bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Critical Review of Zebrafish Neurological Disease Models−1. The Premise: Neuroanatomical, Cellular and Genetic Homology and Experimental Tractability
Authors: Burgess Harold A , Burton Edward A 
Published: January 2023

AbstractThe last decade has seen a dramatic rise in the number of genes linked to neurological disorders, necessitating new models to explore underlying mechanisms and to test potential therapies. Over a similar period, many laboratories adopted zebrafish as a tractable model for studying brain development, defining neural circuits and performing chemical screens. Here we discuss strengths and limitations of using the zebrafish system to model neurological disorders. The underlying premise for many disease models is the high degree of homology between human and zebrafish genes, coupled with the conserved vertebrate Bauplan and repertoire of neurochemical signaling molecules. Yet, we caution that important evolutionary divergences often limit the extent to which human symptoms can be modeled meaningfully in zebrafish. We outline advances in genetic technologies that allow human mutations to be reproduced faithfully in zebrafish. Together with methods that visualize the development and function of neuronal pathways at the single cell level, there is now an unprecedented opportunity to understand how disease-associated genetic changes disrupt neural circuits, a level of analysis that is ideally suited to uncovering pathogenic changes in human brain disorders.
Endogenous antibody responses in REGN-COV2-treated SARS-CoV-2-infected individuals
Authors: Kurshan Ashwini , Snell Luke B , Prior Lucie , Tam Jerry C H , Graham Carl , Thangarajah Rajeni , Edgeworth Jonathan D , Nebbia Gaia , Doores Katie J 
Published: January 2023

Abstract
Neutralizing monoclonal antibodies (mAbs) targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein have been developed for the treatment of COVID-19. Whilst antibody therapy has been shown to reduce the risk of COVID-19-associated hospitalization and death, there is limited understanding of the endogenous immunity to SARS-CoV-2 generated in mAb-treated patients and therefore ongoing susceptibility to future infections. Here we measure the endogenous antibody response in SARS-CoV-2-infected individuals treated with REGN-COV2 (Ronapreve). We show that in the majority of unvaccinated, delta-infected REGN-COV2-treated individuals, an endogenous antibody response is generated, but, like untreated, delta-infected individuals, there was a limited neutralization breadth. However, some vaccinated individuals who were seronegative at SARS-CoV-2 infection baseline and some unvaccinated individuals failed to produce an endogenous immune response following infection and REGN-COV2 treatment demonstrating the importance of mAb therapy in some patient populations.
Priority topics for child and family health research in community-based paediatric health care according to caregivers and health care professionals
Authors: Eaton Andrea , Dyson Michele P , Gokiert Rebecca , Rajani Hasu , O’Neill Marcus , Ladha Tehseen , Zhang Mona , Birken Catherine S , Maguire Jonathon L , Ball Geoff D C 
Published: January 2023

Abstract

Background
Patient-oriented research (POR) aligns research with stakeholders’ priorities to improve health services and outcomes. Community-based health care settings offer an opportunity to engage stakeholders to determine the most important research topics to them. Our objectives were to identify unanswered questions that stakeholders had regarding any aspect of child and family health and prioritize their ‘top 10’ questions.

Methods
We followed the James Lind Alliance (JLA) priority setting methodology in partnership with stakeholders from the Northeast Community Health Centre (NECHC; Edmonton, Canada). We partnered with stakeholders (five caregivers, five health care professionals [HCPs]) to create a steering committee. Stakeholders were surveyed in two rounds (n = 125 per survey) to gather and rank-order unanswered questions regarding child and family health. A final priority setting workshop was held to finalize the ‘top 10’ list.

Results
Our initial survey generated 1,265 submissions from 100 caregivers and 25 HCPs. Out of scope submissions were removed and similar questions were combined to create a master list of questions (n = 389). Only unanswered questions advanced (n = 108) and were rank-ordered through a second survey by 100 caregivers and 25 HCPs. Stakeholders (n = 12) gathered for the final workshop to discuss and finalize the ‘top 10’ list. Priority questions included a range of topics, including mental health, screen time, COVID-19, and behaviour.

Conclusion
Our stakeholders prioritized diverse questions within our ‘top 10’ list; questions regarding mental health were the most common. Future patient-oriented research at this site will be guided by priorities that were most important to caregivers and HCPs.
The Mutual Inhibition between PLETHORAs and ARABIDOPSIS RESPONSE REGULATORs Controls Root Zonation
Authors: Shtin Margaryta , Polverari Laura , Svolacchia Noemi , Bertolotti Gaia , Unterholzner Simon J , Di Mambro Riccardo , Costantino Paolo , Dello Ioio Raffaele , Sabatini Sabrina 
Published: January 2023

AbstractDuring organogenesis, a key step toward the development of a functional organ is the separation of cells into specific domains with different activities. Mutual inhibition of gene expression has been shown to be sufficient to establish and maintain these domains during organogenesis in several multicellular organisms. Here, we show that the mutual inhibition between the PLETHORA transcription factors (PLTs) and the ARABIDOPSIS RESPONSE REGULATORs (ARRs) transcription factors is sufficient to separate cell division and cell differentiation during root organogenesis. In particular, we show that ARR1 suppresses PLT activities and that PLTs suppress ARR1 and ARR12 by targeting their proteins for degradation via the KISS ME DEADLY 2 F-box protein. These findings reveal new important aspects of the complex process of root zonation and development.
Microstructure and Texture of a Spinel Corona Around a Basalt Hosted Corundum Xenocrystal
Authors: Schuster Roman , Tiede Lisa , Ageeva Olga , Griffiths Thomas A , Abart Rainer , Habler Gerlinde 
Published: January 2023

AbstractThe microstructural and textural characteristics of a spinel corona that formed around a faceted corundum xenocrystal by reaction with the hosting basaltic melt in the Siebengebirge volcanic field demonstrate that the crystallographic and shape preferred orientation of spinel is influenced by the orientation of the reaction interface with respect to the corundum crystal lattice. The spinel roughly shows the common topotactic orientation relationships with corundum, where one of the $\{111\}_{Spl}$ planes is parallel to the (0001)$_{Crn}$ plane, and three of the $\{110\}_{Spl}$ planes are parallel to the $\{10\overline {1}0\}_{Crn}$ planes. In detail, there are subtle but systematic deviations from this topotactic relationship due to small rotations about the c-axis and/or an a-axis of corundum. The former is observed when the corundum c-axis is closely parallel to the interface plane, while the latter require a corundum a-axis orientation perpendicular to the interface. In this case, the preferred sense of rotation depends on the sign of the a-axis direction, irrespective of the spinel growth direction being parallel or antiparallel to this axis. Additionally, the selection of either one or both of two spinel twin variants that equally fulfill the topotactic orientation relationship depends on the orientation of the corundum-spinel interface with respect to the lattices of both the corundum and the spinel. Finally, also the grain boundary character is controlled by the interface orientation and the corundum lattice. Despite the differences between corona segments, the nature of these textures are persistent along and across each segment. We emphasize that all these microstructural and textural features are ascribed to the period of spinel growth in magmatic environment. The extent to which prominent slip planes in spinel are aligned parallel with the corundum-spinel interface seems to be of crucial importance for the nature of the spinel texture and microstructure, indicating that the activity of dislocations pertaining to these slip systems ease the accommodation of lattice misfit across the corundum-spinel interface. By comparison with experimentally grown spinel layers, we infer predominantly interface reaction controlled growth of the studied spinel corona.
Zeaxanthin is required for eyespot formation and phototaxis inEuglena gracilis
Authors: Tamaki Shun , Ozasa Kazunari , Nomura Toshihisa , Ishikawa Marumi , Yamada Koji , Suzuki Kengo , Mochida Keiichi 
Published: January 2023

AbstractThe eyespot apparatus is an organelle that forms carotenoid-rich globules in diverse flagellated microalgae and functions in phototaxis. The euglenophytes have structurally and functionally distinct eyespot apparatuses from chlorophytes. β-Carotene is the most abundant pigment detected in chlorophytes’ eyespots, while xanthophylls such as zeaxanthin and diadinoxanthin have been suggested to function in euglenophytes’ eyespots. Here, we investigated the association between carotenoid composition and eyespot formation via pathway-scale mutagenesis using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated genome editing in the euglenophyte Euglena gracilis. Lycopene cyclase (lcy) mutants exhibited sole lycopene accumulation, defective red eyespots, and phototactic insensitivity. Conversely, β-carotene hydroxylase (cytochrome P450 97h1, cyp97h1) mutants accumulated β-carotene and its hydroxylated products β-cryptoxanthin and zeaxanthin and formed phototactic eyespot apparatuses, while cyp97h1 cyp97f2 double mutants were deficient in β-carotene hydroxylation and mostly lacked functional eyespots. Thus, zeaxanthin is required for the stable formation of functional eyespots in E. gracilis, highlighting evolutionary differences between euglenophytes and chlorophytes in the metabolic regulation of photoreactive organelle formation.
Apple SUMO E3 ligase MdSIZ1 regulates cuticular wax biosynthesis by SUMOylating transcription factor MdMYB30
Authors: Zhang Ya-Li , Tian Yi , Man Yao-Yang , Zhang Chun-Ling , Wang Yi , You Chun-Xiang , Li Yuan-Yuan 
Published: January 2023

AbstractA key function of SUMOylation is the coordinated modification of numerous proteins to optimize plant growth and resistance to environmental stress. Plant cuticular wax is deposited on the surface of primary plant organs to form a barrier that provides protection against changes in terrestrial environments. Many recent studies have examined cuticular wax biosynthetic pathways and regulation. However, whether SUMOylation is involved in the regulation of cuticle wax deposition at the posttranslational level remains unclear. Here, we demonstrate that a small ubiquitin-like modifier (SUMO) E3 ligase, SAP AND MIZ1 DOMAIN CONTAINING LIGASE1 (MdSIZ1), regulates wax accumulation and cuticle permeability in apple (Malus domestica Borkh), SUMO E2 CONJUGATING ENZYME 1(MdSCE1) physically interacts with MdMYB30, a transcription factor involved in the regulation of cuticle wax accumulation. MdSIZ1 mediates the SUMOylation and accumulation of MdMYB30 by inhibiting its degradation through the 26S proteasome pathway. Furthermore, MdMYB30 directly binds to the β-KETOACYL-COA SYNTHASE 1 (MdKCS1) promoter to activate its expression and promote wax biosynthesis. These findings indicate that the MdSIZ1–MdMYB30–MdKCS1 module positively regulates cuticular wax biosynthesis in apples. Overall, the findings of our study provide insights into the regulation pathways involved in cuticular wax biosynthesis.
Effective cell membrane tension is independent of polyacrylamide substrate stiffness
Authors: Kreysing Eva , Hugh Jeffrey Mc , Foster Sarah K , Andresen Kurt , Greenhalgh Ryan D , Pillai Eva K , Dimitracopoulos Andrea , Keyser Ulrich F , Franze Kristian 
Published: January 2023

Abstract
Most animal cells are surrounded by a cell membrane and an underlying actomyosin cortex. Both structures are linked, and they are under tension. In-plane membrane tension and cortical tension both influence many cellular processes, including cell migration, division, and endocytosis. However, while actomyosin tension is regulated by substrate stiffness, how membrane tension responds to mechanical substrate properties is currently poorly understood. Here, we probed the effective membrane tension of neurons and fibroblasts cultured on glass and polyacrylamide substrates of varying stiffness using optical tweezers. In contrast to actomyosin-based traction forces, both peak forces and steady-state tether forces of cells cultured on hydrogels were independent of substrate stiffness and did not change after blocking myosin II activity using blebbistatin, indicating that tether and traction forces are not directly linked. Peak forces in fibroblasts on hydrogels were about twice as high as those in neurons, indicating stronger membrane–cortex adhesion in fibroblasts. Steady-state tether forces were generally higher in cells cultured on hydrogels than on glass, which we explain by a mechanical model. Our results provide new insights into the complex regulation of effective membrane tension and pave the way for a deeper understanding of the biological processes it instructs.
A “grappling hook” interaction connects self-assembly and chaperone activity of Nucleophosmin 1
Authors: Saluri Mihkel , Leppert Axel , Gese Genis Valentin , Sahin Cagla , Lama Dilraj , Kaldmäe Margit , Chen Gefei , Elofsson Arne , Allison Timothy M , Arsenian-Henriksson Marie , Johansson Jan , Lane David P , Hällberg B Martin , Landreh Michael 
Published: January 2023

Abstract
How the self-assembly of partially disordered proteins generates functional compartments in the cytoplasm and particularly in the nucleus is poorly understood. Nucleophosmin 1 (NPM1) is an abundant nucleolar protein that forms large oligomers and undergoes liquid–liquid phase separation by binding RNA or ribosomal proteins. It provides the scaffold for ribosome assembly but also prevents protein aggregation as part of the cellular stress response. Here, we use aggregation assays and native mass spectrometry (MS) to examine the relationship between the self-assembly and chaperone activity of NPM1. We find that oligomerization of full-length NPM1 modulates its ability to retard amyloid formation in vitro. Machine learning-based structure prediction and cryo-electron microscopy reveal fuzzy interactions between the acidic disordered region and the C-terminal nucleotide-binding domain, which cross-link NPM1 pentamers into partially disordered oligomers. The addition of basic peptides results in a tighter association within the oligomers, reducing their capacity to prevent amyloid formation. Together, our findings show that NPM1 uses a “grappling hook” mechanism to form a network-like structure that traps aggregation-prone proteins. Nucleolar proteins and RNAs simultaneously modulate the association strength and chaperone activity, suggesting a mechanism by which nucleolar composition regulates the chaperone activity of NPM1.
Histone deacetylation regulates de novo shoot regeneration
Authors: Temman Haruka , Sakamoto Takuya , Ueda Minoru , Sugimoto Kaoru , Migihashi Masako , Yamamoto Kazunari , Tsujimoto-Inui Yayoi , Sato Hikaru , Shibuta Mio K , Nishino Norikazu , Nakamura Tomoe , Shimada Hiroaki , Taniguchi Yukimi Y , Takeda Seiji , Aida Mitsuhiro , Suzuki Takamasa , Seki Motoaki , Matsunaga Sachihiro 
Published: January 2023

AbstractDuring de novo plant organ regeneration, auxin induction mediates the formation of a pluripotent cell mass called callus, which regenerates shoots upon cytokinin induction. However, molecular mechanisms underlying transdifferentiation remain unknown. Here, we showed that the loss of HDA19, a histone deacetylase (HDAC) family gene, suppresses shoot regeneration. Treatment with an HDAC inhibitor revealed that the activity of this gene is essential for shoot regeneration. Further, we identified target genes whose expression was regulated through HDA19-mediated histone deacetylation during shoot induction and found that ENHANCER OF SHOOT REGENERATION 1 and CUP-SHAPED COTYLEDON 2 play important roles in shoot apical meristem formation. Histones at the loci of these genes were hyperacetylated and markedly upregulated in hda19. Transient ESR1 or CUC2 overexpression impaired shoot regeneration, as observed in hda19. Therefore, HDA19 mediates direct histone deacetylation of CUC2 and ESR1 loci to prevent their overexpression at the early stages of shoot regeneration.
Effect of alanine versus serine at position 88 of human transthyretin mutants on the protein stability
Authors: Lee Kyung-Hoon , Kuczera Krzysztof 
Published: January 2023

Abstract
Human transthyretin (TTR) is a homo-tetrameric plasma protein associated with a high percentage of β-sheet forming amyloid fibrils. It accumulates in tissues or extracellular matrices to cause amyloid diseases. Free energy simulations with thermodynamic integration based on all-atom molecular dynamics simulations have been carried out to analyze the effects of the His88 → Ala and Ser mutations on the stability of human TTR. The calculated free energy change differences (ΔΔG) caused by the His88 → Ala and His88 → Ser mutations are −1.84 ± 0.86 and 7.56 ± 0.55 kcal/mol, respectively, which are in excellent agreement with prior reported experimental values. The simulation results show that the H88A mutant is more stable than the wild type, whereas the H88S mutant is less stable than the wild type. The free energy component analysis shows that the contribution to the free energy change difference (ΔΔG) for the His88 → Ala and His88 → Ser mutations mainly arise from electrostatic and van der Waals interactions, respectively. The electrostatic term stabilizes the H88A mutant more than the wild type, but the van der Waals interaction destabilizes the H88S mutant relative to the wild type. Individual residue contributions to the free energy change show neighboring residues exert stabilizing and destabilizing influence on the mutants. The implications of the simulation results for understanding the stabilizing and destabilizing effect and its contribution to protein stability are discussed.
Effect of Variation in Early Rehabilitation on Hospital Readmission After Hip Fracture
Authors: Kumar Amit , Roy Indrakshi , Falvey Jason , Rudolph James L , Rivera-Hernandez Maricruz , Shaibi Stefany , Sood Pallavi , Childers Christine , Karmarkar Amol 
Published: January 2023

Abstract

Objective
Provision of early rehabilitation services during acute hospitalization after a hip fracture is vital for improving patient outcomes. The purpose of this study was to examine the association between the amount of rehabilitation services received during the acute care stay and hospital readmission in older patients after a hip fracture.

Methods
Medicare claims data (2016–2017) for older adults admitted to acute hospitals for a hip fracture (n = 131,127) were used. Hospital-based rehabilitation (physical therapy, occupational therapy, or both) was categorized into tertiles by minutes per day as low (median = 17.5), middle (median = 30.0), and high (median = 48.8). The study outcome was risk-adjusted 7-day and 30-day all-cause hospital readmission.

Results
The median hospital stay was 5 days (interquartile range [IQR] = 4–6 days). The median rehabilitation minutes per day was 30 (IQR = 21–42.5 minutes), with 17 (IQR = 12.6–20.6 minutes) in the low tertile, 30 (IQR = 12.6–20.6 minutes) in the middle tertile, and 48.8 (IQR = 42.8–60.0 minutes) in the high tertile. Compared with high therapy minutes groups, those in the low and middle tertiles had higher odds of a 30-day readmission (low tertile: odds ratio [OR] = 1.11, 95% CI = 1.06–1.17; middle tertile: OR = 1.07, 95% CI = 1.02–1.12). In addition, patients who received low rehabilitation volume had higher odds of a 7-day readmission (OR = 1.20; 95% CI = 1.10–1.30) compared with high volume.

Conclusion
Elderly patients with hip fractures who received less rehabilitation were at higher risk of readmission within 7 and 30 days.

Impact
These findings confirm the need to update clinical guidelines in the provision of early rehabilitation services to improve patient outcomes during acute hospital stays for individuals with hip fracture.

Lay summary
There is significant individual- and hospital-level variation in the amount of hospital-based rehabilitation delivered to older adults during hip fracture hospitalization. Higher intensity of hospital-based rehabilitation care was associated with a lower risk of hospital readmission within 7 and 30 days.
On why the COVID-19 pandemic has not changed the world
Authors: Maboloc Christopher Ryan 
Published: January 2023

Abstract
This paper reacts to the proposal of Virgilio Rivas with respect to the role of art as a response to the threat of meaning that was brought forth by the COVID-19 pandemic. It will be argued that the purported new normal in which changes in the ways of life of people had been expected never actually occurred post-pandemic as power and economic interests still dominate the global order. The pandemic, in this regard, was simply a short pause from the hegemonic relationship among nations in the global order. The paper maintains that, in the end, people must continue to pursue human decency.
Digital exclusion as a potential cause of inequalities in access to care: a survey in people with inflammatory rheumatic diseases
Authors: Hider Samantha , Muller Sara , Gray Lauren , Manning Fay , Brooks Mike , Heining Dominic , Menon Ajit , Packham Jonathan , Raghuvanshi Subhra , Roddy Edward , Ryan Sarah , Scott Ian , Paskins Zoe 
Published: January 2023

Abstract

Objectives
COVID-19 led to rapid uptake of digital health care. We sought to examine digital access, health and digital literacy, and impact on confidence and satisfaction with remote consultations in people with inflammatory rheumatic diseases (IRDs).

Methods
People with IRDs (n = 2024) were identified from their electronic health record and invited to participate in a cross-sectional survey, using short message service (SMS) and postal approaches. Data were collected on demographics, self-reported diagnosis, access to and use of internet-enabled devices, health and digital literacy, together with confidence and satisfaction with remote consultations. Ethical approval was obtained (Ref 21/PR/0867).

Results
Six hundred and thirty-nine (639) people completed the survey [mean (s.d.) age 64.5 (13.1) years, 384 (60.1%) female]. Two hundred and eighty-seven (44.9%) completed it online. One hundred and twenty-six (19.7%) people reported not having access to an internet-enabled device. Ninety-three (14.6%) reported never accessing the internet; this proportion was highest (23%) in people with RA. One hundred and seventeen (18%) reported limited health literacy. Even in those reporting internet use, digital literacy was only moderate. People with limited health or digital literacy or without internet access were less likely to report confidence or satisfaction with remote consultations.

Conclusion
Limited health and digital literacy, lack of digital access and low reported internet use were common, especially in older people with RA. People with limited health literacy or limited digital access reported lower confidence and satisfaction with remote consultations. Digital implementation roll-out needs to take account of people requiring extra support to enable them to access care digitally or risks exacerbating health inequalities.