bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of RE-1 silencing transcription factor accelerates exocrine damage from pancreatic injury
Authors: Bray Julie K. , Elgamal Ola A. , Jiang Jinmai , Wright Lais S. , Sutaria Dhruvitkumar S. , Badawi Mohamed , Borcyk Madeline G. , Liu Xiuli , Fredenburg Kristianna M. , Campbell-Thompson Martha L. , Schmittgen Thomas D. 
Published: February 2020

AbstractRegulation of pancreas plasticity is critical for preventing injury and promoting regeneration upon tissue damage. The intricate process of pancreatic differentiation is governed by an orchestrated network of positive and negative transcription factors for appropriate gene expression. While the transcriptional repressor REST is well characterized as a silencer of neuronal genes in non-neuronal cells, the role of REST in regulating exocrine pancreas cell identity remains largely unexplored. Rest expression is increased upon injury in the mouse pancreas, such as induced acute and chronic pancreatitis and ductal adenocarcinoma. At the cellular level, Rest expression is lower in mature acinar cells compared with pancreas progenitor and ductal cells. To investigate the role of REST activity in pancreatic transdifferentiation and homeostasis, we developed a novel mouse model (Cre/RESTfl/fl) with conditional knockout (KO) of Rest expression within pancreas cells. The high Cre-mediated excision efficiency of Rest exon two KO caused decreased Rest expression and activity within the pancreas. Short-term organoid cultures of pancreatic acini to undergo acinar-to-ductal metaplasia (ADM) showed that loss of REST impedes induced ADM, while overexpression of REST increases ADM. Interestingly, REST ablation accelerated acute pancreatitis in mice treated with the cholecystokinin analog caerulein, as indicated by cellular morphology, elevated serum amylase levels and pancreatic edema. Furthermore, Cre/RESTfl/fl mice were more sensitive to acute pancreatitis injury and displayed augmented tissue damage and cellular lesions. These results suggest REST has a novel protective role against pancreatic tissue damage by acting as a regulator of exocrine cell identity.
ID1 confers cancer cell chemoresistance through STAT3/ATF6-mediated induction of autophagy
Authors: Meng Jiao , Liu Kaiyi , Shao Yang , Feng Xu , Ji Zhaodong , Chang Bin , Wang Yan , Xu Ling , Yang Gong 
Published: February 2020

AbstractChemoresistance is one of the major reasons leading to ovarian cancer high mortality and poor survival. Studies have shown that the alteration of cellular autophagy is associated with cancer cell chemoresistance. Here, we investigated whether the ovarian cancer chemoresistance is associated with the autophagy induced by the inhibitor of DNA binding 1 (ID1). By using gene overexpression or silencing, luciferase assay and human specimens, we show that ID1 induces high autophagy and confers cancer cell chemoresistance. The mechanistic study demonstrates that ID1 first activates the NF-κB signaling through facilitating the nuclear translocation of NF-κB p65, which strengthens the expression and secretion of IL-6 from cancer cells to subsequently activate the signal transducer and activator of transcription 3 (STAT3) through the protein phosphorylation at Y705. We further identified that STAT3 functions to promote the transcription of the activating transcription factor 6 (ATF6), which induces endoplasmic reticulum stress to promote cellular autophagy, granting cancer cell resistance to both cisplatin and paclitaxel treatment. Moreover, we found a significant correlation between the expression of ID1 and ATF6 in 1104 high grade serous ovarian cancer tissues, and that patients with the high expression of ID1 or ATF6 were resistant to platinum treatment and had the poor overall survival and progression-free survival. Thus, we have uncovered a mechanism in which ID1 confers cancer cell chemoresistance largely through the STAT3/ATF6-induced autophagy. The involved molecules, including ID1, STAT3, and ATF6, may have a potential to be targeted in combination with chemotherapeutic agents to improve ovarian cancer survival.
Rapid morphological divergence following a human-mediated introduction: the role of drift and directional selection
Authors: Sendell-Price Ashley T. , Ruegg Kristen C. , Clegg Sonya. M. 
Published: February 2020

AbstractTheory predicts that when populations are established by few individuals, random founder effects can facilitate rapid phenotypic divergence even in the absence of selective processes. However, empirical evidence from historically documented colonisations suggest that, in most cases, drift alone is not sufficient to explain the rate of morphological divergence. Here, using the human-mediated introduction of the silvereye (Zosterops lateralis) to French Polynesia, which represents a potentially extreme example of population founding, we reassess the potential for morphological shifts to arise via drift alone. Despite only 80 years of separation from their New Zealand ancestors, French Polynesian silvereyes displayed significant changes in body and bill size and shape, most of which could be accounted for by drift, without the need to invoke selection. However, signatures of selection at genes previously identified as candidates for bill size and body shape differences in a range of bird species, also suggests a role for selective processes in driving morphological shifts within this population. Twenty-four SNPs in our RAD-Seq dataset were also found to be strongly associated with phenotypic variation. Hence, even under population founding extremes, when it is difficult to reject drift as the sole mechanism based on rate tests of phenotypic shifts, the additional role of divergent natural selection in novel environments can be revealed at the level of the genome.
Impact of two of the world's largest protected areas on longline fishery catch rates
Authors: Lynham John , Nikolaev Anton , Raynor Jennifer , Vilela Thaís , Villaseñor-Derbez Juan Carlos 
Published: February 2020

AbstractTwo of the largest protected areas on earth are U.S. National Monuments in the Pacific Ocean. Numerous claims have been made about the impacts of these protected areas on the fishing industry, but there has been no ex post empirical evaluation of their effects. We use administrative data documenting individual fishing events to evaluate the economic impact of the expansion of these two monuments on the Hawaii longline fishing fleet. Surprisingly, catch and catch-per-unit-effort are higher since the expansions began. To disentangle the causal effect of the expansions from confounding factors, we use unaffected control fisheries to perform a difference-in-differences analysis. We find that the monument expansions had little, if any, negative impacts on the fishing industry, corroborating ecological models that have predicted minimal impacts from closing large parts of the Pacific Ocean to fishing.
Migration, hotspots, and dispersal of HIV infection in Rakai, Uganda
Authors: Kate Grabowski Mary , Lessler Justin , Bazaale Jeremiah , Nabukalu Dorean , Nankinga Justine , Nantume Betty , Ssekasanvu Joseph , Reynolds Steven J. , Ssekubugu Robert , Nalugoda Fred , Kigozi Godfrey , Kagaayi Joseph , Santelli John S. , Kennedy Caitlin , Wawer Maria J. , Serwadda David , Chang Larry W. , Gray Ronald H. 
Published: February 2020

AbstractHIV prevalence varies markedly throughout Africa, and it is often presumed areas of higher HIV prevalence (i.e., hotspots) serve as sources of infection to neighboring areas of lower prevalence. However, the small-scale geography of migration networks and movement of HIV-positive individuals between communities is poorly understood. Here, we use population-based data from ~22,000 persons of known HIV status to characterize migratory patterns and their relationship to HIV among 38 communities in Rakai, Uganda with HIV prevalence ranging from 9 to 43%. We find that migrants moving into hotspots had significantly higher HIV prevalence than migrants moving elsewhere, but out-migration from hotspots was geographically dispersed, contributing minimally to HIV burden in destination locations. Our results challenge the assumption that high prevalence hotspots are drivers of transmission in regional epidemics, instead suggesting that migrants with high HIV prevalence, particularly women, selectively migrate to these areas.
Impaired mitophagy links mitochondrial disease to epithelial stress in methylmalonyl-CoA mutase deficiency
Authors: Luciani Alessandro , Schumann Anke , Berquez Marine , Chen Zhiyong , Nieri Daniela , Failli Mario , Debaix Huguette , Festa Beatrice Paola , Tokonami Natsuko , Raimondi Andrea , Cremonesi Alessio , Carrella Diego , Forny Patrick , Kölker Stefan , Diomedi Camassei Francesca , Diaz Francisca , Moraes Carlos T. , Di Bernardo Diego , Baumgartner Matthias R. , Devuyst Olivier 
Published: February 2020

AbstractDeregulation of mitochondrial network in terminally differentiated cells contributes to a broad spectrum of disorders. Methylmalonic acidemia (MMA) is one of the most common inherited metabolic disorders, due to deficiency of the mitochondrial methylmalonyl-coenzyme A mutase (MMUT). HowMMUTdeficiency triggers cell damage remains unknown, preventing the development of disease–modifying therapies. Here we combine genetic and pharmacological approaches to demonstrate thatMMUTdeficiency induces metabolic and mitochondrial alterations that are exacerbated by anomalies in PINK1/Parkin–mediated mitophagy, causing the accumulation of dysfunctional mitochondria that trigger epithelial stress and ultimately cell damage. Using drug–disease network perturbation modelling, we predict targetable pathways, whose modulation repairs mitochondrial dysfunctions in patient–derived cells and alleviate phenotype changes inmmut–deficient zebrafish. These results suggest a link between primaryMMUTdeficiency, diseased mitochondria, mitophagy dysfunction and epithelial stress, and provide potential therapeutic perspectives for MMA.
Continuous-wave quantum dot photonic crystal lasers grown on on-axis Si (001)
Authors: Zhou Taojie , Tang Mingchu , Xiang Guohong , Xiang Boyuan , Hark Suikong , Martin Mickael , Baron Thierry , Pan Shujie , Park Jae-Seong , Liu Zizhuo , Chen Siming , Zhang Zhaoyu , Liu Huiyun 
Published: February 2020

AbstractSemiconductor III–V photonic crystal (PC) laser is regarded as a promising ultra-compact light source with unique advantages of ultralow energy consumption and small footprint for the next generation of Si-based on-chip optical interconnects. However, the significant material dissimilarities between III-V materials and Si are the fundamental roadblock for conventional monolithic III-V-on-silicon integration technology. Here, we demonstrate ultrasmall III-V PC membrane lasers monolithically grown on CMOS-compatible on-axis Si (001) substrates by using III-V quantum dots. The optically pumped InAs/GaAs quantum-dot PC lasers exhibit single-mode operation with an ultra-low threshold of ~0.6 μW and a large spontaneous emission coupling efficiency up to 18% under continuous-wave condition at room temperature. This work establishes a new route to form the basis of future monolithic light sources for high-density optical interconnects in future large-scale silicon electronic and photonic integrated circuits.
A global assessment of the drivers of threatened terrestrial species richness
Authors: Howard Christine , Flather Curtis H. , Stephens Philip A. 
Published: February 2020

AbstractHigh numbers of threatened species might be expected to occur where overall species richness is also high; however, this explains only a proportion of the global variation in threatened species richness. Understanding why many areas have more or fewer threatened species than would be expected given their species richness, and whether that is consistent across taxa, is essential for identifying global conservation priorities. Here, we show that, after controlling for species richness, environmental factors, such as temperature and insularity, are typically more important than human impacts for explaining spatial variation in global threatened species richness. Human impacts, nevertheless, have an important role, with relationships varying between vertebrate groups and zoogeographic regions. Understanding this variation provides a framework for establishing global conservation priorities, identifying those regions where species are inherently more vulnerable to the effects of threatening human processes, and forecasting how threatened species might be distributed in a changing world.
Genome of Tripterygium wilfordii and identification of cytochrome P450 involved in triptolide biosynthesis
Authors: Tu Lichan , Su Ping , Zhang Zhongren , Gao Linhui , Wang Jiadian , Hu Tianyuan , Zhou Jiawei , Zhang Yifeng , Zhao Yujun , Liu Yuan , Song Yadi , Tong Yuru , Lu Yun , Yang Jian , Xu Cao , Jia Meirong , Peters Reuben J. , Huang Luqi , Gao Wei 
Published: February 2020

AbstractTriptolide is a trace natural product of Tripterygium wilfordii. It has antitumor activities, particularly against pancreatic cancer cells. Identification of genes and elucidation of the biosynthetic pathway leading to triptolide are the prerequisite for heterologous bioproduction. Here, we report a reference-grade genome of T. wilfordii with a contig N50 of 4.36 Mb. We show that copy numbers of triptolide biosynthetic pathway genes are impacted by a recent whole-genome triplication event. We further integrate genomic, transcriptomic, and metabolomic data to map a gene-to-metabolite network. This leads to the identification of a cytochrome P450 (CYP728B70) that can catalyze oxidation of a methyl to the acid moiety of dehydroabietic acid in triptolide biosynthesis. We think the genomic resource and the candidate genes reported here set the foundation to fully reveal triptolide biosynthetic pathway and consequently the heterologous bioproduction.
Tracing tumorigenesis in a solid tumor model at single-cell resolution
Authors: Praktiknjo Samantha D. , Obermayer Benedikt , Zhu Qionghua , Fang Liang , Liu Haiyue , Quinn Hazel , Stoeckius Marlon , Kocks Christine , Birchmeier Walter , Rajewsky Nikolaus 
Published: February 2020

AbstractCharacterizing the complex composition of solid tumors is fundamental for understanding tumor initiation, progression and metastasis. While patient-derived samples provide valuable insight, they are heterogeneous on multiple molecular levels, and often originate from advanced tumor stages. Here, we use single-cell transcriptome and epitope profiling together with pathway and lineage analyses to study tumorigenesis from a developmental perspective in a mouse model of salivary gland squamous cell carcinoma. We provide a comprehensive cell atlas and characterize tumor-specific cells. We find that these cells are connected along a reproducible developmental trajectory: initiated in basal cells exhibiting an epithelial-to-mesenchymal transition signature, tumorigenesis proceeds through Wnt-differential cancer stem cell-like subpopulations before differentiating into luminal-like cells. Our work provides unbiased insights into tumor-specific cellular identities in a whole tissue environment, and emphasizes the power of using defined genetic model systems.
Jouvence a small nucleolar RNA required in the gut extends lifespan in Drosophila
Authors: Soulé Stéphanie , Mellottée Lucille , Arab Abdelkrim , Chen Chongjian , Martin Jean-René 
Published: February 2020

AbstractLongevity is influenced by genetic and environmental factors, but the underlying mechanisms remain elusive. Here, we functionally characterise a Drosophila small nucleolar RNA (snoRNA), named jouvence whose loss of function reduces lifespan. The genomic region of jouvence rescues the longevity in mutant, while its overexpression in wild-type increases lifespan. Jouvence is required in enterocytes. In mutant, the epithelium of the gut presents more hyperplasia, while the overexpression of jouvence prevents it. Molecularly, the mutant lack pseudouridylation on 18S and 28S-rRNA, a function rescued by targeted expression of jouvence in the gut. A transcriptomic analysis performed from the gut reveals that several genes are either up- or down-regulated, while restoring the mRNA level of two genes (ninaD or CG6296) rescue the longevity. Since snoRNAs are structurally and functionally well conserved throughout evolution, we identified putative jouvence orthologue in mammals including humans, suggesting that its function in longevity could be conserved.
Robust temporal pumping in a magneto-mechanical topological insulator
Authors: Grinberg Inbar Hotzen , Lin Mao , Harris Cameron , Benalcazar Wladimir A. , Peterson Christopher W. , Hughes Taylor L. , Bahl Gaurav 
Published: February 2020

AbstractThe transport of energy through 1-dimensional (1D) waveguiding channels can be affected by sub-wavelength disorder, resulting in undesirable localization and backscattering phenomena. However, quantized disorder-resilient transport is observable in the edge currents of 2-dimensional (2D) topological band insulators with broken time-reversal symmetry. Topological pumps are able to reduce this higher-dimensional topological insulator phenomena to lower dimensionality by utilizing a pumping parameter (either space or time) as an artificial dimension. Here we demonstrate a temporal topological pump that produces on-demand, robust transport of mechanical energy using a 1D magneto-mechanical metamaterial. We experimentally demonstrate that the system is uniquely resilient to defects occurring in both space and time. Our findings open a path towards exploration of higher-dimensional topological physics with time as a synthetic dimension.
Energy consumption and cooperation for optimal sensing
Authors: Ngampruetikorn Vudtiwat , Schwab David J. , Stephens Greg J. 
Published: February 2020

AbstractThe reliable detection of environmental molecules in the presence of noise is an important cellular function, yet the underlying computational mechanisms are not well understood. We introduce a model of two interacting sensors which allows for the principled exploration of signal statistics, cooperation strategies and the role of energy consumption in optimal sensing, quantified through the mutual information between the signal and the sensors. Here we report that in general the optimal sensing strategy depends both on the noise level and the statistics of the signals. For joint, correlated signals, energy consuming (nonequilibrium), asymmetric couplings result in maximum information gain in the low-noise, high-signal-correlation limit. Surprisingly we also find that energy consumption is not always required for optimal sensing. We generalise our model to incorporate time integration of the sensor state by a population of readout molecules, and demonstrate that sensor interaction and energy consumption remain important for optimal sensing.
Physically-interpretable classification of biological network dynamics for complex collective motions
Authors: Fujii Keisuke , Takeishi Naoya , Hojo Motokazu , Inaba Yuki , Kawahara Yoshinobu 
Published: February 2020

AbstractUnderstanding biological network dynamics is a fundamental issue in various scientific and engineering fields. Network theory is capable of revealing the relationship between elements and their propagation; however, for complex collective motions, the network properties often transiently and complexly change. A fundamental question addressed here pertains to the classification of collective motion network based on physically-interpretable dynamical properties. Here we apply a data-driven spectral analysis called graph dynamic mode decomposition, which obtains the dynamical properties for collective motion classification. Using a ballgame as an example, we classified the strategic collective motions in different global behaviours and discovered that, in addition to the physical properties, the contextual node information was critical for classification. Furthermore, we discovered the label-specific stronger spectra in the relationship among the nearest agents, providing physical and semantic interpretations. Our approach contributes to the understanding of principles of biological complex network dynamics from the perspective of nonlinear dynamical systems.
GHz Ultrasonic Chip-Scale Device Induces Ion Channel Stimulation in Human Neural Cells
Authors: Balasubramanian Priya S. , Singh Ankur , Xu Chris , Lal Amit 
Published: February 2020

AbstractEmergent trends in the device development for neural prosthetics have focused on establishing stimulus localization, improving longevity through immune compatibility, reducing energy re-quirements, and embedding active control in the devices. Ultrasound stimulation can single-handedly address several of these challenges. Ultrasonic stimulus of neurons has been studied extensively from 100 kHz to 10 MHz, with high penetration but less localization. In this paper, a chip-scale device consisting of piezoelectric Aluminum Nitride ultrasonic transducers was engineered to deliver gigahertz (GHz) ultrasonic stimulus to the human neural cells. These devices provide a path towards complementary metal oxide semiconductor (CMOS) integration towards fully controllable neural devices. At GHz frequencies, ultrasonic wavelengths in water are a few microns and have an absorption depth of 10–20 µm. This confinement of energy can be used to control stimulation volume within a single neuron. This paper is the first proof-of-concept study to demonstrate that GHz ultrasound can stimulate neurons in vitro. By utilizing optical calcium imaging, which records calcium ion flux indicating occurrence of an action potential, this paper demonstrates that an application of a nontoxic dosage of GHz ultrasonic waves $$(\ge 0.05\frac{W}{c{m}^{2}})$$
(

≥
0.05

W

c

m

2

)
caused an average normalized fluorescence intensity recordings >1.40 for the calcium transients. Electrical effects due to chip-scale ultrasound delivery was discounted as the sole mechanism in stimulation, with effects tested at α = 0.01 statistical significance amongst all intensities and con-trol groups. Ionic transients recorded optically were confirmed to be mediated by ion channels and experimental data suggests an insignificant thermal contributions to stimulation, with a predicted increase of 0.03 oC for $$1.2\frac{W}{c{m}^{2}}\cdot $$
1.2

W

c

m

2

⋅
This paper paves the experimental framework to further explore chip-scale axon and neuron specific neural stimulation, with future applications in neural prosthetics, chip scale neural engineering, and extensions to different tissue and cell types.
The impacts of Extra-tropical ENSO Precursors on Tropical Pacific Decadal-scale Variability
Authors: Zhao Yingying , Di Lorenzo Emanuele 
Published: February 2020

AbstractOff-equatorial wind anomalies on seasonal timescales from both the North and South Pacific, known as “precursors” of the El Niño Southern Oscillation (ENSO), have been shown to independently trigger the ENSO feedbacks in the tropics and its teleconnections to the extra-tropics. However, the impacts of ENSO precursors on Tropical Pacific Decadal-scale Variability (TPDV) is still not well understood and quantified. We show that the dynamic sequence from extra-tropical ENSO precursors to ENSO (tropics) to extra-tropical ENSO teleconnections is not only important for ENSO, but acts as a primary mechanism to filter (e.g. reddening) the low-frequency variability of the seasonal precursors into the decadal-scale variance of the Pacific basin, accounting for the largest fraction of the TPDV (~65%) and its phase. This process, which contrasts previous theories advocating for a TPDV generated internally in the tropics (e.g. ENSO residuals), is inherently unpredictable and not well reproduced in climate models and raises challenges for understanding and predicting the role of internal TPDV in future climate change scenarios.