bluuebunny/crossref_metadata_2025 huggingface dataset:
Designing organised clusters as social actors: a meta-organisational approach
Authors: Lupova-Henry Evgeniya , Blili Sam , Dal Zotto Cinzia
Published: January 2021

In this paper, we aim at exploring whether and how ‘organised’ clusters can be conceived of as deliberate actors within their contexts. Seeing such clusters as meta-organisations, we suggest that these can make ‘organisationality’ design choices, or decisions regarding full or partial implementation of the five elements constitutive of formal organisations: membership, hierarchy, rules, monitoring, and sanctions. To explore the relationship between clusters’ organisationality and actorhood, we conduct two qualitative case studies of organised clusters in Australia. Our findings suggest that clusters can deliberately ‘construct’ themselves both as organisations and social actors. Furthermore, drawing upon the institutional work perspective, we propose that clusters can engage in deliberate identity, boundary, and practice work. However, in doing so, they address both internal and external legitimating audiences. Finally, our findings suggest that clusters’ organisationality design choices may influence the locus of their actorhood resulting in more or less collaborative approaches to institutional work.
Ecological risk assessment of heavy metal-contaminated soils of selected villages in Zamfara State, Nigeria
Authors: Yahaya Sharhabil Musa , Abubakar Fatima , Abdu Nafiu
Published: January 2021

The incidence of heavy metal contamination in Zamfara State, northern Nigeria, due to artisanal mining in some villages has resulted in the pollution of a vast area of land and water. This study evaluated the extent of environmental risks caused by heavy metals. It involved five (5) villages (Bagega, Dareta, Sunke, Tunga, and Abare) where mining activities were taking place and Anka town with no record of mining activities served as control. In each of the five villages, three sites (3) were identified as a mining site, processing site, and village making a total of sixteen (16) sites. Bulked soil samples were collected in triplicate and analyzed for iron, lead, cadmium, chromium, zinc, and nickel using flame atomic absorption spectrophotometry. Measured concentrations of the heavy metals in soils were then used to calculate the pollution and ecological risk pose by heavy metals. Their concentrations were in the order Fe > Pb > Cr > Zn > Cd > Ni, with Pb and Cd having a concentration higher than permissible levels for soils and accounted for 98.64% of the total potential ecological risk. Also, all the different pollution indices examined showed that all the sites were polluted with Cd, and all the processing sites were polluted with Pb. This reveals that processing sites pose more risk to heavy metal contamination. Correlation analysis showed a highly significant (p < 0.001) positive correlation between Pb and Zn, Cr and Ni, and a significant (p < 0.01) positive correlation between Fe and Pb, Zn and Cr. The principal component analysis suggested that Pb, Zn, Cr, and Ni likely originated from the same source, i.e., mining activities, and Fe and Cd originated from the abundant parent material in the study area.
Cyber-Physical Systems for Micro-/Nano-assembly Operations: a Survey
Authors: Mulet Alberola Jose A , Fassi Irene
Published: January 2021

Purpose of Review

Latest requirements of the global market force manufacturing systems to a change for a new production paradigm (Industry 4.0). Cyber-Physical Systems (CPS) appear as a solution to be deployed in different manufacturing fields, especially those with high added value and technological complexity, high product variants, and short time to market. In this sense, this paper aims at reviewing the introduction level of CPS technologies in micro/nano-manufacturing and how these technologies could cope with these challenging manufacturing requirements.

Recent Findings

The introduction of CPS is still in its infancy on many industrial applications, but it actually demonstrates its potential to support future manufacturing paradigm. However, only few research works in micro/nano-manufacturing considered CPS frameworks, since the concept barely appeared a decade ago.

Some contributions have revealed the potential of CPS technologies to improve manufacturing performance which may be scaled to the micro/nano-manufacturing. IoT-based frameworks with VR/AR technologies allow distributed and collaborative systems, or agent-based architectures with advance algorithm implementations that improve the flexibility and performance of micro-/nano-assembly operations. Future research of CPS in micro-/nano-assembly operations should be followed by more studies of its technical deployment showing its implications under other perspectives, i.e. sustainable, economic, and social point of views, to take full advance of all its features.
Health as a Human Right
Authors: Ferraz Octávio Luiz Motta
Published: January 2021

Does human rights law work? This book engages in this heated debate through a detailed analysis of thirty years of the right to health - perhaps the most complex human right - in Brazil. Are Brazilians better off three decades after the enactment of the right to health in the 1988 Constitution? Has the flurry of litigation experienced in Brazil helped or harmed the majority of the population? This book offers an in-depth analysis of these complex and controversial questions grounded on a wealth of empirical data. The book covers the history of the recognition of health as a human right in the 1988 Constitution through the Sanitary Movement's campaign and the subsequent three decades of what Ferraz calls the politics and judicialization of health. It challenges positions of both optimists and sceptics of human rights law and will be of interest to those looking for a more nuanced analysis.
Bluestockings and Travel Accounts
Authors: Voloshkova Nataliia
Published: January 2021

This Element proposes to relate the eighteenth-century world of travel and travel writing with the bluestocking salon. It locates eminent British travellers and explorers in the female-presided intellectual space and examines their multifaceted interaction with the bluestockings between 1760 and 1799. The study shows how the bluestockings acquired knowledge of the world through reading, discussing, writing and collecting travel accounts. It explores the 'social life' of manuscript and printed travel texts in the circle, their popularity and impact on the bluestockings. This Element builds upon the body of evidence provided by their published and unpublished diaries, correspondence and private library catalogues.
Action and Inaction in a Social World
Authors: Albarracín Dolores
Published: January 2021

This book explains how actions and inactions arise and change in social contexts, including social media and face-to-face communication. Its multidisciplinary perspective covers research from psychology, communication, public health, business studies, and environmental sciences. The reader can use this cutting-edge approach to design and interpret effects of behavioral change interventions as well as replicate the materials and methods implemented to study them. The author provides an organized set of principles that take the reader from the formation of attitudes and goals, to the structure of action and inaction. It also reflects on how cognitive processes explain excesses of action while inaction persists elsewhere. This practical guide summarises the best practices persuasion and behavioral interventions to promote changes in health, consumer, and social behaviors.
The Frontier Complex
Authors: Gardner Kyle J.
Published: January 2021

Kyle J. Gardner reveals the transformation of the historical Himalayan entrepôt of Ladakh into a modern, disputed borderland through an examination of rare British, Indian, Ladakhi, and Kashmiri archival sources. In so doing, he provides both a history of the rise of geopolitics and the first comprehensive history of Ladakh's encounter with the British Empire. He examines how colonial border-making practices transformed geography into a political science and established principles that a network of imperial frontier experts would apply throughout the empire and bequeath to an independent India. Through analyzing the complex of imperial policies and practices, The Frontier Complex reveals how the colonial state transformed, and was transformed by, new ways of conceiving of territory. Yet, despite a century of attempts to craft a suitable border, the British failed. The result is an imperial legacy still playing out across the Himalayas.
Cosmic Messengers
Authors: Harwit Martin
Published: January 2021

Martin Harwit, author of the influential book Cosmic Discovery, asks key questions about the scope of observational astronomy. Humans have long sought to understand the world we inhabit. Recent realization of how our unruly Universe distorts information before it ever reaches us reveals distinct limits on how well we will ultimately understand the Cosmos. Even the best instruments we might conceive will inevitably be thwarted by ever more complex distortions and will never untangle the data completely. Observational astronomy, and the cost of pursuing it, will then have reached an inherent end. Only some totally different lines of approach, as yet unknown and potentially far more costly, might then need to emerge if we wish to learn more. This accessible book is written for all astronomers, astrophysicists, and those curious about how well we will ever understand the Universe and the potential costs of pushing those limits.
Black Resettlement and the American Civil War
Authors: Page Sebastian N.
Published: January 2021

Based on sweeping research in six languages, Black Resettlement and the American Civil War offers the first comprehensive, comparative account of nineteenth-century America's greatest road not taken: the mass resettlement of African Americans outside the United States. Building on resurgent scholarly interest in the so-called 'colonization' movement, the book goes beyond tired debates about colonization's place in the contest over slavery, and beyond the familiar black destinations of Liberia, Canada, and Haiti. Striding effortlessly from Pittsburgh to Panama, Toronto to Trinidad, and Lagos to Louisiana, it synthesizes a wealth of individual, state-level, and national considerations to reorient the field and set a new standard for Atlantic history. Along the way, it shows that what haunted politicians from Thomas Jefferson to Abraham Lincoln was not whether it was right to abolish slavery, but whether it was safe to do so unless the races were separated.
Defending Joint Acceptance Accounts of Justification
Authors: Schwengerer Lukas
Published: January 2021

Jennifer Lackey (2016) challenged group acceptance accounts of justification by arguing that these accounts make the possession of evidence arbitrary and hence lead to illegitimate manipulation of the group's evidence. She proposes that the only way out is to rely on the epistemic propriety of the individual group members, which leads to a dilemma for group acceptance views: either they are wrong about justification, or they cease to rely only on group acceptances. I argue that there is a third option based on general expectations of epistemic propriety that restricts the group's maximal justification. A group cannot be more justified than any individual in the group's position could be expected to be. I motivate this solution by a discussion of normative defeat and epistemic expectations as proposed by Goldberg (2018).
Data Protection Commissioner v. Facebook Ireland Ltd. and Maximillian Schrems (C.J.E.U.)
Authors: Aktipis Michael S. , Katwan Ron B.
Published: January 2021

On July 16, 2020, the Court of Justice of the European Union (CJEU) issued its ruling in Data Protection Commissioner v. Facebook Ireland Limited and Maximillian Schrems, commonly known as Schrems II, invalidating the EU–U.S. Privacy Shield as a valid transfer mechanism under the EU's General Data Protection Regulation (GDPR) and creating significant legal uncertainty for the continued availability of another widely used transfer mechanism, Standard Contractual Clauses (SCCs), for transfers of EU personal data from commercial entities in the EU to the United States. The widely anticipated ruling marked the second time in five years that the CJEU had invalidated the legal foundation for such data transfers, which in both cases had been the result of a carefully negotiated compromise balancing European data privacy concerns with statutory and constitutional limitations of the U.S. system (see Schrems I).
A new epistemological case for theism
Authors: DE RAY CHRISTOPHE
Published: January 2021

Relying on inference to the best explanation (IBE) requires one to hold the intuition that the world is ‘intelligible’, that is, such that states of affairs at least generally have explanations for their obtaining. I argue that metaphysical naturalists are rationally required to withhold this intuition, unless they cease to be naturalists. This is because all plausible naturalistic aetiologies of the intuition entail that the intuition and the state of affairs which it represents are not causally connected in an epistemically appropriate way. Given that one ought to rely on IBE, naturalists are forced to pick the latter and change their world-view. Traditional theists, in contrast, do not face this predicament. This, I argue, is strong grounds for preferring traditional theism to naturalism.
Can Nepal achieve nutritional targets by 2030? A trend analysis of childhood undernutrition in Nepal from 2001 to 2016
Authors: Adhikari Sasmita Poudel , Zhou Huan , Adhikari Ramesh , Ye Ruixue , al-Zangabila Khaled , Wang Qingzhi , Sunil Thankam S
Published: January 2021

Objective:

This study assesses the prevalence of childhood undernutrition from 2001 to 2016 and estimate projections of undernutrition for 2016–2030 in Nepal.

Design:

The study used data from four rounds of a cross-sectional survey of Nepal Demographic and Health Survey (NDHS) conducted in 2001, 2006, 2011 and 2016. Descriptive analyses were conducted to calculate prevalence, binary logistic regression was used to test the significance of trends over time and autoregressive integrated moving average model was used to forecast the prevalence of childhood undernutrition.

Settings:

The children and household member datasets from four NDHS were merged to assess the trends of childhood undernutrition in Nepal.

Participants:

A total of 16 613 children (8399 male and 8214 female) under 5 years of age were selected for anthropometric measurements using a stratified cluster random sampling method.

Results:

Overall results show a decline in prevalence of stunting from 57·2 % to 35·8 % (P < 0·001), underweight from 42·7 % to 27 % (P < 0·001) and wasting from 11·2 % to 9·7 % (P < 0·05) from 2001 to 2016. However, different population subgroups have a higher prevalence of undernutrition than national average. Further, the analyses show that the prevalence of stunting will decline to 14·3 % and wasting to 8·4 % by 2030.

Conclusion:

A remarkable decrease in the prevalence of stunting and underweight has been observed over the last 15 years. Nepal is likely to achieve the nutritional targets for stunting but not for wasting by 2030. Given large subpopulation variations, further improvement in undernutrition require more specific, targeted and localised programmes.
Last Actor Standing Against Populism? The Role of the Catholic Church in Italy and its Defence of Social Assistance and Migration Policies
Authors: Pavolini Emmanuele , Arlotti Marco , Ascoli Ugo
Published: January 2021

Churches’ positions and preferences in social policy are often described in the literature as fixed over time. The article challenges this assumption. In particular, it shows how the Italian Catholic Church (CC) changed over time its position toward social assistance and migration policies. In relation to social assistance, the CC has shifted from an antagonist approach to public intervention to the support of a universal public minimum income scheme. At a time of increasing aversion towards migrants, the Catholic Church has also become one of the few core actors in Italian society advocating explicitly for more welcoming migration policies and criticising national governments, especially the populist ones. Four factors explain these changes: the way institutions have worked in this policy field, CC material interests, how new ideas on social rights and social justice have been re-elaborated within the CC and its moral authority in politics.
Hope as a Process in Understanding Positive Mood and Suicide Protection
Authors: Chang Edward C. , Jiang Xinying , Tian Weiyi , Yi Shangwen , Liu Jiting , Liang Pengwei , Liang Yongyi , Lai Siyu , Shi Xiaoxuan , Li Mingqi , Chang Olivia D. , Hirsch Jameson K.
Published: January 2021

Abstract. Background: According to the broaden-and-build model of positive mood, positive emotions are believed to broaden cognition resources and build psychological resiliency, to help incur positive psychological outcomes. Aim: We examined hope as a potential mediator of the association between positive mood and suicide protection (viz., life satisfaction and reasons for living) in adults. We hypothesized that positive mood would be associated with greater suicide protection through broadening hope agency and building hope pathways. Method: A sample of 320 college students completed measures of positive emotions, hope, and suicide protection. Results: Results from bootstrapped mediation testing indicated that hope agency, but not hope pathways, partially or fully mediated the relationship between positive mood and suicide protection. Limitations: It is not clear whether these findings are generalizable to a more diverse adult population. Also, it is not possible to rule out alternative causal models involving positive emotions and suicide protection. Conclusion: These findings provide some promising preliminary evidence for how positive emotions might help build hope agency to foster greater suicide protection in adults.
Implementation of a Pilot SMS-Based Crisis Support Service in Australia
Authors: Fildes Dave , Williams Kathryn , Bradford Sally , Grootemaat Pam , Kobel Conrad , Gordon Rob
Published: January 2021

Abstract. Background: Australia's first short message service (SMS) crisis support service was launched by Lifeline Australia in July 2018. The pilot program was independently evaluated over a 240-day period. Aims: We aimed to examine the experiences of key staff employed in the Lifeline Text pilot and identify the skills and types of support required to deliver a high-quality SMS-based crisis support service. Method: In total, 22 interviews were conducted with 14 Lifeline Text crisis supporters and in-shift supervisors (supervisors) at two time points in September 2018 and March 2019. A modified framework approach was adopted to undertake qualitative data analyses. Results: Delivering crisis support via text was initially challenging as a result of the need to translate skills from telephone crisis support to the SMS platform. This was compounded by the high degree of suicidality of help-seekers and volatility in demand for the service. Limitations: The independent evaluators were not involved in the design of the pilot. Conclusion: Lifeline text is providing an important and necessary service, using a novel mode of delivery in Australia. Maintaining service quality at peak demand, with many distressed and suicidal help-seekers, requires specialized training, experience, and exceptional skills.
The Delayed Ionospheric Response to the 27‐day Solar Rotation Period Analyzed With GOLD and IGS TEC Data
Authors: Schmölter Erik , Berdermann Jens , Codrescu Mihail
Published: January 2021

The delayed ionospheric response is analyzed for two well‐defined 27‐day solar rotation periods in the year 2019 with solar radio flux index F10.7 and Global‐scale Observations of the Limb and Disk (GOLD) data, like solar extreme ultraviolet (EUV) flux proxy, O/N2 column density ratio and peak electron density, as well as International Global Navigation Satellite System Service rapid high‐rate total electron content (TEC) map data. Although the correlation between GOLD solar EUV flux proxy and TEC is similar to the correlation between F10.7 and TEC, it is shown that the estimated delays based on GOLD data are in much better agreement with recent studies using EUV measurements compared to the delays based on F10.7 data. The GOLD peak electron density correlates well with TEC and allows insight to a local time interval when the ionosphere is not controlled by solar activity changes (17:00 LT to 21:00 LT). The present study investigates the impact of the solar activity (F10.7, GOLD EUV flux proxy) and O/N2 column density ratio on the ionospheric delay for two representative solar rotation periods. The capabilities of GOLD data for future research on the ionospheric response to the 27‐day solar rotation period are demonstrated and discussed. These results are crucial information for precise ionospheric models and forecasts.
A Lagrangian Perspective on Tropical Anvil Cloud Lifecycle in Present and Future Climate
Authors: Gasparini Blaž , Rasch Philip J. , Hartmann Dennis L. , Wall Casey J. , Dütsch Marina
Published: January 2021

The evolution of tropical anvil clouds from their origin in deep convective cores to their slow decay determines the climatic effects of clouds in tropical convective regions. Despite the relevance of anvil clouds for climate and responses of clouds to global warming, processes dominating their evolution are not well understood. Currently available observational data reveal instantaneous snapshots of anvil cloud properties, but cannot provide a process‐based perspective on anvil evolution. We therefore conduct simulations with the high resolution version of the exascale earth system model in which we track mesoscale convective systems over the tropical Western Pacific and compute trajectories that follow air parcels detrained from peaks of convective activity. With this approach we gain new insight into the anvil cloud evolution both in present day and future climate.

Comparison with geostationary satellite data shows that the model is able to simulate maritime mesoscale convective systems reasonably well. Trajectory results indicate that anvil cloud lifetime is about 15 h with no significant change in a warmer climate. The anvil ice mixing ratio is larger in a warmer climate due to a larger source of ice by detrainment and larger depositional growth leading to a more negative net cloud radiative effect along detrained trajectories. However, the increases in sources are counteracted by increases in sinks of ice, particularly snow formation and sedimentation. Furthermore, we find that the mean anvil cloud feedback along trajectories is positive and consistent with results from more traditional cloud feedback calculation methods.
Regional Exhumation and Tectonic History of the Shanxi Rift and Taihangshan, North China
Authors: Clinkscales Christopher , Kapp Paul , Thomson Stuart , Wang Houqi , Laskowski Andrew , Orme Devon A. , Pullen Alex
Published: January 2021

This study presents a comprehensive low‐temperature thermochronometric data set from the Shanxi Rift, Taihangshan, and eastern Ordos block in North China, including new apatite fission track and apatite (U‐Th‐Sm)/He data and published apatite and zircon fission track and (U‐Th‐Sm)/He data. We use these data and new thermal history inversion models to reveal that the Shanxi Rift and Taihangshan experienced an increase in cooling rates between ca. 110–70 Ma and ca. 50–30 Ma. A preceding ca. 160–135 Ma cooling event is generally restricted to the western rift margin in the Lüliangshan and Hengshan. In contrast, the ca. 50–30 Ma cooling event was widespread and occurred coevally with the opening of the Bohai Basin and slip across the NNE‐striking Eastern Taihangshan fault. In the southern rift zone, however, exhumation beginning ca. 50 Ma was likely associated with fault block uplift across the ESE–striking Qinling and Huashan faults, which accompanied the extensional opening of the Weihe Graben. Coeval fault slip along the NNE–striking Eastern Taihangshan faults and ESE–striking Qinling and Huashan faults was associated with NW‐SE extension in North China related to oblique subduction of the Pacific plate under Eastern Asia and slow convergence rates. The Shanxi Rift is commonly attributed to Late Miocene and younger extension, but our new thermochronologic data do not precisely record the onset of rifting. However, our inversion models do suggest ≤∼50°C of Neogene–Quaternary cooling, consistent with ≤∼2 km of footwall uplift across most range‐bounding faults.
Enhanced third-harmonic generation by manipulating the twist angle of bilayer graphene
Authors: Ha Seongju , Park Nam Hun , Kim Hyeonkyeong , Shin Jiseon , Choi Jungseok , Park Sungmin , Moon Ji-Yun , Chae Kwanbyung , Jung Jeil , Lee Jae-Hyun , Yoo Youngdong , Park Ji-Yong , Ahn Kwang Jun , Yeom Dong-Il
Published: January 2021

Twisted bilayer graphene (tBLG) has received substantial attention in various research fields due to its unconventional physical properties originating from Moiré superlattices. The electronic band structure in tBLG modified by interlayer interactions enables the emergence of low-energy van Hove singularities in the density of states, allowing the observation of intriguing features such as increased optical conductivity and photocurrent at visible or near-infrared wavelengths. Here, we show that the third-order optical nonlinearity can be considerably modified depending on the stacking angle in tBLG. The third-harmonic generation (THG) efficiency is found to significantly increase when the energy gap at the van Hove singularity matches the three-photon resonance of incident light. Further study on electrically tuneable optical nonlinearity reveals that the gate-controlled THG enhancement varies with the twist angle in tBLG, resulting in a THG enhanced up to 60 times compared to neutral monolayer graphene. Our results prove that the twist angle opens up a new way to control and increase the optical nonlinearity of tBLG, suggesting rotation-induced tuneable nonlinear optics in stacked two-dimensional material systems.
Interplay between Yersinia pestis and its flea vector in lipoate metabolism
Authors: Bouvenot Typhanie , Dewitte Amélie , Bennaceur Nadia , Pradel Elizabeth , Pierre François , Bontemps-Gallo Sébastien , Sebbane Florent
Published: January 2021

To thrive, vector-borne pathogens must survive in the vector’s gut. How these pathogens successfully exploit this environment in time and space has not been extensively characterized. Using Yersinia pestis (the plague bacillus) and its flea vector, we developed a bioluminescence-based approach and employed it to investigate the mechanisms of pathogenesis at an unprecedented level of detail. Remarkably, lipoylation of metabolic enzymes, via the biosynthesis and salvage of lipoate, increases the Y. pestis transmission rate by fleas. Interestingly, the salvage pathway’s lipoate/octanoate ligase LplA enhances the first step in lipoate biosynthesis during foregut colonization but not during midgut colonization. Lastly, Y. pestis primarily uses lipoate provided by digestive proteolysis (presumably as lipoyl peptides) rather than free lipoate in blood, which is quickly depleted by the vector. Thus, spatial and temporal factors dictate the bacterium’s lipoylation strategies during an infection, and replenishment of lipoate by digestive proteolysis in the vector might constitute an Achilles’ heel that is exploited by pathogens.
Cable bacteria extend the impacts of elevated dissolved oxygen into anoxic sediments
Authors: Liu Feifei , Wang Zhenyu , Wu Bo , Bjerg Jesper T , Hu Wenzhe , Guo Xue , Guo Jun , Nielsen Lars Peter , Qiu Rongliang , Xu Meiying
Published: January 2021

Profound biogeochemical responses of anoxic sediments to the fluctuation of dissolved oxygen (DO) concentration in overlaying water are often observed, despite oxygen having a limited permeability in sediments. This contradiction is indicative of previously unrecognized mechanism that bridges the oxic and anoxic sediment layers. Using sediments from an urban river suffering from long-term polycyclic aromatic hydrocarbons (PAHs) contamination, we analyzed the physicochemical and microbial responses to artificially elevated DO (eDO) in the overlying water over 9 weeks of incubation. Significant changes in key environmental parameters and microbial diversity were detected over the 0–6 cm sediment depth, along with accelerated degradation of PAHs, despite that eDO only increased the porewater DO in the millimeter subfacial layer. The dynamics of physicochemical and microbial properties coincided well with significantly increased presence of centimeter-long sulfide-oxidizing cable bacteria filaments under eDO, and were predominantly driven by cable bacteria metabolic activities. Phylogenetic ecological network analyses further revealed that eDO reinforced cable bacteria associated interspecific interactions with functional microorganisms such as sulfate reducers, PAHs degraders, and electroactive microbes, suggesting enhanced microbial syntrophy taking advantage of cable bacteria metabolism for the regeneration of SO42− and long-distance electron transfer. Together, our results suggest cable bacteria may mediate the impacts of eDO in anaerobic sediments by altering sediment physiochemical properties and by reinforcing community interactions. Our findings highlight the ecological importance of cable bacteria in sediments.
Pilot validation of blood-based biomarkers during pregnancy and postpartum in women with prior or current depression
Authors: Redei E. E. , Ciolino J. D. , Wert S. L. , Yang A. , Kim S. , Clark C. , Zumpf K. B. , Wisner K. L.
Published: January 2021

Major depressive disorder (MDD) is more common in women than in men, and evidence of gender-related subtypes of depression is emerging. Previously identified blood-based transcriptomic biomarkers distinguished male and female subjects with MDD from those without the disorder. In the present pilot study, we investigated the performance of these biomarkers in pregnant and postpartum women with prior major depressive episodes, some of whom had current symptomatology. The symptom scores of 13 pregnant and 15 postpartum women were identified by the Inventory of Depressive Symptoms (IDS-SR-30) at the time of blood sampling. Blood levels of the 20 transcriptomic biomarkers and that of estrogen receptor 2 (ESR2), membrane progesterone receptor alpha and beta (mPRα, mPRβ) were measured. In pregnant women, transcript levels of ADCY3, ASAH1, ATP11C, CDR2, ESR2, FAM46A, mPRβ, NAGA, RAPH1, TLR7, and ZNF291/SCAPER showed significant association with IDS-SR-30 scores, of which ADCY3, FAM46A, RAPH1, and TLR7 were identified in previous studies for their diagnostic potential for major depression. ASAH1 and ATP11C were previously also identified as potential markers of treatment efficacy. In postpartum women, transcript levels of CAT, CD59, and RAPH1 demonstrated a trend of association with IDS-SR-30 scores. Transcript levels of ADCY3, ATP11C, FAM46A, RAPH1, and ZNF291/SCAPER correlated with ESR2 and mPRβ expressions in pregnant women, whereas these associations only existed for mPRβ in postpartum women. These results suggest that a blood biomarker panel can identify depression symptomatology in pregnant women and that expression of these biomarker genes are affected by estrogen and/or progesterone binding differently during pregnancy and postpartum.
Maternal acute and chronic inflammation in pregnancy is associated with common neurodevelopmental disorders: a systematic review
Authors: Han Velda X. , Patel Shrujna , Jones Hannah F. , Nielsen Timothy C. , Mohammad Shekeeb S. , Hofer Markus J. , Gold Wendy , Brilot Fabienne , Lain Samantha J. , Nassar Natasha , Dale Russell C.
Published: January 2021

Inflammation is increasingly recognized as a cause or consequence of common problems of humanity including obesity, stress, depression, pollution and disease states such as autoimmunity, asthma, and infection. Maternal immune activation (MIA), triggered by both acute and systemic chronic inflammation, is hypothesized to be one of the mechanisms implicated in the pathogenesis of neurodevelopmental disorders (NDD). Although there is substantial preclinical evidence to support the MIA hypothesis, the human evidence is disparate. We performed a systematic review on human studies examining associations between maternal inflammatory states and offspring NDDs (autism spectrum disorder- ASD, attention deficit hyperactivity disorder-ADHD, Tourette syndrome-TS). 32 meta-analyses and 26 additional individual studies were identified. Maternal states associated with ASD include obesity, gestational diabetes mellitus, pre-eclampsia, pollution, stress, depression, autoimmune diseases, and infection. Maternal states associated with ADHD include obesity, pre-eclampsia, smoking, low socioeconomic status (SES), stress, autoimmune disease, and asthma. Maternal states associated with TS include low SES, depression, and autoimmune diseases. Diverse maternal inflammatory states in pregnancy are associated with common offspring NDDs. Given the increased prevalence of NDDs, there is urgent need to explore relative and cumulative maternal risk factors and disease mechanisms. Defining preventable risk factors in high-risk pregnancies could mitigate the expression and severity of NDDs.
EEF1A2 interacts with HSP90AB1 to promote lung adenocarcinoma metastasis via enhancing TGF-β/SMAD signalling
Authors: Jia Liqing , Ge Xiaolu , Du Chao , Chen Linna , Zhou Yanhong , Xiong Wei , Xiang Juanjuan , Li Guiyuan , Xiao Gaoming , Fang Li , Li Zheng
Published: January 2021

Background

Eukaryotic protein translation elongation factor 1α2 (EEF1A2) is an oncogene that promotes the progression of breast and pancreatic cancer. In this study, we aimed to elucidate the oncogenic function of EEF1A2 in the metastasis of lung adenocarcinoma (LUAD).

Methods

Immunohistochemistry and western blot were used to study EEF1A2 expression levels in LUAD tissues and cells, respectively. The role of EEF1A2 in LUAD progression were investigated in vitro and in vivo. We identified potential EEF1A2-binding proteins by liquid chromatography-electrospray mass spectrometry (LC-MS)/MS. Protein–protein interactions were determined by immunofluorescence and co-immunoprecipitation (Co-IP).

Results

In this study, we report that EEF1A2 mediates the epithelial–mesenchymal transformation (EMT), to promote the metastasis of LUAD cells in vitro and in vivo. Moreover, EEF1A2 interacts with HSP90AB1 to increase TGFβ Receptor (TβR)-I, and TβRII expression, followed by enhanced SMAD3 and pSMAD3 expression and nuclear localisation, which promotes the EMT of LUAD cells. Overexpression of EEF1A2 in cancer tissues is associated with poor prognosis and short survival of patients with LUAD.

Conclusions

These findings underscore the molecular functions of EEF1A2 in LUAD metastasis and indicate that EEF1A2 represents a promising target in the treatment of aggressive LUAD.
Acidic fibroblast growth factor attenuates type 2 diabetes-induced demyelination via suppressing oxidative stress damage
Authors: Li Rui , Wang Beini , Wu Chengbiao , Li Duohui , Wu Yanqing , Ye Libing , Ye Luxia , Chen Xiongjian , Li Peifeng , Yuan Yuan , Zhang Hongyu , Xie Ling , Li Xiaokun , Xiao Jian , Wang Jian
Published: January 2021

Prolonged type 2 diabetes mellitus (T2DM) produces a common complication, peripheral neuropathy, which is accompanied by nerve fiber disorder, axon atrophy, and demyelination. Growing evidence has characterized the beneficial effects of acidic fibroblast growth factor (aFGF) and shown that it relieves hyperglycemia, increases insulin sensitivity, and ameliorates neuropathic impairment. However, there is scarce evidence on the role of aFGF on remodeling of aberrant myelin under hyperglycemia condition. Presently, we observed that the expression of aFGF was rapidly decreased in a db/db T2DM mouse model. Administration of exogenous aFGF was sufficient to block acute demyelination and nerve fiber disorganization. Furthermore, this strong anti-demyelinating effect was most likely dominated by an aFGF-mediated increase of Schwann cell (SC) proliferation and migration as well as suppression of its apoptosis. Mechanistically, the beneficial biological effects of aFGF on SC behavior and abnormal myelin morphology were likely due to the inhibition of hyperglycemia-induced oxidative stress activation, which was most likely activated by kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid-derived-like 2 (Nrf2) signaling. Thus, this evidence indicates that aFGF is a promising protective agent for relieving myelin pathology through countering oxidative stress signaling cascades under diabetic conditions.
Nanohole-boosted electron transport between nanomaterials and bacteria as a concept for nano–bio interactions
Authors: Shi Tonglei , Hou Xuan , Guo Shuqing , Zhang Lei , Wei Changhong , Peng Ting , Hu Xiangang
Published: January 2021

Biofilms contribute to bacterial infection and drug resistance and are a serious threat to global human health. Antibacterial nanomaterials have attracted considerable attention, but the inhibition of biofilms remains a major challenge. Herein, we propose a nanohole-boosted electron transport (NBET) antibiofilm concept. Unlike known antibacterial mechanisms (e.g., reactive oxygen species production and cell membrane damage), nanoholes with atomic vacancies and biofilms serve as electronic donors and receptors, respectively, and thus boost the high electron transport capacity between nanomaterials and biofilms. Electron transport effectively destroys the critical components (proteins, intercellularly adhered polysaccharides and extracellular DNA) of biofilms, and the nanoholes also significantly downregulate the expression of genes related to biofilm formation. The anti-infection capacity is thoroughly verified both in vitro (human cells) and in vivo (rat ocular and mouse intestinal infection models), and the nanohole-enabled nanomaterials are found to be highly biocompatible. Importantly, compared with typical antibiotics, nanomaterials are nonresistant and thereby exhibit high potential for use in various applications. As a proof-of-principle demonstration, these findings hold promise for the use of NBET in treatments for pathogenic bacterial infection and antibiotic drug resistance.
The rise of angiosperms strengthened fire feedbacks and improved the regulation of atmospheric oxygen
Authors: Belcher Claire M. , Mills Benjamin J. W. , Vitali Rayanne , Baker Sarah J. , Lenton Timothy M. , Watson Andrew J.
Published: January 2021

The source of oxygen to Earth’s atmosphere is organic carbon burial, whilst the main sink is oxidative weathering of fossil carbon. However, this sink is to insensitive to counteract oxygen rising above its current level of about 21%. Biogeochemical models suggest that wildfires provide an additional regulatory feedback mechanism. However, none have considered how the evolution of different plant groups through time have interacted with this feedback. The Cretaceous Period saw not only super-ambient levels of atmospheric oxygen but also the evolution of the angiosperms, that then rose to dominate Earth’s ecosystems. Here we show, using the COPSE biogeochemical model, that angiosperm-driven alteration of fire feedbacks likely lowered atmospheric oxygen levels from ~30% to 25% by the end of the Cretaceous. This likely set the stage for the emergence of closed-canopy angiosperm tropical rainforests that we suggest would not have been possible without angiosperm enhancement of fire feedbacks.
Preclinical assessment of the efficacy and specificity of GD2-B7H3 SynNotch CAR-T in metastatic neuroblastoma
Authors: Moghimi Babak , Muthugounder Sakunthala , Jambon Samy , Tibbetts Rachelle , Hung Long , Bassiri Hamid , Hogarty Michael D. , Barrett David M. , Shimada Hiroyuki , Asgharzadeh Shahab
Published: January 2021

The ability to utilize preclinical models to predict the clinical toxicity of chimeric antigen receptor (CAR) T cells in solid tumors is tenuous, thereby necessitating the development and evaluation of gated systems. Here we found that murine GD2 CAR-T cells, specific for the tumor-associated antigen GD2, induce fatal neurotoxicity in a costimulatory domain-dependent manner. Meanwhile, human B7H3 CAR-T cells exhibit efficacy in preclinical models of neuroblastoma. Seeking a better CAR, we generated a SynNotch gated CAR-T, GD2-B7H3, recognizing GD2 as the gate and B7H3 as the target. GD2-B7H3 CAR-T cells control the growth of neuroblastoma in vitro and in metastatic xenograft mouse models, with high specificity and efficacy. These improvements come partly from the better metabolic fitness of GD2-B7H3 CAR-T cells, as evidenced by their naïve T-like post-cytotoxicity oxidative metabolism and lower exhaustion profile.
Inherited predisposition to breast cancer in the Carolina Breast Cancer Study
Authors: Walsh Tom , Gulsuner Suleyman , Lee Ming K. , Troester Melissa A. , Olshan Andrew F. , Earp H. Shelton , Perou Charles M. , King Mary-Claire
Published: January 2021

The Carolina Breast Cancer Study (CBCS) phases I–II was a case-control study of biological and social risk factors for invasive breast cancer that enrolled cases and controls between 1993 and 1999. Case selection was population-based and stratified by ancestry and age at diagnosis. Controls were matched to cases by age, self-identified race, and neighborhood of residence. Sequencing genomic DNA from 1370 cases and 1635 controls yielded odds ratios (with 95% confidence limits) for breast cancer of all subtypes of 26.7 (3.59, 189.1) for BRCA1, 8.8 (3.44, 22.48) for BRCA2, and 9.0 (2.06, 39.60) for PALB2; and for triple-negative breast cancer (TNBC) of 55.0 (7.01, 431.4) for BRCA1, 12.1 (4.18, 35.12) for BRCA2, and 10.8 (1.97, 59.11) for PALB2. Overall, 5.6% of patients carried a pathogenic variant in BRCA1, BRCA2, PALB2, or TP53, the four most highly penetrant breast cancer genes. Analysis of cases by tumor subtype revealed the expected association of TNBC versus other tumor subtypes with BRCA1, and suggested a significant association between TNBC versus other tumor subtypes with BRCA2 or PALB2 among African-American (AA) patients [2.95 (1.18, 7.37)], but not among European-American (EA) patients [0.62 (0.18, 2.09)]. AA patients with pathogenic variants in BRCA2 or PALB2 were 11 times more likely to be diagnosed with TNBC versus another tumor subtype than were EA patients with pathogenic variants in either of these genes (P = 0.001). If this pattern is confirmed in other comparisons of similarly ascertained AA and EA breast cancer patients, it could in part explain the higher prevalence of TNBC among AA breast cancer patients.
Dysregulation of epithelial ion transport and neurochemical changes in the colon of a parkinsonian primate
Authors: Coletto Erika , Tough Iain R. , Pritchard Sara , Hikima Atsuko , Jackson Michael J. , Jenner Peter , Ray Chaudhuri K. , Cox Helen M. , Iravani Mahmoud M. , Rose Sarah
Published: January 2021

The pathological changes underlying gastrointestinal (GI) dysfunction in Parkinson’s disease (PD) are poorly understood and the symptoms remain inadequately treated. In this study we compared the functional and neurochemical changes in the enteric nervous system in the colon of adult, L-DOPA-responsive, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmoset, with naïve controls. Measurement of mucosal vectorial ion transport, spontaneous longitudinal smooth muscle activity and immunohistochemical assessment of intrinsic innervation were each performed in discrete colonic regions of naïve and MPTP-treated marmosets. The basal short circuit current (Isc) was lower in MPTP-treated colonic mucosa while mucosal resistance was unchanged. There was no difference in basal cholinergic tone, however, there was an increased excitatory cholinergic response in MPTP-treated tissues when NOS was blocked with L-Nω-nitroarginine. The amplitude and frequency of spontaneous contractions in longitudinal smooth muscle as well as carbachol-evoked post-junctional contractile responses were unaltered, despite a decrease in choline acetyltransferase and an increase in the vasoactive intestinal polypeptide neuron numbers per ganglion in the proximal colon. There was a low-level inflammation in the proximal but not the distal colon accompanied by a change in α-synuclein immunoreactivity. This study suggests that MPTP treatment produces long-term alterations in colonic mucosal function associated with amplified muscarinic mucosal activity but decreased cholinergic innervation in myenteric plexi and increased nitrergic enteric neurotransmission. This suggests that long-term changes in either central or peripheral dopaminergic neurotransmission may lead to adaptive changes in colonic function resulting in alterations in ion transport across mucosal epithelia that may result in GI dysfunction in PD.
Astrogliosis and sexually dimorphic neurodegeneration and microgliosis in the olfactory bulb in Parkinson’s disease
Authors: Flores-Cuadrado Alicia , Saiz-Sanchez Daniel , Mohedano-Moriano Alicia , Lamas-Cenjor Elena , Leon-Olmo Victor , Martinez-Marcos Alino , Ubeda-Bañon Isabel
Published: January 2021

Hyposmia is prodromal, and male sex is a risk marker for an enhanced likelihood ratio of Parkinson’s disease. The literature regarding olfactory bulb volume reduction is controversial, although the olfactory bulb has been largely reported as an early and preferential site for α-synucleinopathy. These pathological deposits have been correlated with neural loss in Nissl-stained material. However, microgliosis has rarely been studied, and astrogliosis has been virtually neglected. In the present report, α-synucleinopathy (α-synuclein), neurodegeneration (Neu-N), astrogliosis (GFAP), and microgliosis (Iba-1) were quantified, using specific markers and stereological methods. Disease, sex, age, disease duration, and post-mortem interval were considered variables for statistical analysis. No volumetric changes have been identified regarding disease or sex. α-Synucleinopathy was present throughout the OB, mainly concentrated on anterior olfactory nucleus. Neurodegeneration (reduction in Neu-N-positive cells) was statistically significant in the diseased group. Astrogliosis (increased GFAP labeling) and microgliosis (increased Iba-1 labeling) were significantly enhanced in the Parkinson’s disease group. When analyzed per sex, neurodegeneration and microgliosis differences are only present in men. These data constitute the demonstration of sex differences in neurodegeneration using specific neural markers, enhanced astrogliosis and increased microgliosis, also linked to male sex, in the human olfactory bulb in Parkinson’s disease.
The effects of tobacco control policies on global smoking prevalence
Authors: Flor Luisa S. , Reitsma Marissa B. , Gupta Vinay , Ng Marie , Gakidou Emmanuela
Published: January 2021

Substantial global effort has been devoted to curtailing the tobacco epidemic over the past two decades, especially after the adoption of the Framework Convention on Tobacco Control1 by the World Health Organization in 2003. In 2015, in recognition of the burden resulting from tobacco use, strengthened tobacco control was included as a global development target in the 2030 Agenda for Sustainable Development2. Here we show that comprehensive tobacco control policies—including smoking bans, health warnings, advertising bans and tobacco taxes—are effective in reducing smoking prevalence; amplified positive effects are seen when these policies are implemented simultaneously within a given country. We find that if all 155 countries included in our counterfactual analysis had adopted smoking bans, health warnings and advertising bans at the strictest level and raised cigarette prices to at least 7.73 international dollars in 2009, there would have been about 100 million fewer smokers in the world in 2017. These findings highlight the urgent need for countries to move toward an accelerated implementation of a set of strong tobacco control practices, thus curbing the burden of smoking-attributable diseases and deaths.