bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real Time Control of Rainwater Harvesting Systems: The Benefits of Increasing Rainfall Forecast Window
Authors: Xu Wei D. , Fletcher Tim D. , Burns Matthew J. , Cherqui Frédéric 
Published: August 2020

AbstractUse of real time control (RTC) technology in rainwater harvesting systems can improve performance across water supply, flood protection, and environmental flow provision. Such systems make the most of rainfall forecast information, to release water prior to storm events and thus minimize uncontrolled overflows. To date, most advanced applications have adopted 24‐hr forecast information, leaving longer‐term forecasts largely untested. In this study, we aimed to predict the performance of four different RTC strategies, based on different forecast lead time and preferred objectives. RTC systems were predicted to yield comparatively less harvested rainwater than conventional passive systems but delivered superior performance in terms of flood mitigation and delivery of environmental water for streamflow restoration. More importantly, using a 7‐day rainfall forecast was shown to enhance the ability of RTC in mitigating flood risks and delivering an outflow regime that is close to the natural (reference) streamflow. Such a finding suggests that RTC combined with 7‐day forecast can enhance the functionality of rainwater harvesting systems to restore and even mimic the entire natural flow regimes in receiving streams. This also opens up a new opportunity for practitioners to implement smart technology in managing urban stormwater in a range of contexts and for a range of stream health objectives.
Using Remote Sensing Data‐Based Hydrological Model Calibrations for Predicting Runoff in Ungauged or Poorly Gauged Catchments
Authors: Huang Qi , Qin Guanghua , Zhang Yongqiang , Tang Qiuhong , Liu Changming , Xia Jun , Chiew Francis H. S. , Post David 
Published: August 2020

AbstractBecause remote sensing (RS) data are spatially and temporally explicit and available across the globe, they have the potential to be used for predicting runoff in ungauged catchments and poorly gauged regions, a challenging area of research in hydrology. There is potential to use remotely sensed data for calibrating hydrological models in regions with limited streamflow gauges. This study conducts a comprehensive investigation on how to incorporate gridded remotely sensed evapotranspiration (AET) and water storage data for constraining hydrological model calibration in order to predict daily and monthly runoff in 30 catchments in the Yalong River basin in China. To this end, seven RS data calibration schemes are explored and compared to direct calibration against observed runoff and traditional regionalization using spatial proximity to predict runoff in ungauged catchments. The results show that using bias‐corrected remotely sensed AET (bias‐corrected PML‐AET data) for constraining model calibration performs much better than using the raw remotely sensed AET data (nonbias‐corrected AET obtained from PML model estimate). Using the bias‐corrected PML‐AET data in a gridded way is much better than using lumped data and outperforms the traditional regionalization approach especially in headwater and large catchments. Combining the bias‐corrected PML‐AET and GRACE water storage data performs similarly to using the bias‐corrected PML‐AET data only. This study demonstrates that there is great potential in using bias‐corrected RS‐AET data to calibrating hydrological models (without the need for gauged streamflow data) to estimate daily and monthly runoff time series in ungauged catchments and sparsely gauged regions.
Presenilin 1 phosphorylation regulates amyloid-β degradation by microglia
Authors: Ledo Jose Henrique , Liebmann Thomas , Zhang Ran , Chang Jerry C. , Azevedo Estefania P. , Wong Eitan , Silva Hernandez Moura , Troyanskaya Olga G. , Bustos Victor , Greengard Paul 
Published: August 2020

AbstractAmyloid-β peptide (Aβ) accumulation in the brain is a hallmark of Alzheimer’s Disease. An important mechanism of Aβ clearance in the brain is uptake and degradation by microglia. Presenilin 1 (PS1) is the catalytic subunit of γ-secretase, an enzyme complex responsible for the maturation of multiple substrates, such as Aβ. Although PS1 has been extensively studied in neurons, the role of PS1 in microglia is incompletely understood. Here we report that microglia containing phospho-deficient mutant PS1 display a slower kinetic response to micro injury in the brain in vivo and the inability to degrade Aβ oligomers due to a phagolysosome dysfunction. An Alzheimer’s mouse model containing phospho-deficient PS1 show severe Aβ accumulation in microglia as well as the postsynaptic protein PSD95. Our results demonstrate a novel mechanism by which PS1 modulates microglial function and contributes to Alzheimer’s -associated phenotypes.
A novel N6-methyladenosine (m6A)-dependent fate decision for the lncRNA THOR
Authors: Liu Hongmei , Xu Yuxin , Yao Bing , Sui Tingting , Lai Liangxue , Li Zhanjun 
Published: August 2020

AbstractPrevious studies have revealed the critical roles of the N6-methyladenosine (m6A) modification of long non-coding RNAs (lncRNAs) in cancers, but the relationship between the oncogenic role of the lncRNATHOR(a representative of cancer/testis lncRNAs) and m6A modification remains unclear. Here, we show that the internal m6A modification of the lncRNATHORvia an m6A-reader-dependent modality regulates the proliferation of cancer cells. Our findings demonstrated that the loss of the lncRNATHORinhibits the proliferation, migration, and invasion of cancer cells in vitro and in vivo. In addition, m6A is highly enriched on lncRNATHORtranscripts, which contain GA (m6A) CA, GG (m6A) CU, and UG (m6A) CU sequence motifs. RIP-qRT-PCR and RNA pull-down assay results revealed that the specific m6A readers YTHDF1 and YTHDF2 can read the m6A motifs and regulate the stability of the lncRNATHOR(stabilization and decay). These m6A-dependent RNA-protein interactions can maintain the oncogenic role of the lncRNATHOR. Collectively, these findings highlight the critical role of the m6A modification in oncogenic lncRNATHORand reveal a novel long non-coding RNA regulatory mechanism, providing a new way to explore RNA epigenetic regulatory patterns in the future.
The circular RNA circ-GRB10 participates in the molecular circuitry inhibiting human intervertebral disc degeneration
Authors: Guo Wei , Mu Kun , Zhang Bin , Sun Chao , Zhao Ling , Li Hao-Ran , Dong Zhan-Yin , Cui Qing 
Published: August 2020

AbstractIntervertebral disc degeneration (IDD) is the most common degenerative disease all over the word. Our previous study confirmed that the downregulated circ-GRB10 directly interacts with miR-328-5p, which modulate ERBB2 and leads to the degeneration of intervertebral disc; however, the underpinning mechanism of circ-GRB10 dysregulation remains unclear. We identified that FUS and demonstrated that circ-GBR10 biosynthesis in nucleus pulposus (NP) cells was promoted by FUS, whose expression was controlled by miR-141-3p. In addition, ERBB2 downregulation led to decreased Erk1/2 phosphorylation which enhanced miR-141-3p production in NP cells. In vivo data indicated that circ-GRB10 inhibited IDD in rat model. The present study revealed that miR-141-3p and FUS are key factors that regulate circ-GRB10 synthesis in NP cells. In addition, circ-GBR10 participates in the molecular circuitry that controls human IDD development. These findings provide a basis for further functional, diagnostic and therapeutic studies of circ-GRB10 in IDD.
Turn-on chemiluminescence probes and dual-amplification of signal for detection of amyloid beta species in vivo
Authors: Yang Jing , Yin Wei , Van Richard , Yin Keyi , Wang Peng , Zheng Chao , Zhu Biyue , Ran Kathleen , Zhang Can , Kumar Mohanraja , Shao Yihan , Ran Chongzhao 
Published: August 2020

AbstractTurn-on fluorescence imaging is routinely studied; however, turn-on chemiluminescence has been rarely explored for in vivo imaging. Herein, we report the design and validation of chemiluminescence probe ADLumin-1 as a turn-on probe for amyloid beta (Aβ) species. Two-photon imaging indicates that ADLumin-1 can efficiently cross the blood–brain barrier and provides excellent contrast for Aβ plaques and cerebral amyloid angiopathy. In vivo brain imaging shows that the chemiluminescence signal of ADLumin-1 from 5-month-old transgenic 5xFAD mice is 1.80-fold higher than that from the age-matched wild-type mice. Moreover, we demonstrate that it is feasible to further dually-amplify signal via chemiluminescence resonance energy transfer (DAS-CRET) using two non-conjugated smart probes (ADLumin-1 and CRANAD-3) in solutions, brain homogenates, and in vivo whole brain imaging. Our results show that DAS-CRET can provide a 2.25-fold margin between 5-month-old 5xFAD mice and wild type mice. We believe that our strategy could be extended to other aggregating-prone proteins.
Deep neural networks enable quantitative movement analysis using single-camera videos
Authors: Kidziński Łukasz , Yang Bryan , Hicks Jennifer L. , Rajagopal Apoorva , Delp Scott L. , Schwartz Michael H. 
Published: August 2020

AbstractMany neurological and musculoskeletal diseases impair movement, which limits people’s function and social participation. Quantitative assessment of motion is critical to medical decision-making but is currently possible only with expensive motion capture systems and highly trained personnel. Here, we present a method for predicting clinically relevant motion parameters from an ordinary video of a patient. Our machine learning models predict parameters include walking speed (r = 0.73), cadence (r = 0.79), knee flexion angle at maximum extension (r = 0.83), and Gait Deviation Index (GDI), a comprehensive metric of gait impairment (r = 0.75). These correlation values approach the theoretical limits for accuracy imposed by natural variability in these metrics within our patient population. Our methods for quantifying gait pathology with commodity cameras increase access to quantitative motion analysis in clinics and at home and enable researchers to conduct large-scale studies of neurological and musculoskeletal disorders.
Pancreatic cancers suppress negative feedback of glucose transport to reprogram chromatin for metastasis
Authors: Bechard Matthew E. , Smalling Rana , Hayashi Akimasa , Zhong Yi , Word Anna E. , Campbell Sydney L. , Tran Amanda V. , Weiss Vivian L. , Iacobuzio-Donahue Christine , Wellen Kathryn E. , McDonald Oliver G. 
Published: August 2020

AbstractAlthough metastasis is the most common cause of cancer deaths, metastasis-intrinsic dependencies remain largely uncharacterized. We previously reported that metastatic pancreatic cancers were dependent on the glucose-metabolizing enzyme phosphogluconate dehydrogenase (PGD). Surprisingly, PGD catalysis was constitutively elevated without activating mutations, suggesting a non-genetic basis for enhanced activity. Here we report a metabolic adaptation that stably activates PGD to reprogram metastatic chromatin. High PGD catalysis prevents transcriptional up-regulation of thioredoxin-interacting protein (TXNIP), a gene that negatively regulates glucose import. This allows glucose consumption rates to rise in support of PGD, while simultaneously facilitating epigenetic reprogramming through a glucose-fueled histone hyperacetylation pathway. Restoring TXNIP normalizes glucose consumption, lowers PGD catalysis, reverses hyperacetylation, represses malignant transcripts, and impairs metastatic tumorigenesis. We propose that PGD-driven suppression of TXNIP allows pancreatic cancers to avidly consume glucose. This renders PGD constitutively activated and enables metaboloepigenetic selection of additional traits that increase fitness along glucose-replete metastatic routes.
ABHD11 maintains 2-oxoglutarate metabolism by preserving functional lipoylation of the 2-oxoglutarate dehydrogenase complex
Authors: Bailey Peter S. J. , Ortmann Brian M. , Martinelli Anthony W. , Houghton Jack W. , Costa Ana S. H. , Burr Stephen P. , Antrobus Robin , Frezza Christian , Nathan James A. 
Published: August 2020

Abstract2-oxoglutarate (2-OG or α-ketoglutarate) relates mitochondrial metabolism to cell function by modulating the activity of 2-OG dependent dioxygenases involved in the hypoxia response and DNA/histone modifications. However, metabolic pathways that regulate these oxygen and 2-OG sensitive enzymes remain poorly understood. Here, using CRISPR Cas9 genome-wide mutagenesis to screen for genetic determinants of 2-OG levels, we uncover a redox sensitive mitochondrial lipoylation pathway, dependent on the mitochondrial hydrolase ABHD11, that signals changes in mitochondrial 2-OG metabolism to 2-OG dependent dioxygenase function. ABHD11 loss or inhibition drives a rapid increase in 2-OG levels by impairing lipoylation of the 2-OG dehydrogenase complex (OGDHc)—the rate limiting step for mitochondrial 2-OG metabolism. Rather than facilitating lipoate conjugation, ABHD11 associates with the OGDHc and maintains catalytic activity of lipoyl domain by preventing the formation of lipoyl adducts, highlighting ABHD11 as a regulator of functional lipoylation and 2-OG metabolism.
Gsta4 controls apoptosis of differentiating adult oligodendrocytes during homeostasis and remyelination via the mitochondria-associated Fas-Casp8-Bid-axis
Authors: Carlström Karl E. , Zhu Keying , Ewing Ewoud , Krabbendam Inge E. , Harris Robert A. , Falcão Ana Mendanha , Jagodic Maja , Castelo-Branco Gonçalo , Piehl Fredrik 
Published: August 2020

AbstractArrest of oligodendrocyte (OL) differentiation and remyelination following myelin damage in multiple sclerosis (MS) is associated with neurodegeneration and clinical worsening. We show that Glutathione S-transferase 4α (Gsta4) is highly expressed during adult OL differentiation and that Gsta4 loss impairs differentiation into myelinating OLs in vitro. In addition, we identify Gsta4 as a target of both dimethyl fumarate, an existing MS therapy, and clemastine fumarate, a candidate remyelinating agent in MS. Overexpression of Gsta4 reduces expression of Fas and activity of the mitochondria-associated Casp8-Bid-axis in adult oligodendrocyte precursor cells, leading to improved OL survival during differentiation. The Gsta4 effect on apoptosis during adult OL differentiation was corroborated in vivo in both lysolecithin-induced demyelination and experimental autoimmune encephalomyelitis models, where Casp8 activity was reduced in Gsta4-overexpressing OLs. Our results identify Gsta4 as an intrinsic regulator of OL differentiation, survival and remyelination, as well as a potential target for future reparative MS therapies.
The impact of transposable elements on tomato diversity
Authors: Domínguez Marisol , Dugas Elise , Benchouaia Médine , Leduque Basile , Jiménez-Gómez José M , Colot Vincent , Quadrana Leandro 
Published: August 2020

AbstractTomatoes come in a multitude of shapes and flavors despite a narrow genetic pool. Here, we leverage whole-genome resequencing data available for 602 cultivated and wild accessions to determine the contribution of transposable elements (TEs) to tomato diversity. We identify 6,906 TE insertions polymorphisms (TIPs), which result from the mobilization of 337 distinct TE families. Most TIPs are low frequency variants and TIPs are disproportionately located within or adjacent to genes involved in environmental responses. In addition, genic TE insertions tend to have strong transcriptional effects and they can notably lead to the generation of multiple transcript isoforms. Using genome-wide association studies (GWAS), we identify at least 40 TIPs robustly associated with extreme variation in major agronomic traits or secondary metabolites and in most cases, no SNP tags the TE insertion allele. Collectively, these findings highlight the unique role of TE mobilization in tomato diversification, with important implications for breeding.
Cellular and molecular properties of neural progenitors in the developing mammalian hypothalamus
Authors: Zhou Xin , Zhong Suijuan , Peng Honghai , Liu Jing , Ding Wenyu , Sun Le , Ma Qiang , Liu Zeyuan , Chen Ruiguo , Wu Qian , Wang Xiaoqun 
Published: August 2020

AbstractThe neuroendocrine hypothalamus is the central regulator of vital physiological homeostasis and behavior. However, the cellular and molecular properties of hypothalamic neural progenitors remain unexplored. Here, hypothalamic radial glial (hRG) and hypothalamic mantle zone radial glial (hmRG) cells are found to be neural progenitors in the developing mammalian hypothalamus. The hmRG cells originate from hRG cells and produce neurons. During the early development of hypothalamus, neurogenesis occurs in radial columns and is initiated from hRG cells. The radial glial fibers are oriented toward the locations of hypothalamic subregions which act as a scaffold for neuronal migration. Furthermore, we use single-cell RNA sequencing to reveal progenitor subtypes in human developing hypothalamus and characterize specific progenitor genes, such as TTYH1, HMGA2, and FAM107A. We also demonstrate that HMGA2 is involved in E2F1 pathway, regulating the proliferation of progenitor cells by targeting on the downstream MYBL2. Different neuronal subtypes start to differentiate and express specific genes of hypothalamic nucleus at gestational week 10. Finally, we reveal the developmental conservation of nuclear structures and marker genes in mouse and human hypothalamus. Our identification of cellular and molecular properties of neural progenitors provides a basic understanding of neurogenesis and regional formation of the non-laminated hypothalamus.
Lattice oxygen activation enabled by high-valence metal sites for enhanced water oxidation
Authors: Zhang Ning , Feng Xiaobin , Rao Dewei , Deng Xi , Cai Lejuan , Qiu Bocheng , Long Ran , Xiong Yujie , Lu Yang , Chai Yang 
Published: August 2020

AbstractAnodic oxygen evolution reaction (OER) is recognized as kinetic bottleneck in water electrolysis. Transition metal sites with high valence states can accelerate the reaction kinetics to offer highly intrinsic activity, but suffer from thermodynamic formation barrier. Here, we show subtle engineering of highly oxidized Ni4+ species in surface reconstructed (oxy)hydroxides on multicomponent FeCoCrNi alloy film through interatomically electronic interplay. Our spectroscopic investigations with theoretical studies uncover that Fe component enables the formation of Ni4+ species, which is energetically favored by the multistep evolution of Ni2+→Ni3+→Ni4+. The dynamically constructed Ni4+ species drives holes into oxygen ligands to facilitate intramolecular oxygen coupling, triggering lattice oxygen activation to form Fe-Ni dual-sites as ultimate catalytic center with highly intrinsic activity. As a result, the surface reconstructed FeCoCrNi OER catalyst delivers outstanding mass activity and turnover frequency of 3601 A gmetal−1 and 0.483 s−1 at an overpotential of 300 mV in alkaline electrolyte, respectively.
Prognostic significance of residual nodal disease after neoadjuvant endocrine therapy for hormone receptor-positive breast cancer
Authors: Kantor Olga , Wong Stephanie , Weiss Anna , Metzger Otto , Mittendorf Elizabeth A. , King Tari A. 
Published: August 2020

AbstractAxillary management after NET has not been well studied and the significance of residual axillary node disease after NET remains uncertain. We used the National Cancer Data Base to examine the prognostic significance of residual nodal disease after NET. From 2010–2016, 4,496 patients received NET for cT1–3N0–1M0 hormone receptor-positive, HER2-negative breast cancer. Among cN0 patients treated with NET, final node status was ypN0 in 65%, isolated tumor cells (ITCs) in 3%, ypN1mi in 6%, and ypN1 in 26%. In cN1 patients, nodal pathologic complete response was uncommon (10%), and residual nodal disease included ITCs in 1%, ypN1mi in 3%, and ypN1 in 86%. There were no differences in 5-year overall survival (OS) between patients with pathologic node-negative disease, ITCs, or micrometastases after NET. When compared to a matched cohort of upfront surgery patients, there were also no differences in 5-year OS between NET and upfront surgery patients for any residual nodal disease category. These findings suggest NET patient outcomes mirror those of upfront surgery patients and present an opportunity to consider de-escalation of axillary management strategies in NET patients.
Correlated states in magic angle twisted bilayer graphene under the optical conductivity scrutiny
Authors: Calderón María J. , Bascones Elena 
Published: August 2020

AbstractMoiré systems displaying flat bands have emerged as novel platforms to study correlated electron phenomena. Insulating and superconducting states appear upon doping magic angle twisted bilayer graphene (TBG), and there is evidence of correlation induced effects at the charge neutrality point (CNP) which could originate from spontaneous symmetry breaking. Our theoretical calculations show how optical conductivity measurements can distinguish different symmetry breaking states, and reveal the nature of the correlated states. In the specific case of nematic order, which breaks the discrete rotational symmetry of the lattice, we find that the Dirac cones are displaced, not only in momentum space but also in energy, inducing finite Drude weight at the CNP. We also show that the sign of the Drude weight anisotropy induced by a nematic order depends on the degree of lattice relaxation, the doping and the nature of the symmetry breaking.
A candidate vaccine for human visceral leishmaniasis based on a specific T cell epitope-containing chimeric protein protects mice against Leishmania infantum infection
Authors: Lage Daniela P. , Ribeiro Patrícia A. F. , Dias Daniel S. , Mendonça Débora V. C. , Ramos Fernanda F. , Carvalho Lívia M. , de Oliveira Daysiane , Steiner Bethina T. , Martins Vívian T. , Perin Luísa , Machado Amanda S. , Santos Thaís T. O. , Tavares Grasiele S. V. , Oliveira-da-Silva João A. , Oliveira Jamil S. , Roatt Bruno M. , Machado-de-Ávila Ricardo A. , Teixeira Antônio L. , Humbert Maria V. , Coelho Eduardo A. F. , Christodoulides Myron 
Published: August 2020

AbstractLeishmaniases are neglected diseases caused by infection with Leishmania parasites and there are currently no prophylactic vaccines. In this study, we designed in silico a synthetic recombinant vaccine against visceral leishmaniasis (VL) called ChimeraT, which contains specific T-cell epitopes from Leishmania Prohibitin, Eukaryotic Initiation Factor 5a and the hypothetical LiHyp1 and LiHyp2 proteins. Subcutaneous delivery of ChimeraT plus saponin stimulated a Th1 cell-mediated immune response and protected mice against L. infantum infection, significantly reducing the parasite load in distinct organs. ChimeraT/saponin vaccine stimulated significantly higher levels of IFN-γ, IL-12, and GM-CSF cytokines by both murine CD4+ and CD8+ T cells, with correspondingly low levels of IL-4 and IL-10. Induced antibodies were predominantly IgG2a isotype and homologous antigen-stimulated spleen cells produced significant nitrite as a proxy for nitric oxide. ChimeraT also induced lymphoproliferative responses in peripheral blood mononuclear cells from VL patients after treatment and healthy subjects, as well as higher IFN-γ and lower IL-10 secretion into cell supernatants. Thus, ChimeraT associated with a Th1 adjuvant could be considered as a potential vaccine candidate to protect against human disease.