bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of soil properties and bulk δ15N to assess decadal changes in floodplain denitrification following restoration
Authors: Galella Joseph G. , Rahman Md. Moklesur , Yaculak Alexis M. , Peipoch Marc , Kan Jinjun , Sena Matthew , Joshi Bisesh , Kaushal Sujay S. , Inamdar Shreeram
Published: October 2024

Stream and floodplain restoration is a popular billion‐dollar industry in the United States, with many restorations being conducted to satisfy water pollution regulations and nutrient reduction goals. The long‐term efficacy of these restorations is, however, not well studied, and key soil metrics that can be used for performance assessments have not been developed. We evaluated a chronosequence of 12 restoration sites spanning an age range of 0–22 years to assess changes in denitrification rates and associated soil parameters. Restored versus unrestored reaches were compared for denitrification rate and functional gene nosZ, bulk soil δ15N, soil organic carbon (SOC), soil organic matter (SOM), bulk density, and soil moisture. Denitrification, SOM, SOC, and soil moisture were all found to increase with site age at restored sites, with the largest increase for the 10–22 age category. Bulk density decreased with time, with a significant decrease in restored floodplain soils. Bulk soil δ15N was highest immediately after restoration, decreased with restoration age, and was not positively correlated with denitrification. This may reduce its potential as a proxy for denitrification. Overall, this study reveals that selected soil metrics (SOC, SOM, soil moisture, and bulk density) could serve as a valuable proxy for denitrification and could help assess the denitrification effectiveness of floodplain restorations at the decadal time scales. Ideally, the soil metrics should be combined with other short‐term assessment measures, such as those for stream and groundwaters, for a robust performance assessment of restored floodplains.
How Does the Adoption of e‐Commerce Impact the Selling Prices of Agricultural Products? Empirical Evidence From Apple Farmers in China
Authors: Liu Min , Liu Tianjun , Ren Yanjun , Wu Leslie
Published: October 2024

The sale of products through e‐commerce is emerging in rural China, and it cuts out intermediaries and allows farmers direct access to the market. To understand how adopting e‐commerce impacts the selling prices of agricultural products and who benefits more from adopting e‐commerce, we interviewed 480 apple farmers from the three representative provinces in China. The Propensity Score Matching approach combined with sensitivity analysis is employed to address the potential self‐selection bias in estimating the impacts of adopting e‐commerce. We find that adopting of e‐commerce drives significant increases in the selling prices of apple products, including the average price, the maximum price and the minimum price. The heterogeneity analysis suggests that the adoption of e‐commerce has significant heterogeneous effects on selling prices across various ages and education of household heads, land area, distance to the local town centre and social capital. The analysis of potential pathways reveals that increases in selling prices are attributed to farmers achieving more marketing flexibility through more adaptable sale times and extended sale periods due to adopting e‐commerce. The research findings provide rigorous evidence on optimal future policy design regarding the development of rural e‐commerce for poverty alleviation in China and other developing countries.
A novel RAV transcription factor from pear interacts with viral RNA‐silencing suppressors to inhibit viral infection
Authors: Xie Yin‐Shuai , Zeng Qi , Huang Wen‐Ting , Wang Jin‐Ying , Li Han‐Wei , Yu Shang‐Zhen , Liu Can , Zhang Xue‐Qing , Feng Chen‐Lu , Zhang Wen‐Hao , Li Tian‐Zhong , Cheng Yu‐Qin
Published: October 2024

In plants, RNA silencing constitutes a strong defense against viral infection, which viruses counteract with RNA‐silencing suppressors (RSSs). Understanding the interactions between viral RSSs and host factors is crucial for elucidating the molecular arms race between viruses and host plants. We report that the helicase motif (Hel) of the replicase encoded by apple stem grooving virus (ASGV)—the main virus affecting pear trees in China—is an RSS that can inhibit both local and systemic RNA silencing, possibly by binding double‐stranded (ds) siRNA. The transcription factor related to ABSCISIC ACID INSENSITIVE3/VIVIPAROUS1 from pear (PbRAV1) enters the cytoplasm and binds Hel through its C terminus, thereby attenuating its RSS activity by reducing its binding affinity to 21‐ and 24‐nt ds siRNA, and suppressing ASGV infection. PbRAV1 can also target p24, an RSS encoded by grapevine leafroll‐associated virus 2 (GLRaV‐2), with similar negative effects on p24's suppressive function and inhibition of GLRaV‐2 infection. Moreover, like the positive role of the PbRAV1 homolog from grapevine (VvRAV1) in p24's previously reported RSS activity, ASGV Hel can also hijack VvRAV1 and employ the protein to sequester 21‐nt ds siRNA, thereby enhancing its own RSS activity and promoting ASGV infection. Furthermore, PbRAV1 neither interacts with CP, an RSS encoded by grapevine inner necrosis virus, nor has any obvious effect on CP's RSS activity. Our results identify an RSS encoded by ASGV and demonstrate that PbRAV1, representing a novel type of RAV transcription factor, plays a defensive role against viral infection by targeting viral RSSs.
A modified approach to portal placement for arthroscopic management of osteochondritis dissecans lesions of the tarsocrural joint in 15 dogs (19 tarsi)
Authors: Cruciani Benoît , Gros Lucile , Ragetly Guillaume
Published: October 2024

Objective

To describe the surgical technique and outcomes of arthroscopic treatment for talar osteochondritis dissecans (OCD) in dogs, using scope and instrument portals placed on the same side of the joint as the lesion.

Study design

Retrospective case series.

Animals

Fifteen client‐owned dogs (19 tarsi).

Methods

The records of dogs with talar OCD lesions managed by arthroscopy using this modified approach to portal placement were reviewed. Signalment, owner‐completed questionnaires—the Canine Brief Pain Inventory (CBPI) and a visual analog scale (VAS)—together with clinical and imaging data, surgical techniques, and postoperative complications were recorded. Mid‐ to long‐term outcomes (over 6 months) were assessed using orthopedic examinations, osteoarthritis radiographic scores, and owner‐completed questionnaires.

Results

Visualization of the affected articular structures was adequate in all cases. The multiple OCD fragments identified on CT scans were removed without intraoperative complication in 17 tarsi. Mini‐arthrotomy was performed in one dog and mini‐tenotomy of the deep digital flexor sheath was performed in another. Minor postoperative complications (synovial cysts) were reported in four cases. Mid‐ to long‐term outcomes were good to excellent in 11 of the 14 dogs with substantial improvement in lameness, CBPI, and VAS scores compared with preoperative results. Degenerative joint disease progression was observed in 10 of the 14 cases.

Conclusion

The modified arthroscopic technique resulted in few complications, rapid clinical improvement, and full or acceptable function in most cases.

Clinical significance

This modified approach to portal placement is an appealing and suitable alternative to the approach described previously for managing tarsal OCD lesions.
Experience‐driven competition in neural reorganization after stroke
Authors: Jones Theresa A. , Nemchek Victoria , Fracassi Michela
Published: October 2024

Behavioural experiences interact with regenerative responses to shape patterns of neural reorganization after stroke. This review is focused on the competitive nature of these behavioural experience effects. Interactions between learning‐related plasticity and regenerative reactions have been found to underlie the establishment of new compensatory behaviours and the efficacy of motor rehabilitative training in rodent stroke models. Learning in intact brains depends on competitive and cooperative mechanisms of synaptic plasticity. Synapses are added in response to learning and selectively maintained and strengthened via activity‐dependent competition. Long‐term memories for experiences that occur closely in time can be weakened or enhanced by competitive or cooperative interactions in the time‐dependent process of stabilizing synaptic changes. Rodent stroke model findings suggest that compensatory reliance on the non‐paretic hand after stroke can shape and stabilize synaptic reorganization patterns in both hemispheres, to compete with the capacity for experiences of the paretic side to do so. However, the competitive edge of the non‐paretic side can be countered by overlapping experiences of the paretic hand, and might even be shifted in a cooperative direction with skilfully coordinated bimanual experience. Advances in the basic understanding of learning‐related synaptic competition are helping to inform the basis of experience‐dependent variations in stroke outcome.

image
Noninvasive modulation of the hippocampal-entorhinal complex during spatial navigation in humans
Authors: Beanato Elena , Moon Hyuk-June , Windel Fabienne , Vassiliadis Pierre , Wessel Maximillian J. , Popa Traian , Pauline Menoud , Neufeld Esra , De Falco Emanuela , Gauthier Baptiste , Steiner Melanie , Blanke Olaf , Hummel Friedhelm C.
Published: October 2024

Because of the depth of the hippocampal-entorhinal complex (HC-EC) in the brain, understanding of its role in spatial navigation via neuromodulation was limited in humans. Here, we aimed to better elucidate this relationship in healthy volunteers, using transcranial temporal interference electric stimulation (tTIS), a noninvasive technique allowing to selectively neuromodulate deep brain structures. We applied tTIS to the right HC-EC in either continuous or intermittent theta-burst stimulation patterns (cTBS or iTBS), compared to a control condition, during a virtual reality–based spatial navigation task and concomitant functional magnetic resonance imaging. iTBS improved spatial navigation performance, correlated with hippocampal activity modulation, and decreased grid cell–like activity in EC. Collectively, these data provide the evidence that human HC-EC activity can be directly and noninvasively modulated leading to changes of spatial navigation behavior. These findings suggest promising perspectives for patients suffering from cognitive impairment such as following traumatic brain injury or dementia.
Calcite precipitation: The forgotten piece of lakes’ carbon cycle
Authors: Many Gaël , Escoffier Nicolas , Perolo Pascal , Bärenbold Fabian , Bouffard Damien , Perga Marie-Elodie
Published: October 2024

Lakes emit substantial amounts of carbon dioxide (CO
2
) into the atmosphere, but why they do remains debated. The long-standing vision of lakes as solely respirators of the organic matter leaking from the soils has been challenged by evidence that inorganic carbon produced by weathering of the catchment bedrock could also support lake CO
2
emissions. How inorganic carbon inputs ultimately generate lake CO
2
outgassing remains a blind spot. We develop and introduce a calcite module in a coupled one-dimensional physical-biogeochemical model that we use to simulate the carbon cycle of the large Lake Geneva over the past 40 years. We mechanistically demonstrate how the so-far neglected process of calcite precipitation boosts net CO
2
emissions at the annual scale. Far from being anecdotal, we show that calcite precipitation could explain CO
2
outgassing across various lakes globally, including some of the largest lakes in the world.
Amyloid fibril structures and ferroptosis activation induced by ALS-causing SOD1 mutations
Authors: Wang Li-Qiang , Ma Yeyang , Zhang Mu-Ya , Yuan Han-Ye , Li Xiang-Ning , Xia Wencheng , Zhao Kun , Huang Xi , Chen Jie , Li Dan , Zou Liangyu , Wang Zhengzhi , Le Weidong , Liu Cong , Liang Yi
Published: October 2024

Over 200 genetic mutations in copper-zinc superoxide dismutase (SOD1) have been linked to amyotrophic lateral sclerosis (ALS). Among these, two ALS-causing mutants, histidine-46→arginine (H46R) and glycine-85→arginine (G85R), exhibit a decreased capacity to bind metal ions. Here, we report two cryo–electron microscopy structures of amyloid fibrils formed by H46R and G85R. These mutations lead to the formation of amyloid fibrils with unique structures distinct from those of the native fibril. The core of these fibrils features a serpentine arrangement with seven or eight β strands, secured by a hydrophobic cavity and a salt bridge between arginine-85 and aspartic acid–101 in the G85R fibril. We demonstrate that these mutant fibrils are notably more toxic and capable of promoting the aggregation of wild-type SOD1 more effectively, causing mitochondrial impairment and activating ferroptosis in cell cultures, compared to wild-type SOD1 fibrils. Our study provides insights into the structural mechanisms by which SOD1 mutants aggregate and induce cytotoxicity in ALS.
Decisive role of mDia-family formins in cell cortex function of highly adherent cells
Authors: Scholz Jonas , Stephan Till , Pérez Aina Gallemí , Csiszár Agnes , Hersch Nils , Fischer Lisa S. , Brühmann Stefan , Körber Sarah , Litschko Christof , Mijanovic Lucija , Kaufmann Thomas , Lange Felix , Springer Ronald , Pich Andreas , Jakobs Stefan , Peckham Michelle , Tarantola Marco , Grashoff Carsten , Merkel Rudolf , Faix Jan
Published: October 2024

Cortical formins, pivotal for the assembly of linear actin filaments beneath the membrane, exert only minor effects on unconfined cell migration of weakly and moderately adherent cells. However, their impact on migration and mechanostability of highly adherent cells remains poorly understood. Here, we demonstrate that loss of cortical actin filaments generated by the formins mDia1 and mDia3 drastically compromises cell migration and mechanics in highly adherent fibroblasts. Biophysical analysis of the mechanical properties of the mutant cells revealed a markedly softened cell cortex in the poorly adherent state. Unexpectedly, in the highly adherent state, associated with a hyperstretched morphology with exaggerated focal adhesions and prominent high-strain stress fibers, they exhibited even higher cortical tension compared to control. Notably, misguidance of intracellular forces, frequently accompanied by stress-fiber rupture, culminated in the formation of tension- and contractility-induced macroapertures, which was instantly followed by excessive lamellipodial protrusion at the periphery, providing critical insights into mechanotransduction of mechanically stressed and highly adherent cells.
Metropolitan-scale heralded entanglement of solid-state qubits
Authors: Stolk Arian J. , van der Enden Kian L. , Slater Marie-Christine , te Raa-Derckx Ingmar , Botma Pieter , van Rantwijk Joris , Biemond J. J. Benjamin , Hagen Ronald A. J. , Herfst Rodolf W. , Koek Wouter D. , Meskers Adrianus J. H. , Vollmer René , van Zwet Erwin J. , Markham Matthew , Edmonds Andrew M. , Geus J. Fabian , Elsen Florian , Jungbluth Bernd , Haefner Constantin , Tresp Christoph , Stuhler Jürgen , Ritter Stephan , Hanson Ronald
Published: October 2024

A key challenge toward future quantum internet technology is connecting quantum processors at metropolitan scale. Here, we report on heralded entanglement between two independently operated quantum network nodes separated by 10 kilometers. The two nodes hosting diamond spin qubits are linked with a midpoint station via 25 kilometers of deployed optical fiber. We minimize the effects of fiber photon loss by quantum frequency conversion of the qubit-native photons to the telecom L-band and by embedding the link in an extensible phase-stabilized architecture enabling the use of the loss-resilient single-click entangling protocol. By capitalizing on the full heralding capabilities of the network link in combination with real-time feedback logic on the long-lived qubits, we demonstrate the delivery of a predefined entangled state on the nodes irrespective of the heralding detection pattern. Addressing key scaling challenges and being compatible with different qubit systems, our architecture establishes a generic platform for exploring metropolitan-scale quantum networks.
Hybridized and engineered microbe for catalytic generation of peroxynitrite and cancer immunotherapy under sonopiezo initiation
Authors: Wang Liping , Ji Penghao , Yu Jiadie , Qiu Shuwen , An Bolin , Huo Minfeng , Shi Jianlin
Published: October 2024

Living therapeutics is an emerging antitumor modality by living microorganisms capable of selective tropism and effective therapeutics. Nevertheless, primitive microbes could only present limited therapeutic functionalities against tumors. Hybridization of the microbes with multifunctional nanocatalysts is of great significance to achieve enhanced tumor catalytic therapy. In the present work, nitric oxide synthase (NOS)–engineered
Escherichia coli
strain MG1655 (NOBac) was used to hybridize with the sonopiezocatalytic BaTiO
3
nanoparticles (BTO NPs) for efficient tumor-targeted accumulation and antitumor therapy. Under ultrasound irradiation, superoxide anions created by the piezocatalytic reaction of BTO NPs could immediately react with nitric oxide (NO) generated from NOBac to produce highly oxidative peroxynitrite ONOO
−
species in cascade, resulting in robust tumor piezocatalytic therapeutic efficacy, prompting prominent and sustained antitumoral immunoactivation simultaneously. The present work presents a promising cancer immunotherapy based on the engineered and hybridized microbes for highly selective and sonopiezo-controllable tumor catalytic therapy.
Reducing the mitochondrial oxidative burden alleviates lipid-induced muscle insulin resistance in humans
Authors: Fiorenza Matteo , Onslev Johan , Henríquez-Olguín Carlos , Persson Kaspar W. , Hesselager Sofie A. , Jensen Thomas E. , Wojtaszewski Jørgen F. P. , Hostrup Morten , Bangsbo Jens
Published: October 2024

Preclinical models suggest mitochondria-derived oxidative stress as an underlying cause of insulin resistance. However, it remains unknown whether this pathophysiological mechanism is conserved in humans. Here, we used an invasive in vivo mechanistic approach to interrogate muscle insulin action while selectively manipulating the mitochondrial redox state in humans. To this end, we conducted insulin clamp studies combining intravenous infusion of a lipid overload with intake of a mitochondria-targeted antioxidant (mitoquinone). Under lipid overload, selective modulation of mitochondrial redox state by mitoquinone enhanced insulin-stimulated glucose uptake in skeletal muscle. Mechanistically, mitoquinone did not affect canonical insulin signaling but augmented insulin-stimulated glucose transporter type 4 (GLUT4) translocation while reducing the mitochondrial oxidative burden under lipid oversupply. Complementary ex vivo studies in human muscle fibers exposed to high intracellular lipid levels revealed that mitoquinone improves features of mitochondrial bioenergetics, including diminished mitochondrial H
2
O
2
emission. These findings provide translational and mechanistic evidence implicating mitochondrial oxidants in the development of lipid-induced muscle insulin resistance in humans.
Self-powered visualized tactile-acoustic sensor for accurate artificial perception with high brightness and record-low detection limit
Authors: Su Li , Kuang Shuangyang , Zhao Yong , Li Junhuan , Zhao Guodong , Wang Zhong Lin , Zi Yunlong
Published: October 2024

The growth of the Internet of Things has focused attention on visualized sensors as a key technology. However, it remains challenging to achieve high sensing accuracy and self-power ability. Here, we propose a self-powered visualized tactile-acoustic sensor (SVTAS) based on an elaborated triboelectrification-induced electroluminescence (TIEL) unit. To date, it features a high brightness of 0.5 mW cm
−2
(32 cd m
−2
) and a record-low detection limit of 0.5 kPa in horizontal-sliding mode. Meanwhile, the SVTAS is applicable to convert acoustic waves into TIEL signals in contact-separation mode, showing the highest response to the 44.07 Hz sound, a high signal-to-noise ratio of 8.7 dB
−1
, and an ultrafast response time of 0.8 ms. Furthermore, advanced artificial visualized perception systems are constructed with excellent performance in recognizing motion trajectories and human speech with different words/sentences. This work paves the way for the highly efficient and sustainable development of new-generation self-powered visualized perception systems, contributing a solution to wireless communication free from electromagnetic interference.
Closing the inland water carbon cycle
Authors: Middelburg Jack J.
Published: October 2024

Inland water carbon dioxide emissions mirror the ocean’s carbon uptake and are driven not only by ecosystem heterotrophy but also by chemical equilibration and calcification.
Advancing scientific discovery with the aid of robotics
Authors: Matsiko Amos
Published: October 2024

Robots can be powerful tools to advance basic scientific discovery.
Protumoral lipid droplet–loaded macrophages are enriched in human glioblastoma and can be therapeutically targeted
Authors: Governa Valeria , de Oliveira Kelin Gonçalves , Bång-Rudenstam Anna , Offer Svenja , Cerezo-Magaña Myriam , Li Jiaxin , Beyer Sarah , Johansson Maria C. , Månsson Ann-Sofie , Edvardsson Charlotte , Durmo Faris , Gustafsson Emma , Boukredine Axel , Jeannot Pauline , Schmidt Katja , Gezelius Emelie , Menard Julien A. , Garza Raquel , Jakobsson Johan , de Neergaard Therese , Sundgren Pia C. , Tiihonen Aliisa M. , Haapasalo Hannu , Rautajoki Kirsi J. , Nordenfelt Pontus , Darabi Anna , Forsberg-Nilsson Karin , Pietras Alexander , Talbot Hugo , Bengzon Johan , Belting Mattias
Published: October 2024

Glioblastoma presents a formidable clinical challenge because of its complex microenvironment. Here, we characterized tumor-associated foam cells (TAFs), a type of lipid droplet–loaded macrophage, in human glioblastoma. Through extensive analyses of patient tumors, together with in vitro and in vivo investigations, we found that TAFs exhibit distinct protumorigenic characteristics related to hypoxia, mesenchymal transition, angiogenesis, and impaired phagocytosis, and their presence correlates with worse outcomes for patients with glioma. We further demonstrated that TAF formation is facilitated by lipid scavenging from extracellular vesicles released by glioblastoma cells. We found that targeting key enzymes involved in lipid droplet formation, such as diacylglycerol
O
-acyltransferase or long-chain acyl-CoA synthetase, effectively disrupted TAF functionality. Together, these data highlight TAFs as a prominent immune cell population in glioblastoma and provide insights into their contribution to the tumor microenvironment. Disrupting lipid droplet formation to target TAFs may represent an avenue for future therapeutic development for glioblastoma.
ARGONAUT-IV: susceptibility of carbapenemase-producing
Klebsiella pneumoniae
to the oral bicyclic boronate β-lactamase inhibitor ledaborbactam combined with ceftibuten
Authors: Jacobs Michael R. , Good Caryn E. , Abdelhamed Ayman M. , Mack Andrew R. , Bethel Christopher R. , Marshall Steven H. , Hujer Andrea M. , Hujer Kristine M. , Patel Robin , van Duin David , Fowler Vance G. , Rhoads Daniel D. , Six David A. , Moeck Greg , Uehara Tsuyoshi , Papp-Wallace Krisztina M. , Bonomo Robert A.
Published: October 2024

Ledaborbactam (formerly VNRX-5236), a bicyclic boronate β-lactamase inhibitor with activity against class A, C, and D β-lactamases, is under development as an orally bioavailable etzadroxil prodrug (VNRX-7145) in combination with ceftibuten for the treatment of urinary tract infections. At ceftibuten breakpoints of ≤1 mg/L (EUCAST) and ≤8 mg/L (CLSI), 92.5% and 99.0%, respectively, of 200 carbapenem-resistant
Klebsiella pneumoniae
isolates, predominantly
K. pneumoniae
carbapenemase producing, were susceptible to ceftibuten-ledaborbactam (ledaborbactam tested at a fixed concentration of 4 mg/L) compared to 4.5% and 30.5%, respectively, to ceftibuten alone.
C→U transition biases in SARS-CoV-2: still rampant 4 years from the start of the COVID-19 pandemic
Authors: Simmonds Peter
Published: October 2024

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the pandemic and post-pandemic periods has been characterized by rapid adaptive changes that confer immune escape and enhanced human-to-human transmissibility. Sequence change is additionally marked by an excess number of C→U transitions suggested as being due to host-mediated genome editing. To investigate how these influence the evolutionary trajectory of SARS-CoV-2, 2,000 high-quality, coding complete genome sequences of SARS-CoV-2 variants collected pre-September 2020 and from each subsequently appearing alpha, delta, BA.1, BA.2, BA.5, XBB, EG, HK, and JN.1 lineages were downloaded from NCBI Virus in April 2024. C→U transitions were the most common substitution during the diversification of SARS-CoV-2 lineages over the 4-year observation period. A net loss of C bases and accumulation of U’s occurred at a constant rate of approximately 0.2%–0.25%/decade. C→U transitions occurred in over a quarter of all sites with a C (26.5%; range 20.0%–37.2%) around five times more than observed for the other transitions (5.3%–6.8%). In contrast to an approximately random distribution of other transitions across the genome, most C→U substitutions occurred at statistically preferred sites in each lineage. However, only the most C→U polymorphic sites showed evidence for a preferred 5′U context previously associated with APOBEC 3A editing. There was a similarly weak preference for unpaired bases suggesting much less stringent targeting of RNA than mediated by A3 deaminases in DNA editing. Future functional studies are required to determine editing preferences, impacts on replication fitness
in vivo
of SARS-CoV-2 and other RNA viruses, and impact on host tropism.

IMPORTANCE

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the pandemic and post-pandemic periods has shown a remarkable capacity to adapt and evade human immune responses and increase its human-to-human transmissibility. The genome of SARS-CoV-2 is also increasingly scarred by the effects of multiple C→U mutations from host genome editing as a cellular defense mechanism akin to restriction factors for retroviruses. Through the analysis of large data sets of SARS-CoV-2 isolate sequences collected throughout the pandemic period and beyond, we show that C→U transitions have driven a base compositional change over time amounting to a net loss of C bases and accumulation of U’s at a rate of approximately 0.2%–0.25%/decade. Most C→U substitutions occurred in the absence of the preferred upstream-base context or targeting of unpaired RNA bases previously associated with the host RNA editing protein, APOBEC 3A. The analyses provide a series of testable hypotheses that can be experimentally investigated in the future.
Unprecedented N
2
O production by nitrate-ammonifying
Geobacteraceae
with distinctive N
2
O isotopocule signatures
Authors: Xu Zhenxing , Hattori Shohei , Masuda Yoko , Toyoda Sakae , Koba Keisuke , Yu Pei , Yoshida Naohiro , Du Zong-Jun , Senoo Keishi
Published: October 2024

Dissimilatory nitrate reduction to ammonium (DNRA), driven by nitrate-ammonifying bacteria, is an increasingly appreciated nitrogen-cycling pathway in terrestrial ecosystems. This process reportedly generates nitrous oxide (N
2
O), a strong greenhouse gas with ozone-depleting effects. However, it remains poorly understood how N
2
O is produced by environmental nitrate-ammonifiers and how to identify DNRA-derived N
2
O. In this study, we characterize two novel enzymatic pathways responsible for N
2
O production in
Geobacteraceae
strains, which are predominant nitrate-ammonifying bacteria in paddy soils. The first pathway involves a membrane-bound nitrate reductase (Nar) and a hybrid cluster protein complex (Hcp–Hcr) that catalyzes the conversion of NO
2
−
to NO and subsequently to N
2
O. The second pathway is observed in Nar-deficient bacteria, where the nitrite reductase (NrfA) generates NO, which is then reduced to N
2
O by Hcp–Hcr. These enzyme combinations are prevalent across the domain Bacteria. Moreover, we observe distinctive isotopocule signatures of DNRA-derived N
2
O from other established N
2
O production pathways, especially through the highest
15
N-site preference (SP) values (43.0‰–49.9‰) reported so far, indicating a robust means for N
2
O source partitioning. Our findings demonstrate two novel N
2
O production pathways in DNRA that can be isotopically distinguished from other pathways.

IMPORTANCE

Stimulation of DNRA is a promising strategy to improve fertilizer efficiency and reduce N
2
O emission in agriculture soils. This process converts water-leachable NO
3
−
and NO
2
−
into soil-adsorbable NH
4
+
, thereby alleviating nitrogen loss and N
2
O emission resulting from denitrification. However, several studies have noted that DNRA can also be a source of N
2
O, contributing to global warming. This contribution is often masked by other N
2
O generation processes, leading to a limited understanding of DNRA as an N
2
O source. Our study reveals two widespread yet overlooked N
2
O production pathways in
Geobacteraceae
, the predominant DNRA bacteria in paddy soils, along with their distinctive isotopocule signatures. These findings offer novel insights into the role of the DNRA bacteria in N
2
O production and underscore the significance of N
2
O isotopocule signatures in microbial N
2
O source tracking.
An orphan kinesin in
Trypanosoma brucei
regulates hook complex assembly and Golgi biogenesis
Authors: Zhou Qing , Kurasawa Yasuhiro , Hu Huiqing , Souza Onofre Thiago , Li Ziyin
Published: October 2024

Kinesins are microtubule-based motor proteins that play diverse cellular functions by regulating microtubule dynamics and intracellular transport in eukaryotes. The early branching kinetoplastid protozoan
Trypanosoma brucei
has an expanded repertoire of kinetoplastid-specific kinesins and orphan kinesins, many of which have unknown functions. We report here the identification of an orphan kinesin named KIN-G that plays an essential role in maintaining hook complex integrity and promoting Golgi biogenesis in
T. brucei
. KIN-G localizes to the distal portion of the centrin arm of the flagellum-associated hook complex through association with the centrin arm protein TbCentrin4. Knockdown of KIN-G in
T. brucei
disrupts the integrity of the hook complex by reducing the length of the centrin arm and eliminating the shank part of the hook complex, thereby impairing flagellum attachment zone elongation and flagellum positioning, which leads to unequal cytokinesis. KIN-G associates with Golgi through a centrin arm-localized Golgi peripheral protein named CAAP1, which maintains Golgi-centrin arm association to facilitate Golgi biogenesis. Knockdown of KIN-G impairs Golgi biogenesis by disrupting CAAP1 at the centrin arm, thereby impairing the maturation of centrin arm-associated Golgi.
In vitro
microtubule gliding assays demonstrate that KIN-G is a plus end-directed motor protein, and its motor activity is required for hook complex assembly and Golgi biogenesis. Together, these results identify a kinesin motor protein for promoting hook complex assembly and uncover a control mechanism for Golgi biogenesis through KIN-G-mediated maintenance of Golgi-hook complex association.

IMPORTANCE

Trypanosoma brucei
has a motile flagellum, which controls cell motility, cell morphogenesis, cell division, and cell-cell communication, and a set of cytoskeletal structures, including the hook complex and the centrin arm, associates with the flagellum. Despite the essentiality of these flagellum-associated cytoskeletal structures, their mechanistic roles and the function of their associated proteins remain poorly understood. Here, we demonstrate that the orphan kinesin KIN-G functions to promote the biogenesis of the hook complex and the Golgi apparatus. KIN-G exerts this function by mediating the association between centrin arm and Golgi through the centrin arm protein TbCentrin4 and a novel Golgi scaffold protein named CAAP1, thereby bridging the two structures and maintaining their close association to facilitate the assembly of the two structures. These findings uncover the essential involvement of a kinesin motor protein in regulating the biogenesis of the hook complex and the Golgi in trypanosomes.
Circulating extracellular vesicles from severe COVID-19 patients induce lung inflammation
Authors: Qian Huifeng , Zang Ruoxi , Zhang Ruoyang , Zheng Guoping , Qiu Guanguan , Meng Jianbiao , Wang Jiangmei , Xia Jie , Huang Ruoqiong , Le Zhenkai , Shu Qiang , Xu Jianguo
Published: October 2024

Circulating extracellular vesicles (EVs) have been associated with the development of COVID-19 due to their roles in viral infection, inflammatory response, and thrombosis. However, the direct induction of lung inflammation by circulating EVs from severe COVID-19 patients remains unknown. EVs were extracted from the plasma of severe COVID-19 patients admitted to intensive care and healthy controls. To study the effect of COVID-19 EVs on lung inflammation, mice were intratracheally instilled with EVs. To examine the proinflammatory effects of EVs
in vitro
, bone marrow-derived macrophages were treated with EVs. COVID-19 but not control EVs triggered lung inflammation, as assessed by total protein level, total cell count, neutrophil count, and levels of proinflammatory cytokines in the bronchoalveolar lavage. COVID-19 EVs also promoted M1 polarization of alveolar macrophages
in vivo
. Treatment of bone marrow-derived macrophages with COVID-19 EVs enhanced the M1 phenotype and augmented the production of IL-1β, IL-6, and TNF-α. In summary, circulating EVs from severe COVID-19 patients induce lung inflammation in mice. EVs could become a potential therapeutic target for alleviating lung injury in COVID-19.

IMPORTANCE

Extracellular vesicles (EVs) have been reported to facilitate cytokine storm, coagulation, vascular dysfunction, and the spread of the virus in COVID-19. The direct role of circulating EVs from severe COVID-19 patients in lung injury remains unrecognized. Our study demonstrated that plasma EVs obtained from severe COVID-19 patients induced lung inflammation and polarization of alveolar macrophages
in vivo
.
In vitro
experiments also revealed the proinflammatory effects of COVID-19 EVs. The present study sheds fresh insight into the mechanisms of COVID-19-induced lung injury, highlighting EVs as a potential therapeutic target in combating the disease.
Multicyclic Phanerozoic orogeny recorded in the Qaidam continent, northern Tibet: Implications for the tectonic evolution of the Tethyan orogenic system
Authors: Wu Chen , Zhao Yonghui , Li Jie , Liu Wenyou , Zuza Andrew V. , Haproff Peter J. , Ding Lin
Published: October 2024

The growth and evolution of the Eurasian continent involved the progressive closure of major ocean basins during the Phanerozoic, including the Tethyan and Paleo-Asian oceanic realms. Unraveling this complicated history requires interpreting multiple overprinted episodes of subduction-related magmatism and collisional orogeny, the products of which were later affected by the Cenozoic construction of the Himalayan-Tibetan orogen due to the India-Asia collision. In particular, the tectonic evolution of northern Tibet surrounding the Cenozoic Qaidam Basin is poorly resolved due to several phases of Phanerozoic orogeny that have been reactivated during the Cenozoic deformation. In this study, we investigated the geology of the northern Qaidam continent, which experienced Paleozoic–Mesozoic tectonic activity associated with the development of the Eastern Kunlun orogen to the south and the Qilian orogen to the north. We combined new and published field observations, geochronologic and thermochronologic ages, and geochemical data to construct regional tectonostratigraphic sections and bracket phases of Paleozoic–Mesozoic magmatism associated with oceanic subduction and continental collision. Results suggest that the Qaidam continent experienced two major phases of subduction magmatism and collision. First, a Cambrian–Ordovician magmatic arc developed in the northern Qaidam continent due to south-dipping subduction. This phase was followed by the closure of the Qilian Ocean and the collision of the North China craton and Qaidam continent, resulting in Silurian–Devonian orogeny and the development of a regional unconformity across northern Tibet. A subsequent Permian–Triassic magmatic arc developed across the northern Qaidam continent due to north-dipping subduction. This phase was followed by the closure of the Neo-Kunlun Ocean and the collision of the Songpan Ganzi terrane in the south and Qaidam continent. These interpretations are incorporated into a new and comprehensive model for the Phanerozoic formation of northern Tibet and the Eurasia continent.
Boron isotopes identify deep-slab serpentinite in the source of Aleutian arc magma
Authors: Jensen Owen , Waldman Ryan , Yogodzinski Gene , Bizimis Michael , Ryan Jeffrey , Leeman William , Scher Howie , Hoernle Kaj
Published: October 2024

Seafloor lavas of the Western Aleutian arc have isotopically heavy boron (δ11B to +13.4‰) that is negatively correlated with B content (ppm). Endmember samples are primitive dacites and rhyodacites (δ11B > +10‰, SiO2 = 63%–70%, Mg# > 0.60) with adakitic trace-element and isotopic characteristics that require roles for residual garnet and rutile in their formation. The source of isotopically heavy B is likely serpentinite in the mantle section of the subducting plate, which dewaters into an inverted geothermal gradient and drives melting within the overlying volcanic section at depths where prior effects of seawater alteration were minimal. Most volcanic rocks from the Aleutian Island locations have 10–30 ppm B with an average δ11B of ~+1.0‰ ± 1.3‰, reflecting a mixed source dominated by subducted sediment. A subset of island samples has B that is isotopically light (δ11B < –2.4‰) and at low concentrations (<11.0 ppm), which is typical of arc lavas globally from rear-arc settings where depth-to-slab is high, and where δ11B may be interpreted to reflect a source in dehydrated (isotopically light) altered oceanic crust. Mass balance modeling indicates that isotopically heavy B from deep-slab serpentinite is present in the Aleutian source arc-wide but is typically masked by sediment-derived B at volcanic centers outside of the westernmost segment of the arc.
Diverse intrusion modes during the construction of a high-silica magma reservoir: Evidence from La Obra–Cerro Blanco intrusive suite (central Chile)
Authors: Payacán Ítalo , Covarrubias María Alejandra , Rodríguez Nicolás , Tavazzani Lorenzo , Gutiérrez Francisco , Roperch Pierrick , Poblete Fernando , Meyer Martín
Published: October 2024

Several conceptual models have been proposed for the amalgamation of granitoid plutons, which range from incremental growth to single-stage emplacement of these systems. This diversity of views has led to intense debate about the thermomechanical state of silicic intrusions and the magma differentiation paths within the crust. In this contribution, we present a comprehensive petrologic, geochronologic, and magnetic fabric data set from the La Obra–Cerro Blanco intrusive suite, which allows us to explore the petrogenesis and magma emplacement processes in the upper crust.

This intrusive suite is composed of (1) a vertically zoned granitoid intrusion in spatial association with mafic layers and stocks and (2) a cupola-like high-silica granite. We interpret this intrusive suite as assembled by diverse but coexisting intrusion mechanisms over a time span of ~1.4 m.y. from 21.4 to 19.9 Ma. As indicated by the subhorizontal magnetic lineation, the first stage was dominated by horizontal emplacement of sheet-like intrusions of intermediate compositions, which became increasingly silicic after plagioclase and amphibole fractionation throughout the crustal column. The latest stage was instead dominated by cooling, crystallization, and differentiation of a thickened granitoid body and the formation of a high-silica magma chamber. The steep magnetic lineation and the abundance of aplite and rhyolitic dikes observed in the cupola-like, high-silica granites suggest that this portion acted as an evacuation channel of high-silica magma toward shallower levels, offering a rare opportunity to understand not only silicic magma accumulation and storage in the upper crust, but also the processes connecting the plutonic and volcanic environments.
Isolated retinal astrocytic hamartoma masquerading as viral retinitis
Authors: Das Dipanjana , Jain Tanya , Saxena Rushil Kumar , Agarwal Manisha
Published: October 2024

A female in her early 50s presented with a yellowish-white retinal lesion with fluffy margins along with flame-shaped haemorrhages and cystoid macular oedema in the left eye. Due to a recent history of fever, a presumptive diagnosis of viral retinitis was made. Following no response to antiviral therapy, the patient underwent a revision of the diagnosis using multimodal imaging. Fundus fluorescein angiography and optical coherence tomography angiography (OCTA) revealed a dense vascular network in the lesion, suggestive of an isolated retinal astrocytic hamartoma (RAH). All ongoing treatment was stopped, and the patient was kept under observation. She was stable without any treatment at 1-year follow-up. This is an unusual case of isolated RAH without any systemic involvement, acting as a potential masquerade. Multimodal imaging, including OCTA, is diagnostic of RAH. This helps avoid unnecessary treatment with corticosteroids and antiviral therapy.
Changes in physical activity and all-cause mortality among individuals with dementia: a cohort study using the National Health Insurance Service Database in Korea
Authors: Park Kye-Yeung , Huh Youn , Nam Ga Eun , Han Kyungdo , Jung Jin-Hyung , Cho Yoon Jeong , Kim Seon Mee , Hwang Hwan-Sik , Park Yong-Moon Mark
Published: October 2024

Objective

To examine associations between the amount and changes in regular physical activity (PA) before and after diagnosis of dementia and all-cause mortality risk, and whether these associations differ by PA intensity (light, moderate or vigorous).

Methods

This retrospective cohort study used data from the Korean National Health Insurance Service Database, including 60 252 individuals newly diagnosed with dementia between 2010 and 2016 who underwent health examinations both before and after diagnosis. PA was assessed using the International Physical Activity Questionnaire–Short Form. Multivariable Cox proportional hazards regression models were used to analyse the associations between PA (amount and changes) and all-cause mortality risk.

Results

During a mean follow-up of 3.7 years, 16 431 (27.3%) deaths occurred. Higher PA levels after dementia diagnosis were associated with a dose-dependent decrease in mortality risk (p for trend <0.001). Maintaining regular PA, compared with remaining inactive, was associated with the lowest mortality risk (HR=0.71, 95% CI 0.65 to 0.79). Sustained engagement in PA of any intensity was associated with decreased mortality risk: light (HR=0.70, 95% CI 0.67 to 0.75), moderate (HR=0.74, 95% CI 0.64 to 0.86) and vigorous PA (HR=0.70, 95% CI 0.61 to 0.79). Initiating any PA intensity after dementia diagnosis was associated with at least 20% reduced mortality risk. These associations were consistent in Alzheimer’s disease.

Conclusions

Maintaining or initiating regular PA, regardless of intensity, after dementia diagnosis was associated with a reduced risk of all-cause mortality. Lifestyle modifications promoting PA might offer survival benefits for individuals with dementia.
Major vascular events after first incident stroke: a population-based study
Authors: Malek Rayka , Alasiri Salha , Wolfe Charles D A , Douiri Abdel
Published: October 2024

Background

Recent advances in stroke care have led to improvements in survival and rates of stroke recurrence. However, there is a lack of data on trends of major vascular events, and risk factors associated with non-fatal and fatal outcomes. We aim to identify demographical and clinical factors leading to incidence of subsequent major vascular events after the first-ever stroke.

Methods

6051 patients’ records with first-ever stroke between 1995 and 2018 in South London, UK were analysed. Semicompeting risks models were constructed to estimate factors affecting time to incidence of recurrent stroke, myocardial infarction (MI), mortality and transitions from poststroke recurrence/MI to mortality (indirect mortality). Cumulative incidence functions were plotted for each major vascular event, stratified by stroke subtypes. All models were adjusted for age, sex, socioeconomic status, comorbidities, stroke severity and stroke subtype.

Results

Five years of cumulative incidences were 9.2% (95% CI (8.4% to 10.0%)) for recurrent stroke, 4.4% (95% CI 3.9% to 5.0%) for MI, and 45% (95% CI 44% to 47%) for mortality. Prior atrial fibrillation was associated with 47% increased risk of mortality (HR=1.47 (95% CI 1.23 to 1.75)) and a previous diagnosis of MI was the strongest risk factor for poststroke MI (HR=9.17 (95% CI 6.28 to 13.39)). Stroke unit was associated with a 40% lower hazard of mortality without having a recurrent stroke/MI (HR=0.60 (95% CI 0.50 to 0.72)) and a 39% lower hazard of indirect mortality (HR=0.57 (95% CI 0.37 to 0.87)).

Conclusion

Major vascular events are prevalent after stroke, particularly among those with concurrent vascular conditions. The rate of stroke recurrence plateaued in the last decade, yet MI incidence increased. Targeted strategies to control risk factors are required to reduce the incidence of a second vascular event and prevent progression to mortality in these high-risk groups.
Desipramine reverses remote memory deficits by activating calmodulin-CaMKII pathway in aUTXknockout mouse model of Kabuki syndrome
Authors: Chen Lei , Li Yuting , Liu Minggang , Lan Zhaohui , Zhang Xu , Yang Xiujuan , Zhao Qian , Wang Shuai , Xu Longyong , Zhou Ying , Kuang Yifang , Suzuki Tatsuo , Tabuchi Katsuhiko , Takahashi Eiki , Zhou Miou , Chen Charlie Degui , Xu Tianle , Li Weidong
Published: October 2024

Background

Kabuki syndrome (KS) is a rare developmental disorder characterised by multiple congenital anomalies and intellectual disability.UTX(ubiquitously transcribed tetratricopeptide repeat, X chromosome), which encodes a histone demethylase, is one of the two major pathogenic risk genes for KS. Although intellectual disability is a key phenotype of KS, the role ofUTXin cognitive function remains unclear. Currently, no targeted therapies are available for KS.

Aims

This study aimed to investigate howUTXregulates cognition, to explore the mechanisms underlyingUTXdysfunction and to identify potential molecular targets for treatment.

Methods

We generatedUTXconditional knockout mice and found thatUTXdeletion downregulated calmodulin transcription by disrupting H3K27me3 (trimethylated histone H3 at lysine 27) demethylation.

Results

UTX-knockout mice showed decreased phosphorylation of calcium / calmodulin-dependent protein kinase II, impaired long-term potentiation and deficit in remote contextual fear memory. These effects were reversed by an Food and Drug Administration-approved drug desipramine.

Conclusions

Our results reveal an epigenetic mechanism underlying the important role ofUTXin synaptic plasticity and cognitive function, and suggest that desipramine could be a potential treatment for KS.