bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structurally restricted Bi(III) metallation of apo-βMT1a: metal-induced tangling
Authors: Korkola Natalie C , Hudson Elyse , Stillman Martin J 
Published: April 2021

AbstractNon-toxic bismuth salts are used in anti-ulcer medications and to protect against nephrotoxicity from anticancer drugs. Bismuth salts also induce metallothionein (MT), a metal-binding protein that lacks a formal secondary structure. We report the impact on the metallation properties of Bi(III) to the 9-cysteine β fragment of MT as a function of cysteine accessibility using electrospray ionization mass spectrometry. At pH 7.4, Bi2βMT formed cooperatively. Cysteine modification shows that each Bi(III) was terminally bound to three cysteinyl thiolates. Non-cooperative Bi(III) binding was observed at pH 2.3, where cysteine accessibility is increased. However, competition from H4EDTA inhibited Bi(III) binding. When GdmCl, a well-known denaturing agent, was used to increase cysteine accessibility of the apoβMT at pH 7.4, a greater fraction of Bi3βMT formed using all nine cysteines. The change in binding profile and equilibrium of Bi2βMT was determined as a function of acidification, which changed as a result of competition with H4EDTA. There was no Bi(III) transfer between Bi2βMT, Cd3βMT, and Zn3βMT. This lack of metal exchange and the resistance towards binding the third Bi(III) suggest a rigidity in the Bi2βMT binding sites that inhibits Bi(III) mobility. These experiments emphasize the conformational control of metallation that results in substantially different metallated products: at pH 7.4 (many cysteines buried) Bi2βMT, whereas at pH 7.4 (all cysteines accessible) enhanced formation of Bi3βMT. These data suggest that the addition of the first two Bi(III) crosslinks the protein, blocking access to the remaining three cysteines for the third Bi(III), as a result of tangle formation.
Structural recognition of the MYC promoter G-quadruplex by a quinoline derivative: insights into molecular targeting of parallel G-quadruplexes
Authors: Dickerhoff Jonathan , Dai Jixun , Yang Danzhou 
Published: April 2021

Abstract
DNA G-Quadruplexes (G4s) formed in oncogene promoters regulate transcription. The oncogene MYC promoter G4 (MycG4) is the most prevalent G4 in human cancers. However, the most studied MycG4 sequence bears a mutated 3′-residue crucial for ligand recognition. Here, we report a new drug-like small molecule PEQ without a large aromatic moiety that specifically binds MycG4. We determined the NMR solution structures of the wild-type MycG4 and its 2:1 PEQ complex, as well as the structure of the 2:1 PEQ complex of the widely used mutant MycG4. Comparison of the two complex structures demonstrates specific molecular recognition of MycG4 and shows the clear effect of the critical 3′-mutation on the drug binding interface. We performed a systematic analysis of the four available complex structures involving the same mutant MycG4, which can be considered a model system for parallel G4s, and revealed for the first time that the flexible flanking residues are recruited in a conserved and sequence-specific way, as well as unused potential for selective ligand-G4 hydrogen-bond interactions. Our results provide the true molecular basis for MycG4-targeting drugs and new critical insights into future rational design of drugs targeting MycG4 and parallel G4s that are prevalent in promoter and RNA G4s.
dSPRINT: predicting DNA, RNA, ion, peptide and small molecule interaction sites within protein domains
Authors: Etzion-Fuchs Anat , Todd David A , Singh Mona 
Published: April 2021

Abstract
Domains are instrumental in facilitating protein interactions with DNA, RNA, small molecules, ions and peptides. Identifying ligand-binding domains within sequences is a critical step in protein function annotation, and the ligand-binding properties of proteins are frequently analyzed based upon whether they contain one of these domains. To date, however, knowledge of whether and how protein domains interact with ligands has been limited to domains that have been observed in co-crystal structures; this leaves approximately two-thirds of human protein domain families uncharacterized with respect to whether and how they bind DNA, RNA, small molecules, ions and peptides. To fill this gap, we introduce dSPRINT, a novel ensemble machine learning method for predicting whether a domain binds DNA, RNA, small molecules, ions or peptides, along with the positions within it that participate in these types of interactions. In stringent cross-validation testing, we demonstrate that dSPRINT has an excellent performance in uncovering ligand-binding positions and domains. We also apply dSPRINT to newly characterize the molecular functions of domains of unknown function. dSPRINT’s predictions can be transferred from domains to sequences, enabling predictions about the ligand-binding properties of 95% of human genes. The dSPRINT framework and its predictions for 6503 human protein domains are freely available at http://protdomain.princeton.edu/dsprint.
InterEvDock3: a combined template-based and free docking server with increased performance through explicit modeling of complex homologs and integration of covariation-based contact maps
Authors: Quignot Chloé , Postic Guillaume , Bret Hélène , Rey Julien , Granger Pierre , Murail Samuel , Chacón Pablo , Andreani Jessica , Tufféry Pierre , Guerois Raphaël 
Published: April 2021

AbstractThe InterEvDock3 protein docking server exploits the constraints of evolution by multiple means to generate structural models of protein assemblies. The server takes as input either several sequences or 3D structures of proteins known to interact. It returns a set of 10 consensus candidate complexes, together with interface predictions to guide further experimental validation interactively. Three key novelties were implemented in InterEvDock3 to help obtain more reliable models: users can (i) generate template-based structural models of assemblies using close and remote homologs of known 3D structure, detected through an automated search protocol, (ii) select the assembly models most consistent with contact maps from external methods that implement covariation-based contact prediction with or without deep learning and (iii) exploit a novel coevolution-based scoring scheme at atomic level, which leads to significantly higher free docking success rates. The performance of the server was validated on two large free docking benchmark databases, containing respectively 230 unbound targets (Weng dataset) and 812 models of unbound targets (PPI4DOCK dataset). Its effectiveness has also been proven on a number of challenging examples. The InterEvDock3 web interface is available at http://bioserv.rpbs.univ-paris-diderot.fr/services/InterEvDock3/.
A novel bipartite antitermination system widespread in conjugative elements of Gram-positive bacteria
Authors: Miguel-Arribas Andrés , Val-Calvo Jorge , Gago-Córdoba César , Izquierdo José M , Abia David , Wu Ling Juan , Errington Jeff , Meijer Wilfried J J 
Published: April 2021

AbstractTranscriptional regulation allows adaptive and coordinated gene expression, and is essential for life. Processive antitermination systems alter the transcription elongation complex to allow the RNA polymerase to read through multiple terminators in an operon. Here, we describe the discovery of a novel bipartite antitermination system that is widespread among conjugative elements from Gram-positive bacteria, which we named conAn. This system is composed of a large RNA element that exerts antitermination, and a protein that functions as a processivity factor. Besides allowing coordinated expression of very long operons, we show that these systems allow differential expression of genes within an operon, and probably contribute to strict regulation of the conjugation genes by minimizing the effects of spurious transcription. Mechanistic features of the conAn system are likely to decisively influence its host range, with important implications for the spread of antibiotic resistance and virulence genes.
Intracranial Meningiomas Decrease in Volume on Magnetic Resonance Imaging After Discontinuing Progestin
Authors: Voormolen Eduard H J , Champagne Pierre Olivier , Roca Elena , Giammattei Lorenzo , Passeri Thibault , di Russo Paolo , Sanchez Miguel Marigil , Bernat Anne Laure , Yoldjian Isabelle , Fontanel Sylvie , Weill Alain , Mandonnet Emmanuel , Froelich Sébastien 
Published: April 2021

Abstract

BACKGROUND
The behavior of meningiomas under influence of progestin therapy remains unclear.

OBJECTIVE
To investigate the relationship between growth kinetics of intracranial meningiomas and usage of the progestin cyproterone acetate (PCA).

METHODS
This study prospectively followed 108 women with 262 intracranial meningiomas and documented PCA use. A per-meningioma analysis was conducted. Changes in meningioma volumes over time, and meningioma growth velocities, were measured on magnetic resonance imaging (MRI) after stopping PCA treatment.

RESULTS
Mean follow-up time was 30 (standard deviation [SD] 29) mo. Ten (4%) meningiomas were treated surgically at presentation. The other 252 meningiomas were followed after stopping PCA treatment. Overall, followed meningiomas decreased their volumes by 33% on average (SD 28%). A total of 188 (72%) meningiomas decreased, 51 (20%) meningiomas remained stable, and 13 (4%) increased in volume of which 3 (1%) were surgically treated because of radiological progression during follow-up after PCA withdrawal. In total, 239 of 262 (91%) meningiomas regressed or stabilized during follow-up. Subgroup analysis in 7 women with 19 meningiomas with follow-up before and after PCA withdrawal demonstrated that meningioma growth velocity changed statistically significantly (P = .02). Meningiomas grew (average velocity of 0.25 mm3/day) while patients were using PCA and shrank (average velocity of −0.54 mm3/day) after discontinuation of PCA.

CONCLUSION
Ninety-one percent of intracranial meningiomas in female patients with long-term PCA use decrease or stabilize on MRI after stopping PCA treatment. Meningioma growth kinetics change significantly from growth during PCA usage to shrinkage after PCA withdrawal.
Transportation of AIE-visualized nanoliposomes is dominated by the protein corona
Authors: Wang Yi-Feng , Zhang Chunqiu , Yang Keni , Wang Yufei , Shan Shaobo , Yan Yan , Dawson Kenneth A , Wang Chen , Liang Xing-Jie 
Published: April 2021

Abstract
Liposomes, especially cationic liposomes, are the most common and well-investigated nanocarriers for biomedical applications, such as drug and gene delivery. Like other types of nanomaterials, once liposomes are incubated in a biological milieu, their surface can be immediately cloaked by biological components to form a protein corona, which confers a new ‘biological identity’ and modulates downstream interactions with cells. However, it remains unclear how the protein corona affects the transportation mechanism after liposomes interact with cells. Here, we employed home-made aggregation-induced-emission-visualized nanoliposomes TR4@Lipo as a model to investigate transportation with or without the protein corona by optical imaging techniques. The results show that the protein corona can change the cellular transportation mechanism of TR4@Lipo from energy-independent membrane fusion to energy-dependent endocytosis. The protein corona also modulates the intracellular distribution of loaded cargoes. This knowledge furthers our understanding of bio-nano interactions and is important for the efficient use of cationic liposomes.
The distinct morphological phenotypes of Southeast Asian aborigines are shaped by novel mechanisms for adaptation to tropical rainforests
Authors: Zhang Xiaoming , Liu Qi , Zhang Hui , Zhao Shilei , Huang Jiahui , Sovannary Tuot , Bunnath Long , Aun Hong Seang , Samnom Ham , Su Bing , Chen Hua 
Published: April 2021

AbstractSoutheast Asian aborigines, the hunter-gatherer populations living in tropical rainforests, exhibit distinct morphological phenotypes, including short stature, dark skin, curly hair and a wide and snub nose. The underlying genetic architecture and evolutionary mechanism of these phenotypes remain a long-term mystery. We conducted whole genome deep sequencing of 81 Cambodian aborigines from eight ethnic groups. Through a genome-wide scan of selective sweeps, we discovered key genes harboring Cambodian-enriched mutations that may contribute to their phenotypes, including two hair morphogenesis genes (TCHH and TCHHL1), one nasal morphology gene (PAX3) and a set of genes (such as ENTPD1-AS1) associated with short stature. The identified new genes and novel mutations suggest an independent origin of the distinct phenotypes in Cambodian aborigines through parallel evolution, refuting the long-standing argument on the common ancestry of these phenotypes among the worldwide rainforest hunter-gatherers. Notably, our discovery reveals that various types of molecular mechanisms, including antisense transcription and epigenetic regulation, contribute to human morphogenesis, providing novel insights into the genetics of human environmental adaptation.
Image-Guided Right T10 Costotransverse Joint Resection for Costotransversitis: Operative Technique and Nuances: 2-Dimensional Operative Video
Authors: De Biase Gaetano , Gassie Kelly , Abode-Iyamah Kingsley , Nottmeier Eric 
Published: April 2021

Abstract
We describe the operative approach and management for costotransverse joint inflammation in a 49-yr-old man with worsening midthoracic pain radiating to the right paraspinal area. He underwent physical therapy with no relief of his symptoms. Thoracic spine magnetic resonance imaging (MRI) revealed severe arthritic changes involving the right T10 costotransverse joint. Scoliosis X-rays showed a dextroconvex curvature in the midthoracic spine, without any significant imbalance. Single-photon emission computed tomography (SPECT) scan revealed focal increased uptake of the right T10 costotransverse joint. T10 costotransverse joint lidocaine injection did not provide any relief. We performed a computed tomography (CT)-guided biopsy, which was negative for malignancy and also cultures were negative. MRI revealed a significant enhancement in this area and the patient's C-reactive Protein was elevated. Decision was made to perform open biopsy and costotransverse joint resection. We present a case of minimally invasive, image-guided costotransverse joint resection, which has not been described in the literature. The right T10 costotransverse joint was dissected out with the image-guided dilator, and tubular retractors were inserted. Under the microscope, using the image-guided drill, the right T10 costotransverse joint was drilled out. The lateral aspect of the right T10 process was drilled out as well as the medial-dorsal aspect of the right T10 rib. The patient recovered from surgery well with abatement of his preoperative thoracic pain, which remained abated at 6-mo follow-up. This case highlights the complex technical nuances of this procedure, and the importance of a thorough preoperative evaluation with a bone SPECT scan to help localize the pain generator.
Patient consented for the procedures and for the publication of the video.
Erard
Authors: Adelson Robert 
Published: April 2021

Abstract
Sébastien Erard’s (1752–1831) inventions have had an enormous impact on instruments and musical life and are still at the foundation of piano building today. Drawing on an unusually rich set of archives from both the Erard firm and the Erard family, Robert Adelson shows how the Erard piano played an important and often leading role in the history of the instrument, beginning in the late eighteenth century and continuing into the final decades of the nineteenth. The Erards were the first piano builders in France to prioritise the more sonorous grand piano, sending gifts of their new model to both Haydn and Beethoven. Erard’s famous double-escapement action, which improved the instrument’s response while at the same time producing a more powerful tone, revolutionised both piano construction and repertoire. Thanks to these inventions, the Erard firm developed close relationships with the greatest pianist composers of the nineteenth century, including Hummel, Liszt, Moscheles, and Mendelssohn. The book also presents new evidence concerning Pierre Erard’s homosexuality, which helps us to understand his reluctance to found a family to carry on the Erard tradition, a reluctance that would spell the end of the golden era of the firm and lead to its eventual demise. The book closes with the story of Pierre’s widow Camille, who directed the firm from 1855 until 1889. Her influential position in the male-dominated world of instrument building was unique for a woman of her time.
The mechanism by which noncoding RNAs regulate muscle wasting in cancer cachexia
Authors: Zhou Xueer , Hu Shoushan , Zhang Yunan , Du Guannan , Li Yi 
Published: April 2021

AbstractCancer cachexia (CC) is a complex metabolic syndrome that accelerates muscle wasting and affects up to 80% of patients with cancer; however, timely diagnostic methods and effective cures are lacking. Although a considerable number of studies have focused on the mechanism of CC-induced muscle atrophy, few novel therapies have been applied in the last decade. In recent years, noncoding RNAs (ncRNAs) have attracted great attention as many differentially expressed ncRNAs in cancer cachectic muscles have been reported to participate in the inhibition of myogenesis and activation of proteolysis. In addition, extracellular vesicles (EVs), which function as ncRNA carriers in intercellular communication, are closely involved in changing ncRNA expression profiles in muscle and promoting the development of muscle wasting; thus, EV-related ncRNAs may represent potential therapeutic targets. This review comprehensively describes the process of ncRNA transmission through EVs and summarizes the pathways and targets of ncRNAs that lead to CC-induced muscle atrophy.
Predicting Recurrent Care Seeking of Physical Therapy for Musculoskeletal Pain Conditions
Authors: George Steven Z , Giczewska Anna , Alhanti Brooke , Lutz Adam D , Shanley Ellen , Thigpen Charles A , Bhavsar Nrupen A 
Published: April 2021

AbstractObjectiveMusculoskeletal pain conditions are a leading cause of pain and disability internationally and a common reason to seek health care. Accurate prediction of recurrence of health care seeking due to musculoskeletal conditions could allow for better tailoring of treatment. The aim of this project was to characterize patterns of recurrent physical therapy seeking for musculoskeletal pain conditions and to develop a preliminary prediction model to identify those at increased risk of recurrent care seeking.DesignRetrospective cohort.SettingAmbulatory care.SubjectsPatients (n = 578,461) seeking outpatient physical therapy (United States).MethodsPotential predictor variables were extracted from the electronic medical record, and patients were placed into three different recurrent care categories. Logistic regression models were used to identify individual predictors of recurrent care seeking, and the least absolute shrinkage and selection operator (LASSO) was used to develop multivariate prediction models.ResultsThe accuracy of models for different definitions of recurrent care ranged from 0.59 to 0.64 (c-statistic), and individual predictors were identified from multivariate models. Predictors of increased risk of recurrent care included receiving workers’ compensation and Medicare insurance, having comorbid arthritis, being postoperative at the time of the first episode, age range of 44–64 years, and reporting night sweats or night pain. Predictors of decreased risk of recurrent care included lumbar pain, chronic injury, neck pain, pregnancy, age range of 25–44 years, and smoking.ConclusionThis analysis identified a preliminary predictive model for recurrence of care seeking of physical therapy, but model accuracy needs to improve to better guide clinical decision-making.
The yellow vests roundabout revolt, seen through the lens of household budgets
Authors: Blavier Pierre 
Published: April 2021

AbstractThe ‘yellow vest movement’ that emerged in France in Autumn 2018 raises a serious question for political economy, because many of those who participated did not come from the most fragile sectors of the population. Based on ethnographic fieldwork, but also quantitative data, this article takes an in-depth look at the household budget of one ‘yellow vest’ family. It reveals the increasing tensions lower middle-class peri-urban families are confronted with, and the different ways they address them. In order to understand how they make ends meet, various spheres like the labour and housing market, the transport system, and social mobility must absolutely be interconnected. Contemporary economic reforms impact heavily on these households, lending support to the argument of an ‘attack on household budgets’, particularly as far as road transport is concerned. This approach also allows us to observe the gap between the socio-economic reality of these people and the overly unidimensional statistical indicators available. This budgetary data paves the way for a fair comparison with other contemporary political changes—Brexit for example—to see if similar mechanisms are at work in those cases.
ALiEM Connect: Large-Scale, Interactive, Virtual Residency Programming in Response to COVID-19
Authors: Rose Christian C. , Haas Mary Rose Calderone , Yilmaz Yusuf , Alvarez Al’ai , Mott Sarah E. , Landry Adaira I. , Gisondi Michael A. , Ankel Felix , Lin Michelle , Chan Teresa M. 
Published: April 2021

Problem
The COVID-19 pandemic restricted in-person gatherings, including residency conferences. The pressure to quickly reorganize educational conferences and convert content to a remote format overwhelmed many programs. This article describes the pilot event of a large-scale, interactive, virtual educational conference modeled, designed, and implemented by Academic Life in Emergency Medicine (ALiEM), called ALiEM Connect.

Approach
The pilot ALiEM Connect event was conceptualized and implemented within a 2-week period in March 2020. The pilot was livestreamed via a combination of Zoom and YouTube and was archived by YouTube. Slack was used as a backchannel to allow interaction with other participants and engagement with the speakers (via moderators who posed questions from the backchannel to the speakers live during the videoconference).

Outcomes
The RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework was used for program evaluation, showing that 64 U.S. Accreditation Council for Graduate Medical Education–accredited emergency medicine residency programs participated in the pilot event, with 1,178 unique users during the event (reach). For effectiveness, 93% (139/149) of trainees reported the pilot as enjoyable and 85% (126/149) reported it was equivalent to or better than their usual academic proceedings. Adoption for ALiEM Connect was fairly good with 64/237 (27%) of invited residency programs registering and participating in the pilot event. Implementation was demonstrated by nearly half of the livestream viewers (47%, 553/1,178) interacting in the backchannel discussion, sending a total of 4,128 messages in the first 4 hours.

Next Steps
The final component of the RE-AIM framework, maintenance, will take more time to evaluate. Further study is required to measure the educational impact of events like the ALiEM Connect pilot. The ALiEM Connect model could potentially be used to replace educational conferences that have been canceled or to implement and/or augment a large-scale, shared curriculum among residency programs in the future.