bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetic state determines inflammatory sensing in neuroblastoma
Authors: Wolpaw Adam J. , Grossmann Liron D. , Dong May M. , Dessau Jessica L. , Brafford Patricia A. , Volgina Darya , Rodriguez-Garcia Alba , Uzun Yasin , Powell Daniel J. , Tan Kai , Hogarty Michael D. , Maris John M. , Dang Chi V.
Published: January 2021

Immunotherapy has revolutionized cancer treatment, but many cancers are not impacted by currently available immunotherapeutic strategies. Here, we investigated inflammatory signaling pathways in neuroblastoma, a classically “cold” pediatric cancer. By testing the functional response of a panel of 20 diverse neuroblastoma cell lines to three different inflammatory stimuli, we found that all cell lines have intact interferon signaling and all but one lack functional cGAS-STING signaling. However, toll-like receptor (TLR) signaling, particularly through TLR3, was heterogeneous. Six cell lines showed robust response, five of which are in the mesenchymal epigenetic state, while all 14 unresponsive cell lines are in the adrenergic state. Genetically switching the adrenergic BE2(c) cell line towards the mesenchymal state fully restored TLR responsiveness. In responsive cells, TLR3 activation results in the secretion of pro-inflammatory cytokines, enrichment of inflammatory transcriptomic signatures, and increased tumor killing by T-cellsin vitro. Using single cell RNA sequencing data, we show that human neuroblastoma cells with stronger mesenchymal signatures have a higher basal inflammatory state, demonstrating intra-tumoral heterogeneity in inflammatory signaling that has significant implications for immunotherapeutic strategies in this aggressive childhood cancer.
The environment topography alters the transition from single-cell populations to multicellular structures inMyxococcus xanthus
Authors: Hernández Ramos Karla C. , Rodríguez-Sánchez Edna , Arias del Angel Juan Antonio , Arzola Alejandro V. , Benítez Mariana , Escalante Ana E. , Franci Alessio , Volpe Giovanni , Rivera-Yoshida Natsuko
Published: January 2021

The social soil-dwelling bacteria Myxococcus xanthus can form multicellular structures, known as fruiting bodies. Experiments in homogeneous environments have shown that this process is affected by the physico-chemical properties of the substrate, but they have largely neglected the role of complex topographies. We experimentally demonstrate that the topography alters single-cell motility and multicellular organization in M. xanthus. In topographies realized by randomly placing silica particles over agar plates, we observe that the cells’ interaction with particles drastically modifies the dynamics of cellular aggregation, leading to changes in the number, size and shape of the fruiting bodies, and even to arresting their formation in certain conditions. We further explore this type of cell-particle interaction in a minimal computational model. These results provide fundamental insights into how the environment topography influences the emergence of complex multicellular structures from single cells, which is a fundamental problem of biological, ecological and medical relevance.
Unbiased interrogation of memory B cells from convalescent COVID-19 patients reveals a broad antiviral humoral response targeting SARS-CoV-2 antigens beyond the spike protein
Authors: DiMuzio Jillian M. , Heimbach Baron C. , Howanski Raymond J. , Dowling John P. , Patel Nirja B. , Henriquez Noeleya , Nicolescu Chris , Nath Mitchell , Polley Antonio , Bingaman Jamie L. , Smith Todd , Harman Benjamin C. , Robinson Matthew K. , Morin Michael J. , Nikitin Pavel A.
Published: January 2021

Patients who recover from SARS-CoV-2 infections produce antibodies and antigen-specific T cells against multiple viral proteins. Here, an unbiased interrogation of the anti-viral memory B cell repertoire of convalescent patients has been performed by generating large, stable hybridoma libraries and screening thousands of monoclonal antibodies to identify specific, high-affinity immunoglobulins (Igs) directed at distinct viral components. As expected, a significant number of antibodies were directed at the Spike (S) protein, a majority of which recognized the full-length protein. These full-length Spike specific antibodies included a group of somatically hypermutated IgMs. Further, all but one of the six COVID-19 convalescent patients produced class-switched antibodies to a soluble form of the receptor-binding domain (RBD) of S protein. Functional properties of anti-Spike antibodies were confirmed in a pseudovirus neutralization assay. Importantly, more than half of all of the antibodies generated were directed at non-S viral proteins, including structural nucleocapsid (N) and membrane (M) proteins, as well as auxiliary open reading frame-encoded (ORF) proteins. The antibodies were generally characterized as having variable levels of somatic hypermutations (SHM) in all Ig classes and sub-types, and a diversity of VLand VHgene usage. These findings demonstrated that an unbiased, function-based approach towards interrogating the COVID-19 patient memory B cell response may have distinct advantages relative to genomics-based approaches when identifying highly effective anti-viral antibodies directed at SARS-CoV-2.
Low-cost, scalable, and automated fluid sampling for fluidics applications
Authors: Booeshaghi A. Sina , Kil Yeokyoung (Anne) , (Joseph) Min Kyung Hoi , Gehring Jase , Pachter Lior
Published: January 2021

We present colosseum, a low-cost, modular, and automated fluid sampling device for scalable fluidic applications. The colosseum fraction collector uses a single motor, can be built for less than $100 using off-the-shelf and 3D-printed components, and can be assembled in less than an hour. Build Instructions and source files are available athttps://github.com/pachterlab/colosseum.
Thermal laser ablation with tunable lesion size reveals multiple origins of seizure-like convulsions inCaenorhabditis elegans
Authors: Fouad Anthony D. , Liu Alice , Du Angelica , Bhirgoo Priya D. , Fang-Yen Christopher
Published: January 2021

Laser microsurgery has long been an important means of assessing the functions of specific cells and tissues. Most laser ablation systems use short, highly focused laser pulses to create plasma-mediated lesions with dimensions on the order of the wavelength of light. While the small size of the lesion enables ablation with high spatial resolution, it also makes it difficult to ablate larger structures. We developed an infrared laser ablation system capable of thermally lesioning tissues with spot sizes tunable by the duration and amplitude of laser pulses. We used our laser system in the roundwormC. elegansto kill single neurons and to sever the dorsal and ventral nerve cords, structures that are difficult to lesion using a plasma-based ablation system. We used these ablations to investigate the source of convulsions in a gain-of-function mutant for the acetylcholine receptor ACR-2. Severing the ventral nerve cord caused convulsions to occur independently anterior and posterior to the lesion, suggesting that convulsions can arise independently from distinct subsets of the motor circuit.
Genome-scale metabolic modeling reveals SARS-CoV-2-induced metabolic changes and antiviral targets
Authors: Cheng Kuoyuan , Martin-Sancho Laura , Pal Lipika R. , Pu Yuan , Riva Laura , Yin Xin , Sinha Sanju , Nair Nishanth Ulhas , Chanda Sumit K. , Ruppin Eytan
Published: January 2021

Tremendous progress has been made to control the COVID-19 pandemic caused by the SARS-CoV-2 virus. However, effective therapeutic options are still rare. Drug repurposing and combination represent practical strategies to address this urgent unmet medical need. Viruses, including coronaviruses, are known to hijack host metabolism to facilitate viral proliferation, making targeting host metabolism a promising antiviral approach. Here, we describe an integrated analysis of 12 publishedin vitroand human patient gene expression datasets on SARS-CoV-2 infection using genome-scale metabolic modeling (GEM), revealing complicated host metabolism reprogramming during SARS-CoV-2 infection. We next applied the GEM-based metabolic transformation algorithm to predict anti-SARS-CoV-2 targets that counteract the virus-induced metabolic changes. We successfully validated these targets using published drug and genetic screen data and by performing an siRNA assay in Caco-2 cells. Further generating and analyzing RNA-sequencing data of remdesivir-treated Vero E6 cell samples, we predicted metabolic targets acting in combination with remdesivir, an approved anti-SARS-CoV-2 drug. Our study provides clinical data-supported candidate anti-SARS-CoV-2 targets for future evaluation, demonstrating host metabolism-targeting as a promising antiviral strategy.
N-terminally truncated helper NLRNRG1Cantagonizes immunity mediated by its full-length neighborsNRG1AandNRG1B
Authors: Wu Zhongshou , Tian Lei , Li Xin
Published: January 2021

Both animals and plants utilize nucleotide-binding leucine-rich repeat immune receptors (NLRs) to perceive the presence of pathogen-derived molecules and induce immune responses.NLRgenes are far more abundant and diverse in higher plants. Interestingly, truncated NLRs, which lack one or more of the canonical domains, are also commonly encoded in plant genomes. However, little is known about their functions, especially regarding the N-terminally truncated ones. Here, we show thatArabidopsis thaliana(A. thaliana) N-terminally truncated helper NLR geneNRG1C(N REQUIREMENT GENE 1) is highly induced upon pathogen infection and in autoimmune mutants. The immune response and cell death conferred by some TIR (Toll/interleukin-1 receptor)-type NLRs (TNLs) are compromised in theNRG1Coverexpression lines. Detailed genetic analysis revealed that NRG1C antagonizes the immunity mediated by its full-length neighborsNRG1AandNRG1B. Biochemical tests indicate that NRG1C possibly interferes with the EDS1-SAG101 complex, which likely signals together with NRG1A/1B. Interestingly, Brassicaceae NRG1Cs are functionally exchangeable, and theNicotiana benthamiana(N. benthamiana) N-terminally truncated helper NLR NRG2 antagonizes NRG1 in tobacco. Together, our study uncovers an unexpected negative role of N-terminally truncated helper NLRs in different plants.
Pipeline for generating stable large genomic deletions in zebrafish, from small domains to whole gene excisions
Authors: Tromp Alisha , Robinson Kate , Hall Thomas E. , Mowry Bryan , Giacomotto Jean
Published: January 2021

Here we describe a short feasibility study and methodological framework for the production of stable, CRISPR/Cas9-based, large genomic deletions in zebrafish, ranging from several base pairs (bp) to hundreds of kilobases (kb). Using a cocktail of four sgRNAs targeting a single genomic region mixed with a marker-sgRNA against the pigmentation genetyrosinase(tyr), we demonstrate that one can easily and accurately excise genomic regions such as promoters, protein domains, specific exons or whole genes. We exemplify this technique with a complex gene family, neurexins, composed of three duplicated genes with multiple promoters and intricate splicing processes leading to thousands of isoforms. We precisely deleted small regions such as their transmembrane domains (150bp deletion in average) to their entire genomic locus (300kb deletion fornrxn1Afor instance). We find that both the concentration and ratio of Cas9/sgRNAs are critical for the successful generation of these large deletions and, interestingly, that their transmission frequency does not decrease with increasing distance between sgRNA target sites. Considering the growing reports and debate about genetically compensated small indel mutants, the use of large-deletion approaches is likely to be widely adopted in studies of gene function. This strategy will also be key to the study of non-coding genomic regions.
Phage Cocktails can Prevent the Evolution of Phage-ResistantEnterococcus
Authors: Wandro Stephen , Ghatbale Pooja , Attai Hedieh , Hendrickson Clark , Samillano Cyril , Suh Joy , Pride David T. , Whiteson Katrine
Published: January 2021

Antibiotic resistantEnterococcusinfections are a major health crisis that requires the development of alternative therapies. Phage therapy could be an alternative to antibiotics and has shown promise inin vitroand in early clinical studies. Phage therapy is often deployed as a cocktail of phages, but there is little understanding of how to most effectively combine phages. Here we utilized a collection of 20Enterococcusphages to test principles of phage cocktail design and determine the phenotypic effects of evolving phage resistance inEnterococcusisolates that were susceptible or resistant to antibiotics (e.g., Vancomycin Resistant Enterococcus (VRE)). We tested the ability of each phage to clearEnterococcushost cultures and prevent the emergence of phage resistantEnterococcus. We found that some phages which were ineffective individually were effective at clearing the bacterial culture when used in cocktails. To understand the dynamics within phage cocktails, we used qPCR to track which phages increased in abundance in each cocktail, and saw dynamics ranging from one dominant phage to even phage growth. Further, we isolated several phage-resistant mutants to test for altered Vancomycin sensitivity. We found that mutants tended to have no change or slightly increased resistance to Vancomycin. By demonstrating the efficacy of phage cocktails in suppressing growth of antibiotic susceptible and VRE clinical isolates when exposed to phages, this work will help to inform cocktail design for future phage therapy applications.

IMPORTANCE

Antibiotic resistantEnterococcusinfections are a major health crisis that requires the development of alternative therapies. Phage therapy could be an alternative to antibiotics and has shown promise inin vitroand in early clinical studies. Phage therapy in the form of cocktails is often suggested, with similar goals as the combination therapy that has been successful in the treatment of HIV infection, but there is little understanding about how to combine phages most effectively. Here we utilized a collection of 20Enterococcusphages to test whether several phage cocktails could prevent the host from evolving resistance to therapy and to determine whether evolving resistance to phages affected host susceptibility to antibiotics. We showed that cocktails of two or three unrelated phages often prevented the growth of phage-resistant mutants, when the same phages applied individually were not able to.
Diminished miRNA activity is associated with aberrant cytoplasmic intron retention in ALS pathogenesis
Authors: Petric-Howe Marija , Crerar Hamish , Neeves Jacob , Tyzack Giulia E. , Patani Rickie , Luisier Raphaëlle
Published: January 2021

Intron retention (IR) is now recognized as a dominant splicing event during motor neuron (MN) development, however the role and regulation of intron-retaining transcripts (IRTs) localized to the cytoplasm remain particularly understudied. By resolving the spatiotemporal dynamics of IR underlying distinct stages of MN lineage restriction, we identify a cytoplasmic group of IRTs that is not associated with reduced expression of their own genes but instead with an upregulation of predicted target genes of specific miRNAs, the motifs of which are enriched within the intronic sequences of this group. Next, we show that ALS-causing VCP mutations lead to a selective increase in IR of this particular class of introns. This in turn temporally coincides with an increase in the expression level of predicted target genes of these miRNAs, providing a potential mechanistic insight into ALS pathogenesis. Altogether, we propose a novel role for the cytoplasmic intronic sequences in regulating miRNA activity through miRNA sequestration, which potentially contributes to ALS pathogenesis.
Vasopressin V2 is a promiscuous G protein-coupled receptor that is biased by its peptide ligands
Authors: Heydenreich Franziska M. , Plouffe Bianca , Rizk Aurélien , Milić Dalibor , Zhou Joris , Breton Billy , Le Gouill Christian , Inoue Asuka , Bouvier Michel , Veprintsev Dmitry B.
Published: January 2021

Activation of the G protein-coupled receptors by agonists may result in the activation of one or more G proteins, and in the recruitment of arrestins. The balance of activation of different pathways can be influenced by the ligand. Using BRET-based biosensors, we showed that the vasopressin V2 receptor activates or at least engages many different G proteins across all G protein subfamilies in response to its native agonist arginine vasopressin (AVP). This includes members of the Gi/o and G12/13 families that have not been previously reported. These signalling pathways are also activated by the synthetic peptide desmopressin and natural homologs of AVP, namely oxytocin and the non-mammalian hormone vasotocin. They demonstrated varying degrees of functional selectivity relative to AVP, as quantified using the operational model for quantifying ligand bias. Additionally, we modelled G protein activation as a Michaelis-Menten reaction. This approach provided a complementary way to quantify signalling bias, with an added benefit of clear separation of the effects of ligand affinity from the intrinsic activity of the receptor. These results showed that V2 receptor is not only promiscuous in its ability to engage several G proteins, but also that its signalling profile could be easily biased by small structural changes in the ligand.
IL-6 blockade suppresses the blood-brain barrier disorder, leading to prevention of onset of NMOSD
Authors: Takeshita Yukio , Fujikawa Susumu , Serizawa Kenichi , Fujisawa Miwako , Matsuo Kinya , Nemoto Joe , Shimizu Fumitaka , Sano Yasuteru , Tomizawa-Shinohara Haruna , Miyake Shota , Ransohoff Richard M. , Kanda Takashi
Published: January 2021

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy caused by antibodies against the aquaporin 4(AQP4) in end-feet of astrocytes. Breakdown of the blood–brain barrier (BBB) allowing ingress of AQP4 antibodies into the central nervous system (CNS) plays a key role in NMOSD. Although IL-6 blockade therapies such as satralizumab are effective in NMOSD, the therapeutic mechanism of IL-6 blockade, especially with respect to BBB disruption, are not fully understood because of the lack of the human models that are specialized to evaluate the BBB function.

We constructed new in vitro human BBB models for evaluating continued barrier function, leukocyte transmigration and intracerebral transferability of IgGs utilizing the newly established triple co-culture system. In vitro and vivo experiments revealed that NMO-IgG increased intracerebral transferability of satralizumab, and that satralizumab suppressed the NMO-IgG-induced transmigration of T cells and barrier dysfunction. These results suggest that satralizumab, which can pass through the BBB in the presence of NMO-IgG, suppresses the barrier dysfunction and the disrupting controlled cellular infiltration at the BBB, leading to prevention of onset of NMOSD.

One sentence summary

Satralizumab and IL-6 blockade prevent lymphocyte migration and barrier dysfunction induced by NMO-IgG in EAE and novel triple co-culture BBB models.
Structural insights into a novel family of integral membrane siderophore reductases
Authors: Josts Inokentijs , Veith Katharina , Normant Vincent , Schalk Isabelle J. , Tidow Henning
Published: January 2021

Gram-negative bacteria take up the essential ion Fe3+as ferric-siderophore complexes through their outer membrane using TonB-dependent transporters. However, the subsequent route through the inner membrane differs across many bacterial species and siderophore chemistries and is not understood in detail. Here, we report the crystal structure of the inner membrane protein FoxB (fromP. aeruginosa) that is involved in Fe-siderophore uptake. The structure revealed a novel fold with two tightly-bound heme molecules. In combination with functional studies these results establish FoxB as an inner membrane reductase involved in the release of iron from ferrioxamine during Fe-siderophore uptake.
Interneuron activity-structural plasticity association is driven by context-dependent sensory experience
Authors: Saha Soham , Meng John Hongyu , Riecke Hermann , Agoranos Georgios , Sailor Kurt A. , Lledo Pierre-Marie
Published: January 2021

Neuronal dendritic spine dynamics provide a plasticity mechanism for altering brain circuit connectivity to integrate new information for learning and memory. Previousin vivostudies in the olfactory bulb (OB) showed that regional increases in activity caused localized spine stability, at a population level, yet how activity affects spine dynamics at an individual neuron level remains unknown. In this study, we trackedin vivothe correlation between an individual neuron’s activity and its dendritic spine dynamics of OB granule cell (GC) interneurons. Odor experience caused a consistent correlation between individual GC activity and spine stability. Dissecting the components of the OB circuit showed that increased principal cell (MC) activity was sufficient to drive this correlation, whereas cell-autonomously driven GC activity had no effect. A mathematical model was able to replicate the GC activity-spine stability correlation and showed MC output having improved odor discriminability while retaining odor memory. These results reveal that GC spine plasticity provides a sufficient network mechanism to decorrelate odors and maintain a memory trace.
Differential chemoarchitecture of Purkinje neurons contributes to intrinsic firing properties
Authors: Brandenburg Cheryl , Smith Lindsey A. , Kilander Michaela B.C. , Bridi Morgan S. , Lin Yu-Chih , Huang Shiyong , Blatt Gene J.
Published: January 2021

Purkinje cells (PCs) are central to cerebellar information coding and appreciation for the diversity of their firing patterns and molecular profiles is growing. Heterogeneous subpopulations of PCs have been identified that display differences in intrinsic firing properties without clear mechanistic insight into what underlies the divergence in firing parameters. Although long used as a general PC marker, we report that the calcium binding protein parvalbumin labels a subpopulation of PCs with a conserved distribution pattern across the animals examined. We trained a convolutional neural network to recognize the parvalbumin-positive subtype and create maps of whole cerebellar distribution and find that PCs within these areas have differences in spontaneous firing that can be modified by altering calcium buffer content. These subtypes also show differential responses to potassium and calcium channel blockade, suggesting a mechanistic role for variability in PC intrinsic firing through differences in ion channel composition. It is proposed that ion channels drive the diversity in PC intrinsic firing phenotype and parvalbumin calcium buffering provides capacity for the highest firing rates observed. These findings open new avenues for detailed classification of PC subtypes.
Effect of germanium auto-diffusion on the bond lengths of Ga and P atoms in GaP/Ge(111) investigated by using X-ray absorption spectroscopy
Authors: Roychowdhury R. , Rajput P. , Kumar Shailendra , Kumar R. , Bose A. , Jha S. N. , Sharma T. K. , Dixit V. K.
Published: January 2021

The germanium auto-diffusion effects on the inter-atomic distance between the nearest neighbors of the Ga atom in GaP epilayers are investigated using high-resolution X-ray diffraction (HRXRD) and X-ray absorption spectroscopy. The GaP layers grown on Ge (111) are structurally coherent and relaxed but they show the presence of residual strain which is attributed to the auto-diffusion of Ge from the results of secondary ion mass spectrometry and electrochemical capacitance voltage measurements. Subsequently, the inter-atomic distances between the nearest neighbors of Ga atom in GaP are determined from X-ray absorption fine-structure spectra performed at the Ga K-edge. The estimated local bond lengths of Ga with its first and second nearest neighbors show asymmetric variation for the in-plane and out-of-plane direction of GaP/Ge(111). The magnitude and direction of in-plane and out-of-plane microscopic residual strain present in the GaP/Ge are calculated from the difference in bond lengths which explains the presence of macroscopic residual tensile strain estimated from HRXRD. Modified nearest neighbor configurations of Ga in the auto-diffused GaP epilayer are proposed for new possibilities within the GaP/Ge hetero-structure, such as the conversion from indirect to direct band structures and engineering the tensile strain quantum dot structures on (111) surfaces.
A half-salamo-based pyridine-containing ligand and its novel NiII complexes including different auxiliary ligands: syntheses, structures, fluorescence properties, DFT calculations and Hirshfeld surface analysis
Authors: Feng Tao , Li Li-Li , Li Ya-Juan , Dong Wen-Kui
Published: January 2021

Three novel multinuclear NiII complexes, namely, bis{μ-2-methoxy-6-[8-(pyridin-2-yl)-3,6-dioxa-2,7-diazaocta-1,7-dien-1-yl]phenolato}bis[thiocyanatonickel(II)], [Ni2(L)2(NCS)2], 1, bis{μ-2-methoxy-6-[8-(pyridin-2-yl)-3,6-dioxa-2,7-diazaocta-1,7-dien-1-yl]phenolato}bis[azidonickel(II)], [Ni2(L)2(N3)2], 2, and catena-poly[[{2-methoxy-6-[8-(pyridin-2-yl)-3,6-dioxa-2,7-diazaocta-1,7-dien-1-yl]phenolato}nickel(II)]-μ-dicyanamidato], [Ni(L)(dca)]
n
, 3 {dca is dicyanamide, C2N3, and HL is 2-methoxy-6-[8-(pyridin-2-yl)-3,6-dioxa-2,7-diazaocta-1,7-dien-1-yl]phenol, C16H17N3O4}, with a half-salamo-based pyridine-containing HL ligand have been synthesized and characterized by FT–IR, UV–Vis absorption spectroscopy, X-ray crystallography, Hirshfeld surface analysis and density functional theory (DFT) calculations. The central NiII ions in complexes 1–3 are hosted in the half-salamo-based N3O-donor cavity of the organic ligand. Complex 1 is a centrosymmetric dimer and two [Ni(L)(NCS)] units form a centrosymmetric dimeric structure, which is bridged by two phenolate O atoms. The two N atoms at the axial ends are provided by two NCS− ligands. In complex 1, each NiII ion has a six-coordinated octahedral geometry. Complex 2 is similar to 1, but they differ in that the auxiliary NCS− ligand is replaced by N3
−. However, complex 3 is a one-dimensional coordination polymer constructed from [Ni(L)(dca)] units, which are connected by the auxiliary bidentate dca ligand via
N-donor atoms. As with complexes 1 and 2, the NiII ion in 3 has a six-coordinated octahedral geometry.
The crystal structure of Cu2GeSe3 and the structure-types of the I2-IV-VI3 family of semiconducting compounds
Authors: Dugarte-Dugarte Analio , Ramírez Pineda Nahum , Nieves Luis , Henao José Antonio , Díaz de Delgado Graciela , Delgado José Miguel
Published: January 2021

Almost 50 years after the initial report, the crystal structure of Cu2GeSe3, a I2-IV-VI3 semiconductor, has been revised using modern single-crystal X-ray diffraction data. The structure of this material can be properly described in the monoclinic space group Cc (No. 9) with unit-cell parameters a = 6.7703 (4) Å, b = 11.8624 (5) Å, c = 6.7705 (4) Å, β = 108.512 (6)°, V = 515.62 (5) Å3, Z = 4, rather than in the orthorhombic space group Imm2 (No. 44) with unit-cell parameters a = 11.860 (3), b = 3.960 (1), c = 5.485 (2) Å, V = 257.61 Å3, Z = 2, as originally proposed [Parthé & Garín (1971). Monatsh. Chem.
102, 1197–1208]. Contrary to what was observed in the orthorhombic structure, the distortions of the tetrahedra in the monoclinic structure are consistent with the distortions expected from considerations derived from the bond valence model. A brief revision of the structures reported for the I2-IV-VI3 family of semiconducting compounds (I: Cu, Ag; IV: Si, Ge, Sn; and VI: S, Se, Te) is also presented.
The income elasticity of import demand: A meta‐survey
Authors: El‐Shagi Makram , Sawyer William C. , Tochkov Kiril
Published: January 2021

Import demand has been a major research topic in international economics for the past 80 years because of its importance for analyzing trade and evaluating trade policies. The goal of this paper is to survey the literature and conduct a meta‐analysis of empirical studies on import demand with the intention of clarifying the effect of economic development on income elasticity. In particular, we test the hypothesis that higher income levels are associated with a more elastic import demand. We apply a combination of parametric and non‐parametric methods on estimates from a sample of 152 papers published over the period 1975–2014 and find that this relationship is significant and robust. Specifically, kernel densities of income elasticity estimates for high‐income countries in North America and Europe are shown to exceed those for poorer parts of the world. The results from quantile regressions confirm this pattern and establish its robustness when controlling for the effect of model specifications.
Midterm results of salvage surgery for autogenous dialysis access in aneurysmal arteriovenous fistulas
Authors: Ecevit Ata Niyazi , Karaca Okay Güven , Kalender Mehmet , Darçın Osman Tansel
Published: January 2021

Autologous arteriovenous fistulas are commonly constructed in patients undergoing hemodialysis for end‐stage renal disease. However, they are associated with a high rate of aneurysm formation, and aneurysmal arteriovenous fistulas that have become symptomatic require surgical intervention. This study was performed to evaluate the midterm results of salvage surgery for autogenous dialysis access in patients with aneurysmal arteriovenous fistulas. Of 1326 arteriovenous fistula operations, 81 involving surgery for aneurysmal arteriovenous fistulas between January 2008 and January 2012 were included in this study. The database was searched to identify all complicated arteriovenous fistula patients undergoing surgery for vascular access. The number of complicated arteriovenous fistula surgeries, for example for aneurysms, was greater than the number of patients undergoing surgery to create a new arteriovenous fistula. We performed three different surgical procedures to treat arteriovenous‐related aneurysms in our clinic: primary repair, resection and saphenous vein interposition, and resection and polytetrafluoroethylene (PTFE) interposition. We compared the patency rates at the 12‐ and 24‐month follow‐ups among these three techniques. The study population consisted of 24 cases of primary repair, 29 cases of resection and saphenous vein interposition, and 30 cases of resection and PTFE graft interposition. True aneurysms occurring in patients undergoing hemodialysis did not require treatment unless they were symptomatic. Arteriovenous access salvage therapy is recommended after the aneurysm has become symptomatic. Symptomatic arteriovenous fistula aneurysms can be treated by maintaining arteriovenous fistula continuity. Moreover, patient safety is ensured by long‐term patency.
Infrapatellar branch of the saphenous nerve: A review
Authors: Boyle Jerome , Eason Alastair , Hartnett Nigel , Marks Paul
Published: January 2021

Iatrogenic injury to the infrapatellar branch of the saphenous nerve (IPBSN) is an uncommon but important complication of both open and arthroscopic procedures causing neuropathic pain symptoms in the anteromedial aspect of the knee. Whilst the use of ultrasound in the assessment of peripheral neuropathies is well‐established, sonographic knowledge in the routine assessment of the IPBSN remains poor. We describe the sonographic assessment of the IPBSN by means of a review article, promulgating radiology’s role in providing anatomical information pertaining to the IPBSN and its relationship to adjacent anatomical structures, surgical fixations or fibrous scar tissue.
A combination of infraclavicular and suprascapular nerve blocks for total shoulder arthroplasty: A case series
Authors: Musso Dario , Klaastad Øivind , Ytrebø Lars M.
Published: January 2021

Background

Shoulder arthroplasty is associated with significant post‐operative pain. Interscalene plexus block is the gold standard for pain management in patients undergoing this surgery, however, alternatives are currently being developed. We hypothesized that a combination of anterior suprascapular nerve block and lateral sagittal infraclavicular block would provide effective post‐operative analgesia. Primary aims for this study were to document numeric rating scale (NRS) pain score and use of oral morphine equivalents (OMEq) during the first 24 hours after surgery. Secondary aim was to determine the incidence of hemidiaphragmatic paralysis.

Methods

Twenty patients (ASA physical status I‐III) scheduled for shoulder arthroplasty were studied. Four mL ropivacaine 0.5% was administered for the suprascapular nerve block and 15 mL ropivacaine 0.75% for the infraclavicular block. Surgery was performed under general anaesthesia. Paracetamol and prolonged‐release oxycodone were prescribed as post‐operative analgesics. Morphine and oxycodone were prescribed as rescue pain medication. Diaphragm status was assessed by ultrasound.

Results

Median NRS (0‐10) at 1, 3, 6, 8 and 24 hours post‐operatively were 1, 0, 0, 0 and 3, respectively. NRS at rest during the first 24 post‐operative hours was 4 (2.5‐4.5 [0‐5]), median (IQR [range]). Maximum NRS was 6.5 (5‐8 [0‐10]) median (IQR [range]). Total OMEq during the first 24 post‐operative hours was 52.5 mg (30‐60 [26.4‐121.5]) median (IQR [range]). Hemidiaphragmatic paralysis was diagnosed in one patient (5%).

Conclusions

The combination of suprascapular and infraclavicular nerve block shows an encouraging post‐operative analgesic profile and a low risk for hemidiaphragmatic paralysis after total shoulder arthroplasty.
Blunt thoracic aorta injuries, an Australian single centre's perspective
Authors: Dinh Krystal , Limmer Alexandra , Ngai Carlin , Cho Tae , Young Noel , Hsu Jeremy
Published: January 2021

Background

Blunt thoracic aortic injuries (BTAI) are potentially life‐threatening emergencies. The management paradigm has shifted from open repair to a predominantly endovascular approach. We evaluated the trends in managing BTAI at our centre over the last decade and compared them to current international guidelines.

Methods

We retrospectively reviewed all patients who presented with BTAI to our level one trauma centre, Westmead Hospital, New South Wales, Australia between 1 January 2010 and 31 December 2019. Patient demographics, injury grade and location, imaging features, management details and outcomes were analysed.

Results

BTAI is rare, with 39 patients identified at our institute over the last 10 years. Of these, seven died in the emergency department from their associated injuries (17.9%). Of the 32 survivors, 27 underwent surgical management with an endovascular stent‐graft placement, and the remaining five patients were treated non‐operatively. No patients were treated via an open surgical approach. All patients were diagnosed via computed tomography angiography. There were one death and two endoleaks amongst patients who underwent Thoracic endovascular aortic repair (TEVAR). The death occurred secondary to severe traumatic brain injury. Two patients illustrated neurological changes however these were associated with the original injury. No patients failed non‐operative management.

Conclusion

This study demonstrates that at our level one trauma centre, patients with BTAI are managed in accordance with international guidelines. All patients underwent computed tomography angiography for diagnosis and grading of injury. All patients requiring surgical management underwent TEVAR. Furthermore, our data support that select patients with grade I injuries can safely be managed non‐operatively.
Beta‐blocker‐associated hypoglycaemia: New insights from a real‐world pharmacovigilance study
Authors: Carnovale Carla , Gringeri Michele , Battini Vera , Mosini Giulia , Invernizzi Elena , Mazhar Faizan , Bergamaschi Francesco , Fumagalli Mara , Zuccotti Gianvincenzo , Clementi Emilio , Radice Sonia , Fabiano Valentina
Published: January 2021

Aims

To investigate the statistical association between hypoglycaemia and β‐blocker use and to define what patient and drug characteristics could potentially increase the risk for its occurrence.

Methods

We investigated the relationship between pharmacological parameters of β‐blockers and the occurrence of hypoglycaemia by conducting a case/non case analysis using the Food and Drug Administration Adverse Event Reporting System database. Pharmacological properties that could represent a predictive factor for hypoglycaemia were analysed through a multilinear binary logistic regression (null hypothesis rejected for values ofP< .05). We also performed a systematic review of clinical studies on this association.

Results

Of 83 954 selected reports, 1465 cases (1.75%) of hypoglycaemia were identified. The association was found statistically significant for nadolol (reporting odds ratio [95% confidence interval]: 6.98 [5.40–9.03]), celiprolol (2.35 [1.35–4.10]), propranolol (2.14 [1.87–2.46]) and bisoprolol (1.42 [1.25–1.61]). Paediatric cases (n =310) showed a positive association with hypoglycaemia for long half‐life drugs (odds ratio [95% confidence interval]: 2.232 [1.398–3.563]) and a negative association for β1‐selectivity (0.644 [0.414–0.999]). Seven papers were included in the systematic review. Because of great heterogeneity in study design and demographics, hypoglycaemia incidence rates varied greatly among studies, occurring in 1.73% of the cases for propranolol treatment (ntotal participants = 575), 6.6% for atenolol (n =30) and 10% for carvedilol (n =20).

Conclusion

Nadolol appears to be the β‐blocker significantly most associated with hypoglycaemia and children represent the most susceptible sample. Furthermore, long half‐life and nonselective β‐blockers seem to increase the risk for its occurrence.
A phenotypic risk score for predicting mortality in sickle cell disease
Authors: Sachdev Vandana , Tian Xin , Gu Yuan , Nichols James , Sidenko Stanislav , Li Wen , Beri Andrea , Layne W. Austin , Allen Darlene , Wu Colin O. , Thein Swee Lay
Published: January 2021

Risk assessment for patients with sickle cell disease (SCD) remains challenging as it depends on an individual physician’s experience and ability to integrate a variety of test results. We aimed to provide a new risk score that combines clinical, laboratory, and imaging data. In a prospective cohort of 600 adult patients with SCD, we assessed the relationship of 70 baseline covariates to all‐cause mortality. Random survival forest and regularised Cox regression machine learning (ML) methods were used to select top predictors. Multivariable models and a risk score were developed and internally validated. Over a median follow‐up of 4·3 years, 131 deaths were recorded. Multivariable models were developed using nine independent predictors of mortality: tricuspid regurgitant velocity, estimated right atrial pressure, mitral E velocity, left ventricular septal thickness, body mass index, blood urea nitrogen, alkaline phosphatase, heart rate and age. Our prognostic risk score had superior performance with a bias‐corrected C‐statistic of 0·763. Our model stratified patients into four groups with significantly different 4‐year mortality rates (3%, 11%, 35% and 75% respectively). Using readily available variables from patients with SCD, we applied ML techniques to develop and validate a mortality risk scoring method that reflects the summation of cardiopulmonary, renal and liver end‐organ damage.

Trial Registration: ClinicalTrials.gov Identifier: NCT#00011648.
Parental Job Loss and Early Child Development in the Great Recession
Authors: Mari Gabriele , Keizer Renske
Published: January 2021

The study examines whether and why parental job loss may stifle early child development, relying on cohort data from the population of children born in Ireland in 2007–2008 (N = 6,303) and followed around the time of the Great Recession (2008–2013). A novel approach to mediation analysis is deployed, testing expectations from models of family investment and family stress.

Parental job loss exacerbates problem behavior at ages 3 and 5 (.05–.08 SDs), via the channels of parental income and maternal negative parenting. By depressing parental income, job loss also hampers children’s verbal ability at age 3 (.03 SDs). This is tied to reduced affordability of formal childcare, highlighting a policy lever that might tame the intergenerational toll of job loss.
Spatial Ability and Theory of Mind: A Mediating Role of Visual Perspective Taking
Authors: Tian Mi , Luo Tianrui , Ding Jinxia , Wang Xin , Cheung Him
Published: January 2021

This research tests the role of visual perspective taking (VPT) in mediating the relation between spatial ability and theory of mind (ToM). Study 1 demonstrated such mediation correlationally in seventy 3.5‐ to 4‐year olds. In Study 2, twenty‐three 3.5‐ to 4‐year‐olds were trained on using play blocks to copy preassembled models as a way to promote spatial ability. Resultant increases in VPT and ToM were compared to those from a control group learning to draw instead (n = 23). Both studies showed that the effect of spatial ability on ToM depended on VPT, suggesting a role of embodiment in ToM development in early childhood. These findings provide an alternative way to think about ToM development and the psychological mechanism that may be involved.
tsRNAs: Novel small molecules from cell function and regulatory mechanism to therapeutic targets
Authors: Zong Tingyu , Yang Yanyan , Zhao Hui , Li Lin , Liu Meixin , Fu Xiuxiu , Tang Guozhang , Zhou Hong , Aung Lynn Htet Htet , Li Peifeng , Wang Jianxun , Wang Zhibin , Yu Tao
Published: January 2021

tsRNAs are small fragments of RNAs with specific lengths that are generated by particular ribonucleases, such as dicer and angiogenin (ANG), clipping on the rings of transfer RNAs (tRNAs) in specific cells and tissues under specific conditions. Depending on where the splicing site is, tsRNAs can be segmented into two main types, tRNA‐derived stress‐induced RNAs (tiRNAs) and tRNA‐derived fragments (tRFs). Many studies have shown that tsRNAs are functional molecules, not the random degradative products of tRNAs. Notably, due to their regulatory mechanism in regulating mRNA stability, transcription, ribosomal RNA (rRNA) synthesis and RNA reverse transcription, tsRNAs are significantly involved in the cell function, such as cell proliferation, migration, cycle and apoptosis, as well as the occurrence and development of a variety of diseases. In addition, tsRNAs may represent a new generation of clinical biomarkers or therapeutic targets because of their stable structures, high conservation and widely distribution, particularly in the peripheral tissues, bodily fluids and exosomes. In this review, we describe the generation, function and mechanism of tsRNAs and illustrate the current research progress of tsRNAs in various diseases, highlight their potentials as biomarkers and therapeutic targets in clinical application. Although our understanding of tsRNAs is still in infancy, the application prospects shown in this field deserve further exploration.
Mitigating poverty through solar panels adoption in developing economies
Authors: Feng Zhuo , He Qiao‐Chu , Ma Guangrui
Published: January 2021

Motivated by a widely practiced strategy to combine the growth of the solar energy sector with poverty mitigation, we propose stylized models of households selling extra solar energy back to the grid, which generates a steady stream of income to overcome adoption barriers for solar panels, that is, high adoption cost and generation variability. By considering households' strategic consumption shifting behavior in response to varying intertemporal market electricity prices, we have presented the equilibrium adoption number and households' equilibrium profit. We have also demonstrated the government's optimal subsidy to reach a socially optimal adoption level. Furthermore, we investigate the popular Public Private Partnership (PPP) model in developing countries to promote the investment of solar panels. Under the PPP program, the private firms share both upfront cost and electricity revenue with households, while the government may provide subsidy to further encourage adoption. Despite the popularity of the PPP scheme, our model documents an unexpected negative implication by inducing a lower overall adoption level than the traditional scheme: As the PPP scheme relieves budgetary burden of households in adopting solar panels (infrastructure cost), anticipating the long‐term revenue loss, they are less likely to participate in the first place. However, combined with the government intervention via adoption subsidy, the PPP scheme can lead to a win‐win solution for all.
Urgent endoscopic ultrasound‐guided choledochoduodenostomy for adenocarcinoma of the ampulla of Vater with scirrhous invasion
Authors: Tanaka Takamitsu , Omoto Shunsuke , Takenaka Mamoru
Published: January 2021

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Retroflexion technique in the descending part of the duodenum for endoscopic mucosal resection
Authors: Masunaga Teppei , Kato Motohiko
Published: January 2021

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New method of esophageal endoscopic ultrasonography with injected gel: Endoscopic ultrasonography‐gel filling method
Authors: Miyamoto Shuichi , Takahashi Kazuhiro , Ohya Tomohiko R.
Published: January 2021

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Protein cysteine palmitoylation in immunity and inflammation
Authors: Lin Hening
Published: January 2021

Protein cysteine palmitoylation, or S‐palmitoylation, has been known for about 40 years, and thousands of proteins in humans are known to be modified. Because of the large number of proteins modified, the importance and physiological functions of S‐palmitoylation are enormous. However, most of the known physiological functions of S‐palmitoylation can be broadly classified into two categories, neurological or immunological. This review provides a summary on the function of S‐palmitoylation from the immunological perspective. Several important immune signaling pathways are discussed, including STING, NOD1/2, JAK‐STAT in cytokine signaling, T‐cell receptor signaling, chemotactic GPCR signaling, apoptosis, phagocytosis, and endothelial and epithelial integrity. This review is not meant to be comprehensive, but rather focuses on specific examples to highlight the versatility of palmitoylation in regulating immune signaling, as well as the potential and challenges of targeting palmitoylation to treat immune diseases.
Detection of genome‐edited and endogenously expressed G protein‐coupled receptors
Authors: Soave Mark , Stoddart Leigh A. , White Carl W. , Kilpatrick Laura E. , Goulding Joëlle , Briddon Stephen J. , Hill Stephen J.
Published: January 2021

G protein‐coupled receptors (GPCRs) are the largest family of membrane receptors and major targets for FDA‐approved drugs. The ability to quantify GPCR expression and ligand binding characteristics in different cell types and tissues is therefore important for drug discovery. The advent of genome editing along with developments in fluorescent ligand design offers exciting new possibilities to probe GPCRs in their native environment. This review provides an overview of the recent technical advances employed to study the localisation and ligand binding characteristics of genome‐edited and endogenously expressed GPCRs.