bluuebunny/crossref_metadata_2025 huggingface dataset:
CRISPR-powered optothermal nanotweezers: Diverse bio-nanoparticle manipulation and single nucleotide identification
Authors: Chen Jiajie , Chen Zhi , Meng Changle , Zhou Jianxing , Peng Yuhang , Dai Xiaoqi , Li Jingfeng , Zhong Yili , Chen Xiaolin , Yuan Wu , Ho Ho-Pui , Gao Bruce Zhi , Qu Junle , Zhang Xueji , Zhang Han , Shao Yonghong
Published: November 2023

Optothermal nanotweezers have emerged as an innovative optical manipulation technique in the past decade, which revolutionized classical optical manipulation by efficiently capturing a broader range of nanoparticles. However, the optothermal temperature field was merely employed for in-situ manipulation of nanoparticles, its potential for identifying bio-nanoparticles remains largely untapped. Hence, based on the synergistic effect of optothermal manipulation and CRIPSR-based bio-detection, we developed CRISPR-powered optothermal nanotweezers (CRONT). Specifically, by harnessing diffusiophoresis and thermo-osmotic flows near the substrate upon optothermal excitation, we successfully trapped and enriched DNA functionalized gold nanoparticles, CRISPR-associated proteins, as well as DNA strands. Remarkably, we built an optothermal scheme for enhancing CRISPR-based single-nucleotide polymorphism (SNP) detection at single molecule level, while also introducing a novel CRISPR methodology for observing nucleotide cleavage. Therefore, this innovative approach has endowed optical tweezers with DNA identification ability in aqueous solution which was unattainable before. With its high specificity and feasibility for in-situ bio-nanoparticle manipulation and identification, CRONT will become a universal tool in point-of-care diagnosis, biophotonics, and bio-nanotechnology.
Clinical EEG slowing induced by electroconvulsive therapy is better described by increased frontal aperiodic activity
Authors: Smith Sydney E. , Ma Vincent , Gonzalez Celene , Chapman Angela , Printz David , Voytek Bradley , Soltani Maryam
Published: November 2023

Electroconvulsive therapy (ECT) is one of the most efficacious interventions for treatment-resistant depression. Despite its efficacy, ECT’s neural mechanism of action remains unknown. Although ECT has been associated with “slowing” in the electroencephalogram (EEG), how this change relates to clinical improvement is unresolved. Until now, increases in slow-frequency power have been assumed to indicate increases in slow oscillations, without considering the contribution of aperiodic activity, a process with a different physiological mechanism. In this exploratory study of nine MDD patients, we show that aperiodic activity, indexed by the aperiodic exponent, increases with ECT treatment. This increase better explains EEG “slowing” when compared to power in oscillatory peaks in the delta (1–3 Hz) range and is correlated to clinical improvement. In accordance with computational models of excitation-inhibition balance, these increases in aperiodic exponent are linked to increasing levels of inhibitory activity, suggesting that ECT might ameliorate depressive symptoms by restoring healthy levels of inhibition in frontal cortices.
Classification, function, and advances in tsRNA in non-neoplastic diseases
Authors: Zhang Liou , Liu Jie , Hou Yang
Published: November 2023

tRNA-derived small RNAs (tsRNAs) are non-coding small RNAs produced by specific endonucleases following the processing and splicing of precursor or mature tRNAs upon starvation, oxidative stress, hypoxia, and other adverse conditions. tRNAs are classified into two major categories, tRNA fragments (tRFs) and tRNA-derived stress-induced small RNAs (tiRNAs), based on differences in splice sites. With the development of high-throughput sequencing technologies in recent years, tsRNAs have been found to have important biological functions, including inhibition of apoptosis, epigenetic regulation, cell–cell communication, translation, and regulation of gene expression. Additionally, these molecules have been found to be aberrantly expressed in various diseases and to be involved in several pathological processes. In this article, the classification and nomenclature, biological functions, and potential use of tsRNAs as diagnostic biomarkers and therapeutic targets in non-neoplastic diseases are reviewed. Although tsRNA research is at its infancy, their potential in the treatment of non-tumor diseases warrants further investigation.
Flavones provide resistance to DUX4-induced toxicity via an mTor-independent mechanism
Authors: Cohen Justin , Huang Shushu , Koczwara Katherine E. , Woods Kristen T. , Ho Vincent , Woodman Keryn G. , Arbiser Jack L. , Daman Katelyn , Lek Monkol , Emerson Charles P. , DeSimone Alec M.
Published: November 2023

Facioscapulohumeral muscular dystrophy (FSHD) is among the most common of the muscular dystrophies, affecting nearly 1 in 8000 individuals, and is a cause of profound disability. Genetically, FSHD is linked to the contraction and/or epigenetic de-repression of the D4Z4 repeat array on chromosome 4, thereby allowing expression of the DUX4 gene in skeletal muscle. If the DUX4 transcript incorporates a stabilizing polyadenylation site the myotoxic DUX4 protein will be synthesized, resulting in muscle wasting. The mechanism of toxicity remains unclear, as many DUX4-induced cytopathologies have been described, however cell death does primarily occur through caspase 3/7-dependent apoptosis. To date, most FSHD therapeutic development has focused on molecular methods targeting DUX4 expression or the DUX4 transcript, while therapies targeting processes downstream of DUX4 activity have received less attention. Several studies have demonstrated that inhibition of multiple signal transduction pathways can ameliorate DUX4-induced toxicity, and thus compounds targeting these pathways have the potential to be developed into FSHD therapeutics. To this end, we have screened a group of small molecules curated based on their reported activity in relevant pathways and/or structural relationships with known toxicity-modulating molecules. We have identified a panel of five compounds that function downstream of DUX4 activity to inhibit DUX4-induced toxicity. Unexpectedly, this effect was mediated through an mTor-independent mechanism that preserved expression of ULK1 and correlated with an increase in a marker of active cellular autophagy. This identifies these flavones as compounds of interest for therapeutic development, and potentially identifies the autophagy pathway as a target for therapeutics.
RBMS3-induced circHECTD1 encoded a novel protein to suppress the vasculogenic mimicry formation in glioblastoma multiforme
Authors: Ruan Xuelei , Liu Yunhui , Wang Ping , Liu Libo , Ma Teng , Xue Yixue , Dong Weiwei , Zhao Yubo , E Tiange , Lin Hongda , Wang Di , Yang Chunqing , Song Jian , Liu Jiate , Deng Meiqi , An Ping , Lin Yang , Yang Jin , Cui Zheng , Cao Yaming , Liu Xiaobai
Published: November 2023

Glioblastoma multiforme (GBM) is a highly vascularized malignant cancer of the central nervous system, and the presence of vasculogenic mimicry (VM) severely limits the effectiveness of anti-vascular therapy. In this study, we identified downregulated circHECTD1, which acted as a key VM-suppressed factor in GBM. circHECTD1 elevation significantly inhibited cell proliferation, migration, invasion and tube-like structure formation in GBM. RIP assay was used to demonstrate that the flanking intron sequence of circHECTD1 can be specifically bound by RBMS3, thereby inducing circHECTD1 formation to regulate VM formation in GBM. circHECTD1 was confirmed to possess a strong protein-encoding capacity and the encoded functional peptide 463aa was identified by LC-MS/MS. Both circHECTD1 and 463aa significantly inhibited GBM VM formation in vivo and in vitro. Analysis of the 463aa protein sequence revealed that it contained a ubiquitination-related domain and promoted NR2F1 degradation by regulating the ubiquitination of the NR2F1 at K396. ChIP assay verified that NR2F1 could directly bind to the promoter region of MMP2, MMP9 and VE-cadherin, transcriptionally promoting the expression of VM-related proteins, which in turn enhanced VM formation in GBM. In summary, we clarified a novel pathway for RBMS3-induced circHECTD1 encoding functional peptide 463aa to mediate the ubiquitination of NR2F1, which inhibited VM formation in GBM. This study aimed to reveal new mechanisms of GBM progression in order to provide novel approaches and strategies for the anti-vascular therapy of GBM.
Mitoribosomal synthetic lethality overcomes multidrug resistance in MYC-driven neuroblastoma
Authors: Borankova Karolina , Krchniakova Maria , Leck Lionel Y. W. , Kubistova Adela , Neradil Jakub , Jansson Patric J. , Hogarty Michael D. , Skoda Jan
Published: November 2023

Mitochondria are central for cancer responses to therapy-induced stress signals. Refractory tumors often show attenuated sensitivity to apoptotic signaling, yet clinically relevant molecular actors to target mitochondria-mediated resistance remain elusive. Here, we show that MYC-driven neuroblastoma cells rely on intact mitochondrial ribosome (mitoribosome) processivity and undergo cell death following pharmacological inhibition of mitochondrial translation, regardless of their multidrug/mitochondrial resistance and stem-like phenotypes. Mechanistically, inhibiting mitoribosomes induced the mitochondrial stress-activated integrated stress response (ISR), leading to downregulation of c-MYC/N-MYC proteins prior to neuroblastoma cell death, which could be both rescued by the ISR inhibitor ISRIB. The ISR blocks global protein synthesis and shifted the c-MYC/N-MYC turnover toward proteasomal degradation. Comparing models of various neuroectodermal tumors and normal fibroblasts revealed overexpression of MYC proteins phosphorylated at the degradation-promoting site T58 as a factor that predetermines vulnerability of MYC-driven neuroblastoma to mitoribosome inhibition. Reducing N-MYC levels in a neuroblastoma model with tunable MYCN expression mitigated cell death induction upon inhibition of mitochondrial translation and functionally validated the propensity of neuroblastoma cells for MYC-dependent cell death in response to the mitochondrial ISR. Notably, neuroblastoma cells failed to develop significant resistance to the mitoribosomal inhibitor doxycycline over a long-term repeated (pulsed) selection. Collectively, we identify mitochondrial translation machinery as a novel synthetic lethality target for multidrug-resistant MYC-driven tumors.
Specific intracellular retention of circSKA3 promotes colorectal cancer metastasis by attenuating ubiquitination and degradation of SLUG
Authors: Deng Jingwen , Liao Shaoxia , Chen Chaoyi , Han Fengyan , Lei Siqin , Lai Xuan , Ye Kehong , Han Qizheng , E Fang , Lu Chao , Lai Maode , Liu Fanlong , Zhang Honghe
Published: November 2023

Our previous study demonstrated that tumor-suppressor circular RNAs (circRNAs) can be specifically secreted outside of colorectal cancer (CRC) cells within exosomes to maintain tumor cell fitness. However, whether tumor-driving circRNAs can be specifically retained in cells to facilitate tumor progression remains unknown. In this study, circRNA-seq showed that circSKA3 was significantly upregulated in CRC tissues but downregulated in serum samples from CRC patients. In addition, circSKA3 promoted CRC progression in vitro and in vivo and was retained in CRC cells via a specific cellmotif element. Interestingly, the cellmotif element was also the site of interaction of circSKA3 with SLUG, which inhibited SLUG ubiquitination degradation and promoted CRC epithelial–mesenchymal transition (EMT). Moreover, FUS was identified as a key circularization regulator of circSKA3 that bound to the key element. Finally, we designed and synthesized specific antisense oligonucleotides (ASOs) targeting circularization and cellmotif elements, which repressed circSKA3 expression, abolished the SLUG–circSKA3 interaction, and further inhibited CRC EMT and metastasis in vitro and in vivo.
Keep in touch: a perspective on the mitochondrial social network and its implication in health and disease
Authors: Barabino Silvia , Lombardi Silvia , Zilocchi Mara
Published: November 2023

Mitochondria have been the focus of extensive research for decades since their dysfunction is linked to more than 150 distinct human disorders. Despite considerable efforts, researchers have only been able to skim the surface of the mitochondrial social complexity and the impact of inter-organelle and inter-organ communication alterations on human health. While some progress has been made in deciphering connections among mitochondria and other cytoplasmic organelles through direct (i.e., contact sites) or indirect (i.e., inter-organelle trafficking) crosstalk, most of these efforts have been restricted to a limited number of proteins involved in specific physiological pathways or disease states. This research bottleneck is further narrowed by our incomplete understanding of the cellular alteration timeline in a specific pathology, which prevents the distinction between a primary organelle dysfunction and the defects occurring due to the disruption of the organelle’s interconnectivity. In this perspective, we will (i) summarize the current knowledge on the mitochondrial crosstalk within cell(s) or tissue(s) in health and disease, with a particular focus on neurodegenerative disorders, (ii) discuss how different large-scale and targeted approaches could be used to characterize the different levels of mitochondrial social complexity, and (iii) consider how investigating the different expression patterns of mitochondrial proteins in different cell types/tissues could represent an important step forward in depicting the distinctive architecture of inter-organelle communication.
Stereoselectivity control in Rh-catalyzed β-OH elimination for chiral allene formation
Authors: Wang Jie , Zheng Wei-Feng , Zhang Xue , Qian Hui , Ma Shengming
Published: November 2023

Stereoselectivity control and understanding in the metal-catalyzed reactions are fundamental issues in catalysis. Here we report sterically controlled rhodium-catalyzed SN2’-type substitution reactions of optically active tertiary propargylic alcohols with arylmetallic species affording the non-readily available enantioenriched tetrasubstituted allenes via either exclusive syn- or anti-β-OH elimination, respectively, under two sets of different reaction parameters. Detailed mechanistic experiments and density functional theory (DFT) studies reveal that the exclusive anti-Rh(I)-OH elimination is dictated by the simultaneous aid of in situ generated boric acid and ambient water, which act as the shuttle in the hydroxy relay to facilitate the Rh(I)-OH elimination process via a unique ten-membered cyclic transition state (anti-TS2_u). By contrast, the syn-Rh(III)-OH elimination in C–H bond activation-based allenylation reaction is controlled by a four-membered cyclic transition state (syn-TS3) due to the steric surroundings around the Rh(III) center preventing the approach of the other assisting molecules. Under the guidance of these mechanistic understandings, a stereodivergent protocol to construct the enantiomer of optically active tetrasubstituted allenes from the same starting materials is successfully developed.
Indocyanine green fluorescence imaging-guided versus conventional laparoscopic lymphadenectomy for gastric cancer: long-term outcomes of a phase 3 randomised clinical trial
Authors: Chen Qi-Yue , Zhong Qing , Liu Zhi-Yu , Li Ping , Lin Guang-Tan , Zheng Qiao-Ling , Wang Jia-Bin , Lin Jian-Xian , Lu Jun , Cao Long-Long , Lin Mi , Tu Ru-Hong , Huang Ze-Ning , Zeng Gui-Rong , Jiang Mei-Chen , Wang Hua-Gen , Huang Xiao-Bo , Xu Kai-Xiang , Li Yi-Fan , Zheng Chao-Hui , Xie Jian-Wei , Huang Chang-Ming
Published: November 2023

Indocyanine green (ICG) fluorescence imaging-guided lymphadenectomy has been demonstrated to be effective in increasing the number of lymph nodes (LNs) retrieved in laparoscopic gastrectomy for gastric cancer (GC). Previously, we reported the primary outcomes and short-term secondary outcomes of a phase 3, open-label, randomized clinical trial (NCT03050879) investigating the use of ICG for image-guided lymphadenectomy in patients with potentially resectable GC. Patients were randomly (1:1 ratio) assigned to either the ICG or non-ICG group. The primary outcome was the number of LNs retrieved and has been reported. Here, we report the primary outcome and long-term secondary outcomes including three-year overall survival (OS), three-year disease-free survival (DFS), and recurrence patterns. The per-protocol analysis set population is used for all analyses (258 patients, ICG [n = 129] vs. non-ICG group [n = 129]). The mean total LNs retrieved in the ICG group significantly exceeds that in the non-ICG group (50.5 ± 15.9 vs 42.0 ± 10.3, P < 0.001). Both OS and DFS in the ICG group are significantly better than that in the non-ICG group (log-rank P = 0.015; log-rank P = 0.012, respectively). There is a difference in the overall recurrence rates between the ICG and non-ICG groups (17.8% vs 31.0%). Compared with conventional lymphadenectomy, ICG guided laparoscopic lymphadenectomy is safe and effective in prolonging survival among patients with resectable GC.
Circadian disturbances and frailty risk in older adults
Authors: Cai Ruixue , Gao Lei , Gao Chenlu , Yu Lei , Zheng Xi , Bennett David A. , Buchman Aron S. , Hu Kun , Li Peng
Published: November 2023

Frailty is characterized by diminished resilience to stressor events. It is associated with adverse future health outcomes and impedes healthy aging. The circadian system orchestrates ~24-h rhythms in bodily functions in synchrony with the day-night cycle, and disturbed circadian regulation plays an important role in many age-related health consequences. We investigated prospective associations of circadian disturbances with incident frailty in over 1000 older adults who had been followed annually for up to 16 years. We found that decreased rhythm strength, reduced stability, or increased variation were associated with a higher risk of incident frailty and faster progress of frailty over time. Perturbed circadian rest-activity rhythms may be an early sign or risk factor for frailty in older adults.
A toolbox of astrocyte-specific, serotype-independent adeno-associated viral vectors using microRNA targeting sequences
Authors: Gleichman Amy J. , Kawaguchi Riki , Sofroniew Michael V. , Carmichael S. Thomas
Published: November 2023

Astrocytes, one of the most prevalent cell types in the central nervous system (CNS), are critically involved in neural function. Genetically manipulating astrocytes is an essential tool in understanding and affecting their roles. Adeno-associated viruses (AAVs) enable rapid genetic manipulation; however, astrocyte specificity of AAVs can be limited, with high off-target expression in neurons and sparsely in endothelial cells. Here, we report the development of a cassette of four copies of six miRNA targeting sequences (4x6T) which triggers transgene degradation specifically in neurons and endothelial cells. In combination with the GfaABC1D promoter, 4x6T increases astrocytic specificity of Cre with a viral reporter from <50% to >99% in multiple serotypes in mice, and confers astrocyte specificity in multiple recombinases and reporters. We also present empty vectors to add 4x6T to other cargo, independently and in Cre/Dre-dependent forms. This toolbox of AAVs allows rapid manipulation of astrocytes throughout the CNS, is compatible with different AAV serotypes, and demonstrates the efficacy of using multiplexed miRNA targeting sequences to decrease expression in multiple off-target cell populations simultaneously.
Simulation-guided engineering of split GFPs with efficient β-strand photodissociation
Authors: Shamsudin Yasmin , Walker Alice R. , Jones Chey M. , Martínez Todd J. , Boxer Steven G.
Published: November 2023

Green fluorescent proteins (GFPs) are ubiquitous for protein tagging and live-cell imaging. Split-GFPs are widely used to study protein-protein interactions by fusing proteins of interest to split GFP fragments that create a fluorophore upon typically irreversible complementation. Thus, controlled dissociation of the fragments is desirable. Although we have found that split strands can be photodissociated, the quantum efficiency of light-induced photodissociation of split GFPs is low. Traditional protein engineering approaches to increase efficiency, including extensive mutagenesis and screening, have proved difficult to implement. To reduce the search space, key states in the dissociation process are modeled by combining classical and enhanced sampling molecular dynamics with QM/MM calculations, enabling the rational design and engineering of split GFPs with up to 20-fold faster photodissociation rates using non-intuitive amino acid changes. This demonstrates the feasibility of modeling complex molecular processes using state-of-the-art computational methods, and the potential of integrating computational methods to increase the success rate in protein engineering projects.
Unconventional structure and mechanisms for membrane interaction and translocation of the NF-κB-targeting toxin AIP56
Authors: Lisboa Johnny , Pereira Cassilda , Pinto Rute D. , Rodrigues Inês S. , Pereira Liliana M. G. , Pinheiro Bruno , Oliveira Pedro , Pereira Pedro José Barbosa , Azevedo Jorge E. , Durand Dominique , Benz Roland , do Vale Ana , dos Santos Nuno M. S.
Published: November 2023

Bacterial AB toxins are secreted key virulence factors that are internalized by target cells through receptor-mediated endocytosis, translocating their enzymatic domain to the cytosol from endosomes (short-trip) or the endoplasmic reticulum (long-trip). To accomplish this, bacterial AB toxins evolved a multidomain structure organized into either a single polypeptide chain or non-covalently associated polypeptide chains. The prototypical short-trip single-chain toxin is characterized by a receptor-binding domain that confers cellular specificity and a translocation domain responsible for pore formation whereby the catalytic domain translocates to the cytosol in an endosomal acidification-dependent way. In this work, the determination of the three-dimensional structure of AIP56 shows that, instead of a two-domain organization suggested by previous studies, AIP56 has three-domains: a non-LEE encoded effector C (NleC)-like catalytic domain associated with a small middle domain that contains the linker-peptide, followed by the receptor-binding domain. In contrast to prototypical single-chain AB toxins, AIP56 does not comprise a typical structurally complex translocation domain; instead, the elements involved in translocation are scattered across its domains. Thus, the catalytic domain contains a helical hairpin that serves as a molecular switch for triggering the conformational changes necessary for membrane insertion only upon endosomal acidification, whereas the middle and receptor-binding domains are required for pore formation.
Mesenchymal stromal cells alleviate depressive and anxiety-like behaviors via a lung vagal-to-brain axis in male mice
Authors: Huang Jing , Huang Weijun , Yi Junzhe , Deng Yiwen , Li Ruijie , Chen Jieying , Shi Jiahao , Qiu Yuan , Wang Tao , Chen Xiaoyong , Zhang Xiaoran , Xiang Andy Peng
Published: November 2023

Major depressive disorder (MDD) is one of the most common and disabling mental disorders, and current strategies remain inadequate. Although mesenchymal stromal cells (MSCs) have shown beneficial effects in experimental models of depression, underlying mechanisms remain elusive. Here, using murine depression models, we demonstrated that MSCs could alleviate depressive and anxiety-like behaviors not due to a reduction in proinflammatory cytokines, but rather activation of dorsal raphe nucleus (DRN) 5-hydroxytryptamine (5-HT) neurons. Mechanistically, peripheral delivery of MSCs activated pulmonary innervating vagal sensory neurons, which projected to the nucleus tractus solitarius, inducing the release of 5-HT in DRN. Furthermore, MSC-secreted brain-derived neurotrophic factor activated lung sensory neurons through tropomyosin receptor kinase B (TrkB), and inhalation of a TrkB agonist also achieved significant therapeutic effects in male mice. This study reveals a role of peripheral MSCs in regulating central nervous system function and demonstrates a potential “lung vagal-to-brain axis” strategy for MDD.
Profiling stress-triggered RNA condensation with photocatalytic proximity labeling
Authors: Ren Ziqi , Tang Wei , Peng Luxin , Zou Peng
Published: November 2023

Stress granules (SGs) are highly dynamic cytoplasmic membrane-less organelles that assemble when cells are challenged by stress. RNA molecules are sorted into SGs where they play important roles in maintaining the structural stability of SGs and regulating gene expression. Herein, we apply a proximity-dependent RNA labeling method, CAP-seq, to comprehensively investigate the content of SG-proximal transcriptome in live mammalian cells. CAP-seq captures 457 and 822 RNAs in arsenite- and sorbitol-induced SGs in HEK293T cells, respectively, revealing that SG enrichment is positively correlated with RNA length and AU content, but negatively correlated with translation efficiency. The high spatial specificity of CAP-seq dataset is validated by single-molecule FISH imaging. We further apply CAP-seq to map dynamic changes in SG-proximal transcriptome along the time course of granule assembly and disassembly processes. Our data portray a model of AU-rich and translationally repressed SG nanostructure that are memorized long after the removal of stress.
High-sensitive spatially resolved T cell receptor sequencing with SPTCR-seq
Authors: Benotmane Jasim Kada , Kueckelhaus Jan , Will Paulina , Zhang Junyi , Ravi Vidhya M. , Joseph Kevin , Sankowski Roman , Beck Jürgen , Lee-Chang Catalina , Schnell Oliver , Heiland Dieter Henrik
Published: November 2023

Spatial resolution of the T cell repertoire is essential for deciphering cancer-associated immune dysfunction. Current spatially resolved transcriptomic technologies are unable to directly annotate T cell receptors (TCR). We present spatially resolved T cell receptor sequencing (SPTCR-seq), which integrates optimized target enrichment and long-read sequencing for highly sensitive TCR sequencing. The SPTCR computational pipeline achieves yield and coverage per TCR comparable to alternative single-cell TCR technologies. Our comparison of PCR-based and SPTCR-seq methods underscores SPTCR-seq’s superior ability to reconstruct the entire TCR architecture, including V, D, J regions and the complementarity-determining region 3 (CDR3). Employing SPTCR-seq, we assess local T cell diversity and clonal expansion across spatially discrete niches. Exploration of the reciprocal interaction of the tumor microenvironmental and T cells discloses the critical involvement of NK and B cells in T cell exhaustion. Integrating spatially resolved omics and TCR sequencing provides as a robust tool for exploring T cell dysfunction in cancers and beyond.
Tracking lake drainage events and drained lake basin vegetation dynamics across the Arctic
Authors: Chen Yating , Cheng Xiao , Liu Aobo , Chen Qingfeng , Wang Chengxin
Published: November 2023

Widespread lake drainage can lead to large-scale drying in Arctic lake-rich areas, affecting hydrology, ecosystems and permafrost carbon dynamics. To date, the spatio-temporal distribution, driving factors, and post-drainage dynamics of lake drainage events across the Arctic remain unclear. Using satellite remote sensing and surface water products, we identify over 35,000 (~0.6% of all lakes) lake drainage events in the northern permafrost zone between 1984 and 2020, with approximately half being relatively understudied non-thermokarst lakes. Smaller, thermokarst, and discontinuous permafrost area lakes are more susceptible to drainage compared to their larger, non-thermokarst, and continuous permafrost area counterparts. Over time, discontinuous permafrost areas contribute more drained lakes annually than continuous permafrost areas. Following drainage, vegetation rapidly colonizes drained lake basins, with thermokarst drained lake basins showing significantly higher vegetation growth rates and greenness levels than their non-thermokarst counterparts. Under warming, drained lake basins are likely to become more prevalent and serve as greening hotspots, playing an important role in shaping Arctic ecosystems.
Topographic axonal projection at single-cell precision supports local retinotopy in the mouse superior colliculus
Authors: Molotkov Dmitry , Ferrarese Leiron , Boissonnet Tom , Asari Hiroki
Published: November 2023

Retinotopy, like all long-range projections, can arise from the axons themselves or their targets. The underlying connectivity pattern, however, remains elusive at the fine scale in the mammalian brain. To address this question, we functionally mapped the spatial organization of the input axons and target neurons in the female mouse retinocollicular pathway at single-cell resolution using in vivo two-photon calcium imaging. We found a near-perfect retinotopic tiling of retinal ganglion cell axon terminals, with an average error below 30 μm or 2° of visual angle. The precision of retinotopy was relatively lower for local neurons in the superior colliculus. Subsequent data-driven modeling ascribed it to a low input convergence, on average 5.5 retinal ganglion cell inputs per postsynaptic cell in the superior colliculus. These results indicate that retinotopy arises largely from topographically precise input from presynaptic cells, rather than elaborating local circuitry to reconstruct the topography by postsynaptic cells.
A neotropical perspective on the uniqueness of the Holocene among interglacials
Authors: Schiferl J. , Kingston M. , Åkesson C. M. , Valencia B. G. , Rozas-Davila A. , McGee D. , Woods A. , Chen C. Y. , Hatfield R. G. , Rodbell D. T. , Abbott M. B. , Bush M. B.
Published: November 2023

Understanding how tropical systems have responded to large-scale climate change, such as glacial-interglacial oscillations, and how human impacts have altered those responses is key to current and future ecology. A sedimentary record recovered from Lake Junín, in the Peruvian Andes (4085 m elevation) spans the last 670,000 years and represents the longest continuous and empirically-dated record of tropical vegetation change to date. Spanning seven glacial-interglacial oscillations, fossil pollen and charcoal recovered from the core showed the general dominance of grasslands, although during the warmest times some Andean forest trees grew above their modern limits near the lake. Fire was very rare until the last 12,000 years, when humans were in the landscape. Here we show that, due to human activity, our present interglacial, the Holocene, has a distinctive vegetation composition and ecological trajectory compared with six previous interglacials. Our data reinforce the view that modern vegetation assemblages of high Andean grasslands and the presence of a defined tree line are aspects of a human-modified landscape.
A palisade-shaped membrane reservoir is required for rapid ring cell inflation in Drechslerella dactyloides
Authors: Chen Yue , Liu Jia , Kang Seogchan , Wei Dongsheng , Fan Yani , Xiang Meichun , Liu Xingzhong
Published: November 2023

Fusion of individual vesicles carrying membrane-building materials with the plasma membrane (PM) enables gradual cell expansion and shape change. Constricting ring (CR) cells of carnivorous fungi triple in size within 0.1-1 s to capture passing nematodes. Here, we investigated how a carnivorous fungus, Drechslerella dactyloides, executes rapid and irreversible PM expansion during CR inflation. During CR maturation, vesicles carrying membrane-building materials accumulate and fuse, forming a structure named the Palisade-shaped Membrane-building Structure (PMS) around the rumen side of ring cells. After CR inflation, the PMS disappears, with partially inflated cells displaying wavy PM and fully inflated cells exhibiting smooth PM, suggesting that the PMS serves as the reservoir for membrane-building materials to enable rapid and extensive PM expansion. The DdSnc1, a v-SNARE protein, accumulates at the inner side of ring cells and is necessary for PMS formation and CR inflation. This study elucidates the unique cellular mechanisms underpinning rapid CR inflation.
Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape
Authors: Goovaerts Seppe , Hoskens Hanne , Eller Ryan J. , Herrick Noah , Musolf Anthony M. , Justice Cristina M. , Yuan Meng , Naqvi Sahin , Lee Myoung Keun , Vandermeulen Dirk , Szabo-Rogers Heather L. , Romitti Paul A. , Boyadjiev Simeon A. , Marazita Mary L. , Shaffer John R. , Shriver Mark D. , Wysocka Joanna , Walsh Susan , Weinberg Seth M. , Claes Peter
Published: November 2023

The cranial vault in humans is highly variable, clinically relevant, and heritable, yet its genetic architecture remains poorly understood. Here, we conduct a joint multi-ancestry and admixed multivariate genome-wide association study on 3D cranial vault shape extracted from magnetic resonance images of 6772 children from the ABCD study cohort yielding 30 genome-wide significant loci. Follow-up analyses indicate that these loci overlap with genomic risk loci for sagittal craniosynostosis, show elevated activity cranial neural crest cells, are enriched for processes related to skeletal development, and are shared with the face and brain. We present supporting evidence of regional localization for several of the identified genes based on expression patterns in the cranial vault bones of E15.5 mice. Overall, our study provides a comprehensive overview of the genetics underlying normal-range cranial vault shape and its relevance for understanding modern human craniofacial diversity and the etiology of congenital malformations.
Genomic profiling and pre-clinical modelling of breast cancer leptomeningeal metastasis reveals acquisition of a lobular-like phenotype
Authors: Fitzpatrick Amanda , Iravani Marjan , Mills Adam , Vicente David , Alaguthurai Thanussuyah , Roxanis Ioannis , Turner Nicholas C. , Haider Syed , Tutt Andrew N. J. , Isacke Clare M.
Published: November 2023

Breast cancer leptomeningeal metastasis (BCLM), where tumour cells grow along the lining of the brain and spinal cord, is a devastating development for patients. Investigating this metastatic site is hampered by difficulty in accessing tumour material. Here, we utilise cerebrospinal fluid (CSF) cell-free DNA (cfDNA) and CSF disseminated tumour cells (DTCs) to explore the clonal evolution of BCLM and heterogeneity between leptomeningeal and extracranial metastatic sites. Somatic alterations with potential therapeutic actionability were detected in 81% (17/21) of BCLM cases, with 19% detectable in CSF cfDNA only. BCLM was enriched in genomic aberrations in adherens junction and cytoskeletal genes, revealing a lobular-like breast cancer phenotype. CSF DTCs were cultured in 3D to establish BCLM patient-derived organoids, and used for the successful generation of BCLM in vivo models. These data reveal that BCLM possess a unique genomic aberration profile and highlight potential cellular dependencies in this hard-to-treat form of metastatic disease.
The structural and functional investigation into an unusual nitrile synthase
Authors: Li Hao , Huang Jian-Wen , Dai Longhai , Zheng Haibin , Dai Si , Zhang Qishan , Yao Licheng , Yang Yunyun , Yang Yu , Min Jian , Guo Rey-Ting , Chen Chun-Chi
Published: November 2023

The biosynthesis of neurotoxin aetokthonotoxin (AETX) that features a unique structure of pentabrominated biindole nitrile involves a first-of-its-kind nitrile synthase termed AetD, an enzyme that shares very low sequence identity to known structures and catalyzes an unprecedented mechanism. In this study, we resolve the crystal structure of AetD in complex with the substrate 5,7-di-Br-L-Trp. AetD adopts the heme oxygenase like fold and forms a hydrophobic cavity within a helical bundle to accommodate the indole moiety. A diiron cluster comprising two irons that serves as a catalytic center binds to the carboxyl O and the amino N of the substrate. Notably, we demonstrate that the AetD-catalyzed reaction is independent of the bromination of the substrate and also solved crystal structures of AetD in complex with 5-Br-L-Trp and L-Trp. Altogether, the present study reveals the substrate-binding pattern and validates the diiron cluster-comprising active center of AetD, which should provide important basis to support the mechanistic investigations into this class of nitrile synthase.
Quantitative three-dimensional imaging of chemical short-range order via machine learning enhanced atom probe tomography
Authors: Li Yue , Wei Ye , Wang Zhangwei , Liu Xiaochun , Colnaghi Timoteo , Han Liuliu , Rao Ziyuan , Zhou Xuyang , Huber Liam , Dsouza Raynol , Gong Yilun , Neugebauer Jörg , Marek Andreas , Rampp Markus , Bauer Stefan , Li Hongxiang , Baker Ian , Stephenson Leigh T. , Gault Baptiste
Published: November 2023

Chemical short-range order (CSRO) refers to atoms of specific elements self-organising within a disordered crystalline matrix to form particular atomic neighbourhoods. CSRO is typically characterized indirectly, using volume-averaged or through projection microscopy techniques that fail to capture the three-dimensional atomistic architectures. Here, we present a machine-learning enhanced approach to break the inherent resolution limits of atom probe tomography enabling three-dimensional imaging of multiple CSROs. We showcase our approach by addressing a long-standing question encountered in body-centred-cubic Fe-Al alloys that see anomalous property changes upon heat treatment. We use it to evidence non-statistical B2-CSRO instead of the generally-expected D03-CSRO. We introduce quantitative correlations among annealing temperature, CSRO, and nano-hardness and electrical resistivity. Our approach is further validated on modified D03-CSRO detected in Fe-Ga. The proposed strategy can be generally employed to investigate short/medium/long-range ordering phenomena in different materials and help design future high-performance materials.
Inorganic–organic hybrid quantum dots for AOP-mediated photodegradation of ofloxacin and para-nitrophenol in diverse water matrices
Authors: Mishra Soumya Ranjan , Gadore Vishal , Ahmaruzzaman Md.
Published: November 2023

Due to concerns about the accessibility of clean water and the quality of treated wastewater, developing a suitable solution to enhance the water quality is critical. Thus, the current study focused on the synthesis of cadmium-doped CdIn2S4 incorporated in chitosan, forming Cd/CdIn2S4@Ch quantum dots using a solvothermal technique for the efficient photodegradation of hazardous pollutants like ofloxacin and para-nitrophenol through H2O2-mediated AOP. Cd/CdIn2S4@Ch quantum dots were characterized by several advanced methods, including XRD, PL, UV-DRS, FTIR, SEM, HR-TEM, XPS, DSC, TGA, EDX, and Elemental mapping analysis. The influence of varying reaction parameters, such as the effect of organic compounds, inorganic ions, and water matrices, was also investigated. The prepared composite showed outstanding photodegradation efficiency of 85.51 ± 1.35% and 96.70 ± 1.31%, with a rate constant of 0.02334 and 0.15134 min−1, which is about 1.24 and 2.07 times higher than pristine CdIn2S4 for ofloxacin and para-nitrophenol, respectively. The COD values were reduced to 80.67 ± 1.67% for ofloxacin and 88.36 ± 1.43% for para-nitrophenol, whereas the TOC values reduced to 73.49% and 86.34%, respectively, from their initial values. The improved performance is ascribed to the encapsulation of CdIn2S4 by chitosan, leading to the self-doping of cadmium into the photocatalyst, as the incorporated cadmium doping site can generate a local electron accumulation point, improving the charge separation efficacy and surface charge mitigation capability of chitosan nanosheets even further. The scavenger experiments showed that hydroxyl and superoxide radicals played a significant part in the photodegradation of contaminants. Additionally, the quantum dots showed excellent constancy and were recyclable up to six times, suggesting exceptional stability and reusability of the manufactured photocatalyst. The fabricated Cd/CdIn2S4@Ch quantum dots could be an excellent photocatalyst for removing organic pollutants from wastewater in the near future.
The unequal effects of the health–economy trade-off during the COVID-19 pandemic
Authors: Pangallo Marco , Aleta Alberto , del Rio-Chanona R. Maria , Pichler Anton , Martín-Corral David , Chinazzi Matteo , Lafond François , Ajelli Marco , Moro Esteban , Moreno Yamir , Vespignani Alessandro , Farmer J. Doyne
Published: November 2023

Despite the global impact of the coronavirus disease 2019 pandemic, the question of whether mandated interventions have similar economic and public health effects as spontaneous behavioural change remains unresolved. Addressing this question, and understanding differential effects across socioeconomic groups, requires building quantitative and fine-grained mechanistic models. Here we introduce a data-driven, granular, agent-based model that simulates epidemic and economic outcomes across industries, occupations and income levels. We validate the model by reproducing key outcomes of the first wave of coronavirus disease 2019 in the New York metropolitan area. The key mechanism coupling the epidemic and economic modules is the reduction in consumption due to fear of infection. In counterfactual experiments, we show that a similar trade-off between epidemic and economic outcomes exists both when individuals change their behaviour due to fear of infection and when non-pharmaceutical interventions are imposed. Low-income workers, who perform in-person occupations in customer-facing industries, face the strongest trade-off.
Transcriptome profiles of Streptomyces clavuligerus strains producing different titers of clavulanic acid
Authors: Gong Junpyo , Yi Jeong Sang , Cho Hang Su , Shin Chang Hun , Won Hyung-Jin , Cho Byung-Kwan , Noh Minsoo , Yoon Yeo Joon
Published: November 2023

Streptomyces clavuligerus NRRL 3585 is a native producer of clavulanic acid (CA), a clinically used β-lactamase inhibitor, and is widely used as an industrial strain for the production of antibiotics. Selective random mutagenesis has successfully generated the improved CA-producing S. clavuligerus mutant strains as well as the strain with the loss of CA biosynthesis. To understand the molecular mechanisms associated with the improved CA-production potential, genome-scale RNA-sequencing-based transcriptional data were obtained for the wild-type S. clavuligerus strain and its three mutant strains. Total RNA samples for each strain were collected across four different growth stages, and all 32 sequencing data points exhibited an average Phred score of 36. The high-quality genome-scale transcriptional profile of S. clavuligerus strains with varied CA biosynthetic potential provides valuable insights and new opportunities for discovering efficient metabolic engineering strategies for the development of improved industrial strains.
Effects of the angiotensin-converting enzyme inhibitor captopril on occlusal-disharmony-induced cardiac dysfunction in mice
Authors: Ito Aiko , Ohnuki Yoshiki , Suita Kenji , Matsuo Ichiro , Ishikawa Misao , Mitsubayashi Takao , Mototani Yasumasa , Kiyomoto Kenichi , Tsunoda Michinori , Morii Akinaka , Nariyama Megumi , Hayakawa Yoshio , Tomonari Hiroshi , Okumura Satoshi
Published: November 2023

Occlusal disharmony is known to affect not only the oral cavity environment, but also the autonomic nervous system in the heart. Since the renin-angiotensin system (RAS) inhibitor captopril (Cap) is one of the first-line drugs for preventing cardiac remodeling in patients with heart failure, we hypothesized that Cap might prevent cardiac dysfunction induced by occlusal disharmony. Here, to test this idea, we used our bite-opening (BO) mouse model, which was developed by cementing a suitable appliance onto the mandibular incisor. Mice were divided into four groups: (1) Control, (2) BO, (3) Cap, and (4) BO + Cap. After 2 weeks, we evaluated cardiac function by echocardiography and confirmed that cardiac function was significantly decreased in the BO group compared to the control, while Cap ameliorated the dysfunction. Cardiac fibrosis, myocyte apoptosis and oxidative stress-induced myocardial damage in the BO group were significantly increased versus the control, and these increases were suppressed by Cap. Cardiac dysfunction induced by BO was associated with dual phosphorylation on PKCδ (Tyr-311/Thr-505), leading to activation of CaMKII with increased phosphorylation of RyR2 and phospholamban. Our results suggest that the RAS might play an important role in the development of cardiac diseases induced by occlusal anomalies.
Impacts investigation of gas barrier on effective thermal conductivity and service life of vacuum insulation panel
Authors: Shi Mingxiao , Yang Lixia , Chen Zhaofeng , Kan Ankang , Chen Shijie , He Tianhao , Zhang Jiaxiang
Published: November 2023

Vacuum Insulation Panels (VIPs) are highly efficient thermal insulation materials with extremely low thermal conductivity based on the vacuum principle. With the sealing properties of the gas barrier envelopes, a long service life of the VIP is obtained. The mechanism and influence factors of gas and water vapor permeability were mathematically analyzed to explore the influence of gas barrier envelopes on the thermal performance of VIPs. Three typical gas barriers were studied, and the selection of the gas barrier and other aspects of optimization were involved. The relationships among temperature, humidity, solubility coefficient, diffusion coefficient, and permeability were concluded, which shows that temperature has a much greater effect on the permeability of the gas barrier relative to humidity. The numerical analysis and influencing factors of VIPs’ service life were also exemplified with three different types of gas barrier envelopes. The experimental results show that depending on the environment, the temperature has a major impact on the effective thermal conductivity and service life of VIP. The research was significant in the selection of gas barriers, the optimization of the performance, and the development of vacuum insulation material.
Resistive switching transparent SnO2 thin film sensitive to light and humidity
Authors: Kalateh Asiyeh , Jalali Ali , Kamali Ashtiani Mohammad Javad , Mohammadimasoudi Mohammad , Bastami Hajieh , Mohseni Majid
Published: November 2023

Designing and manufacturing memristor devices with simple and less complicated methods is highly promising for their future development. Here, an Ag/SnO2/FTO(F-SnO2) structure is used through the deposition of the SnO2 layer attained by its sol via the air-brush method on an FTO substrate. This structure was investigated in terms of the memristive characteristics. The negative differential resistance (NDR) effect was observed in environment humidity conditions. In this structure, valance change memory and electrometalization change memory mechanisms cause the current peak in the NDR region by forming an OH− conductive filament. In addition, the photoconductivity effect was found under light illumination and this structure shows the positive photoconductance effect by increasing the conductivity. Memristivity was examined for up to 100 cycles and significant stability was observed as a valuable advantage for neuromorphic computing. Our study conveys a growth mechanism of an optical memristor that is sensitive to light and humidity suitable for sensing applications.