bluuebunny/crossref_metadata_2025 huggingface dataset:
A Non‐Intrusive Machine Learning Framework for Debiasing Long‐Time Coarse Resolution Climate Simulations and Quantifying Rare Events Statistics
Authors: Barthel Sorensen B. , Charalampopoulos A. , Zhang S. , Harrop B. E. , Leung L. R. , Sapsis T. P.
Published: March 2024

Due to the rapidly changing climate, the frequency and severity of extreme weather is expected to increase over the coming decades. As fully‐resolved climate simulations remain computationally intractable, policy makers must rely on coarse‐models to quantify risk for extremes. However, coarse models suffer from inherent bias due to the ignored “sub‐grid” scales. We propose a framework tonon‐intrusivelydebias coarse‐resolution climate predictions using neural‐network (NN) correction operators. Previous efforts have attempted to train such operators using loss functions that match statistics. However, this approach falls short with events that have longer return period than that of the training data, since the reference statistics have not converged. Here, the scope is to formulate a learning method that allows for correction of dynamics and quantification of extreme events with longer return period than the training data. The key obstacle is the chaotic nature of the underlying dynamics. To overcome this challenge, we introduce a dynamical systems approach where the correction operator is trained using reference data and a coarse model simulationnudgedtoward that reference. The method is demonstrated on debiasing an under‐resolved quasi‐geostrophic model and the Energy Exascale Earth System Model (E3SM). For the former, our method enables the quantification of events that have return period two orders longer than the training data. For the latter, when trained on 8 years of ERA5 data, our approach is able to correct the coarse E3SM output to closely reflect the 36‐year ERA5 statistics for all prognostic variables and significantly reduce their spatial biases.
Immunophenotypes in psychosis: is it a premature inflamm-aging disorder?
Authors: Chen Song , Tan Yunlong , Tian Li
Published: March 2024

Immunopsychiatric field has rapidly accumulated evidence demonstrating the involvement of both innate and adaptive immune components in psychotic disorders such as schizophrenia. Nevertheless, researchers are facing dilemmas of discrepant findings of immunophenotypes both outside and inside the brains of psychotic patients, as discovered by recent meta-analyses. These discrepancies make interpretations and interrogations on their roles in psychosis remain vague and even controversial, regarding whether certain immune cells are more activated or less so, and whether they are causal or consequential, or beneficial or harmful for psychosis. Addressing these issues for psychosis is not at all trivial, as immune cells either outside or inside the brain are an enormously heterogeneous and plastic cell population, falling into a vast range of lineages and subgroups, and functioning differently and malleably in context-dependent manners. This review aims to overview the currently known immunophenotypes of patients with psychosis, and provocatively suggest the premature immune “burnout” or inflamm-aging initiated since organ development as a potential primary mechanism behind these immunophenotypes and the pathogenesis of psychotic disorders.
Associations between antipsychotics-induced weight gain and brain networks of impulsivity
Authors: Grosu Claire , Klauser Paul , Dwir Daniella , Khadimallah Ines , Alemán-Gómez Yasser , Laaboub Nermine , Piras Marianna , Fournier Margot , Preisig Martin , Conus Philippe , Draganski Bogdan , Eap Chin B.
Published: March 2024

Given the unpredictable rapid onset and ubiquitous consequences of weight gain induced by antipsychotics, there is a pressing need to get insights into the underlying processes at the brain system level that will allow stratification of “at risk” patients. The pathophysiological hypothesis at hand is focused on brain networks governing impulsivity that are modulated by neuro-inflammatory processes. To this aim, we investigated brain anatomy and functional connectivity in patients with early psychosis (median age: 23 years, IQR = 21–27) using anthropometric data and magnetic resonance imaging acquired one month to one year after initiation of AP medication. Our analyses included 19 patients with high and rapid weight gain (i.e., ≥5% from baseline weight after one month) and 23 patients with low weight gain (i.e., <5% from baseline weight after one month). We replicated our analyses in young (26 years, IQR = 22–33, N = 102) and middle-aged (56 years, IQR = 51–62, N = 875) healthy individuals from the general population. In early psychosis patients, higher weight gain was associated with poor impulse control score (β = 1.35; P = 0.03). Here, the observed brain differences comprised nodes of impulsivity networks - reduced frontal lobe grey matter volume (Pcorrected = 0.007) and higher striatal volume (Pcorrected = 0.048) paralleled by disruption of fronto-striatal functional connectivity (R = −0.32; P = 0.04). Weight gain was associated with the inflammatory biomarker plasminogen activator inhibitor-1 (β = 4.9, P = 0.002). There was no significant association between increased BMI or weight gain and brain anatomy characteristics in both cohorts of young and middle-aged healthy individuals. Our findings support the notion of weight gain in treated psychotic patients associated with poor impulse control, impulsivity-related brain networks and chronic inflammation.
End-stage ADPKD with a low-frequency PKD1 mosaic variant accelerated by chemoradiotherapy
Authors: Hanafusa Hiroaki , Yamaguchi Hiroshi , Morisada Naoya , YE Ming Juan , Matsumoto Riki , Nagase Hiroaki , Nozu Kandai
Published: March 2024

Autosomal dominant polycystic kidney disease (ADPKD) is commonly caused by PKD1, and mosaic PKD1 variants result in milder phenotypes. We present the case of a 32 year-old male with chronic active Epstein–Barr virus who underwent bone marrow transplantation with chemoradiotherapy at age 9. Despite a low-frequency mosaic splicing PKD1 variant, he developed severe renal cysts and end-stage renal disease in his 30 s. This case highlights how environmental factors may contribute to the genetic predisposition to ADPKD.
Remodeling of the postsynaptic proteome in male mice and marmosets during synapse development
Authors: Kaizuka Takeshi , Suzuki Takehiro , Kishi Noriyuki , Tamada Kota , Kilimann Manfred W. , Ueyama Takehiko , Watanabe Masahiko , Shimogori Tomomi , Okano Hideyuki , Dohmae Naoshi , Takumi Toru
Published: March 2024

Postsynaptic proteins play crucial roles in synaptic function and plasticity. During brain development, alterations in synaptic number, shape, and stability occur, known as synapse maturation. However, the postsynaptic protein composition changes during development are not fully understood. Here, we show the trajectory of the postsynaptic proteome in developing male mice and common marmosets. Proteomic analysis of mice at 2, 3, 6, and 12 weeks of age shows that proteins involved in synaptogenesis are differentially expressed during this period. Analysis of published transcriptome datasets shows that the changes in postsynaptic protein composition in the mouse brain after 2 weeks of age correlate with gene expression changes. Proteomic analysis of marmosets at 0, 2, 3, 6, and 24 months of age show that the changes in the marmoset brain can be categorized into two parts: the first 2 months and after that. The changes observed in the first 2 months are similar to those in the mouse brain between 2 and 12 weeks of age. The changes observed in marmoset after 2 months old include differential expression of synaptogenesis-related molecules, which hardly overlap with that in mice. Our results provide a comprehensive proteomic resource that underlies developmental synapse maturation in rodents and primates.
A dual diffusion model enables 3D molecule generation and lead optimization based on target pockets
Authors: Huang Lei , Xu Tingyang , Yu Yang , Zhao Peilin , Chen Xingjian , Han Jing , Xie Zhi , Li Hailong , Zhong Wenge , Wong Ka-Chun , Zhang Hengtong
Published: March 2024

Structure-based generative chemistry is essential in computer-aided drug discovery by exploring a vast chemical space to design ligands with high binding affinity for targets. However, traditional in silico methods are limited by computational inefficiency, while machine learning approaches face bottlenecks due to auto-regressive sampling. To address these concerns, we have developed a conditional deep generative model, PMDM, for 3D molecule generation fitting specified targets. PMDM consists of a conditional equivariant diffusion model with both local and global molecular dynamics, enabling PMDM to consider the conditioned protein information to generate molecules efficiently. The comprehensive experiments indicate that PMDM outperforms baseline models across multiple evaluation metrics. To evaluate the applications of PMDM under real drug design scenarios, we conduct lead compound optimization for SARS-CoV-2 main protease (Mpro) and Cyclin-dependent Kinase 2 (CDK2), respectively. The selected lead optimization molecules are synthesized and evaluated for their in-vitro activities against CDK2, displaying improved CDK2 activity.
Accounting for albedo change to identify climate-positive tree cover restoration
Authors: Hasler Natalia , Williams Christopher A. , Denney Vanessa Carrasco , Ellis Peter W. , Shrestha Surendra , Terasaki Hart Drew E. , Wolff Nicholas H. , Yeo Samantha , Crowther Thomas W. , Werden Leland K. , Cook-Patton Susan C.
Published: March 2024

Restoring tree cover changes albedo, which is the fraction of sunlight reflected from the Earth’s surface. In most locations, these changes in albedo offset or even negate the carbon removal benefits with the latter leading to global warming. Previous efforts to quantify the global climate mitigation benefit of restoring tree cover have not accounted robustly for albedo given a lack of spatially explicit data. Here we produce maps that show that carbon-only estimates may be up to 81% too high. While dryland and boreal settings have especially severe albedo offsets, it is possible to find places that provide net-positive climate mitigation benefits in all biomes. We further find that on-the-ground projects are concentrated in these more climate-positive locations, but that the majority still face at least a 20% albedo offset. Thus, strategically deploying restoration of tree cover for maximum climate benefit requires accounting for albedo change and we provide the tools to do so.
Structure and function of Semaphorin-5A glycosaminoglycan interactions
Authors: Nagy Gergely N. , Zhao Xiao-Feng , Karlsson Richard , Wang Karen , Duman Ramona , Harlos Karl , El Omari Kamel , Wagner Armin , Clausen Henrik , Miller Rebecca L. , Giger Roman J. , Jones E. Yvonne
Published: March 2024

Integration of extracellular signals by neurons is pivotal for brain development, plasticity, and repair. Axon guidance relies on receptor-ligand interactions crosstalking with extracellular matrix components. Semaphorin-5A (Sema5A) is a bifunctional guidance cue exerting attractive and inhibitory effects on neuronal growth through the interaction with heparan sulfate (HS) and chondroitin sulfate (CS) glycosaminoglycans (GAGs), respectively. Sema5A harbors seven thrombospondin type-1 repeats (TSR1-7) important for GAG binding, however the underlying molecular basis and functions in vivo remain enigmatic. Here we dissect the structural basis for Sema5A:GAG specificity and demonstrate the functional significance of this interaction in vivo. Using x-ray crystallography, we reveal a dimeric fold variation for TSR4 that accommodates GAG interactions. TSR4 co-crystal structures identify binding residues validated by site-directed mutagenesis. In vitro and cell-based assays uncover specific GAG epitopes necessary for TSR association. We demonstrate that HS-GAG binding is preferred over CS-GAG and mediates Sema5A oligomerization. In vivo, Sema5A:GAG interactions are necessary for Sema5A function and regulate Plexin-A2 dependent dentate progenitor cell migration. Our study rationalizes Sema5A associated developmental and neurological disorders and provides mechanistic insights into how multifaceted guidance functions of a single transmembrane cue are regulated by proteoglycans.
The IL-33/ST2 axis is protective against acute inflammation during the course of periodontitis
Authors: Liu Anhao , Hayashi Mikihito , Ohsugi Yujin , Katagiri Sayaka , Akira Shizuo , Iwata Takanori , Nakashima Tomoki
Published: March 2024

Periodontitis, which is induced by repeated bacterial invasion and the ensuing immune reactions that follow, is the leading cause of tooth loss. Periodontal tissue is comprised of four different components, each with potential role in pathogenesis, however, most studies on immune responses focus on gingival tissue. Here, we present a modified ligature-induced periodontitis model in male mice to analyze the pathogenesis, which captures the complexity of periodontal tissue. We find that the inflammatory response in the peri-root tissues and the expression of IL-6 and RANKL by Thy-1.2− fibroblasts/stromal cells are prominent throughout the bone destruction phase, and present already at an early stage. The initiation phase is characterized by high levels of ST2 (encoded by Il1rl1) expression in the peri-root tissue, suggesting that the IL-33/ST2 axis is involved in the pathogenesis. Both Il1rl1- and Il33-deficient mice exhibit exacerbated bone loss in the acute phase of periodontitis, along with macrophage polarization towards a classically activated phenotype and increased neutrophil infiltration, indicating a protective role of the IL-33/ST2 axis in acute inflammation. Thus, our findings highlight the hidden role of the peri-root tissue and simultaneously advance our understanding of the etiology of periodontitis via implicating the IL-33/ST2 axis.
Using rare genetic mutations to revisit structural brain asymmetry
Authors: Kopal Jakub , Kumar Kuldeep , Shafighi Kimia , Saltoun Karin , Modenato Claudia , Moreau Clara A. , Huguet Guillaume , Jean-Louis Martineau , Martin Charles-Olivier , Saci Zohra , Younis Nadine , Douard Elise , Jizi Khadije , Beauchamp-Chatel Alexis , Kushan Leila , Silva Ana I. , van den Bree Marianne B. M. , Linden David E. J. , Owen Michael J. , Hall Jeremy , Lippé Sarah , Draganski Bogdan , Sønderby Ida E. , Andreassen Ole A. , Glahn David C. , Thompson Paul M. , Bearden Carrie E. , Zatorre Robert , Jacquemont Sébastien , Bzdok Danilo
Published: March 2024

Asymmetry between the left and right hemisphere is a key feature of brain organization. Hemispheric functional specialization underlies some of the most advanced human-defining cognitive operations, such as articulated language, perspective taking, or rapid detection of facial cues. Yet, genetic investigations into brain asymmetry have mostly relied on common variants, which typically exert small effects on brain-related phenotypes. Here, we leverage rare genomic deletions and duplications to study how genetic alterations reverberate in human brain and behavior. We designed a pattern-learning approach to dissect the impact of eight high-effect-size copy number variations (CNVs) on brain asymmetry in a multi-site cohort of 552 CNV carriers and 290 non-carriers. Isolated multivariate brain asymmetry patterns spotlighted regions typically thought to subserve lateralized functions, including language, hearing, as well as visual, face and word recognition. Planum temporale asymmetry emerged as especially susceptible to deletions and duplications of specific gene sets. Targeted analysis of common variants through genome-wide association study (GWAS) consolidated partly diverging genetic influences on the right versus left planum temporale structure. In conclusion, our gene-brain-behavior data fusion highlights the consequences of genetically controlled brain lateralization on uniquely human cognitive capacities.
Synthetically-primed adaptation of Pseudomonas putida to a non-native substrate D-xylose
Authors: Dvořák Pavel , Burýšková Barbora , Popelářová Barbora , Ebert Birgitta E. , Botka Tibor , Bujdoš Dalimil , Sánchez-Pascuala Alberto , Schöttler Hannah , Hayen Heiko , de Lorenzo Víctor , Blank Lars M. , Benešík Martin
Published: March 2024

To broaden the substrate scope of microbial cell factories towards renewable substrates, rational genetic interventions are often combined with adaptive laboratory evolution (ALE). However, comprehensive studies enabling a holistic understanding of adaptation processes primed by rational metabolic engineering remain scarce. The industrial workhorse Pseudomonas putida was engineered to utilize the non-native sugar D-xylose, but its assimilation into the bacterial biochemical network via the exogenous xylose isomerase pathway remained unresolved. Here, we elucidate the xylose metabolism and establish a foundation for further engineering followed by ALE. First, native glycolysis is derepressed by deleting the local transcriptional regulator gene hexR. We then enhance the pentose phosphate pathway by implanting exogenous transketolase and transaldolase into two lag-shortened strains and allow ALE to finetune the rewired metabolism. Subsequent multilevel analysis and reverse engineering provide detailed insights into the parallel paths of bacterial adaptation to the non-native carbon source, highlighting the enhanced expression of transaldolase and xylose isomerase along with derepressed glycolysis as key events during the process.
Abundant pleiotropy across neuroimaging modalities identified through a multivariate genome-wide association study
Authors: Tissink E. P. , Shadrin A. A. , van der Meer D. , Parker N. , Hindley G. , Roelfs D. , Frei O. , Fan C. C. , Nagel M. , Nærland T. , Budisteanu M. , Djurovic S. , Westlye L. T. , van den Heuvel M. P. , Posthuma D. , Kaufmann T. , Dale A. M. , Andreassen O. A.
Published: March 2024

Genetic pleiotropy is abundant across spatially distributed brain characteristics derived from one neuroimaging modality (e.g. structural, functional or diffusion magnetic resonance imaging [MRI]). A better understanding of pleiotropy across modalities could inform us on the integration of brain function, micro- and macrostructure. Here we show extensive genetic overlap across neuroimaging modalities at a locus and gene level in the UK Biobank (N = 34,029) and ABCD Study (N = 8607). When jointly analysing phenotypes derived from structural, functional and diffusion MRI in a genome-wide association study (GWAS) with the Multivariate Omnibus Statistical Test (MOSTest), we boost the discovery of loci and genes beyond previously identified effects for each modality individually. Cross-modality genes are involved in fundamental biological processes and predominantly expressed during prenatal brain development. We additionally boost prediction of psychiatric disorders by conditioning independent GWAS on our multimodal multivariate GWAS. These findings shed light on the shared genetic mechanisms underlying variation in brain morphology, functional connectivity, and tissue composition.
Engineering biology and climate change mitigation: Policy considerations
Authors: Symons Jonathan , Dixon Thomas A. , Dalziell Jacqueline , Curach Natalie , Paulsen Ian T. , Wiskich Anthony , Pretorius Isak S.
Published: March 2024

Engineering biology (EngBio) is a dynamic field that uses gene editing, synthesis, assembly, and engineering to design new or modified biological systems. EngBio applications could make a significant contribution to achieving net zero greenhouse gas emissions. Yet, policy support will be needed if EngBio is to fulfil its climate mitigation potential. What form should such policies take, and what EngBio applications should they target? This paper reviews EngBio’s potential climate contributions to assist policymakers shape regulations and target resources and, in so doing, to facilitate democratic deliberation on desirable futures.
Casein kinase II promotes piRNA production through direct phosphorylation of USTC component TOFU-4
Authors: Zhang Gangming , Zheng Chunwei , Ding Yue-he , Mello Craig
Published: March 2024

Piwi-interacting RNAs (piRNAs) are genomically encoded small RNAs that engage Piwi Argonaute proteins to direct mRNA surveillance and transposon silencing. Despite advances in understanding piRNA pathways and functions, how the production of piRNA is regulated remains elusive. Here, using a genetic screen, we identify casein kinase II (CK2) as a factor required for piRNA pathway function. We show that CK2 is required for the localization of PRG-1 and for the proper localization of several factors that comprise the ‘upstream sequence transcription complex’ (USTC), which is required for piRNA transcription. Loss of CK2 impairs piRNA levels suggesting that CK2 promotes USTC function. We identify the USTC component twenty-one-U fouled-up 4 (TOFU-4) as a direct substrate for CK2. Our findings suggest that phosphorylation of TOFU-4 by CK2 promotes the assembly of USTC and piRNA transcription. Notably, during the aging process, CK2 activity declines, resulting in the disassembly of USTC, decreased piRNA production, and defects in piRNA-mediated gene silencing, including transposons silencing. These findings highlight the significance of posttranslational modification in regulating piRNA biogenesis and its implications for the aging process. Overall, our study provides compelling evidence for the involvement of a posttranslational modification mechanism in the regulation of piRNA biogenesis.
Defects in the cell wall and its deposition caused by loss-of-function of three RLKs alter root hydrotropism in Arabidopsis thaliana
Authors: Chang Jinke , Li Xiaopeng , Shen Juan , Hu Jun , Wu Liangfan , Zhang Xueyao , Li Jia
Published: March 2024

Root tips can sense moisture gradients and grow into environments with higher water potential. This process is called root hydrotropism. Here, we report three closely related receptor-like kinases (RLKs) that play critical roles in root hydrotropism: ALTERED ROOT HYDROTROPIC RESPONSE 1 (ARH1), FEI1, and FEI2. Overexpression of these RLKs strongly reduce root hydrotropism, but corresponding loss-of-function mutants exhibit an increased hydrotropic response in their roots. All these RLKs show polar localization at the plasma membrane regions in root tips. The biosynthesis of the cell wall, cutin, and wax (CCW) is significantly impaired in root tips of arh1-2 fei1-C fei2-C. A series of known CCW mutants also exhibit increased root hydrotropism and reduced osmotic tolerance, similar to the characteristics of the triple mutant. Our results demonstrat that the integrity of the cell wall, cutin, and root cap wax mediate a trade-off between root hydrotropism and osmotic tolerance.
RETRACTED ARTICLE: Metal free cross-dehydrogenative N-N coupling of primary amides with Lewis basic amines
Authors: Kathiravan Subban , Dhillon Prakriti , Zhang Tianshu , Nicholls Ian A.
Published: March 2024

Hydrazides, N-N containing structural motifs, are important due to their presence in a wide variety of biologically significant compounds. While the homo N-N coupling of two NH moieties to form the hydrazide N-N bond is well developed, the cross-dehydrogenative hetero N-N coupling remains very unevolved. Here we present an efficient intermolecular N-N cross-coupling of a series of primary benzamides with broad range of Lewis basic primary and secondary amines using PhI(OAc)2as both a terminal oxidant and a cross-coupling mediator, without the need for metal catalysts, high temperatures, and inert atmospheres, and with substantial potential for use in the late-stage functionalization of drugs.
Quantifying the interfacial triboelectricity in inorganic-organic composite mechanoluminescent materials
Authors: Pan Xin , Zhuang Yixi , He Wei , Lin Cunjian , Mei Lefu , Chen Changjian , Xue Hao , Sun Zhigang , Wang Chunfeng , Peng Dengfeng , Zheng Yanqing , Pan Caofeng , Wang Lixin , Xie Rong-Jun
Published: March 2024

Mechanoluminescence (ML) sensing technologies open up new opportunities for intelligent sensors, self-powered displays and wearable devices. However, the emission efficiency of ML materials reported so far still fails to meet the growing application requirements due to the insufficiently understood mechano-to-photon conversion mechanism. Herein, we propose to quantify the ability of different phases to gain or lose electrons under friction (defined as triboelectric series), and reveal that the inorganic-organic interfacial triboelectricity is a key factor in determining the ML in inorganic-organic composites. A positive correlation between the difference in triboelectric series and the ML intensity is established in a series of composites, and a 20-fold increase in ML intensity is finally obtained by selecting an appropriate inorganic-organic combination. The interfacial triboelectricity-regulated ML is further demonstrated in multi-interface systems that include an inorganic phosphor-organic matrix and organic matrix-force applicator interfaces, and again confirmed by self-oxidization and reduction of emission centers under continuous mechanical stimulus. This work not only gives direct experimental evidences for the underlying mechanism of ML, but also provides guidelines for rationally designing high-efficiency ML materials.
Precise prediction of phase-separation key residues by machine learning
Authors: Sun Jun , Qu Jiale , Zhao Cai , Zhang Xinyao , Liu Xinyu , Wang Jia , Wei Chao , Liu Xinyi , Wang Mulan , Zeng Pengguihang , Tang Xiuxiao , Ling Xiaoru , Qing Li , Jiang Shaoshuai , Chen Jiahao , Chen Tara S. R. , Kuang Yalan , Gao Jinhang , Zeng Xiaoxi , Huang Dongfeng , Yuan Yong , Fan Lili , Yu Haopeng , Ding Junjun
Published: March 2024

Understanding intracellular phase separation is crucial for deciphering transcriptional control, cell fate transitions, and disease mechanisms. However, the key residues, which impact phase separation the most for protein phase separation function have remained elusive. We develop PSPHunter, which can precisely predict these key residues based on machine learning scheme. In vivo and in vitro validations demonstrate that truncating just 6 key residues in GATA3 disrupts phase separation, enhancing tumor cell migration and inhibiting growth. Glycine and its motifs are enriched in spacer and key residues, as revealed by our comprehensive analysis. PSPHunter identifies nearly 80% of disease-associated phase-separating proteins, with frequent mutated pathological residues like glycine and proline often residing in these key residues. PSPHunter thus emerges as a crucial tool to uncover key residues, facilitating insights into phase separation mechanisms governing transcriptional control, cell fate transitions, and disease development.
Genetic similarity between relatives provides evidence on the presence and history of assortative mating
Authors: Sunde Hans Fredrik , Eftedal Nikolai Haahjem , Cheesman Rosa , Corfield Elizabeth C. , Kleppesto Thomas H. , Seierstad Anne Caroline , Ystrom Eivind , Eilertsen Espen Moen , Torvik Fartein Ask
Published: March 2024

Assortative mating – the non-random mating of individuals with similar traits – is known to increase trait-specific genetic variance and genetic similarity between relatives. However, empirical evidence is limited for many traits, and the implications hinge on whether assortative mating has started recently or many generations ago. Here we show theoretically and empirically that genetic similarity between relatives can provide evidence on the presence and history of assortative mating. First, we employed path analysis to understand how assortative mating affects genetic similarity between family members across generations, finding that similarity between distant relatives is more affected than close relatives. Next, we correlated polygenic indices of 47,135 co-parents from the Norwegian Mother, Father, and Child Cohort Study (MoBa) and found genetic evidence of assortative mating in nine out of sixteen examined traits. The same traits showed elevated similarity between relatives, especially distant relatives. Six of the nine traits, including educational attainment, showed greater genetic variance among offspring, which is inconsistent with stable assortative mating over many generations. These results suggest an ongoing increase in familial similarity for these traits. The implications of this research extend to genetic methodology and the understanding of social and economic disparities.
Engineering the pore environment of antiparallel stacked covalent organic frameworks for capture of iodine pollutants
Authors: Xie Yinghui , Rong Qiuyu , Mao Fengyi , Wang Shiyu , Wu You , Liu Xiaolu , Hao Mengjie , Chen Zhongshan , Yang Hui , Waterhouse Geoffrey I. N. , Ma Shengqian , Wang Xiangke
Published: March 2024

Radioiodine capture from nuclear fuel waste and contaminated water sources is of enormous environmental importance, but remains technically challenging. Herein, we demonstrate robust covalent organic frameworks (COFs) with antiparallel stacked structures, excellent radiation resistance, and high binding affinities toward I2, CH3I, and I3− under various conditions. A neutral framework (ACOF-1) achieves a high affinity through the cooperative functions of pyridine-N and hydrazine groups from antiparallel stacking layers, resulting in a high capacity of ~2.16 g/g for I2 and ~0.74 g/g for CH3I at 25 °C under dynamic adsorption conditions. Subsequently, post-synthetic methylation of ACOF-1 converted pyridine-N sites to cationic pyridinium moieties, yielding a cationic framework (namely ACOF-1R) with enhanced capacity for triiodide ion capture from contaminated water. ACOF-1R can rapidly decontaminate iodine polluted groundwater to drinking levels with a high uptake capacity of ~4.46 g/g established through column breakthrough tests. The cooperative functions of specific binding moieties make ACOF-1 and ACOF-1R promising adsorbents for radioiodine pollutants treatment under practical conditions.
Cell-fate conversion of intestinal cells in adult Drosophila midgut by depleting a single transcription factor
Authors: Guo Xingting , Wang Chenhui , Zhang Yongchao , Wei Ruxue , Xi Rongwen
Published: March 2024

The manipulation of cell identity by reprograming holds immense potential in regenerative medicine, but is often limited by the inefficient acquisition of fully functional cells. This problem can potentially be resolved by better understanding the reprogramming process using in vivo genetic models, which are currently scarce. Here we report that both enterocytes (ECs) and enteroendocrine cells (EEs) in adultDrosophilamidgut show a surprising degree of cell plasticity. Depleting the transcription factor Tramtrack in the differentiated ECs can initiate Prospero-mediated cell transdifferentiation, leading to EE-like cells. On the other hand, depletion of Prospero in the differentiated EEs can lead to the loss of EE-specific transcription programs and the gain of intestinal progenitor cell identity, allowing cell cycle re-entry or differentiation into ECs. We find that intestinal progenitor cells, ECs, and EEs have a similar chromatin accessibility profile, supporting the concept that cell plasticity is enabled by pre-existing chromatin accessibility with switchable transcription programs. Further genetic analysis with this system reveals that the NuRD chromatin remodeling complex, cell lineage confliction, and age act as barriers to EC-to-EE transdifferentiation. The establishment of this genetically tractable in vivo model should facilitate mechanistic investigation of cell plasticity at the molecular and genetic level.
Substantially reducing global PM2.5-related deaths under SDG3.9 requires better air pollution control and healthcare
Authors: Yue Huanbi , He Chunyang , Huang Qingxu , Zhang Da , Shi Peijun , Moallemi Enayat A. , Xu Fangjin , Yang Yang , Qi Xin , Ma Qun , Bryan Brett A.
Published: March 2024

The United Nations’ Sustainable Development Goal (SDG) 3.9 calls for a substantial reduction in deaths attributable to PM2.5 pollution (DAPP). However, DAPP projections vary greatly and the likelihood of meeting SDG3.9 depends on complex interactions among environmental, socio-economic, and healthcare parameters. We project potential future trends in global DAPP considering the joint effects of each driver (PM2.5 concentration, death rate of diseases, population size, and age structure) and assess the likelihood of achieving SDG3.9 under the Shared Socioeconomic Pathways (SSPs) as quantified by the Scenario Model Intercomparison Project (ScenarioMIP) framework with simulated PM2.5 concentrations from 11 models. We find that a substantial reduction in DAPP would not be achieved under all but the most optimistic scenario settings. Even the development aligned with the Sustainability scenario (SSP1-2.6), in which DAPP was reduced by 19%, still falls just short of achieving a substantial (≥20%) reduction by 2030. Meeting SDG3.9 calls for additional efforts in air pollution control and healthcare to more aggressively reduce DAPP.
The SARS-CoV-2 neutralizing antibody response to SD1 and its evasion by BA.2.86
Authors: Zhou Daming , Supasa Piyada , Liu Chang , Dijokaite-Guraliuc Aiste , Duyvesteyn Helen M. E. , Selvaraj Muneeswaran , Mentzer Alexander J. , Das Raksha , Dejnirattisai Wanwisa , Temperton Nigel , Klenerman Paul , Dunachie Susanna J. , Fry Elizabeth E. , Mongkolsapaya Juthathip , Ren Jingshan , Stuart David I. , Screaton Gavin R.
Published: March 2024

Under pressure from neutralising antibodies induced by vaccination or infection the SARS-CoV-2 spike gene has become a hotspot for evolutionary change, leading to the failure of all mAbs developed for clinical use. Most potent antibodies bind to the receptor binding domain which has become heavily mutated. Here we study responses to a conserved epitope in sub-domain-1 (SD1) of spike which have become more prominent because of mutational escape from antibodies directed to the receptor binding domain. Some SD1 reactive mAbs show potent and broad neutralization of SARS-CoV-2 variants. We structurally map the dominant SD1 epitope and provide a mechanism of action by blocking interaction with ACE2. Mutations in SD1 have not been sustained to date, but one, E554K, leads to escape from mAbs. This mutation has now emerged in several sublineages including BA.2.86, reflecting selection pressure on the virus exerted by the increasing prominence of the anti-SD1 response.
Profiling the colonic mucosal response to fecal microbiota transplantation identifies a role for GBP5 in colitis in humans and mice
Authors: Luu Laurence D. W. , Pandey Abhimanu , Paramsothy Sudarshan , Ngo Chinh , Castaño-Rodríguez Natalia , Liu Cheng , Kamm Michael A. , Borody Thomas J. , Man Si Ming , Kaakoush Nadeem O.
Published: March 2024

Host molecular responses to fecal microbiota transplantation (FMT) in ulcerative colitis are not well understood. Here, we profile the human colonic mucosal transcriptome prior to and following FMT or placebo to identify molecules regulated during disease remission. FMT alters the transcriptome above the effect of placebo (n = 75 vs 3 genes, q < 0.05), including modulation of structural, metabolic and inflammatory pathways. This response is attributed to responders with no consistency observed in non-responders. Regulated pathways in responders include tight junctions, calcium signalling and xenobiotic metabolism. Genes significantly regulated longitudinally in responders post-FMT could discriminate them from responders and non-responders at baseline and non-responders post-FMT, with GBP5 and IRF4 downregulation being associated with remission. Female mice with a deletion of GBP5 are more resistant to developing colitis than their wild-type littermates, showing higher colonic IRF4 phosphorylation. The colonic mucosal response discriminates UC remission following FMT, with GBP5 playing a detrimental role in colitis.
Meta-analysis shows the impacts of ecological restoration on greenhouse gas emissions
Authors: He Tiehu , Ding Weixin , Cheng Xiaoli , Cai Yanjiang , Zhang Yulong , Xia Huijuan , Wang Xia , Zhang Jiehao , Zhang Kerong , Zhang Quanfa
Published: March 2024

International initiatives set ambitious targets for ecological restoration, which is considered a promising greenhouse gas mitigation strategy. Here, we conduct a meta-analysis to quantify the impacts of ecological restoration on greenhouse gas emissions using a dataset compiled from 253 articles. Our findings reveal that forest and grassland restoration increase CH4 uptake by 90.0% and 30.8%, respectively, mainly due to changes in soil properties. Conversely, wetland restoration increases CH4 emissions by 544.4%, primarily attributable to elevated water table depth. Forest and grassland restoration have no significant effect on N2O emissions, while wetland restoration reduces N2O emissions by 68.6%. Wetland restoration enhances net CO2 uptake, and the transition from net CO2 sources to net sinks takes approximately 4 years following restoration. The net ecosystem CO2 exchange of the restored forests decreases with restoration age, and the transition from net CO2 sources to net sinks takes about 3-5 years for afforestation and reforestation sites, and 6-13 years for clear-cutting and post-fire sites. Overall, forest, grassland and wetland restoration decrease the global warming potentials by 327.7%, 157.7% and 62.0% compared with their paired control ecosystems, respectively. Our findings suggest that afforestation, reforestation, rewetting drained wetlands, and restoring degraded grasslands through grazing exclusion, reducing grazing intensity, or converting croplands to grasslands can effectively mitigate greenhouse gas emissions.
Structure of the intact tail machine of Anabaena myophage A-1(L)
Authors: Yu Rong-Cheng , Yang Feng , Zhang Hong-Yan , Hou Pu , Du Kang , Zhu Jie , Cui Ning , Xu Xudong , Chen Yuxing , Li Qiong , Zhou Cong-Zhao
Published: March 2024

The Myoviridae cyanophage A-1(L) specifically infects the model cyanobacteria Anabaena sp. PCC 7120. Following our recent report on the capsid structure of A-1(L), here we present the high-resolution cryo-EM structure of its intact tail machine including the neck, tail and attached fibers. Besides the dodecameric portal, the neck contains a canonical hexamer connected to a unique pentadecamer that anchors five extended bead-chain-like neck fibers. The 1045-Å-long contractile tail is composed of a helical bundle of tape measure proteins surrounded by a layer of tube proteins and a layer of sheath proteins, ended with a five-component baseplate. The six long and six short tail fibers are folded back pairwise, each with one end anchoring to the baseplate and the distal end pointing to the capsid. Structural analysis combined with biochemical assays further enable us to identify the dual hydrolytic activities of the baseplate hub, in addition to two host receptor binding domains in the tail fibers. Moreover, the structure of the intact A-1(L) also helps us to reannotate its genome. These findings will facilitate the application of A-1(L) as a chassis cyanophage in synthetic biology.
Keto-anthraquinone covalent organic framework for H2O2 photosynthesis with oxygen and alkaline water
Authors: Zhang Xiangcheng , Cheng Silian , Chen Chao , Wen Xue , Miao Jie , Zhou Baoxue , Long Mingce , Zhang Lizhi
Published: March 2024

Hydrogen peroxide photosynthesis suffers from insufficient catalytic activity due to the high energy barrier of hydrogen extraction from H2O. Herein, we report that mechanochemically synthesized keto-form anthraquinone covalent organic framework which is able to directly synthesize H2O2 (4784 μmol h−1 g−1 at λ > 400 nm) from oxygen and alkaline water (pH = 13) in the absence of any sacrificial reagents. The strong alkalinity resulted in the formation of OH-(H2O)n clusters in water, which were adsorbed on keto moieties within the framework and then dissociated into O2 and active hydrogen, because the energy barrier of hydrogen extraction was largely lowered. The produced hydrogen reacted with anthraquinone to generate anthrahydroquinone, which was subsequently oxidized by O2 to produce H2O2. This study ultimately sheds light on the importance of hydrogen extraction from H2O for H2O2 photosynthesis and demonstrates that H2O2 synthesis is achievable under alkaline conditions.
Grave-to-cradle photothermal upcycling of waste polyesters over spent LiCoO2
Authors: Lou Xiangxi , Yan Penglei , Jiao Binglei , Li Qingye , Xu Panpan , Wang Lei , Zhang Liang , Cao Muhan , Wang Guiling , Chen Zheng , Zhang Qiao , Chen Jinxing
Published: March 2024

Lithium-ion batteries (LIBs) and plastics are pivotal components of modern society; nevertheless, their escalating production poses formidable challenges to resource sustainability and ecosystem integrity. Here, we showcase the transformation of spent lithium cobalt oxide (LCO) cathodes into photothermal catalysts capable of catalyzing the upcycling of diverse waste polyesters into high-value monomers. The distinctive Li deficiency in spent LCO induces a contraction in the Co−O6 unit cell, boosting the monomer yield exceeding that of pristine LCO by a factor of 10.24. A comprehensive life-cycle assessment underscores the economic viability of utilizing spent LCO as a photothermal catalyst, yielding returns of 129.6 $·kgLCO−1, surpassing traditional battery recycling returns (13–17 $·kgLCO−1). Solar-driven recycling 100,000 tons of PET can reduce 3.459 × 1011 kJ of electric energy and decrease 38,716 tons of greenhouse gas emissions. This work unveils a sustainable solution for the management of spent LIBs and plastics.
Synergistically optimized electron and phonon transport in high-performance copper sulfides thermoelectric materials via one-pot modulation
Authors: Zhang Yi-Xin , Huang Qin-Yuan , Yan Xi , Wang Chong-Yu , Yang Tian-Yu , Wang Zi-Yuan , Shi Yong-Cai , Shan Quan , Feng Jing , Ge Zhen-Hua
Published: March 2024

Optimizing thermoelectric conversion efficiency requires the compromise of electrical and thermal properties of materials, which are hard to simultaneously improve due to the strong coupling of carrier and phonon transport. Herein, a one-pot approach realizing simultaneous second phase and Cu vacancies modulation is proposed, which is effective in synergistically optimizing thermoelectric performance in copper sulfides. Multiple lattice defects, including nanoprecipitates, dislocations, and nanopores are produced by adding a refined ratio of Sn and Se. Phonon transport is significantly suppressed by multiple mechanisms. An ultralow lattice thermal conductivity is therefore obtained. Furthermore, extra Se is added in the copper sulfide for optimizing electrical transport properties by inducing generating Cu vacancies. Ultimately, an excellent figure of merit of ~1.6 at 873 K is realized in the Cu1.992SSe0.016(Cu2SnSe4)0.004 bulk sample. The simple strategy of inducing compositional and structural modulation for improving thermoelectric parameters promotes low-cost high-performance copper sulfides as alternatives in thermoelectric applications.
Spaceflight effects on human vascular smooth muscle cell phenotype and function
Authors: Scotti Marina M. , Wilson Brandon K. , Bubenik Jodi L. , Yu Fahong , Swanson Maurice S. , Allen Josephine B.
Published: March 2024

The cardiovascular system is strongly impacted by the hazards of spaceflight. Astronauts spending steadily increasing lengths of time in microgravity are subject to cardiovascular deconditioning resulting in loss of vascular tone, reduced total blood volume, and diminished cardiac output. Appreciating the mechanisms by which the cells of the vasculature are altered during spaceflight will be integral to understanding and combating these deleterious effects as the human presence in space advances. In this study, we performed RNA-Seq analysis coupled with review by QIAGEN Ingenuity Pathway Analysis software on human aortic smooth muscle cells (HASMCs) cultured for 3 days in microgravity and aboard the International Space Station to assess the transcriptomic changes that occur during spaceflight. The results of our RNA-Seq analysis show that SMCs undergo a wide range of transcriptional alteration while in space, significantly affecting 4422 genes. SMCs largely down-regulate markers of the contractile, synthetic, and osteogenic phenotypes including smooth muscle alpha actin (αSMA), matrix metalloproteinases (MMPs), and bone morphogenic proteins (BMPs). Additionally, components of several cellular signaling pathways were strongly impacted including the STAT3, NFκB, PI3K/AKT, HIF1α, and Endothelin pathways. This study highlights the significant changes in transcriptional behavior SMCs exhibit during spaceflight and puts these changes in context to better understand vascular function in space.
Deciphering functional roles of protein succinylation and glutarylation using genetic code expansion
Authors: Weyh Maria , Jokisch Marie-Lena , Nguyen Tuan-Anh , Fottner Maximilian , Lang Kathrin
Published: March 2024

Post-translational modifications (PTMs) dynamically regulate cellular processes. Lysine undergoes a range of acylations, including malonylation, succinylation (SucK) and glutarylation (GluK). These PTMs increase the size of the lysine side chain and reverse its charge from +1 to −1 under physiological conditions, probably impacting protein structure and function. To understand the functional roles of these PTMs, homogeneously modified proteins are required for biochemical studies. While the site-specific encoding of PTMs and their mimics via genetic code expansion has facilitated the characterization of the functional roles of many PTMs, negatively charged lysine acylations have defied this approach. Here we describe site-specific incorporation of SucK and GluK into proteins via temporarily masking their negative charge through thioester derivatives. We prepare succinylated and glutarylated bacterial and mammalian target proteins, including non-refoldable multidomain proteins. This allows us to study how succinylation and glutarylation impact enzymatic activity of metabolic enzymes and regulate protein–DNA and protein–protein interactions in biological processes from replication to ubiquitin signalling.
A high-quality chromosome-level genome assembly of the Chinese medaka Oryzias sinensis
Authors: Dong Zhongdian , Wang Jiangman , Chen Guozhu , Guo Yusong , Zhao Na , Wang Zhongduo , Zhang Bo
Published: March 2024

Oryzias sinensis, also known as Chinese medaka or Chinese ricefish, is a commonly used animal model for aquatic environmental assessment in the wild as well as gene function validation or toxicology research in the lab. Here, a high-quality chromosome-level genome assembly of O. sinensis was generated using single-tube long fragment read (stLFR) reads, Nanopore long-reads, and Hi-C sequencing data. The genome is 796.58 Mb, and a total of 712.17 Mb of the assembled sequences were anchored to 23 pseudo-chromosomes. A final set of 22,461 genes were annotated, with 98.67% being functionally annotated. The Benchmarking Universal Single-Copy Orthologs (BUSCO) benchmark of genome assembly and gene annotation reached 95.1% (93.3% single-copy) and 94.6% (91.7% single-copy), respectively. Furthermore, we also use ATAC-seq to uncover chromosome transposase-accessibility as well as related genome area function enrichment for Oryzias sinensis. This study offers a new improved foundation for future genomics research in Chinese medaka.