bluuebunny/crossref_metadata_2025_split huggingface dataset:
Depletion of G9A attenuates imiquimod-induced psoriatic dermatitis via targeting EDAR-NF-κB signaling in keratinocyte
Authors: Fang Zhiqin , Wang Yutong , Huang Bo , Chen Xiang , Jiang Rundong , Yin Mingzhu 
Published: September 2023

AbstractPsoriasis is a common and recurrent inflammatory skin disease characterized by inflammatory cells infiltration of the dermis and excessive proliferation, reduced apoptosis, and abnormal keratosis of the epidermis. In this study, we found that G9A, an important methyltransferase that mainly mediates the mono-methylation (me1) and di-methylation (me2) of histone 3 lysine 9 (H3K9), is highly expressed in lesions of patients with psoriasis and imiquimod (IMQ)-induced psoriasis-like mouse model. Previous studies have shown that G9A is involved in the pathogenesis of various tumors by regulating apoptosis, proliferation, differentiation, and invasion. However, the role of G9A in skin inflammatory diseases such as psoriasis remains unclear. Our data so far suggest that topical administration of G9A inhibitor BIX01294 as well as keratinocyte-specific deletion of G9A greatly alleviated IMQ-induced psoriatic alterations in mice for the first time. Mechanistically, the loss function of G9A causes the downregulation of Ectodysplasin A receptor (EDAR), consequently inhibiting the activation of NF-κB pathway, resulting in impaired proliferation and increased apoptosis of keratinocytes, therefore ameliorating the psoriatic dermatitis induced by IMQ. In total, we show that inhibition of G9A improves psoriatic-like dermatitis mainly by regulating cell proliferation and apoptosis rather than inflammatory processes, and that this molecule may be considered as a potential therapeutic target for keratinocyte hyperproliferative diseases such as psoriasis.
Analysis of 72,469 UK Biobank exomes links rare variants to male-pattern hair loss
Authors: Henne Sabrina Katrin , Aldisi Rana , Sivalingam Sugirthan , Hochfeld Lara Maleen , Borisov Oleg , Krawitz Peter Michael , Maj Carlo , Nöthen Markus Maria , Heilmann-Heimbach Stefanie 
Published: September 2023

AbstractMale-pattern hair loss (MPHL) is common and highly heritable. While genome-wide association studies (GWAS) have generated insights into the contribution of common variants to MPHL etiology, the relevance of rare variants remains unclear. To determine the contribution of rare variants to MPHL etiology, we perform gene-based and single-variant analyses in exome-sequencing data from 72,469 male UK Biobank participants. While our population-level risk prediction suggests that rare variants make only a minor contribution to general MPHL risk, our rare variant collapsing tests identified a total of five significant gene associations. These findings provide additional evidence for previously implicated genes (EDA2R, WNT10A) and highlight novel risk genes at and beyond GWAS loci (HEPH, CEPT1, EIF3F). Furthermore, MPHL-associated genes are enriched for genes considered causal for monogenic trichoses. Together, our findings broaden the MPHL-associated allelic spectrum and provide insights into MPHL pathobiology and a shared basis with monogenic hair loss disorders.
Intrinsic 1$${T}^{{\prime} }$$ phase induced in atomically thin 2H-MoTe2 by a single terahertz pulse
Authors: Shi Jiaojian , Bie Ya-Qing , Zong Alfred , Fang Shiang , Chen Wei , Han Jinchi , Cao Zhaolong , Zhang Yong , Taniguchi Takashi , Watanabe Kenji , Fu Xuewen , Bulović Vladimir , Kaxiras Efthimios , Baldini Edoardo , Jarillo-Herrero Pablo , Nelson Keith A. 
Published: September 2023

AbstractThe polymorphic transition from 2H to 1$${T}^{{\prime} }$$

T

′

-MoTe2, which was thought to be induced by high-energy photon irradiation among many other means, has been intensely studied for its technological relevance in nanoscale transistors due to the remarkable improvement in electrical performance. However, it remains controversial whether a crystalline 1$${T}^{{\prime} }$$

T

′

phase is produced because optical signatures of this putative transition are found to be associated with the formation of tellurium clusters instead. Here we demonstrate the creation of an intrinsic 1$${T}^{{\prime} }$$

T

′

lattice after irradiating a mono- or few-layer 2H-MoTe2 with a single field-enhanced terahertz pulse. Unlike optical pulses, the low terahertz photon energy limits possible structural damages. We further develop a single-shot terahertz-pump-second-harmonic-probe technique and reveal a transition out of the 2H-phase within 10 ns after photoexcitation. Our results not only provide important insights to resolve the long-standing debate over the light-induced polymorphic transition in MoTe2 but also highlight the unique capability of strong-field terahertz pulses in manipulating quantum materials.
A branching model of lineage differentiation underpinning the neurogenic potential of enteric glia
Authors: Laddach Anna , Chng Song Hui , Lasrado Reena , Progatzky Fränze , Shapiro Michael , Erickson Alek , Sampedro Castaneda Marisol , Artemov Artem V. , Bon-Frauches Ana Carina , Amaniti Eleni-Maria , Kleinjung Jens , Boeing Stefan , Ultanir Sila , Adameyko Igor , Pachnis Vassilis 
Published: September 2023

AbstractGlial cells have been proposed as a source of neural progenitors, but the mechanisms underpinning the neurogenic potential of adult glia are not known. Using single cell transcriptomic profiling, we show that enteric glial cells represent a cell state attained by autonomic neural crest cells as they transition along a linear differentiation trajectory that allows them to retain neurogenic potential while acquiring mature glial functions. Key neurogenic loci in early enteric nervous system progenitors remain in open chromatin configuration in mature enteric glia, thus facilitating neuronal differentiation under appropriate conditions. Molecular profiling and gene targeting of enteric glial cells in a cell culture model of enteric neurogenesis and a gut injury model demonstrate that neuronal differentiation of glia is driven by transcriptional programs employed in vivo by early progenitors. Our work provides mechanistic insight into the regulatory landscape underpinning the development of intestinal neural circuits and generates a platform for advancing glial cells as therapeutic agents for the treatment of neural deficits.
Genotypic diversity and unrecognized antifungal resistance among populations of Candida glabrata from positive blood cultures
Authors: Badrane Hassan , Cheng Shaoji , Dupont Christopher L. , Hao Binghua , Driscoll Eileen , Morder Kristin , Liu Guojun , Newbrough Anthony , Fleres Giuseppe , Kaul Drishti , Espinoza Josh L. , Clancy Cornelius J. , Nguyen M. Hong 
Published: September 2023

AbstractThe longstanding model is that most bloodstream infections (BSIs) are caused by a single organism. We perform whole genome sequencing of five-to-ten strains from blood culture (BC) bottles in each of ten patients with Candida glabrata BSI. We demonstrate that BCs contain mixed populations of clonal but genetically diverse strains. Genetically distinct strains from two patients exhibit phenotypes that are potentially important during BSIs, including differences in susceptibility to antifungal agents and phagocytosis. In both patients, the clinical microbiology lab recovered a fluconazole-susceptible index strain, but we identify mixed fluconazole-susceptible and –resistant populations. Diversity in drug susceptibility is likely clinically relevant, as fluconazole-resistant strains were subsequently recovered by the clinical laboratory during persistent or relapsing infections. In one patient, unrecognized respiration-deficient small colony variants are fluconazole-resistant and significantly attenuated for virulence during murine candidiasis. Our data suggest a population-based model of C. glabrata genotypic and phenotypic diversity during BSIs.
3D covalent organic framework membrane with fast and selective ion transport
Authors: Zhu Tianhao , Kong Yan , Lyu Bohui , Cao Li , Shi Benbing , Wang Xiaoyao , Pang Xiao , Fan Chunyang , Yang Chao , Wu Hong , Jiang Zhongyi 
Published: September 2023

Abstract3D ionic covalent organic framework (COF) membranes, which are envisioned to be able to break the trade-off between ion conductivity and ion selectivity, are waiting for exploitation. Herein, we report the fabrication of a 3D sulfonic acid-functionalized COF membrane (3D SCOF) for efficient and selective ion transport, using dual acid-mediated interfacial polymerization strategy. The 3D SCOF membranes possess highly interconnected ion transport channels, ultramicroporous pore sizes (0.97 nm), and abundant sulfonate groups (with a high ion exchange capacity of 4.1 mmol g−1), leading to high proton conductivity of 843 mS cm−1 at 90 °C. When utilized in osmotic energy conversion, a high power density of 21.2 W m−2, and a remarkable selectivity of 0.976 and thus an exceptional energy conversion efficiency of 45.3% are simultaneously achieved. This work provides an alternative approach to 3D ionic COF membranes and promotes the applications of 3D COFs in ion transport and separation.
Distinct sub-second dopamine signaling in dorsolateral striatum measured by a genetically-encoded fluorescent sensor
Authors: Salinas Armando G. , Lee Jeong Oen , Augustin Shana M. , Zhang Shiliang , Patriarchi Tommaso , Tian Lin , Morales Marisela , Mateo Yolanda , Lovinger David M. 
Published: September 2023

AbstractThe development of genetically encoded dopamine sensors such as dLight has provided a new approach to measuring slow and fast dopamine dynamics both in brain slices and in vivo, possibly enabling dopamine measurements in areas like the dorsolateral striatum (DLS) where previously such recordings with fast-scan cyclic voltammetry (FSCV) were difficult. To test this, we first evaluated dLight photometry in mouse brain slices with simultaneous FSCV and found that both techniques yielded comparable results, but notable differences in responses to dopamine transporter inhibitors, including cocaine. We then used in vivo fiber photometry with dLight in mice to examine responses to cocaine in DLS. We also compared dopamine responses during Pavlovian conditioning across the striatum. We show that dopamine increases were readily detectable in DLS and describe transient dopamine kinetics, as well as slowly developing signals during conditioning. Overall, our findings indicate that dLight photometry is well suited to measuring dopamine dynamics in DLS.
Conformational dynamics of cohesin/Scc2 loading complex are regulated by Smc3 acetylation and ATP binding
Authors: Kaushik Aditi , Than Thane , Petela Naomi J. , Voulgaris Menelaos , Percival Charlotte , Daniels Peter , Rafferty John B. , Nasmyth Kim A. , Hu Bin 
Published: September 2023

AbstractThe ring-shaped cohesin complex is a key player in sister chromatid cohesion, DNA repair, and gene transcription. The loading of cohesin to chromosomes requires the loader Scc2 and is regulated by ATP. This process is hindered by Smc3 acetylation. However, the molecular mechanism underlying this inhibition remains mysterious. Here, using Saccharomyces cerevisiae as a model system, we identify a novel configuration of Scc2 with pre-engaged cohesin and reveal dynamic conformations of the cohesin/Scc2 complex in the loading reaction. We demonstrate that Smc3 acetylation blocks the association of Scc2 with pre-engaged cohesin by impairing the interaction of Scc2 with Smc3’s head. Lastly, we show that ATP binding induces the cohesin/Scc2 complex to clamp DNA by promoting the interaction between Scc2 and Smc3 coiled coil. Our results illuminate a dynamic reconfiguration of the cohesin/Scc2 complex during loading and indicate how Smc3 acetylation and ATP regulate this process.
SENP6 regulates localization and nuclear condensation of DNA damage response proteins by group deSUMOylation
Authors: Claessens Laura A. , Verlaan-de Vries Matty , de Graaf Ilona J. , Vertegaal Alfred C. O. 
Published: September 2023

AbstractThe SUMO protease SENP6 maintains genomic stability, but mechanistic understanding of this process remains limited. We find that SENP6 deconjugates SUMO2/3 polymers on a group of DNA damage response proteins, including BRCA1-BARD1, 53BP1, BLM and ERCC1-XPF. SENP6 maintains these proteins in a hypo-SUMOylated state under unstressed conditions and counteracts their polySUMOylation after hydroxyurea-induced stress. Co-depletion of RNF4 leads to a further increase in SUMOylation of BRCA1, BARD1 and BLM, suggesting that SENP6 antagonizes targeting of these proteins by RNF4. Functionally, depletion of SENP6 results in uncoordinated recruitment and persistence of SUMO2/3 at UVA laser and ionizing radiation induced DNA damage sites. Additionally, SUMO2/3 and DNA damage response proteins accumulate in nuclear bodies, in a PML-independent manner driven by multivalent SUMO-SIM interactions. These data illustrate coordinated regulation of SUMOylated DNA damage response proteins by SENP6, governing their timely localization at DNA damage sites and nuclear condensation state.
BAP1 promotes osteoclast function by metabolic reprogramming
Authors: Rohatgi Nidhi , Zou Wei , Li Yongjia , Cho Kevin , Collins Patrick L. , Tycksen Eric , Pandey Gaurav , DeSelm Carl J. , Patti Gary J. , Dey Anwesha , Teitelbaum Steven L. 
Published: September 2023

AbstractTreatment of osteoporosis commonly diminishes osteoclast number which suppresses bone formation thus compromising fracture prevention. Bone formation is not suppressed, however, when bone degradation is reduced by retarding osteoclast functional resorptive capacity, rather than differentiation. We find deletion of deubiquitinase, BRCA1-associated protein 1 (Bap1), in myeloid cells (Bap1∆LysM), arrests osteoclast function but not formation. Bap1∆LysM osteoclasts fail to organize their cytoskeleton which is essential for bone degradation consequently increasing bone mass in both male and female mice. The deubiquitinase activity of BAP1 modifies osteoclast function by metabolic reprogramming. Bap1 deficient osteoclast upregulate the cystine transporter, Slc7a11, by enhanced H2Aub occupancy of its promoter. SLC7A11 controls cellular reactive oxygen species levels and redirects the mitochondrial metabolites away from the tricarboxylic acid cycle, both being necessary for osteoclast function. Thus, in osteoclasts BAP1 appears to regulate the epigenetic-metabolic axis and is a potential target to reduce bone degradation while maintaining osteogenesis in osteoporotic patients.
Hypoxanthine phosphoribosyl transferase 1 metabolizes temozolomide to activate AMPK for driving chemoresistance of glioblastomas
Authors: Yin Jianxing , Wang Xiefeng , Ge Xin , Ding Fangshu , Shi Zhumei , Ge Zehe , Huang Guang , Zhao Ningwei , Chen Dongyin , Zhang Junxia , Agnihotri Sameer , Cao Yuandong , Ji Jing , Lin Fan , Wang Qianghu , Zhou Qigang , Wang Xiuxing , You Yongping , Lu Zhimin , Qian Xu 
Published: September 2023

AbstractTemozolomide (TMZ) is a standard treatment for glioblastoma (GBM) patients. However, TMZ has moderate therapeutic effects due to chemoresistance of GBM cells through less clarified mechanisms. Here, we demonstrate that TMZ-derived 5-aminoimidazole-4-carboxamide (AICA) is converted to AICA ribosyl-5-phosphate (AICAR) in GBM cells. This conversion is catalyzed by hypoxanthine phosphoribosyl transferase 1 (HPRT1), which is highly expressed in human GBMs. As the bona fide activator of AMP-activated protein kinase (AMPK), TMZ-derived AICAR activates AMPK to phosphorylate threonine 52 (T52) of RRM1, the catalytic subunit of ribonucleotide reductase (RNR), leading to RNR activation and increased production of dNTPs to fuel the repairment of TMZ-induced-DNA damage. RRM1 T52A expression, genetic interruption of HPRT1-mediated AICAR production, or administration of 6-mercaptopurine (6-MP), a clinically approved inhibitor of HPRT1, blocks TMZ-induced AMPK activation and sensitizes brain tumor cells to TMZ treatment in mice. In addition, HPRT1 expression levels are positively correlated with poor prognosis in GBM patients who received TMZ treatment. These results uncover a critical bifunctional role of TMZ in GBM treatment that leads to chemoresistance. Our findings underscore the potential of combined administration of clinically available 6-MP to overcome TMZ chemoresistance and improve GBM treatment.
Epigenomic analysis of formalin-fixed paraffin-embedded samples by CUT&Tag
Authors: Henikoff Steven , Henikoff Jorja G. , Ahmad Kami , Paranal Ronald M. , Janssens Derek H. , Russell Zachary R. , Szulzewsky Frank , Kugel Sita , Holland Eric C. 
Published: September 2023

AbstractFor more than a century, formalin-fixed paraffin-embedded (FFPE) sample preparation has been the preferred method for long-term preservation of biological material. However, the use of FFPE samples for epigenomic studies has been difficult because of chromatin damage from long exposure to high concentrations of formaldehyde. Previously, we introduced Cleavage Under Targeted Accessible Chromatin (CUTAC), an antibody-targeted chromatin accessibility mapping protocol based on CUT&Tag. Here we show that simple modifications of our CUTAC protocol either in single tubes or directly on slides produce high-resolution maps of paused RNA Polymerase II at enhancers and promoters using FFPE samples. We find that transcriptional regulatory element differences produced by FFPE-CUTAC distinguish between mouse brain tumors and identify and map regulatory element markers with high confidence and precision, including microRNAs not detectable by RNA-seq. Our simple workflows make possible affordable epigenomic profiling of archived biological samples for biomarker identification, clinical applications and retrospective studies.
A de novo evolved gene contributes to rice grain shape difference between indica and japonica
Authors: Chen Rujia , Xiao Ning , Lu Yue , Tao Tianyun , Huang Qianfeng , Wang Shuting , Wang Zhichao , Chuan Mingli , Bu Qing , Lu Zhou , Wang Hanyao , Su Yanze , Ji Yi , Ding Jianheng , Gharib Ahmed , Liu Huixin , Zhou Yong , Tang Shuzhu , Liang Guohua , Zhang Honggen , Yi Chuandeng , Zheng Xiaoming , Cheng Zhukuan , Xu Yang , Li Pengcheng , Xu Chenwu , Huang Jinling , Li Aihong , Yang Zefeng 
Published: September 2023

AbstractThe role of de novo evolved genes from non-coding sequences in regulating morphological differentiation between species/subspecies remains largely unknown. Here, we show that a rice de novo gene GSE9 contributes to grain shape difference between indica/xian and japonica/geng varieties. GSE9 evolves from a previous non-coding region of wild rice Oryza rufipogon through the acquisition of start codon. This gene is inherited by most japonica varieties, while the original sequence (absence of start codon, gse9) is present in majority of indica varieties. Knockout of GSE9 in japonica varieties leads to slender grains, whereas introgression to indica background results in round grains. Population evolutionary analyses reveal that gse9 and GSE9 are derived from wild rice Or-I and Or-III groups, respectively. Our findings uncover that the de novo GSE9 gene contributes to the genetic and morphological divergence between indica and japonica subspecies, and provide a target for precise manipulation of rice grain shape.
Capturing the microbial dark matter in desert soils using culturomics-based metagenomics and high-resolution analysis
Authors: Li Shuai , Lian Wen-Hui , Han Jia-Rui , Ali Mukhtiar , Lin Zhi-Liang , Liu Yong-Hong , Li Li , Zhang Dong-Ya , Jiang Xian-Zhi , Li Wen-Jun , Dong Lei 
Published: September 2023

AbstractDeserts occupy one-third of the Earth’s terrestrial surface and represent a potentially significant reservoir of microbial biodiversity, yet the majority of desert microorganisms remain uncharacterized and are seen as “microbial dark matter”. Here, we introduce a multi-omics strategy, culturomics-based metagenomics (CBM) that integrates large-scale cultivation, full-length 16S rRNA gene amplicon, and shotgun metagenomic sequencing. The results showed that CBM captured a significant amount of taxonomic and functional diversity missed in direct sequencing by increasing the recovery of amplicon sequence variants (ASVs) and high/medium-quality metagenome-assembled genomes (MAGs). Importantly, CBM allowed the post hoc recovery of microbes of interest (e.g., novel or specific taxa), even those with extremely low abundance in the culture. Furthermore, strain-level analyses based on CBM and direct sequencing revealed that the desert soils harbored a considerable number of novel bacterial candidates (1941, 51.4%), of which 1095 (from CBM) were culturable. However, CBM would not exactly reflect the relative abundance of true microbial composition and functional pathways in the in situ environment, and its use coupled with direct metagenomic sequencing could provide greater insight into desert microbiomes. Overall, this study exemplifies the CBM strategy with high-resolution is an ideal way to deeply explore the untapped novel bacterial resources in desert soils, and substantially expands our knowledge on the microbial dark matter hidden in the vast expanse of deserts.
AdsorbML: a leap in efficiency for adsorption energy calculations using generalizable machine learning potentials
Authors: Lan Janice , Palizhati Aini , Shuaibi Muhammed , Wood Brandon M. , Wander Brook , Das Abhishek , Uyttendaele Matt , Zitnick C. Lawrence , Ulissi Zachary W. 
Published: September 2023

AbstractComputational catalysis is playing an increasingly significant role in the design of catalysts across a wide range of applications. A common task for many computational methods is the need to accurately compute the adsorption energy for an adsorbate and a catalyst surface of interest. Traditionally, the identification of low-energy adsorbate-surface configurations relies on heuristic methods and researcher intuition. As the desire to perform high-throughput screening increases, it becomes challenging to use heuristics and intuition alone. In this paper, we demonstrate machine learning potentials can be leveraged to identify low-energy adsorbate-surface configurations more accurately and efficiently. Our algorithm provides a spectrum of trade-offs between accuracy and efficiency, with one balanced option finding the lowest energy configuration 87.36% of the time, while achieving a ~2000× speedup in computation. To standardize benchmarking, we introduce the Open Catalyst Dense dataset containing nearly 1000 diverse surfaces and ~100,000 unique configurations.
Large sliding regulation in van der waals layered nonlinear optical ternary chalcogenides
Authors: Wu Qingchen , Kang Lei , Wu Jian , Lin Zheshuai 
Published: September 2023

AbstractInterlayer sliding modulation in van der Waals (vdW) layered materials opens opportunities to seek tunable applications for photonics and optoelectronics at the nanoscale. In this work, focusing on ternary chalcogenides, dozens of typical vdW layered materials with the formula of A2MZ4(A, M = metal cation; Z = S/Se) were systematically classified and studied to illustrate the interlayer sliding modulation performance on nonlinear optical (NLO) effect and underlying mechanism. Based on first-principles analysis, the screened Cd2GeSe4exhibits large second harmonic generation (SHG) deviation (>36 times between high- and low-SHG states) under sliding among all studied materials. This phenomenon arises from the polarization modulation induced by the vdW interlayer charge redistribution of two tetrahedral primitives in the ternary edge-sharing tetrahedral structures. Our findings present a strategy to substantially modulate NLO properties by altering the interlayer charge coupling which is commonly thought to be very weak in vdW layered materials.