bluuebunny/crossref_metadata_2025 huggingface dataset:
Racial Attitudes and Vote Choice in National Canadian Elections
Authors: Hale Isaac
Published: July 2023

This article examines the effect of racial attitudes on the electoral performance of the New Democratic Party (NDP). Since 2017, the NDP has been led by Jagmeet Singh, the first non-white leader of a nationally competitive Canadian political party. Voters’ racial attitudes and the race of party leaders have a significant effect on vote choice in the United States. Less is known about whether similar effects exist in Canadian elections. I show that NDP vote choice polarized on the basis of racial attitudes following Singh's ascension to party leader. Voters with cold feelings toward racial minorities were less likely to vote for the NDP in 2019 and 2021 than in comparable historical elections. In contrast, there is no significant difference between 2019/2021 and prior elections in support for the Liberals and Conservatives among such voters. These results suggest that racial attitudes are salient in Canadian elections and that national parties may face an electoral penalty when selecting non-white party leaders.
“The Year of Jubilee is Come”: Black Millerites and the Politics of Christian Apocalypticism
Authors: Baker Benjamin
Published: July 2023

This article explores the experiences of black people who accepted the teaching of William Miller that Christ would return to the earth in 1843–1844. Heretofore, black Millerites have been almost completely ignored in the substantial historiography of Millerism, millennialism and apocalypticism, and black religion. In this article, I argue that the black experience in Millerism deserves to be studied because it articulates the central concerns of blacks at a critical juncture in antebellum America. I show that enslaved and free blacks embraced Miller's doctrine because of the failure of America, particularly its politics and churches, to provide them the basic human right of freedom. As they did in the Christian churches they joined during the Awakenings, blacks fashioned Millerism in their image, using it for purpose, empowerment, expression, community, and liberation. This exploration of black Millerites contributes to broader discussions on the motivations of marginalized people who gravitate toward the eschatological and the impact the apocalyptic has on real-world engagement.
Temoq, Semelai, Semaq Beri and Jakun: Using Orang Asli ethnonyms to reconstruct Orang Asli ethnohistory
Authors: Gianno Rosemary
Published: July 2023

This article investigates the history of the ethnonyms Temoq, Semelai, Semaq Beri and Jakun, which label Orang Asli groups in the south-central lowlands of Peninsular Malaysia. It combines ethnographic and historical accounts and census analysis to argue that each of these ethnonyms, in the twentieth century, became attached to the groups that now carry them by R.J. Wilkinson and other colonial administrator/anthropologists who were primarily concerned with finding traces of supposed primitive ancestors of modern humans, but who determined that language had to be used as a proxy toward that end. Clarifying the basis of that classification makes the system of ethnonyms that became official somewhat clearer. The article delves deepest into the genesis of ‘Temoq’, through an analysis of the ethnography of H.D. Collings and through the linguistics of the word. It argues that the Semelai word tmoʔ derives from the Malay word tembok [təmboʔ], meaning ‘tattered and dissolute in appearance’, and has been used by the Semelai to achieve social distance from the Temoq, who the Semelai also call /smaʔ bri/ ‘forest people’. It further suggests that the people now known as Temoq may themselves have once been known as ‘Semelai’.
A Parochial Approach: Colonial Entomology on the Plantations of Nineteenth-Century Sri Lanka
Authors: Holmes Matthew
Published: July 2023

The coffee plantations of late nineteenth-century Ceylon (modern-day Sri Lanka) were rocked by a series of crises, including the appearance of numerous insect pests. Scholars have demonstrated that nineteenth-century plantations were both ecologically vulnerable and reliant on exploited labour, with entomology deployed in their defence across the British Empire. Yet this paper argues that, despite its global reach, colonial entomology was sometimes conducted by individuals in pursuit of such parochial concerns as their local reputation and social standing. This case study examines the beetles of Ceylon through the eyes of Scottish plantation owner and amateur naturalist Robert Camperdown Haldane. His 1881 tract All About Grub erroneously identified the island's beetles as relatives of the European cockchafer (Melolontha melolontha). Although Haldane was a well-travelled individual who adopted a global science, he was also a product of Ceylon's plantation society: touchy about his social status and dismissive of his Indian labourers. The insular priorities of individuals or tight-knit communities could direct an enterprise with superficially global characteristics.
Policies that Support and Hinder Families as Partners in Care during COVID-19 Pandemic: Comparative Policy Learning from England, British Columbia, and the Netherlands
Authors: Keefe Janice M. , Krawchenko Tamara
Published: July 2023

The COVID-19 pandemic has taken a devastating toll on long-term care (LTC) residents, families, and staff. In an effort to keep residents safe from COVID-19, public health measures were implemented early in the pandemic to restrict visitation with residents in many countries, with subsequent adjustments made over the course of the pandemic. It is critical to understand the implementation process and how restrictions on visitations have impacted residents, families, and staff. This research note shares a summary of research interviews conducted with key informants in British Columbia (Canada), England (United Kingdom), and The Netherlands on the implementation of visitation programs in the COVID-19 context. It highlights leading practices and key challenges from these jurisdictions.
You’ve Got E-Mail: A Pilot Study Examining the Feasibility and Impact of a Group-Based Technology-Training Intervention Among Older Adults Living in Residential Care
Authors: Ysseldyk Renate , Morton Thomas A. , Haslam Catherine , Haslam S. Alexander , Boger Jennifer , Giau Emily , Macdonald Erin P. , Matharu Amy , McCoy Madeline
Published: July 2023

Older adults living in residential care often experience challenges in sustaining meaningful social relationships, which can result in compromised health and well-being. Online social networking has the potential to mitigate this problem, but few studies have investigated its implementation and its effectiveness in maintaining or enhancing well-being. This pilot study used a cluster-randomized pre–post design to examine the feasibility of implementing a 12-week group-based technology-training intervention for older adults (n= 48) living in residential care by exploring how cognitive health, mental health, and confidence in technology were impacted. Analysis of variance revealed significant increases in life satisfaction, positive attitudes toward computer use, and self-perceived competence among participants who received the intervention, but increased depressive symptoms for the control group. These findings suggest that, despite challenges in implementing the intervention in residential care, group-based technology training may enhance confidence among older adults while maintaining or enhancing mental health.
Not every countable complete distributive lattice is sober
Authors: Miao Hualin , Xi Xiaoyong , Li Qingguo , Zhao Dongsheng
Published: July 2023

The study of the sobriety of Scott spaces has got a relatively long history in domain theory. Lawson and Hoffmann independently proved that the Scott space of every continuous directed complete poset (usually called domain) is sober. Johnstone constructed the first directed complete poset whose Scott space is non-sober. Soon after, Isbell gave a complete lattice with a non-sober Scott space. Based on Isbell’s example, Xu, Xi, and Zhao showed that there is even a complete Heyting algebra whose Scott space is non-sober. Achim Jung then asked whether every countable complete lattice has a sober Scott space. The main aim of this paper is to answer Jung’s problem by constructing a countable complete lattice whose Scott space is non-sober. This lattice is then modified to obtain a countable distributive complete lattice with a non-sober Scott space. In addition, we prove that the topology of the product space
$\Sigma P\times \Sigma Q$
coincides with the Scott topology of the product poset
$P\times Q$
if the set Id(P) and Id(Q) of all incremental ideals of posets P and Q are both countable. Based on this, it is deduced that a directed complete poset P has a sober Scott space, if Id(P) is countable and
$\Sigma P$
is coherent and well filtered. In particular, every complete lattice L with Id(L) countable has a sober Scott space.
Wilful daughters, domestic goddesses, pious Muslims, and rebels: Islam, fashion, commodities, and emotions among upper class women in Pakistan, 1947–1962
Authors: Iob Elisabetta
Published: July 2023

Pakistan, 15 January 1950. Impeccably dressed, Zarina is going out to celebrate the wedding of her partner-in-gossip-crime, Fizza. Her busy life makes her feel anxious. The wrongdoings of the home helpers and her parents’ constant bickering fill her family life. Fashion magazines, get-togethers at the association she has just joined, and ladies’ glamorous parties are her only antidotes to stress.

This article explores the history of Zarina and her fellow upper class women's emotions, everyday lives, and daily perception of religious and socio-political ideas of change in Pakistan's momentous formative years (1947–1962). By relying on Francis Robinson's research on religious change, self, and the fashioning of Muslim identity, it provides the first historical ethnography of how upper class women in Pakistan understood and experienced socio-political change through the transformation of their emotions, religious views, lifestyle, and behaviour.

Drawing on material and visual culture and a rich selection of newspaper clippings and government records, this article lifts the curtain on the material and immaterial ‘stuff’ of women's dreams, taste in fashion, private lives, and political and religious ideas. Finally, it illuminates how women and their gendered agency became the key ‘sites’ for a new and, at times, surprising Islamic revival.
Matteo Ricci as an Islamicate informant. Two moments of connection in the Persian afterlives of a Latin account of China
Authors: Green Nile
Published: July 2023

Three centuries after the Mongol-era historian Rashid al-Din (1247–1318) wrote his influential account of China, an émigré Christian convert from Islam translated Matteo Ricci's book on China into Persian in Mughal Delhi. In doing so, he provided a remarkably detailed depiction of the rulers, religions, and regulations of the Ming empire that greatly updated, and superseded, Rashid al-Din's celebrated account. Nonetheless, by the very virtue of its triangulated origins—between China, Europe, and India; between Chinese, Latin, and Persian—this was a fraught endeavour. For Chinese cultural traditions had to be rendered into Islamicate Persian terms that were approximate equivalents for Latin Christian terms which themselves inevitably misrepresented Confucian terms that in turn provided biased depictions of Buddhist and Daoist beliefs. By looking at two moments of the transmission of Ricci into Persian—in the early modern era of manuscripts and amid the colonial ascent of Indian print—this article uses translation as a lens through which to observe both the reach and limits of the cross-cultural connections that have captivated global historians in recent decades.
Marshall Hodgson's ideas on cores and modernity in Islam: a critique
Authors: Eaton Richard Maxwell
Published: July 2023

Marshall Hodgson has been rightly admired for his vast contributions in the fields of both Islam and world history. Despite the many decades since the publication of his works on these topics, his ideas have largely survived the test of time and continue to be influential. There are two respects, however, in which Hodgson's ideas appear to have been fundamentally flawed—namely, his notion of cultural cores versus peripheries in the Islamic world, and his understanding of modernity. This article explores both of these themes.
Sedation in pediatric palliative care: The role of pediatric palliative care teams
Authors: Peláez Cantero Maria José , Morales Asencio Jose Miguel , Parra Plantagenet-Whyte Fátima , Leyva Carmona Moisés , Rosique Antonelli Mireille , Gili Bigatá Teresa , Martino Alba Ricardo
Published: July 2023

Objectives

Palliative sedation (PS) consists of the use of drugs to alleviate the suffering of patients with refractory symptoms, through a reduction in consciousness. The aim of this study is to describe the incidence of and indications for PS in patients treated by pediatric palliative care teams (PPCT), and the relationship between PS, the place of death, and the characteristics of the care teams.

Methods

Ambispective study with the participation of 14 PPCT working in Spain.

Results

From January to December 2019, a total of 164 patients attended by these PPCT died. Of these, 83 (50.6%) received PS during their last 24 hours. The most frequent refractory symptoms were terminal suffering (n = 40, 48.2%), dyspnea (n = 9, 10.8%), pain (n = 8, 9.6%), and convulsive state (n = 7, 8.4%). Sedation in the last 24 hours of life was more likely if the patient died in hospital, rather than at home (62.9% vs. 33.3%, p < 0.01); if the parents had not expressed their preference regarding the place of death (69.2% vs. 45.2%, p = 0.009); and if the PPCT had less than 5 years’ experience (66.7% vs. 45.5%, p = 0.018).

Significance of results

PS is a real possibility in pediatric end-of-life care and relates to care planning and team expertise.
Organic Alkalinity as an Important Constituent of Total Alkalinity and the Buffering System in River‐To‐Coast Transition Zones
Authors: Song Shuzhen , Bellerby Richard Garth James , Wang Zhaohui Aleck , Wurgaft Eyal , Li Daoji
Published: July 2023

Organic acid‐base species in the dissolved organic carbon pool have been shown to make an important contribution (i.e., organic alkalinity; OrgAlk) to the total alkalinity (TA) in many coastal systems. This study documents an intensive investigation of OrgAlk characteristics in the river‐to‐coast transition zones of six southeast Chinese rivers. OrgAlk, mainly originating from river input, accounted for an important proportion of TA (0.3%–12%) in six estuaries. Carboxylic acid groups were commonly present in all estuaries. Notable differences in the TA values (1–18 μmol kg−1) determined by several established TA measurement approaches were identified in estuaries where organic acids with pKa <5.2 were abundant. The most widely used open‐cell titration method, in comparison with closed‐cell titration and single‐step titration, is the best approach to incorporate OrgAlk in titrated TA when the pKa values of organic acids were >5 in the study estuaries. Across our study sites, OrgAlk might modify H+ concentrations by 3%–69% (i.e., pH by 0.01–0.78) and aragonite saturation states by 1%–72%, indicating that OrgAlk can play a significant role in the coastal carbonate buffering system. It is essential to improve current TA measurement approaches to more accurately represent OrgAlk in the coastal system and assess impacts of OrgAlk on coastal carbonate chemistry.
A Physical Perspective of Recurrent Water Quality Degradation: A Case Study in the Jiangsu Coastal Waters, China
Authors: Chen Shufen , Jiang Long , Cheng Xuhua , Liao Guanghong , Gerkema Theo
Published: July 2023

Estuarine‐coastal systems receive pollutants from various sources at an alarming rate. Some systems are extremely susceptible to terrestrial input, as a relatively small amount of pollutant loading induces lasting water quality degradation. The Jiangsu coastal waters (JCWs), located in the southwestern Yellow Sea, are such areas that lack large river discharge but suffer from recurrent eutrophication recently. We hypothesize that the low flushing efficiency in the JCWs largely accounted for the susceptibility to coastal pollution. To test it, transit time (TT) and pollutant flushing rates in the JCWs were estimated under various scenarios using a validated three‐dimensional hydrodynamic model. Results show that TT in many inshore waters of the JCWs and the northern radial sand ridges is >240 days, which are consistent with the observed frequently eutrophic areas. The JCWs are better flushed and thus less eutrophic in summer, as a consequence of the stronger tidal residual coastal circulation. The baroclinic pressure gradient, modulated by the formation and destruction of thermal stratification in offshore waters, poses a dominant control on the seasonal variations of the coastal circulation and flushing rates, while wind effects are secondary. River‐borne pollutants from the Yangtze and Jiangsu local rivers are shown to primarily affect regions south and north of 32.5°N, respectively. Our study interprets the vulnerability of the JCWs to pollutant enrichment from a physical perspective and finds the flushing efficiency to be a good indicator of eutrophication, providing references for environmental managers of local and global estuarine‐coastal systems with recurrent pollution.
Numerical Study of Coupled Water and Vapor Flow, Heat Transfer, and Solute Transport in Variably‐Saturated Deformable Soil During Freeze‐Thaw Cycles
Authors: Huang Xiang , Rudolph David L.
Published: July 2023

As climate change intensifies, soil water flow, heat transfer, and solute transport in the active, unfrozen zones within permafrost and seasonally frozen ground exhibit progressively more complex interactions that are difficult to elucidate with measurements alone. For example, frozen conditions impede water flow and solute transport in soil, while heat and mass transfer are significantly affected by high thermal inertia generated from water‐ice phase change during the freeze‐thaw cycle. To assist in understanding these subsurface processes, the current study presents a coupled two‐dimensional model, which examines heat conduction‐convection with water‐ice phase change, soil water (liquid water and vapor) and groundwater flow, advective‐dispersive solute transport with sorption, and soil deformation (frost heave and thaw settlement) in variably saturated soils subjected to freeze‐thaw actions. This coupled multiphysics problem is numerically solved using the finite element method. The model's performance is first verified by comparison to a well‐documented freezing test on unsaturated soil in a laboratory environment obtained from the literature. Then based on the proposed model, we quantify the impacts of freeze‐thaw cycles on the distribution of temperature, water content, displacement history, and solute concentration in three distinct soil types, including sand, silt and clay textures. The influence of fluctuations in the air temperature, groundwater level, hydraulic conductivity, and solute transport parameters was also comparatively studied. The results show that (a) there is a significant bidirectional exchange between groundwater in the saturated zone and soil water in the vadose zone during freeze‐thaw periods, and its magnitude increases with the combined influence of higher hydraulic conductivity and higher capillarity; (b) the rapid dewatering ahead of the freezing front causes local volume shrinkage within the non‐frozen region when the freezing front propagates downward during the freezing stage and this volume shrinkage reduces the impact of frost heave due to ice formation. This gradually recovers when the thawed water replenishes the water loss zone during the thawing stage; and (c) the profiles of soil moisture, temperature, displacement, and solute concentration during freeze‐thaw cycles are sensitive to the changes in amplitude and freeze‐thaw period of the sinusoidal varying air temperature near the ground surface, hydraulic conductivity of soil texture, and the initial groundwater levels. Our modeling framework and simulation results highlight the need to account for coupled thermal‐hydraulic‐mechanical‐chemical behaviors to better understand soil water and groundwater dynamics during freeze‐thaw cycles and further help explain the observed changes in water cycles and landscape evolution in cold regions.
Radiocarbon Measurements Reveal Underestimated Fossil CH4 and CO2 Emissions in London
Authors: Zazzeri Giulia , Graven Heather , Xu Xiaomei , Saboya Eric , Blyth Liam , Manning Alistair J. , Chawner Hannah , Wu Dien , Hammer Samuel
Published: July 2023

Radiocarbon (14C) is a powerful tracer of fossil emissions because fossil fuels are entirely depleted in 14C, but observations of 14CO2 and especially 14CH4 in urban regions are sparse. We present the first observations of 14C in both methane (CH4) and carbon dioxide (CO2) in an urban area (London) using a recently developed sampling system. We find that the fossil fraction of CH4 and the atmospheric concentration of fossil CO2 are consistently higher than simulated values using the atmospheric dispersion model NAME coupled with emission inventories. Observed net biospheric uptake in June–July is not well correlated with simulations using the SMURF model with NAME. The results show the partitioning of fossil and biospheric CO2 and CH4 in cities can be evaluated and improved with 14C observations when the nuclear power plants influence is negligible.
3D GUMICS Simulations of Northward IMF Magnetotail Structure
Authors: Fryer L. J. , Fear R. C. , Gingell I. L. , Coxon J. C. , Palmroth M. , Hoilijoki S. , Janhunen P. , Kullen A. , Cassak P. A.
Published: July 2023

This study presents a re‐evaluation of the Kullen and Janhunen (2004, https://doi.org/10.5194/angeo-22-951-2004) global northward interplanetary magnetic field (IMF) simulation, using the Grand Unified Magnetosphere–Ionosphere Coupling Simulation version 4 (GUMICS‐4), a global MHD model. We investigate the dynamic coupling between northward IMF conditions and the Earth’s magnetotail and compare the results to observation‐based mechanisms for the formation of transpolar arcs. The results of this study reveal that under northward IMF conditions (and northward IMF initialization), a large closed field line region forms in the magnetotail, with similarities to transpolar arc structures observed from spacecraft data. This interpretation is supported by the simultaneous increase of closed flux measured in the magnetotail. However, the reconnection configuration differs in several respects from previously theorized magnetotail structures that have been inferred from both observations and simulations results and associated with transpolar arcs. We observe that dawn–dusk lobe regions form as a result of high‐latitude reconnection during the initialization stages, which later come into contact as the change in the IMF By component causes the magnetotail to twist. We conclude that in the GUMICS simulation, transpolar arc‐like structures are formed as a result of reconnection in the magnetotail, rather than high‐latitude reconnection or due to the mapping of the plasma sheet through a twisted magnetotail as interpreted from previous analysis of GUMICS simulations.
Decadal Indian Ocean Influence on the ENSO‐Indian Monsoon Teleconnection Mostly Apparent
Authors: Bódai Tamás , Aneesh Sundaresan , Lee June‐Yi , Lee Sun‐Seon
Published: July 2023

“Decadal influence” on the El Niño–Southern Oscillation‐Indian summer monsoon teleconnection has been much studied but with plurality and ambiguity about the concept of influence. Here (a) we provide formal definitions of the apparent influence of a specific factor on the teleconnection, as correlation coefficients, which enable us to test them as null‐hypotheses. Using the recently released Community Earth System Model v2 Large Ensemble data, we show that a 50% chance for the detection of the apparent Indian Ocean influence under stationary conditions might take 2,000 years of data. However, (b) we find that this influence is mostly apparent, causally not dominant, indeed, as it originates more dominantly from fluctuations of the decadal moving window El Niño–Southern Oscillation variability, which causally influences an Indian Ocean Dipole‐like moving window mean state. (c) We also show that unattributed so‐called “decadal influence,” defined as a deviation from a linear regression model of the teleconnection as a null‐hypothesis, cannot be detected in twentieth century observations in South Asia even regionally. However, as a new insight, we find our new simple influence concept as a significant correlation coefficient to be possibly consistent with such a null‐hypothesis.
Tree‐Ring Derived Avalanche Frequency and Climate Associations in a High‐Latitude, Maritime Climate
Authors: Peitzsch E. H. , Hood E. , Harley J. R. , Stahle D. K. , Kichas N. E. , Wolken G. J.
Published: July 2023

Snow avalanches are a natural hazard in mountainous areas worldwide with severe impacts that include fatalities, damage to infrastructure, disruption to commerce, and landscape disturbance. Understanding long‐term avalanche frequency patterns, and associated climate and weather influences, improves our understanding of how climate change may affect avalanche activity. We used dendrochronological techniques to evaluate the historical frequency of large magnitude avalanches (LMAs) in the high‐latitude climate of southeast Alaska, United States. We collected 434 cross sections throughout six avalanche paths near Juneau, Alaska. This resulted in 2706 identified avalanche growth disturbances between 1720 and 2018, which allowed us to reconstruct 82 years with LMA activity across three sub‐regions. By combining this tree‐ring‐derived avalanche data set with a suite of climate and atmospheric variables and applying a generalized linear model to fit a binomial regression, we found that February and March precipitation and the Oceanic Niño Index (ONI) were significant predictors of LMA activity in the study area. Specifically, LMA activity occurred during winters with substantial February and March precipitation and neutral or negative (cold) ONI values, while years not characterized by LMAs occur more frequently during warm winters (positive ONI values). Our examination of the climate‐avalanche relationship in southeast Alaska sheds light on important climate variables and physical processes associated with LMA years. These results can be used to inform long‐term infrastructure planning and avalanche mitigation operations in an urban area, such as Juneau, where critical infrastructure is subject to substantial avalanche hazard.
ChatGPT for shaping the future of dentistry: the potential of multi-modal large language model
Authors: Huang Hanyao , Zheng Ou , Wang Dongdong , Yin Jiayi , Wang Zijin , Ding Shengxuan , Yin Heng , Xu Chuan , Yang Renjie , Zheng Qian , Shi Bing
Published: July 2023

The ChatGPT, a lite and conversational variant of Generative Pretrained Transformer 4 (GPT-4) developed by OpenAI, is one of the milestone Large Language Models (LLMs) with billions of parameters. LLMs have stirred up much interest among researchers and practitioners in their impressive skills in natural language processing tasks, which profoundly impact various fields. This paper mainly discusses the future applications of LLMs in dentistry. We introduce two primary LLM deployment methods in dentistry, including automated dental diagnosis and cross-modal dental diagnosis, and examine their potential applications. Especially, equipped with a cross-modal encoder, a single LLM can manage multi-source data and conduct advanced natural language reasoning to perform complex clinical operations. We also present cases to demonstrate the potential of a fully automatic Multi-Modal LLM AI system for dentistry clinical application. While LLMs offer significant potential benefits, the challenges, such as data privacy, data quality, and model bias, need further study. Overall, LLMs have the potential to revolutionize dental diagnosis and treatment, which indicates a promising avenue for clinical application and research in dentistry.
N-Acetyltransferase 9 ameliorates Aβ42-mediated neurodegeneration in the Drosophila eye
Authors: Deshpande Prajakta , Chimata Anuradha Venkatakrishnan , Snider Emily , Singh Aditi , Kango-Singh Madhuri , Singh Amit
Published: July 2023

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, manifests as accumulation of amyloid-beta-42 (Aβ42) plaques and intracellular accumulation of neurofibrillary tangles (NFTs) that results in microtubule destabilization. Targeted expression of human Aβ42 (GMR > Aβ42) in developing Drosophila eye retinal neurons results in Aβ42 plaque(s) and mimics AD-like extensive neurodegeneration. However, there remains a gap in our understanding of the underlying mechanism(s) for Aβ42-mediated neurodegeneration. To address this gap in information, we conducted a forward genetic screen, and identified N-acetyltransferase 9 (Mnat9) as a genetic modifier of GMR > Aβ42 neurodegenerative phenotype. Mnat9 is known to stabilize microtubules by inhibiting c-Jun-N- terminal kinase (JNK) signaling. We found that gain-of-function of Mnat9 rescues GMR > Aβ42 mediated neurodegenerative phenotype whereas loss-of-function of Mnat9 exhibits the converse phenotype of enhanced neurodegeneration. Here, we propose a new neuroprotective function of Mnat9 in downregulating the JNK signaling pathway to ameliorate Aβ42-mediated neurodegeneration, which is independent of its acetylation activity. Transgenic flies expressing human NAT9 (hNAT9), also suppresses Aβ42-mediated neurodegeneration thereby suggesting functional conservation in the interaction of fly Mnat9 or hNAT9 with JNK-mediated neurodegeneration. These studies add to the repertoire of molecular mechanisms that mediate cell death response following accumulation of Aβ42 and may provide new avenues for targeting neurodegeneration.
UCHL1 facilitates protein aggregates clearance to enhance neural stem cell activation in spinal cord injury
Authors: Ding Lu , Chu Weiwei , Xia Yu , Shi Ming , Li Tian , Zhou Feng-Quan , Deng David Y. B.
Published: July 2023

Activation of endogenous neural stem cells (NSCs) is greatly significant for the adult neurogenesis; however, it is extremely limited in the spinal cord after injury. Recent evidence suggests that accumulation of protein aggregates impairs the ability of quiescent NSCs to activate. Ubiquitin c-terminal hydrolase l-1 (UCHL1), an important deubiquitinating enzyme, plays critical roles in protein aggregations clearance, but its effects on NSC activation remains unknown. Here, we show that UCHL1 promotes NSC activation by clearing protein aggregates through ubiquitin-proteasome approach. Upregulation of UCHL1 facilitated the proliferation of spinal cord NSCs after spinal cord injury (SCI). Based on protein microarray analysis of SCI cerebrospinal fluid, it is further revealed that C3+ neurotoxic reactive astrocytes negatively regulated UCHL1 and proteasome activity via C3/C3aR signaling, led to increased abundances of protein aggregations and decreased NSC proliferation. Furthermore, blockade of reactive astrocytes or C3/C3aR pathway enhanced NSC activation post-SCI by reserving UCHL1 and proteasome functions. Together, this study elucidated a mechanism regulating NSC activation in the adult spinal cord involving the UCHL1-proteasome approach, which may provide potential molecular targets and new insights for NSC fate regulation.
Administration of AG490 decreases the senescence of umbilical cord-mesenchymal stem cells and promotes the cytotherapeutic effect in liver fibrosis
Authors: Jiang Chenhao , Chen Huaxin , Kang Yinqian , He Xinyi , Huang Jianyang , Lu Tongyu , Sui Xin , Chen Haitian , Xiao Jiaqi , Zhang Jiebin , Zhang Hanwen , Zheng Jun , Yang Yang , Yao Jia , Cai Jianye , Zhang Yingcai
Published: July 2023

The therapeutic potential of umbilical cord-mesenchymal stem cell (UC-MSC) transplantation in liver fibrosis has been highlighted. However, the fate of transplanted MSCs in the fibrotic microenvironment remains unclear. In this study, we aim to uncover the fate of transplanted MSCs and develop targeting strategies that could enhance the therapeutic efficacy of MSC therapy in liver fibrosis. We used human UC-MSCs as the study object. For in vitro experiments, we stimulated UC-MSCs with several fibrotic-related factors (Liver fibrotic Factors, LF), including TGFβ, TNFα and IFNγ for downstream investigations. We co-cultured LF-treated UC-MSCs with hepatic stellate cell line LX-2 to assess the anti-fibrotic effect. We showed that upon LF stimulation, UC-MSCs exhibited reduced anti-fibrotic activity and underwent rapid senescence. Pathway analysis showed that JAK/STAT3 signaling was highly activated upon LF stimulation, which significantly elevated senescence-associated secretory phenotype (SASP) and senescence in UC-MSCs and could be reversed by a specific JAK inhibitor AG490. Moreover, using both carbon tetrachloride (CCl4) and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induce fibrosis models, we demonstrated that AG490 pretreatment promoted UC-MSCs survival within the fibrotic liver microenvironment and exhibited enhance therapeutic efficacy. Overall, we showed that targeting MSC senescence in vivo through AG490 pretreatment could enhance the anti-fibrotic activities of UC-MSCs.
Research progress on post-translational modification of proteins and cardiovascular diseases
Authors: Cheng XueLi , Wang Kai , Zhao Yan , Wang Kun
Published: July 2023

Cardiovascular diseases (CVDs) such as atherosclerosis, myocardial remodeling, myocardial ischemia-reperfusion (I/R) injury, heart failure, and oxidative stress are among the greatest threats to human health worldwide. Cardiovascular pathogenesis has been studied for decades, and the influence of epigenetic changes on CVDs has been extensively studied. Post-translational modifications (PTMs), including phosphorylation, glycosylation, methylation, acetylation, ubiquitination, ubiquitin-like and nitrification, play important roles in the normal functioning of the cardiovascular system. Over the past decade, with the application of high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), an increasing number novel acylation modifications have been discovered, including propionylation, crotonylation, butyrylation, succinylation, lactylation, and isonicotinylation. Each change in protein conformation has the potential to alter protein function and lead to CVDs, and this process is usually reversible. This article summarizes the mechanisms underlying several common PTMs involved in the occurrence and development of CVDs.
Ionizing radiation triggers mitophagy to enhance DNA damage in cancer cells
Authors: Ren Yanxian , Yang Pengfei , Li Chenghao , Wang Wen-an , Zhang Tianyi , Li Jin , Li Haining , Dong Chunlu , Meng Wenbo , Zhou Heng
Published: July 2023

Radiotherapy is an important cancer treatment strategy that causes DNA damage in tumor cells either directly or indirectly. Autophagy is a physiological process linked to DNA damage. Mitophagy is a form of autophagy, which specifically targets and eliminates impaired mitochondria, thereby upholding cellular homeostasis. However, the connection between DNA damage and mitophagy has yet to be fully elucidated. We found that mitophagy, as an upstream signal, increases ionizing radiation-induced DNA damage by downregulating or overexpressing key mitophagy proteins Parkin and BNIP3. Enhancing the basal level of mitophagy in conjunction with X-ray irradiation can potentially diminish cell cycle arrest at the G2/M phase, substantially elevate the accumulation of γ-H2AX, 53BP1, and PARP1 foci within the nucleus, augment DNA damage, and facilitate the demise of tumor cells. Consequently, this approach prolongs the survival of melanoma-bearing mice. The findings of this study are anticipated to offer a therapeutic approach for enhancing the therapeutic effectiveness of radiotherapy.
Host susceptibility and structural and immunological insight of S proteins of two SARS-CoV-2 closely related bat coronaviruses
Authors: Ou Xiuyuan , Xu Ge , Li Pei , Liu Yan , Zan Fuwen , Liu Pan , Hu Jiaxin , Lu Xing , Dong Siwen , Zhou Yao , Mu Zhixia , Wu Zhiqiang , Wang Jianwei , Jin Qi , Liu Pinghuang , Lu Jian , Wang Xiangxi , Qian Zhaohui
Published: July 2023

The bat coronaviruses (CoV) BANAL-20-52 and BANAL-20-236 are two newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) closely related coronaviruses (SC2r-CoV) and the genome of BANAL-20-52 shares the highest homology with SARS-CoV-2. However, the risk of their potential zoonotic transmission has not been fully evaluated. Here, we determined their potential host susceptibility among 13 different bat species and 26 different animal species, and found that both might have extensive host ranges, indicating high zoonotic transmission potential. We also determined the cryo-EM structures of BANAL-20-52 and BANAL-20-236 S proteins at pH 5.5 and the complex of BANAL-20-236 S1 and Rhinolophus affinis ACE2, and found that both trimeric S proteins adopt all three receptor binding domains (RBDs) in “closed” conformation and are more compact than SARS-CoV-2. Strikingly, the unique sugar moiety at N370 of bat SC2r-CoVs acts like a “bolt” and crosses over two neighboring subunits, facilitating the S proteins in the locked conformation and underpinning the architecture stability. Removal of the glycosylation at N370 by a T372A substitution substantially enhances virus infectivity but becomes highly sensitive to trypsin digestion at pH 5.5, a condition roughly mimicking the insectivorous bat’s stomach digestion. In contrast, WT S proteins of SC2r-CoVs showed considerable resistance to trypsin digestion at pH 5.5, indicating that the highly conserved T372 in bat CoVs might result from the selective advantages in stability during the fecal-oral transmission over A372. Moreover, the results of cross-immunogenicity among S proteins of SARS-CoV-2, BANAL-20-52, and BANAL-20-236 showed that A372 pseudoviruses are more sensitive to anti-S sera than T372, indicating that immune evasion might also play a role in the natural selection of T372 over A372 during evolution. Finally, residues 493 and 498 of the S protein affect host susceptibility, and residue 498 also influences the immunogenicity of the S protein. Together, our findings aid a better understanding of the molecular basis of CoV entry, selective evolution, and immunogenicity and highlight the importance of surveillance of susceptible hosts of these viruses to prevent potential outbreaks.
Generation of out-of-plane polarized spin current by spin swapping
Authors: Hazra Binoy K. , Pal Banabir , Jeon Jae-Chun , Neumann Robin R. , Göbel Börge , Grover Bharat , Deniz Hakan , Styervoyedov Andriy , Meyerheim Holger , Mertig Ingrid , Yang See-Hun , Parkin Stuart S. P.
Published: July 2023

The generation of spin currents and their application to the manipulation of magnetic states is fundamental to spintronics. Of particular interest are chiral antiferromagnets that exhibit properties typical of ferromagnetic materials even though they have negligible magnetization. Here, we report the generation of a robust spin current with both in-plane and out-of-plane spin polarization in epitaxial thin films of the chiral antiferromagnet Mn3Sn in proximity to permalloy thin layers. By employing temperature-dependent spin-torque ferromagnetic resonance, we find that the chiral antiferromagnetic structure of Mn3Sn is responsible for an in-plane polarized spin current that is generated from the interior of the Mn3Sn layer and whose temperature dependence follows that of this layer’s antiferromagnetic order. On the other hand, the out-of-plane polarized spin current is unrelated to the chiral antiferromagnetic structure and is instead the result of scattering from the Mn3Sn/permalloy interface. We substantiate the later conclusion by performing studies with several other non-magnetic metals all of which are found to exhibit out-of-plane polarized spin currents arising from the spin swapping effect.
NPC1-dependent alterations in KV2.1–CaV1.2 nanodomains drive neuronal death in models of Niemann-Pick Type C disease
Authors: Casas Maria , Murray Karl D. , Hino Keiko , Vierra Nicholas C. , Simó Sergi , Trimmer James S. , Dixon Rose E. , Dickson Eamonn J.
Published: July 2023

Lysosomes communicate through cholesterol transfer at endoplasmic reticulum (ER) contact sites. At these sites, the Niemann Pick C1 cholesterol transporter (NPC1) facilitates the removal of cholesterol from lysosomes, which is then transferred to the ER for distribution to other cell membranes. Mutations in NPC1 result in cholesterol buildup within lysosomes, leading to Niemann-Pick Type C (NPC) disease, a progressive and fatal neurodegenerative disorder. The molecular mechanisms connecting NPC1 loss to NPC-associated neuropathology remain unknown. Here we show both in vitro and in an animal model of NPC disease that the loss of NPC1 function alters the distribution and activity of voltage-gated calcium channels (CaV). Underlying alterations in calcium channel localization and function are KV2.1 channels whose interactions drive calcium channel clustering to enhance calcium entry and fuel neurotoxic elevations in mitochondrial calcium. Targeted disruption of KV2–CaVinteractions rescues aberrant CaV1.2 clustering, elevated mitochondrial calcium, and neurotoxicity in vitro. Our findings provide evidence that NPC is a nanostructural ion channel clustering disease, characterized by altered distribution and activity of ion channels at membrane contacts, which contribute to neurodegeneration.
Subunit gating resulting from individual protonation events in Kir2 channels
Authors: Maksaev Grigory , Bründl-Jirout Michael , Stary-Weinzinger Anna , Zangerl-Plessl Eva-Maria , Lee Sun-Joo , Nichols Colin G.
Published: July 2023

Inwardly rectifying potassium (Kir) channels open at the ‘helix bundle crossing’ (HBC), formed by the M2 helices at the cytoplasmic end of the transmembrane pore. Introduced negative charges at the HBC (G178D) in Kir2.2 channels forces opening, allowing pore wetting and free movement of permeant ions between the cytoplasm and the inner cavity. Single-channel recordings reveal striking, pH-dependent, subconductance behaviors in G178D (or G178E and equivalent Kir2.1[G177E]) mutant channels, with well-resolved non-cooperative subconductance levels. Decreasing cytoplasmic pH shifts the probability towards lower conductance levels. Molecular dynamics simulations show how protonation of Kir2.2[G178D], or the D173 pore-lining residues, changes solvation, K+ ion occupancy, and K+ conductance. Ion channel gating and conductance are classically understood as separate processes. The present data reveal how individual protonation events change the electrostatic microenvironment of the pore, resulting in step-wise alterations of ion pooling, and hence conductance, that appear as ‘gated’ substates.
Enantioselectivity of discretized helical supramolecule consisting of achiral cobalt phthalocyanines via chiral-induced spin selectivity effect
Authors: Aizawa Hiroki , Sato Takuro , Maki-Yonekura Saori , Yonekura Koji , Takaba Kiyofumi , Hamaguchi Tasuku , Minato Taketoshi , Yamamoto Hiroshi M.
Published: July 2023

Enantioselectivity of helical aggregation is conventionally directed either by its homochiral ingredients or by introduction of chiral catalysis. The fundamental question, then, is whether helical aggregation that consists only of achiral components can obtain enantioselectivity in the absence of chiral catalysis. Here, by exploiting enantiospecific interaction due to chiral-induced spin selectivity (CISS) that has been known to work to enantio-separate a racemic mixture of chiral molecules, we demonstrate the enantioselectivity in the assembly of mesoscale helical supramolecules consisting of achiral cobalt phthalocyanines. The helical nature in our supramolecules is revealed to be mesoscopically incorporated by dislocation-induced discretized twists, unlike the case of chiral molecules whose chirality are determined microscopically by chemical bond. The relevance of CISS effect in the discretized helical supramolecules is further confirmed by the appearance of spin-polarized current through the system. These observations mean that the application of CISS-based enantioselectivity is no longer limited to systems with microscopic chirality but is expanded to the one with mesoscopic chirality.
Affinity-matured homotypic interactions induce spectrum of PfCSP structures that influence protection from malaria infection
Authors: Martin Gregory M. , Torres Jonathan L. , Pholcharee Tossapol , Oyen David , Flores-Garcia Yevel , Gibson Grace , Moskovitz Re’em , Beutler Nathan , Jung Diana D. , Copps Jeffrey , Lee Wen-Hsin , Gonzalez-Paez Gonzalo , Emerling Daniel , MacGill Randall S. , Locke Emily , King C. Richter , Zavala Fidel , Wilson Ian A. , Ward Andrew B.
Published: July 2023

The generation of high-quality antibody responses to Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP), the primary surface antigen of Pf sporozoites, is paramount to the development of an effective malaria vaccine. Here we present an in-depth structural and functional analysis of a panel of potent antibodies encoded by the immunoglobulin heavy chain variable (IGHV) gene IGHV3-33, which is among the most prevalent and potent antibody families induced in the anti-PfCSP immune response and targets the Asn-Ala-Asn-Pro (NANP) repeat region. Cryo-electron microscopy (cryo-EM) reveals a remarkable spectrum of helical antibody-PfCSP structures stabilized by homotypic interactions between tightly packed fragments antigen binding (Fabs), many of which correlate with somatic hypermutation. We demonstrate a key role of these mutated homotypic contacts for high avidity binding to PfCSP and in protection from Pf malaria infection. Together, these data emphasize the importance of anti-homotypic affinity maturation in the frequent selection of IGHV3–33 antibodies and highlight key features underlying the potent protection of this antibody family.
Elucidating electrochemical nitrate and nitrite reduction over atomically-dispersed transition metal sites
Authors: Murphy Eamonn , Liu Yuanchao , Matanovic Ivana , Rüscher Martina , Huang Ying , Ly Alvin , Guo Shengyuan , Zang Wenjie , Yan Xingxu , Martini Andrea , Timoshenko Janis , Cuenya Beatriz Roldán , Zenyuk Iryna V. , Pan Xiaoqing , Spoerke Erik D. , Atanassov Plamen
Published: July 2023

Electrocatalytic reduction of waste nitrates (NO3−) enables the synthesis of ammonia (NH3) in a carbon neutral and decentralized manner. Atomically dispersed metal-nitrogen-carbon (M-N-C) catalysts demonstrate a high catalytic activity and uniquely favor mono-nitrogen products. However, the reaction fundamentals remain largely underexplored. Herein, we report a set of 14; 3d-, 4d-, 5d- and f-block M-N-C catalysts. The selectivity and activity of NO3− reduction to NH3 in neutral media, with a specific focus on deciphering the role of the NO2− intermediate in the reaction cascade, reveals strong correlations (R=0.9) between the NO2− reduction activity and NO3− reduction selectivity for NH3. Moreover, theoretical computations reveal the associative/dissociative adsorption pathways for NO2− evolution, over the normal M-N4 sites and their oxo-form (O-M-N4) for oxyphilic metals. This work provides a platform for designing multi-element NO3RR cascades with single-atom sites or their hybridization with extended catalytic surfaces.