bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune-responsive gene 1/itaconate activates nuclear factor erythroid 2-related factor 2 in microglia to protect against spinal cord injury in mice
Authors: Ni Libin , Xiao Jian , Zhang Di , Shao Zhenxuan , Huang Chongan , Wang Sheng , Wu Yaosen , Tian Naifeng , Sun Liaojun , Wu Aimin , Zhou Yifei , Wang Xiangyang , Zhang Xiaolei
Published: February 2022

The pathophysiology of spinal cord injury (SCI) involves primary injury and secondary injury. Secondary injury is a major target for SCI therapy, whereas microglia play an important role in secondary injury. The immunoresponsive gene 1 (Irg-1) has been recorded as one of the most significantly upregulated genes in SCI tissues in gene chip data; however, its role in SCI remains unclear. This study aims to illustrate the role of Irg-1 as well as its regulated metabolite itaconate in SCI. It was demonstrated that the expression of Irg-1 was increased in spinal cord tissues in mice as well as in microglia stimulated by lipopolysaccharides (LPS). It was also shown that overexpression of Irg-1 may suppress LPS-induced inflammation in microglia, while these protective effects were attenuated by Nrf2 silencing. In vivo, overexpression of Irg-1 was shown to suppress neuroinflammation and improve motor function recovery. Furthermore, treatment of microglia with itaconate demonstrated similar inflammation suppressive effects as Irg-1 overexpression in vitro and improved motor function recovery in vivo. In conclusion, the current study shows that Irg-1 and itaconate are involved in the recovery process of SCI, either Irg-1 overexpression or itaconate treatment may provide a promising strategy for the treatment of SCI.
ADRB3 induces mobilization and inhibits differentiation of both breast cancer cells and myeloid-derived suppressor cells
Authors: Zhou Zhiling , Zhan Jiaxin , Luo Qiong , Hou Xinghua , Wang Shuxia , Xiao Dingzhang , Xie Zhi , Liang Haidan , Lin Shuguang , Zheng Meng
Published: February 2022

Metastatic tumors are mainly composed of neoplastic cells escaping from the primary tumor and inflammatory cells egressing from bone marrow. Cancer cell and inflammatory cell are remained in the state of immaturity during migration to distant organs. Here, we show that ADRB3 is crucial in cell mobilization and differentiation. Immunohistochemistry revealed ADRB3 expression is significantly more frequent in breast cancer tissues than in adjacent noncancerous tissues (92.1% vs. 31.5%). Expression of ADRB3 correlated with malignant degree, TNM stage and poor prognosis. Moreover, ADRB3 expression was markedly high in activated disseminated tumor cells, myeloid-derived suppressor cells (MDSCs), lymphocytes and neutrophil extracellular traps of patients. Importantly, ADRB3 promoted the expansion of MDSC through stimulation of bone marrow mobilization and inhibiting of the differentiation of immature myeloid cells. Furthermore, ADRB3 promoted MCF-7 cells proliferation and inhibited transdifferentiation into adipocyte-like cell by activating mTOR pathway. Ultimately, the MDSC-deficient phenotype of ADRB3 -/- PyMT mice was associated with impairment of mammary tumorigenesis and reduction in pulmonary metastasis. Collectively, ADRB3 promotes metastasis by inducing mobilization and inhibiting differentiation of both breast cancer cells and MDSCs.
Overlooked and widespread pennate diatom-diazotroph symbioses in the sea
Authors: Schvarcz Christopher R. , Wilson Samuel T. , Caffin Mathieu , Stancheva Rosalina , Li Qian , Turk-Kubo Kendra A. , White Angelicque E. , Karl David M. , Zehr Jonathan P. , Steward Grieg F.
Published: February 2022

Persistent nitrogen depletion in sunlit open ocean waters provides a favorable ecological niche for nitrogen-fixing (diazotrophic) cyanobacteria, some of which associate symbiotically with eukaryotic algae. All known marine examples of these symbioses have involved either centric diatom or haptophyte hosts. We report here the discovery and characterization of two distinct marine pennate diatom-diazotroph symbioses, which until now had only been observed in freshwater environments. Rhopalodiaceae diatomsEpithemia pelagicasp. nov. andEpithemia catenatasp. nov. were isolated repeatedly from the subtropical North Pacific Ocean, and analysis of sequence libraries reveals a global distribution. These symbioses likely escaped attention because the endosymbionts lack fluorescent photopigments, havenifHgene sequences similar to those of free-living unicellular cyanobacteria, and are lost in nitrogen-replete medium. Marine Rhopalodiaceae-diazotroph symbioses are a previously overlooked but widespread source of bioavailable nitrogen in marine habitats and provide new, easily cultured model organisms for the study of organelle evolution.
Structures of highly flexible intracellular domain of human α7 nicotinic acetylcholine receptor
Authors: Bondarenko Vasyl , Wells Marta M. , Chen Qiang , Tillman Tommy S. , Singewald Kevin , Lawless Matthew J. , Caporoso Joel , Brandon Nicole , Coleman Jonathan A. , Saxena Sunil , Lindahl Erik , Xu Yan , Tang Pei
Published: February 2022

The intracellular domain (ICD) of Cys-loop receptors mediates diverse functions. To date, no structure of a full-length ICD is available due to challenges stemming from its dynamic nature. Here, combining nuclear magnetic resonance (NMR) and electron spin resonance experiments with Rosetta computations, we determine full-length ICD structures of the human α7 nicotinic acetylcholine receptor in a resting state. We show that ~57% of the ICD residues are in highly flexible regions, primarily in a large loop (loop L) with the most mobile segment spanning ~50 Å from the central channel axis. Loop L is anchored onto the MA helix and virtually forms two smaller loops, thereby increasing its stability. Previously known motifs for cytoplasmic binding, regulation, and signaling are found in both the helices and disordered flexible regions, supporting the essential role of the ICD conformational plasticity in orchestrating a broad range of biological processes.
Cotranslational N-degron masking by acetylation promotes proteome stability in plants
Authors: Linster Eric , Forero Ruiz Francy L. , Miklankova Pavlina , Ruppert Thomas , Mueller Johannes , Armbruster Laura , Gong Xiaodi , Serino Giovanna , Mann Matthias , Hell Rüdiger , Wirtz Markus
Published: February 2022

N-terminal protein acetylation (NTA) is a prevalent protein modification essential for viability in animals and plants. The dominant executor of NTA is the ribosome tethered Nα-acetyltransferase A (NatA) complex. However, the impact of NatA on protein fate is still enigmatic. Here, we demonstrate that depletion of NatA activity leads to a 4-fold increase in global protein turnover via the ubiquitin-proteasome system in Arabidopsis. Surprisingly, a concomitant increase in translation, actioned via enhanced Target-of-Rapamycin activity, is also observed, implying that defective NTA triggers feedback mechanisms to maintain steady-state protein abundance. Quantitative analysis of the proteome, the translatome, and the ubiquitome reveals that NatA substrates account for the bulk of this enhanced turnover. A targeted analysis of NatA substrate stability uncovers that NTA absence triggers protein destabilization via a previously undescribed and widely conserved nonAc/N-degron in plants. Hence, the imprinting of the proteome with acetylation marks is essential for coordinating proteome stability.
Engineering and exploiting synthetic allostery of NanoLuc luciferase
Authors: Guo Zhong , Parakra Rinky D. , Xiong Ying , Johnston Wayne A. , Walden Patricia , Edwardraja Selvakumar , Moradi Shayli Varasteh , Ungerer Jacobus P. J. , Ai Hui-wang , Phillips Jonathan J. , Alexandrov Kirill
Published: February 2022

Allostery enables proteins to interconvert different biochemical signals and form complex metabolic and signaling networks. We hypothesize that circular permutation of proteins increases the probability of functional coupling of new N- and C- termini with the protein’s active center through increased local structural disorder. To test this we construct a synthetically allosteric version of circular permutated NanoLuc luciferase that can be activated through ligand-induced intramolecular non-covalent cyclisation. This switch module is tolerant of the structure of binding domains and their ligands, and can be used to create biosensors of proteins and small molecules. The developed biosensors covers a range of emission wavelengths and displays sensitivity as low as 50pM and dynamic range as high as 16-fold and could quantify their cognate ligand in human fluids. We apply hydrogen exchange kinetic mass spectroscopy to analyze time resolved structural changes in the developed biosensors and observe ligand-mediated folding of newly created termini.
Schizophrenia-associated SAP97 mutations increase glutamatergic synapse strength in the dentate gyrus and impair contextual episodic memory in rats
Authors: Kay Yuni , Tsan Linda , Davis Elizabeth A. , Tian Chen , Décarie-Spain Léa , Sadybekov Anastasiia , Pushkin Anna N. , Katritch Vsevolod , Kanoski Scott E. , Herring Bruce E.
Published: February 2022

Mutations in the putative glutamatergic synapse scaffolding protein SAP97 are associated with the development of schizophrenia in humans. However, the role of SAP97 in synaptic regulation is unclear. Here we show that SAP97 is expressed in the dendrites of granule neurons in the dentate gyrus but not in the dendrites of other hippocampal neurons. Schizophrenia-related perturbations of SAP97 did not affect CA1 pyramidal neuron synapse function. Conversely, these perturbations produce dramatic augmentation of glutamatergic neurotransmission in granule neurons that can be attributed to a release of perisynaptic GluA1-containing AMPA receptors into the postsynaptic densities of perforant pathway synapses. Furthermore, inhibiting SAP97 function in the dentate gyrus was sufficient to impair contextual episodic memory. Together, our results identify a cell-type-specific synaptic regulatory mechanism in the dentate gyrus that, when disrupted, impairs contextual information processing in rats.
Small molecule SWELL1 complex induction improves glycemic control and nonalcoholic fatty liver disease in murine Type 2 diabetes
Authors: Gunasekar Susheel K. , Xie Litao , Kumar Ashutosh , Hong Juan , Chheda Pratik R. , Kang Chen , Kern David M. , My-Ta Chau , Maurer Joshua , Heebink John , Gerber Eva E. , Grzesik Wojciech J. , Elliot-Hudson Macaulay , Zhang Yanhui , Key Phillip , Kulkarni Chaitanya A. , Beals Joseph W. , Smith Gordon I. , Samuel Isaac , Smith Jessica K. , Nau Peter , Imai Yumi , Sheldon Ryan D. , Taylor Eric B. , Lerner Daniel J. , Norris Andrew W. , Klein Samuel , Brohawn Stephen G. , Kerns Robert , Sah Rajan
Published: February 2022

Type 2 diabetes is associated with insulin resistance, impaired pancreatic β-cell insulin secretion, and nonalcoholic fatty liver disease. Tissue-specific SWELL1 ablation impairs insulin signaling in adipose, skeletal muscle, and endothelium, and impairs β-cell insulin secretion and glycemic control. Here, we show that ICl,SWELL and SWELL1 protein are reduced in adipose and β-cells in murine and human diabetes. Combining cryo-electron microscopy, molecular docking, medicinal chemistry, and functional studies, we define a structure activity relationship to rationally-design active derivatives of a SWELL1 channel inhibitor (DCPIB/SN-401), that bind the SWELL1 hexameric complex, restore SWELL1 protein, plasma membrane trafficking, signaling, glycemic control and islet insulin secretion via SWELL1-dependent mechanisms. In vivo, SN-401 restores glycemic control, reduces hepatic steatosis/injury, improves insulin-sensitivity and insulin secretion in murine diabetes. These findings demonstrate that SWELL1 channel modulators improve SWELL1-dependent systemic metabolism in Type 2 diabetes, representing a first-in-class therapeutic approach for diabetes and nonalcoholic fatty liver disease.
Bioinspired desaturation of alcohols enabled by photoredox proton-coupled electron transfer and cobalt dual catalysis
Authors: Huang Long , Ji Tengfei , Zhu Chen , Yue Huifeng , Zhumabay Nursaya , Rueping Magnus
Published: February 2022

In the biosynthesis sterols an enzyme-catalyzed demethylation is achieved via a stepwise oxidative transformation of alcohols to olefins. The overall demethylation proceeds through two sequential monooxygenation reactions and a subsequent dehydroformylative saturation. To mimic the desaturation processes observed in nature, we have successfully integrated photoredox proton-coupled electron transfer (PCET) and cobaloxime chemistry for the acceptorless dehydrogenation of alcohols. The state-of-the-art remote and precise desaturation of ketones proceeds efficiently through the activation of cyclic alcohols using bond-dissociation free energy (BDFE) as thermodynamic driving force. The resulting transient alkoxyl radical allows C-C bond scission to generate the carbon-centered radical remote to the carbonyl moiety. This key intermediate is subsequently combined with cobaloxime photochemistry to furnish the alkene. Moreover, the mild protocol can be extended to desaturation of linear alcohols as well as aromatic hydrocarbons. Application to bioactive molecules and natural product derivatives is also presented.
A metal-supported single-atom catalytic site enables carbon dioxide hydrogenation
Authors: Hung Sung-Fu , Xu Aoni , Wang Xue , Li Fengwang , Hsu Shao-Hui , Li Yuhang , Wicks Joshua , Cervantes Eduardo González , Rasouli Armin Sedighian , Li Yuguang C. , Luo Mingchuan , Nam Dae-Hyun , Wang Ning , Peng Tao , Yan Yu , Lee Geonhui , Sargent Edward H.
Published: February 2022

Nitrogen-doped graphene-supported single atoms convert CO2 to CO, but fail to provide further hydrogenation to methane – a finding attributable to the weak adsorption of CO intermediates. To regulate the adsorption energy, here we investigate the metal-supported single atoms to enable CO2 hydrogenation. We find a copper-supported iron-single-atom catalyst producing a high-rate methane. Density functional theory calculations and in-situ Raman spectroscopy show that the iron atoms attract surrounding intermediates and carry out hydrogenation to generate methane. The catalyst is realized by assembling iron phthalocyanine on the copper surface, followed by in-situ formation of single iron atoms during electrocatalysis, identified using operando X-ray absorption spectroscopy. The copper-supported iron-single-atom catalyst exhibits a CO2-to-methane Faradaic efficiency of 64% and a partial current density of 128 mA cm−2, while the nitrogen-doped graphene-supported one produces only CO. The activity is 32 times higher than a pristine copper under the same conditions of electrolyte and bias.
Plant conversions and abatement technologies cannot prevent stranding of power plant assets in 2 °C scenarios
Authors: Lu Yangsiyu , Cohen Francois , Smith Stephen M. , Pfeiffer Alexander
Published: February 2022

Continued fossil fuel development puts existing assets at risk of exceeding the capacity compatible with limiting global warming below 2 °C. However, it has been argued that plant conversions and new abatement technologies may allow for a smoother transition. We quantify the impact of future technology availability on the need for fossil fuel power plants to be stranded, i.e. decommissioned or underused. Even with carbon capture and storage (CCS) and bioenergy widely deployed in the future, a total of 267 PWh electricity generation (ten times global electricity production in 2018) may still be stranded. Coal-to-gas conversions could prevent 10–30 PWh of stranded generation. CCS retrofits, combined with biomass co-firing, could prevent 33–68 PWh. In contrast, lack of deployment of CCS or bioenergy could increase stranding by 69 or 45 percent respectively. Stranding risks remain under optimistic technology assumptions and even more so if CCS and bioenergy are not deployed at scale.
Smart textile lighting/display system with multifunctional fibre devices for large scale smart home and IoT applications
Authors: Choi Hyung Woo , Shin Dong-Wook , Yang Jiajie , Lee Sanghyo , Figueiredo Cátia , Sinopoli Stefano , Ullrich Kay , Jovančić Petar , Marrani Alessio , Momentè Roberto , Gomes João , Branquinho Rita , Emanuele Umberto , Lee Hanleem , Bang Sang Yun , Jung Sung-Min , Han Soo Deok , Zhan Shijie , Harden-Chaters William , Suh Yo-Han , Fan Xiang-Bing , Lee Tae Hoon , Chowdhury Mohamed , Choi Youngjin , Nicotera Salvatore , Torchia Andrea , Moncunill Francesc Mañosa , Candel Virginia Garcia , Durães Nelson , Chang Kiseok , Cho Sunghee , Kim Chul-Hong , Lucassen Marcel , Nejim Ahmed , Jiménez David , Springer Martijn , Lee Young-Woo , Cha SeungNam , Sohn Jung Inn , Igreja Rui , Song Kyungmin , Barquinha Pedro , Martins Rodrigo , Amaratunga Gehan A. J. , Occhipinti Luigi G. , Chhowalla Manish , Kim Jong Min
Published: February 2022

Smart textiles consist of discrete devices fabricated from—or incorporated onto—fibres. Despite the tremendous progress in smart textiles for lighting/display applications, a large scale approach for a smart display system with integrated multifunctional devices in traditional textile platforms has yet to be demonstrated. Here we report the realisation of a fully operational 46-inch smart textile lighting/display system consisting of RGB fibrous LEDs coupled with multifunctional fibre devices that are capable of wireless power transmission, touch sensing, photodetection, environmental/biosignal monitoring, and energy storage. The smart textile display system exhibits full freedom of form factors, including flexibility, bendability, and rollability as a vivid RGB lighting/grey-level-controlled full colour display apparatus with embedded fibre devices that are configured to provide external stimuli detection. Our systematic design and integration strategies are transformational and provide the foundation for realising highly functional smart lighting/display textiles over large area for revolutionary applications on smart homes and internet of things (IoT).
Nickel(II)-catalyzed living polymerization of diazoacetates toward polycarbene homopolymer and polythiophene-block-polycarbene copolymers
Authors: Zhou Li , Xu Lei , Song Xue , Kang Shu-Ming , Liu Na , Wu Zong-Quan
Published: February 2022

Diazoacetate polymerization has attracted considerable research attention because it is an effective approach for fabricating carbon–carbon (C–C) main chain polymers. However, diazoacetate polymerization based on inexpensive catalysts has been a long-standing challenge. Herein, we report a Ni(II) catalyst that can promote the living polymerization of various diazoacetates, yielding well-defined C–C main chain polymers, polycarbenes, with a predictable molecular weight (Mn) and low dispersity (Mw/Mn). Moreover, the Ni(II)-catalyzed sequential living polymerization of thiophene and diazoacetate monomers affords interesting π-conjugated poly(3-hexylthiophene)-block-polycarbene copolymers in high yields with a controlled Mn, variable compositions, and low Mw/Mn, although the structure and polymerization mechanism of the two monomers differ. Using this strategy, amphiphilic block copolymers comprising hydrophobic poly(3-hexylthiophene) and hydrophilic polycarbene blocks are facilely prepared, which were self-assembled into well-defined supramolecular architectures with tunable photoluminescence.
Atomic mechanism of near threshold fatigue crack growth in vacuum
Authors: Zhao Mingjie , Gu Wenjia , Warner Derek H.
Published: February 2022

Structural failures resulting from prolonged low-amplitude loading are particularly problematic. Over the past century a succession of mechanisms have been hypothesized, as experimental validation has remained out of reach. Here we show by atomistic modeling that sustained fatigue crack growth in vacuum requires emitted dislocations to change slip planes prior to their reabsorption into the crack on the opposite side of the loading cycle. By harnessing a new implementation of a concurrent multiscale method we (1) assess the validity of long-hypothesized material separation mechanisms thought to control near-threshold fatigue crack growth in vacuum, and (2) reconcile reports of crack growth in atomistic simulations at loading amplitudes below experimental crack growth thresholds. Our results provide a mechanistic foundation to relate fatigue crack growth tendency to fundamental material properties, e.g. stacking fault energies and elastic moduli, opening the door for improved prognosis and the design of novel fatigue resistance alloys.
GLI transcriptional repression is inert prior to Hedgehog pathway activation
Authors: Lex Rachel K. , Zhou Weiqiang , Ji Zhicheng , Falkenstein Kristin N. , Schuler Kaleigh E. , Windsor Kathryn E. , Kim Joseph D. , Ji Hongkai , Vokes Steven A.
Published: February 2022

The Hedgehog (HH) pathway regulates a spectrum of developmental processes through the transcriptional mediation of GLI proteins. GLI repressors control tissue patterning by preventing sub-threshold activation of HH target genes, presumably even before HH induction, while lack of GLI repression activates most targets. Despite GLI repression being central to HH regulation, it is unknown when it first becomes established in HH-responsive tissues. Here, we investigate whether GLI3 prevents precocious gene expression during limb development. Contrary to current dogma, we find that GLI3 is inert prior to HH signaling. While GLI3 binds to most targets, loss of Gli3 does not increase target gene expression, enhancer acetylation or accessibility, as it does post-HH signaling. Furthermore, GLI repression is established independently of HH signaling, but after its onset. Collectively, these surprising results challenge current GLI pre-patterning models and demonstrate that GLI repression is not a default state for the HH pathway.
A new approach exploiting thermally activated delayed fluorescence molecules to optimize solar thermal energy storage
Authors: Meng Fan-Yi , Chen I-Han , Shen Jiun-Yi , Chang Kai-Hsin , Chou Tai-Che , Chen Yi-An , Chen Yi-Ting , Chen Chi-Lin , Chou Pi-Tai
Published: February 2022

We propose a new concept exploiting thermally activated delayed fluorescence (TADF) molecules as photosensitizers, storage units and signal transducers to harness solar thermal energy. Molecular composites based on the TADF core phenoxazine–triphenyltriazine (PXZ-TRZ) anchored with norbornadiene (NBD) were synthesized, yielding compounds PZDN and PZTN with two and four NBD units, respectively. Upon visible-light excitation, energy transfer to the triplet state of NBD occurred, followed by NBD → quadricyclane (QC) conversion, which can be monitored by changes in steady-state or time-resolved spectra. The small S1-T1 energy gap was found to be advantageous in optimizing the solar excitation wavelength. Upon tuning the molecule’s triplet state energy lower than that of NBD (61 kcal/mol), as achieved by another composite PZQN, the efficiency of the NBD → QC conversion decreased drastically. Upon catalysis, the reverse QC → NBD reaction occurred at room temperature, converting the stored chemical energy back to heat with excellent reversibility.
Defining molecular glues with a dual-nanobody cannabidiol sensor
Authors: Cao Shiyun , Kang Shoukai , Mao Haibin , Yao Jiayu , Gu Liangcai , Zheng Ning
Published: February 2022

“Molecular glue” (MG) is a term coined to describe the mechanism of action of the plant hormone auxin and subsequently used to characterize synthetic small molecule protein degraders exemplified by immune-modulatory imide drugs (IMiDs). Prospective development of MGs, however, has been hampered by its elusive definition and thermodynamic characteristics. Here, we report the crystal structure of a dual-nanobody cannabidiol-sensing system, in which the ligand promotes protein-protein interaction in a manner analogous to auxin. Through quantitative analyses, we draw close parallels among the dual-nanobody cannabidiol sensor, the auxin perception complex, and the IMiDs-bound CRL4CRBN E3, which can bind and ubiquitinate “neo-substrates”. All three systems, including the recruitment of IKZF1 and CK1α to CRBN, are characterized by the lack of ligand binding activity in at least one protein partner and an under-appreciated preexisting low micromolar affinity between the two proteinaceous subunits that is enhanced by the ligand to reach the nanomolar range. These two unifying features define MGs as a special class of proximity inducers distinct from bifunctional compounds and can be used as criteria to guide target selection for future rational discovery of MGs.
Superior Colliculus to VTA pathway controls orienting response and influences social interaction in mice
Authors: Solié Clément , Contestabile Alessandro , Espinosa Pedro , Musardo Stefano , Bariselli Sebastiano , Huber Chieko , Carleton Alan , Bellone Camilla
Published: February 2022

Social behaviours characterize cooperative, mutualistic, aggressive or parental interactions that occur among conspecifics. Although the Ventral Tegmental Area (VTA) has been identified as a key substrate for social behaviours, the input and output pathways dedicated to specific aspects of conspecific interaction remain understudied. Here, in male mice, we investigated the activity and function of two distinct VTA inputs from superior colliculus (SC-VTA) and medial prefrontal cortex (mPFC-VTA). We observed that SC-VTA neurons display social interaction anticipatory calcium activity, which correlates with orienting responses towards an unfamiliar conspecific. In contrast, mPFC-VTA neuron population activity increases after initiation of the social contact. While protracted phasic stimulation of SC-VTA pathway promotes head/body movements and decreases social interaction, inhibition of this pathway increases social interaction. Here, we found that SC afferents mainly target a subpopulation of dorsolateral striatum (DLS)-projecting VTA dopamine (DA) neurons (VTADA-DLS). While, VTADA-DLS pathway stimulation decreases social interaction, VTADA-Nucleus Accumbens stimulation promotes it. Altogether, these data support a model by which at least two largely anatomically distinct VTA sub-circuits oppositely control distinct aspects of social behaviour.
Arctic glaciers record wavier circumpolar winds
Authors: Sasgen Ingo , Salles Annette , Wegmann Martin , Wouters Bert , Fettweis Xavier , Noël Brice P. Y. , Beck Christoph
Published: February 2022

Glaciers in the Arctic respond sensitively to climate change, recording the polar amplification of global warming with increasing mass loss. Here, we use glacier mass balances in Svalbard and northern Arctic Canada to categorize tropospheric variability and the associated summer circulation over the Arctic. We establish a link between annual glacier mass balances and their respective atmospheric forcings since 1950 using GRACE/GRACE-FO satellite data (2002–2021), as well as regional climate models and reanalysis data (1950–2019). We find that asynchronous behaviour of mass balance between the regions has become very likely since the early 2000s, exceeding the range of previous decadal variability. Related tropospheric circulation exhibits more meridional patterns, a greater influence of meridional heat advection and a wavier summer circulation. The traceable impact on glacier mass balances emphasizes the importance of dynamic next to thermodynamic climate changes for the future of glacier mass loss, Arctic ecology and societal impacts.
African heritage sites threatened as sea-level rise accelerates
Authors: Vousdoukas Michalis I. , Clarke Joanne , Ranasinghe Roshanka , Reimann Lena , Khalaf Nadia , Duong Trang Minh , Ouweneel Birgitt , Sabour Salma , Iles Carley E. , Trisos Christopher H. , Feyen Luc , Mentaschi Lorenzo , Simpson Nicholas P.
Published: February 2022

The African coast contains heritage sites of ‘Outstanding Universal Value’ that face increasing risk from anthropogenic climate change. Here, we generated a database of 213 natural and 71 cultural African heritage sites to assess exposure to coastal flooding and erosion under moderate (RCP 4.5) and high (RCP 8.5) greenhouse gas emission scenarios. Currently, 56 sites (20%) are at risk from a 1-in-100-year coastal extreme event, including the iconic ruins of Tipasa (Algeria) and the North Sinai Archaeological Sites Zone (Egypt). By 2050, the number of exposed sites is projected to more than triple, reaching almost 200 sites under high emissions. Emissions mitigation from RCP 8.5 to RCP 4.5 reduces the number of very highly exposed sites by 25%. These findings highlight the urgent need for increased climate change adaptation for heritage sites in Africa, including governance and management approaches, site-specific vulnerability assessments, exposure monitoring, and protection strategies.
Biallelic mutations in cancer genomes reveal local mutational determinants
Authors: Demeulemeester Jonas , Dentro Stefan C. , Gerstung Moritz , Van Loo Peter
Published: February 2022

The infinite sites model of molecular evolution posits that every position in the genome is mutated at most once1. By restricting the number of possible mutation histories, haplotypes and alleles, it forms a cornerstone of tumor phylogenetic analysis2and is often implied when calling, phasing and interpreting variants3,4or studying the mutational landscape as a whole5. Here we identify 18,295 biallelic mutations, where the same base is mutated independently on both parental copies, in 559 (21%) bulk sequencing samples from the Pan-Cancer Analysis of Whole Genomes study. Biallelic mutations reveal ultraviolet light damage hotspots at E26 transformation-specific (ETS) and nuclear factor of activated T cells (NFAT) binding sites, and hypermutable motifs inPOLE-mutant and other cancers. We formulate recommendations for variant calling and provide frameworks to model and detect biallelic mutations. These results highlight the need for accurate models of mutation rates and tumor evolution, as well as their inference from sequencing data.
CRISPR and biochemical screens identify MAZ as a cofactor in CTCF-mediated insulation at Hox clusters
Authors: Ortabozkoyun Havva , Huang Pin-Yao , Cho Hyunwoo , Narendra Varun , LeRoy Gary , Gonzalez-Buendia Edgar , Skok Jane A. , Tsirigos Aristotelis , Mazzoni Esteban O. , Reinberg Danny
Published: February 2022

CCCTC-binding factor (CTCF) is critical to three-dimensional genome organization. Upon differentiation, CTCF insulates active and repressed genes within Hox gene clusters. We conducted a genome-wide CRISPR knockout (KO) screen to identify genes required for CTCF-boundary activity at the HoxA cluster, complemented by biochemical approaches. Among the candidates, we identified Myc-associated zinc-finger protein (MAZ) as a cofactor in CTCF insulation. MAZ colocalizes with CTCF at chromatin borders and, similar to CTCF, interacts with the cohesin subunit RAD21. MAZ KO disrupts gene expression and local contacts within topologically associating domains. Similar to CTCF motif deletions, MAZ motif deletions lead to derepression of posterior Hox genes immediately after CTCF boundaries upon differentiation, giving rise to homeotic transformations in mouse. Thus, MAZ is a factor contributing to appropriate insulation, gene expression and genomic architecture during development.
Climate Stability Index maps, a global high resolution cartography of climate stability from Pliocene to 2100
Authors: Herrando-Moraira Sonia , Nualart Neus , Galbany-Casals Mercè , Garcia-Jacas Núria , Ohashi Haruka , Matsui Tetsuya , Susanna Alfonso , Tang Cindy Q. , López-Pujol Jordi
Published: February 2022

Climate changes are top biodiversity shapers, both during the past and future. Mapping the most climatic stable and unstable zones on Earth could improve our understanding of biodiversity distribution and evolution. Here, we present a set of maps based on a global scale, high resolution (ca. 5 km) new Climate Stability Index (CSI). The CSI considers bioclimatic variables for two different time ranges: (1) from Pliocene (3.3 Ma) to the present (CSI-past map set), using 12 time periods of PaleoClim representing warm and cold cycles; and (2) from present to the year 2100 (CSI-future), using nine general circulation models of climate change of four periods available from WorldClim. We calculated standard deviation of the variables and selected an uncorrelated set for summing, normalizing and obtaining the CSI maps. Our approach is useful for fields such as biogeography, earth sciences, agriculture, or sociology. However, CSI is an index that can be re-calculated according to particular criteria and objectives (e.g. temperature variables); maps are, therefore, customizable to every user.
Four years of daily stable water isotope data in stream water and precipitation from three Swiss catchments
Authors: von Freyberg Jana , Rücker Andrea , Zappa Massimiliano , Schlumpf Alessandro , Studer Bjørn , Kirchner James W.
Published: February 2022

Time series of the natural isotopic composition (2H, 18O) of precipitation and streamwater can provide important insights into ecohydrological phenomena at the catchment scale. However, multi-year, high-frequency isotope datasets are generally scarce, limiting our ability to study highly dynamic short-term ecohydrological processes. Here we present four years of daily isotope measurements in streamwater and precipitation at the Alp catchment (area 47 km2) in Central Switzerland and two of its tributaries (0.7 km2 and 1.6 km2). This data set reveals short-term responses of streamflow isotopes to precipitation events, which otherwise remain obscured when isotopes are sampled weekly or monthly. The observations span the period June 2015 through May 2019, during which several hydrometeorologic extreme events occurred, including a very dry summer in 2018 and below-average snow accumulation in winter 2016/2017. In addition, we provide daily time series of key hydrometeorological variables that, in combination with the isotope data, can be useful for assessing the robustness of ecohydrological models.
Analysis of spatial patterns and driving factors of provincial tourism demand in China
Authors: Ma Xuankai , Yang Zhaoping , Zheng Jianghua
Published: February 2022

Modeling and forecasting tourism demand across destinations has become a priority in tourism research. Most tourism demand studies rely on annual statistics with small sample sizes and lack research on spatial heterogeneity and drivers of tourism demand. This study proposes a new framework for measuring inter-provincial tourism demand's spatiotemporal distribution using search engine indices based on a geographic perspective. A combination of spatial autocorrelation and Geodetector is utilized to recognize the spatiotemporal distribution patterns of tourism demand in 2011 and 2018 in 31 provinces of mainland China and detect its driving mechanisms. The results reveal that the spatial distribution of tourism demand manifests a vital stratification phenomenon with significant spatial aggregation in the southwest and northeast of China. Traffic conditions, social-economic development level, and physical conditions compose a constant and robust interaction network, which dominates the spatial distribution of tourism demand in different development stages through different interactions.
A miniature robotic steerable endoscope for maxillary sinus surgery called PliENT
Authors: Legrand Julie , Ourak Mouloud , Van Gerven Laura , Vander Poorten Vincent , Vander Poorten Emmanuel
Published: February 2022

In endoscopic maxillary sinus surgery, the maxillary sinus is accessed through the nasal cavity which constitutes a narrow and tortuous pathway. However, surgeons still use rigid endoscopes and rigid, straight or pre-bent instruments for this procedure. Resection of the uncinate process and creation of a medial antrostomy is warranted to access the pathology inside the maxillary sinus and depending on the location of the pathology (lateral, inferior or anterior wall), additional resection of healthy tissue and/or functional structures like the lacrimal duct and/or inferior turbinate is necessary to gain optimal access. In order to avoid this additional resection, a functional single-handed, steerable endoscope for endoscopic maxillary sinus surgery has been designed and built. This endoscope is, to our knowledge, the most slender active steerable endoscope ever reported for maxillary sinus surgery. The performance of the endoscope was validated by two surgeons on a cadaver. An increased field of view was found in comparison to currently used endoscopes. As a direct consequence, a reduced need for resection of healthy tissue was confirmed.
Macro-seepage based potential new hydrocarbon prospects in Assam-Arakan Basin, India
Authors: Boruah Annapurna , Verma Sumit , Rasheed Abdul , Siddharth Gairola Gaurav , Gogoi Anuj
Published: February 2022

Active macro seepages of methane that occur in between the north bank of the Brahmaputra river and Himalayan foothill region of Assam Arakan Basin, India, indicate the presence of hydrocarbon accumulation in the subsurface, but the hydrocarbon prospects in this region are not well studied. We carried out an extensive field sampling, which included a total of 58 sediment core collections from an active gas seepage location and nearby areas at a depth of 2–2.5 m. Our sample locations are placed at 1 km intervals laterally. We performed laboratory investigations and mapped near-surface chemical alterations associated with active macro seepages and microseepages. The analysis of geochemical composition of hydrocarbon gases in the sediment indicates both the biogenic and thermogenic origins of seeped hydrocarbons. The stable isotope analysis of methane suggests the presence of thermogenic as well as mixed biogenic-thermogenic gases. The presence of such mixing of gases is caused by the secondary alteration processes during their migration through potential faults and fractures. The trace elements of the sediments show anomalous concentrations at different parts of the study area, with a wide range of concentrations for Ba (54 to 492 ppm), Cu (1–25 ppm), Cr (61–329 ppm), Ni (1–42 ppm), Pb (2–48 ppm), Th (2–32 ppm), U (4–39 ppm), V (19–133 ppm) and U (0.87–6.5 ppm). There are higher concentrations of adsorbed gases, trace elements, and microbes along the identified lineaments. Such higher concentration can be triggered by high hydrocarbon-oxidizing bacteria count, which is greater than 104cfu/gm of soil of bacterial growth around the lineaments. We identified potential hydrocarbon prospects based on the macro and micro seepage analysis using integrated geological, geochemical and microbial techniques in the study area.
RETRACTED ARTICLE: Numerical assessment of the influence of helical baffle on the hydrothermal aspects of nanofluid turbulent forced convection inside a heat exchanger
Authors: Yang Li , Baghaei Shaghayegh , Suksatan Wanich , Barnoon Pouya , sharma Sandhir , Davidyants Alla , El-Shafay A. S.
Published: February 2022

This study is devoted to the numerical assessment of the influence of helical baffle on the hydrothermal aspects and irreversibility behavior of the turbulent forced convection flow of water-CuO nanofluid (NF) inside a hairpin heat exchanger with 100 mm length, 10 mm inner tube internal diameter, and 15 mm outer diameter internal diameter. The variations of the first-law and second-law performance metrics are investigated in terms of Reynolds number (Re = 5000–10,000), volume concentration of NF ($$\varphi =0-4\mathrm{\%}$$

φ
=
0
-
4
%

) and baffle pitch (B = 25–100 mm). The results show that the NF Nusselt number grows with the rise of both the Re and $$\varphi$$
φ
whereas it declines with the rise of B. In addition, the outcomes depicted that the rise of both Re and $$\varphi$$
φ
results in the rise of pressure drop, while it declines with the increase of B. Moreover, it was found that the best thermal performance of NF is equal to 1.067, which belongs to the case B = 33.3 mm, $$\varphi$$
φ
=2%, and Re = 10,000. Furthermore, it was shown that irreversibilities due to fluid friction and heat transfer augment with the rise of Re while the rise of B results in the decrease of frictional irreversibilities. Finally, the outcomes revealed that with the rise of B, the heat transfer irreversibilities first intensify and then diminish.
Deep learning of quantitative ultrasound multi-parametric images at pre-treatment to predict breast cancer response to chemotherapy
Authors: Taleghamar Hamidreza , Jalalifar Seyed Ali , Czarnota Gregory J. , Sadeghi-Naini Ali
Published: February 2022

In this study, a novel deep learning-based methodology was investigated to predict breast cancer response to neo-adjuvant chemotherapy (NAC) using the quantitative ultrasound (QUS) multi-parametric imaging at pre-treatment. QUS multi-parametric images of breast tumors were generated using the data acquired from 181 patients diagnosed with locally advanced breast cancer and planned for NAC followed by surgery. The ground truth response to NAC was identified for each patient after the surgery using the standard clinical and pathological criteria. Two deep convolutional neural network (DCNN) architectures including the residual network and residual attention network (RAN) were explored for extracting optimal feature maps from the parametric images, with a fully connected network for response prediction. In different experiments, the features maps were derived from the tumor core only, as well as the core and its margin. Evaluation results on an independent test set demonstrate that the developed model with the RAN architecture to extract feature maps from the expanded parametric images of the tumor core and margin had the best performance in response prediction with an accuracy of 88% and an area under the receiver operating characteristic curve of 0.86. Ten-year survival analyses indicate statistically significant differences between the survival of the responders and non-responders identified based on the model prediction at pre-treatment and the standard criteria at post-treatment. The results of this study demonstrate the promising capability of DCNNs with attention mechanisms in predicting breast cancer response to NAC prior to the start of treatment using QUS multi-parametric images.
Demarcating the boundary conditions of memory reconsolidation: An unsuccessful replication
Authors: Stemerding Lotte E. , Stibbe Danielle , van Ast Vanessa A. , Kindt Merel
Published: February 2022

Disrupting memory reconsolidation provides an opportunity to abruptly reduce the behavioural expression of fear memories with long-lasting effects. The success of a reconsolidation intervention is, however, not guaranteed as it strongly depends on the destabilization of the memory. Identifying the necessary conditions to trigger destabilization remains one of the critical challenges in the field. We aimed to replicate a study from our lab, showing that the occurrence of a prediction error (PE) during reactivation is necessary but not sufficient for destabilization. We tested the effectiveness of a reactivation procedure consisting of a single PE, compared to two control groups receiving no or multiple PEs. All participants received propranolol immediately after reactivation and were tested for fear retention 24 h later. In contrast to the original results, we found no evidence for a reconsolidation effect in the single PE group, but a straightforward interpretation of these results is complicated by the lack of differential fear retention in the control groups. Our results corroborate other failed reconsolidation studies and exemplify the complexity of experimentally investigating this process in humans. Thorough investigation of the interaction between learning and memory reactivation is essential to understand the inconsistencies in the literature and to improve reconsolidation interventions.
Heat flow saturate of Ag/MgO-water hybrid nanofluid in heated trigonal enclosure with rotate cylindrical cavity by using Galerkin finite element
Authors: Redouane Fares , Jamshed Wasim , Devi S. Suriya Uma , Prakash M. , Nasir Nor Ain Azeany Mohd , Hammouch Zakia , Eid Mohamed R. , Nisar Kottakkaran Sooppy , Mahammed A. Belhadj , Abdel-Aty Abdel-Haleem , Yahia I. S. , Eed Emad M.
Published: February 2022

MHD Natural convection, which is one of the principal types of convective heat transfer in numerous research of heat exchangers and geothermal energy systems, as well as nanofluids and hybrid nanofluids. This work focuses on the investigation of Natural convective heat transfer evaluation inside a porous triangular cavity filled with silver-magnesium oxide/water hybrid nanofluid [H2O/Ag-MgO]hnf under a consistent magnetic field. The laminar and incompressible nanofluid flow is taken to account while Darcy–Forchheimer model takes account of the advection inertia effect in the porous sheet. Controlled equations of the work have been approached nondimensional and resolved by Galerkin finite element technique. The numerical analyses were carried out by varying the Darcy, Hartmann, and Rayleigh numbers, porosity, and characteristics of solid volume fraction and flow fields. Further, the findings are reported in streamlines, isotherms and Nusselt numbers. For this work, the parametric impact may be categorized into two groups. One of them has an effect on the structural factors such as triangular form and scale on the physical characteristics of the important outputs such as fluidity and thermal transfer rates. The significant findings are the parameters like Rayleigh and slightly supported by Hartmann along with Darcy number, minimally assists by solid-particle size and rotating factor as clockwise assists the cooler flow at the center and anticlockwise direction assists the warmer flow. Clear raise in heat transporting rate can be obtained for increasing solid-particle size.
Molecular assays to reliably detect and quantify predation on a forest pest in bats faeces
Authors: Baroja Unai , Garin Inazio , Vallejo Nerea , Caro Amaia , Ibáñez Carlos , Basso Andrea , Goiti Urtzi
Published: February 2022

Targeted molecular methods such as conventional PCR (cPCR) and quantitative PCR (qPCR), combined with species-specific primers and probes, are widely applied for pest species detection. Besides, the potential of qPCR to quantify DNA in samples makes it an invaluable molecular tool to infer the predation levels on specific prey by analysing predators’ stools. Nevertheless, studies on the diet of bats failed to find any empirical relationship, and it remains to be evaluated. Thus, we developed and evaluated two species-specific PCR assays to detect and quantify DNA of a major forest pest, the pine processionary, Thaumetopoea pityocampa, in bats’ faeces. Further, we empirically compared a range of different known DNA concentrations (input) of the target species mixed with mocks and bat faecal samples against DNA abundances yielded by qPCR (output) for a quantitative assessment. Overall, cPCR showed a lower detection rate than qPCR, but augmenting the replicate effort from one to three replicates led to a greater increase in the detection rate of the cPCR (from 57 to 80%) than the qPCR (from 90 to 99%). The quantitative experiment results showed a highly significant correlation between the input and output DNA concentrations (t = 10.84, p < 0.001) with a mean slope value of 1.05, indicating the accuracy of our qPCR assay to estimate DNA abundance of T. pityocampa in bat faeces. The framework of this study can be taken as a model to design similar assays applicable to other species of interest, such as agricultural pests or insects of public health concern.