bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Hunt for Ancient Prions: Archaeal Prion-Like Domains Form Amyloid-Based Epigenetic Elements
Authors: Zajkowski Tomasz , Lee Michael D , Mondal Shamba S , Carbajal Amanda , Dec Robert , Brennock Patrick D , Piast Radoslaw W , Snyder Jessica E , Bense Nicholas B , Dzwolak Wojciech , Jarosz Daniel F , Rothschild Lynn J 
Published: January 2021

Abstract
Prions, proteins that can convert between structurally and functionally distinct states and serve as non-Mendelian mechanisms of inheritance, were initially discovered and only known in eukaryotes, and consequently considered to likely be a relatively late evolutionary acquisition. However, the recent discovery of prions in bacteria and viruses has intimated a potentially more ancient evolutionary origin. Here, we provide evidence that prion-forming domains exist in the domain archaea, the last domain of life left unexplored with regard to prions. We searched for archaeal candidate prion-forming protein sequences computationally, described their taxonomic distribution and phylogeny, and analyzed their associated functional annotations. Using biophysical in vitro assays, cell-based and microscopic approaches, and dye-binding analyses, we tested select candidate prion-forming domains for prionogenic characteristics. Out of the 16 tested, eight formed amyloids, and six acted as protein-based elements of information transfer driving non-Mendelian patterns of inheritance. We also identified short peptides from our archaeal prion candidates that can form amyloid fibrils independently. Lastly, candidates that tested positively in our assays had significantly higher tyrosine and phenylalanine content than candidates that tested negatively, an observation that may help future archaeal prion predictions. Taken together, our discovery of functional prion-forming domains in archaea provides evidence that multiple archaeal proteins are capable of acting as prions—thus expanding our knowledge of this epigenetic phenomenon to the third and final domain of life and bolstering the possibility that they were present at the time of the last universal common ancestor.
Structure of a reaction intermediate mimic in t6A biosynthesis bound in the active site of the TsaBD heterodimer from Escherichia coli
Authors: Kopina Brett J , Missoury Sophia , Collinet Bruno , Fulton Mark G , Cirio Charles , van Tilbeurgh Herman , Lauhon Charles T 
Published: January 2021

Abstract
The tRNA modification N6-threonylcarbamoyladenosine (t6A) is universally conserved in all organisms. In bacteria, the biosynthesis of t6A requires four proteins (TsaBCDE) that catalyze the formation of t6A via the unstable intermediate l-threonylcarbamoyl-adenylate (TC-AMP). While the formation and stability of this intermediate has been studied in detail, the mechanism of its transfer to A37 in tRNA is poorly understood. To investigate this step, the structure of the TsaBD heterodimer from Escherichia coli has been solved bound to a stable phosphonate isosteric mimic of TC-AMP. The phosphonate inhibits t6A synthesis in vitro with an IC50 value of 1.3 μM in the presence of millimolar ATP and L-threonine. The inhibitor binds to TsaBD by coordination to the active site Zn atom via an oxygen atom from both the phosphonate and the carboxylate moieties. The bound conformation of the inhibitor suggests that the catalysis exploits a putative oxyanion hole created by a conserved active site loop of TsaD and that the metal essentially serves as a binding scaffold for the intermediate. The phosphonate bound crystal structure should be useful for the rational design of potent, drug-like small molecule inhibitors as mechanistic probes or potentially novel antibiotics.
NMR structural study on the self-trimerization of d(GTTAGG) into a dynamic trimolecular G-quadruplex assembly preferentially in Na+ solution with a moderate K+ tolerance
Authors: Jing Haitao , Fu Wenqiang , Hu Wenxuan , Xu Suping , Xu Xiaojuan , He Miao , Liu Yangzhong , Zhang Na 
Published: January 2021

Abstract
Vast G-quadruplexes (GQs) are primarily folded by one, two, or four G-rich oligomers, rarely with an exception. Here, we present the first NMR solution structure of a trimolecular GQ (tri-GQ) that is solely assembled by the self-trimerization of d(GTTAGG), preferentially in Na+ solution tolerant to an equal amount of K+ cation. Eight guanines from three asymmetrically folded strands of d(GTTAGG) are organized into a two-tetrad core, which features a broken G-column and two width-irregular grooves. Fast strand exchanges on a timescale of second at 17°C spontaneously occur between folded tri-GQ and unfolded single-strand of d(GTTAGG) that both species coexist in dynamic equilibrium. Thus, this tri-GQ is not just simply a static assembly but rather a dynamic assembly. Moreover, another minor tetra-GQ that has putatively tetrameric (2+2) antiparallel topology becomes noticeable only at an extremely high strand concentration above 18 mM. The major tri-GQ and minor tetra-GQ are considered to be mutually related, and their reversible interconversion pathways are proposed accordingly. The sequence d(GTTAGG) could be regarded as either a reading frame shifted single repeat of human telomeric DNA or a 1.5 repeat of Bombyx mori telomeric DNA. Overall, our findings provide new insight into GQs and expect more functional applications.
Paleolithic Hunter-Gatherers of Nubia
Authors: Masojć Mirosław 
Published: January 2021

AbstractThe chapter is devoted to the earliest human settlement in Nubia, which took place in the Pleistocene, with numerous references to neighboring areas, especially Upper Egypt. Paleolithic groups of humans probably appeared in Nubia in the Early Pleistocene, but well-documented sites—connected with Lower Paleolithic-Acheulean complex industries—are dated only to Middle Pleistocene (MIS 9-7). Some of the oldest Middle Stone Age (MSA) assemblages in Africa were discovered in Nubia (ca. 220 ka, MIS 7). Numerous MSA sites (ca. 220–40 ka, MIS 7-3) with predominating Levallois technology are situated within the Nile valley and the neighboring deserts, mainly in oases. The onset of Upper Paleolithic (ca. 40–20 ka, MIS 3-2) blade technology was recorded together with the oldest mining. Late Paleolithic groups of humans (20–11 ka, MIS 2), characterized by considerable diversity in the hyper-arid period, lived only in the Nile valley. Local examples of rock paintings come from that period. Pleistocene human remains from Nubia are extremely rare; they all represent H. sapiens. Cemeteries with numerous burials, some of which display evidence of violence, were also discovered in this area.
Indo-European Languages of the Caucasus
Authors: Belyaev Oleg 
Published: January 2021

AbstractIndo-European languages have been spoken in the Caucasus over millenia, alongside languages of the three indigenous families of the region. This chapter provides a general overview of four languages whose core area is situated in the Caucasus (both the North Caucasus and Transcaucasia): Eastern Armenian (which together with Western Armenian forms a separate branch of Indo-European) and three Iranian languages: Ossetic, spoken in North Ossetia, part of Russia, and South Ossetia beyond the mountain range; Judeo-Tat, spoken by Mountain Jews in Dagestan and Azerbaijan; and Talyshi, spoken by the Talysh people mainly in the south of Azerbaijan, but also in neighboring regions of Iran. The chapter captures the current understanding of the core areas of phonology and grammar of these languages and provides information on features that could possibly have been induced by contact with the neighboring Caucasian languages.
Fifteenth-Century Eastern Reception of Aquinas
Authors: Golitsis Pantelis 
Published: January 2021

AbstractThe Eastern reception of Aquinas in the fifteenth century was determined by the theological repercussions that occurred in Byzantium in the preceding century, namely the association of Thomism with Barlaamism and Akindynism (the denial of a real distinction between God’s essence and energies or of God’s having energies at all), the use of Aristotle’s syllogistic theory in establishing the Filioque, and the vision of God’s essence in statu patriae. Nevertheless, Aquinas’ two Summae were used and tacitly excerpted (in the translations of the brothers Kydones) by Palamite theologians for settling other theological matters, whereas there was an open vindication of Aquinas both as a philosopher and as a reliable guide in the exposition of the Scriptures by George Scholarios (Patriarch Gennadios II).
Concentration and Visualization Techniques in Buddhist Meditation
Authors: Yamabe Nobuyoshi 
Published: January 2021

Abstract
This chapter outlines the early form and development of Buddhist meditation. First, it discusses the “application of mindfulness,” especially “mindfulness of the body,” which can be largely classified into two types of practice. One is “mindfulness per se,” without reflective thought, and the other is a more reflective or visual approach. “Mindfulness per se” (in particular, mindful breathing) was transmitted to East Asia and remains the cardinal method there. The chapter discusses close ties between traditional mindfulness and Japanese Sōtō practice. It then moves on to describe meditation on the decomposition of a corpse, which is a representative form of the more reflective and visual type of practice, involving the observation of a dead body in its stages of decomposition. This is found in early scriptures. Later texts came to teach a more elaborate method of “grasping the images” of a corpse. A notable development in visualization is that the images seen by the practitioner came to include ones that were more enigmatic. The discussion finally turns to another significant development in Buddhist meditation, one which involves Buddha visualization. Its undeveloped form is found in early Mahayana sutras, but a fully developed version employing statues as aides for visualization is found in later meditation texts from the fifth century onward. This type of visualization was inherited by Esoteric Buddhism and is still practiced today.
Did Theresa May Kill the War Powers Convention? Comparing Parliamentary Debates on UK Intervention in Syria in 2013 and 2018
Authors: Strong James 
Published: January 2021

ABSTRACT
This article asks whether Prime Minister Theresa May’s decision to bypass the House of Commons and order military action in Syria in 2018 killed the UK’s nascent War Powers Convention, established most visibly when MPs vetoed an essentially similar operation under Prime Minister David Cameron in 2013. It finds that the War Powers Convention survives, but in a weakened state, subject to new caveats that significantly narrow its scope. What happens next depends on the dynamic, unpredictable interaction between what future prime ministers believe, what strategic questions arise and what MPs will accept.
Open-label phase 3 study of intravenous golimumab in patients with polyarticular juvenile idiopathic arthritis
Authors: Ruperto Nicolino , Brunner Hermine I , Pacheco-Tena César , Louw Ingrid , Vega-Cornejo Gabriel , Spindler Alberto J , Kingsbury Daniel J , Schmeling Heinrike , Borzutzky Arturo , Cuttica Rubén , Inman C J , Malievskiy Victor , Scott Christiaan , Keltsev Vladimir , Terreri Maria Teresa , Viola Diego Oscar , Xavier Ricardo M , Fernandes Taciana A Pedrosa , Velázquez María del Rocío Maldonado , Henrickson Michael , Clark Michael B , Bensley Karen A , Li Xiaoming , Lo Kim Hung , Leu Jocelyn H , Hsu Chyi-Hung , Hsia Elizabeth C , Xu Zhenhua , Martini Alberto , Lovell Daniel J ,   for the Pediatric Rheumatology Collaborative Study Group (PRCSG) and the Paediatric Rheumatology International Trials Organisation (PRINTO), Appenzeller Simone , Oliveira Sheila , Silva Clóvis Arthur , Levy Deborah , Navarrete Carmen , Aviel Yonatan Butbul , Uziel Yosef , Alexeeva Ekaterina , Chasnyk Vladimir , Spivakovsky Yury , Gottlieb Beth , Rabinovich Egla , Zeft Andrew , Griffin Thomas , De Ranieri Deirdre , Carrasco Ruy 
Published: January 2021

Abstract

Objectives
To assess efficacy, pharmacokinetics (PK) and safety of intravenous (i.v.) golimumab in patients with polyarticular-course JIA (pc-JIA).

Methods
Children aged 2 to &lt;18 years with active pc-JIA despite MTX therapy for ≥2 months received 80 mg/m2 golimumab at weeks 0, 4, then every 8 weeks through week 52 plus MTX weekly through week 28. The primary and major secondary endpoints were PK exposure and model-predicted steady-state area under the curve (AUCss) over an 8-week dosing interval at weeks 28 and 52, respectively. JIA ACR response and safety were also assessed.

Results
In total, 127 children were treated with i.v. golimumab. JIA ACR 30, 50, 70, and 90 response rates were 84%, 80%, 70% and 47%, respectively, at week 28 and were maintained through week 52. Golimumab serum concentrations and AUCss were 0.40 µg/ml and 399 µg ⋅ day/ml at week 28. PK exposure was maintained at week 52. Steady-state trough golimumab concentrations and AUCss were consistent across age categories and comparable to i.v. golimumab dosed 2 mg/kg in adults with rheumatoid arthritis. Golimumab antibodies and neutralizing antibodies were detected via a highly sensitive drug-tolerant assay in 31% (39/125) and 19% (24/125) of patients, respectively. Median trough golimumab concentration was lower in antibody-positive vs antibody-negative patients. Serious infections were reported in 6% of patients, including one death due to septic shock.

Conclusion
Body surface area-based dosing of i.v. golimumab was well tolerated and provided adequate PK exposure for clinical efficacy in paediatric patients with active pc-JIA.
ClinicalTrials.gov number NCT02277444
Metastatic Melanoma With Features of Desmoplastic Melanoma in a Patient With Primary Cutaneous Superficial Spreading Melanoma With Epithelioid Features
Authors: Modi Mitul B. , Moshiri Ata S. , Klein Walter M. , Karakousis Giorgos , Shafique Khurram , Xu Xiaowei 
Published: January 2021

Abstract:The synchronous incidence of 2 different subtypes of melanoma is very rare. Desmoplastic melanoma (DM) can be a diagnostic challenge because of its frequent appearance as a dermal banal spindle cell proliferation. We present a case of a 30-year-old man who developed an irregular, purple, tender plaque measuring 2.5 cm on the right pretibial region. Wide excision of the right leg lesion showed superficial spreading melanoma with epithelioid cells and no spindle cell component. Sentinel lymph node (SLN) biopsy showed an atypical melanocytic proliferation involving one inguinal lymph node with subcapsular and intraparenchymal components. There were spindled tumor cells in lymph node capsule with hyperchromatic nuclei, which were nested within desmoplastic stroma, and were S100- and SOX10-positive and MART1- and HMB-45 negative; in addition to epithelioid tumor cells, which were S100-, SOX10-, and MART1-positive. Multiple discontinuous foci, subcapsular atypical melanocytes, and extracapsular extension helped in excluding capsular nevus. These findings were consistent with DM. Herein, we present an unusual case of primary cutaneous superficial spreading melanoma of the right leg with a predominantly epithelioid morphology that developed metastases to the SLN. The metastasis exhibited divergent differentiation, including both epithelioid morphology identical to the primary, but with additional features of DM that were nonoverlapping with the primary lesion.
Chemosensing in enteroendocrine cells: mechanisms and therapeutic opportunities
Authors: Yang Ming , Reimann Frank , Gribble Fiona M. 
Published: January 2021

Purpose of review
Enteroendocrine cells (EECs) are scattered chemosensory cells in the intestinal epithelium that release hormones with a wide range of actions on intestinal function, food intake and glucose homeostasis. The mechanisms by which gut hormones are secreted postprandially, or altered by antidiabetic agents and surgical interventions are of considerable interest for future therapeutic development.

Recent findings
EECs are electrically excitable and express a repertoire of G-protein coupled receptors that sense nutrient and nonnutrient stimuli, coupled to intracellular Ca2+ and cyclic adenosine monophosphate. Our knowledge of EEC function, previously developed using mouse models, has recently been extended to human cells. Gut hormone release in humans is enhanced by bariatric surgery, as well as by some antidiabetic agents including sodium-coupled glucose transporter inhibitors and metformin.

Summary
EECs are important potential therapeutic targets. A better understanding of their chemosensory mechanisms will enhance the development of new therapeutic strategies to treat metabolic and gastrointestinal diseases.
The Scope of Hospital-Based Simulation
Authors: Gilbert Marie , Waxman KT , Gilbert Gregory E. , Congenie Kari 
Published: January 2021

BACKGROUND
Healthcare simulation has expanded dramatically; however, little is known about the scope of simulation in acute care hospitals.

METHODS
A descriptive, cross-sectional online survey was used. Participants included nurse executives from acute care hospitals in California.

RESULTS
Most organizations (96%) used simulation primarily for education, 37% used simulation for health system integration and systems testing, 30% used it for error investigation, 15% used it for research, and 15% used it for patient/family education.

CONCLUSIONS
Organizations have a substantial opportunity to increase the scope of simulation beyond education to include systems integration, clinical systems testing, and other translational simulation activities. This targeted focus on patient safety and quality will allow hospitals to improve financial performance and maximize scarce resources.
Hospital Nurses’ Willingness to Respond in a Disaster
Authors: Choi Hye Seung , Lee Jong-Eun 
Published: January 2021

OBJECTIVE
This study examined the factors associated with nurses' willingness to respond in a disaster.

BACKGROUND
Nurses are key personnel in case of disasters, and therefore, understanding factors associated with willingness to respond is important.

METHODS
Questionnaires were distributed to 200 nurses recruited from 2 public hospitals in Seoul, Korea. Data were collected in January and February 2018 and 181 responses were analyzed.

RESULTS
Factors predicting willingness to respond in a disaster among public hospital nurses were level of education, self-efficacy, and disaster management competency.

CONCLUSIONS
Providing well-organized disaster preparedness and response training programs would enhance nurses' level of knowledge about disasters. In addition, training could improve nurses' self-efficacy and disaster management competency, which should enhance willingness to respond in a disaster.
Distinct Patterns of Emergence of SARS-CoV-2 Spike Variants including N501Y in Clinical Samples in Columbus Ohio
Authors: Tu Huolin , Avenarius Matthew R , Kubatko Laura , Hunt Matthew , Pan Xiaokang , Ru Peng , Garee Jason , Thomas Keelie , Mohler Peter , Pancholi Preeti , Jones Dan 
Published: January 2021

AbstractFollowing the worldwide emergence of the p.Asp614Gly shift in the Spike (S) gene of SARS-CoV-2, there have been few recurring pathogenic shifts occurring during 2020, as assessed by genomic sequencing. This situation has evolved in the last several months with the emergence of several distinct variants (first identified in the United Kingdom and South Africa) that manifest multiple changes in the S gene, particularly p.Asn501Tyr (N501Y), that likely have clinical impact. We report here the emergence in Columbus, Ohio in December 2020 of two novel SARS-CoV-2 clade 20G variants. One variant, that has become the predominant virus found in nasopharyngeal swabs in the December 2020-January 2021 period, harbors S p.Gln677His (Q677H), affecting a consensus QTQTN domain near the S1/S2 furin cleavage site, nucleocapsid (N) p.Asp377Tyr (D377Y) and membrane glycoprotein (M) p.Ala85Ser (A85S) mutations, with additional S mutations in subsets. The other variant present in two samples, contains S N501Y, which is a marker of the UK-B.1.1.7 (clade 20I/501Y.V1) strain, but lacks all other mutations from that virus. The Ohio variant is from a different clade and shares multiple mutations with the clade 20G viruses circulating in the area prior to December 2020. These two SARS-CoV-2 viruses, which we show are also present and evolving currently in several other parts of North America, add to the diversity of S gene shifts occurring worldwide. These and other shifts in this period of the pandemic support multiple independent acquisition of functionally significant and potentially complementing mutations affecting the S QTQTN site (Q675H or Q677H) and certain receptor binding domain mutations (e.g., E484K and N501Y).
Spatio-temporal evolution of urban thermal environment and its driving factors: Case study of Nanjing, China
Authors: Menghan Zhang , Suocheng Dong , Hao Cheng , Fujia Li 
Published: January 2021

AbstractIn recent years, with the rapid urbanization, the urban underlying surface has changed dramatically. Various urban eco-environmental problems have emerged in the world, among which the urban heat island effect has become one of the most obvious urban eco-environmental problems. In this study, Nanjing, China is chosen as the study area. Based on the Landsat8 remote sensing image data in Nanjing from 2014 to 2018, the land surface temperature is retrieved, the spatiotemporal variation track and characteristics of the thermal environment pattern are systematically depicted, and its driving factors are revealed. The results show that: in the past five years, the spatial pattern of heat field in Nanjing has changed from scattered distribution in the periphery of the city to centralized in the center of the city, and the heat island intensity has increased year by year. The changes of administrative divisions, the layout of transportation trunk lines, the transfer of industrial centers, and ecological construction projects are important driving factors for the evolution of land surface thermal environment pattern of these regions. The research results will provide scientific and technological support for similar cities with typical heat island effect in the world to make urban planning and development decisions, and to govern and improve urban ecological environment.