bluuebunny/crossref_metadata_2025_split huggingface dataset:
The 20S as a stand-alone proteasome in cells can degrade the ubiquitin tag
Authors: Sahu Indrajit , Mali Sachitanand M. , Sulkshane Prasad , Xu Cong , Rozenberg Andrey , Morag Roni , Sahoo Manisha Priyadarsini , Singh Sumeet K. , Ding Zhanyu , Wang Yifan , Day Sharleen , Cong Yao , Kleifeld Oded , Brik Ashraf , Glickman Michael H. 
Published: October 2021

AbstractThe proteasome, the primary protease for ubiquitin-dependent proteolysis in eukaryotes, is usually found as a mixture of 30S, 26S, and 20S complexes. These complexes have common catalytic sites, which makes it challenging to determine their distinctive roles in intracellular proteolysis. Here, we chemically synthesize a panel of homogenous ubiquitinated proteins, and use them to compare 20S and 26S proteasomes with respect to substrate selection and peptide-product generation. We show that 20S proteasomes can degrade the ubiquitin tag along with the conjugated substrate. Ubiquitin remnants on branched peptide products identified by LC-MS/MS, and flexibility in the 20S gate observed by cryo-EM, reflect the ability of the 20S proteasome to proteolyze an isopeptide-linked ubiquitin-conjugate. Peptidomics identifies proteasome-trapped ubiquitin-derived peptides and peptides of potential 20S substrates in Hi20S cells, hypoxic cells, and human failing-heart. Moreover, elevated levels of 20S proteasomes appear to contribute to cell survival under stress associated with damaged proteins.
Structural basis for protein glutamylation by the Legionella pseudokinase SidJ
Authors: Adams Michael , Sharma Rahul , Colby Thomas , Weis Felix , Matic Ivan , Bhogaraju Sagar 
Published: October 2021

AbstractLegionella pneumophila (LP) avoids phagocytosis by secreting nearly 300 effector proteins into the host cytosol. SidE family of effectors (SdeA, SdeB, SdeC and SidE) employ phosphoribosyl ubiquitination to target multiple host Rab GTPases and innate immune factors. To suppress the deleterious toxicity of SidE enzymes in a timely manner, LP employs a metaeffector named SidJ. Upon activation by host Calmodulin (CaM), SidJ executes an ATP-dependent glutamylation to modify the catalytic residue Glu860 in the mono-ADP-ribosyl transferase (mART) domain of SdeA. SidJ is a unique glutamylase that adopts a kinase-like fold but contains two nucleotide-binding pockets. There is a lack of consensus about the substrate recognition and catalytic mechanism of SidJ. Here, we determined the cryo-EM structure of SidJ in complex with its substrate SdeA in two different states of catalysis. Our structures reveal that both phosphodiesterase (PDE) and mART domains of SdeA make extensive contacts with SidJ. In the pre-glutamylation state structure of the SidJ-SdeA complex, adenylylated E860 of SdeA is inserted into the non-canonical (migrated) nucleotide-binding pocket of SidJ. Structure-based mutational analysis indicates that SidJ employs its migrated pocket for the glutamylation of SdeA. Finally, using mass spectrometry, we identified several transient autoAMPylation sites close to both the catalytic pockets of SidJ. Our data provide unique insights into the substrate recognition and the mechanism of protein glutamylation by the pseudokinase SidJ.
Clonal hematopoiesis with JAK2V617F promotes pulmonary hypertension with ALK1 upregulation in lung neutrophils
Authors: Kimishima Yusuke , Misaka Tomofumi , Yokokawa Tetsuro , Wada Kento , Ueda Koki , Sugimoto Koichi , Minakawa Keiji , Nakazato Kazuhiko , Ishida Takafumi , Oshima Motohiko , Koide Shuhei , Shide Kotaro , Shimoda Kazuya , Iwama Atsushi , Ikeda Kazuhiko , Takeishi Yasuchika 
Published: October 2021

AbstractPulmonary hypertension (PH) is a progressive cardiopulmonary disease characterized by pulmonary arterial remodeling. Clonal somatic mutations including JAK2V617F, the most frequent driver mutation among myeloproliferative neoplasms, have recently been identified in healthy individuals without hematological disorders. Here, we reveal that clonal hematopoiesis with JAK2V617F exacerbates PH and pulmonary arterial remodeling in mice. JAK2V617F-expressing neutrophils specifically accumulate in pulmonary arterial regions, accompanied by increases in neutrophil-derived elastase activity and chemokines in chronic hypoxia-exposed JAK2V617F transgenic (JAK2V617F) mice, as well as recipient mice transplanted with JAK2V617F bone marrow cells. JAK2V617F progressively upregulates Acvrl1 (encoding ALK1) during the differentiation from bone marrow stem/progenitor cells peripherally into mature neutrophils of pulmonary arterial regions. JAK2V617F-mediated STAT3 phosphorylation upregulates ALK1-Smad1/5/8 signaling. ALK1/2 inhibition completely prevents the development of PH in JAK2V617F mice. Finally, our prospective clinical study identified JAK2V617F-positive clonal hematopoiesis is more common in PH patients than in healthy subjects. These findings indicate that clonal hematopoiesis with JAK2V617F causally leads to PH development associated with ALK1 upregulation.
Hot exciplexes in U-shaped TADF molecules with emission from locally excited states
Authors: Schleper A. Lennart , Goushi Kenichi , Bannwarth Christoph , Haehnle Bastian , Welscher Philipp J. , Adachi Chihaya , Kuehne Alexander J. C. 
Published: October 2021

AbstractFast emission and high color purity are essential characteristics of modern opto-electronic devices, such as organic light emitting diodes (OLEDs). These properties are currently not met by the latest generation of thermally activated delayed fluorescence (TADF) emitters. Here, we present an approach, called “hot exciplexes” that enables access to both attributes at the same time. Hot exciplexes are produced by coupling facing donor and acceptor moieties to an anthracene bridge, yielding an exciplex with large T1 to T2 spacing. The hot exciplex model is investigated using optical spectroscopy and quantum chemical simulations. Reverse intersystem crossing is found to occur preferentially from the T3 to the S1 state within only a few nanoseconds. Application and practicality of the model are shown by fabrication of organic light-emitting diodes with up to 32 % hot exciplex contribution and low efficiency roll-off.
Precise measurements of chromatin diffusion dynamics by modeling using Gaussian processes
Authors: Oliveira Guilherme M. , Oravecz Attila , Kobi Dominique , Maroquenne Manon , Bystricky Kerstin , Sexton Tom , Molina Nacho 
Published: October 2021

AbstractThe spatiotemporal organization of chromatin influences many nuclear processes: from chromosome segregation to transcriptional regulation. To get a deeper understanding of these processes, it is essential to go beyond static viewpoints of chromosome structures, to accurately characterize chromatin’s diffusion properties. We present GP-FBM: a computational framework based on Gaussian processes and fractional Brownian motion to extract diffusion properties from stochastic trajectories of labeled chromatin loci. GP-FBM uses higher-order temporal correlations present in the data, therefore, outperforming existing methods. Furthermore, GP-FBM allows to interpolate incomplete trajectories and account for substrate movement when two or more particles are present. Using our method, we show that average chromatin diffusion properties are surprisingly similar in interphase and mitosis in mouse embryonic stem cells. We observe surprising heterogeneity in local chromatin dynamics, correlating with potential regulatory activity. We also present GP-Tool, a user-friendly graphical interface to facilitate usage of GP-FBM by the research community.
Alpine-style nappes thrust over ancient North China continental margin demonstrate large Archean horizontal plate motions
Authors: Zhong Yating , Kusky Timothy , Wang Lu , Polat Ali , Liu Xuanyu , Peng Yaying , Luan Zhikang , Wang Chuanhai , Wang Junpeng , Deng Hao 
Published: October 2021

AbstractWhether modern-style plate tectonics operated on early Earth is debated due to a paucity of definitive records of large-scale plate convergence, subduction, and collision in the Archean geological record. Archean Alpine-style sub-horizontal fold/thrust nappes in the Precambrian basement of China contain a Mariana-type subduction-initiation sequence of mid-ocean ridge basalt blocks in a 1600-kilometer-long mélange belt, overthrusting picritic-boninitic and island-arc tholeiite bearing nappes, in turn emplaced over a passive margin capping an ancient Archean continental fragment. Picrite-boninite and tholeiite units are 2698 ± 30 million years old marking the age of subduction initiation, with nappes emplaced over the passive margin at 2520 million years ago. Here, we show the life cycle of the subduction zone and ocean spanned circa 178 million years; conservative plate velocities of 2 centimeters per year yield a lateral transport distance of subducted oceanic crust of 3560 kilometers, providing direct positive evidence for horizontal plate tectonics in the Archean.
Full shell coating or cation exchange enhances luminescence
Authors: Zhang Yi , Lei Pengpeng , Zhu Xiaohui , Zhang Yong 
Published: October 2021

AbstractCore-shell structure is routinely used for enhancing luminescence of optical nanoparticles, where the luminescent core is passivated by an inert shell. It has been intuitively accepted that the luminescence would gradually enhance with the coverage of inert shell. Here we report an “off-on” effect at the interface of core-shell upconversion nanoparticles, i.e., regardless of the shell coverage, the luminescence is not much enhanced unless the core is completely encapsulated. This effect indicates that full shell coating on the luminescent core is critical to significantly enhance luminescence, which is usually neglected. Inspired by this observation, a cation exchange approach is used to block the energy transfer between core nanoparticle and surface quenchers. We find that the luminescent core exhibits enhanced luminescence after cation exchange creates an effective shell region. These findings are believed to provide a better understanding of the interfacial energy dynamics and subsequent luminescence changes.
Rhesus macaques self-curing from a schistosome infection can display complete immunity to challenge
Authors: Amaral Murilo Sena , Santos Daisy Woellner , Pereira Adriana S. A. , Tahira Ana Carolina , Malvezzi João V. M. , Miyasato Patrícia Aoki , Freitas Rafaela de Paula , Kalil Jorge , Tjon Kon Fat Elisa M. , de Dood Claudia J. , Corstjens Paul L. A. M. , van Dam Govert J. , Nakano Eliana , Castro Simone de Oliveira , Mattaraia Vânia Gomes de Moura , Augusto Ronaldo de Carvalho , Grunau Christoph , Wilson R. Alan , Verjovski-Almeida Sergio 
Published: October 2021

AbstractThe rhesus macaque provides a unique model of acquired immunity against schistosomes, which afflict >200 million people worldwide. By monitoring bloodstream levels of parasite-gut-derived antigen, we show that from week 10 onwards an established infection withSchistosoma mansoniis cleared in an exponential manner, eliciting resistance to reinfection. Secondary challenge at week 42 demonstrates that protection is strong in all animals and complete in some. Antibody profiles suggest that antigens mediating protection are the released products of developing schistosomula. In culture they are killed by addition of rhesus plasma, collected from week 8 post-infection onwards, and even more efficiently with post-challenge plasma. Furthermore, cultured schistosomula lose chromatin activating marks at the transcription start site of genes related to worm development and show decreased expression of genes related to lysosomes and lytic vacuoles involved with autophagy. Overall, our results indicate that enhanced antibody responses against the challenge migrating larvae mediate the naturally acquired protective immunity and will inform the route to an effective vaccine.
The cell envelope of Staphylococcus aureus selectively controls the sorting of virulence factors
Authors: Zheng Xuhui , Marsman Gerben , Lacey Keenan A. , Chapman Jessica R. , Goosmann Christian , Ueberheide Beatrix M. , Torres Victor J. 
Published: October 2021

AbstractStaphylococcus aureus bi-component pore-forming leukocidins are secreted toxins that directly target and lyse immune cells. Intriguingly, one of the leukocidins, Leukocidin AB (LukAB), is found associated with the bacterial cell envelope in addition to secreted into the extracellular milieu. Here, we report that retention of LukAB on the bacterial cells provides S. aureus with a pre-synthesized active toxin that kills immune cells. On the bacteria, LukAB is distributed as discrete foci in two distinct compartments: membrane-proximal and surface-exposed. Through genetic screens, we show that a membrane lipid, lysyl-phosphatidylglycerol (LPG), and lipoteichoic acid (LTA) contribute to LukAB deposition and release. Furthermore, by studying non-covalently surface-bound proteins we discovered that the sorting of additional exoproteins, such as IsaB, Hel, ScaH, and Geh, are also controlled by LPG and LTA. Collectively, our study reveals a multistep secretion system that controls exoprotein storage and protein translocation across the S. aureus cell wall.
Tuning the selectivity of catalytic nitriles hydrogenation by structure regulation in atomically dispersed Pd catalysts
Authors: Liu Zhibo , Huang Fei , Peng Mi , Chen Yunlei , Cai Xiangbin , Wang Linlin , Hu Zenan , Wen Xiaodong , Wang Ning , Xiao Dequan , Jiang Hong , Sun Hongbin , Liu Hongyang , Ma Ding 
Published: October 2021

AbstractThe product selectivity in catalytic hydrogenation of nitriles is strongly correlated with the structure of the catalyst. In this work, two types of atomically dispersed Pd species stabilized on the defect-rich nanodiamond-graphene (ND@G) hybrid support: single Pd atoms (Pd1/ND@G) and fully exposed Pd clusters with average three Pd atoms (Pdn/ND@G), were fabricated. The two catalysts show distinct difference in the catalytic transfer hydrogenation of nitriles. The Pd1/ND@G catalyst preferentially generates secondary amines (Turnover frequency (TOF@333 K 709 h−1, selectivity >98%), while the Pdn/ND@G catalyst exhibits high selectivity towards primary amines (TOF@313 K 543 h−1, selectivity >98%) under mild reaction conditions. Detailed characterizations and density functional theory (DFT) calculations show that the structure of atomically dispersed Pd catalysts governs the dissociative adsorption pattern of H2 and also the hydrogenation pathway of the benzylideneimine (BI) intermediate, resulting in different product selectivity over Pd1/ND@G and Pdn/ND@G, respectively. The structure-performance relationship established over atomically dispersed Pd catalysts provides valuable insights for designing catalysts with tunable selectivity.
MinION sequencing from sea ice cryoconites leads to de novo genome reconstruction from metagenomes
Authors: Maggiori Catherine , Raymond-Bouchard Isabelle , Brennan Laura , Touchette David , Whyte Lyle 
Published: October 2021

AbstractGenome reconstruction from metagenomes enables detailed study of individual community members, their metabolisms, and their survival strategies. Obtaining high quality metagenome-assembled genomes (MAGs) is particularly valuable in extreme environments like sea ice cryoconites, where the native consortia are recalcitrant to culture and strong astrobiology analogues. We evaluated three separate approaches for MAG generation from Allen Bay, Nunavut sea ice cryoconites—HiSeq-only, MinION-only, and hybrid (HiSeq + MinION)—where field MinION sequencing yielded a reliable metagenome. The hybrid assembly produced longer contigs, more coding sequences, and more total MAGs, revealing a microbial community dominated by Bacteroidetes. The hybrid MAGs also had the highest completeness, lowest contamination, and highest N50. A putatively novel species ofOctadecabacteris among the hybrid MAGs produced, containing the genus’s only known instances of genomic potential for nitrate reduction, denitrification, sulfate reduction, and fermentation. This study shows that the inclusion of MinION reads in traditional short read datasets leads to higher quality metagenomes and MAGs for more accurate descriptions of novel microorganisms in this extreme, transient habitat and has produced the first hybrid MAGs from an extreme environment.
Characterizing non-critically ill COVID-19 survivors with and without in-hospital rehabilitation
Authors: Musheyev Benjamin , Janowicz Rebeca , Borg Lara , Matarlo Michael , Boyle Hayle , Hou Wei , Duong Tim Q. 
Published: October 2021

AbstractThis study investigated pre-COVID-19 admission dependency, discharge assistive equipment, discharge medical follow-up recommendation, and functional status at hospital discharge of non-critically ill COVID-19 survivors, stratified by those with (N = 155) and without (N = 162) in-hospital rehabilitation. “Mental Status”, intensive-care-unit (ICU) Mobility, and modified Barthel Index scores were assessed at hospital discharge. Relative to the non-rehabilitation patients, rehabilitation patients were older, had more comorbidities, worse pre-admission dependency, were discharged with more assistive equipment and supplemental oxygen, spent more days in the hospital, and had more hospital-acquired acute kidney injury, acute respiratory failure, and more follow-up referrals (p < 0.05 for all). Cardiology, vascular medicine, urology, and endocrinology were amongst the top referrals. Functional scores of many non-critically ill COVID-19 survivors were abnormal at discharge (p < 0.05) and were associated with pre-admission dependency (p < 0.05). Some functional scores were negatively correlated with age, hypertension, coronary artery disease, chronic kidney disease, psychiatric disease, anemia, and neurological disorders (p < 0.05). In-hospital rehabilitation providing restorative therapies and assisting discharge planning were challenging in COVID-19 circumstances. Knowledge of the functional status, discharge assistive equipment, and follow-up medical recommendations at discharge could enable appropriate and timely post-discharge care. Follow-up studies of COVID-19 survivors are warranted as many will likely have significant post-acute COVID-19 sequela.
Triazolopyrimidine herbicides are potent inhibitors of Aspergillus fumigatus acetohydroxyacid synthase and potential antifungal drug leads
Authors: Low Y. S. , Garcia M. D. , Lonhienne T. , Fraser J. A. , Schenk G. , Guddat L. W. 
Published: October 2021

AbstractAspergillus fumigatus is a fungal pathogen whose effects can be debilitating and potentially fatal in immunocompromised patients. Current drug treatment options for this infectious disease are limited to just a few choices (e.g. voriconazole and amphotericin B) and these themselves have limitations due to potentially adverse side effects. Furthermore, the likelihood of the development of resistance to these current drugs is ever present. Thus, new treatment options are needed for this infection. A new potential antifungal drug target is acetohydroxyacid synthase (AHAS; EC 2.2.1.6), the first enzyme in the branched chain amino acid biosynthesis pathway, and a target for many commercial herbicides. In this study, we have expressed, purified and characterised the catalytic subunit of AHAS from A. fumigatus and determined the inhibition constants for several known herbicides. The most potent of these, penoxsulam and metosulam, have Ki values of 1.8 ± 0.9 nM and 1.4 ± 0.2 nM, respectively. Molecular modelling shows that these compounds are likely to bind into the herbicide binding pocket in a mode similar to Candida albicans AHAS. We have also shown that these two compounds inhibit A. fumigatus growth at a concentration of 25 µg/mL. Thus, AHAS inhibitors are promising leads for the development of new anti-aspergillosis therapeutics.
The new SRS/FSRT technique HyperArc for benign brain lesions: a dosimetric analysis
Authors: Ho Hsiu-Wen , Yang Ching-Chieh , Lin Hsiu-Man , Chen Hsiao-Yun , Huang Chun-Chiao , Wang Shih-Chang , Lin Yu-Wei 
Published: October 2021

AbstractTo evaluate the potential benefit of HyperArc (HA) fractionated stereotactic radiotherapy (FSRT) for the benign brain lesion. Sixteen patients with a single deep-seated, centrally located benign brain lesion treated by CyberKnife (CK, G4 cone-based model) were enrolled. Treatment plans for HA with two different optimization algorithms (SRS NTO and ALDO) and coplanar RapidArc (RA) were generated for each patient to meet the corresponding treatment plan criteria. These four FSRT treatment plans were divided into two groups—the homogeneous delivery group (HA-SRS NTO and coplanar RA) and the inhomogeneous delivery group (HA-ALDO and cone-based CK)—to compare for dosimetric outcomes. For homogeneous delivery, the brain V5, V12, and V24 and the mean brainstem dose were significantly lower with the HA-SRS NTO plans than with the coplanar RA plans. The conformity index, high and intermediate dose spillage, and gradient radius were significantly better with the HA-SRS NTO plans than with the coplanar RA plans. For inhomogeneous delivery, the HA-ALDO exhibited superior PTV coverage levels to the cone-based CK plans. Almost all the doses delivered to organs at risk and dose distribution metrics were significantly better with the HA-ALDO plans than with the cone-based CK plans. Good dosimetric distribution makes HA an attractive FSRT technique for the treatment of benign brain lesions.
Indocyanine green lymphangiography is superior to clinical staging in breast cancer-related lymphedema
Authors: Jørgensen Mads Gustaf , Hermann Anne Pernille , Madsen Anette Riis , Christensen Steffanie , Sørensen Jens Ahm 
Published: October 2021

AbstractPrecise staging of breast cancer-related lymphedema (BCRL) is important to guide treatment-decision making. Recent studies have suggested staging of BCRL using indocyanine green lymphangiography (ICG-L) based on the extent of lymphatic injury and dermal backflow patterns. Currently, the benefits of ICG-L compared to conventional clinical staging are unknown. For this study, we included 200 patients with unilateral BCRL. All BCRL patients were staged using ICG-L and clinical exam. The amounts of excess arm volume, fat mass and lean mass were compared between stages using Dual Energy X-Ray Absorptiometry. Multivariate regression models were used to adjust for confounders. For each increase in the patient's ICG-L stage, the excess arm volume, fat mass and lean mass was increased by 8, 12 and 6.5 percentage points respectively (P < 0.001). For each increase in the patient's clinical ISL stage, the volume was increased by 3.5 percentage points (P < 0.05), however no statistically significant difference in the lean and fat mass content of the arm was observed for ascending stages. However, the residual plots showed a high degree of variance for both ICG-L and clinical staging. This study found that ICG-L staging of BCRL was superior to clinical staging in forecasting BCRL excess arm volume, fat mass, and lean mass. However, there was a high degree of variance in excess arm volume, fat mass, and lean mass within each staging system, and neither the ICG-L nor clinical staging forecasted perfectly.