bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ab initio perspective of ultra-scaled CMOS from 2D-material fundamentals to dynamically doped transistors
Authors: Afzalian Aryan 
Published: January 2021

AbstractUsing accurate dissipative DFT-NEGF atomistic-simulation techniques within the Wannier-Function formalism, we give a fresh look at the possibility of sub-10-nm scaling for high-performance complementary metal oxide semiconductor (CMOS) applications. We show that a combination of good electrostatic control together with high mobility is paramount to meet the stringent roadmap targets. Such requirements typically play against each other at sub-10-nm gate length for MOS transistors made of conventional semiconductor materials like Si, Ge, or III–V and dimensional scaling is expected to end ~12 nm gate-length (pitch of 40 nm). We demonstrate that using alternative 2D channel materials, such as the less-explored HfS2or ZrS2, high-drive current down to ~6 nm is, however, achievable. We also propose a dynamically doped field-effect transistor concept, that scales better than its MOSFET counterpart. Used in combination with a high-mobility material such as HfS2, it allows for keeping the stringent high-performance CMOS on current and competitive energy-delay performance, when scaling down to virtually 0 nm gate length using a single-gate architecture and an ultra-compact design (pitch of 22 nm). The dynamically doped field-effect transistor further addresses the grand-challenge of doping in ultra-scaled devices and 2D materials in particular.
Human visual search follows a suboptimal Bayesian strategy revealed by a spatiotemporal computational model and experiment
Authors: Zhou Yunhui , Yu Yuguo 
Published: January 2021

AbstractThere is conflicting evidence regarding whether humans can make spatially optimal eye movements during visual search. Some studies have shown that humans can optimally integrate information across fixations and determine the next fixation location, however, these models have generally ignored the control of fixation duration and memory limitation, and the model results do not agree well with the details of human eye movement metrics. Here, we measured the temporal course of the human visibility map and performed a visual search experiment. We further built a continuous-time eye movement model that considers saccadic inaccuracy, saccadic bias, and memory constraints. We show that this model agrees better with the spatial and temporal properties of human eye movements and predict that humans have a memory capacity of around eight previous fixations. The model results reveal that humans employ a suboptimal eye movement strategy to find a target, which may minimize costs while still achieving sufficiently high search performance.
Outer-membrane-acting peptides and lipid II-targeting antibiotics cooperatively kill Gram-negative pathogens
Authors: Li Qian , Cebrián Rubén , Montalbán-López Manuel , Ren Huan , Wu Weihui , Kuipers Oscar P. 
Published: January 2021

AbstractThe development and dissemination of antibiotic-resistant bacterial pathogens is a growing global threat to public health. Novel compounds and/or therapeutic strategies are required to face the challenge posed, in particular, by Gram-negative bacteria. Here we assess the combined effect of potent cell-wall synthesis inhibitors with either natural or synthetic peptides that can act on the outer-membrane. Thus, several linear peptides, either alone or combined with vancomycin or nisin, were tested against selected Gram-negative pathogens, and the best one was improved by further engineering. Finally, peptide D-11 and vancomycin displayed a potent antimicrobial activity at low μM concentrations against a panel of relevant Gram-negative pathogens. This combination was highly active in biological fluids like blood, but was non-hemolytic and non-toxic against cell lines. We conclude that vancomycin and D-11 are safe at >50-fold their MICs. Based on the results obtained, and as a proof of concept for the newly observed synergy, a Pseudomonas aeruginosa mouse infection model experiment was also performed, showing a 4 log10 reduction of the pathogen after treatment with the combination. This approach offers a potent alternative strategy to fight (drug-resistant) Gram-negative pathogens in humans and mammals.
Multiple memories can be simultaneously reactivated during sleep as effectively as a single memory
Authors: Schechtman Eitan , Antony James W. , Lampe Anna , Wilson Brianna J. , Norman Kenneth A. , Paller Ken A. 
Published: January 2021

AbstractMemory consolidation involves the reactivation of memory traces during sleep. If different memories are reactivated each night, how much do they interfere with one another? We examined whether reactivating multiple memories incurs a cost to sleep-related benefits by contrasting reactivation of multiple memories versus single memories during sleep. First, participants learned the on-screen location of different objects. Each object was part of a semantically coherent group comprised of either one, two, or six items (e.g., six different cats). During sleep, sounds were unobtrusively presented to reactivate memories for half of the groups (e.g., “meow”). Memory benefits for cued versus non-cued items were independent of the number of items in the group, suggesting that reactivation occurs in a simultaneous and promiscuous manner. Intriguingly, sleep spindles and delta-theta power modulations were sensitive to group size, reflecting the extent of previous learning. Our results demonstrate that multiple memories may be consolidated in parallel without compromising each memory’s sleep-related benefit. These findings highlight alternative models for parallel consolidation that should be considered in future studies.
Obese mother offspring have hepatic lipidic modulation that contributes to sex-dependent metabolic adaptation later in life
Authors: Savva Christina , Helguero Luisa A. , González-Granillo Marcela , Couto Daniela , Melo Tânia , Li Xidan , Angelin Bo , Domingues Maria Rosário , Kutter Claudia , Korach-André Marion 
Published: January 2021

AbstractWith the increasing prevalence of obesity in women of reproductive age, there is an urgent need to understand the metabolic impact on the fetus. Sex-related susceptibility to liver diseases has been demonstrated but the underlying mechanism remains unclear. Here we report that maternal obesity impacts lipid metabolism differently in female and male offspring. Males, but not females, gained more weight and had impaired insulin sensitivity when born from obese mothers compared to control. Although lipid mass was similar in the livers of female and male offspring, sex-specific modifications in the composition of fatty acids, triglycerides and phospholipids was observed. These overall changes could be linked to sex-specific regulation of genes controlling metabolic pathways. Our findings revised the current assumption that sex-dependent susceptibility to metabolic disorders is caused by sex-specific postnatal regulation and instead we provide molecular evidence supporting in utero metabolic adaptations in the offspring of obese mothers.
Exploiting genetic diversity and gene synthesis to identify superior nitrogenase NifH protein variants to engineer N2-fixation in plants
Authors: Jiang Xi , Payá-Tormo Lucía , Coroian Diana , García-Rubio Inés , Castellanos-Rueda Rocío , Eseverri Álvaro , López-Torrejón Gema , Burén Stefan , Rubio Luis Manuel 
Published: January 2021

AbstractEngineering nitrogen fixation in eukaryotes requires high expression of functional nitrogenase structural proteins, a goal that has not yet been achieved. Here we build a knowledge-based library containing 32 nitrogenase nifH sequences from prokaryotes of diverse ecological niches and metabolic features and combine with rapid screening in tobacco to identify superior NifH variants for plant mitochondria expression. Three NifH variants outperform in tobacco mitochondria and are further tested in yeast. Hydrogenobacter thermophilus (Aquificae) NifH is isolated in large quantities from yeast mitochondria and fulfills NifH protein requirements for efficient N2 fixation, including electron transfer for substrate reduction, P-cluster maturation, and FeMo-co biosynthesis. H. thermophilus NifH expressed in tobacco leaves shows lower nitrogenase activity than that from yeast. However, transfer of [Fe4S4] clusters from NifU to NifH in vitro increases 10-fold the activity of the tobacco-isolated NifH, revealing that plant mitochondria [Fe-S] cluster availability constitutes a bottleneck to engineer plant nitrogenases.
Progerinin, an optimized progerin-lamin A binding inhibitor, ameliorates premature senescence phenotypes of Hutchinson-Gilford progeria syndrome
Authors: Kang So-mi , Yoon Min-Ho , Ahn Jinsook , Kim Ji-Eun , Kim So Young , Kang Seock Yong , Joo Jeongmin , Park Soyoung , Cho Jung-Hyun , Woo Tae-Gyun , Oh Ah-Young , Chung Kyu Jin , An So Yon , Hwang Tae Sung , Lee Soo Yong , Kim Jeong-Su , Ha Nam-Chul , Song Gyu-Yong , Park Bum-Joon 
Published: January 2021

AbstractPrevious work has revealed that progerin-lamin A binding inhibitor (JH4) can ameliorate pathological features of Hutchinson-Gilford progeria syndrome (HGPS) such as nuclear deformation, growth suppression in patient’s cells, and very short life span in an in vivo mouse model. Despite its favorable effects, JH4 is rapidly eliminated in in vivo pharmacokinetic (PK) analysis. Thus, we improved its property through chemical modification and obtained an optimized drug candidate, Progerinin (SLC-D011). This chemical can extend the life span of LmnaG609G/G609G mouse for about 10 weeks and increase its body weight. Progerinin can also extend the life span of LmnaG609G/+ mouse for about 14 weeks via oral administration, whereas treatment with lonafarnib (farnesyl-transferase inhibitor) can only extend the life span of LmnaG609G/+ mouse for about two weeks. In addition, progerinin can induce histological and physiological improvement in LmnaG609G/+ mouse. These results indicate that progerinin is a strong drug candidate for HGPS.
DeepSleep convolutional neural network allows accurate and fast detection of sleep arousal
Authors: Li Hongyang , Guan Yuanfang 
Published: January 2021

AbstractSleep arousals are transient periods of wakefulness punctuated into sleep. Excessive sleep arousals are associated with symptoms such as sympathetic activation, non-restorative sleep, and daytime sleepiness. Currently, sleep arousals are mainly annotated by human experts through looking at 30-second epochs (recorded pages) manually, which requires considerable time and effort. Here we present a deep learning approach for automatically segmenting sleep arousal regions based on polysomnographic recordings. Leveraging a specific architecture that ‘translates’ input polysomnographic signals to sleep arousal labels, this algorithm ranked first in the “You Snooze, You Win” PhysioNet Challenge. We created an augmentation strategy by randomly swapping similar physiological channels, which notably improved the prediction accuracy. Our algorithm enables fast and accurate delineation of sleep arousal events at the speed of 10 seconds per sleep recording. This computational tool would greatly empower the scoring process in clinical settings and accelerate studies on the impact of arousals.
Systemic viral spreading and defective host responses are associated with fatal Lassa fever in macaques
Authors: Baillet Nicolas , Reynard Stéphanie , Perthame Emeline , Hortion Jimmy , Journeaux Alexandra , Mateo Mathieu , Carnec Xavier , Schaeffer Justine , Picard Caroline , Barrot Laura , Barron Stéphane , Vallve Audrey , Duthey Aurélie , Jacquot Frédéric , Boehringer Cathy , Jouvion Grégory , Pietrosemoli Natalia , Legendre Rachel , Dillies Marie-Agnès , Allan Richard , Legras-Lachuer Catherine , Carbonnelle Caroline , Raoul Hervé , Baize Sylvain 
Published: January 2021

AbstractLassa virus (LASV) is endemic in West Africa and induces a viral hemorrhagic fever (VHF) with up to 30% lethality among clinical cases. The mechanisms involved in control of Lassa fever or, in contrast, the ensuing catastrophic illness and death are poorly understood. We used the cynomolgus monkey model to reproduce the human disease with asymptomatic to mild or fatal disease. After initial replication at the inoculation site, LASV reached the secondary lymphoid organs. LASV did not spread further in nonfatal disease and was rapidly controlled by balanced innate and T-cell responses. Systemic viral dissemination occurred during severe disease. Massive replication, a cytokine/chemokine storm, defective T-cell responses, and multiorgan failure were observed. Clinical, biological, immunological, and transcriptomic parameters resembled those observed during septic-shock syndrome, suggesting that similar pathogenesis is induced during Lassa fever. The outcome appears to be determined early, as differentially expressed genes in PBMCs were associated with fatal and non-fatal Lassa fever outcome very early after infection. These results provide a full characterization and important insights into Lassa fever pathogenesis and could help to develop early diagnostic tools.
Host relatedness and landscape connectivity shape pathogen spread in the puma, a large secretive carnivore
Authors: Fountain-Jones Nicholas M. , Kraberger Simona , Gagne Roderick B. , Trumbo Daryl R. , Salerno Patricia E. , Chris Funk W. , Crooks Kevin , Biek Roman , Alldredge Mathew , Logan Ken , Baele Guy , Dellicour Simon , Ernest Holly B. , VandeWoude Sue , Carver Scott , Craft Meggan E. 
Published: January 2021

AbstractUrban expansion can fundamentally alter wildlife movement and gene flow, but how urbanization alters pathogen spread is poorly understood. Here, we combine high resolution host and viral genomic data with landscape variables to examine the context of viral spread in puma (Puma concolor) from two contrasting regions: one bounded by the wildland urban interface (WUI) and one unbounded with minimal anthropogenic development (UB). We found landscape variables and host gene flow explained significant amounts of variation of feline immunodeficiency virus (FIV) spread in the WUI, but not in the unbounded region. The most important predictors of viral spread also differed; host spatial proximity, host relatedness, and mountain ranges played a role in FIV spread in the WUI, whereas roads might have facilitated viral spread in the unbounded region. Our research demonstrates how anthropogenic landscapes can alter pathogen spread, providing a more nuanced understanding of host-pathogen relationships to inform disease ecology in free-ranging species.
Nerve growth factor interacts with CHRM4 and promotes neuroendocrine differentiation of prostate cancer and castration resistance
Authors: Chen Wei-Yu , Wen Yu-Ching , Lin Shian-Ren , Yeh Hsiu-Lien , Jiang Kuo-Ching , Chen Wei-Hao , Lin Yow-Sien , Zhang Qingfu , Liew Phui-Ly , Hsiao Michael , Huang Jiaoti , Liu Yen-Nien 
Published: January 2021

AbstractNerve growth factor (NGF) contributes to the progression of malignancy. However, the functional role and regulatory mechanisms of NGF in the development of neuroendocrine prostate cancer (NEPC) are unclear. Here, we show that an androgen-deprivation therapy (ADT)-stimulated transcription factor, ZBTB46, upregulated NGF via ZBTB46 mediated-transcriptional activation of NGF. NGF regulates NEPC differentiation by physically interacting with a G-protein-coupled receptor, cholinergic receptor muscarinic 4 (CHRM4), after ADT. Pharmacologic NGF blockade and NGF knockdown markedly inhibited CHRM4-mediated NEPC differentiation and AKT-MYCN signaling activation. CHRM4 stimulation was associated with ADT resistance and was significantly correlated with increased NGF in high-grade and small-cell neuroendocrine prostate cancer (SCNC) patient samples. Our results reveal a role of the NGF in the development of NEPC that is linked to ZBTB46 upregulation and CHRM4 accumulation. Our study provides evidence that the NGF-CHRM4 axis has potential to be considered as a therapeutic target to impair NEPC progression.
Age-related injury responses of human oligodendrocytes to metabolic insults: link to BCL-2 and autophagy pathways
Authors: Fernandes Milton Guilherme Forestieri , Luo Julia Xiao Xuan , Cui Qiao-Ling , Perlman Kelly , Pernin Florian , Yaqubi Moein , Hall Jeffery A. , Dudley Roy , Srour Myriam , Couturier Charles P. , Petrecca Kevin , Larochelle Catherine , Healy Luke M. , Stratton Jo Anne , Kennedy Timothy E. , Antel Jack P. 
Published: January 2021

AbstractMyelin destruction and oligodendrocyte (OL) death consequent to metabolic stress is a feature of CNS disorders across the age spectrum. Using cells derived from surgically resected tissue, we demonstrate that young (<age 5) pediatric-aged sample OLs are more resistant to in-vitro metabolic injury than fetal O4+ progenitor cells, but more susceptible to cell death and apoptosis than adult-derived OLs. Pediatric but not adult OLs show measurable levels of TUNEL+ cells, a feature of the fetal cell response. The ratio of anti- vs pro-apoptotic BCL-2 family genes are increased in adult vs pediatric (<age 5) mature OLs and in more mature OL lineage cells. Lysosomal gene expression was increased in adult and pediatric compared to fetal OL lineage cells. Cell death of OLs was increased by inhibiting pro-apoptotic BCL-2 gene and autophagy activity. These distinct age-related injury responses should be considered in designing therapies aimed at reducing myelin injury.
Activation of mitochondrial TUFM ameliorates metabolic dysregulation through coordinating autophagy induction
Authors: Kim Dasol , Hwang Hui-Yun , Ji Eun Sun , Kim Jin Young , Yoo Jong Shin , Kwon Ho Jeong 
Published: January 2021

AbstractDisorders of autophagy, a key regulator of cellular homeostasis, cause a number of human diseases. Due to the role of autophagy in metabolic dysregulation, there is a need to identify autophagy regulators as therapeutic targets. To address this need, we conducted an autophagy phenotype-based screen and identified the natural compound kaempferide (Kaem) as an autophagy enhancer. Kaem promoted autophagy through translocation of transcription factor EB (TFEB) without MTOR perturbation, suggesting it is safe for administration. Moreover, Kaem accelerated lipid droplet degradation in a lysosomal activity-dependent manner in vitro and ameliorated metabolic dysregulation in a diet-induced obesity mouse model. To elucidate the mechanism underlying Kaem’s biological activity, the target protein was identified via combined drug affinity responsive target stability and LC–MS/MS analyses. Kaem directly interacted with the mitochondrial elongation factor TUFM, and TUFM absence reversed Kaem-induced autophagy and lipid degradation. Kaem also induced mitochondrial reactive oxygen species (mtROS) to sequentially promote lysosomal Ca2+ efflux, TFEB translocation and autophagy induction, suggesting a role of TUFM in mtROS regulation. Collectively, these results demonstrate that Kaem is a potential therapeutic candidate/chemical tool for treating metabolic dysregulation and reveal a role for TUFM in autophagy for metabolic regulation with lipid overload.
Dust arriving in the Amazon basin over the past 7,500 years came from diverse sources
Authors: Nogueira Juliana , Evangelista Heitor , Valeriano Claudio de Morisson , Sifeddine Abdelfettah , Neto Carla , Vaz Gilberto , Moreira Luciane S. , Cordeiro Renato C. , Turcq Bruno , Aniceto Keila Cristina , Neto Artur Bastos , Martins Gabriel , Barbosa Cybelli G. G. , Godoi Ricardo H. M. , Shimizu Marilia H. 
Published: January 2021

AbstractA large amount of dust from the Sahara reaches the Amazon Basin, as observed with satellite imagery. This dust is thought to carry micronutrients that could help fertilize the rainforest. However, considering different atmospheric transport conditions, different aridity levels in South America and Africa and active volcanism, it is not clear if the same pathways for dust have occurred throughout the Holocene. Here we present analyses of Sr-Nd isotopic ratios of a lacustrine sediment core from remote Lake Pata in the Amazon region that encompasses the past 7,500 years before present, and compare these ratios to dust signatures from a variety of sources. We find that dust reaching the western Amazon region during the study period had diverse origins, including the Andean region and northern and southern Africa. We suggest that the Sahara Desert was not the dominant source of dust throughout the vast Amazon basin over the past 7,500 years.
Advanced analysis of satellite data reveals ground deformation precursors to the Brumadinho Tailings Dam collapse
Authors: Grebby Stephen , Sowter Andrew , Gluyas Jon , Toll David , Gee David , Athab Ahmed , Girindran Renoy 
Published: January 2021

AbstractCatastrophic failure of a tailings dam at an iron ore mine complex in Brumadinho, Brazil, on 25th January 2019 released 11.7 million m3 of tailings downstream. Although reportedly monitored using an array of geotechnical techniques, the collapse occurred without any apparent warning. It claimed more than 200 lives and caused considerable environmental damage. Here we present the Intermittent Small Baseline Subset (ISBAS) technique on satellite-based interferometric synthetic aperture radar (InSAR) data to assess the course of events. We find that parts of the dam wall and tailings were experiencing deformation not consistent with consolidation settlement preceding the collapse. Furthermore, we show that the timing of the dam collapse would have been foreseeable based on this observed precursory deformation. We conclude that satellite-based monitoring techniques may help mitigate similar catastrophes in the future.
Dysregulation of endocannabinoid concentrations in human subcutaneous adipose tissue in obesity and modulation by omega-3 polyunsaturated fatty acids
Authors: Fisk Helena L. , Childs Caroline E. , Miles Elizabeth A. , Ayres Robert , Noakes Paul S. , Paras-Chavez Carolina , Kuda Ondrej , Kopecký Jan , Antoun Elie , Lillycrop Karen A. , Calder Philip C. 
Published: January 2021

Abstract
Obesity is believed to be associated with a dysregulated endocannabinoid system which may reflect enhanced inflammation. However, reports of this in human white adipose tissue (WAT) are limited and inconclusive. Marine long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) have anti-inflammatory actions and therefore may improve obesity-associated adipose tissue inflammation. Therefore, fatty acid (FA) concentrations, endocannabinoid concentrations, and gene expression were assessed in subcutaneous WAT (scWAT) biopsies from healthy normal weight individuals (BMI 18.5–25 kg/m2) and individuals living with metabolically healthy obesity (BMI 30–40 kg/m2) prior to and following a 12-week intervention with 3 g fish oil/day (1.1 g eicosapentaenoic acid (EPA) + 0.8 g DHA) or 3 g corn oil/day (placebo). WAT from individuals living with metabolically healthy obesity had higher n-6 PUFAs and EPA, higher concentrations of two endocannabinoids (anandamide (AEA) and eicosapentaenoyl ethanolamide (EPEA)), higher expression of phospholipase A2 Group IID (PLA2G2D) and phospholipase A2 Group IVA (PLA2G4A), and lower expression of CNR1. In response to fish oil intervention, WAT EPA increased to a similar extent in both BMI groups, and WAT DHA increased by a greater extent in normal weight individuals. WAT EPEA and docosahexaenoyl ethanolamide (DHEA) increased in normal weight individuals only and WAT 2-arachidonyl glycerol (2-AG) decreased in individuals living with metabolically healthy obesity only. Altered WAT fatty acid, endocannabinoid, and gene expression profiles in metabolically healthy obesity at baseline may be linked. WAT incorporates n-3 PUFAs when their intake is increased which affects the endocannabinoid system; however, effects appear greater in normal weight individuals than in those living with metabolically healthy obesity.