bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiocarbon Analyses Quantify Peat Carbon Losses With Increasing Temperature in a Whole Ecosystem Warming Experiment
Authors: Wilson Rachel M. , Griffiths Natalie A. , Visser Ate , McFarlane Karis J. , Sebestyen Stephen D. , Oleheiser Keith C. , Bosman Samantha , Hopple Anya M. , Tfaily Malak M. , Kolka Randall K. , Hanson Paul J. , Kostka Joel E. , Bridgham Scott D. , Keller Jason K. , Chanton Jeffrey P. 
Published: October 2021

AbstractClimate warming is expected to accelerate peatland degradation and release rates of carbon dioxide (CO2) and methane (CH4). Spruce and Peatlands Responses Under Changing Environments is an ecosystem‐scale climate manipulation experiment, designed to examine peatland ecosystem response to climate forcings. We examined whether heating up to +9 °C to 3 m‐deep in a peat bog over a 7‐year period led to higher C turnover and CO2 and CH4 emissions, by measuring 14C of solid peat, dissolved organic carbon (DOC), CH4, and dissolved CO2 (DIC). DOC, a major substrate for heterotrophic respiration, increased significantly with warming. There was no 7‐year trend in the DI14 C of the ambient plots which remained similar to their DO14 C. At +6.75 °C and +9 °C, the 14C of DIC, a product of microbial respiration, initially resembled ambient plots but became more depleted over 7 years of warming. We attributed the shifts in DI14 C to the increasing importance of solid phase peat as a substrate for microbial respiration and quantified this shift via the radiocarbon mass balance. The mass‐balance model revealed increases in peat‐supported respiration of the catotelm depths in heated plots over time and relative to ambient enclosures, from a baseline of 20%–25% in ambient enclosures, to 35%–40% in the heated plots. We find that warming stimulates microorganisms to respire ancient peat C, deposited under prior climate (cooler) conditions. This apparent destabilization of the large peat C reservoir has implications for peatland‐climate feedbacks especially if the balance of the peatland is tipped from net C sink to C source.
Inhibition of keratinocyte ferroptosis suppresses psoriatic inflammation
Authors: Shou Yanhong , Yang Lu , Yang Yongsheng , Xu Jinhua 
Published: October 2021

AbstractPsoriasis is a common, chronic, and recurrent inflammatory disease. It is characterized by hyperproliferation and abnormal differentiation of keratinocytes. Keratinocyte death is also involved in many pathophysiological conditions and amplifies the inflammatory cascade. As a newly recognized form of cell death, ferroptosis is involved in several inflammatory diseases. In this study, we aimed to investigate a previously unrecognized role for ferroptosis in psoriasis. Ferroptosis is mediated by lipid peroxidation and iron overload. Compared with normal lesions, the mRNA expression of acyl-CoA synthetase long-chain family member 4 (ACSL4), prostaglandin-endoperoxide synthase 2 (PTGS2), and transferrin receptor (TFRC) were highly expressed in psoriatic lesions, with decreased levels of glutathione peroxidase 4 (GPX4), ferritin light chain (FTL), and ferritin heavy chain 1 (FTH1). The protein levels of ACSL4 and GPX4 were consistent with their mRNA levels. A similar tendency of ferroptosis was also observed in erastin-treated human primary keratinocytes and the Imiquimod (IMQ)-induced model of psoriasis. To investigate the correlation between inflammation and peroxidation, we analyzed single-cell RNA-sequencing data and identified 15 cell types. There was a high correlation between the activity of the lipid oxidation and the Th22/Th17 response in keratinocytes at a single-cell level. Moreover, ferrostatin-1 (Fer-1), a potent inhibitor of lipid peroxidation, suppressed ferroptosis-related changes in erastin-treated keratinocytes and alleviated psoriasiform dermatitis of IMQ-induced models. Additionally, Fer-1 blocked inflammatory responses in vitro and in vivo, reducing the production of cytokines including TNF-α, IL-6, IL-1α, IL-1β, IL-17, IL-22, and IL-23. This study revealed an expression pattern of ferroptosis in which specific molecules enhance inflammatory reactions in psoriasis.
Microcavity phonon polaritons from the weak to the ultrastrong phonon–photon coupling regime
Authors: Barra-Burillo María , Muniain Unai , Catalano Sara , Autore Marta , Casanova Fèlix , Hueso Luis E. , Aizpurua Javier , Esteban Ruben , Hillenbrand Rainer 
Published: October 2021

AbstractStrong coupling between molecular vibrations and microcavity modes has been demonstrated to modify physical and chemical properties of the molecular material. Here, we study the less explored coupling between lattice vibrations (phonons) and microcavity modes. Embedding thin layers of hexagonal boron nitride (hBN) into classical microcavities, we demonstrate the evolution from weak to ultrastrong phonon-photon coupling when the hBN thickness is increased from a few nanometers to a fully filled cavity. Remarkably, strong coupling is achieved for hBN layers as thin as 10 nm. Further, the ultrastrong coupling in fully filled cavities yields a polariton dispersion matching that of phonon polaritons in bulk hBN, highlighting that the maximum light-matter coupling in microcavities is limited to the coupling strength between photons and the bulk material. Tunable cavity phonon polaritons could become a versatile platform for studying how the coupling strength between photons and phonons may modify the properties of polar crystals.
A non-canonical, interferon-independent signaling activity of cGAMP triggers DNA damage response signaling
Authors: Banerjee Daipayan , Langberg Kurt , Abbas Salar , Odermatt Eric , Yerramothu Praveen , Volaric Martin , Reidenbach Matthew A. , Krentz Kathy J. , Rubinstein C. Dustin , Brautigan David L. , Abbas Tarek , Gelfand Bradley D. , Ambati Jayakrishna , Kerur Nagaraj 
Published: October 2021

AbstractCyclic guanosine monophosphate-adenosine monophosphate (cGAMP), produced by cyclic GMP-AMP synthase (cGAS), stimulates the production of type I interferons (IFN). Here we show that cGAMP activates DNA damage response (DDR) signaling independently of its canonical IFN pathways. Loss of cGAS dampens DDR signaling induced by genotoxic insults. Mechanistically, cGAS activates DDR in a STING-TBK1-dependent manner, wherein TBK1 stimulates the autophosphorylation of the DDR kinase ATM, with the consequent activation of the CHK2-p53-p21 signal transduction pathway and the induction of G1 cell cycle arrest. Despite its stimulatory activity on ATM, cGAMP suppresses homology-directed repair (HDR) through the inhibition of polyADP-ribosylation (PARylation), in which cGAMP reduces cellular levels of NAD+; meanwhile, restoring NAD+ levels abrogates cGAMP-mediated suppression of PARylation and HDR. Finally, we show that cGAMP also activates DDR signaling in invertebrate species lacking IFN (Crassostrea virginica and Nematostella vectensis), suggesting that the genome surveillance mechanism of cGAS predates metazoan interferon-based immunity.
Histone H4 lysine 16 acetylation controls central carbon metabolism and diet-induced obesity in mice
Authors: Pessoa Rodrigues Cecilia , Chatterjee Aindrila , Wiese Meike , Stehle Thomas , Szymanski Witold , Shvedunova Maria , Akhtar Asifa 
Published: October 2021

AbstractNoncommunicable diseases (NCDs) account for over 70% of deaths world-wide. Previous work has linked NCDs such as type 2 diabetes (T2D) to disruption of chromatin regulators. However, the exact molecular origins of these chronic conditions remain elusive. Here, we identify the H4 lysine 16 acetyltransferase MOF as a critical regulator of central carbon metabolism. High-throughput metabolomics unveil a systemic amino acid and carbohydrate imbalance in Mof deficient mice, manifesting in T2D predisposition. Oral glucose tolerance testing (OGTT) reveals defects in glucose assimilation and insulin secretion in these animals. Furthermore, Mof deficient mice are resistant to diet-induced fat gain due to defects in glucose uptake in adipose tissue. MOF-mediated H4K16ac deposition controls expression of the master regulator of glucose metabolism, Pparg and the entire downstream transcriptional network. Glucose uptake and lipid storage can be reconstituted in MOF-depleted adipocytes in vitro by ectopic Glut4 expression, PPARγ agonist thiazolidinedione (TZD) treatment or SIRT1 inhibition. Hence, chronic imbalance in H4K16ac promotes a destabilisation of metabolism triggering the development of a metabolic disorder, and its maintenance provides an unprecedented regulatory epigenetic mechanism controlling diet-induced obesity.
Microtubule-based transport is essential to distribute RNA and nascent protein in skeletal muscle
Authors: Denes Lance T. , Kelley Chase P. , Wang Eric T. 
Published: October 2021

AbstractWhile the importance of RNA localization in highly differentiated cells is well appreciated, basic principles of RNA localization in skeletal muscle remain poorly characterized. Here, we develop a method to detect and quantify single molecule RNA localization patterns in skeletal myofibers, and uncover a critical role for directed transport of RNPs in muscle. We find that RNAs localize and are translated along sarcomere Z-disks, dispersing tens of microns from progenitor nuclei, regardless of encoded protein function. We find that directed transport along the lattice-like microtubule network of myofibers becomes essential to achieve this localization pattern as muscle development progresses; disruption of this network leads to extreme accumulation of RNPs and nascent protein around myonuclei. Our observations suggest that global active RNP transport may be required to distribute RNAs in highly differentiated cells and reveal fundamental mechanisms of gene regulation, with consequences for myopathies caused by perturbations to RNPs or microtubules.
Deep learning-based segmentation of lithium-ion battery microstructures enhanced by artificially generated electrodes
Authors: Müller Simon , Sauter Christina , Shunmugasundaram Ramesh , Wenzler Nils , De Andrade Vincent , De Carlo Francesco , Konukoglu Ender , Wood Vanessa 
Published: October 2021

AbstractAccurate 3D representations of lithium-ion battery electrodes, in which the active particles, binder and pore phases are distinguished and labeled, can assist in understanding and ultimately improving battery performance. Here, we demonstrate a methodology for using deep-learning tools to achieve reliable segmentations of volumetric images of electrodes on which standard segmentation approaches fail due to insufficient contrast. We implement the 3D U-Net architecture for segmentation, and, to overcome the limitations of training data obtained experimentally through imaging, we show how synthetic learning data, consisting of realistic artificial electrode structures and their tomographic reconstructions, can be generated and used to enhance network performance. We apply our method to segment x-ray tomographic microscopy images of graphite-silicon composite electrodes and show it is accurate across standard metrics. We then apply it to obtain a statistically meaningful analysis of the microstructural evolution of the carbon-black and binder domain during battery operation.
TMK-based cell-surface auxin signalling activates cell-wall acidification
Authors: Lin Wenwei , Zhou Xiang , Tang Wenxin , Takahashi Koji , Pan Xue , Dai Jiawei , Ren Hong , Zhu Xiaoyue , Pan Songqin , Zheng Haiyan , Gray William M. , Xu Tongda , Kinoshita Toshinori , Yang Zhenbiao 
Published: October 2021

AbstractThe phytohormone auxin controls many processes in plants, at least in part through its regulation of cell expansion1. The acid growth hypothesis has been proposed to explain auxin-stimulated cell expansion for five decades, but the mechanism that underlies auxin-induced cell-wall acidification is poorly characterized. Auxin induces the phosphorylation and activation of the plasma membrane H+-ATPase that pumps protons into the apoplast2, yet how auxin activates its phosphorylation remains unclear. Here we show that the transmembrane kinase (TMK) auxin-signalling proteins interact with plasma membrane H+-ATPases, inducing their phosphorylation, and thereby promoting cell-wall acidification and hypocotyl cell elongation in Arabidopsis. Auxin induced interactions between TMKs and H+-ATPases in the plasma membrane within seconds, as well as TMK-dependent phosphorylation of the penultimate threonine residue on the H+-ATPases. Our genetic, biochemical and molecular evidence demonstrates that TMKs directly phosphorylate plasma membrane H+-ATPase and are required for auxin-induced H+-ATPase activation, apoplastic acidification and cell expansion. Thus, our findings reveal a crucial connection between auxin and plasma membrane H+-ATPase activation in regulating apoplastic pH changes and cell expansion through TMK-based cell surface auxin signalling.
The structure of neurofibromin isoform 2 reveals different functional states
Authors: Naschberger Andreas , Baradaran Rozbeh , Rupp Bernhard , Carroni Marta 
Published: October 2021

AbstractThe autosomal dominant monogenetic disease neurofibromatosis type 1 (NF1) affects approximately one in 3,000 individuals and is caused by mutations in the NF1 tumour suppressor gene, leading to dysfunction in the protein neurofibromin (Nf1)1,2. As a GTPase-activating protein, a key function of Nf1 is repression of the Ras oncogene signalling cascade. We determined the human Nf1 dimer structure at an overall resolution of 3.3 Å. The cryo-electron microscopy structure reveals domain organization and structural details of the Nf1 exon 23a splicing3 isoform 2 in a closed, self-inhibited, Zn-stabilized state and an open state. In the closed conformation, HEAT/ARM core domains shield the GTPase-activating protein-related domain (GRD) so that Ras binding is sterically inhibited. In a distinctly different, open conformation of one protomer, a large-scale movement of the GRD occurs, which is necessary to access Ras, whereas Sec14-PH reorients to allow interaction with the cellular membrane4. Zn incubation of Nf1 leads to reduced Ras-GAP activity with both protomers in the self-inhibited, closed conformation stabilized by a Zn binding site between the N-HEAT/ARM domain and the GRD–Sec14-PH linker. The transition between closed, self-inhibited states of Nf1 and open states provides guidance for targeted studies deciphering the complex molecular mechanism behind the widespread neurofibromatosis syndrome and Nf1 dysfunction in carcinogenesis.
The orbitofrontal cortex maps future navigational goals
Authors: Basu Raunak , Gebauer Robert , Herfurth Tim , Kolb Simon , Golipour Zahra , Tchumatchenko Tatjana , Ito Hiroshi T. 
Published: October 2021

AbstractAccurate navigation to a desired goal requires consecutive estimates of spatial relationships between the current position and future destination throughout the journey. Although neurons in the hippocampal formation can represent the position of an animal as well as its nearby trajectories1–7, their role in determining the destination of the animal has been questioned8,9. It is, thus, unclear whether the brain can possess a precise estimate of target location during active environmental exploration. Here we describe neurons in the rat orbitofrontal cortex (OFC) that form spatial representations persistently pointing to the subsequent goal destination of an animal throughout navigation. This destination coding emerges before the onset of navigation, without direct sensory access to a distal goal, and even predicts the incorrect destination of an animal at the beginning of an error trial. Goal representations in the OFC are maintained by destination-specific neural ensemble dynamics, and their brief perturbation at the onset of a journey led to a navigational error. These findings suggest that the OFC is part of the internal goal map of the brain, enabling animals to navigate precisely to a chosen destination that is beyond the range of sensory perception.
The genomic origins of the Bronze Age Tarim Basin mummies
Authors: Zhang Fan , Ning Chao , Scott Ashley , Fu Qiaomei , Bjørn Rasmus , Li Wenying , Wei Dong , Wang Wenjun , Fan Linyuan , Abuduresule Idilisi , Hu Xingjun , Ruan Qiurong , Niyazi Alipujiang , Dong Guanghui , Cao Peng , Liu Feng , Dai Qingyan , Feng Xiaotian , Yang Ruowei , Tang Zihua , Ma Pengcheng , Li Chunxiang , Gao Shizhu , Xu Yang , Wu Sihao , Wen Shaoqing , Zhu Hong , Zhou Hui , Robbeets Martine , Kumar Vikas , Krause Johannes , Warinner Christina , Jeong Choongwon , Cui Yinqiu 
Published: October 2021

AbstractThe identity of the earliest inhabitants of Xinjiang, in the heart of Inner Asia, and the languages that they spoke have long been debated and remain contentious1. Here we present genomic data from 5 individuals dating to around 3000–2800 bc from the Dzungarian Basin and 13 individuals dating to around 2100–1700 bc﻿ from the Tarim Basin, representing the earliest yet discovered human remains from North and South Xinjiang, respectively. We find that the Early Bronze Age Dzungarian individuals exhibit a predominantly Afanasievo ancestry with an additional local contribution, and the Early–Middle Bronze Age Tarim individuals contain only a local ancestry. The Tarim individuals from the site of Xiaohe further exhibit strong evidence of milk proteins in their dental calculus, indicating a reliance on dairy pastoralism at the site since its founding. Our results do not support previous hypotheses for the origin of the Tarim mummies, who were argued to be Proto-Tocharian-speaking pastoralists descended from the Afanasievo1,2 or to have originated among the Bactria–Margiana Archaeological Complex3 or Inner Asian Mountain Corridor cultures4. Instead, although Tocharian may have been plausibly introduced to the Dzungarian Basin by Afanasievo migrants during the Early Bronze Age, we find that the earliest Tarim Basin cultures appear to have arisen from a genetically isolated local population that adopted neighbouring pastoralist and agriculturalist practices, which allowed them to settle and thrive along the shifting riverine oases of the Taklamakan Desert.
No causal effect of school closures in Japan on the spread of COVID-19 in spring 2020
Authors: Fukumoto Kentaro , McClean Charles T. , Nakagawa Kuninori 
Published: October 2021

AbstractAmong tool kits to combat the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, school closures are one of the most frequent non-pharmaceutical interventions. However, school closures bring about substantial costs, such as learning loss. To date, studies have not reached a consensus about the effectiveness of these policies at mitigating community transmission, partly because they lack rigorous causal inference. Here we assess the causal effect of school closures in Japan on reducing the spread of COVID-19 in spring 2020. By matching each municipality with open schools to a municipality with closed schools that is the most similar in terms of potential confounders, we can estimate how many cases the municipality with open schools would have had if it had closed its schools. We do not find any evidence that school closures in Japan reduced the spread of COVID-19. Our null results suggest that policies on school closures should be reexamined given the potential negative consequences for children and parents.
Negative inotropic mechanisms of β-cardiotoxin in cardiomyocytes by depression of myofilament ATPase activity without activation of the classical β-adrenergic pathway
Authors: Lertwanakarn Tuchakorn , Suntravat Montamas , Sánchez Elda E. , Wolska Beata M. , Solaro R. John , de Tombe Pieter P. , Tachampa Kittipong 
Published: October 2021

AbstractBeta-cardiotoxin (β-CTX) from the king cobra venom (Ophiophagus hannah) was previously proposed as a novel β-adrenergic blocker. However, the involvement of β-adrenergic signaling by this compound has never been elucidated. The objectives of this study were to investigate the underlying mechanisms of β-CTX as a β-blocker and its association with the β-adrenergic pathway. The effects of β-CTX on isolated cardiac myocyte functions, calcium homeostasis, the phosphorylation level of targeted proteins, and the myofibrillar ATPase activity were studied. Healthy Sprague Dawley rats were used for cardiomyocytes isolation. Like propranolol, β-CTX attenuated the cardiomyocyte inotropy and calcium transient alterations as induced by isoproterenol stimulation. In contrast, these effects were not observed in forskolin-treated cells. Interestingly, cardiomyocytes treated with β-CTX showed no changes in phosphorylation level at any PKA-targeted sites in the myofilaments as demonstrated in Western blot analysis. The skinned fibers study revealed no change in myofilament kinetics by β-CTX. However, this protein exhibited the direct inhibition of myofibrillar ATPase activity with calcium de-sensitization of the enzyme. In summary, the negative inotropic mechanism of β-CTX was discovered. β-CTX exhibits an atypical β-blocker mechanism. These properties of β-CTX may benefit in developing a novel agent aid to treat hypertrophic cardiomyopathy.
Robust multi-input multi-output adaptive fuzzy terminal sliding mode control of deep brain stimulation in Parkinson’s disease: a simulation study
Authors: Rouhani Ehsan , Fathi Yaser 
Published: October 2021

AbstractDeep brain stimulation (DBS) has become an effective therapeutic solution for Parkinson’s disease (PD). Adaptive closed-loop DBS can be used to minimize stimulation-induced side effects by automatically determining the stimulation parameters based on the PD dynamics. In this paper, by modeling the interaction between the neurons in populations of the thalamic, the network-level modulation of thalamic is represented in a standard canonical form as a multi-input multi-output (MIMO) nonlinear first-order system with uncertainty and external disturbances. A class of fast and robust MIMO adaptive fuzzy terminal sliding mode control (AFTSMC) has been presented for control of membrane potential of thalamic neuron populations through continuous adaptive DBS current applied to the thalamus. A fuzzy logic system (FLS) is used to estimate the unknown nonlinear dynamics of the model, and the weights of FLS are adjusted online to guarantee the convergence of FLS parameters to optimal values. The simulation results show that the proposed AFTSMC not only significantly produces lower tracking errors in comparison with the classical adaptive fuzzy sliding mode control (AFSMC), but also makes more robust and reliable outputs. The results suggest that the proposed AFTSMC provides a more robust and smooth control input which is highly desirable for hardware design and implementation.