bluuebunny/crossref_metadata_2025 huggingface dataset:
Different Formation Modes of the North–South‐Trending Rifts in Southern Tibet: Implications From Ambient Noise Tomography
Authors: Li Dandan , Tian Xiaobo , Liang Xiaofeng , Nie Shitan
Published: May 2024

Understanding how the Miocene N–S‐trending rifts on the southern Tibetan Plateau formed is crucial for understanding the evolution of the plateau. Most competing models suggest that all the rifts developed uniformly, but there are differences in magmatism among them. We conducted ambient noise tomography based on a broadband seismic array deployed across the rifts. A mid‐crustal low‐Vs layer extends laterally beneath the Tangra Yum Co Rift and the Pumqu‐Xianza Rift, implying that E‒W stretching of the ductile middle crust segmented the brittle upper crust, causing rifting and subsequent magmatism. In contrast, the Yadong‐Gulu Rift, which experienced prerifting magmatism, is characterized by an isolated low‐Vs anomaly extending subvertically from the surface to the middle crust, indicating that the crust experienced magmatic intrusion and local disruption, which promoted the later formation of a large rift. The results suggest that the various rifts might have distinct formation modes.
Acceleration of Pick‐Up Ions in the Martian Magnetosheath: A Tianwen‐1 Case Study
Authors: Qiao Fuhao , Li Lei , Xie Lianghai , Li Wenya , Kong Linggao , Tang Binbin , Zhang Yiteng , Zhang Aibing , Xu Qi , Wang Limin , Jin Taifeng , Ma Jijie , Sun Fuyu
Published: May 2024

This study delves into a Pick‐Up Ion (PUI) event captured by the Mars Ion and Neutral Particle Analyzer aboard Tianwen‐1, revealing a faster acceleration than expected within the Martian magnetosheath. This event suggests the presence of a convection electric field considerably stronger than that typically observed in the solar wind. Through Magnetohydrodynamic simulation, we identified two regions of intensified convection electric fields within the inner magnetosheath, prominently manifested at mid to high solar zenith angles (SZA = 40°–70°) in the X‐Z plane of the Mars Solar Electric field coordinates. Tianwen‐1 observed that the peak of the electric field strength, up to five times of that in the solar wind, is located at the upper edge or within the Magnetic Pileup Boundary. Further study by test particle simulations showed acceleration by the electric field effectively doubles the energy gain of PUIs, in comparison to scenarios absent of this extra acceleration. It is revealed that the presence of such electric field regions within the Martian magnetosheath is a prevailing feature, shaped by the solar wind's interaction with Mars and modulated by the planet's rotating crustal magnetic fields.
Exploring the relationship between admixture and genetic susceptibility to attention deficit hyperactivity disorder in two Latin American cohorts
Authors: Garzón Rodríguez Nicolás , Briceño-Balcázar Ignacio , Nicolini Humberto , Martínez-Magaña José Jaime , Genis-Mendoza Alma D. , Flores-Lázaro Julio C. , Villatoro Velázquez Jorge A. , Bustos Gamiño Marycarmen , Medina-Mora Maria Elena , Quiroz-Padilla Maria Fernanda
Published: May 2024

Contemporary research on the genomics of Attention Deficit Hyperactivity Disorder (ADHD) often underrepresents admixed populations of diverse genomic ancestries, such as Latin Americans. This study explores the relationship between admixture and genetic associations for ADHD in Colombian and Mexican cohorts. Some 546 participants in two groups, ADHD and Control, were genotyped with Infinium PsychArray®. Global ancestry levels were estimated using overall admixture proportions and principal component analysis, while local ancestry was determined using a method to estimate ancestral components along the genome. Genome-wide association analysis (GWAS) was conducted to identify significant associations. Differences between Colombia and Mexico were evaluated using appropriate statistical tests. 354 Single-nucleotide polymorphisms (SNPs) and Single-nucleotide variants (SNVs) related to some genes and intergenic regions exhibited suggestive significance (p-value < 5*10e−5) in the GWAS. None of the variants revealed genome-wide significance (p-value < 5*10e−8). The study identified a significant relationship between risk SNPs and the European component of admixture, notably observed in the LOC105379109 gene. Despite differences in risk association loci, such as FOXP2, our findings suggest a possible homogeneity in genetic variation’s impact on ADHD between Colombian and Mexican populations. Current reference datasets for ADHD predominantly consist of samples with high European ancestry, underscoring the need for further research to enhance the representation of reference populations and improve the identification of ADHD risk traits in Latin Americans.
Risk of traumatic brain injury among patients with ADHD and their unaffected siblings
Authors: Wu Ping-Chung , Tsai Shih-Jen , Hsu Ju-Wei , Huang Kai-Lin , Chen Tzeng-Ji , Pan Tai-Long , Chen Mu-Hong
Published: May 2024

Background

As the relationship between attention deficit hyperactivity disorder (ADHD) and traumatic brain injury (TBI) is gaining increasing attention, the TBI risk in patients with ADHD, unaffected siblings of ADHD probands, and non-ADHD controls remains unclear.

Methods

Overall, 18,645 patients with ADHD, 18,880 unaffected siblings of ADHD probands, and 188,800 age-/sex-matched controls were followed up from enrollment to the end of 2011. The cases of TBI and TBI requiring hospitalization were identified during follow-up.

Results

Patients with ADHD (hazard ratio [HR]: 1.57) and unaffected siblings (HR: 1.20) had an increased risk of any TBI compared with non-ADHD controls. Surprisingly, the likelihood of developing TBI requiring hospitalization during follow-up was higher in the unaffected siblings group (HR: 1.21) than in the control group, whereas it was lower in the ADHD probands group (HR: 0.86).

Conclusions

Patients with ADHD and unaffected siblings of ADHD probands were more likely to develop any TBI during follow-up than controls. Unaffected siblings of patients with ADHD exhibited the highest risk of subsequent TBI requiring hospitalization compared with patients with ADHD and healthy controls. Therefore, TBI risk in patients with ADHD and their unaffected siblings would require further investigation.

Impact

ADHD diagnosis and ADHD trait are associated with risk of traumatic brain injury (TBI).

Both patients with ADHD and their unaffected siblings were more likely to develop TBI during the follow-up compared with the control group.

TBI requiring hospitalization occurred more in the sibling group than in the proband group.

TBI risk should be closely monitored among unaffected siblings of patients with ADHD.
Contextual and combinatorial structure in sperm whale vocalisations
Authors: Sharma Pratyusha , Gero Shane , Payne Roger , Gruber David F. , Rus Daniela , Torralba Antonio , Andreas Jacob
Published: May 2024

Sperm whales (Physeter macrocephalus) are highly social mammals that communicate using sequences of clicks called codas. While a subset of codas have been shown to encode information about caller identity, almost everything else about the sperm whale communication system, including its structure and information-carrying capacity, remains unknown. We show that codas exhibit contextual and combinatorial structure. First, we report previously undescribed features of codas that are sensitive to the conversational context in which they occur, and systematically controlled and imitated across whales. We call these rubato and ornamentation. Second, we show that codas form a combinatorial coding system in which rubato and ornamentation combine with two context-independent features we call rhythm and tempo to produce a large inventory of distinguishable codas. Sperm whale vocalisations are more expressive and structured than previously believed, and built from a repertoire comprising nearly an order of magnitude more distinguishable codas. These results show context-sensitive and combinatorial vocalisation can appear in organisms with divergent evolutionary lineage and vocal apparatus.
A comprehensive genetic map of cytokine responses in Lyme borreliosis
Authors: Botey-Bataller Javier , Vrijmoeth Hedwig D. , Ursinus Jeanine , Kullberg Bart-Jan , van den Wijngaard Cees C. , ter Hofstede Hadewych , Alaswad Ahmed , Gupta Manoj K. , Roesner Lennart M. , Huehn Jochen , Werfel Thomas , Schulz Thomas F. , Xu Cheng-Jian , Netea Mihai G. , Hovius Joppe W. , Joosten Leo A. B. , Li Yang
Published: May 2024

The incidence of Lyme borreliosis has risen, accompanied by persistent symptoms. The innate immune system and related cytokines are crucial in the host response and symptom development. We characterized cytokine production capacity before and after antibiotic treatment in 1,060 Lyme borreliosis patients. We observed a negative correlation between antibody production and IL-10 responses, as well as increased IL-1Ra responses in patients with disseminated disease. Genome-wide mapping the cytokine production allowed us to identify 34 cytokine quantitative trait loci (cQTLs), with 31 novel ones. We pinpointed the causal variant at the TLR1-6-10 locus and validated the regulation of IL-1Ra responses at transcritpome level using an independent cohort. We found that cQTLs contribute to Lyme borreliosis susceptibility and are relevant to other immune-mediated diseases. Our findings improve the understanding of cytokine responses in Lyme borreliosis and provide a genetic map of immune function as an expanded resource.
Spin disorder control of topological spin texture
Authors: Zhang Hongrui , Shao Yu-Tsun , Chen Xiang , Zhang Binhua , Wang Tianye , Meng Fanhao , Xu Kun , Meisenheimer Peter , Chen Xianzhe , Huang Xiaoxi , Behera Piush , Husain Sajid , Zhu Tiancong , Pan Hao , Jia Yanli , Settineri Nick , Giles-Donovan Nathan , He Zehao , Scholl Andreas , N’Diaye Alpha , Shafer Padraic , Raja Archana , Xu Changsong , Martin Lane W. , Crommie Michael F. , Yao Jie , Qiu Ziqiang , Majumdar Arun , Bellaiche Laurent , Muller David A. , Birgeneau Robert J. , Ramesh Ramamoorthy
Published: May 2024

Stabilization of topological spin textures in layered magnets has the potential to drive the development of advanced low-dimensional spintronics devices. However, achieving reliable and flexible manipulation of the topological spin textures beyond skyrmion in a two-dimensional magnet system remains challenging. Here, we demonstrate the introduction of magnetic iron atoms between the van der Waals gap of a layered magnet, Fe3GaTe2, to modify local anisotropic magnetic interactions. Consequently, we present direct observations of the order-disorder skyrmion lattices transition. In addition, non-trivial topological solitons, such as skyrmioniums and skyrmion bags, are realized at room temperature. Our work highlights the influence of random spin control of non-trivial topological spin textures.
Seasonal antigenic prediction of influenza A H3N2 using machine learning
Authors: Shah Syed Awais W. , Palomar Daniel P. , Barr Ian , Poon Leo L. M. , Quadeer Ahmed Abdul , McKay Matthew R.
Published: May 2024

Antigenic characterization of circulating influenza A virus (IAV) isolates is routinely assessed by using the hemagglutination inhibition (HI) assays for surveillance purposes. It is also used to determine the need for annual influenza vaccine updates as well as for pandemic preparedness. Performing antigenic characterization of IAV on a global scale is confronted with high costs, animal availability, and other practical challenges. Here we present a machine learning model that accurately predicts (normalized) outputs of HI assays involving circulating human IAV H3N2 viruses, using their hemagglutinin subunit 1 (HA1) sequences and associated metadata. Each season, the model learns an updated nonlinear mapping of genetic to antigenic changes using data from past seasons only. The model accurately distinguishes antigenic variants from non-variants and adaptively characterizes seasonal dynamics of HA1 sites having the strongest influence on antigenic change. Antigenic predictions produced by the model can aid influenza surveillance, public health management, and vaccine strain selection activities.
A filtering reconfigurable intelligent surface for interference-free wireless communications
Authors: Liang Jing Cheng , Zhang Lei , Luo Zhangjie , Jiang Rui Zhe , Cheng Zhang Wen , Wang Si Ran , Sun Meng Ke , Jin Shi , Cheng Qiang , Cui Tie Jun
Published: May 2024

The powerful capability of reconfigurable intelligent surfaces (RISs) in tailoring electromagnetic waves and fields has put them under the spotlight in wireless communications. However, the current designs are criticized due to their poor frequency selectivity, which hinders their applications in real-world scenarios where the spectrum is becoming increasingly congested. Here we propose a filtering RIS to feature sharp frequency-selecting and 2-bit phase-shifting properties. It permits the signals in a narrow bandwidth to transmit but rejects the out-of-band ones; meanwhile, the phase of the transmitted signals can be digitally controlled, enabling flexible manipulations of signal propagations. A prototype is designed, fabricated, and measured, and its high quality factor and phase-shifting characteristics are validated by scattering parameters and beam-steering phenomena. Further, we conduct a wireless communication experiment to illustrate the intriguing functions of the RIS. The filtering behavior enables the RIS to perform wireless signal manipulations with anti-interference ability, thus showing big potential to advance the development of next-generation wireless communications.
Distinct cellular immune responses in children en route to type 1 diabetes with different first-appearing autoantibodies
Authors: Starskaia Inna , Valta Milla , Pietilä Sami , Suomi Tomi , Pahkuri Sirpa , Kalim Ubaid Ullah , Rasool Omid , Rydgren Emilie , Hyöty Heikki , Knip Mikael , Veijola Riitta , Ilonen Jorma , Toppari Jorma , Lempainen Johanna , Elo Laura L. , Lahesmaa Riitta
Published: May 2024

Previous studies have revealed heterogeneity in the progression to clinical type 1 diabetes in children who develop islet-specific antibodies either to insulin (IAA) or glutamic acid decarboxylase (GADA) as the first autoantibodies. Here, we test the hypothesis that children who later develop clinical disease have different early immune responses, depending on the type of the first autoantibody to appear (GADA-first or IAA-first). We use mass cytometry for deep immune profiling of peripheral blood mononuclear cell samples longitudinally collected from children who later progressed to clinical disease (IAA-first, GADA-first, ≥2 autoantibodies first groups) and matched for age, sex, and HLA controls who did not, as part of the Type 1 Diabetes Prediction and Prevention study. We identify differences in immune cell composition of children who later develop disease depending on the type of autoantibodies that appear first. Notably, we observe an increase in CD161 expression in natural killer cells of children with ≥2 autoantibodies and validate this in an independent cohort. The results highlight the importance of endotype-specific analyses and are likely to contribute to our understanding of pathogenic mechanisms underlying type 1 diabetes development.
Early warning signals of the termination of the African Humid Period(s)
Authors: Trauth Martin H. , Asrat Asfawossen , Fischer Markus L. , Hopcroft Peter O. , Foerster Verena , Kaboth-Bahr Stefanie , Kindermann Karin , Lamb Henry F. , Marwan Norbert , Maslin Mark A. , Schaebitz Frank , Valdes Paul J.
Published: May 2024

The transition from a humid green Sahara to today’s hyperarid conditions in northern Africa ~5.5 thousand years ago shows the dramatic environmental change to which human societies were exposed and had to adapt to. In this work, we show that in the 620,000-year environmental record from the Chew Bahir basin in the southern Ethiopian Rift, with its decadal resolution, this one thousand year long transition is particularly well documented, along with 20–80 year long droughts, recurring every ~160 years, as possible early warnings. Together with events of extreme wetness at the end of the transition, these droughts form a pronounced climate “flickering”, which can be simulated in climate models and is also present in earlier climate transitions in the Chew Bahir environmental record, indicating that transitions with flickering are characteristic of this region.
The miR-144/Hmgn2 regulatory axis orchestrates chromatin organization during erythropoiesis
Authors: Kretov Dmitry A. , Folkes Leighton , Mora-Martin Alexandra , Walawalkar Isha A. , Imrat  , Syedah Noreen , Vanuytsel Kim , Moxon Simon , Murphy George J. , Cifuentes Daniel
Published: May 2024

Differentiation of stem and progenitor cells is a highly regulated process that involves the coordinated action of multiple layers of regulation. Here we show how the post-transcriptional regulatory layer instructs the level of chromatin regulation via miR-144 and its targets to orchestrate chromatin condensation during erythropoiesis. The loss of miR-144 leads to impaired chromatin condensation during erythrocyte maturation. Among the several targets of miR-144 that influence chromatin organization, the miR-144-dependent regulation of Hmgn2 is conserved from fish to humans. Our genetic probing of the miR-144/Hmgn2 regulatory axis establish that intact miR-144 target sites in the Hmgn2 3’UTR are necessary for the proper maturation of erythrocytes in both zebrafish and human iPSC-derived erythroid cells while loss of Hmgn2 rescues in part the miR-144 null phenotype. Altogether, our results uncover miR-144 and its target Hmgn2 as the backbone of the genetic regulatory circuit that controls the terminal differentiation of erythrocytes in vertebrates.
In-silico-assisted derivatization of triarylboranes for the catalytic reductive functionalization of aniline-derived amino acids and peptides with H2
Authors: Hisata Yusei , Washio Takashi , Takizawa Shinobu , Ogoshi Sensuke , Hoshimoto Yoichi
Published: May 2024

Cheminformatics-based machine learning (ML) has been employed to determine optimal reaction conditions, including catalyst structures, in the field of synthetic chemistry. However, such ML-focused strategies have remained largely unexplored in the context of catalytic molecular transformations using Lewis-acidic main-group elements, probably due to the absence of a candidate library and effective guidelines (parameters) for the prediction of the activity of main-group elements. Here, the construction of a triarylborane library and its application to an ML-assisted approach for the catalytic reductive alkylation of aniline-derived amino acids and C-terminal-protected peptides with aldehydes and H2 is reported. A combined theoretical and experimental approach identified the optimal borane, i.e., B(2,3,5,6-Cl4-C6H)(2,6-F2-3,5-(CF3)2-C6H)2, which exhibits remarkable functional-group compatibility toward aniline derivatives in the presence of 4-methyltetrahydropyran. The present catalytic system generates H2O as the sole byproduct.
Effects of management practices on the ecosystem-service multifunctionality of temperate grasslands
Authors: Richter Franziska J. , Suter Matthias , Lüscher Andreas , Buchmann Nina , El Benni Nadja , Feola Conz Rafaela , Hartmann Martin , Jan Pierrick , Klaus Valentin H.
Published: May 2024

Human wellbeing depends on ecosystem services, highlighting the need for improving the ecosystem-service multifunctionality of food and feed production systems. We study Swiss agricultural grasslands to assess how employing and combining three widespread aspects of grassland management and their interactions can enhance 22 plot-level ecosystem service indicators, as well as ecosystem-service multifunctionality. The three management aspects we assess are i) organic production system, ii) an eco-scheme prescribing extensive management (without fertilization), and iii) harvest type (pasture vs. meadow). While organic production system and interactions between the three management aspects play a minor role, the main effects of eco-scheme and harvest type considerably shape single services. Moreover, the eco-scheme ‘extensive management’ and the harvest type ‘pasture’ enhance plot-scale ecosystem-service multifunctionality, mostly through facilitating cultural services at the expense of provisioning services. These changes in ecosystem-service supply occur mainly via changes in land-use intensity, i.e., reduced fertilizer input and harvest frequency. In conclusion, diversifying grassland management where this is currently homogeneous across farms and landscapes depicts an important first step to improve landscape-scale multifunctionality for sustainable grassland systems. To meet societal ecosystem services demand, the three studied management aspects can be systematically combined to increase ecosystem services that are in short supply.
Allosteric regulation by c-di-AMP modulates a complete N-acetylglucosamine signaling cascade in Saccharopolyspora erythraea
Authors: You Di , Zhao Liu-Chang , Fu Yu , Peng Zhi-Yao , Chen Zong-Qin , Ye Bang-Ce
Published: May 2024

c-di-AMP is an essential and widespread nucleotide second messenger in bacterial signaling. For most c-di-AMP synthesizing organisms, c-di-AMP homeostasis and the molecular mechanisms pertaining to its signal transduction are of great concern. Here we show that c-di-AMP binds the N-acetylglucosamine (GlcNAc)-sensing regulator DasR, indicating a direct link between c-di-AMP and GlcNAc signaling. Beyond its foundational role in cell-surface structure, GlcNAc is attractive as a major nutrient and messenger molecule regulating multiple cellular processes from bacteria to humans. We show that increased c-di-AMP levels allosterically activate DasR as a master repressor of GlcNAc utilization, causing the shutdown of the DasR-mediated GlcNAc signaling cascade and leading to a consistent enhancement in the developmental transition and antibiotic production in Saccharopolyspora erythraea. The expression of disA, encoding diadenylate cyclase, is directly repressed by the regulator DasR in response to GlcNAc signaling, thus forming a self-sustaining transcriptional feedback loop for c-di-AMP synthesis. These findings shed light on the allosteric regulation by c-di-AMP, which appears to play a prominent role in global signal integration and c-di-AMP homeostasis in bacteria and is likely widespread in streptomycetes that produce c-di-AMP.
The genomic landscape of Vk*MYC myeloma highlights shared pathways of transformation between mice and humans
Authors: Maura Francesco , Coffey David G. , Stein Caleb K. , Braggio Esteban , Ziccheddu Bachisio , Sharik Meaghen E. , Du Megan T. , Tafoya Alvarado Yuliza , Shi Chang-Xin , Zhu Yuan Xiao , Meermeier Erin W. , Morgan Gareth J. , Landgren Ola , Bergsagel P. Leif , Chesi Marta
Published: May 2024

Multiple myeloma (MM) is a heterogeneous disease characterized by frequent MYC translocations. Sporadic MYC activation in the germinal center of genetically engineered Vk*MYC mice is sufficient to induce plasma cell tumors in which a variety of secondary mutations are spontaneously acquired and selected over time. Analysis of 119 Vk*MYC myeloma reveals recurrent copy number alterations, structural variations, chromothripsis, driver mutations, apolipoprotein B mRNA-editing enzyme, catalytic polypeptide (APOBEC) mutational activity, and a progressive decrease in immunoglobulin transcription that inversely correlates with proliferation. Moreover, we identify frequent insertional mutagenesis by endogenous retro-elements as a murine specific mechanism to activate NF-kB and IL6 signaling pathways shared with human MM. Despite the increased genomic complexity associated with progression, advanced tumors remain dependent on MYC. In summary, here we credential the Vk*MYC mouse as a unique resource to explore MM genomic evolution and describe a fully annotated collection of diverse and immortalized murine MM tumors.
High SARS-CoV-2 incidence and asymptomatic fraction during Delta and Omicron BA.1 waves in The Gambia
Authors: Jarju Sheikh , Wenlock Rhys D. , Danso Madikoi , Jobe Dawda , Jagne Ya Jankey , Darboe Alansana , Kumado Michelle , Jallow Yusupha , Touray Mamlie , Ceesay Ebrima A. , Gaye Hoja , Gaye Biran , Tunkara Abdoulie , Kandeh Sheriff , Gomes Marie , Sylva Ellen Lena , Toure Fatoumata , Hornsby Hailey , Lindsey Benjamin B. , Nicklin Martin J. , Sayers Jon R. , Sesay Abdul K. , Kucharski Adam , Hodgson David , Kampmann Beate , de Silva Thushan I.
Published: May 2024

Little is known about SARS-CoV-2 infection risk in African countries with high levels of infection-driven immunity and low vaccine coverage. We conducted a prospective cohort study of 349 participants from 52 households in The Gambia between March 2021 and June 2022, with routine weekly SARS-CoV-2 RT-PCR and 6-monthly SARS-CoV-2 serology. Attack rates of 45% and 57% were seen during Delta and Omicron BA.1 waves respectively. Eighty-four percent of RT-PCR-positive infections were asymptomatic. Children under 5-years had a lower incidence of infection than 18-49-year-olds. One prior SARS-CoV-2 infection reduced infection risk during the Delta wave only, with immunity from ≥2 prior infections required to reduce the risk of infection with early Omicron lineage viruses. In an African population with high levels of infection-driven immunity and low vaccine coverage, we find high attack rates during SARS-CoV-2 waves, with a high proportion of asymptomatic infections and young children remaining relatively protected from infection.
SARS-CoV-2 Mpro responds to oxidation by forming disulfide and NOS/SONOS bonds
Authors: Reinke Patrick Y. A. , Schubert Robin , Oberthür Dominik , Galchenkova Marina , Rahmani Mashhour Aida , Günther Sebastian , Chretien Anaïs , Round Adam , Seychell Brandon Charles , Norton-Baker Brenna , Kim Chan , Schmidt Christina , Koua Faisal H. M. , Tolstikova Alexandra , Ewert Wiebke , Peña Murillo Gisel Esperanza , Mills Grant , Kirkwood Henry , Brognaro Hévila , Han Huijong , Koliyadu Jayanath , Schulz Joachim , Bielecki Johan , Lieske Julia , Maracke Julia , Knoska Juraj , Lorenzen Kristina , Brings Lea , Sikorski Marcin , Kloos Marco , Vakili Mohammad , Vagovic Patrik , Middendorf Philipp , de Wijn Raphael , Bean Richard , Letrun Romain , Han Seonghyun , Falke Sven , Geng Tian , Sato Tokushi , Srinivasan Vasundara , Kim Yoonhee , Yefanov Oleksandr M. , Gelisio Luca , Beck Tobias , Doré Andrew S. , Mancuso Adrian P. , Betzel Christian , Bajt Saša , Redecke Lars , Chapman Henry N. , Meents Alke , Turk Dušan , Hinrichs Winfried , Lane Thomas J.
Published: May 2024

The main protease (Mpro) of SARS-CoV-2 is critical for viral function and a key drug target. Mpro is only active when reduced; turnover ceases upon oxidation but is restored by re-reduction. This suggests the system has evolved to survive periods in an oxidative environment, but the mechanism of this protection has not been confirmed. Here, we report a crystal structure of oxidized Mpro showing a disulfide bond between the active site cysteine, C145, and a distal cysteine, C117. Previous work proposed this disulfide provides the mechanism of protection from irreversible oxidation. Mpro forms an obligate homodimer, and the C117-C145 structure shows disruption of interactions bridging the dimer interface, implying a correlation between oxidation and dimerization. We confirm dimer stability is weakened in solution upon oxidation. Finally, we observe the protein’s crystallization behavior is linked to its redox state. Oxidized Mpro spontaneously forms a distinct, more loosely packed lattice. Seeding with crystals of this lattice yields a structure with an oxidation pattern incorporating one cysteine-lysine-cysteine (SONOS) and two lysine-cysteine (NOS) bridges. These structures further our understanding of the oxidative regulation of Mpro and the crystallization conditions necessary to study this structurally.
Radiative cooling and indoor light management enabled by a transparent and self-cleaning polymer-based metamaterial
Authors: Huang Gan , Yengannagari Ashok R. , Matsumori Kishin , Patel Prit , Datla Anurag , Trindade Karina , Amarsanaa Enkhlen , Zhao Tonghan , Köhler Uwe , Busko Dmitry , Richards Bryce S.
Published: May 2024

Transparent roofs and walls offer a compelling solution for harnessing natural light. However, traditional glass roofs and walls face challenges such as glare, privacy concerns, and overheating issues. In this study, we present a polymer-based micro-photonic multi-functional metamaterial. The metamaterial diffuses 73% of incident sunlight, creating a more comfortable and private indoor environment. The visible spectral transmittance of the metamaterial (95%) surpasses that of traditional glass (91%). Furthermore, the metamaterial is estimated to enhance photosynthesis efficiency by ~9% compared to glass roofs. With a high emissivity (~0.98) close to that of a mid-infrared black body, the metamaterial is estimated to have a cooling capacity of ~97 W/m2 at ambient temperature. The metamaterial was about 6 °C cooler than the ambient temperature in humid Karlsruhe. The metamaterial exhibits superhydrophobic performance with a contact angle of 152°, significantly higher than that of glass (26°), thus potentially having excellent self-cleaning properties.
Structural basis for the intracellular regulation of ferritin degradation
Authors: Hoelzgen Fabian , Nguyen Thuy T. P. , Klukin Elina , Boumaiza Mohamed , Srivastava Ayush K. , Kim Elizabeth Y. , Zalk Ran , Shahar Anat , Cohen-Schwartz Sagit , Meyron-Holtz Esther G. , Bou-Abdallah Fadi , Mancias Joseph D. , Frank Gabriel A.
Published: May 2024

The interaction between nuclear receptor coactivator 4 (NCOA4) and the iron storage protein ferritin is a crucial component of cellular iron homeostasis. The binding of NCOA4 to the FTH1 subunits of ferritin initiates ferritinophagy—a ferritin-specific autophagic pathway leading to the release of the iron stored inside ferritin. The dysregulation of NCOA4 is associated with several diseases, including neurodegenerative disorders and cancer, highlighting the NCOA4-ferritin interface as a prime target for drug development. Here, we present the cryo-EM structure of the NCOA4-FTH1 interface, resolving 16 amino acids of NCOA4 that are crucial for the interaction. The characterization of mutants, designed to modulate the NCOA4–FTH1 interaction, is used to validate the significance of the different features of the binding site. Our results explain the role of the large solvent-exposed hydrophobic patch found on the surface of FTH1 and pave the way for the rational development of ferritinophagy modulators.
An interphase actin wave promotes mitochondrial content mixing and organelle homeostasis
Authors: Coscia Stephen M. , Moore Andrew S. , Thompson Cameron P. , Tirrito Christian F. , Ostap E. Michael , Holzbaur Erika L. F.
Published: May 2024

Across the cell cycle, mitochondrial dynamics are regulated by a cycling wave of actin polymerization/depolymerization. In metaphase, this wave induces actin comet tails on mitochondria that propel these organelles to drive spatial mixing, resulting in their equitable inheritance by daughter cells. In contrast, during interphase the cycling actin wave promotes localized mitochondrial fission. Here, we identify the F-actin nucleator/elongator FMNL1 as a positive regulator of the wave. FMNL1-depleted cells exhibit decreased mitochondrial polarization, decreased mitochondrial oxygen consumption, and increased production of reactive oxygen species. Accompanying these changes is a loss of hetero-fusion of wave-fragmented mitochondria. Thus, we propose that the interphase actin wave maintains mitochondrial homeostasis by promoting mitochondrial content mixing. Finally, we investigate the mechanistic basis for the observation that the wave drives mitochondrial motility in metaphase but mitochondrial fission in interphase. Our data indicate that when the force of actin polymerization is resisted by mitochondrial tethering to microtubules, as in interphase, fission results.
Impact of distinct FG nucleoporin repeats on Nup98 self-association
Authors: Ibáñez de Opakua Alain , Pantoja Christian F. , Cima-Omori Maria-Sol , Dienemann Christian , Zweckstetter Markus
Published: May 2024

Nucleoporins rich in phenylalanine/glycine (FG) residues form the permeability barrier within the nuclear pore complex and are implicated in several pathological cellular processes, including oncogenic fusion condensates. The self-association of FG-repeat proteins and interactions between FG-repeats play a critical role in these activities by forming hydrogel-like structures. Here we show that mutation of specific FG repeats of Nup98 can strongly decrease the protein’s self-association capabilities. We further present a cryo-electron microscopy structure of a Nup98 peptide fibril with higher stability per residue compared with previous Nup98 fibril structures. The high-resolution structure reveals zipper-like hydrophobic patches which contain a GLFG motif and are less compatible for binding to nuclear transport receptors. The identified distinct molecular properties of different regions of the nucleoporin may contribute to spatial variations in the self-association of FG-repeats, potentially influencing transport processes through the nuclear pore.
Persistent and multiclonal malaria parasite dynamics despite extended artemether-lumefantrine treatment in children
Authors: Goodwin Justin , Kajubi Richard , Wang Kaicheng , Li Fangyong , Wade Martina , Orukan Francis , Huang Liusheng , Whalen Meghan , Aweeka Francesca T. , Mwebaza Norah , Parikh Sunil
Published: May 2024

Standard diagnostics used in longitudinal antimalarial studies are unable to characterize the complexity of submicroscopic parasite dynamics, particularly in high transmission settings. We use molecular markers and amplicon sequencing to characterize post-treatment stage-specific malaria parasite dynamics during a 42 day randomized trial of 3- versus 5 day artemether-lumefantrine in 303 children with and without HIV (ClinicalTrials.gov number NCT03453840). The prevalence of parasite-derived 18S rRNA is >70% in children throughout follow-up, and the ring-stage marker SBP1 is detectable in over 15% of children on day 14 despite effective treatment. We find that the extended regimen significantly lowers the risk of recurrent ring-stage parasitemia compared to the standard 3 day regimen, and that higher day 7 lumefantrine concentrations decrease the probability of ring-stage parasites in the early post-treatment period. Longitudinal amplicon sequencing reveals remarkably dynamic patterns of multiclonal infections that include new and persistent clones in both the early post-treatment and later time periods. Our data indicate that post-treatment parasite dynamics are highly complex despite efficacious therapy, findings that will inform strategies to optimize regimens in the face of emerging partial artemisinin resistance in Africa.
Integrated optimization modelling framework for low-carbon and green regional transitions through resource-based industrial symbiosis
Authors: Xie Xin , Fu Hang , Zhu Qisheng , Hu Shanying
Published: May 2024

The development and utilization of bulk resources provide the basic material needs for industrial systems. However, most current resource utilization patterns are unsustainable, with low efficiencies and high carbon emissions. Here, we report a quantitative tool for resource-based industries to facilitate sustainable and low-carbon transitions within the regional economy. To evaluate the effectiveness of this tool, the saline Qinghai Lake region was chosen as a case study. After optimizing the industrial structure, the benefits of economic output, resource efficiency, energy consumption, solid waste reduction, and carbon emission reduction can be obtained. The scenario analyses exhibit disparities in different transition paths, where the carbon mitigation, economic output, and resource efficiency that benefit from optimal development paths are significantly better than those of the traditional path, indicating the urgency of adopting cleaner technology and industrial symbiosis for regional industries.
Towards accurate prediction of configurational disorder properties in materials using graph neural networks
Authors: Fang Zhenyao , Yan Qimin
Published: May 2024

The prediction of configurational disorder properties, such as configurational entropy and order-disorder phase transition temperature, of compound materials relies on efficient and accurate evaluations of configurational energies. Previous cluster expansion methods are not applicable to configurationally-complex material systems, including those with atomic distortions and long-range orders. In this work, we propose to leverage the versatile expressive capabilities of graph neural networks (GNNs) for efficient evaluations of configurational energies and present a workflow combining attention-based GNNs and Monte Carlo simulations to calculate the disorder properties. Using the dataset of face-centered tetragonal gold copper without and with local atomic distortions as an example, we demonstrate that the proposed data-driven framework enables the prediction of phase transition temperatures close to experimental values. We also elucidate that the variance of the energy deviations among configurations controls the prediction accuracy of disorder properties and can be used as the target loss function when training and selecting the GNN models. The work serves as a fundamental step toward a data-driven paradigm for the accelerated design of configurationally-complex functional material systems.
Ultrasensitive textile strain sensors redefine wearable silent speech interfaces with high machine learning efficiency
Authors: Tang Chenyu , Xu Muzi , Yi Wentian , Zhang Zibo , Occhipinti Edoardo , Dong Chaoqun , Ravenscroft Dafydd , Jung Sung-Min , Lee Sanghyo , Gao Shuo , Kim Jong Min , Occhipinti Luigi Giuseppe
Published: May 2024

This work introduces a silent speech interface (SSI), proposing a few-layer graphene (FLG) strain sensing mechanism based on thorough cracks and AI-based self-adaptation capabilities that overcome the limitations of state-of-the-art technologies by simultaneously achieving high accuracy, high computational efficiency, and fast decoding speed while maintaining excellent user comfort. We demonstrate its application in a biocompatible textile-integrated ultrasensitive strain sensor embedded into a smart choker, which conforms to the user’s throat. Thanks to the structure of ordered through cracks in the graphene-coated textile, the proposed strain gauge achieves a gauge factor of 317 with <5% strain, corresponding to a 420% improvement over existing textile strain sensors fabricated by printing and coating technologies reported to date. Its high sensitivity allows it to capture subtle throat movements, simplifying signal processing and enabling the use of a computationally efficient neural network. The resulting neural network, based on a one-dimensional convolutional model, reduces computational load by 90% while maintaining a remarkable 95.25% accuracy in speech decoding. The synergy in sensor design and neural network optimization offers a promising solution for practical, wearable SSI systems, paving the way for seamless, natural silent communication in diverse settings.
Cerebral organoids display dynamic clonal growth and tunable tissue replenishment
Authors: Lindenhofer Dominik , Haendeler Simon , Esk Christopher , Littleboy Jamie B. , Brunet Avalos Clarisse , Naas Julia , Pflug Florian G. , van de Ven Eline G. P. , Reumann Daniel , Baffet Alexandre D. , von Haeseler Arndt , Knoblich Jürgen A.
Published: May 2024

During brain development, neural progenitors expand through symmetric divisions before giving rise to differentiating cell types via asymmetric divisions. Transition between those modes varies among individual neural stem cells, resulting in clones of different sizes. Imaging-based lineage tracing allows for lineage analysis at high cellular resolution but systematic approaches to analyse clonal behaviour of entire tissues are currently lacking. Here we implement whole-tissue lineage tracing by genomic DNA barcoding in 3D human cerebral organoids, to show that individual stem cell clones produce progeny on a vastly variable scale. By using stochastic modelling we find that variable lineage sizes arise because a subpopulation of lineages retains symmetrically dividing cells. We show that lineage sizes can adjust to tissue demands after growth perturbation via chemical ablation or genetic restriction of a subset of cells in chimeric organoids. Our data suggest that adaptive plasticity of stem cell populations ensures robustness of development in human brain organoids.
Decrypting the molecular basis of cellular drug phenotypes by dose-resolved expression proteomics
Authors: Eckert Stephan , Berner Nicola , Kramer Karl , Schneider Annika , Müller Julian , Lechner Severin , Brajkovic Sarah , Sakhteman Amirhossein , Graetz Christian , Fackler Jonas , Dudek Michael , Pfaffl Michael W. , Knolle Percy , Wilhelm Stephanie , Kuster Bernhard
Published: May 2024

Proteomics is making important contributions to drug discovery, from target deconvolution to mechanism of action (MoA) elucidation and the identification of biomarkers of drug response. Here we introduce decryptE, a proteome-wide approach that measures the full dose–response characteristics of drug-induced protein expression changes that informs cellular drug MoA. Assaying 144 clinical drugs and research compounds against 8,000 proteins resulted in more than 1 million dose–response curves that can be interactively explored online in ProteomicsDB and a custom-built Shiny App. Analysis of the collective data provided molecular explanations for known phenotypic drug effects and uncovered new aspects of the MoA of human medicines. We found that histone deacetylase inhibitors potently and strongly down-regulated the T cell receptor complex resulting in impaired human T cell activation in vitro and ex vivo. This offers a rational explanation for the efficacy of histone deacetylase inhibitors in certain lymphomas and autoimmune diseases and explains their poor performance in treating solid tumors.
Functional variants in a TTTG microsatellite on 15q26.1 cause familial nonautoimmune thyroid abnormalities
Authors: Narumi Satoshi , Nagasaki Keisuke , Kiriya Mitsuo , Uehara Erika , Akiba Kazuhisa , Tanase-Nakao Kanako , Shimura Kazuhiro , Abe Kiyomi , Sugisawa Chiho , Ishii Tomohiro , Miyako Kenichi , Hasegawa Yukihiro , Maruo Yoshihiro , Muroya Koji , Watanabe Natsuko , Nishihara Eijun , Ito Yuka , Kogai Takahiko , Kameyama Kaori , Nakabayashi Kazuhiko , Hata Kenichiro , Fukami Maki , Shima Hirohito , Kikuchi Atsuo , Takayama Jun , Tamiya Gen , Hasegawa Tomonobu
Published: May 2024

Insufficient thyroid hormone production in newborns is referred to as congenital hypothyroidism. Multinodular goiter (MNG), characterized by an enlarged thyroid gland with multiple nodules, is usually seen in adults and is recognized as a separate disorder from congenital hypothyroidism. Here we performed a linkage analysis of a family with both nongoitrous congenital hypothyroidism and MNG and identified a signal at 15q26.1. Follow-up analyses with whole-genome sequencing and genetic screening in congenital hypothyroidism and MNG cohorts showed that changes in a noncoding TTTG microsatellite on 15q26.1 were frequently observed in congenital hypothyroidism (137 in 989) and MNG (3 in 33) compared with controls (3 in 38,722). Characterization of the noncoding variants with epigenomic data and in vitro experiments suggested that the microsatellite is located in a thyroid-specific transcriptional repressor, and its activity is disrupted by the variants. Collectively, we presented genetic evidence linking nongoitrous congenital hypothyroidism and MNG, providing unique insights into thyroid abnormalities.
Genomic analyses reveal the stepwise domestication and genetic mechanism of curd biogenesis in cauliflower
Authors: Chen Rui , Chen Ke , Yao Xingwei , Zhang Xiaoli , Yang Yingxia , Su Xiao , Lyu Mingjie , Wang Qian , Zhang Guan , Wang Mengmeng , Li Yanhao , Duan Lijin , Xie Tianyu , Li Haichao , Yang Yuyao , Zhang Hong , Guo Yutong , Jia Guiying , Ge Xianhong , Sarris Panagiotis F. , Lin Tao , Sun Deling
Published: May 2024

Cauliflower (Brassica oleracea L. var. botrytis) is a distinctive vegetable that supplies a nutrient-rich edible inflorescence meristem for the human diet. However, the genomic bases of its selective breeding have not been studied extensively. Herein, we present a high-quality reference genome assembly C-8 (V2) and a comprehensive genomic variation map consisting of 971 diverse accessions of cauliflower and its relatives. Genomic selection analysis and deep-mined divergences were used to explore a stepwise domestication process for cauliflower that initially evolved from broccoli (Curd-emergence and Curd-improvement), revealing that three MADS-box genes, CAULIFLOWER1 (CAL1), CAL2 and FRUITFULL (FUL2), could have essential roles during curd formation. Genome-wide association studies identified nine loci significantly associated with morphological and biological characters and demonstrated that a zinc-finger protein (BOB06G135460) positively regulates stem height in cauliflower. This study offers valuable genomic resources for better understanding the genetic bases of curd biogenesis and florescent development in crops.
Association of diabetic retinopathy on all-cause and cause-specific mortality in older adults with diabetes: National Health and Nutrition Examination Survey, 2005–2008
Authors: Liang Kun , Gui Siyu , Wang Xinchen , Wang Qianqian , Qiao Jianchao , Tao Liming , Liu Heting , Jiang Zhengxuan , Gao Jie
Published: May 2024

To evaluate the effect of diabetic retinopathy (DR) status or severity on all-cause and cause-specific mortality among diabetic older adults in the United States using the most recent National Health and Nutrition Examination Survey (NHANES) follow-up mortality data. The severity of DR was graded according to the Early Treatment Diabetic Retinopathy Study (ETDRS) grading scale. Multiple covariate-adjusted Cox proportional hazards regression models, Fine and Gray competing risk regression models, and propensity score matching (PSM) methods were used to assess the risk of all-cause and cause-specific mortality in individuals with diabetes. All analyses adopted the weighted data and complex stratified design approach proposed by the NHANES guidelines. Time to death was calculated based on the time between baseline and date of death or December 31, 2019, whichever came first. Ultimately 1077 participants, representing 3,025,316 US non-hospitalized individuals with diabetes, were included in the final analysis. After a median follow-up of 12.24 years (IQR, 11.16–13.49), 379 participants were considered deceased from all-causes, with 43.90% suffering from DR, including mild DR (41.50%), moderate to severe DR (46.77%), and proliferative DR (PDR) (67.21%). DR was associated with increased all-cause, cardiovascular disease (CVD) and diabetes mellitus (DM)-specific mortality, which remained consistent after propensity score matching (PSM). Results of DR grading assessment suggested that the presence of mild, moderate to severe NPDR was significantly associated with increased risk of all-cause and CVD-specific mortality, while the presence and severity of any DR was associated with increased DM-specific mortality, with a positive trend. The presence of DR in elderly individuals with diabetes is significantly associated with the elevated all-cause and CVD mortality. The grading or severity of DR may reflect the severity of cardiovascular disease status and overall mortality risk in patients with diabetes.