bluuebunny/crossref_metadata_2025 huggingface dataset:
Baseline gut microbiota and metabolome predict durable immunogenicity to SARS-CoV-2 vaccines
Authors: Peng Ye , Zhang Lin , Mok Chris K. P. , Ching Jessica Y. L. , Zhao Shilin , Wong Matthew K. L. , Zhu Jie , Chen Chunke , Wang Shilan , Yan Shuai , Qin Biyan , Liu Yingzhi , Zhang Xi , Cheung Chun Pun , Cheong Pui Kuan , Ip Ka Long , Fung Adrian C. H. , Wong Kenneth K. Y. , Hui David S. C. , Chan Francis K. L. , Ng Siew C. , Tun Hein M.
Published: September 2023

The role of gut microbiota in modulating the durability of COVID-19 vaccine immunity is yet to be characterised. In this cohort study, we collected blood and stool samples of 121 BNT162b2 and 40 CoronaVac vaccinees at baseline, 1 month, and 6 months post vaccination (p.v.). Neutralisation antibody, plasma cytokine and chemokines were measured and associated with the gut microbiota and metabolome composition. A significantly higher level of neutralising antibody (at 6 months p.v.) was found in BNT162b2 vaccinees who had higher relative abundances of Bifidobacterium adolescentis, Bifidobacterium bifidum, and Roseburia faecis as well as higher concentrations of nicotinic acid (Vitamin B) and γ-Aminobutyric acid (P < 0.05) at baseline. CoronaVac vaccinees with high neutralising antibodies at 6 months p.v. had an increased relative abundance of Phocaeicola dorei, a lower relative abundance of Faecalibacterium prausnitzii, and a higher concentration of L-tryptophan (P < 0.05) at baseline. A higher antibody level at 6 months p.v. was also associated with a higher relative abundance of Dorea formicigenerans at 1 month p.v. among CoronaVac vaccinees (Rho = 0.62, p = 0.001, FDR = 0.123). Of the species altered following vaccination, 79.4% and 42.0% in the CoronaVac and BNT162b2 groups, respectively, recovered at 6 months. Specific to CoronaVac vaccinees, both bacteriome and virome diversity depleted following vaccination and did not recover to baseline at 6 months p.v. (FDR < 0.1). In conclusion, this study identified potential microbiota-based adjuvants that may extend the durability of immune responses to SARS-CoV-2 vaccines.
Cultivation and genomic characterization of novel and ubiquitous marine nitrite-oxidizing bacteria from the Nitrospirales
Authors: Mueller Anna J , Daebeler Anne , Herbold Craig W , Kirkegaard Rasmus H , Daims Holger
Published: September 2023

Nitrospirales, including the genus Nitrospira, are environmentally widespread chemolithoautotrophic nitrite-oxidizing bacteria. These mostly uncultured microorganisms gain energy through nitrite oxidation, fix CO2, and thus play vital roles in nitrogen and carbon cycling. Over the last decade, our understanding of their physiology has advanced through several new discoveries, such as alternative energy metabolisms and complete ammonia oxidizers (comammox Nitrospira). These findings mainly resulted from studies of terrestrial species, whereas less attention has been given to marine Nitrospirales. In this study, we cultured three new marine Nitrospirales enrichments and one isolate. Three of these four NOB represent new Nitrospira species while the fourth represents a novel genus. This fourth organism, tentatively named “Ca. Nitronereus thalassa”, represents the first cultured member of a Nitrospirales lineage that encompasses both free-living and sponge-associated nitrite oxidizers, is highly abundant in the environment, and shows distinct habitat distribution patterns compared to the marine Nitrospira species. Partially explaining this, “Ca. Nitronereus thalassa” harbors a unique combination of genes involved in carbon fixation and respiration, suggesting differential adaptations to fluctuating oxygen concentrations. Furthermore, “Ca. Nitronereus thalassa” appears to have a more narrow substrate range compared to many other marine nitrite oxidizers, as it lacks the genomic potential to utilize formate, cyanate, and urea. Lastly, we show that the presumed marine Nitrospirales lineages are not restricted to oceanic and saline environments, as previously assumed.
Targeting survivin with Tanshinone IIA inhibits tumor growth and overcomes chemoresistance in colorectal cancer
Authors: Cao Yaoquan , Tang Haibo , Wang Guohui , Li Pengzhou , Song Zhi , Li Weizheng , Sun Xulong , Zhong Xiaoxiao , Yu Qianqian , Zhu Shaihong , Zhu Liyong
Published: September 2023

The inhibitor of apoptosis protein survivin has a critical regulatory role in carcinogenesis and treatment tolerance in colorectal cancer (CRC). However, the targeted drugs for survivin protein are extremely limited. In the present research, we discovered that Tanshinone IIA (Tan IIA) played a dual regulatory role in inhibiting tumorigenesis and reversing 5-Fu tolerance via modulating the expression and phosphorylation of survivin in CRC cells. Mechanistically, Tan IIA suppressed the Akt/WEE1/CDK1 signaling pathway, which led to the downregulation of survivin Thr34 phosphorylation and destruction of the interaction between USP1 and survivin to promote survivin ubiquitination and degradation. Furthermore, Tan IIA significantly facilitated chemoresistant CRC cells to 5-Fu sensitivity. These results revealed that Tan IIA possessed a strong antitumor activity against CRC cells and could act as an up-and-coming agent for treating CRC and overcoming chemotherapy resistance.
SMCHD1 has separable roles in chromatin architecture and gene silencing that could be targeted in disease
Authors: Tapia del Fierro Andres , den Hamer Bianca , Benetti Natalia , Jansz Natasha , Chen Kelan , Beck Tamara , Vanyai Hannah , Gurzau Alexandra D. , Daxinger Lucia , Xue Shifeng , Ly Thanh Thao Nguyen , Wanigasuriya Iromi , Iminitoff Megan , Breslin Kelsey , Oey Harald , Krom Yvonne D. , van der Hoorn Dinja , Bouwman Linde F. , Johanson Timothy M. , Ritchie Matthew E. , Gouil Quentin A. , Reversade Bruno , Prin Fabrice , Mohun Timothy , van der Maarel Silvère M. , McGlinn Edwina , Murphy James M. , Keniry Andrew , de Greef Jessica C. , Blewitt Marnie E.
Published: September 2023

The interplay between 3D chromatin architecture and gene silencing is incompletely understood. Here, we report a novel point mutation in the non-canonical SMC protein SMCHD1 that enhances its silencing capacity at endogenous developmental targets. Moreover, it also results in enhanced silencing at the facioscapulohumeral muscular dystrophy associated macrosatellite-array, D4Z4, resulting in enhanced repression of DUX4 encoded by this repeat. Heightened SMCHD1 silencing perturbs developmental Hox gene activation, causing a homeotic transformation in mice. Paradoxically, the mutant SMCHD1 appears to enhance insulation against other epigenetic regulators, including PRC2 and CTCF, while depleting long range chromatin interactions akin to what is observed in the absence of SMCHD1. These data suggest that SMCHD1’s role in long range chromatin interactions is not directly linked to gene silencing or insulating the chromatin, refining the model for how the different levels of SMCHD1-mediated chromatin regulation interact to bring about gene silencing in normal development and disease.
Myo9b mutations are associated with altered dendritic cell functions and increased susceptibility to autoimmune diabetes onset
Authors: Zhang Jing , Zou Yuan , Chen Longmin , Sun Fei , Xu Qianqian , Zhou Qing , Wang Yi , Luo Xi , Wang Na , Li Yang , Zhang Shu , Xiong Fei , Yang Ping , Liu Shiwei , Yang Tao , Weng Jianping , Eizirik Décio L. , Yan Jinhua , Zhou Zhiguang , Wang Cong-Yi
Published: September 2023

The regulation of autoimmunity against pancreatic islet β cells for type 1 diabetes (T1D) onset is still unclear. NOD/ShiLtJ (NOD) mice are prone to the onset of autoimmune diabetes, but its congenic strain, ALR/Lt (ALR), is not. Here we show that dendritic cells (DC) in ALR mice have impaired migratory and T-cell priming capability. Genomic comparative analysis maps a 33-bp deletion in the ALR Myosin IXb (Myo9b) gene when compared with NOD genome; meanwhile, data from knock-in models show that this ALR Myo9b allele impairs phenotypic and functional maturation of DCs, and prevents the development and progression of spontaneous autoimmune diabetes in NOD mice. In parallel, while the ALR 33-bp deletion of Myo9b is not conserved in human, we find a MYO9B R133Q polymorphism associating with increased risk of T1D and enhanced DC function in patients with T1D. Our results thus hint that alterations in Myo9b may contribute to altered DC function and autoimmune diabetes onset.
A net-zero emissions strategy for China’s power sector using carbon-capture utilization and storage
Authors: Fan Jing-Li , Li Zezheng , Huang Xi , Li Kai , Zhang Xian , Lu Xi , Wu Jianzhong , Hubacek Klaus , Shen Bo
Published: September 2023

Decarbonized power systems are critical to mitigate climate change, yet methods to achieve a reliable and resilient near-zero power system are still under exploration. This study develops an hourly power system simulation model considering high-resolution geological constraints for carbon-capture-utilization-and-storage to explore the optimal solution for a reliable and resilient near-zero power system. This is applied to 31 provinces in China by simulating 10,450 scenarios combining different electricity storage durations and interprovincial transmission capacities, with various shares of abated fossil power with carbon-capture-utilization-and-storage. Here, we show that allowing up to 20% abated fossil fuel power generation in the power system could reduce the national total power shortage rate by up to 9.0 percentages in 2050 compared with a zero fossil fuel system. A lowest-cost scenario with 16% abated fossil fuel power generation in the system even causes 2.5% lower investment costs in the network (or $16.8 billion), and also increases system resilience by reducing power shortage during extreme climatic events.
A common East-Asian ALDH2 mutation causes metabolic disorders and the therapeutic effect of ALDH2 activators
Authors: Chang Yi-Cheng , Lee Hsiao-Lin , Yang Wenjin , Hsieh Meng-Lun , Liu Cai-Cin , Lee Tung-Yuan , Huang Jing-Yong , Nong Jiun-Yi , Li Fu-An , Chuang Hsiao-Li , Ding Zhi-Zhong , Su Wei-Lun , Chueh Li-Yun , Tsai Yi-Ting , Chen Che-Hong , Mochly-Rosen Daria , Chuang Lee-Ming
Published: September 2023

Obesity and type 2 diabetes have reached pandemic proportion. ALDH2 (acetaldehyde dehydrogenase 2, mitochondrial) is the key metabolizing enzyme of acetaldehyde and other toxic aldehydes, such as 4-hydroxynonenal. A missense Glu504Lys mutation of the ALDH2 gene is prevalent in 560 million East Asians, resulting in reduced ALDH2 enzymatic activity. We find that male Aldh2 knock-in mice mimicking human Glu504Lys mutation were prone to develop diet-induced obesity, glucose intolerance, insulin resistance, and fatty liver due to reduced adaptive thermogenesis and energy expenditure. We find reduced activity of ALDH2 of the brown adipose tissue from the male Aldh2 homozygous knock-in mice. Proteomic analyses of the brown adipose tissue from the male Aldh2 knock-in mice identifies increased 4-hydroxynonenal-adducted proteins involved in mitochondrial fatty acid oxidation and electron transport chain, leading to markedly decreased fatty acid oxidation rate and mitochondrial respiration of brown adipose tissue, which is essential for adaptive thermogenesis and energy expenditure. AD-9308 is a water-soluble, potent, and highly selective ALDH2 activator. AD-9308 treatment ameliorates diet-induced obesity and fatty liver, and improves glucose homeostasis in both male Aldh2 wild-type and knock-in mice. Our data highlight the therapeutic potential of reducing toxic aldehyde levels by activating ALDH2 for metabolic diseases.
Deep learning-enabled realistic virtual histology with ultraviolet photoacoustic remote sensing microscopy
Authors: Martell Matthew T. , Haven Nathaniel J. M. , Cikaluk Brendyn D. , Restall Brendon S. , McAlister Ewan A. , Mittal Rohan , Adam Benjamin A. , Giannakopoulos Nadia , Peiris Lashan , Silverman Sveta , Deschenes Jean , Li Xingyu , Zemp Roger J.
Published: September 2023

The goal of oncologic surgeries is complete tumor resection, yet positive margins are frequently found postoperatively using gold standard H&E-stained histology methods. Frozen section analysis is sometimes performed for rapid intraoperative margin evaluation, albeit with known inaccuracies. Here, we introduce a label-free histological imaging method based on an ultraviolet photoacoustic remote sensing and scattering microscope, combined with unsupervised deep learning using a cycle-consistent generative adversarial network for realistic virtual staining. Unstained tissues are scanned at rates of up to 7 mins/cm2, at resolution equivalent to 400x digital histopathology. Quantitative validation suggests strong concordance with conventional histology in benign and malignant prostate and breast tissues. In diagnostic utility studies we demonstrate a mean sensitivity and specificity of 0.96 and 0.91 in breast specimens, and respectively 0.87 and 0.94 in prostate specimens. We also find virtual stain quality is preferred (P = 0.03) compared to frozen section analysis in a blinded survey of pathologists.
Characterization and structure-based protein engineering of a regiospecific saponin acetyltransferase from Astragalus membranaceus
Authors: Wang Linlin , Jiang Zhihui , Zhang Jiahe , Chen Kuan , Zhang Meng , Wang Zilong , Wang Binju , Ye Min , Qiao Xue
Published: September 2023

Acetylation contributes to the bioactivity of numerous medicinally important natural products. However, little is known about the acetylation on sugar moieties. Here we report a saponin acetyltransferase fromAstragalus membranaceus. AmAT7-3 is discovered through a stepwise gene mining approach and characterized as the xylose C3′/C4′-O-acetyltransferse of astragaloside IV (1). To elucidate its catalytic mechanism, complex crystal structures of AmAT7-3/1and AmAT7-3A310G/1are obtained, which reveal a large active pocket decided by a specific sequence AADAG. Combining with QM/MM computation, the regiospecificity of AmAT7-3 is determined by sugar positioning modulated by surrounding amino acids including #A310 and #L290. Furthermore, a small mutant library is built using semi-rational design, where variants A310G and A310W are found to catalyze specific C3′-Oand C4′-Oacetylation, respectively. AmAT7-3 and its variants are also employed to acetylate other bioactive saponins. This work expands the understanding of saponin acetyltransferases, and provide efficient catalytic tools for saponin acetylation.
Blockade of interferon signaling decreases gut barrier integrity and promotes severe West Nile virus disease
Authors: Lin Shih-Ching , Zhao Fang R. , Janova Hana , Gervais Adrian , Rucknagel Summer , Murray Kristy O. , Casanova Jean-Laurent , Diamond Michael S.
Published: September 2023

The determinants of severe disease caused by West Nile virus (WNV) and why only ~1% of individuals progress to encephalitis remain poorly understood. Here, we use human and mouse enteroids, and a mouse model of pathogenesis, to explore the capacity of WNV to directly infect gastrointestinal (GI) tract cells and contribute to disease severity. At baseline, WNV poorly infects human and mouse enteroid cultures and enterocytes in mice. However, when STAT1 or type I interferon (IFN) responses are absent, GI tract cells become infected, and this is associated with augmented GI tract and blood-brain barrier (BBB) permeability, accumulation of gut-derived molecules in the brain, and more severe WNV disease. The increased gut permeability requires TNF-α signaling, and is absent in WNV-infected IFN-deficient germ-free mice. To link these findings to human disease, we measured auto-antibodies against type I IFNs in serum from WNV-infected human cohorts. A greater frequency of auto- and neutralizing antibodies against IFN-α2 or IFN-ω is present in patients with severe WNV infection, whereas virtually no asymptomatic WNV-infected subjects have such antibodies (odds ratio 24 [95% confidence interval: 3.0 − 192.5;P = 0.003]). Overall, our experiments establish that blockade of type I IFN signaling extends WNV tropism to enterocytes, which correlates with increased gut and BBB permeability, and more severe disease.
Structural insights into the mechanism of GTP initiation of microtubule assembly
Authors: Zhou Ju , Wang Anhui , Song Yinlong , Liu Nan , Wang Jia , Li Yan , Liang Xin , Li Guohui , Chu Huiying , Wang Hong-Wei
Published: September 2023

In eukaryotes, the dynamic assembly of microtubules (MT) plays an important role in numerous cellular processes. The underlying mechanism of GTP triggering MT assembly is still unknown. Here, we present cryo-EM structures of tubulin heterodimer at their GTP- and GDP-bound states, intermediate assembly states of GTP-tubulin, and final assembly stages of MT. Both GTP- and GDP-tubulin heterodimers adopt similar curved conformations with subtle flexibility differences. In head-to-tail oligomers of tubulin heterodimers, the inter-dimer interface of GDP-tubulin exhibits greater flexibility, particularly in tangential bending. Cryo-EM of the intermediate assembly states reveals two types of tubulin lateral contacts, “Tube-bond” and “MT-bond”. Further, molecular dynamics (MD) simulations show that GTP triggers lateral contact formation in MT assembly in multiple sequential steps, gradually straightening the curved tubulin heterodimers. Therefore, we propose a flexible model of GTP-initiated MT assembly, including the formation of longitudinal and lateral contacts, to explain the nucleation and assembly of MT.
Magnetically-dressed CrSBr exciton-polaritons in ultrastrong coupling regime
Authors: Wang Tingting , Zhang Dingyang , Yang Shiqi , Lin Zhongchong , Chen Quan , Yang Jinbo , Gong Qihuang , Chen Zuxin , Ye Yu , Liu Wenjing
Published: September 2023

Over the past few decades, exciton-polaritons have attracted substantial research interest due to their half-light-half-matter bosonic nature. Coupling exciton-polaritons with magnetic orders grants access to rich many-body phenomena, but has been limited by the availability of material systems that exhibit simultaneous exciton resonances and magnetic ordering. Here we report magnetically-dressed microcavity exciton-polaritons in the van der Waals antiferromagnetic (AFM) semiconductor CrSBr coupled to a Tamm plasmon microcavity. Using angle-resolved spectroscopy, we reveal an exceptionally high exciton-photon coupling strength, up to 169 meV, demonstrating ultrastrong coupling that persists up to room temperature. By performing temperature-dependent spectroscopy, we show the magnetic nature of the exciton-polaritons in CrSBr microcavity as the magnetic order changes from AFM to paramagnetic. By applying an out-of-plane magnetic field, we achieve effective tuning of the polariton energy while maintaining the ultrastrong exciton-photon coupling strength. We attribute this to the spin canting process that modulates the interlayer exciton interaction.
Evolution of lasR mutants in polymorphic Pseudomonas aeruginosa populations facilitates chronic infection of the lung
Authors: Zhao Kelei , Yang Xiting , Zeng Qianglin , Zhang Yige , Li Heyue , Yan Chaochao , Li Jing Shirley , Liu Huan , Du Liangming , Wu Yi , Huang Gui , Huang Ting , Zhang Yamei , Zhou Hui , Wang Xinrong , Chu Yiwen , Zhou Xikun
Published: September 2023

Chronic infection with the bacterial pathogen Pseudomonas aeruginosa often leads to coexistence of heterogeneous populations carrying diverse mutations. In particular, loss-of-function mutations affecting the quorum-sensing regulator LasR are often found in bacteria isolated from patients with lung chronic infection and cystic fibrosis. Here, we study the evolutionary dynamics of polymorphic P. aeruginosa populations using isolates longitudinally collected from patients with chronic obstructive pulmonary disease (COPD). We find that isolates deficient in production of different sharable extracellular products are sequentially selected in COPD airways, and lasR mutants appear to be selected first due to their quorum-sensing defects. Polymorphic populations including lasR mutants display survival advantages in animal models of infection and modulate immune responses. Our study sheds light on the multistage evolution of P. aeruginosa populations during their adaptation to host lungs.
Deterministic photon source interfaced with a programmable silicon-nitride integrated circuit
Authors: Wang Ying , Faurby Carlos F. D. , Ruf Fabian , Sund Patrik I. , Nielsen Kasper , Volet Nicolas , Heck Martijn J. R. , Bart Nikolai , Wieck Andreas D. , Ludwig Arne , Midolo Leonardo , Paesani Stefano , Lodahl Peter
Published: September 2023

We develop a quantum photonic platform that interconnects a high-quality quantum dot single-photon source and a low-loss photonic integrated circuit made in silicon nitride. The platform is characterized and programmed to demonstrate various multiphoton applications, including bosonic suppression laws and photonic entanglement generation. The results show a promising technological route forward to scale-up photonic quantum hardware.
Rapid emergence and transmission of virulence-associated mutations in the oral poliovirus vaccine following vaccination campaigns
Authors: Walter Katharine S. , Altamirano Jonathan , Huang ChunHong , Carrington Yuan J. , Zhou Frank , Andrews Jason R. , Maldonado Yvonne
Published: September 2023

There is an increasing burden of circulating vaccine-derived polioviruses (cVDPVs) due to the continued use of oral poliovirus vaccine (OPV). However, the informativeness of routine OPV VP1 sequencing for the early identification of viruses carrying virulence-associated reversion mutations has not been directly evaluated in a controlled setting. We prospectively collected 15,331 stool samples to track OPV shedding from children receiving OPV and their contacts for ten weeks following an immunization campaign in Veracruz State, Mexico and sequenced VP1 genes from 358 samples. We found that OPV was genetically unstable and evolves at an approximately clocklike rate that varies across serotypes and by vaccination status. Overall, 61% (11/18) of OPV-1, 71% (34/48) OPV-2, and 96% (54/56) OPV-3 samples with available data had evidence of a reversion at the key 5’ UTR attenuating position and 28% (13/47) of OPV-1, 12% (14/117) OPV-2, and 91% (157/173) OPV-3 of Sabin-like viruses had ≥1 known reversion mutations in the VP1 gene. Our results are consistent with previous work documenting rapid reversion to virulence of OPV and underscores the need for intensive surveillance following OPV use.
Allometrically scaling tissue forces drive pathological foreign-body responses to implants via Rac2-activated myeloid cells
Authors: Padmanabhan Jagannath , Chen Kellen , Sivaraj Dharshan , Henn Dominic , Kuehlmann Britta A. , Kussie Hudson C. , Zhao Eric T. , Kahn Anum , Bonham Clark A. , Dohi Teruyuki , Beck Thomas C. , Trotsyuk Artem A. , Stern-Buchbinder Zachary A. , Than Peter A. , Hosseini Hadi S. , Barrera Janos A. , Magbual Noah J. , Leeolou Melissa C. , Fischer Katharina S. , Tigchelaar Seth S. , Lin John Q. , Perrault David P. , Borrelli Mimi R. , Kwon Sun Hyung , Maan Zeshaan N. , Dunn James C. Y. , Nazerali Rahim , Januszyk Michael , Prantl Lukas , Gurtner Geoffrey C.
Published: September 2023

Small animals do not replicate the severity of the human foreign-body response (FBR) to implants. Here we show that the FBR can be driven by forces generated at the implant surface that, owing to allometric scaling, increase exponentially with body size. We found that the human FBR is mediated by immune-cell-specific RAC2 mechanotransduction signalling, independently of the chemistry and mechanical properties of the implant, and that a pathological FBR that is human-like at the molecular, cellular and tissue levels can be induced in mice via the application of human-tissue-scale forces through a vibrating silicone implant. FBRs to such elevated extrinsic forces in the mice were also mediated by the activation of Rac2 signalling in a subpopulation of mechanoresponsive myeloid cells, which could be substantially reduced via the pharmacological or genetic inhibition of Rac2. Our findings provide an explanation for the stark differences in FBRs observed in small animals and humans, and have implications for the design and safety of implantable devices.
The interface of condensates of the hnRNPA1 low-complexity domain promotes formation of amyloid fibrils
Authors: Linsenmeier Miriam , Faltova Lenka , Morelli Chiara , Capasso Palmiero Umberto , Seiffert Charlotte , Küffner Andreas M. , Pinotsi Dorothea , Zhou Jiangtao , Mezzenga Raffaele , Arosio Paolo
Published: September 2023

The maturation of liquid-like protein condensates into amyloid fibrils has been associated with several neurodegenerative diseases. However, the molecular mechanisms underlying this liquid-to-solid transition have remained largely unclear. Here we analyse the amyloid formation mediated by condensation of the low-complexity domain of hnRNPA1, a protein involved in amyotrophic lateral sclerosis. We show that phase separation and fibrillization are connected but distinct processes that are modulated by different regions of the protein sequence. By monitoring the spatial and temporal evolution of amyloid formation we demonstrate that the formation of fibrils does not occur homogeneously inside the droplets but is promoted at the interface of the condensates. We further show that coating the interface of the droplets with surfactant molecules inhibits fibril formation. Our results reveal that the interface of biomolecular condensates of hnRNPA1 promotes fibril formation, therefore suggesting interfaces as a potential novel therapeutic target against the formation of aberrant amyloids mediated by condensation.
Climate extremes likely to drive land mammal extinction during next supercontinent assembly
Authors: Farnsworth Alexander , Lo Y. T. Eunice , Valdes Paul J. , Buzan Jonathan R. , Mills Benjamin J. W. , Merdith Andrew S. , Scotese Christopher R. , Wakeford Hannah R.
Published: September 2023

Mammals have dominated Earth for approximately 55 Myr thanks to their adaptations and resilience to warming and cooling during the Cenozoic. All life will eventually perish in a runaway greenhouse once absorbed solar radiation exceeds the emission of thermal radiation in several billions of years. However, conditions rendering the Earth naturally inhospitable to mammals may develop sooner because of long-term processes linked to plate tectonics (short-term perturbations are not considered here). In ~250 Myr, all continents will converge to form Earth’s next supercontinent, Pangea Ultima. A natural consequence of the creation and decay of Pangea Ultima will be extremes in $$p_{\mathrm{CO}_2}$$

p

CO

2

due to changes in volcanic rifting and outgassing. Here we show that increased $$p_{\mathrm{CO}_2}$$

p

CO

2

, solar energy (F⨀; approximately +2.5% W m−2 greater than today) and continentality (larger range in temperatures away from the ocean) lead to increasing warming hostile to mammalian life. We assess their impact on mammalian physiological limits (dry bulb, wet bulb and Humidex heat stress indicators) as well as a planetary habitability index. Given mammals’ continued survival, predicted background $$p_{\mathrm{CO}_2}$$

p

CO

2

levels of 410–816 ppm combined with increased F⨀ will probably lead to a climate tipping point and their mass extinction. The results also highlight how global landmass configuration, $$p_{\mathrm{CO}_2}$$

p

CO

2

and F⨀ play a critical role in planetary habitability.
Nanopore sequencing of DNA-barcoded probes for highly multiplexed detection of microRNA, proteins and small biomarkers
Authors: Koch Caroline , Reilly-O’Donnell Benedict , Gutierrez Richard , Lucarelli Carla , Ng Fu Siong , Gorelik Julia , Ivanov Aleksandar P. , Edel Joshua B.
Published: September 2023

There is an unmet need to develop low-cost, rapid and highly multiplexed diagnostic technology platforms for quantitatively detecting blood biomarkers to advance clinical diagnostics beyond the single biomarker model. Here we perform nanopore sequencing of DNA-barcoded molecular probes engineered to recognize a panel of analytes. This allows for highly multiplexed and simultaneous quantitative detection of at least 40 targets, such as microRNAs, proteins and neurotransmitters, on the basis of the translocation dynamics of each probe as it passes through a nanopore. Our workflow is built around a commercially available MinION sequencing device, offering a one-hour turnaround time from sample preparation to results. We also demonstrate that the strategy can directly detect cardiovascular disease-associated microRNA from human serum without extraction or amplification. Due to the modularity of barcoded probes, the number and type of targets detected can be significantly expanded.
Distinguishing features of long COVID identified through immune profiling
Authors: Klein Jon , Wood Jamie , Jaycox Jillian R. , Dhodapkar Rahul M. , Lu Peiwen , Gehlhausen Jeff R. , Tabachnikova Alexandra , Greene Kerrie , Tabacof Laura , Malik Amyn A. , Silva Monteiro Valter , Silva Julio , Kamath Kathy , Zhang Minlu , Dhal Abhilash , Ott Isabel M. , Valle Gabrielee , Peña-Hernández Mario , Mao Tianyang , Bhattacharjee Bornali , Takahashi Takehiro , Lucas Carolina , Song Eric , McCarthy Dayna , Breyman Erica , Tosto-Mancuso Jenna , Dai Yile , Perotti Emily , Akduman Koray , Tzeng Tiffany J. , Xu Lan , Geraghty Anna C. , Monje Michelle , Yildirim Inci , Shon John , Medzhitov Ruslan , Lutchmansingh Denyse , Possick Jennifer D. , Kaminski Naftali , Omer Saad B. , Krumholz Harlan M. , Guan Leying , Dela Cruz Charles S. , van Dijk David , Ring Aaron M. , Putrino David , Iwasaki Akiko
Published: September 2023

Post-acute infection syndromes may develop after acute viral disease1. Infection with SARS-CoV-2 can result in the development of a post-acute infection syndrome known as long COVID. Individuals with long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions2–4. However, the biological processes that are associated with the development and persistence of these symptoms are unclear. Here 275 individuals with or without long COVID were enrolled in a cross-sectional study that included multidimensional immune phenotyping and unbiased machine learning methods to identify biological features associated with long COVID. Marked differences were noted in circulating myeloid and lymphocyte populations relative to the matched controls, as well as evidence of exaggerated humoral responses directed against SARS-CoV-2 among participants with long COVID. Furthermore, higher antibody responses directed against non-SARS-CoV-2 viral pathogens were observed among individuals with long COVID, particularly Epstein–Barr virus. Levels of soluble immune mediators and hormones varied among groups, with cortisol levels being lower among participants with long COVID. Integration of immune phenotyping data into unbiased machine learning models identified the key features that are most strongly associated with long COVID status. Collectively, these findings may help to guide future studies into the pathobiology of long COVID and help with developing relevant biomarkers.
Molecular mechanisms of inorganic-phosphate release from the core and barbed end of actin filaments
Authors: Oosterheert Wout , Blanc Florian E. C. , Roy Ankit , Belyy Alexander , Sanders Micaela Boiero , Hofnagel Oliver , Hummer Gerhard , Bieling Peter , Raunser Stefan
Published: September 2023

The release of inorganic phosphate (Pi) from actin filaments constitutes a key step in their regulated turnover, which is fundamental to many cellular functions. The mechanisms underlying Pi release from the core and barbed end of actin filaments remain unclear. Here, using human and bovine actin isoforms, we combine cryo-EM with molecular-dynamics simulations and in vitro reconstitution to demonstrate how actin releases Pi through a ‘molecular backdoor’. While constantly open at the barbed end, the backdoor is predominantly closed in filament-core subunits and opens only transiently through concerted amino acid rearrangements. This explains why Pi escapes rapidly from the filament end but slowly from internal subunits. In a nemaline-myopathy-associated actin variant, the backdoor is predominantly open in filament-core subunits, resulting in accelerated Pi release and filaments with drastically shortened ADP-Pi caps. Our results provide the molecular basis for Pi release from actin and exemplify how a disease-linked mutation distorts the nucleotide-state distribution and atomic structure of the filament.
Thermodynamic flow of radiative induced magneto modified Maxwell Sutterby fluid model at stretching sheet/cylinder
Authors: Abbas Nadeem , Shatanawi Wasfi , Hasan Fady , Mustafa Zead
Published: September 2023

A steady flow of Maxwell Sutterby fluid is considered over a stretchable cylinder. The magnetic Reynolds number is considered very high and induced magnetic and electric fields are applied on the fluid flow. Joule heating and radiation impacts are studied under the temperature-dependent properties of the liquid. Having the above assumptions, the mathematical model has been evolving via differential equations. The differential equations are renovated in the dimensionless form of ordinary differential equations using the appropriate transformations. The numerical results have been developed employing numerical techniques on the ordinary differential equations. The impact of involving physical factors on velocity, induced magneto hydrodynamic, and temperature function is debated in graphical and tabular form. The velocity profile is boosted by thicker momentum boundary layers, which are caused by higher values of the magnetic field factor. So, the fluid flow becomes higher velocity due to enlarging values of the magnetic field factor. Heat transfer factor and friction at surface factor boosted up for increment of $${\gamma }_{0}$$

γ
0

 (Magnetic field factor). The $${\gamma }_{0}$$

γ
0

(Magnetic field factor) is larger which better-quality of heat transfer at surface and also offered the results of friction factor boosting up in both cases of stretching sheet/cylinder. The $${\lambda }_{0}$$

λ
0

(Magnetic Prandtl number) increased which provided better-quality of heat transfer at surface.
Neural mechanism facilitating PM2.5-related cardiac arrhythmias through cardiovascular autonomic and calcium dysregulation in a rat model
Authors: Tsai Tsung-Ying , Lo Li-Wei , Lin Wei-Lun , Chou Yu-Hui , Cheng Wen-Han , Liu Shin-Hui , Yang Cheryl C. H. , Kuo Terry B. J. , Chen Shih-Ann
Published: September 2023

Particulate matter < 2.5 μm (PM2.5) exposure is associated with increased arrhythmia events and cardiovascular mortality, but the detailed mechanism remained elusive. In the current study, we aimed to investigate the autonomic alterations in a rodent model after acute exposure to PM2.5. Twelve male WKY rats were randomized to control and PM2.5 groups. All were treated with 2 exposures of oropharyngeal aerosol inhalations (1 μg PM2.5 per gram of body weight in 100 μL normal saline for the PM2.5 group) separately by 7 days. Polysomnography and electrocardiography were surgically installed 7 days before oropharyngeal inhalation and monitored for 7 days after each inhalation. Physiologic monitors were used to define active waking (AW), quiet sleep (QS), and paradoxical sleep (PS). Autonomic regulations were measured by heart rate variability (HRV). The protein expression of ventricular tissue of the 2 groups was compared at the end of the experiment. In sleep pattern analysis, QS interruption of the PM2.5 group was significantly higher than the control group (0.52 ± 0.13 events/min, 0.35 ± 0.10 events/min, p = 0.002). In HRV analysis, the LF/HF was significantly higher for the PM2.5 group than the control group (1.15 ± 0.16, 0.64± 0.30, p = 0.003), largely driven by LF/HF increase during the QS phase. Ionic channel protein expression from Western blots showed that the PM2.5 group had significantly lower L-type calcium channel and higher SERCA2 and rectifier potassium channel expressions than the control group, respectively. Our results showed that acute PM2.5 exposure leads to interruption of QS, sympathetic activation, and recruitment of compensatory calcium handling proteins. The autonomic and calcium dysregulations developed after PM 2.5 exposure may explain the risk of sleep disturbance and sleep-related arrhythmia.
Extrusion and characterization of recycled polyethylene terephthalate (rPET) filaments compounded with chain extender and impact modifiers for material-extrusion additive manufacturing
Authors: Rashwan Ola , Koroneos Zachary , Townsend Trent G. , Caputo Matthew P. , Bylone Robert J. , Wodrig Brennan , Cantor Kirk
Published: September 2023

The continuous growth of annual production and consumption of polyethylene terephthalate (PET) is coined with increasing waste that leaks into the environment, landfills and oceans as microplastics and nano plastics fragments. Upcycling the recycled PET to make a feedstock for the fast-growing material-extrusion additive manufacturing (MEX-AM) technology can contribute to the solution and supports the concept of sustainable materials. In this work, extrudable filaments comprising recycled polyethylene terephthalate (rPET) with low-cost additives, such as pyromellitic dianhydride (PMDA) as a chain extender, styrene-ethylene-butylene-styrene terpolymer functionalized with maleic anhydride (SEBS-g-MA), a thermal modifier and toughening agent, ethylene-ethyl acrylate-glycidyl methacrylate terpolymer (E-EA-GMA), a functional reactive elastomeric impact modifier and ethylene-ethyl-acrylate (EEA), a non-reactive elastomeric impact modifier, have been fabricated using the twin-screw extruder. The optimum extrusion process parameters for producing uniform filaments of different rPET compounded formulations have been identified, this includes the extrusion die temperature of 280 °C and the screw speed of 150 ± 3 rpm. The compounded filaments are then printed into standard ASTM test specimens for thermal characterization and mechanical characterization, including glass transition and melting temperatures, crystallinity and crystallization temperature, tensile strength, tensile modulus, ductility, flexural strength, and Izod impact energy. Furthermore, the melt flow index for the filaments was measured. More significantly, the experimental data showed that compounding rPET with such additives in the reactive twin-screw extrusion process results in uniform filaments that display advantageous thermal and mechanical properties and can be used as a feedstock in the MEX-AM technology. This study suggests that compounding the recycled PET pellets with low-cost additives while extruding them into filaments for MEX-AM offers excellent potential to make high-value-added customized products from a sustainable polymer feedstock, such as prototyping, tooling, testing components or end-use internal components for small machines and cars.
The chloroplast protein HCF164 is predicted to be associated with Coffea SH9 resistance factor against Hemileia vastatrix
Authors: Guerra-Guimarães Leonor , Pinheiro Carla , Oliveira Ana Sofia F. , Mira-Jover Andrea , Valverde Javier , Guedes Fernanda A. de F. , Azevedo Herlander , Várzea Vitor , Muñoz Pajares Antonio Jesús
Published: September 2023

To explore the connection between chloroplast and coffee resistance factors, designated as SH1 to SH9, whole genomic DNA of 42 coffee genotypes was sequenced, and entire chloroplast genomes were de novo assembled. The chloroplast phylogenetic haplotype network clustered individuals per species instead of SH factors. However, for the first time, it allowed the molecular validation of Coffea arabica as the maternal parent of the spontaneous hybrid “Híbrido de Timor”. Individual reads were also aligned on the C. arabica reference genome to relate SH factors with chloroplast metabolism, and an in-silico analysis of selected nuclear-encoded chloroplast proteins (132 proteins) was performed. The nuclear-encoded thioredoxin-like membrane protein HCF164 enabled the discrimination of individuals with and without the SH9 factor, due to specific DNA variants linked to chromosome 7c (from C. canephora-derived sub-genome). The absence of both the thioredoxin domain and redox-active disulphide center in the HCF164 protein, observed in SH9 individuals, raises the possibility of potential implications on redox regulation. For the first time, the identification of specific DNA variants of chloroplast proteins allows discriminating individuals according to the SH profile. This study introduces an unexplored strategy for identifying protein/genes associated with SH factors and candidate targets of H. vastatrix effectors, thereby creating new perspectives for coffee breeding programs.
Loss of HES1 expression is associated with extracellular matrix remodeling and tumor immune suppression in KRAS mutant colon adenocarcinomas
Authors: Wang Lei , Gu Wenchao , Zou Bingqing , Kalady Matthew , Xin Wei , Zhou Lan
Published: September 2023

The loss of HES1, a canonical Notch signaling target, may cooperate with KRAS mutations to remodel the extracellular matrix and to suppress the anti-tumor immune response. While HES1 expression is normal in benign hyperplastic polyps and normal colon tissue, HES1 expression is often lost in sessile serrated adenomas/polyps (SSAs/SSPs) and colorectal cancers (CRCs) such as those right-sided CRCs that commonly harbor BRAF or KRAS mutations. To develop a deeper understanding of interaction between KRAS and HES1 in colorectal carcinogenesis, we selected microsatellite stable (MSS) and KRAS mutant or KRAS wild type CRCs that show aberrant expression of HES1 by immunohistochemistry. By comparing the transcriptional landscapes of microsatellite stable (MSS) CRCs with or without nuclear HES1 expression, we investigated differentially expressed genes and activated pathways. We identified pathways and markers in the extracellular matrix and immune microenvironment that are associated with mutations in KRAS. We found that loss of HES1 expression positively correlated with matrix remodeling and epithelial-mesenchymal transition but negatively correlated with tumor cell proliferation. Furthermore, loss of HES1 expression in KRAS mutant CRCs correlates with a higher M2 macrophage polarization and activation of IL6 and IL10 immunosuppressive signature. Identifying these HES1-related markers may be useful for prognosis stratification and developing treatment for KRAS-mutant CRCs.
Cracking and damage analysis of a masonry structure based on joint masonry model caused by a obliquely undercrossing tunnel
Authors: Jin Junwei , Zhang Qinglong , Fu Boyi , Chen Jian , Li Mingyu , Jin Qianqian
Published: September 2023

The damage variation of a masonry structure during shield tunneling has been investigated. Furthermore, the damage degree of the masonry building has been investigated by combining the field measurement, finite element method results, and theoretical method. The results show that compared with the theoretical calculation method LSTM, the method provide by this paper can give the detail damage location of the masonry structure caused by shield construction. Due to the existence of door and window openings, the result of JMM is larger than LSTM result, the differences can be modified by concept of “characteristic tensile strain”. The wall of the masonry building encounter the shield face first suffers more damage than the later ones. At the beginning of tunnlling, the damage were generated from a small area at the bottom for wall 1, but a larger area at the top of the building for wall 2. The damage area increase more at the top of the building as tunneling advanced, but the maximum damage occurred at the bottom of the building.
Convergence of the Laplace and the alternative multipole expansion approximation series for the Coulomb potential
Authors: Jobunga E. O. , Wandera C. O. , Okeyo O. S.
Published: September 2023

Multipole expansion is a powerful technique used in many-body physics to solve dynamical problems involving correlated interactions between constituent particles. The Laplace multipole expansion series of the Coulomb potential is well established in literature. We compare its convergence with our recently developed perturbative and analytical alternative multipole expansion series of the Coulomb potential. In our working, we confirm that the Laplace and the analytical alternative multipole expansion series are equivalent as expected. In terms of performance, the perturbative alternative multipole expansion series underapproximate the expected results to some extent while the Laplace and the analytical alternative multipole expansion series yield results which are relatively accurate but oscillatory in nature even with a higher number of angular momentum terms employed. As a practical example, we have evaluated the Slater double integrals for two-electron systems using the multipole expansion techniques and a mean field approximation. The estimated results show that only spherical interactions are dominant while the higher-order interactions are negligible. To highlight the discrepancy in the application of each of the formulations of the multipole expansion series for the electron-electron interaction potential, an estimation of the non-relativistic groundstate energies of some helium-like systems, evaluated using the spherical approximation of the multipole potential, is provided. Our findings are likely to be useful in the treatment of the Coulomb potential in electronic structure calculations as well as in celestial mechanics.
Effect of forest-based biochar on maturity indices and bio-availability of heavy metals during the composting process of organic fraction of municipal solid waste (OFMSW)
Authors: Hassanzadeh Moghimi Omid , Nabi Bidhendi Gholamreza , Daryabeigi Zand Ali , Rabiee Abyaneh Maryam , Nabi Bidhendi Amir
Published: September 2023

The main objective of this study was to investigate the effect of biochar on the composting process of the organic fraction of municipal solid waste (OFMSW) under real conditions. Different doses of biochar (1%, 3%, and 5%) were mixed with compost piles to evaluate the variation of temperature, moisture content (MC), organic matter (OM), carbon (C), nitrogen (N), C/N ratio, and heavy metal (HM) contents in comparison with the control treatment (with 0% biochar addition). The results of this study showed that the compost piles combined with different doses of biochar had higher MC. The use of biochar as an additive, even at low doses (1%), was able to increase the compost quality through the reduction of N losses during the composting process. The highest reduction of OM during the composting process was observed in the control pile (without biochar addition) by 48.06%, whereas biochar affected the biodegradability of OM and prevented the reduction of nutrients during the composting process under real conditions. The contents of HMs (Pb, Zn, Ni, Cd, and Cu) showed a significant reduction in all of the compost piles combined with biochar in comparison with the control treatment. Considering that in terms of all compost quality indicators, the piles combined with biochar can regarded as high standard product, the composts obtained from combining the OFMSW with different biochar doses have desirable features to be used as an amendment agent to improve agricultural soil quality.