bluuebunny/crossref_metadata_2025 huggingface dataset:
ACE2-lentiviral transduction enables mouse SARS-CoV-2 infection and mapping of receptor interactions
Authors: Rawle Daniel J. , Le Thuy T. , Dumenil Troy , Yan Kexin , Tang Bing , Bishop Cameron , Suhrbier Andreas
Published: February 2021

SARS-CoV-2 uses the human ACE2 (hACE2) receptor for cell attachment and entry, with mouse ACE2 (mACE2) unable to support infection. Herein we describe an ACE2-lentivirus system and illustrate its utility forin vitroandin vivoSARS-CoV-2 infection models. Transduction of non-permissive cell lines with hACE2 imparted replication competence, and transduction with mACE2 containing N30D, N31K, F83Y and H353K substitutions, to match hACE2, rescued SARS-CoV-2 replication. Intranasal hACE2-lentivirus transduction of C57BL/6J mice permitted significant virus replication in lungs. RNA-Seq analyses illustrated that the model involves an acute inflammatory disease followed by resolution and tissue repair, with a transcriptomic profile similar to that seen in COVID-19 patients. Intranasal hACE2-lentivirus transduction of IFNAR-/-and IL-28RA-/-mice lungs was used to illustrate that loss of type I or III interferon responses have no significant effect on virus replication. However, their importance in driving inflammatory responses was illustrated by RNA-Seq analyses. We also demonstrate the utility of the hACE2-lentivirus transduction system for vaccine evaluation in C57BL/6J mice. The ACE2-lentivirus system thus has broad application in SARS-CoV-2 research, providing a tool for both mutagenesis studies and mouse model development.

AUTHOR SUMMARY

SARS-CoV-2 uses the human ACE2 (hACE2) receptor to infect cells, but cannot infect mice because the virus cannot bind mouse ACE2 (mACE2). We use an ACE2-lentivirus systemin vitroto identify four key amino acids in mACE2 that explain why SARS-CoV-2 cannot infect mice. hACE2-lentivirus was used to express hACE2 in mouse lungsin vivo, with the inflammatory responses after SARS-CoV-2 infection similar to those seen in human COVID-19. Genetically modified mice were used to show that type I and III interferon signaling is required for the inflammatory responses. We also show that the hACE2-lentivirus mouse model can be used to test vaccines. Overall this paper demonstrates that our hACE2-lentivirus system has multiple applications in SARS-CoV-2 and COVID-19 research.
A rigid body framework for multi-cellular modelling
Authors: Brown Phillip J. , Green J. Edward F. , Binder Benjamin J. , Osborne James M.
Published: February 2021

Multi-cellular modelling, where tissues and organs are represented by a collection of individual interacting agents, is a well established field, encapsulating several different approaches. In particular, off-lattice models, which represent cells using points that are free to move in space, have been applied to numerous biological problems in both two and three dimensions. The fact that a cell can be represented by point objects is useful in a wide range of settings, particularly when large populations are involved. However, a purely point-based representation is not naturally equipped to deal with objects that inherently have length like cell boundaries or external membranes.

In this paper we introduce a novel off-lattice modelling framework that exploits rigid body mechanics to represent cells using a collection of one-dimensional edges (rather than zero-dimensional points) in a viscosity-dominated system. The rigid body framework can be used, among other things, to represent cells as free moving polygons, to allow epithelial layers to smoothly interact with themselves, and to model rod shaped cells like bacteria. We demonstrate the value of our new framework by using it in these three applications, showing that this approach can replicate established results, as well as offer solutions to problems that limit the scope of current off-lattice multi-cellular models.
Long non-coding RNA Neat1 and paraspeckle components are translational regulators in hypoxia
Authors: Godet Anne-Claire , Roussel Emilie , David Florian , Hantelys Fransky , Morfoisse Florent , Alves Joffrey , Pujol Françoise , Ader Isabelle , Bertrand Edouard , Burlet-Schiltz Odile , Froment Carine , Henras Anthony K. , Vitali Patrice , Lacazette Eric , Tatin Florence , Garmy-Susini Barbara , Prats Anne-Catherine
Published: February 2021

Internal ribosome entry sites (IRESs) drive translation initiation during stress. In response to hypoxia, (lymph)angiogenic factors responsible for tissue revascularization in ischemic diseases are induced by the IRES-dependent mechanism. Here we searched for IREStrans-acting factors (ITAFs) active in early hypoxia in mouse cardiomyocytes. Using knock-down and proteomics approaches, we show a link between a stressed-induced nuclear body, the paraspeckle, and IRES-dependent translation. Furthermore, smiFISH experiments demonstrate the recruitment of IRES-containing mRNA into paraspeckle during hypoxia. Our data reveal that the long non-coding RNA Neat1, an essential paraspeckle component, is a key translational regulator, active on IRESs of (lymph)angiogenic and cardioprotective factor mRNAs. In addition, paraspeckle proteins p54nrband PSPC1 as well as nucleolin and Rps2, two p54nrb-interacting proteins identified by mass spectrometry, are ITAFs for IRES subgroups. Paraspeckle thus appears as a platform to recruit IRES-containing mRNAs and possibly host IRESome assembly. Polysome PCR array shows that Neat1 isoforms regulate IRES-dependent translation and, more widely, translation of mRNAs involved in stress response.

Highlights

Paraspeckle formation correlates with activation of translation via internal ribosome entry sites (IRES) in mouse hypoxic cardiomyocytes as well as in tumoral cells.

The long non-coding RNA Neat1, an essential paraspeckle component, is a key translational regulator of (lymph)angiogenic and cardioprotective factor expression in this process.

IRES-containing mRNA is recruited into paraspeckles during hypoxia.

Paraspeckle proteins p54nrband PSPC1 as well as two p54nrb-interacting proteins, nucleolin and RPS2, contribute to this process.

Paraspeckle appears as a platform for IRESome formation in the nucleus.

The Neat1 isoforms widely regulate the translation of mRNAs containing IRESs and of genes involved in the stress response.

GRAPHICAL ABSTRACT
A screen for Twist-interacting proteins identifies Twinstar as a regulator of muscle development during embryogenesis
Authors: Balakrishnan Mridula , Howard Austin , Yu Shannon F. , Sommer Katie , Nowak Scott J. , Baylies Mary K.
Published: February 2021

Myogenesis inDrosophilarelies on the activity of the transcription factor Twist during several key events of mesoderm differentiation. To identify the mechanism(s) by which Twist establishes a unique gene expression profile in specific spatial and temporal locales, we employed a yeast-based double interaction screen to discover new Twist-interacting proteins (TIPs) at themyocyte enhancer factor 2 (mef2)andtinman (tinB)myogenic enhancers. We identified a number of proteins that interacted with Twist at one or both enhancers, and whose interactions with Twist and roles in muscle development were previously unknown. Through genetic interaction studies, we find that Twinstar (Tsr), and its regulators are required for muscle formation. Loss of function and null mutations intsrand its regulators result in missing and/or misattached muscles. Our data suggest that the yeast double interaction screen is a worthy approach to investigate spatial-temporal mechanisms of transcriptional regulation in muscle and in other tissues.
Capturing effects of blood flow on the transplanted decellularized nephron with intravital microscopy
Authors: Corridon Peter R.
Published: February 2021

Organ decellularization creates cell-free, collagen-based extracellular matrices that can be used as scaffolds for tissue engineering applications. This technique has recently gained much attention, yet adequate scaffold repopulation and implantation remain a challenge. Specifically, there still needs to be a greater understanding of scaffold responses post-transplantation and ways we can improve scaffold durability to withstand the in vivo environment. Recent studies have outlined vascular events that limit organ decellularization/recellularization scaffold viability for long-term transplantation. However, these insights have relied on in vitro/in vivo approaches that need enhanced spatial and temporal resolutions to investigate such issues at the microvascular level. This study uses intravital microscopy to gain instant feedback on their structure, function, and deformation dynamics. Thus, the objective of this study was to capture the effects of in vivo blood flow on the decellularized glomerulus, peritubular capillaries, and tubules after autologous and allogeneic orthotopic transplantation into rats. Large molecular weight dextran molecules label the vasculature. They revealed substantial degrees of translocation from glomerular and peritubular capillary tracks to the decellularized tubular epithelium and lumen as early as 12 hours after transplantation, providing real-time evidence of the increases in microvascular permeability. Macromolecular extravasation persisted for a week, during which the decellularized microarchitecture was significantly and comparably compromised and thrombosed in both autologous and allogeneic approaches. These results indicate that in vivo multiphoton microscopy is a powerful approach for studying scaffold viability and identifying ways to promote scaffold longevity and vasculogenesis in bioartificial organs.
CD29 enriches for cytotoxic human CD4+T cells
Authors: Nicolet Benoît P. , Guislain Aurelie , Wolkers Monika C.
Published: February 2021

CD4+T cell are key contributors in the induction of adaptive immune responses against pathogens. Even though CD4+T cells are primarily classified as non-cytotoxic helper T cells, it has become appreciated that a subset of CD4+T cells is cytotoxic. However, tools to identify these cytotoxic CD4+T cells are lacking. We recently showed that CD29 (Integrin Beta 1, ITGB1) expression on human CD8+T cells enriches for the most potent cytotoxic T cells. Here, we questioned whether CD29 expression also associates with cytotoxic CD4+T cells. We show that human peripheral blood-derived CD29hiCD4+T cells display a cytotoxic gene expression profile, which closely resembles that of CD29hicytotoxic CD8+T cells. This CD29hicytotoxic phenotype was observedex vivoand was maintained inin vitrocultures. CD29 expression enriched for CD4+T cells, which effectively produced the pro-inflammatory cytokines IFN-γ, IL-2, and TNF-α, and cytotoxic molecules. Lastly, CD29-expressing CD4+T cells transduced with a MART-1 specific TCR showed target cell killingin vitro. In conclusion, we here demonstrate that CD29 can be employed to enrich for cytotoxic human CD4+T cells.
Vertical stratification of environmental DNA in the open ocean captures ecological patterns and behavior of deep-sea fishes
Authors: Canals Oriol , Mendibil Iñaki , Santos María , Irigoien Xabier , Rodríguez-Ezpeleta Naiara
Published: February 2021

The deep-sea remains among the most unknown ecosystems on Earth despite its relevant role in carbon sequestration and increasing threat due to interest by fishing and mining industries. This, together with the recent discovery that the upper layer of this ecosystem (mesopelagic zone) harbors about 90% of the fish biomass on Earth, claims for a deeper understanding of the deep-sea so that the foundations for a sustainable use of its resources can be established. The analysis of environmental DNA (eDNA) collected from the water column emerges as an alternative to traditional methods to acquire this elusive information, but its application to the deep ocean is still incipient. Here, we have amplified and sequenced the fish eDNA contained in vertical profile samples (from surface to 2000 m depth) collected during day and night-time throughout the Bay of Biscay. We found that eDNA-derived deep-sea fish richness and abundance follow a day-night pattern that is consistent with the diel migratory behavior of many mesopelagic species, and that eDNA can reveal species-specific distribution and movement through the water column. These results highlight the potential of eDNA-based studies to improve our knowledge on the species inhabiting the dark ocean before this still pristine ecosystem is exploited.
Full-likelihood genomic analysis clarifies a complex history of species divergence and introgression: the example of theerato-saragroup ofHeliconiusbutterflies
Authors: Thawornwattana Yuttapong , Seixas Fernando A. , Yang Ziheng , Mallet James
Published: February 2021

Abstract

Introgressive hybridization plays a key role in adaptive evolution and species diversification in many groups of species. However, frequent hybridization and gene flow between species makes estimation of the species phylogeny and key population parameters challenging. Here, we show that by accounting for phasing and using full-likelihood analysis methods, introgression histories and population parameters can be estimated reliably from whole-genome sequence data. We employ full-likelihood methods under the multispecies coalescent (MSC) model with and without gene flow to analyze the genomic data from six members of theerato-saraclade ofHeliconiusbutterflies and infer the species phylogeny and cross-species introgression events. The methods naturally accommodate random fluctuations in genealogical history across the genome due to deep coalescence. To avoid heterozygote phasing errors in haploid sequences commonly produced by genome assembly methods, we process and compile unphased diploid sequence alignments and use analytical methods to average over uncertainties in heterozygote phase resolution. There is robust evidence for introgression across the genome, both among distantly related species deep in the phylogeny and between sister species in shallow parts of the tree. We obtain chromosome-specific estimates of key population parameters such as introgression directions, times and probabilities, as well as species divergence times and population sizes for modern and ancestral species. We confirm ancestral gene flow between thesaraclade and an ancestral population ofH. telesiphe, a likely hybrid speciation origin forH. hecalesia, and gene flow between sister speciesH. eratoandH. himera. Inferred introgression among ancestral species also explains the history of two chromosomal inversions deep in the phylogeny of the group. This study illustrates how a full-likelihood approach based on the multispecies coalescent makes it possible to extract rich historical information of species divergence and gene flow from genomic data.
Key experiences for the transdisciplinary approach: fieldwork-based training in sustainability science education
Authors: Kudo Shogo , Omi Kanako , Florentin Kevin , Allasiw Doreen Ingosan
Published: February 2021

Purpose

This paper aims to describe how a sustainability-focused program in higher education can provide training and key experiences for implementing transdisciplinary approaches. The case is a fieldwork-based training course called the Global Field Exercise (GFE) at the Graduate Program in Sustainability Science, The University of Tokyo. The GFE is a methodological training course that emphasizes generating locally relevant research questions on sustainability.

Design/methodology/approach

This research is a case study regarding how a sustainability science program can offer a fieldwork-based training course that focuses on a transdisciplinary approach. Five students from diverse academic disciplines and cultural backgrounds participated in the GFE in QwaQwa where they conducted semi-structured interviews with six local entrepreneurs to identify the challenges and opportunities of entrepreneurship. The authors investigated the learning process and outcomes of the students through participatory observation in preparatory meetings, daily reflection sessions during fieldwork and a content analysis of feedback reports.

Findings

Four learning outcomes of the students were suggested: the reexamination of assumptions, managing misunderstanding and miscommunication, mutual learning and being empathic toward the local people.

Research limitations/implications

This paper suggests three key opportunistic experiences for the transdisciplinary approach: discuss the normative dimension of sustainability; build intersubjectivity among team members and adopt methodological pluralism; and become empathetic to diverse stakeholder groups to facilitate the cogeneration of knowledge.

Originality/value

How to design training on a transdisciplinary approach in educational programs remains an area for further exploration. This study addresses this knowledge gap by establishing a link between sustainability education and sustainability in practice.
Exige-stential leadership: exploring the limits of leadership in a crisis
Authors: Stoten David William
Published: February 2021

Purpose

The purpose of this paper is to explore how leadership can better respond to a crisis. It aims to integrate ideas from existentialism into a discussion of how leadership could develop and provoke debate.

Design/methodology/approach

A review of the literature on leadership, crisis management and existentialism was adopted for the preferred research methodology.

Findings

This paper identified a gap in the literature on leadership in an exigency and offered an alternative to the technical-rationalist conceptions of leadership behaviour.

Practical implications

Reference is made to the benefits of counselling for leaders following a crisis.

Originality/value

This paper is an original contribution to the work on leadership. Through the concept of exige-stential leadership, this paper integrates ideas taken from existentialist philosophy, to provide a new way of conceptualising leadership in an exigency.
Evaluation of the COVID-19 regulations in the Visegrad group
Authors: Urbanovics Anna , Sasvári Péter , Teleki Bálint
Published: February 2021

Purpose

The purpose of this paper is to analyse the legal and political background of COVID-19 related measures introduced during the first wave of the pandemic in the Visegrad Group. These countries introduced measures within the state of emergency that may be violation against the values of the European Union, such as the rule of law.

Design/methodology/approach

A mixed approach methodology is used. Firstly, the examined countries are analysed and compared from the aspect of constructional law and political science in the form of case studies. Then, empirical research is conducted based on social media analysis limited to Twitter contents.

Findings

The authors found that, however, in every analysed country, the measures challenge the European values these are not expressed in the social media equally. While Slovakia is displayed from a cooperative aspect, the Czech Republic has a few critics. Poland and Hungary have a biased, negative reputation filled with heavy critics.

Research limitations/implications

The limitation of this paper lies in the empirical research, as social media analysis was conducted based on keyword search and within a defined time scope.

Practical implications

Findings help decision-makers concentrate on and modify their communication concerning the extraordinary regulations during a worldwide crisis, such as the COVID-19 pandemic.

Social implications

The feedback of social media users analysed is valuable for politicians and government officials as well.

Originality/value

The socio-political impacts of the COVID-19 pandemic have not been elaborated in the literature yet with respect to the V4 countries. The V4-countries are a special entity as an intergovernmental platform within the EU, whose reputation as democracies is rather heterogeneous.
Effects of plant hydraulic traits on the flammability of live fine canopy fuels
Authors: Scarff Fiona R. , Lenz Tanja , Richards Anna E. , Zanne Amy E. , Wright Ian J. , Westoby Mark
Published: February 2021

Plant species vary in how they regulate moisture and this has implications for their flammability during wildfires. We explored how fuel moisture is shaped by variation within five hydraulic traits: saturated moisture content, cell wall rigidity, cell solute potential, symplastic water fraction and tissue capacitance.

Using pressure–volume curves, we measured these hydraulic traits in twigs and distal shoots (i.e. twigs + leaves) in 62 plant species across four wooded communities in south‐eastern Australia. Moisture content of fine fuels was then estimated for circumstances typical of fire weather. These projections were made assuming that under the hot, dry, windy conditions typical of large wildfires, leaves and fine twigs would function at internal water pressures close to wilting point (i.e. turgor loss point, TLP). The effect of different moisture contents at TLP on ignition time was then modelled using a fully mechanistic, finite element model of biomass ignition based on standard principles of physical chemistry.

We also measured predawn water potential, an indication of plant access to soil water that is influenced by root architecture. These data were used to model how root traits influence fuel moisture and ignition time.

Most variation among species in fuel moisture under fire weather conditions arose from differences in saturated moisture content (3.4‐ to 3.6‐fold variation). Twig capacitance was also an important driver of fuel moisture under these weather conditions (1.9‐ to 2.2‐fold variation in moisture content). A suite of other leaf and root traits influencing how much shoots dry out as they approach wilting point each contributed 1.0‐ to 1.6‐fold variation in projected fuel moisture during fire weather. Fuel moisture variation in turn drove variation in flammability by modifying predicted ignition time.

Two main life‐history types in fire‐prone habitats are obligate seeders and resprouters. There were no significant differences between these species groups in estimated fuel moisture during fire weather, nor in any measured hydraulic traits.

Live fuel moisture is an important determinant of wildfire activity. Our data show that variation in tissue saturated moisture content among co‐occurring species represents an important ecological store of variation in flammability in the study communities.

A free Plain Language Summary can be found within the Supporting Information of this article.
Revealing environmentally driven population dynamics of an Arctic diatom using a novel microsatellite PoolSeq barcoding approach
Authors: Wolf Klara K. E. , Hoppe Clara J. M. , Leese Florian , Weiss Martina , Rost Björn , Neuhaus Stefan , Gross Thilo , Kühne Nancy , John Uwe
Published: February 2021

Ecological stability under environmental change is determined by both interspecific and intraspecific processes. Particularly for planktonic microorganisms, it is challenging to follow intraspecific dynamics over space and time. We propose a new method, microsatellite PoolSeq barcoding (MPB), for tracing allele frequency changes in protist populations. We successfully applied this method to experimental community incubations and field samples of the diatom Thalassiosira hyalina from the Arctic, a rapidly changing ecosystem. Validation of the method found compelling accuracy in comparison with established genotyping approaches within different diversity contexts. In experimental and environmental samples, we show that MPB can detect meaningful patterns of population dynamics, resolving allelic stability and shifts within a key diatom species in response to experimental treatments as well as different bloom phases and years. Through our novel MPB approach, we produced a large dataset of populations at different time‐points and locations with comparably little effort. Results like this can add insights into the roles of selection and plasticity in natural protist populations under stable experimental but also variable field conditions. Especially for organisms where genotype sampling remains challenging, MPB holds great potential to efficiently resolve eco‐evolutionary dynamics and to assess the mechanisms and limits of resilience to environmental stressors.
Fission–fusion dynamics of a pelagic delphinid in the arctic: the white‐beaked dolphin (Lagenorhynchus albirostris)
Authors: BERTULLI Chiara G. , RASMUSSEN Marianne H. , ROSSO Massimiliano
Published: February 2021

Delphinids exhibit great variability in their social structures. It is therefore important to document lesser known species, in extreme changing habitats, to compare and contrast mechanisms driving sociality. Here, we describe the first long‐term assessment of social structure of white‐beaked dolphins (Lagenorhynchus albirostris) using a compiled version of SOCPROG 2.8 and an 11‐year photo‐identification dataset (2002–2013) collected from whale‐watching vessels at 2 sites (Faxaflói and Skjálfandi bays) off Iceland. We identified a total of 487 dolphins which are suggested to be part of an open population as shown by the discovery curve obtained analyzing photo‐id data. The social analyses were restricted to 35 adults which were sighted on ≥5 different days. The mean residency time of white‐beaked dolphins in our 2 study areas was of 95 days (SE = 35.63; 95% CI: 23–171), with the “migration‐full interchange” model best describing movements of dolphins in and out of our 2 study sites. Social differentiation in this population was high (Likelihood: S = 0.87, SE = 0.04; r = 0.31, SE = 0.03) indicating diverse, non‐random social relationships. Temporal associations best fit the model of “casual acquaintances” against the standardized lagged association rates with the majority of white‐beaked dolphin associations being short‐term, but with a few long‐term across years. Testing for preferred companionship, long‐term associations are favored over short‐term. In this study, associations among white‐beaked dolphins are short‐term but with desirably long‐term associations fitting into a society with fission–fusion dynamics. This information expands the latitudinal range for which social structure has been described for oceanic dolphin species.
Community‐based population monitoring for large baleen whales: the case study of Bryde's whale in Beibu Gulf of China
Authors: ZHANG Yaoyao , CHEN Mo , CHEN Mao , HAN Yi , HAO Yujiang , WANG Kexiong , MEI Zhigang , WANG Ding
Published: February 2021

Citizen science is a popular method for the long‐term monitoring of the distribution of wild animals. The application of these methods in different species and environments still poses challenges, especially for aquatic animals. In this study, we investigated the distribution of the Bryde's whale (Balaenoptera edeni) in the Beibu Gulf of China by using scientific boat‐based surveys and citizen science approaches using 2 different methods of data collection. First, we built our mobile app (Whale Guard) and installed it on fishermen's phones. Second, we used a popular instant messaging app (WeChat) to create an online fisherman community. We found that the mobile phone app collected far fewer reports (5 reports) than the online community group (42 reports, P < 0.01). By using a variety of incentives, we maintained the fisherman's community's activity without significant user loss (P < 0.01). We also found that the locations collected by social media applications in this study were consistent with observations from scientific boat‐based transect surveys. The sightings distribution of Bryde's whales differed from those in previous surveys in that they were present across larger areas. Social media apps reported that 69% of reports was confirmed by more than one person, whereas Whale Guard reports were much lower (0, P <0.001). Community‐based citizen science can greatly contribute to the long‐term monitoring of Bryde's whales, and it has successfully overcome the challenges of data accessibility, accuracy, and fragmentation. Our study shows how to appropriately use citizen science in different community groups and community‐based approaches make them useful for large baleen whale surveys.
The Geological Significance of the Deformation and Geochronology of the Xiaotian–Mozitan Shear Zone in the Dabie Orogenic Belt (East‐Central China)
Authors: HUANG Peng , SONG Chuanzhong , XIAO Wenjiao , LI Jiahao , ZHOU Kefa , WANG Jinlin , NIJIATI Abuduxun , LI Zhenwei
Published: February 2021

The Xiaotian–Mozitan Shear Zone (XMSZ) is the boundary of the Dabie High‐grade Metamorphic Complex (DHMC) and the North Huaiyang Tectonic Belt. It was deformed in ductile conditions with a top‐to‐NW/WNW movement. Geothermometers applied to mineral parageneses in mylonites of the shear zone give a temperature range of 623–691°C for the predeformation and 515–568°C for the syndeformation, respectively, which indicates a retrograde process of evolution. A few groups of zircon U‐Pb ages were obtained from undeformed granitic veins and different types of deformed rocks in the zone. Zircons from the felsic ultramylonites are all magmatic, producing a weighted mean 206Pb/238U age of 754 ± 8.1 Ma, which indicates the time of magmatic activities caused by rifting in the Neoproterozoic. Zircons from the granitic veins, cutting into the mylonites, are also of magmatic origin, producing a weighted mean 206Pb/238U age of 130 ± 2.5 Ma, which represents the time of regional magmatic activity in the Cretaceous. Zircons from the mylonitic gneisses are of anatectic‐metamorphic origins and are characterized by a core‐mantle interior texture, which yielded several populations of ages including the Neoproterozoic ages with a weighted mean 206Pb/238U age of 762 ± 18 Ma, similar to that of the felsic ultramylonites and the Early Cretaceous ages with a weighted mean 206Pb/238U age of 143 ± 1.8 Ma, indicating the anatectic metamorphism in the Dabie Orogenic Belt (DOB). Based on integrated analysis of the structure, thermal conditions of ductile deformation and the contact relations of the dated rocks, the activation time of the Xiaotian–Mozitan Shear Zone is constrained between ∼143 Ma and 130 Ma, during which the DOB was undergoing a transition in tectonic regime from compression to extension. Therefore, the deformation and evolution of this shear zone plays an instrumental role in fully understanding this process. This research also inclines us to the interpretation of it as an extensional detachment, with regard to the tectonic properties of the shear zone. It may also be part of a continental scale extension in the background of the North China Block's cratonic destruction, dominated by the subduction and roll‐back of the Paleo‐Pacific plate, but more detailed work is needed in order to unravel its complicated development.
Do dual purchasers behave differently? An analysis of purchasing data for households that buy both alcohol and tobacco in the United Kingdom
Authors: Wilson Luke B. , Angus Colin , Pryce Robert , Holmes John , Brennan Alan , Gillespie Duncan
Published: February 2021

Background and Aims

Dual purchasers of alcohol and tobacco are at increased health risk from the interacting health impacts of alcohol and tobacco use. They are also at financial risk from exposure to the dual financial cost of policies that increase alcohol and tobacco prices. Understanding whose alcohol and tobacco use exposes them to these health and financial risks is important for understanding the inequality impacts of control policies. This study explores the extent to which household spending on alcohol and tobacco combined varies between socio‐economic groups and compares this with results for households which purchase only one of the commodities.

Design

Cross‐sectional analysis of household‐level alcohol and tobacco purchasing data.

Setting

United Kingdom, 2012–17.

Participants/Cases

A total of 26 021 households.

Measurements

We analysed transaction‐level data from individual 14‐day spending diaries in the Living Cost and Food Survey (LCFS). We used this to calculate expenditure, volumes of alcohol and tobacco purchased, and the price paid per unit of alcohol (1 unit = 8 g) and per stick of tobacco. This was compared with equivalized total expenditure and quintiles of equivalized household income. Prices were calibrated and pack sizes were imputed using empirical sales data from Nielsen/CGA to correct for reporting bias.

Findings

Dual purchasing households spent [95% confidence interval] more on alcohol and more on tobacco than their single‐purchasing counterparts. In general, lower‐income households spent less on both alcohol and tobacco than higher‐income households. Furthermore, dual purchasing households in the lowest income group were most exposed to potential increases in price than were other income groups, with (CI = 12.41–13.15%) of their total household budget spent on alcohol and tobacco.

Conclusions

Dual purchasers of alcohol and tobacco in the United Kingdom appear to be concentrated evenly among income groups. However, dual purchasers may experience particularly large effects from pricing policies, as they spend a substantially higher proportion of their overall household expenditure on alcohol and tobacco than do households that purchase only one of the commodities.
Societal development and the alcohol‐attributable burden of disease
Authors: Shield Kevin D. , Rehm Jürgen
Published: February 2021

Aim

This study aimed to examine if there is an interaction between alcohol use and human development in terms of their associations with alcohol‐attributable health harms.

Design

Statistical modelling of global country‐ and region‐specific data from 2016.

Setting

Global.

Participants/Cases

The units of the analyses were countries (n = 180) and regions (n = 4) based on their Human Development Index (HDI).

Measurements

Alcohol‐attributable harms [deaths, years of life lost (YLL), years lived with disability (YLD) and disability‐adjusted life years (DALYs) lost] and risk relations were based on a recent study using World Health Organization (WHO) estimates for 2016. Human development was measured using the HDI, a summary score of life expectancy, education and gross national income from the United Nations Development Programme. Interactions between HDI and adult per‐capita consumption (APC) affecting alcohol‐attributable harms were assessed using likelihood ratio tests. Differences in alcohol‐attributable harms per litre of APC between HDI groups were assessed using regression analyses and a reference group of low HDI.

Findings

APC is associated with alcohol‐attributable deaths, YLL, YLDs and DALYs lost, while HDI is associated with alcohol‐attributable deaths, YLL and DALYs lost. Statistical analyses indicated there is an interaction between HDI and APC in their associations with alcohol‐attributable deaths, YLL and DALYs lost per 100 000 people. The alcohol‐attributable burden was highest in low HDI countries, with 11.65 [95% confidence interval (CI) = 10.75, 12.40] deaths and 495.61 (95% CI = 461.83, 569.23) DALYs lost per 100 000 people per litre of APC, and lowest in very high HDI countries, with 4.15 (95% CI = 2.46, 5.71) deaths and 200.31 (95% CI = 122.78, 265.10) DALYs lost per 100 000 people per litre of APC. However, no statistical differences between low and very high HDI groupings for these burdens were observed.

Conclusions

There appears to be an interaction between the Human Development Index and alcohol use in their associations with alcohol‐attributable deaths, years of life lost and disability‐adjusted life years lost but not with alcohol‐attributable years lived with disability. Alcohol appears to have a stronger harmful impact per litre of alcohol consumed in lesser developed countries than in developed countries.
Geographic Diversification of the Supply Chains of Japanese Firms
Authors: Todo Yasuyuki , Inoue Hiroyasu
Published: February 2021

Diversifying supply chains has been a policy objective of the Japanese government to construct a robust and resilient economy since the spread of COVID‐19 in the final stages of the Abe Administration. Although geographically expanded supply chains incur a risk of inflows of negative economic shocks from other regions and countries, this risk can be alleviated by more diversification. In addition, diversified supply chains are found to promote the performance of firms. Recently, the domestic supply chains of Japanese firms started to be diversified, but firms still agglomerate in Tokyo substantially. Moreover, the international supply chains of Japanese firms rely considerably on Chinese suppliers and clients. Therefore, more geographic diversification of supply chains of Japanese firms is suggested for the more robust, resilient, and high‐growth economy in the post Abenomics period, including diversifying within Japan, reducing the reliance on China, and strengthening links with developed countries, with the help of the government.
Immunohistochemical study on the expressions of neuropeptides in the superficial and deep gland of the third eyelid of pigs
Authors: Księżarczyk Marlena M. , Arciszewski Marcin B.
Published: February 2021

The superficial gland of the third eyelid (SGTE) and deep gland of the third eyelid (DGTE) are classified as accessory lacrimal glands. The aim of the present study was to immunohistochemically investigate the expression of vasoactive intestinal peptide (VIP), dopamine beta‐hydroxylase (DβH), substance P (SP), galanin, neuropeptide Y (NPY), pituitary adenylate cyclase‐activating peptide (PACAP), somatostatin and calcitonin gene‐related peptide (CGRP) in the porcine SGTE and DGTE. We demonstrated the distribution patterns of VIP, DβH, SP, NPY and galanin in the nerve fibres in the SGTE and DGTE. None of somatostatin‐, PACAP‐ and CGRP‐immunoreactive (IR) nerve fibres were found in the SGTE and DGTE. The majority of VIP‐ and DβH‐IR nerves fibres were found near to glandular acini, tubules, secretory ducts and blood vessels in the SGTE and DGTE. VIP‐IR nerve fibres were found in external connective tissue in SGTE and DGTE and only in interlobular connective tissue in the SGTE. DβH‐IR nerve fibres were found in interlobular and external connective tissue in the DGTE but not in the SGTE. Single galanin‐, SP‐ and NPY‐IR nerve fibres were observed in close proximity to acini and tubules in the SGTE and DGTE. Single galanin‐, SP‐, NPY‐IR nerve fibres were found in close proximity to the secretory ducts in the DGTE, however only SP‐IR nerve fibres were found near to the secretory ducts in SGTE. In conclusion, our research aims to highlight some aspects of SGTE and DGTE innervation in pigs and may also be a source of basic knowledge for further studies.
Genetics background of β‐thalassemia (3.5 kb deletion) in Southern Thailand: Haplotype analysis using novel reverse dot blot hybridization
Authors: Tepakhan Wanicha , Srewaradachpisal Korntip , Kanjanaopas Sataron , Jomoui Wittaya
Published: February 2021

β‐thalassemia (β‐thal) (3.5 kb deletion or NC_000011.10:g.5224302‐5227791del3490bp) is a common mutation in southern Thailand. This study aimed to determine genetic diversity in subjects with β‐thal (3.5 kb deletion) alleles and to ascertain the origin of this mutation using haplotype and phylogenetic analysis. The study was carried out on members of the southern Thai population, including 45 normal individuals, 116 heterozygous β‐thal (3.5 kb deletion) and one homozygous β‐thal (3.5 kb deletion). The 5′‐haplotype in β‐globin gene cluster was examined using newly developed reverse dot blot hybridization (RDB) and compared with polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP). The results showed 100% concordance between the haplotype patterns of these two methods. From a total of 324 chromosomes, nine haplotypes were segregated. Haplotype H2 (+ – – – –) was the predominant haplotype observed in all 118 β‐thal (3.5 kb deletion) chromosomes, which revealed a single origin. The phylogenetic tree demonstrated that β‐thal (3.5 kb deletion) has an older genetic defect in this region. Moreover, the developed RDB is simple, less time‐consuming, inexpensive, and does not restriction enzyme digestion.
Role of nanostructures in allergy: Diagnostics, treatments and safety
Authors: Mayorga Cristobalina , Perez‐Inestrosa Ezequiel , Rojo Javier , Ferrer Marta , Montañez Maria Isabel
Published: February 2021

Nanotechnology is science, engineering and technology conducted at the nanoscale, which is about 1–100 nm. It has led to the development of nanomaterials, which behave very differently from materials with larger scales and can have a wide range of applications in biomedicine. The physical and chemical properties of materials of such small compounds depend mainly on the size, shape, composition and functionalization of the system. Nanoparticles, carbon nanotubes, liposomes, polymers, dendrimers and nanogels, among others, can be nanoengineeried for controlling all parameters, including their functionalization with ligands, which provide the desired interaction with the immunological system, that is dendritic cell receptors to activate and/or modulate the response, as well as specific IgE, or effector cell receptors. However, undesired issues related to toxicity and hypersensitivity responses can also happen and would need evaluation. There are wide panels of accessible structures, and controlling their physico‐chemical properties would permit obtaining safer and more efficient compounds for clinical applications goals, either in diagnosis or treatment. The application of dendrimeric antigens, nanoallergens and nanoparticles in allergy diagnosis is very promising since it can improve sensitivity by increasing specific IgE binding, mimicking carrier proteins or enhancing signal detection. Additionally, in the case of immunotherapy, glycodendrimers, liposomes, polymers and nanoparticles have shown interest, behaving as platforms of allergenic structures, adjuvants or protectors of allergen from degradation or having a depot capacity. Taken together, the application of nanotechnology to allergy shows promising facts facing important goals related to the improvement of diagnosis as well as specific immunotherapy.
Comparative analysis of the role of mast cells in murine asthma models using Kit‐sufficient mast cell‐deficient animals
Authors: Pohlmeier Lea , Sonar Sanchaita Sriwal , Rodewald Hans‐Reimer , Kopf Manfred , Tortola Luigi
Published: February 2021

Background

Asthma is a frequent chronic disease that can potentially severely affect the respiratory capacity and well‐being of patients. Mast cells (MCs) are regarded as major players in human asthma due to their capacity to release crucial inflammatory mediators following allergen exposure. However, unambiguous characterization of their role in animal models has long been hindered by the unavailability of specific MC‐deficient models lacking confounding MC‐unrelated effects. This study aims to examine the role of MCs in Kit‐sufficient MC‐deficient Cpa3Cre/+ mice.

Methods

We used a variety of models of acute and chronic asthma employing distinct routes and regimes of sensitization. These sensitizations were done via the peritoneal cavity, the skin, or the lung. Additionally, different allergens, i.e. ovalbumin and house dust mite extract, were used.

Results

Our results show that the absence of MCs had no impact on the severity of allergic airway inflammation in any of the tested mouse models, as measured by leukocyte infiltration in the airways, cytokine expression, antibody production, airway hyper‐responsiveness and mucus production.

Conclusion

This indicates that MCs do not play a major role in murine allergic airway inflammation.
Paediatric Acute onset Neuropsychiatric Syndrome: Exploratory study finds no evidence of HLA class II association but high rate of autoimmunity in first‐degree relatives
Authors: Fernell Elisabeth , Sundin Mikael , Fasth Anders , Dinkler Lisa , Galazka Martyna , Gillberg Christopher , Johnson Mats
Published: February 2021

Aim

Paediatric acute‐onset neuropsychiatric syndrome (PANS) is defined by an acute onset of obsessive‐compulsive disorder and/or eating restrictions and at least two other severe neuropsychiatric symptoms. The condition is suspected to have an immune‐mediated pathophysiology, but reliable biomarkers have not been identified.

Methods

We hypothesised that PANS, like narcolepsy, might have a human leucocyte antigen (HLA) association, as found in 95% of children developing narcolepsy after H1N1 immunisation. Low resolution genotyping of the MHC class II antigens HLA‐DRB1 and HLA‐DQB1 was performed using two different PCR‐based methods. In addition, parents were interviewed regarding a detailed family history of autoimmune diseases in first‐degree relatives. A total of 18 children, aged 5–14 (mean 8.2) years at onset of PANS met symptom criteria.

Results

No evident association between PANS and the specific HLA alleles examined was observed. In first‐degree relatives of 10 of the 18 children, an autoimmune disease had been diagnosed, and three of the 18 children themselves had an autoimmune disease.

Conclusion

No HLA allele association such as seen in children with narcolepsy after H1N1 immunisation could be confirmed in this group of children with PANS. However, more than half the group had a first‐degree relative with a diagnosed autoimmune disease.
Insulin differentially modulates GABA signalling in hippocampal neurons and, in an age‐dependent manner, normalizes GABA‐activated currents in the tg‐APPSwe mouse model of Alzheimer’s disease
Authors: Hammoud Hayma , Netsyk Olga , Tafreshiha Atieh S. , Korol Sergiy V. , Jin Zhe , Li Jin‐Ping , Birnir Bryndis
Published: February 2021

Aim

We examined if tonic γ‐aminobutyric acid (GABA)‐activated currents in primary hippocampal neurons were modulated by insulin in wild‐type and tg‐APPSwe mice, an Alzheimer's disease (AD) model.

Methods

GABA‐activated currents were recorded in dentate gyrus (DG) granule cells and CA3 pyramidal neurons in hippocampal brain slices, from 8 to 10 weeks old (young) wild‐type mice and in dorsal DG granule cells in adult, 5‐6 and 10‐12 (aged) months old wild‐type and tg‐APPSwe mice, in the absence or presence of insulin, by whole‐cell patch‐clamp electrophysiology.

Results

In young mice, insulin (1 nmol/L) enhanced the total spontaneous inhibitory postsynaptic current (sIPSCT) density in both dorsal and ventral DG granule cells. The extrasynaptic current density was only increased by insulin in dorsal CA3 pyramidal neurons. In absence of action potentials, insulin enhanced DG granule cells and dorsal CA3 pyramidal neurons miniature IPSC (mIPSC) frequency, consistent with insulin regulation of presynaptic GABA release. sIPSCT densities in DG granule cells were similar in wild‐type and tg‐APPSwe mice at 5‐6 months but significantly decreased in aged tg‐APPSwe mice where insulin normalized currents to wild‐type levels. The extrasynaptic current density was increased in tg‐APPSwe mice relative to wild‐type littermates but, only in aged tg‐APPSwe mice did insulin decrease and normalize the current.

Conclusion

Insulin effects on GABA signalling in hippocampal neurons are selective while multifaceted and context‐based. Not only is the response to insulin related to cell‐type, hippocampal axis‐location, age of animals and disease but also to the subtype of neuronal inhibition involved, synaptic or extrasynaptic GABAA receptors‐activated currents.