIT resulted in similar improvements in capillarization and SDH activity. During RT following HIIT, improved capillarization and SDH activity, as well as muscle fiber morphology remained unchanged. The applied RT and HIIT protocols were thus similarly effective in enhancing capillarization and oxidative enzyme activity and RT effectively preserved HIIT-induced adaptations of these parameters. Hence, both, RT and HIIT, are valid training modalities for older men to improve skeletal muscle vascularization.
Visualizing the dynamic change of Ocular Response Analyzer waveform using Variational Autoencoder in association with the peripapillary retinal arteries angle
Authors: Asano Shotaro , Asaoka Ryo , Yamashita Takehiro , Aoki Shuichiro , Matsuura Masato , Fujino Yuri , Murata Hiroshi , Nakakura Shunsuke , Nakao Yoshitaka , Kiuchi Yoshiaki
Published: April 2020

The aim of the current study is to identify possible new Ocular Response Analyzer (ORA) waveform parameters related to changes of retinal structure/deformation, as measured by the peripapillary retinal arteries angle (PRAA), using a generative deep learning method of variational autoencoder (VAE). Fifty-four eyes of 52 subjects were enrolled. The PRAA was calculated from fundus photographs and was used to train a VAE model. By analyzing the ORA waveform reconstructed (noise filtered) using VAE, a novel ORA waveform parameter (Monot1-2), was introduced, representing the change in monotonicity between the first and second applanation peak of the waveform. The variables mostly related to the PRAA were identified from a set of 41 variables including age, axial length (AL), keratometry, ORA corneal hysteresis, ORA corneal resistant factor, 35 well established ORA waveform parameters, and Monot1-2, using a model selection method based on the second-order bias-corrected Akaike information criterion. The optimal model for PRAA was the AL and six ORA waveform parameters, including Monot1-2. This optimal model was significantly better than the model without Monot1-2 (p = 0.0031, ANOVA). The current study suggested the value of a generative deep learning approach in discovering new useful parameters that may have clinical relevance.
Transcriptome-wide shift from photosynthesis and energy metabolism upon endogenous fluid protein depletion in young Nepenthes ampullaria pitchers
Authors: Goh Hoe-Han , Baharin Anis , Mohd Salleh Faris ‘Imadi , Ravee Rishiesvari , Wan Zakaria Wan Nor Adibah , Mohd Noor Normah
Published: April 2020

Carnivorous pitcher plants produce specialised pitcher organs containing secretory glands, which secrete acidic fluids with hydrolytic enzymes for prey digestion and nutrient absorption. The content of pitcher fluids has been the focus of many fluid protein profiling studies. These studies suggest an evolutionary convergence of a conserved group of similar enzymes in diverse families of pitcher plants. A recent study showed that endogenous proteins were replenished in the pitcher fluid, which indicates a feedback mechanism in protein secretion. This poses an interesting question on the physiological effect of plant protein loss. However, there is no study to date that describes the pitcher response to endogenous protein depletion. To address this gap of knowledge, we previously performed a comparative RNA-sequencing experiment of newly opened pitchers (D0) against pitchers after 3 days of opening (D3C) and pitchers with filtered endogenous proteins (>10 kDa) upon pitcher opening (D3L). Nepenthes ampullaria was chosen as a model study species due to their abundance and unique feeding behaviour on leaf litters. The analysis of unigenes with top 1% abundance found protein translation and stress response to be overrepresented in D0, compared to cell wall related, transport, and signalling for D3L. Differentially expressed gene (DEG) analysis identified DEGs with functional enrichment in protein regulation, secondary metabolism, intracellular trafficking, secretion, and vesicular transport. The transcriptomic landscape of the pitcher dramatically shifted towards intracellular transport and defence response at the expense of energy metabolism and photosynthesis upon endogenous protein depletion. This is supported by secretome, transportome, and transcription factor analysis with RT-qPCR validation based on independent samples. This study provides the first glimpse into the molecular responses of pitchers to protein loss with implications to future cost/benefit analysis of carnivorous pitcher plant energetics and resource allocation for adaptation in stochastic environments.
Laparoscopic Long Mesh Surgery with Augmented Round Ligaments: A Novel Uterine Preservation Procedure For Apical Pelvic Organ Prolapse
Authors: Long Cheng-Yu , Wang Chiu-Lin , Lin Kun-Ling , Ker Chin-Ru , Loo Zixi , Liu Yiyin , Wu Pei-Chi
Published: April 2020

We aim to assess the surgical outcomes of our novel hysteropexy procedure, laparoscopic long mesh surgery (LLMS) with augmented round ligaments. Twenty-five consecutive women with stage II or greater main uterine prolapse defined by the POP quantification staging system were referred for LLMS. Long mesh is a synthetic T-shaped mesh, with the body fixed at the uterine cervix and the two arms fixed along the bilateral round ligaments. The clinical evaluations performed before and 6 months after surgery included pelvic examinations, urodynamic studies, and questionnaires for urinary and sexual symptoms. After a follow-up time of 12 to 24 months, the anatomical reduction rate was 92% (23/25) for the apical compartment. The average operative time was 65.4  ±  28.8 minutes. No major complications were recognized during LLMS. The lower urinary tract symptoms and scores on the questionnaires improved significantly after the surgery, except urgency urinary incontinence and nocturia. Neither voiding nor storage dysfunction was observed after the operations. All of the domains and total Female Sexual Function Index (FSFI) scores of the 15 sexually active women did not differ significantly after LLMS. The results of our study suggest that LLMS is an effective, safe, and time-saving hysteropexy surgery for the treatment of apical prolapse.
Predicting miRNA-disease association from heterogeneous information network with GraRep embedding model
Authors: Ji Bo-Ya , You Zhu-Hong , Cheng Li , Zhou Ji-Ren , Alghazzawi Daniyal , Li Li-Ping
Published: April 2020

In recent years, accumulating evidences have shown that microRNA (miRNA) plays an important role in the exploration and treatment of diseases, so detection of the associations between miRNA and disease has been drawn more and more attentions. However, traditional experimental methods have the limitations of high cost and time- consuming, a computational method can help us more systematically and effectively predict the potential miRNA-disease associations. In this work, we proposed a novel network embedding-based heterogeneous information integration method to predict miRNA-disease associations. More specifically, a heterogeneous information network is constructed by combining the known associations among lncRNA, drug, protein, disease, and miRNA. After that, the network embedding method Learning Graph Representations with Global Structural Information (GraRep) is employed to learn embeddings of nodes in heterogeneous information network. In this way, the embedding representations of miRNA and disease are integrated with the attribute information of miRNA and disease (e.g. miRNA sequence information and disease semantic similarity) to represent miRNA-disease association pairs. Finally, the Random Forest (RF) classifier is used for predicting potential miRNA-disease associations. Under the 5-fold cross validation, our method obtained 85.11% prediction accuracy with 80.41% sensitivity at the AUC of 91.25%. In addition, in case studies of three major Human diseases, 45 (Colon Neoplasms), 42 (Breast Neoplasms) and 44 (Esophageal Neoplasms) of top-50 predicted miRNAs are respectively verified by other miRNA-disease association databases. In conclusion, the experimental results suggest that our method can be a powerful and useful tool for predicting potential miRNA-disease associations.
Virtual biopsy using MRI radiomics for prediction of BRAF status in melanoma brain metastasis
Authors: Shofty Ben , Artzi Moran , Shtrozberg Shai , Fanizzi Claudia , DiMeco Francesco , Haim Oz , Peleg Hason Shira , Ram Zvi , Bashat Dafna Ben , Grossman Rachel
Published: April 2020

Brain metastases are common in patients with advanced melanoma and constitute a major cause of morbidity and mortality. Between 40% and 60% of melanomas harbor BRAF mutations. Selective BRAF inhibitor therapy has yielded improvement in clinical outcome; however, genetic discordance between the primary lesion and the metastatic tumor has been shown to occur. Currently, the only way to characterize the genetic landscape of a brain metastasis is by tissue sampling, which carries risks and potential complications. The aim of this study was to investigate the use of radiomics analysis for non-invasive identification of BRAF mutation in patients with melanoma brain metastases, based on conventional magnetic resonance imaging (MRI) data. We applied a machine-learning method, based on MRI radiomics features for noninvasive characterization of the BRAF status of brain metastases from melanoma (BMM) and applied it to BMM patients from two tertiary neuro-oncological centers. All patients underwent surgical resection for BMM, and their BRAF mutation status was determined as part of their oncological work-up. Their routine preoperative MRI study was used for radiomics-based analysis in which 195 features were extracted and classified according to their BRAF status via a support vector machine. The BRAF status of 53 study patients, with 54 brain metastases (25 positive, 29 negative for BRAF mutation) was predicted with mean accuracy = 0.79 ± 0.13, mean precision = 0.77 ± 0.14, mean sensitivity = 0.72 ± 0.20, mean specificity = 0.83 ± 0.11 and with a 0.78 area under the receiver operating characteristic curve for positive BRAF mutation prediction. Radiomics-based noninvasive genetic characterization is feasible and should be further verified using large prospective cohorts.
Author Correction: Development of a novel anti-hepatitis B virus agent via Sp1
Authors: Hayakawa Michiyo , Umeyama Hideaki , Iwadate Mitsuo , Taguchi Y.-H. , Yano Yoshihiko , Honda Takashi , Itami-Matsumoto Saori , Kozuka Ritsuzo , Enomoto Masaru , Tamori Akihiro , Kawada Norifumi , Murakami Yoshiki
Published: April 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: TmRelish is required for regulating the antimicrobial responses to Escherichia coli and Staphylococcus aureus in Tenebrio molitor
Authors: Keshavarz Maryam , Jo Yong Hun , Patnaik Bharat Bhusan , Park Ki Beom , Ko Hye Jin , Kim Chang Eun , Edosa Tariku Tesfaye , Lee Yong Seok , Han Yeon Soo
Published: April 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Dienedioic acid as a useful diene building block via directed Heck-decarboxylate coupling
Authors: Ke Lei , Chen Zhilong
Published: April 2020

The concise construction of diene scaffolds is quite useful in the synthesis of polyenes. Many diene building blocks have been developed based on Suzuki, Still and Hiyama couplings. Herein, the commercially available and environmentally friendly compound dienedioic acid is used as a diene building block. Broad substrate scope, good functional group tolerance, and late-stage derivatization of complex drug molecules are achieved. Different moieties can be conveniently introduced to both sides. Piperine and the methyl ester of azoxymycin C are each prepared in three steps. Additionally, one product shows promising anticancer activities in leukemia K562 and MV-4-11 cells. Mechanistic studies indicate that the reaction proceeds through a Heck-decarboxylate coupling procedure, and the carboxylic group acts as a directing group to promote the reaction and control regioselectivity. Our research suggests that dienedioic acid can serve as a good alternative for diene preparation via a directed Heck-decarboxylate coupling.
Milk fermented with Lactococcus lactis KLDS4.0325 alleviates folate status in deficient mice
Authors: Jiao Wenshu , Wang Song , Guan Jiaqi , Shi Jialu , Evivie Smith Etareri , Yan Fenfen , Li Na , Chen Junliang , Li Bailiang , Huo Guicheng
Published: April 2020

This study proved that milk fermented with L. lactis KLDS4.0325 can alleviate the folate status in deficient mice by animal experiment.
Heterogeneous iron-containing nanocatalysts – promising systems for selective hydrogenation and hydrogenolysis
Authors: Shesterkina Anastasiya A. , Kustov Leonid M. , Strekalova Anna A. , Kazansky Vladimir B.
Published: April 2020

Bimetallic catalytic systems Fe–Me (Pt, Pd, Cu) demonstrate synergy in the activity/selectivity pattern in reactions involving hydrogen: selective hydrogenation of CC bonds, NO2 and carbonyl groups and hydrogenolysis of C–O bonds.
Evaluation of the impact of a rat small intestinal extract on the digestion of four different functional fibers
Authors: Gallego-Lobillo Pablo , Ferreira-Lazarte Alvaro , Hernández-Hernández Oswaldo , Montilla Antonia , Villamiel Mar
Published: April 2020

The degree of digestion, modulated by rat small intestinal extract on different functional fibers was investigated.
Improvement of emulsifying behavior of pea proteins as plant-based emulsifiers via Maillard-induced glycation in electrospun pea protein–maltodextrin fibers
Authors: Kutzli Ines , Griener Daniela , Gibis Monika , Grossmann Lutz , Baier Stefan K. , Weiss Jochen
Published: April 2020

This work studies the interfacial and emulsifying properties of pea protein isolate-maltodextrin conjugates produced via the first step of the Maillard reaction in electrospun protein–polysaccharide fibers.
A combination of borage seed oil and quercetin reduces fat accumulation and improves insulin sensitivity in obese rats
Authors: Aranaz Paula , Zabala María , Romo-Hualde Ana , Navarro-Herrera David , López-Yoldi Miguel , Vizmanos José Luis , Martínez J. Alfredo , Milagro Fermín I. , González-Navarro Carlos J.
Published: April 2020

Borage seed oil (BSO) combined with quercetin improves glucose tolerance, insulin sensitivity, liver steatosis and adiposity in pre-obese rats. The combination also inhibits adipogenesis in vitro by affecting some adipogenesis-key factors.
Biodegradable rare earth fluorochloride nanocrystals for phototheranostics
Authors: Zhao Xinyu , Yu Qi , Yuan Jun , Thakor Nitish V. , Tan Mei Chee
Published: April 2020

The biodegradable Nd doped SrFCl nanoparticles coated with polydopamine (SrFCl:Nd@PDA NPs) have been demonstrated as a phototheranostic agent.
Carbon and graphene quantum dots: a review on syntheses, characterization, biological and sensing applications for neurotransmitter determination
Authors: Tajik Somayeh , Dourandish Zahra , Zhang Kaiqiang , Beitollahi Hadi , Le Quyet Van , Jang Ho Won , Shokouhimehr Mohammadreza
Published: April 2020

Carbon and graphene quantum dots for biological and sensing applications of neurotransmitters.
A simple and cost-effective approach to fabricate tunable length polymeric microneedle patches for controllable transdermal drug delivery
Authors: Chen Yongli , Xian Yiwen , Carrier Andrew J. , Youden Brian , Servos Mark , Cui Shufen , Luan Tiangang , Lin Sujing , Zhang Xu
Published: April 2020

A simple and cost-effective approach to fabricate tunable length polymeric microneedle patches for controllable transdermal drug delivery.
Insights into the competitive adsorption of pollutants on a mesoporous alumina–silica nano-sorbent synthesized from coal fly ash and a waste aluminium foil
Authors: Chatterjee Aditi , Shamim Shahnawaz , Jana Amiya Kumar , Basu Jayanta Kumar
Published: April 2020

A highly efficient and low-cost alumina–silica nano-sorbent was fabricated and characterized to realize the key factors responsible for its superiority over the existing adsorbents in treating the wastewater for the removal of dyes and heavy metals.