bluuebunny/crossref_metadata_2025 huggingface dataset:
Anomalous 3D nanoscale photoconduction in hybrid perovskite semiconductors revealed by tomographic atomic force microscopy
Authors: Song Jingfeng , Zhou Yuanyuan , Padture Nitin P. , Huey Bryan D.
Published: July 2020

While grain boundaries (GBs) in conventional inorganic semiconductors are frequently considered as detrimental for photogenerated carrier transport, their exact role remains obscure for the emerging hybrid perovskite semiconductors. A primary challenge for GB-property investigations is that experimentally they need to be performed at the top surface, which is not only insensitive to depth-dependent inhomogeneities but also could be susceptible to topographic artifacts. Accordingly, we have developed a unique approach based on tomographic atomic force microscopy, achieving a fully-3D, photogenerated carrier transport map at the nanoscale in hybrid perovskites. This reveals GBs serving as highly interconnected conducting channels for carrier transport. We have further discovered the coexistence of two GB types in hybrid perovskites, one exhibiting enhanced carrier mobilities, while the other is insipid. Our approach reveals otherwise inaccessible buried features and previously unresolved conduction pathways, crucial for optimizing hybrid perovskites for various optoelectronic applications including solar cells and photodetectors.
Sub-single exciton optical gain threshold in colloidal semiconductor quantum wells with gradient alloy shelling
Authors: Taghipour Nima , Delikanli Savas , Shendre Sushant , Sak Mustafa , Li Mingjie , Isik Furkan , Tanriover Ibrahim , Guzelturk Burak , Sum Tze Chien , Demir Hilmi Volkan
Published: July 2020

Colloidal semiconductor quantum wells have emerged as a promising material platform for use in solution-processable lasers. However, applications relying on their optical gain suffer from nonradiative Auger decay due to multi-excitonic nature of light amplification in II-VI semiconductor nanocrystals. Here, we show sub-single exciton level of optical gain threshold in specially engineered CdSe/CdS@CdZnS core/crown@gradient-alloyed shell quantum wells. This sub-single exciton ensemble-averaged gain threshold of (Ng)≈ 0.84 (per particle) resulting from impeded Auger recombination, along with a large absorption cross-section of quantum wells, enables us to observe the amplified spontaneous emission starting at an ultralow pump fluence of ~ 800 nJ cm−2, at least three-folds better than previously reported values among all colloidal nanocrystals. Finally, using these gradient shelled quantum wells, we demonstrate a vertical cavity surface-emitting laser operating at a low lasing threshold of 7.5 μJ cm−2. These results represent a significant step towards the realization of solution-processable electrically-driven colloidal lasers.
A thermally activated and highly miscible dopant for n-type organic thermoelectrics
Authors: Yang Chi-Yuan , Ding Yi-Fan , Huang Dazhen , Wang Jue , Yao Ze-Fan , Huang Chun-Xi , Lu Yang , Un Hio-Ieng , Zhuang Fang-Dong , Dou Jin-Hu , Di Chong-an , Zhu Daoben , Wang Jie-Yu , Lei Ting , Pei Jian
Published: July 2020

N-doping plays an irreplaceable role in controlling the electron concentration of organic semiconductors thus to improve performance of organic semiconductor devices. However, compared with many mature p-doping methods, n-doping of organic semiconductor is still of challenges. In particular, dopant stability/processability, counterion-semiconductor immiscibility and doping induced microstructure non-uniformity have restricted the application of n-doping in high-performance devices. Here, we report a computer-assisted screening approach to rationally design of a triaminomethane-type dopant, which exhibit extremely high stability and strong hydride donating property due to its thermally activated doping mechanism. This triaminomethane derivative shows excellent counterion-semiconductor miscibility (counter cations stay with the polymer side chains), high doping efficiency and uniformity. By using triaminomethane, we realize a record n-type conductivity of up to 21 S cm−1 and power factors as high as 51 μW m−1 K−2 even in films with thicknesses over 10 μm, and we demonstrate the first reported all-polymer thermoelectric generator.
Fully stretchable active-matrix organic light-emitting electrochemical cell array
Authors: Liu Jia , Wang Jiechen , Zhang Zhitao , Molina-Lopez Francisco , Wang Ging-Ji Nathan , Schroeder Bob C. , Yan Xuzhou , Zeng Yitian , Zhao Oliver , Tran Helen , Lei Ting , Lu Yang , Wang Yi-Xuan , Tok Jeffrey B.-H. , Dauskardt Reinhold , Chung Jong Won , Yun Youngjun , Bao Zhenan
Published: July 2020

Intrinsically and fully stretchable active-matrix-driven displays are an important element to skin electronics that can be applied to many emerging fields, such as wearable electronics, consumer electronics and biomedical devices. Here, we show for the first time a fully stretchable active-matrix-driven organic light-emitting electrochemical cell array. Briefly, it is comprised of a stretchable light-emitting electrochemical cell array driven by a solution-processed, vertically integrated stretchable organic thin-film transistor active-matrix, which is enabled by the development of chemically-orthogonal and intrinsically stretchable dielectric materials. Our resulting active-matrix-driven organic light-emitting electrochemical cell array can be readily bent, twisted and stretched without affecting its device performance. When mounted on skin, the array can tolerate to repeated cycles at 30% strain. This work demonstrates the feasibility of skin-applicable displays and lays the foundation for further materials development.
Anatomically and functionally distinct thalamocortical inputs to primary and secondary mouse whisker somatosensory cortices
Authors: El-Boustani Sami , Sermet B. Semihcan , Foustoukos Georgios , Oram Tess B. , Yizhar Ofer , Petersen Carl C. H.
Published: July 2020

Subdivisions of mouse whisker somatosensory thalamus project to cortex in a region-specific and layer-specific manner. However, a clear anatomical dissection of these pathways and their functional properties during whisker sensation is lacking. Here, we use anterograde trans-synaptic viral vectors to identify three specific thalamic subpopulations based on their connectivity with brainstem. The principal trigeminal nucleus innervates ventral posterior medial thalamus, which conveys whisker-selective tactile information to layer 4 primary somatosensory cortex that is highly sensitive to self-initiated movements. The spinal trigeminal nucleus innervates a rostral part of the posterior medial (POm) thalamus, signaling whisker-selective sensory information, as well as decision-related information during a goal-directed behavior, to layer 4 secondary somatosensory cortex. A caudal part of the POm, which apparently does not receive brainstem input, innervates layer 1 and 5A, responding with little whisker selectivity, but showing decision-related modulation. Our results suggest the existence of complementary segregated information streams to somatosensory cortices.
Predicting and affecting response to cancer therapy based on pathway-level biomarkers
Authors: Ben-Hamo Rotem , Jacob Berger Adi , Gavert Nancy , Miller Mendy , Pines Guy , Oren Roni , Pikarsky Eli , Benes Cyril H. , Neuman Tzahi , Zwang Yaara , Efroni Sol , Getz Gad , Straussman Ravid
Published: July 2020

Identifying robust, patient-specific, and predictive biomarkers presents a major obstacle in precision oncology. To optimize patient-specific therapeutic strategies, here we couple pathway knowledge with large-scale drug sensitivity, RNAi, and CRISPR-Cas9 screening data from 460 cell lines. Pathway activity levels are found to be strong predictive biomarkers for the essentiality of 15 proteins, including the essentiality of MAD2L1 in breast cancer patients with high BRCA-pathway activity. We also find strong predictive biomarkers for the sensitivity to 31 compounds, including BCL2 and microtubule inhibitors (MTIs). Lastly, we show that Bcl-xL inhibition can modulate the activity of a predictive biomarker pathway and re-sensitize lung cancer cells and tumors to MTI therapy. Overall, our results support the use of pathways in helping to achieve the goal of precision medicine by uncovering dozens of predictive biomarkers.
Real-time gap-free dynamic waveform spectral analysis with nanosecond resolutions through analog signal processing
Authors: Konatham Saikrishna Reddy , Maram Reza , Romero Cortés Luis , Chang Jun Ho , Rusch Leslie , LaRochelle Sophie , Guillet de Chatellus Hugues , Azaña José
Published: July 2020

Real-time tracking of a waveform frequency content is essential for detection and analysis of fast rare events in communications, radar, radio astronomy, spectroscopy, sensing etc. This requires a method that can provide real-time spectrum analysis (RT-SA) of high-speed waveforms in a continuous and gap-free fashion. Digital signal processing is inefficient to perform RT-SA over instantaneous frequency bandwidths above the sub-GHz range and/or to track spectral changes faster than a few microseconds. Analog dispersion-induced frequency-to-time mapping enables RT-SA of short isolated pulse-like signals but cannot be extended to continuous waveforms. Here, we propose a universal analog processing approach for time-mapping a gap-free spectrogram −the prime method for dynamic frequency analysis− of an incoming arbitrary waveform, based on a simple sampling and dispersive delay scheme. In experiments, the spectrograms of GHz-bandwidth microwave signals are captured at a speed of ~5×109 Fourier transforms per second, allowing to intercept nanosecond-duration frequency transients in real time. This method opens new opportunities for dynamic frequency analysis and processing of high-speed waveforms.
Automated design of a convolutional neural network with multi-scale filters for cost-efficient seismic data classification
Authors: Geng Zhi , Wang Yanfei
Published: July 2020

Geoscientists mainly identify subsurface geologic features using exploration-derived seismic data. Classification or segmentation of 2D/3D seismic images commonly relies on conventional deep learning methods for image recognition. However, complex reflections of seismic waves tend to form high-dimensional and multi-scale signals, making traditional convolutional neural networks (CNNs) computationally costly. Here we propose a highly efficient and resource-saving CNN architecture (SeismicPatchNet) with topological modules and multi-scale-feature fusion units for classifying seismic data, which was discovered by an automated data-driven search strategy. The storage volume of the architecture parameters (0.73 M) is only ~2.7 MB, ~0.5% of the well-known VGG-16 architecture. SeismicPatchNet predicts nearly 18 times faster than ResNet-50 and shows an overwhelming advantage in identifying Bottom Simulating Reflection (BSR), an indicator of marine gas-hydrate resources. Saliency mapping demonstrated that our architecture captured key features well. These results suggest the prospect of end-to-end interpretation of multiple seismic datasets at extremely low computational cost.
Effects of climate change on the movement of future landfalling Texas tropical cyclones
Authors: Hassanzadeh Pedram , Lee Chia-Ying , Nabizadeh Ebrahim , Camargo Suzana J. , Ma Ding , Yeung Laurence Y.
Published: July 2020

The movement of tropical cyclones (TCs), particularly around the time of landfall, can substantially affect the resulting damage. Recently, trends in TC translation speed and the likelihood of stalled TCs such as Harvey have received significant attention, but findings have remained inconclusive. Here, we examine how the June-September steering wind and translation speed of landfalling Texas TCs change in the future under anthropogenic climate change. Using several large-ensemble/multi-model datasets, we find pronounced regional variations in the meridional steering wind response over North America, but―consistently across models―stronger June-September-averaged northward steering winds over Texas. A cluster analysis of daily wind patterns shows more frequent circulation regimes that steer landfalling TCs northward in the future. Downscaling experiments show a 10-percentage-point shift from the slow-moving to the fast-moving end of the translation-speed distribution in the future. Together, these analyses indicate increases in the likelihood of faster-moving landfalling Texas TCs in the late 21st century.
Persistent telomere cohesion protects aged cells from premature senescence
Authors: Azarm Kameron , Bhardwaj Amit , Kim Eugenie , Smith Susan
Published: July 2020

Human telomeres are bound by the telomere repeat binding proteins TRF1 and TRF2. Telomere shortening in human cells leads to a DNA damage response that signals replicative senescence. While insufficient loading of TRF2 at shortened telomeres contributes to the DNA damage response in senescence, the contribution of TRF1 to senescence induction has not been determined. Here we show that counter to TRF2 deficiency-mediated induction of DNA damage, TRF1 deficiency serves a protective role to limit induction of DNA damage induced by subtelomere recombination. Shortened telomeres recruit insufficient TRF1 and as a consequence inadequate tankyrase 1 to resolve sister telomere cohesion. Our findings suggest that the persistent cohesion protects short telomeres from inappropriate recombination. Ultimately, in the final division, telomeres are no longer able to maintain cohesion and subtelomere copying ensues. Thus, the gradual loss of TRF1 and concomitant persistent cohesion that occurs with telomere shortening ensures a measured approach to replicative senescence.
Integrated pharmaco-proteogenomics defines two subgroups in isocitrate dehydrogenase wild-type glioblastoma with prognostic and therapeutic opportunities
Authors: Oh Sejin , Yeom Jeonghun , Cho Hee Jin , Kim Ju-Hwa , Yoon Seon-Jin , Kim Hakhyun , Sa Jason K. , Ju Shinyeong , Lee Hwanho , Oh Myung Joon , Lee Wonyeop , Kwon Yumi , Li Honglan , Choi Seunghyuk , Han Jang Hee , Chang Jong Hee , Choi Eunsuk , Kim Jayeon , Her Nam-Gu , Kim Se Hoon , Kang Seok-Gu , Paek Eunok , Nam Do-Hyun , Lee Cheolju , Kim Hyun Seok
Published: July 2020

The prognostic and therapeutic relevance of molecular subtypes for the most aggressive isocitrate dehydrogenase 1/2 (IDH) wild-type glioblastoma (GBM) is currently limited due to high molecular heterogeneity of the tumors that impedes patient stratification. Here, we describe a distinct binary classification ofIDHwild-type GBM tumors derived from a quantitative proteomic analysis of 39IDHwild-type GBMs as well asIDHmutant and low-grade glioma controls. Specifically, GBM proteomic cluster 1 (GPC1) tumors exhibit Warburg-like features, neural stem-cell markers, immune checkpoint ligands, and a poor prognostic biomarker, FKBP prolyl isomerase 9 (FKBP9). Meanwhile, GPC2 tumors show elevated oxidative phosphorylation-related proteins, differentiated oligodendrocyte and astrocyte markers, and a favorable prognostic biomarker, phosphoglycerate dehydrogenase (PHGDH). Integrating these proteomic features with the pharmacological profiles of matched patient-derived cells (PDCs) reveals that the mTORC1/2 dual inhibitor AZD2014 is cytotoxic to the poor prognostic PDCs. Our analyses will guide GBM prognosis and precision treatment strategies.
Engineering monocyte/macrophage−specific glucocerebrosidase expression in human hematopoietic stem cells using genome editing
Authors: Scharenberg Samantha G. , Poletto Edina , Lucot Katherine L. , Colella Pasqualina , Sheikali Adam , Montine Thomas J. , Porteus Matthew H. , Gomez-Ospina Natalia
Published: July 2020

Gaucher disease is a lysosomal storage disorder caused by insufficient glucocerebrosidase activity. Its hallmark manifestations are attributed to infiltration and inflammation by macrophages. Current therapies for Gaucher disease include life−long intravenous administration of recombinant glucocerebrosidase and orally-available glucosylceramide synthase inhibitors. An alternative approach is to engineer the patient’s own hematopoietic system to restore glucocerebrosidase expression, thereby replacing the affected cells, and constituting a potential one-time therapy for this disease. Here, we report an efficient CRISPR/Cas9-based approach that targets glucocerebrosidase expression cassettes with a monocyte/macrophage-specific element to the CCR5 safe-harbor locus in human hematopoietic stem and progenitor cells. The targeted cells generate glucocerebrosidase-expressing macrophages and maintain long-term repopulation and multi-lineage differentiation potential with serial transplantation. The combination of a safe-harbor and a lineage-specific promoter establishes a universal correction strategy and circumvents potential toxicity of ectopic glucocerebrosidase in the stem cells. Furthermore, it constitutes an adaptable platform for other lysosomal enzyme deficiencies.
The Seminavis robusta genome provides insights into the evolutionary adaptations of benthic diatoms
Authors: Osuna-Cruz Cristina Maria , Bilcke Gust , Vancaester Emmelien , De Decker Sam , Bones Atle M. , Winge Per , Poulsen Nicole , Bulankova Petra , Verhelst Bram , Audoor Sien , Belisova Darja , Pargana Aikaterini , Russo Monia , Stock Frederike , Cirri Emilio , Brembu Tore , Pohnert Georg , Piganeau Gwenael , Ferrante Maria Immacolata , Mock Thomas , Sterck Lieven , Sabbe Koen , De Veylder Lieven , Vyverman Wim , Vandepoele Klaas
Published: July 2020

Benthic diatoms are the main primary producers in shallow freshwater and coastal environments, fulfilling important ecological functions such as nutrient cycling and sediment stabilization. However, little is known about their evolutionary adaptations to these highly structured but heterogeneous environments. Here, we report a reference genome for the marine biofilm-forming diatom Seminavis robusta, showing that gene family expansions are responsible for a quarter of all 36,254 protein-coding genes. Tandem duplications play a key role in extending the repertoire of specific gene functions, including light and oxygen sensing, which are probably central for its adaptation to benthic habitats. Genes differentially expressed during interactions with bacteria are strongly conserved in other benthic diatoms while many species-specific genes are strongly upregulated during sexual reproduction. Combined with re-sequencing data from 48 strains, our results offer insights into the genetic diversity and gene functions in benthic diatoms.
Structure-based machine-guided mapping of amyloid sequence space reveals uncharted sequence clusters with higher solubilities
Authors: Louros Nikolaos , Orlando Gabriele , De Vleeschouwer Matthias , Rousseau Frederic , Schymkowitz Joost
Published: July 2020

The amyloid conformation can be adopted by a variety of sequences, but the precise boundaries of amyloid sequence space are still unclear. The currently charted amyloid sequence space is strongly biased towards hydrophobic, beta-sheet prone sequences that form the core of globular proteins and by Q/N/Y rich yeast prions. Here, we took advantage of the increasing amount of high-resolution structural information on amyloid cores currently available in the protein databank to implement a machine learning approach, named Cordax (https://cordax.switchlab.org), that explores amyloid sequence beyond its current boundaries. Clustering by t-Distributed Stochastic Neighbour Embedding (t-SNE) shows how our approach resulted in an expansion away from hydrophobic amyloid sequences towards clusters of lower aliphatic content and higher charge, or regions of helical and disordered propensities. These clusters uncouple amyloid propensity from solubility representing sequence flavours compatible with surface-exposed patches in globular proteins, functional amyloids or sequences associated to liquid-liquid phase transitions.
Association between Serum Essential Metal Elements and the Risk of Schizophrenia in China
Authors: Ma Jiahui , Yan Lailai , Guo Tongjun , Yang Siyu , Liu Yaqiong , Xie Qing , Ni Dawei , Wang Jingyu
Published: July 2020

Numerous essential metal elements (EMEs) are necessary to maintain the proper function of human body. In this case-control study, we investigated the associations of 11 EMEs [Calcium (Ca), potassium (K), magnesium (Mg), sodium (Na), manganese (Mn), selenium (Se), cobalt (Co), Molybdenum (Mo), copper (Cu), zinc (Zn), and iron (Fe)] in serum with the risk of schizophrenia. We recruited first-episode and drug-naïve schizophrenic patients (cases = 99) and age-sex-matched normal subjects (controls = 99) from Tangshan, Hebei Province, China. The 11 EMEs in serum from cases and controls were quantified by inductively coupled plasma atomic emission spectrometry and inductively coupled plasma mass spectrometry. We observed that a higher level of Mn (OR = 2.390; 95%CI: 1.504–3.796) and lower levels of Ca (OR = 0.939; 95%CI: 0.890–0.990), Mg (OR = 0.806; 95%CI: 0.669–0.972), Na (OR = 0.995; 95%CI: 0.993–0.998), and Se (OR = 0.954; 95%CI: 0.937–0.972) were associated with an elevated risk of schizophrenia. Dose–response relationships between serum EME concentrations and the risk of schizophrenia were observed in most of the schizophrenia-associated EMEs. Moreover, the serum concentrations of these schizophrenia-associated EMEs in patients were correlated with the severity of their clinical symptoms. Significant correlations were found between EMEs and biomarkers associated with schizophrenia related to metabolic and oxidative stress. This study suggested that the concentration and profile of EMEs were different between schizophrenic patients and normal controls and revealed potential metabolisms associated with EMEs and schizophrenia, suggesting EMEs might act as biomarkers of schizophrenia to improve the current situation of diagnosis and treatment.
Recursive Consensus Clustering for novel subtype discovery from transcriptome data
Authors: Sonpatki Pranali , Shah Nameeta
Published: July 2020

Large-scale transcriptomic data is used by biologists for the discovery of new molecular patterns or cell subpopulations. Clustering is one of the most popular methods for dimensionality reduction and data analysis for large scale datasets. The major problem while clustering the data is the selection of the optimal number of clusters (k) for each dataset and to discover new insights from it. We have developed Recursive Consensus Clustering (RCC), an unsupervised clustering algorithm for novel subtype discovery from both bulk and single-cell datasets. RCC is available as an R package and facilitates the generation of new biological insights through intuitive visualization of clustering results.
Cytosolic phospholipase A2-α participates in lipid body formation and PGE2 release in human neutrophils stimulated with an l-amino acid oxidase from Calloselasma rhodostoma venom
Authors: Paloschi Mauro Valentino , Lopes Jéssica Amaral , Boeno Charles Nunes , Silva Milena Daniela Souza , Evangelista Jaína Rodrigues , Pontes Adriana Silva , da Silva Setúbal Sulamita , Rego Cristina Matiele Alves , Néry Neriane Monteiro , Ferreira e Ferreira Alex Augusto , Pires Weverson Luciano , Felipin Kátia Paula , Ferreira Gabriel Eduardo Melim , Bozza Patrícia Torres , Zuliani Juliana Pavan
Published: July 2020

Cr-LAAO, an l-amino acid oxidase isolated from Calloselasma rhodosthoma snake venom, has been demonstrated as a potent stimulus for neutrophil activation and inflammatory mediator production. However, the mechanisms involved in Cr-LAAO induced neutrophil activation has not been well characterized. Here we investigated the mechanisms involved in Cr-LAAO-induced lipid body (also known as lipid droplet) biogenesis and eicosanoid formation in human neutrophils. Using microarray analysis, we show for the first time that Cr-LAAO plays a role in the up-regulation of the expression of genes involved in lipid signalling and metabolism. Those include different members of phospholipase A2, mostly cytosolic phospholipase A2-α (cPLA2-α); and enzymes involved in prostaglandin synthesis including cyclooxygenases 2 (COX-2), and prostaglandin E synthase (PTGES). In addition, genes involved in lipid droplet formation, including perilipin 2 and 3 (PLIN 2 and 3) and diacylglycerol acyltransferase 1 (DGAT1), were also upregulated. Furthermore, increased phosphorylation of cPLA2-α, lipid droplet biogenesis and PGE2 synthesis were observed in human neutrophils stimulated with Cr-LAAO. Treatment with cPLA2-α inhibitor (CAY10650) or DGAT-1 inhibitor (A922500) suppressed lipid droplets formation and PGE2 secretion. In conclusion, we demonstrate for the first time the effects of Cr-LAAO to regulate neutrophil lipid metabolism and signalling.
Comparison of 68Ga-PSMA-617 PET/CT with mpMRI for the detection of PCa in patients with a PSA level of 4–20 ng/ml before the initial biopsy
Authors: Li Yu , Han Donghui , Wu Peng , Ren Jing , Ma Shuaijun , Zhang Jingliang , Song Wei , Lin Xiaoyu , Jiao Dian , Shi Shengjia , Yang Fa , Wu Jieheng , Meng Ping , Wen Weihong , Kang Fei , Wang Jing , Qin Weijun
Published: July 2020

The study was aimed at assessing the diagnostic performance of 68Ga-PSMA-617 PET/CT in the detection of prostate cancer (PCa) in patients with a prostate-specific antigen (PSA) level of 4–20 ng/ml and to compare its efficacy with that of multiparametric MRI (mpMRI). We analyzed the data of 67 consecutive patients with PSA levels of 4–20 ng/ml who almost simultaneously underwent 68Ga-PSMA-617 PET/CT and mpMRI. 68Ga-PSMA-617 PET/CT and mpMRI diagnostic performances were compared via receiver operating characteristic (ROC) curve analysis. Of the 67 suspected PCa cases, 33 had pathologically confirmed PCa. 68Ga-PSMA-617 PET/CT showed a patient-based sensitivity, specificity, and positive and negative predictive values (PPVs and NPVs) of 87.88%, 88.24%, 87.88%, and 88.24%, respectively. The corresponding values for mpMRI were 84.85%, 52.94%, 63.64%, and 78.26%. The area under the curve values for 68Ga-PSMA-617 PET/CT and mpMRI were 0.881 and 0.689, respectively. 68Ga-PSMA-617 PET/CT showed a better diagnostic performance than mpMRI in the detection of PCa in patients with PSA levels of 4–20 ng/ml.
GL261 luciferase-expressing cells elicit an anti-tumor immune response: an evaluation of murine glioma models
Authors: Sanchez Victoria E. , Lynes John P. , Walbridge Stuart , Wang Xiang , Edwards Nancy A. , Nwankwo Anthony K. , Sur Hannah P. , Dominah Gifty A. , Obungu Arnold , Adamstein Nicholas , Dagur Pradeep K. , Maric Dragan , Munasinghe Jeeva , Heiss John D. , Nduom Edjah K.
Published: July 2020

Preclinical models that reliably recapitulate the immunosuppressive properties of human gliomas are essential to assess immune-based therapies. GL261 murine glioma cells are widely used as a syngeneic animal model of glioma, however, it has become common practice to transfect these cells with luciferase for fluorescent tumor tracking. The aim of this study was to compare the survival of mice injected with fluorescent or non-fluorescent GL261 cells and characterize the differences in their tumor microenvironment. Mice were intracranially implanted with GL261, GL261 Red-FLuc or GL261-Luc2 cells at varying doses. Cytokine profiles were evaluated by proteome microarray and Kaplan–Meier survival analysis was used to determine survival differences. Median survival for mice implanted with 5 × 104 GL261 cells was 18 to 21 days. The GL261 Red-FLuc implanted mice cells did not reach median survival at any tumor dose. Mice injected with 3 × 105 GL261-Luc2 cells reached median survival at 23 days. However, median survival was significantly prolonged to 37 days in mice implanted with 5 × 104 GL261-Luc2 cells. Additionally, proteomic analyses revealed significantly elevated inflammatory cytokines in the supernatants of the GL261 Red-FLuc cells and GL261-Luc2 cells. Our data suggest that GL261 Red-FLuc and GL261-Luc2 murine models elicit an anti-tumor immune response by increasing pro-inflammatory modulators.
Self-sustained planar intercalations due to mechanosignaling feedbacks lead to robust axis extension during morphogenesis
Authors: Anbari Samira , Buceta Javier
Published: July 2020

Tissue elongation is a necessary process in metazoans to implement their body plans that is not fully understood. Here we propose a mechanism based on the interplay between cellular mechanics and primordia patterning that results in self-sustained planar intercalations. Thus, we show that a location-dependent modulation of the mechanical properties of cells leads to robust axis extension. To illustrate the plausibility of this mechanism, we test it against different patterning models by means of computer simulations of tissues where we implemented mechano-signaling feedbacks. Our results suggest that robust elongation relies on a trade-off between cellular and tissue strains that is orchestrated through the cleavage orientation. In the particular context of axis extension in Turing-patterned tissues, we report that different directional cell activities cooperate synergetically to achieve elongation. Altogether, our findings help to understand how the axis extension phenomenon emerges from the dynamics of individual cells.
Spa therapy with physical rehabilitation is an alternative to usual spa therapy protocol in symptomatic knee osteoarthritis
Authors: Rat Anne-Christine , Loeuille Damien , Vallata Amandine , Bernard Lorraine , Spitz Emmanuel , Desvignes Alexandra , Boulange Michel , Paysant Jean , Guillemin Francis , Chary-Valckenaere Isabelle
Published: July 2020

The objective of the study was to demonstrate the non-inferiority of low-frequency spa therapy combined with rehabilitation (Spa-rehab) versus standard spa therapy at 6 months for symptomatic knee osteoarthritis (KOA). A prospective, randomized, monocenter, non-inferiority trial with recruitment of community-based symptomatic KOA patients was performed. Standard spa therapy comprised standardized spa treatment, 6 days a week for 3 weeks, and Spa-rehab therapy comprised spa sessions, 3 days a week for 3 weeks, followed by a dedicated rehabilitation program, 3 days a week for 3 weeks. The primary endpoint was achieving at 6 months a minimal clinically important improvement (MCII) for pain on a visual analog scale and/or an MCII for function on the WOMAC index and no knee surgery (composite MCII). Secondary endpoints were composite MCII at 3 months and achieving a Patient Acceptable Symptom State (PASS) for pain and function at 3 and 6 months. Among 283 patients included, 145 were allocated to standard spa therapy and 138 to Spa-rehab therapy. We could not demonstrate the non-inferiority of Spa-rehab therapy for the primary endpoint: difference for responders − 0.08 [90% CI (− 0.18 to 0.02), p = 0.14]. However, the difference test between the groups was not significant (p = 0.18). Spa-rehab therapy was not inferior to standard spa therapy for the composite MCII at 3 months or the PASS at 3 and 6 months. Spa-rehab therapy can reasonably be proposed to patients with symptomatic KOA. This protocol may be more cost-effective than standard spa therapy and avoid absenteeism from work and accommodation costs for patients who live close to a centre.
Nanoscale trace metal imprinting of biocalcification of planktic foraminifers by Toba’s super-eruption
Authors: Lemelle L. , Bartolini A. , Simionovici A. , Tucoulou R. , De Nolf W. , Bassinot F. , de Garidel-Thoron T.
Published: July 2020

Bioactive metal releases in ocean surface water, such as those by ash falls during volcanic super-eruptions, might have a potentially toxic impact on biocalcifier planktic microorganisms. Nano-XRF imaging with the cutting-edge synchrotron hard X-ray nano-analysis ID16B beamline (ESRF) revealed for the first time a specific Zn- and Mn-rich banding pattern in the test walls of Globorotalia menardii planktic foraminifers extracted from the Young Toba Tuff layer, and thus contemporaneous with Toba’s super-eruption, 74,000 years ago. The intra-test correlation of Zn and Mn patterns at the nanoscale with the layered calcareous microarchitecture, indicates that the incorporation of these metals is syngenetic to the wall growth. The preferential Mn and Zn sequestration within the incipient stages of chamber formation suggests a selective incorporation mechanism providing a resilience strategy to metal pollution in the test building of planktic foraminifers.
A new method to control error rates in automated species identification with deep learning algorithms
Authors: Villon Sébastien , Mouillot David , Chaumont Marc , Subsol Gérard , Claverie Thomas , Villéger Sébastien
Published: July 2020

Processing data from surveys using photos or videos remains a major bottleneck in ecology. Deep Learning Algorithms (DLAs) have been increasingly used to automatically identify organisms on images. However, despite recent advances, it remains difficult to control the error rate of such methods. Here, we proposed a new framework to control the error rate of DLAs. More precisely, for each species, a confidence threshold was automatically computed using a training dataset independent from the one used to train the DLAs. These species-specific thresholds were then used to post-process the outputs of the DLAs, assigning classification scores to each class for a given image including a new class called “unsure”. We applied this framework to a study case identifying 20 fish species from 13,232 underwater images on coral reefs. The overall rate of species misclassification decreased from 22% with the raw DLAs to 2.98% after post-processing using the thresholds defined to minimize the risk of misclassification. This new framework has the potential to unclog the bottleneck of information extraction from massive digital data while ensuring a high level of accuracy in biodiversity assessment.
Publisher Correction: Cortical-like mini-columns of neuronal cells on zinc oxide nanowire surfaces
Authors: Onesto V. , Villani M. , Narducci R. , Malara N. , Imbrogno A. , Allione M. , Costa N. , Coppedè N. , Zappettini A. , Cannistraci C. V. , Cancedda L. , Amato F. , Di Fabrizio Enzo , Gentile F.
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Functional and transcriptional characterization of complex neuronal co-cultures
Authors: Enright Heather A. , Lam Doris , Sebastian Aimy , Sales Ana Paula , Cadena Jose , Hum Nicholas R. , Osburn Joanne J. , Peters Sandra K. G. , Petkus Bryan , Soscia David A. , Kulp Kristen S. , Loots Gabriela G. , Wheeler Elizabeth K. , Fischer Nicholas O.
Published: July 2020

Brain-on-a-chip systems are designed to simulate brain activity using traditional in vitro cell culture on an engineered platform. It is a noninvasive tool to screen new drugs, evaluate toxicants, and elucidate disease mechanisms. However, successful recapitulation of brain function on these systems is dependent on the complexity of the cell culture. In this study, we increased cellular complexity of traditional (simple) neuronal cultures by co-culturing with astrocytes and oligodendrocyte precursor cells (complex culture). We evaluated and compared neuronal activity (e.g., network formation and maturation), cellular composition in long-term culture, and the transcriptome of the two cultures. Compared to simple cultures, neurons from complex co-cultures exhibited earlier synapse and network development and maturation, which was supported by localized synaptophysin expression, up-regulation of genes involved in mature neuronal processes, and synchronized neural network activity. Also, mature oligodendrocytes and reactive astrocytes were only detected in complex cultures upon transcriptomic analysis of age-matched cultures. Functionally, the GABA antagonist bicuculline had a greater influence on bursting activity in complex versus simple cultures. Collectively, the cellular complexity of brain-on-a-chip systems intrinsically develops cell type-specific phenotypes relevant to the brain while accelerating the maturation of neuronal networks, important features underdeveloped in traditional cultures.
Spatiotemporal clustering analysis of Expanded Program on Immunization (EPI) vaccination coverage in Pakistan
Authors: Umer Muhammad Farooq , Zofeen Shumaila , Hu Wenbiao , Qi Xin , Zhuang Guihua
Published: July 2020

Universal vaccination coverage is still far from desired targets in many global regions including Pakistan, despite the success stories and its scientifically proven benefits. EPI Pakistan vaccination coverage data 2012–2016, at district level was collected from Federal EPI Pakistan. District-wise population data were collected from Pakistan Bureau of Statistics. Descriptive statistics and sequence plots were performed in SPSS 13.0. Purely spatial scanning analysis was done in SaTScan 9.4.4 using discrete Poisson model for detection of low vaccination coverage clusters. Geographical information system (GIS) was used to display spatial patterns and clusters of low vaccination coverage districts in Pakistan. Average annual EPI vaccination coverage in each study year were; 70.98 in 2012, 69.39% in 2013, 66.74% in 2014, 61.47% in 2015, and 67.01% in 2016, respectively. Cumulative average national vaccination rate (2012–2016) for all types of EPI vaccines was 60.60%. Average national vaccination rate for BCG, OPV3, pentavalent3 and measles1 was 67.12%, 58.53%, 58.47%, and 58.29%, respectively. Spatial cluster analysis demonstrated that most of low coverage districts for BCG, OPV3 and pentavalent3 were from FATA and KPK; while measles1 low coverage districts belonged to Balochistan. Future research should probe factors involved in low vaccination coverage in high risk districts.
A novel silkworm infection model with fluorescence imaging using transgenic Trichosporon asahii expressing eGFP
Authors: Matsumoto Yasuhiko , Yamazaki Hideki , Yamasaki Yusuke , Tateyama Yuki , Yamada Tsuyoshi , Sugita Takashi
Published: July 2020

Trichosporon asahii is a pathogenic fungus that causes deep mycosis in patients with neutropenia. Establishing an experimental animal model for quantitatively evaluating pathogenicity and developing a genetic recombination technology will help to elucidate the infection mechanism of T. asahii and promote the development of antifungal drugs. Here we established a silkworm infection model with a transgenic T. asahii strain expressing eGFP. Injecting T. asahii into silkworms eventually killed the silkworms. Moreover, the administration of antifungal agents, such as amphotericin B, fluconazole, and voriconazole, prolonged the survival time of silkworms infected with T. asahii. A transgenic T. asahii strain expressing eGFP was obtained using a gene recombination method with Agrobacterium tumefaciens. The T. asahii strain expressing eGFP showed hyphal formation in the silkworm hemolymph. Both hyphal growth and the inhibition of hyphal growth by the administration of antifungal agents were quantitatively estimated by monitoring fluorescence. Our findings suggest that a silkworm infection model using T. asahii expressing eGFP is useful for evaluating both the pathogenicity of T. asahii and the efficacy of antifungal drugs.
Rare polyandry and common monogamy in the firefly squid, Watasenia scintillans
Authors: Sato Noriyosi , Tsuda Sei-Ichiro , Nur E. Alam Md. , Sasanami Tomohiro , Iwata Yoko , Kusama Satoshi , Inamura Osamu , Yoshida Masa-aki , Hirohashi Noritaka
Published: July 2020

In cephalopods, all species are considered to be polyandrous because of their common life history and reproductive traits reflecting a polyandrous mating system. Contrary to this belief, here we show several lines of evidence for monogamy in the firefly squid, Watasenia scintillans. In this species, females are capable of long-term storage of spermatangia, and of egg spawning even after the complete disappearance of males following the breeding season. The stored spermatangia are distributed equally between bilateral pouches under the female’s neck collar. Such a nonrandom pattern of sperm storage prompted us to hypothesize that females might engage in lifetime monandry. Hence, we genotyped female-stored spermatangia and offspring, and found that in 95% of females (18/19), all the spermatangia had been delivered from a single male and all the embryos in a clutch had been sired by spermatozoa from stored spermatangia. In males, throughout the reproductive season, relative testis mass was much smaller in W. scintillans than in all other cephalopods examined previously. The mean number of male-stored spermatophores was ~ 30, equivalent to only 2.5 matings. Our genetic, demographic and morphometrical data agree with a mathematical model predicting that monogyny is favored when potential mates are scarce. Together, these results suggest mutual monogamy in W. scintillans.
Iron oxides nanobelt arrays rooted in nanoporous surface of carbon tube textile as stretchable and robust electrodes for flexible supercapacitors with ultrahigh areal energy density and remarkable cycling-stability
Authors: Ding Yuying , Tang Shaochun , Han Rubing , Zhang Sheng , Pan Guanjun , Meng Xiangkang
Published: July 2020

We report a significant advance toward the rational design and fabrication of stretchable and robust flexible electrodes with favorable hierarchical architectures constructed by homogeneously distributed α-Fe2O3 nanobelt arrays rooted in the surface layer of nanoporous carbon tube textile (NPCTT). New insight into alkali activation assisted surface etching of carbon and in-situ catalytic anisotropic growth is proposed, and is experimentally demonstrated by the synthesis of the Fe2O3 nanobelt arrays/NPCTT. The Fe2O3/NPCTT electrode shows excellent flexibility and great stretchability, especially has a high specific areal capacitance of 1846 mF cm−2 at 1 mA cm−2 and cycling stability with only 4.8% capacitance loss over 10,000 cycles at a high current density of 20 mA cm−2. A symmetric solid-state supercapacitor with the Fe2O3/NPCTT achieves an operating voltage of 1.75 V and a ultrahigh areal energy density of 176 µWh cm−2 (at power density of 748 µW cm−2), remarkable cycling stability, and outstanding reliability with no capacity degradation under repeated large-angle twisting. Such unique architecture improves both mechanical robustness and electrical conductivity, and allows a strong synergistic attribution of Fe2O3 and NPCTT. The synthetic method can be extended to other composites such as MnO nanosheet arrays/NPCTT and Co3O4 nanowire arrays/NPCTT. This work opens up a new pathway to the design of high-performance devices for wearable electronics.
Increasing trends in childhood overweight have mostly reversed: 30 years of continuous surveillance of Slovenian youth
Authors: Sorić Maroje , Jurak Gregor , Đurić Saša , Kovač Marjeta , Strel Janko , Starc Gregor
Published: July 2020

The aim of this study is to describe trends in overweight and obesity among Slovenian youth for the period 1989–2018. Nearly all schoolchildren in Slovenia had their height and weight measured annually, which lead to a total of 6,738,510 data-points during the 30-year period. The IOTF cut-off points and Joinpoint regression were used to examine annual percent change (APC) in overweight and obesity prevalence across 3 age groups (7–10, 11–14 and 15–18 years). Obesity approximately tripled, while overweight doubled between 1989 and late 2000s in both genders. Since then overweight has been steadily decreasing in all 3 age groups for boys and in 7–10-year-old girls. Obesity has also been declining since 2009, but only in the youngest boys and girls (APC = − 1.9, 95% CI = − 3.2 to − 0.6 and APC = − 1.6, 95% CI = − 3.0 to − 0.2, respectively). Unfavourable trends were noted only in 15–18-year-old girls, with obesity rising at an unchanged rate over the past 30 years (APC = 4.8, 95% CI = 4.5–5.1). Overweight and obesity among Slovenian youth has increased dramatically over the last 3 decades. Still, during the last decade this rise has been reversed or at least stopped. This reversal of trends was more marked in boys than in girls, and in young children compared to adolescents.
Localization of quantitative trait loci for cucumber fruit shape by a population of chromosome segment substitution lines
Authors: Wang Xiangfei , Li Hao , Gao Zhihui , Wang Lina , Ren Zhonghai
Published: July 2020

Cucumber fruit shape, a significant agronomic trait, is controlled by quantitative trait loci (QTLs). Feasibility of chromosome segment substitution lines (CSSLs) is well demonstrated to map QTLs, especially the minor-effect ones. To detect and identify QTLs with CSSLs can provide new insights into the underlying mechanisms regarding cucumber fruit shape. In the present study, 71 CSSLs were built from a population of backcross progeny (BC4F2) by using RNS7 (a round-fruit cucumber) as the recurrent parent and CNS21 (a long-stick-fruit cucumber) as the donor parent in order to globally detect QTLs for cucumber fruit shape. With the aid of 114 InDel markers covering the whole cucumber genome, 21 QTLs were detected for fruit shape-related traits including ovary length, ovary diameter, ovary shape index, immature fruit length, immature fruit diameter, immature fruit shape index, mature fruit length, mature fruit diameter and mature fruit shape index, and 4 QTLs for other traits including fruit ground and flesh color, and seed size were detected as well. Together our results provide important resources for the subsequent theoretical and applied researches on cucumber fruit shape and other traits.
Geometric regulation of histone state directs melanoma reprogramming
Authors: Lee Junmin , Molley Thomas G. , Seward Christopher H. , Abdeen Amr A. , Zhang Huimin , Wang Xiaochun , Gandhi Hetvi , Yang Jia-Lin , Gaus Katharina , Kilian Kristopher A.
Published: July 2020

Malignant melanoma displays a high degree of cellular plasticity during disease progression. Signals in the tumor microenvironment are believed to influence melanoma plasticity through changes in the epigenetic state to guide dynamic differentiation and de-differentiation. Here we uncover a relationship between geometric features at perimeter regions of melanoma aggregates, and reprogramming to a stem cell-like state through histone marks H3K4Me2 and H3K9Ac. Using an in vitro tumor microengineering approach, we find spatial enrichment of these histone modifications with concurrent expression of stemness markers. The epigenetic modifier PRDM14 overlaps with H3K9Ac and shows elevated expression in cells along regions of perimeter curvature. siRNA knockdown of PRDM14 abolishes the MIC phenotype suggesting a role in regulating melanoma heterogeneity. Our results suggest mechanotransduction at the periphery of melanoma aggregates may orchestrate the activity of epigenetic modifiers to regulate histone state, cellular plasticity, and tumorigenicity.
Reconstituted cell-free protein synthesis using in vitro transcribed tRNAs
Authors: Hibi Keita , Amikura Kazuaki , Sugiura Naoki , Masuda Keiko , Ohno Satoshi , Yokogawa Takashi , Ueda Takuya , Shimizu Yoshihiro
Published: July 2020

Entire reconstitution of tRNAs for active protein production in a cell-free system brings flexibility into the genetic code engineering. It can also contribute to the field of cell-free synthetic biology, which aims to construct self-replicable artificial cells. Herein, we developed a system equipped only with in vitro transcribed tRNA (iVTtRNA) based on a reconstituted cell-free protein synthesis (PURE) system. The developed system, consisting of 21 iVTtRNAs without nucleotide modifications, is able to synthesize active proteins according to the redesigned genetic code. Manipulation of iVTtRNA composition in the system enabled genetic code rewriting. Introduction of modified nucleotides into specific iVTtRNAs demonstrated to be effective for both protein yield and decoding fidelity, where the production yield of DHFR reached about 40% of the reaction with native tRNA at 30°C. The developed system will prove useful for studying decoding processes, and may be employed in genetic code and protein engineering applications.