bluuebunny/crossref_metadata_2025 huggingface dataset:
Service user satisfaction with care in a specialist service for young people with attention deficit hyperactivity disorder
Authors: McGrath Jane , Cawley Barbara , McTiernan Daniel , Marques Liliana , Goncerz Ewa , Heron Elizabeth A. , Madden Jamie , Bond Laura , Quinn Catherine , Mulholland Ken , Dowling Brenda
Published: April 2022

Objectives:

Consumer satisfaction is considered one of the most important measures of service quality in child mental health; however, there is limited understanding of factors that influence satisfaction. The objective of this study was to investigate key factors influencing satisfaction with care (SWC) in ADMiRE, a specialist service for young people (YP) with attention deficit hyperactivity disorder (ADHD).

Methods:

Parents/carers (n = 67) and YP > 9 years (n = 44) attending ADMiRE completed an anonymous Experience of Service Questionnaire (ESQ), a quantitative/qualitative measure of service user satisfaction. Parents/carers also completed symptom severity rating scales. Data were analysed to determine (i) overall SWC, (ii) the relationship between parent- and youth-reported SWC and (iii) the impact of symptom severity on SWC. Thematic analysis of qualitative ESQ data was completed.

Results:

Parents/carers were significantly more satisfied than YP (p = 0.028). Symptom severity did not impact significantly on parent/carer satisfaction. YP with severe hyperactive/impulsive and inattentive ADHD symptoms were significantly less satisfied with care than those with less severe ADHD symptoms (p = 0.022 and p = 0.017 respectively). Factors related to the therapeutic alliance were identified as being particularly important to both parents/carers and YP.

Conclusions:

This is the first Irish study that has investigated the impact of symptom severity on service user satisfaction in a child mental health service. The results highlight the different perspectives of YP and parents and provide novel insights into the impact of symptom severity on service user satisfaction. The importance of the therapeutic alliance should not be underestimated in future development of services.
Socially Responsible human resource management and employees' turnover intention: the effect of psychological contract violation and moral identity
Authors: Zhao Hongdan , Chen Yuanhua , Xu Yujuan , Zhou Qiongyao
Published: April 2022

This study explores the impact of socially responsible human resource management (SR-HRM) on the turnover intention by exploring the effects of psychological contract violation (PCV) and moral identity. Using a sample of 284 employees in China, we found that PCV mediated the negative relationship between SR-HRM and turnover intention. Moral identity moderated the direct effect of PCV on turnover intention as well as the indirect effect of SR-HRM on turnover intention via PCV, such that both the direct and indirect effects were stronger for employees with a low level of moral identity compared to those with the high level of moral identity. Findings from this study provide a greater understanding of the internal mechanisms and boundary conditions of SR-HRM that affect turnover intentions. Study findings also provide guidance to organizations seeking to reduce employee turnover.
Does time extend asymmetrically into the past and the future? A multitask crosscultural study
Authors: Callizo-Romero Carmen , Tutnjević Slavica , Pandza Maja , Ouellet Marc , Kranjec Alexander , Ilić Sladjana , Gu Yan , Göksun Tilbe , Chahboun Sobh , Casasanto Daniel , Santiago Julio
Published: April 2022

Does temporal thought extend asymmetrically into the past and the future? Do asymmetries depend on cultural differences in temporal focus? Some studies suggest that people in Western (arguably future-focused) cultures perceive the future as being closer, more valued, and deeper than the past (a future asymmetry), while the opposite is shown in East Asian (arguably past-focused) cultures. The proposed explanations of these findings predict a negative relationship between past and future: the more we delve into the future, the less we delve into the past. Here, we report findings that pose a significant challenge to this view. We presented several tasks previously used to measure temporal asymmetry (self-continuity, time discounting, temporal distance, and temporal depth) and two measures of temporal focus to American, Spanish, Serbian, Bosniak, Croatian, Moroccan, Turkish, and Chinese participants (totalN = 1,075). There was an overall future asymmetry in all tasks except for temporal distance, but the asymmetry only varied with cultural temporal focus in time discounting. Past and future held a positive (instead of negative) relation in the mind: the more we delve into the future, the more we delve into the past. Finally, the findings suggest that temporal thought has a complex underlying structure.
Archaic Period Lithic Technology, Sedentism, and Subsistence in Northern Belize: What Can Debitage at Caye Coco and Fred Smith Tell Us?
Authors: Stemp W. James , Rosenswig Robert M.
Published: April 2022

Despite the abundance of lithic debitage at preceramic sites in the Maya Lowlands, these data have rarely been studied in detail. We analyzed the chipped chert debitage from Caye Coco and Fred Smith, two Archaic period sites in the Freshwater Creek drainage of northern Belize, to evaluate strategies of lithic raw material procurement, stone tool production, and tool use. The technological and use-wear analyses of the debitage demonstrate that the sites’ inhabitants procured most of their tool stone from the Northern Belize Chert-bearing Zone (NBCZ) and relied on hard-hammer percussion to produce flakes for use as expedient tools and some crude bifaces and unifaces. Although similar patterns of raw material procurement and tool production are demonstrated at both sites, some differences exist, including bipolar reduction at Caye Coco. Based on use-wear analysis, the debitage at the island site of Caye Coco was primarily used for working wood, shell, and hard contact materials and for digging soil. On the shore at Fred Smith, most use-wear is consistent with working wood, plants, and hard contact materials, as well as digging soil. For both sites, analyses suggest the increasing importance of a horticultural subsistence strategy with reduced mobility and reliance on some cultigens that were locally produced.
Global variations in regional degradation rates since the Last Glacial Maximum mapped through time and space
Authors: Madoff Risa D. , Putkonen Jaakko
Published: April 2022

Topographic diffusivity is an often-used metric of regolith mobility. It accounts for the collective effects of climate, substrate, fauna, flora, and other factors on hillslope degradation and is used to model natural lowering in landscapes. The present study assesses where temporal variations in diffusivity derived from known past climate fluctuations have occurred. We also determine where significant differences might result when modeling landscape degradation if a long-term constant diffusivity is applied instead of diffusivity that varies through time. A space-for-time substitution approach was implemented. Through use of a transfer function that correlates current diffusivities with air temperatures, we mapped the relative diffusivities globally at a 500 yr temporal resolution for 21 ka. The analyses spanned all land areas from the tropics to the poles with a spatial resolution of 3.70° latitude by 3.75° longitude using paleo-temperature data from the TraCE-21ka global paleoclimate model. The results show Arctic and subarctic regions with the highest relative maximum diffusivities and largest variance from current values. The results suggest strong surficial dynamics in the Arctic and subarctic regions driven by local and spatially transient deglaciation and long-term stability in the tropics that correlates with relatively stable climate there through the past 21 ka.
Naming Others: Translation and Subject Constitution in the Central Highlands of Angola (1926–1961)
Authors: Dulley Iracema
Published: April 2022

This paper proposes an ethnographic theorization of the relationship between naming, translation, and subject constitution via the analysis of forms of interpellation in colonial Angola. It engages critically with systemic/structural renderings of colonial society that portray social positions as oppositional to argue for a deconstructive approach attentive to historical disjunctions between naming and social positioning. Dwelling on core signifiers in Portuguese and Umbundu, the paper describes the iterative chain of substitutions through which subjects have been constituted, that is, reduced and transformed. For instance, how are the Umbundu status signifiersocimbunduandocindelereduced in their respective translations as “black” and “white”? How can translation both re-enact and challenge the constitution of racialized and ethnicized categories of difference? How is this related to transformations in Angolan history? The argument put forth challenges the conventional understanding of social categories in the context of Portuguese colonialism in Angola by arguing that the performativity of naming and translation constitutes subjects via both fixation and displacement. Therefore, the possibility of transformation does not lie in the intentional action of subjects, but in their capacity to operate within the fractures of the relationship between language and society by drawing on disjunctions between signifier and signified, names and social positioning, subjective constitution and sociopolitical context.
Range extension and first record of the deep-sea brittle star Ophiactis abyssicola (Echinodermata: Ophiuroidea) in Canadian waters
Authors: Hamel Jean-François , Stöhr Sabine , Côté David , Casey Kaitlin , Penney Heather D. , Neves Bárbara de Moura , Mercier Annie
Published: April 2022

This paper presents the first records of the brittle star Ophiactis abyssicola in Canadian waters and range extensions of up to 1900 km in the Northwest Atlantic from previously known locations. Samples were collected off northern Labrador and the northern portion of insular Newfoundland (eastern Canada) at 433 and 1097 m depths, respectively. This newly recorded species of brittle star from the bathyal zone off Newfoundland and Labrador adds to the marine biodiversity of Canada and to the general distribution knowledge of O. abyssicola.
Robot assembly theory and simulation of circular-rectangular compound peg-in-hole
Authors: Wu Weiguo , Liu Kexin , Wang Tong
Published: April 2022

In this paper, the assembly problem of circular-rectangular compound peg and hole parts in automatic assembly is proposed for the first time, and an automatic assembly method based on six-dimensional force sensor is summarized. Firstly, according to the quasi-static equilibrium condition, the contact states are summarized. It is concluded that there are 7 categories of 44 contact states in insertion stage and the forces conditions to maintain each contact state; Secondly, according to the analysis of the force/moment relationship, the jamming diagram is drawn, and the conditions of jamming are analyzed. Thirdly, the assembly strategy is discussed, including contact state recognition strategy, hole searching strategy, and pose adjustment strategy. Finally, combined with impedance control, the assembly theory is verified in ADAMS, and the assembly with minimum clearance of 0.1 mm is achieved.
UDE-based task space tracking control of uncertain robot manipulator with input saturation and output constraint
Authors: Wu Yuxiang , Wan Fuxi , Xu Tian , Fang Haoran
Published: April 2022

This paper investigates the trajectory tracking problem of uncertain robot manipulators with input saturation and output constraints. Uncertainty and disturbance estimator (UDE) is used to tackle the model uncertainties and external disturbances. Different from most existing methods, UDE only needs the bandwidth of the unknown plant model for design, which makes it easy to be implemented. Nonlinear state-dependent function is employed to cope with output constraints and a second order auxiliary system is constructed to solve the input saturation. Finally, an UDE-based tracking controller is proposed based on the backstepping method. With the proposed control scheme, the input saturation and the output constraints are not violated, and all signals in the closed-loop system are bounded. The comparative simulation results of a two-link robot manipulator are utilized to validate the effectiveness and superiority of the proposed control method.
A New Foundation for Freedom of Movement in an Age of Sovereign Control: The Liberal Jurisprudence of August Wilhelm Heffter
Authors: Szabla Christopher
Published: April 2022

This article addresses how a once influential but now obscure jurist addressed a potential paradox in liberal thought—between democratic control over borders and transnational rights—as it arose in the mid-nineteenth-century, amid advocacy against authoritarianism and for free trade and movement, on the one hand, and the increasing calling into question of natural law theories that may have best facilitated free movement, on the other. While scholarship has increasingly shown how the boundaries between periods of natural law and positivist hegemony are difficult to distinguish, specific tensions in the mid-nineteenth-century called for an approach that preserved free movement in light of the growing appeal of empiricism and state sovereignty. In this context, August Wilhelm Heffter proposed that states were bound by higher law as a consequence of their free decision to enter international communities: these communities’ purpose, he wrote, bred customary laws facilitating interstate interaction. Heffter’s approximation of “natural” law in a more positivist context and his use of the period’s “customary” logic helps account for his influence not only in periods of free trade and movement’s ascendancy but also the survival of forms of his thought into periods of sovereigntist reaction against them. It therefore holds potential to address what scholarship has termed today’s “liberal paradox” between democracy and migration better than approaches that emphasize a more complete return to natural law.
The use of steroids in treating chylothorax following cardiac surgery in children: a unique perspective
Authors: Saad Dima , Makarem Adham , Fakhri Ghina , Al Amin Farah , Bitar Fadi , El Rassi Issam , Arabi Mariam
Published: April 2022

Background:

Chylothorax is the accumulation of chyle fluid in the pleural space. The incidence of chylothorax is quite common post-cardiac surgeries in pediatrics especially in Fontan procedures. Although several treatment lines are known for the management of chylothorax, steroids were scarcely reported as a treatment option. We present a unique case of a 4-year-old child who underwent Fontan procedure and suffered a long-term consequence of chylothorax. The chylothorax only fully resolved after introducing corticosteroids as part of her management.

Methods:

A literature review about management of chylothorax post-cardiac surgery in children using Ovid Medline (19462021), PubMed, and google scholar was performed.

Conclusion:

Conservative management without additional surgical intervention is adequate in most patients. Additionally, somatostatin can be used with variable success rate. However, a few cases mentioned using steroids in such cases. More research and reporting on the use of steroids in the treatment of chylothorax post-cardiac surgeries in children is needed to prove its effectivity. In this article, we describe a case of chylothorax post-Fontan procedure that supports the use of steroids.
Systematic Investigation of Lanthanoid Transition Heavy Metal Acetates as Electron Staining Reagents for Protein Molecules in Biological Transmission Electron Microscopy
Authors: Ishii Noriyuki
Published: April 2022

Cryo-electron microscopy, widely used for high-resolution protein structure determination, does not require staining. Yet negative staining with heavy metal salts such as uranyl acetate has been in persistent demand since the 1950s due to its image contrasting capabilities at room temperature with a common electron microscope. However, uranium compounds are nuclear fuel materials and are tightly controlled worldwide. Acetates of each lanthanoid series elements except promethium are prepared at the same concentration (2%(w/v)) and used as a model on horse spleen ferritin for electron microscopic analysis to systematically evaluate their effectiveness as electron staining reagents for the protein. Analysis shows that the triacetates of samarium and europium, followed by gadolinium and erbium, and then lanthanum and neodymium could function as electron staining reagents. Thulium-triacetate precipitates thin plate-like crystals and may be used for selecting better imaging fields. Of the 14 lanthanoid-triacetates examined, about half are viable alternatives to uranyl acetate as an electron staining reagent for ferritin, and there appears an optimal range in ionic sizes for promising lanthanoids. This is the first systematic investigation of lanthanoid transition heavy metal triacetates from the viewpoint of lanthanoid contraction, using density distribution histograms of electron micrographs as an indicator for comparison with uranyl acetate.
Checking Activation at the Door: Rethinking the Welfare-Work Nexus in Light of Australia’s Covid-19 Response
Authors: Stambe Rose , Marston Greg
Published: April 2022

Public health measures to address the COVID-19 pandemic have disrupted welfare regimes around the world. The Australian government suspended activation requirements for millions of social security clients and substantially increased payment levels. Both measures go against the dominant policy logic over the past several decades in Australian social policy. When these changes were made, many advocates and academics called for a permanent increase in the rate of payment and a relaxation of activations requirements. The Australian Government insisted the stimulus package was temporary and that there would be a gradual return to the pre-pandemic policy settings. In this article, we examine what was learned during this natural experiment of unconditional higher payments, which temporarily lifted millions of households out of poverty. We argue that a return to pre-pandemic policy settings should not go unchecked as there remains an opportunity to consider alternative approaches to the welfare-work nexus in Australia.
Problembasiertes Curriculum für die generalistische Pflegeausbildung
Authors: Feilhuber Markus , Süßmann Stefanie
Published: April 2022

Zusammenfassung. Die Entwicklungen der Ausbildung zur Pflegefachperson fordern ein breites Fachwissen in der Versorgung von Menschen verschiedener Altersgruppen. Anhand des problembasierten Lernens (PBL) können die Auszubildenden auf vielfältige pflegerische Tätigkeiten vorbereitet werden. Die Methode fordert den Auszubildenden Selbstdisziplin in der Vernetzung der Profession Pflege und der Bezugswissenschaften ab.
Roles of Tidal Cycling, Hyporheic Exchange and Bioirrigation on Metal Release From Estuary Sediments
Authors: Liu Y. , Reible D. , Hussain F.
Published: April 2022

A numerical model is developed to investigate metal release from estuarine sediments. The model includes three‐dimensional (3D) large‐eddy simulation of water above the sediment‐water interface, 3D advective and diffusive transport within sediments by both physical and biological processes (bioturbation and bioirrigation), and biogeochemical processes within the sediment including reduction of electron acceptors, acid‐base reactions, and metal sorption and precipitation. The model was applied to explore the influence of overlying water chemistry and sediment chemical, physical and biological processes on metal release from sediments. Overlying water conditions (pH, salinity, oxygen saturation) may vary diurnally due to tidal cycling and control the short‐term release of metals, while over longer times (months), metals are controlled by long‐term averages of sediment convective processes (groundwater upwelling, hyporheic exchange and bioirrigation). Metal release is significantly enhanced when there is bioroughness and bioirrigation due to local oxidation of surficial sediments.
Single-cell RNA sequencing analysis of human bone-marrow-derived mesenchymal stem cells and functional subpopulation identification
Authors: Xie Zhongyu , Yu Wenhui , Ye Guiwen , Li Jinteng , Zheng Guan , Liu Wenjie , Lin Jiajie , Su Zepeng , Che Yunshu , Ye Feng , Zhang Zhaoqiang , Wang Peng , Wu Yanfeng , Shen Huiyong
Published: April 2022

Mesenchymal stem cells (MSCs) are a common kind of multipotent cell in vivo, but their heterogeneity limits their further applications. To identify MSC subpopulations and clarify their relationships, we performed cell mapping of bone-marrow-derived MSCs through single-cell RNA (scRNA) sequencing. In our study, three main subpopulations, namely, the stemness subpopulation, functional subpopulation, and proliferative subpopulation, were identified using marker genes and further bioinformatic analyses. Developmental trajectory analysis showed that the stemness subpopulation was the root and then became either the functional subpopulation or the proliferative subpopulation. The functional subpopulation showed stronger immunoregulatory and osteogenic differentiation abilities but lower proliferation and adipogenic differentiation. MSCs at different passages or isolated from different donors exhibited distinct cell mapping profiles, which accounted for their corresponding different functions. This study provides new insight into the biological features and clinical use of MSCs at the single-cell level, which may contribute to expanding their application in the clinic.
The impact of perinatal inflammation on the electroencephalogram in preterm infants: a systematic review
Authors: Giraud Antoine , Stephens Carol M. , Boylan Geraldine B. , Walsh Brian H.
Published: April 2022

Background

To summarise the association between perinatal inflammation (PI) exposure and electroencephalography (EEG) features in preterm infants.

Methods

This systematic review included clinical studies of preterm infants born <37 weeks of gestational age (GA), who had both a PI exposure and an EEG assessment performed during the neonatal period. Studies were identified from Medline and Embase databases on the 15th of September 2021. PI was defined by histological chorioamnionitis, clinical chorioamnionitis, or early-onset neonatal infection (EONI). The risk of bias in included studies was assessed using the Joanna Briggs Institute (JBI) appraisal tool. A narrative approach was used to synthesise results. This review followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement.

Results

Two cross-sectional studies enrolling 130 preterm children born <32 weeks of GA assessed with one-channel amplitude-integrated EEG (aEEG) during the first four days of life were included. A PI exposure was described in 39 (30%) infants and was associated with a decrease in amplitude and a reduced incidence of sleep-wake cycling patterns.

Conclusion

These results should be interpreted with caution because of the small number of included studies and their heterogeneity. Further clinical studies evaluating the association of PI with EEG findings are needed.

Impact

A method to assess developmental trajectories following perinatal inflammation is required.

Insufficient data exist to determine EEG features associated with perinatal inflammation.

Further clinical studies evaluating this association are needed.
Reduced bacterial mortality and enhanced viral productivity during sinking in the ocean
Authors: Wei Wei , Chen Xiaowei , Weinbauer Markus G , Jiao Nianzhi , Zhang Rui
Published: April 2022

Particle sinking is an important process in the ocean, influencing the biogeochemical cycle and driving the long-term preservation of carbon into the deep sea via the biological pump. However, as an important component of marine ecosystems, the role of viruses during sinking is still poorly understood. Therefore, we performed a series of transplantation experiments in the South China Sea to simulate environmental changes during sinking and investigate their effects on viral eco-dynamics and life strategy. Our study demonstrated increased viral production but decreased virus-mediated bacterial mortality after transplantation. A larger burst size and switch from the lysogenic to lytic strategy were shown to contribute to enhanced viral productivity. We provide experimental evidence that surface viral ecological characteristics changed dramatically after transplantation into deep-sea waters, indicating a potential importance of viruses during vertical sinking in the ocean. This effect probably provides positive feedback on the efficiency of the biological pump.
Knowledge of undergraduate dental students regarding management of caries lesions
Authors: Jablonski-Momeni Anahita , Korbmacher-Steiner Heike , Temming Alexa , Wernke Pia , Heinzel-Gutenbrunner Monika , Haak Rainer , Krause Felix
Published: April 2022

Objectives

Understanding of lifelong control of disease processes associated with caries and its management is an essential part of dental education. This study evaluated the dental students’ knowledge of caries diagnosis and management using the International Caries Classification and Management System (ICCMS).

Methods

A survey was conducted among undergraduate dental students at two dental schools, attending the sixth (centre 1) and seventh semester (centre 2), respectively. Medical histories, clinical images and radiographs of 12 patients were compiled as anonymous cases. For each case, a specific lesion was to be assessed. In addition, the students should determine the patient’s caries risk and select a treatment option. An expert report (consensus decision) was used as the reference standard. For statistical analysis, kappa statistics and binomial tests were used.

Results

A total of 46 students participated in this study. The percentage of agreement of responses to the reference was: centre 1: 40.7–51.3%, centre 2: 57.9–67.9%. The corresponding Kappa values were: centre 1: 0.073–0.175, centre 2: 0.315–0.432. Overall, students tended to underestimate the codes compared to the reference standard (p < 0.001).

Conclusion

Introducing systematic content about caries diagnosis and management such as ICDAS and ICCMS in the learning objectives of undergraduate dental students can be proposed. However, in order to improve diagnosis and enable a more reliable choice of treatment options, attention should also be given to the way they are didactically taught.
IL-1β-activated mTORC2 promotes accumulation of IFN-γ+ γδ T cells by upregulating CXCR3 to restrict hepatic fibrosis
Authors: Liu Qihui , Yang Quanli , Wu Zengfeng , Chen Yanfang , Xu Miaomiao , Zhang Hua , Zhao Jiliang , Liu Zonghua , Guan Zerong , Luo Jing , Li Zhi-yong , Sun Guodong , Wen Qiong , Xu Yan , Li Zhenhua , Chen Kebing , Ben Xiaosong , He Wanchun , Li Xueshi , Yin Zhinan , Hao Jianlei , Lu Ligong
Published: April 2022

Liver fibrosis represents a severe stage of liver damage, with hallmarks of inflammation, hepatic stellate cell activation, and extracellular matrix accumulation. Although previous studies demonstrated γδ T cells are involved in liver fibrosis, the precise role and mechanisms of γδ T cells migrating to fibrotic liver have not been elucidated. Here, we aim to investigate the functional subsets of γδ T cells in hepatic fibrosis and to further explore the underlying causes and drivers of migration. In this study, we observed that γδ T cells accumulate in fibrotic liver. Adoptive transfer of γδ T, especially Vγ4 γδ T subset, can significantly alleviate liver fibrosis. In addition, CCl4 treatment also leads to activation of mTOR signaling in γδ T cells. Genetic deletion of the Rictor gene, but not Raptor, in γδ T cells markedly exacerbated liver fibrosis. Mechanistically, CCl4-induced liver injury causes macrophage accumulation in the liver, and IL-1β produced by macrophages promotes mTORC2 signaling activation in γδ T cells, which upregulates T-bet expression and eventually promotes CXCR3 transcription to drive γδ T cell migration. Moreover, hepatic γδ T cells ameliorated liver fibrosis by cytotoxicity against activated hepatic stellate cells in FasL-dependent manner, and secrete IFN-γ to inhibit the differentiation of pro-fibrotic Th17 cells. Thus, IL-1β-activated mTORC2 signaling in γδ T cells upregulates CXCR3 expression, which is critical for IFN-γ+ γδ T cells migration into the liver and amelioration of liver fibrosis. Our findings indicate that targeting the mTORC2 or CXCR3 in γδ T cells could be considered as a promising approach for γδ T cell immunotherapy against liver fibrosis.
Class I HDAC overexpression promotes temozolomide resistance in glioma cells by regulating RAD18 expression
Authors: Hanisch Daniela , Krumm Andrea , Diehl Tamara , Stork Carla M. , Dejung Mario , Butter Falk , Kim Ella , Brenner Walburgis , Fritz Gerhard , Hofmann Thomas G. , Roos Wynand P.
Published: April 2022

Overexpression of histone deacetylases (HDACs) in cancer commonly causes resistance to genotoxic-based therapies. Here, we report on the novel mechanism whereby overexpressed class I HDACs increase the resistance of glioblastoma cells to the SN1 methylating agent temozolomide (TMZ). The chemotherapeutic TMZ triggers the activation of the DNA damage response (DDR) in resistant glioma cells, leading to DNA lesion bypass and cellular survival. Mass spectrometry analysis revealed that the catalytic activity of class I HDACs stimulates the expression of the E3 ubiquitin ligase RAD18. Furthermore, the data showed that RAD18 is part of the O6-methylguanine-induced DDR as TMZ induces the formation of RAD18 foci at sites of DNA damage. Downregulation of RAD18 by HDAC inhibition prevented glioma cells from activating the DDR upon TMZ exposure. Lastly, RAD18 or O6-methylguanine-DNA methyltransferase (MGMT) overexpression abolished the sensitization effect of HDAC inhibition on TMZ-exposed glioma cells. Our study describes a mechanism whereby class I HDAC overexpression in glioma cells causes resistance to TMZ treatment. HDACs accomplish this by promoting the bypass of O6-methylguanine DNA lesions via enhancing RAD18 expression. It also provides a treatment option with HDAC inhibition to undermine this mechanism.
Inhibition of RIPK1 by ZJU-37 promotes oligodendrocyte progenitor proliferation and remyelination via NF-κB pathway
Authors: Ma Xiao-Ru , Yang Shu-Ying , Zheng Shuang-Shuang , Yan Huan-Huan , Gu Hui-Min , Wang Fan , Wu Yang , Dong Zhao-Jun , Wang Di-Xian , Wang Yue , Meng Xianhui , Sun Jie , Xia Hong-Guang , Zhao Jing-Wei
Published: April 2022

Receptor interacting serine/threonine protein kinase 1 (RIPK1) activation and necroptosis have been genetically and mechanistically linked with human multiple sclerosis and neurodegenerative diseases for which demyelination is a common key pathology. Demyelination can be healed through remyelination which is mediated by new oligodendrocytes derived from the adult oligodendrocyte progenitor cells (OPCs). Unfortunately, the efficiency of remyelination declines with progressive aging partially due to the depletion of OPCs following chronic or repeated demyelination. However, to our knowledge, so far there is no drug which enhances proliferation of OPCs, and it is unknown whether inhibiting RIPK1 activity directly affect OPCs, the central player of remyelination. Using TNFα induced RIPK1-dependent necroptosis in Jurkat FADD−/− cells as a cell death assay, we screened from 2112 FDA-approved drugs and the drug candidates of new RIPK1 inhibitors selected by ourselves, and identified ZJU-37, a small molecule modified by introducing an amide bond to Nec-1s, is a new RIPK1 kinase inhibitor with higher potency than Nec-1s which has the best reported potency. We unveil in addition to protecting myelin from demyelination and axons from degeneration, ZJU-37 exhibits a new role on promoting proliferation of OPCs and enhancing remyelination by inhibiting RIPK1 kinase activity with higher potency than Nec-1s. Mechanistically, ZJU-37 promotes proliferation of OPCs by enhancing the transcription of platelet derived growth factor receptor alpha via NF-κB pathway. This work identifies ZJU-37 as a new drug candidate which enhances remyelination by promoting proliferation of OPCs, paving the way for a potential drug to enhance myelin repair.
Smart hydrogels with wide visible color tunability
Authors: Wen Guo-Yu , Zhou Xing-Long , Tian Xiao-Yu , Xie Rui , Ju Xiao-Jie , Liu Zhuang , Faraj Yousef , Wang Wei , Chu Liang-Yin
Published: April 2022

Pigmentary coloration can produce viewing angle-independent uniform colors via light absorption by chromophores. However, due to the limited diversity in the changes of the molecular configuration of chromophores to undergo color change, the existing materials cannot produce a wide range of visible colors with tunable color saturation and transmittance. Herein, we propose a novel strategy to create materials with a wide visible color range and highly tunable color saturation and transmittance. We fabricated a hydrogel with poly (acrylamide-co-dopamine acrylamide) networks swollen with Fe3+-containing glycerol/water in which the covalently crosslinked polyacrylamide backbone with pendant catechols can ensure that the hydrogel maintains a very stable shape. Hydrogels containing adjustable catechol-Fe3+ coordination bonds with flexible light-interacting configuration changes can display a wide range of visible colors based on the complementary color principle. The catechol-Fe3+ complexes can dynamically switch between noncoordinated and mono-, bis- and tris-coordinated states to harvest light energy from a specific wavelength across the whole visible spectrum. Therefore, these hydrogels can be yellow, green, blue, and red, covering the three primary colors. Moreover, color saturation and transmittance can be flexibly manipulated by simply adjusting the Fe3+ content in the hydrogel networks. The versatility of these smart hydrogels has been demonstrated through diverse applications, including optical filters for color regulation and colorimetric sensors for detecting UV light and chemical vapors. This proposed smart hydrogel provides a universal color-switchable platform for the development of multifunctional optical systems such as optical filters, sensors, and detectors.
Harnessing phosphonate antibiotics argolaphos biosynthesis enables a synthetic biology-based green synthesis of glyphosate
Authors: Chu Leixia , Luo Xiaoxia , Zhu Taoting , Cao Yingying , Zhang Lili , Deng Zixin , Gao Jiangtao
Published: April 2022

Glyphosate is a widely used herbicide with an annual production of more than one million tons globally. Current commercialized production processes of glyphosate are generally associated with manufacturing hazards and toxic wastes. Recently, many countries have strengthened environmental supervision and law enforcement on glyphosate manufacturing. Therefore, a green source of glyphosate is required. Here, we characterize the genes required for producing aminomethylphosphonate (AMP), one of the intermediates in the biosynthesis of the potent antibiotics argolaphos. We apply a synthetic biology strategy to improve AMP production in Streptomyces lividans, with fermentation titers of 52 mg L-1, a 500-fold improvement over the original strain. Furthermore, we develop an efficient and practical chemical process for converting AMP to glyphosate. Our findings highlight one greenness-driven alternative in the production of glyphosate.
Current progress and open challenges for applying deep learning across the biosciences
Authors: Sapoval Nicolae , Aghazadeh Amirali , Nute Michael G. , Antunes Dinler A. , Balaji Advait , Baraniuk Richard , Barberan C. J. , Dannenfelser Ruth , Dun Chen , Edrisi Mohammadamin , Elworth R. A. Leo , Kille Bryce , Kyrillidis Anastasios , Nakhleh Luay , Wolfe Cameron R. , Yan Zhi , Yao Vicky , Treangen Todd J.
Published: April 2022

Deep Learning (DL) has recently enabled unprecedented advances in one of the grand challenges in computational biology: the half-century-old problem of protein structure prediction. In this paper we discuss recent advances, limitations, and future perspectives of DL on five broad areas: protein structure prediction, protein function prediction, genome engineering, systems biology and data integration, and phylogenetic inference. We discuss each application area and cover the main bottlenecks of DL approaches, such as training data, problem scope, and the ability to leverage existing DL architectures in new contexts. To conclude, we provide a summary of the subject-specific and general challenges for DL across the biosciences.
AF2Complex predicts direct physical interactions in multimeric proteins with deep learning
Authors: Gao Mu , Nakajima An Davi , Parks Jerry M. , Skolnick Jeffrey
Published: April 2022

Accurate descriptions of protein-protein interactions are essential for understanding biological systems. Remarkably accurate atomic structures have been recently computed for individual proteins by AlphaFold2 (AF2). Here, we demonstrate that the same neural network models from AF2 developed for single protein sequences can be adapted to predict the structures of multimeric protein complexes without retraining. In contrast to common approaches, our method, AF2Complex, does not require paired multiple sequence alignments. It achieves higher accuracy than some complex protein-protein docking strategies and provides a significant improvement over AF-Multimer, a development of AlphaFold for multimeric proteins. Moreover, we introduce metrics for predicting direct protein-protein interactions between arbitrary protein pairs and validate AF2Complex on some challenging benchmark sets and the E. coli proteome. Lastly, using the cytochrome c biogenesis system I as an example, we present high-confidence models of three sought-after assemblies formed by eight members of this system.
BRCA2-DSS1 interaction is dispensable for RAD51 recruitment at replication-induced and meiotic DNA double strand breaks
Authors: Mishra Arun Prakash , Hartford Suzanne A. , Sahu Sounak , Klarmann Kimberly , Chittela Rajani Kant , Biswas Kajal , Jeon Albert B. , Martin Betty K. , Burkett Sandra , Southon Eileen , Reid Susan , Albaugh Mary E. , Karim Baktiar , Tessarollo Lino , Keller Jonathan R. , Sharan Shyam K.
Published: April 2022

The interaction between tumor suppressor BRCA2 and DSS1 is essential for RAD51 recruitment and repair of DNA double stand breaks (DSBs) by homologous recombination (HR). We have generated mice with a leucine to proline substitution at position 2431 of BRCA2, which disrupts this interaction. Although a significant number of mutant mice die during embryogenesis, some homozygous and hemizygous mutant mice undergo normal postnatal development. Despite lack of radiation induced RAD51 foci formation and a severe HR defect in somatic cells, mutant mice are fertile and exhibit normal RAD51 recruitment during meiosis. We hypothesize that the presence of homologous chromosomes in close proximity during early prophase I may compensate for the defect in BRCA2-DSS1 interaction. We show the restoration of RAD51 foci in mutant cells when Topoisomerase I inhibitor-induced single strand breaks are converted into DSBs during DNA replication. We also partially rescue the HR defect by tethering the donor DNA to the site of DSBs using streptavidin-fused Cas9. Our findings demonstrate that the BRCA2-DSS1 complex is dispensable for RAD51 loading when the homologous DNA is close to the DSB.
Exploration of the dynamic interplay between lipids and membrane proteins by hydrostatic pressure
Authors: Pozza Alexandre , Giraud François , Cece Quentin , Casiraghi Marina , Point Elodie , Damian Marjorie , Le Bon Christel , Moncoq Karine , Banères Jean-Louis , Lescop Ewen , Catoire Laurent J.
Published: April 2022

Cell membranes represent a complex and variable medium in time and space of lipids and proteins. Their physico-chemical properties are determined by lipid components which can in turn influence the biological function of membranes. Here, we used hydrostatic pressure to study the close dynamic relationships between lipids and membrane proteins. Experiments on the β–barrel OmpX and the α–helical BLT2 G Protein-Coupled Receptor in nanodiscs of different lipid compositions reveal conformational landscapes intimately linked to pressure and lipids. Pressure can modify the conformational landscape of the membrane protein per se, but also increases the gelation of lipids, both being monitored simultaneously at high atomic resolution by NMR. Our study also clearly shows that a membrane protein can modulate, at least locally, the fluidity of the bilayer. The strategy proposed herein opens new perspectives to scrutinize the dynamic interplay between membrane proteins and their surrounding lipids.
Aneuploidy tolerance caused by BRG1 loss allows chromosome gains and recovery of fitness
Authors: Schiavoni Federica , Zuazua-Villar Pedro , Roumeliotis Theodoros I. , Benstead-Hume Graeme , Pardo Mercedes , Pearl Frances M. G. , Choudhary Jyoti S. , Downs Jessica A.
Published: April 2022

Aneuploidy results in decreased cellular fitness in many species and model systems. However, aneuploidy is commonly found in cancer cells and often correlates with aggressive growth, suggesting that the impact of aneuploidy on cellular fitness is context dependent. The BRG1 (SMARCA4) subunit of the SWI/SNF chromatin remodelling complex is frequently lost in cancer. Here, we use a chromosomally stable cell line to test the effect of BRG1 loss on the evolution of aneuploidy. BRG1 deletion leads to an initial loss of fitness in this cell line that improves over time. Notably, we find increased tolerance to aneuploidy immediately upon loss of BRG1, and the fitness recovery over time correlates with chromosome gain. These data show that BRG1 loss creates an environment where karyotype changes can be explored without a fitness penalty. At least in some genetic backgrounds, therefore, BRG1 loss can affect the progression of tumourigenesis through tolerance of aneuploidy.
Bridging the gap between atomically thin semiconductors and metal leads
Authors: Cai Xiangbin , Wu Zefei , Han Xu , Chen Yong , Xu Shuigang , Lin Jiangxiazi , Han Tianyi , He Pingge , Feng Xuemeng , An Liheng , Shi Run , Wang Jingwei , Ying Zhehan , Cai Yuan , Hua Mengyuan , Liu Junwei , Pan Ding , Cheng Chun , Wang Ning
Published: April 2022

Electrically interfacing atomically thin transition metal dichalcogenide semiconductors (TMDSCs) with metal leads is challenging because of undesired interface barriers, which have drastically constrained the electrical performance of TMDSC devices for exploring their unconventional physical properties and realizing potential electronic applications. Here we demonstrate a strategy to achieve nearly barrier-free electrical contacts with few-layer TMDSCs by engineering interfacial bonding distortion. The carrier-injection efficiency of such electrical junction is substantially increased with robust ohmic behaviors from room to cryogenic temperatures. The performance enhancements of TMDSC field-effect transistors are well reflected by the low contact resistance (down to 90 Ωµm in MoS2, towards the quantum limit), the high field-effect mobility (up to 358,000 cm2V−1s−1 in WSe2), and the prominent transport characteristics at cryogenic temperatures. This method also offers possibilities of the local manipulation of atomic structures and electronic properties for TMDSC device design.
Enantioselective functionalization at the C4 position of pyridinium salts through NHC catalysis
Authors: Choi Hangyeol , Mathi Gangadhar Rao , Hong Seonghyeok , Hong Sungwoo
Published: April 2022

A catalytic method for the enantioselective and C4-selective functionalization of pyridine derivatives is yet to be developed. Herein, we report an efficient method for the asymmetric β-pyridylations of enals that involve N-heterocyclic carbene (NHC) catalysis with excellent control over enantioselectivity and pyridyl C4-selectivity. The key strategy for precise stereocontrol involves enhancing interactions between the chiral NHC-bound homoenolate and pyridinium salt in the presence of hexafluorobenzene, which effectively differentiates the two faces of the homoenolate radical. Room temperature is sufficient for this transformation, and reaction efficiency is further accelerated by photo-mediation. This methodology exhibits broad functional group tolerance and enables facile access to a diverse range of enantioenriched β-pyridyl carbonyl compounds under mild and metal-free conditions.
Morphological evolution of creek networks in 10 restored coastal wetlands in the UK
Authors: Chirol C. , Haigh I. D. , Pontee N. , Thompson C. E. L , Gallop S. L.
Published: April 2022

Coastal wetlands provide crucial ecosystem services including flood protection and carbon storage, but are being lost rapidly worldwide to the combined effects of sea-level rise, erosion and coastal urbanisation. Managed Realignment (MR) aims to mitigate for these losses by restoring reclaimed land to tidal influence. Data of creek evolution is critical to assess the performance of design strategies and improve design and implementation practices. This data descriptor provides a dataset of the horizontal morphological evolution of creek systems from various initial conditions in 10 MR schemes across the UK. Using a semi-automated workflow, morphological creek parameters were extracted from 52 lidar datasets at 1 m horizontal resolution spanning 2 to 20 years post-breach. This constitutes the most comprehensive systematic monitoring of MR creek morphology to date. The dataset will assist future MR design and provide baseline morphological information for ecological and biogeochemical surveying.
Association of comorbidities and medications with risk of asthma exacerbation in pediatric patients: a retrospective study using Japanese claims data
Authors: Maeda Shotaro , Kobayashi Shigetoshi , Takahashi Kenzo , Miyata Satoshi
Published: April 2022

Asthma exacerbation impairs the quality of life of pediatric patients and negatively impacts future respiratory function and health economics. Several risk factors associated with exacerbations have been identified; however, most studies report the risk of each factor. Therefore, this study aimed to evaluate the risk of each factor and a combination of factors. We performed a retrospective cohort study using Japanese claims data and extracted factors associated with exacerbations using multivariate Cox proportional hazards regression and stepwise method. Risk scores were then calculated from the extracted factors and validated by tenfold cross validation. Of the 1,748,111 asthma patients in the database, the data of 14,980 were extracted, and 1988 (13.3%) had exacerbation. Factors associated with asthma exacerbation were age of 3–5 years, exacerbation history before cohort entry date, allergic rhinitis, chronic sinusitis, otitis externa, blepharitis, upper respiratory infections, urticaria, LTRA prescription, were determined. A four-level risk score was calculated from 9-factors and the AUC derived from cross validation was 0.700. Most factors extracted in our study are consistent with those of previous studies. We showed that combining each factor is more helpful in assessing the increased risk of asthma exacerbation than assessing each factor alone.