bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Determinants of Tissue Specificity of Flavivirus Nonstructural Protein 1 Interaction with Endothelial Cells
Authors: Lo Nicholas T.N. , Roodsari Susan , Tin Nicole R. , Biering Scott B. , Harris Eva
Published: May 2022

Members of the mosquito-borne flavivirus genus such as dengue (DENV), West Nile (WNV), and Zika (ZIKV) viruses cause distinct diseases and affect different tissues. We previously found that the secreted flaviviral nonstructural protein 1 (NS1) interacts with endothelial cells and disrupts endothelial barrier function in a tissue-specific manner consistent with the disease tropism of the respective viruses. However, the underlying molecular mechanism of this tissue-specific NS1-endothelial cell interaction is not well understood. To elucidate the distinct role(s) that the domains of NS1 (β-roll, wing, and β-ladder) play in NS1 interactions with endothelial cells, we constructed flavivirus NS1 chimeras that exchanged the wing and β-ladder domains in a pair-wise manner between DENV, WNV, and ZIKV NS1. We found that both the NS1 wing and β-ladder domains conferred NS1 tissue-specific endothelial dysfunction, with the wing conferring cell binding and the β-ladder involved in inducing endothelial hyperpermeability as measured by trans-endothelial electrical resistance assay. To narrow down the amino acids dictating cell binding specificity, we utilized the DENV-WNV NS1 chimera and identified residues 91 to 93 (GDI) of DENV NS1 as a molecular motif determining binding specificity. Further, using an in vivo mouse model of localized leak, we found that the GDI motif of the wing domain was essential for triggering DENV NS1-induced vascular leak in mouse dermis. Taken together, we identify molecular determinants of flavivirus NS1 that confer NS1 binding and vascular leak and highlight the importance of the NS1 wing domain for flavivirus pathogenesis.

Importance

Flavivirus NS1 is secreted into the bloodstream from infected cells during a viral infection. Dengue virus NS1 contributes to severe dengue pathology such as endothelial dysfunction and vascular leak independently of the virus. We have shown that multiple flavivirus NS1 proteins result in endothelial dysfunction in a tissue-specific manner consistent with their respective viral tropism. Here, we aimed to identify the molecular determinants that make some, but not other, flavivirus NS1 proteins bind to select endothelial cells in vitro and cause vascular leak in a mouse model. We identified the wing domain of NS1 as a primary determinant conferring differential endothelial dysfunction and vascular leak and narrowed the contributing amino acid residues to a three-residue motif within the wing domain. The insights from this study pave the way for future studies on the effects of flavivirus NS1 on viral dissemination and pathogenesis and offer potential new avenues for antiviral therapies.
Few amino acid mutations in H6 influenza A virus from South American lineage increase pathogenicity in poultry
Authors: Rimondi Agustina , Olivera Valeria S. , Soria Ivana , Parisi Gustavo D. , Rumbo Martin , Perez Daniel R.
Published: May 2022

In chickens, infections with influenza A virus (IAV) can range from mild to severe and lethal. The study of IAV infections in poultry has been mostly limited to strains from the North American and Eurasian lineages, whereas limited information exists on similar studies with strains from the South American lineage (SAm). To better evaluate the risk of introduction of a prototypical SAm IAV strain into poultry, chickens were infected with a wild-type SAm origin strain (WT557/H6N2). The resulting virus progeny was serially passage in chickens 20 times and the immunopathological effects in chickens of the last passage virus, 20Ch557/H6N2, was compared to those of the parental strain. Comparison of complete viral genome sequences indicated that the 20Ch557/H6N2 strain contained 13 amino acid differences compared to the wild type strain. Five of these mutations are in functionally relevant regions of the viral surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). However, despite higher and more prolonged virus shedding in chickens inoculated with the 20Ch557/H6N2 strain compared to those that received the WT557/H6N2 strain, transmission to naïve chickens was not observed for either group. Analyses by flow cytometry of mononuclear cells and lymphocyte subpopulations from the lamina propria and intraepithelial lymphocytic cells (IELs) from ileum revealed significant increase in the percentages of CD3+TCRγδ+ IELs in chickens inoculated with the 20Ch557/H6N2 strain compared to those inoculated with the WT557/H6N2 strain.
Signals Generated by Neutrophil Receptors for Danger Molecules Transactivate Allosterically Modulated FFA2R: Distinct response patterns are mediated by modulators recognized by different allosteric receptor sites
Authors: Lind Simon , Granberg Kenneth L. , Forsman Huamei , Dahlgren Claes
Published: May 2022

Positive allosteric modulators for free fatty acid receptor 2 (FFA2R/GPR43), that affect receptor function through binding to two distinct allosteric binding sites, were used to determine the correlation between the responses induced in neutrophils by two distinct activation modes; FFA2R was activated either by the orthosteric agonist propionate or by a receptor transactivation mechanism that activated FFA2R from the cytosolic side of the neutrophil plasma membrane by signals generated by the neutrophil PAFR (receptor for platelet activating factor), P2Y2R (receptor for ATP), FPR1 (receptor for fMLF) and FPR2 (receptor for WKYMVM). We show that the transactivation signals that activate FFA2R in the absence of any orthosteric agonist were generated downstream of the signaling G protein that couple to PAFR and P2Y2R. This transactivation of allosterically modulated FFA2Rs, by signals generated by PAFR/P2Y2R, represents a novel mechanism by which a G protein coupled receptor can be activated. Weak correlations were obtained when the FFA2R activity was induced by the transactivation signals generated by PAFRs and P2Y2Rs were compared with the FFA2R activity induced by the orthosteric agonist propionate. Comparison of the responses for each allosteric modulator revealed that the ratio values, calculated from the peak values of the ATP and propionate responses, varied from 0.2 to 1. Depending on the allosteric modulator, the response induced by the two different mechanisms (orthosteric activation and receptor transactivation, respectively), was equal or the propionate response was more pronounced. Importantly, we conclude that FFA2R activation from outside (orthosteric activation) and inside (receptor cross-talk/transactivation) can be selectively affected by an allosteric FFA2R modulator.

The allosterically modulated FFA2R is transactivated by signals generated by other GPCRs.

The PAF and ATP receptors transactivate FFA2R from the cytosolic side of the membrane.

The mechanisms that regulates activation of FFA2R from outside and inside differ.
CpG dinucleotide enrichment in the influenza A virus genome as a live attenuated vaccine development strategy
Authors: Sharp Colin P , Thompson Beth H , Nash Tessa J , Diebold Ola , Pinto Rute M , Thorley Luke , Lin Yao-Tang , Sives Samantha , Wise Helen , Hendry Sara Clohisey , Grey Finn , Vervelde Lonneke , Simmonds Peter , Digard Paul , Gaunt Eleanor R
Published: May 2022

Synonymous recoding of RNA virus genomes is a promising approach for generating attenuated viruses to use as vaccines. Problematically, recoding typically hinders virus growth, but this may be rectified using CpG dinucleotide enrichment. CpGs are recognised by cellular zinc-finger antiviral protein (ZAP), and so in principle, removing ZAP sensing from a virus propagation system will reverse attenuation of a CpG-enriched virus, enabling high titre yield of a vaccine virus. We tested this using a vaccine strain of influenza A virus (IAV) engineered for increased CpG content in genome segment 1. Virus attenuation was mediated by the short isoform of ZAP, correlated with the number of CpGs added, and was enacted via turnover of viral transcripts. The CpG-enriched virus was strongly attenuated in mice, yet conveyed protection from a potentially lethal challenge dose of wildtype virus. Importantly for vaccine development, CpG-enriched viruses were genetically stable during serial passage. Unexpectedly, in both MDCK cells and embryonated hens’ eggs that are used to propagate live attenuated influenza vaccines, the ZAP-sensitive virus was fully replication competent. Thus, ZAP- sensitive CpG enriched viruses that are defective in human systems can yield high titre in vaccine propagation systems, providing a realistic, economically viable platform to augment existing live attenuated vaccines.

AUTHOR SUMMARY

CpG dinucleotides are under-represented in vertebrate genomes, wherein cytosines in the CpG conformation are methylated to regulate transcription. Methylated cytosines are prone to deamination, resulting in TpG dinucleotides replacing CpGs. The resultant CpG suppression has provided a route by which vertebrate cells can recognise RNA from invading pathogens, using cellular Zinc-finger Antiviral Protein (ZAP) as a CpG sensor. Vertebrate-infecting RNA viruses also genomically suppress CpGs, and it is believed that this is an evolved trait to evade detection by ZAP. Here, we engineered an influenza A virus (IAV) with elevated CpG content and characterised how this impacts viral replication. CpG addition resulted in viral attenuation, mediated by ZAP activity. CpG suppression is conserved in dog and chicken genomes (relevant for live attenuated IAV vaccine propagation), and it is logical to predict that ZAP-mediated CpG sensing would also be conserved in these species. However, when we propagated ZAP-sensitive IAV in cognate culture systems, we saw no replication defect. This unexpected result raises questions about why viruses infecting these species suppress CpG in their genomes, and importantly delivers a new, tractable approach to augment rational live attenuated IAV vaccine design.
Neryl acetate, the major component of Corsican Helichrysum Italicum essential oil, mediates its biological activities on skin barrier
Authors: Lemaire Géraldine , Olivero Malvina , Rouquet Virginie , Moga Alain , Pagnon Aurélie , Cenizo Valérie , Portes Pascal
Published: May 2022

Corsican Helichrysum Italicum essential oil is characterized by high concentrations of neryl acetate, and we previously demonstrated that Corsican Helichrysum Italicum essential oil increases the expression of genes that are part of the differentiation complex (involucrin, small proline rich proteins, late cornified envelope, S100 protein family). The biological activities of Helichrysum Italicum essential oil and neryl acetate were compared to identify how neryl acetate contributes to Helichrysum Italicum essential oil activity on human skin. Neryl acetate, as a part component of Helichrysum Italicum essential oil, was tested on skin explant models for 24 hours and 5 days in comparison with Helichrysum Italicum essential oil. We analyzed the biological regulations in the skin explant by transcriptomic analysis, skin barrier protein immunofluorescence, lipid staining and ceramide analysis by liquid chromatography-mass spectrometry. Transcriptomic analysis revealed that 41.5% of Helichrysum Italicum essential oil-modulated genes were also regulated by neryl acetate and a selected panel of genes were confirmed by quantitative reverse transcription PCR analysis. Those genes are involved in epidermal differentiation, skin barrier formation and ceramide synthesis. Involucrin, involved in formation of the cornified envelope, was upregulated at both gene and protein levels after 24 hours and 5 days respectively. After 5 days of treatment, total lipids and ceramides were also increased. Our results demonstrate that neryl acetate mediates a large part of Corsican Helichrysum Italicum essential oil activity on skin barrier formation.
Intracellular injection of brain extracts from Alzheimer’s disease patients trigger unregulated Ca2+ release from intracellular stores that hinders cellular bioenergetics
Authors: Pensalfini Anna , Umar Abdul Rahim , Glabe Charles , Parker Ian , Ullah Ghanim , Demuro Angelo
Published: May 2022

Strong evidence indicates that amyloid beta (Aβ) inflicts its toxicity in Alzheimer’s disease (AD) by promoting uncontrolled elevation of cytosolic Ca2+ in neurons. We have previously shown that synthetic Aβ42 oligomers stimulate abnormal intracellular Ca2+ release from the endoplasmic reticulum stores, suggesting that a similar mechanism of Ca2+ toxicity may be common to the endogenous Aβs oligomers. To investigate this possibility, we use human postmortem brain extracts from control and AD-affected patients and test their ability to trigger Ca2+ fluxes when injected intracellularly into Xenopus oocytes. Immunological characterization of samples from AD patients revealed elevated content of soluble Aβ oligomers, detected by the conformation-dependent OC-antibody, whereas no immunoreactivity was detected in the normal samples. Intracellular injection of brain extracts from control patients failed to trigger detectable changes in intracellular Ca2+. Conversely, brain extracts from AD patients triggered Ca2+ events consisting of local and global Ca2+ fluorescent transients rising within few seconds after injection and persisting for several seconds. Pre-incubation of brain extracts with the conformation specific OC antibody completely suppressed brain extract ability to trigger cytosolic Ca2+ events. Comparison of the elementary events triggered by brain extracts and synthetic Aβ42 oligomer showed comparable temporal evolution and amplitudes to events triggered by direct injection of IP3. Moreover, bath application of caffeine reversibly inhibited local and global Ca2+ signals in all the samples confirming the involvement of Ca2+ release from the ER. Analysis of the recorded Ca2+ fluorescence signals by computational modeling allowed quantification of the IP3 and Ca2+ generated by each sample. The model further shows that the abnormal increase of Ca2+ and IP3 may affect mitochondrial bioenergetics. These results, supports the hypothesis that endogenous amyloid oligomer contained in neurons of AD-affected brains may represent the toxic agents responsible for neurons malfunctioning and death, associated with the disruption of neuronal Ca2+ homeostasis.
Atomic model of Vesicular Stomatitis Virus and Mechanism of Assembly
Authors: Zhou Kang , Si Zhu , Ge Peng , Tsao Jun , Luo Ming , Zhou Z. Hong
Published: May 2022

Like other negative-strand RNA viruses (NSVs) such as influenza and rabies, vesicular stomatitis virus (VSV) has a three-layered organization: a layer of matrix protein (M) resides between the membrane envelope, studded by glycoprotein (G), and the nucleocapsid, composed of the nucleocapsid protein (N) and the encapsidated genomic RNA. Lack of in situ atomic structures of these viral components has limited our understanding of the virion assembly mechanism. Here, by cryoEM and sub-particle reconstruction, we have determined the in situ structures of M and N inside VSV at 3.47 Å resolution. In the virion, N and M have a stoichiometry of 1:2. The in situ structures of both N and M differ from their crystal structures in their N-terminal segments and oligomerization loops. N-RNA, N-N, and N-M-M interactions govern the formation of the capsid. A double layer of M contributes to packaging of the helical nucleocapsid: the inner M (IM) joins neighboring turns of the N helix, while the outer M (OM) contacts G and the membrane envelope. The pseudo-crystalline organization of G is further mapped by cryoET. The mechanism of VSV assembly is delineated by the network interactions of these viral components.
Neurocomputational evidence that conflicting prosocial motives guide distributive justice
Authors: Li Yue , Hu Jie , Ruff Christian C. , Zhou Xiaolin
Published: May 2022

In the history of humanity, most conflicts within and between societies have originated from perceived inequality in resource distribution. How humans achieve and maintain distributive justice has therefore been an intensely studied issue. However, most research on the corresponding psychological processes has focused on inequality aversion and has been largely agnostic of other motives that may either align or oppose this behavioral tendency. Here we provide behavioral, computational, and neuroimaging evidence that distribution decisions are guided by three distinct motives - inequality aversion, harm aversion, and rank reversal aversion – that interact and in fact can also deter individuals from pursuing equality. At the neural level, we show that these three motives are encoded by separate neural systems, compete for representation in various brain areas processing equality and harm signals, and are integrated in the striatum, which functions as a crucial hub for translating the motives to behavior. Our findings provide a comprehensive framework for understanding the cognitive and biological processes by which multiple prosocial motives are coordinated in the brain to guide redistribution behaviors. This framework enhances our understanding of the brain mechanisms underlying equality-related behavior, suggests possible neural origins of individual differences in social preferences, and provides a new pathway to understand the cognitive and neural basis of clinical disorders with impaired social functions.
Choosing memory retrieval strategies: a critical role for inhibition in the dentate gyrus
Authors: Albrecht Anne , Müller Iris , Weiglein Aliće , Pollali Evangelia , Çalışkan Gürsel , Stork Oliver
Published: May 2022

Remembering the location of food is essential for survival. Rodents and humans employ mainly hippocampus-dependent spatial strategies, but when being stressed they shift to striatum-mediated stimulus-based strategies. To investigate underlying brain circuits, we tested mice with a heightened stress susceptibility due to a lack of the GABA-synthetizing enzyme GAD65 (GAD65-/- mice) in a dual solution task. Here, GAD65-/- mice preferred to locate a food reward in an open field via a proximal cue, while their wildtype littermates preferred a spatial strategy. The analysis of cFos co-activation across brain regions and of stress-induced mRNA expression changes of GAD65 pointed towards the hippocampal dorsal dentate gyrus (dDG) as a central structure for mediating stress effects on strategy choices via GAD65. Reducing the GAD65 expression locally in the dDG by a shRNA mediated knock down was sufficient to replicate the phenotype of the global GAD65 knock out and to increase dDG excitability. Using DREADD vectors to specifically interfere with dDG circuit activity during dual solution retrieval but not learning confirmed that the dDG modulates strategy choices and that a balanced excitability of this structure is necessary to establish spatial strategy preference. These data highlight the dDG as a critical hub for choosing between spatial and non-spatial foraging strategies.
Gendered sense of safety and coping strategies in public places: a study in Atatürk Meydanı of Izmir
Authors: Şenol Fatma
Published: April 2022

Purpose

A threatened sense of safety in public spaces is a problem for liveable communities. For better public policies, this study investigates multi-dimensional and multi-scalar aspects of gendered perceived safety and strategies by women and men in daily public spaces.

Design/methodology/approach

A face-to-face survey with 40 men and 50 women in a public space (Izmir, Turkey) is deployed. Descriptive statistics and regression analysis compare participants' perceptions of and strategies for safety across the city, neighbourhood and the study site.

Findings

Their experienced-based familiarities in public places increase women's perceived safety. As safety strategies, different place-based and gendered-preconditions appear for women and men going “outside” especially “alone” (i.e. unaccompanied). Reaffirming female vulnerability in public places, gendered preconditions include individuals' attributes. Of place-based preconditions, crowd and police are significant mechanisms for safety but emphasized differently by women and men. Housewives' female companionship in the study site develops a class- and gender-based claim for a safe place away from their underserved neighbourhood.

Practical implications

Gendered- and place preconditions for women's safety can inform design policies about surveillance and permeability of public spaces. Lack of data about class-based differences about perceived safety is a limitation.

Originality/value

Among a few, it takes perceived safety as performative acts with learned strategies across (rather than momentary perceptions in) socio-spatial spaces and provides a research framework that considers such acts with individual and spatial dimensions across multiple socio-spatial scales.
Do comprehensive labor measures reduce the severity of the pandemic? Evidence from India
Authors: Kumar Kujur Sandeep , Goswami Diti
Published: May 2022

Purpose

As a developing country, India initiated several labor measures to contain the Covid-19 pandemic. This study analyzes the impact of the Covid-19-induced comprehensive labor measures by Indian states on the Case Fatality Ratios and Recovery Rates. Such an analysis will provide deeper insights into the importance of labor measures during a health emergency. It will also be a reality check to the existing National Health Policy.

Design/methodology/approach

The study examines the four major aspects of labor measures on migration, social security, state-specific needs and health and human rights. The authors use these to formulate a composite labor measure index to comprehend the Covid-19-induced various labor measures. Additionally, the authors apply pooled ordinary least squares and panel random-effects models with the state-wise monthly data to examine the impact of Covid-19-induced labor measures on the severity of the pandemic.

Findings

Covid-19-induced comprehensive labor measures reduce fatalities and increase recovery rates. In particular, the measures on labor migration, state-specific needs and health and human rights adopted by the Indian states successfully reduce the Covid-19 fatalities and improve the recovery rates. However, the measures taken to address social security have been ineffective in reducing the severity of the pandemic. The study results are robust to various other specifications.

Research limitations/implications

The time period covered in this research is very brief and does not account for the qualitative impact of labor measures on the severity of the pandemic. This study specifically addresses the number of Covid-19-induced labor measures and not the resources allocated to their implementations or the number of people who benefited from the measures.

Practical implications

This study emphasizes the need for subnational comprehensive labor measures to reduce the severity of the pandemic in developing countries. The study confirms the need for effective Covid-19-induced social security measures to cope with the pandemic in India. This study also ascertains the beneficial impact of the measures on migration, state-specific needs and health and human rights.

Originality/value

The authors make a composite labor measure index that captures state-level Covid-19-induced labor measures on diverse aspects, namely migration, social security, state-specific need and health and human rights, hitherto unexplored. In addition, the authors analyze the impact of these labor measures on the severity of the pandemic.
Applying reactance theory to study consumer responses to COVID restrictions: a note on model specification
Authors: Matarazzo Michela , Diamantopoulos Adamantios
Published: May 2022

Purpose

The purpose of the study is to highlight the relevance of reactance theory for modeling consumer responses to COVID restrictions. The study also aims to critically evaluate the appropriateness of the most established reactance model (the intertwined model) for studying reactance specifically in relation to freedom threats arising from measures aimed at combatting the spread of the pandemic.

Design/methodology/approach

Following a conceptual analysis of the intertwined model of reactance, structural equation modeling is applied to Rain's (2013) meta-analytic data to compare the model to alternative model specifications.

Findings

The analysis reveals both conceptual and statistical shortcomings of the intertwined model of reactance in its current/traditional form. It also draws attention to other model specifications that provide just as good statistical fit and offer promising alternative ways of modeling reactance in a COVID context.

Originality/value

The study is the first attempt to explicitly discuss conceptual and statistical problems associated with the most widely accepted model of reactance, illustrate these issues with specific reference to consumer reactions to COVID restrictions, identify alternative promising model specifications and suggest a respecification of the intertwined model.
Dynamic subwindow matching: A new similarity measure for seismic facies analysis
Authors: Song Chengyun , Qiu Lianpeng , Chen Yunqing , Li Kunhong
Published: April 2022

Seismic facies analysis is usually implemented using pattern recognition methods to classify seismic waveforms extracted along a horizon with a fixed time window. The commonly used similarity measures in those technologies are sensitive to the accuracy of horizon interpretation and the window selection and may thus lead to an unsatisfactory facies map. In this paper, we propose a novel similarity measure called dynamic subwindow matching for seismic facies analysis. The proposed measure is the average similarity of a series of short waveforms containing optimal matching subwindows instead of using the whole signal as done in traditional measures. Because of the introduction of nonlinear alignments for seismic reflection events, the proposed measure has the ability to overcome the horizon inaccuracy problem in seismic facies analysis. Furthermore, it can be directly applied to measure the similarity of the waveforms with different time lengths from the targeted interval. Finally, a new method combining the proposed measure and the k‐nearest neighbours method is developed for supervised seismic facies analysis. The synthetic and field data application demonstrate that the proposed measure is robust to amplitude and horizon interpretation noise and provide an effective approach for seismic facies analysis of varying‐thickness reservoirs.
Regularized 2D Savitzky–Golay derivative filter in estimating the second vertical derivative of potential field data
Authors: Roy Indrajit G.
Published: April 2022

A robust method of estimating the second vertical derivative of two‐dimensional (2D) potential field data is proposed. The proposed method uses a 2D variant of Savitzky–Golay derivative filtering. The design of the 2D Savitzky–Golay derivative filter, unlike its one‐dimensional (1D) counterpart, is a non‐trivial exercise. This is due to the inherent complexity associated with 2D polynomial regression, which increases with the increase in the degree of the polynomial and the dimension of the filter window. The measure of complexity increases manifold, as the polynomial order increases from cubic to quintic. A larger polynomial order demands a larger dimension of the filter window patch as a minimum requirement. The large window patch which, in turn, poses computational challenges, becomes anill‐posedproblem and is computationally inefficient. To alleviate such a problem, an appropriate set of filter parameters is proposed, which ensures computational efficiency while maintaining sufficient robustness. The computational issue arising from theill‐posedcondition of the system matrix is addressed viashrinkage‐based regularization. A numerical experiment was conducted on a synthetically generated 2D dataset without and with a moderate amount of Gaussian random noise in order to check the applicability of the proposed method. The performance in terms of robustness was also compared with the other, usually considered as a benchmark, method. The proposed method is then successfully applied to determine the second vertical derivative of the high‐resolution Bouguer gravity anomaly data over an impact crater in Lake Wanapitaei, Canada. A qualitative interpretation of the second vertical derivative map over Lake Wanapitei is given.
Consistency of demographic trade‐offs across 13 (sub)tropical forests
Authors: Kambach Stephan , Condit Richard , Aguilar Salomón , Bruelheide Helge , Bunyavejchewin Sarayudh , Chang‐Yang Chia‐Hao , Chen Yu‐Yun , Chuyong George , Davies Stuart J. , Ediriweera Sisira , Ewango Corneille E. N. , Fernando Edwino S. , Gunatilleke Nimal , Gunatilleke Savitri , Hubbell Stephen P. , Itoh Akira , Kenfack David , Kiratiprayoon Somboon , Lin Yi‐Ching , Makana Jean‐Remy , Mohamad Mohizah Bt. , Pongpattananurak Nantachai , Pérez Rolando , Rodriguez Lillian Jennifer V. , Sun I‐Fang , Tan Sylvester , Thomas Duncan , Thompson Jill , Uriarte Maria , Valencia Renato , Wirth Christian , Wright S. Joseph , Wu Shu‐Hui , Yamakura Takuo , Yao Tze Leong , Zimmerman Jess , Rüger Nadja
Published: April 2022

Organisms of all species must balance their allocation to growth, survival and recruitment. Among tree species, evolution has resulted in different life‐history strategies for partitioning resources to these key demographic processes. Life‐history strategies in tropical forests have often been shown to align along a trade‐off between fast growth and high survival, that is, the well‐known fast–slow continuum. In addition, an orthogonal trade‐off has been proposed between tall stature—resulting from fast growth and high survival—and recruitment success, that is, a stature−recruitment trade‐off. However, it is not clear whether these two independent dimensions of life‐history variation structure tropical forests worldwide.

We used data from 13 large‐scale and long‐term tropical forest monitoring plots in three continents to explore the principal trade‐offs in annual growth, survival and recruitment as well as tree stature. These forests included relatively undisturbed forests as well as typhoon‐disturbed forests. Life‐history variation in 12 forests was structured by two orthogonal trade‐offs, the growth−survival trade‐off and the stature−recruitment trade‐off. Pairwise Procrustes analysis revealed a high similarity of demographic relationships among forests. The small deviations were related to differences between African and Asian plots.

Synthesis. The fast–slow continuum and tree stature are two independent dimensions structuring many, but not all tropical tree communities. Our discovery of the consistency of demographic trade‐offs and life‐history strategies across different forest types from three continents substantially improves our ability to predict tropical forest dynamics worldwide.
Parents' management of alcohol in the context of discourses of ‘competent’ parenting: A qualitative analysis
Authors: Cook Megan , Pennay Amy , MacLean Sarah , Dwyer Robyn , Mugavin Janette , Callinan Sarah
Published: April 2022

How parents manage potential tensions between normative discourses of ‘competent parenting’ and their desires to consume alcohol has received little attention. In this article, we explore the elements that encourage or constrain parents' drinking and investigate how parents consider and manage their alcohol use in the context of multiple social roles with sometimes conflicting demands and expectations around ‘competent parenting’. Our analysis draws on 30 semi‐structured interviews with Australian parents, conducted as part of a broader project which aimed to explore how home drinking is integrated into everyday life. While parents' accounts of drinking alcohol highlighted effects such as embodied experiences of relaxation and facilitating shared adult moments, many participants described drinking less than they otherwise would if their children were not present. Participants discussed various social roles and routines which constrained consumption, with drinking bounded by responsibility. As such, drinking emerged as something needing to be actively negotiated, particularly in light of discourses that frame expectations of what constitutes ‘competent parenting’. When considering parents' alcohol consumption in the future, we argue that it is important to destigmatise their consumption by acknowledging the importance of adults' pleasure and wellbeing, alongside children's needs for safety and modelling of safer alcohol consumption.
Efficient cell factories for the production of N‐methylated amino acids and for methanol‐based amino acid production
Authors: Irla Marta , Wendisch Volker F.
Published: April 2022

The growing world needs commodity amino acids such as L‐glutamate and L‐lysine for use as food and feed, and specialty amino acids for dedicated applications. To meet the supply a paradigm shift regarding their production is required. On the one hand, the use of sustainable and cheap raw materials is necessary to sustain low production cost and decrease detrimental effects of sugar‐based feedstock on soil health and food security caused by competing uses of crops in the feed and food industries. On the other hand, the biotechnological methods to produce functionalized amino acids need to be developed further, and titres enhanced to become competitive with chemical synthesis methods. In the current review, we present successful strain mutagenesis and rational metabolic engineering examples leading to the construction of recombinant bacterial strains for the production of amino acids such as L‐glutamate, L‐lysine, L‐threonine and their derivatives from methanol as sole carbon source. In addition, the fermentative routes for bioproduction of N‐methylated amino acids are highlighted, with focus on three strategies: partial transfer of methylamine catabolism, S‐adenosyl‐L‐methionine dependent alkylation and reductive methylamination of 2‐oxoacids.
Quantitative pupillometry in comatose out‐of‐hospital cardiac arrest patients: A post‐hoc analysis of the TTH48 trial
Authors: Paramanathan Sansuthan , Grejs Anders Morten , Søreide Eldar , Duez Christophe Henri Valdemar , Jeppesen Anni Nørgaard , Reinertsen Åse Johanne , Strand Kristian , Kirkegaard Hans
Published: April 2022

Background

Quantitative pupillometry is an objective method to examine pupil reaction and subsequently grade the response on a neurological pupil index (NPi) scale from 0 to 5. The aim of the present sub‐study was to explore the long‐term prognostic value of NPi in comatose out‐of‐hospital cardiac arrest patients undergoing targeted temperature management (TTM).

Methods

This planned sub‐study of the “Targeted temperature management for 48 versus 24 h and neurological outcome after out‐of‐hospital cardiac arrest: A randomized clinical trial.” NPi was assessed from admission and throughout day 3 and linked to the Cerebral Performance Categories score at 6 months. We compared the prognostic performance of NPi in 65 patients randomized to a target temperature of 33 ± 1°C for 24 or 48 h.

Results

The NPi values were not different between TTM groups (p > .05). When data were pooled, NPi was strongly associated with neurological outcome at day 1 with a mean NPi of 3.6 (95% CI 3.4–3.8) versus NPi 3.9 (3.6–4.1) in the poor versus good outcome group, respectively (p < .01). At day 2, NPi values were 3.6 (3.1–4.0) and 4.1 (3.9–4.2) (p = .01) and at day 3, the values were 3.3 (2.6–4.0) and 4.3 (4.1–4.6), respectively (p < .01). The prognostic ability of NPi, defined by area under the receiver operating characteristic curve was best at day three.

Conclusion

Quantitative pupillometry measured by NPi was not different in the two TTM groups, but overall, significantly associated with good and poor neurological outcomes at 6 months. NPI has a promising diagnostic accuracy, but larger studies are warranted.
Measurement invariance of the University of Rhode Island Change Assessment Scale in Project MATCH: An exploratory structural equation modeling approach
Authors: Richards Dylan K. , Schwebel Frank J. , Cowie Kiefer D. , Pearson Matthew R. , Witkiewitz Katie
Published: April 2022

Background

Progression through the stages of change is a proposed mechanism underlying the effects of treatment for alcohol use disorder (AUD). However, examining stages of change as a mechanism of treatment effects requires that the measure be invariant across patient subgroups, treatment conditions, and time. In this study, we examined measurement invariance of the University of Rhode Island Change Assessment Scale (URICA) in Project MATCH using an exploratory structural equation modeling (ESEM) approach.

Methods

We conducted a secondary analysis of data from Project MATCH (N = 1726; Mage = 40.2, SD = 10.9; 75.7% male; 80% non‐Hispanic white), a multisite randomized clinical trial that tested three AUD treatments: Motivational Enhancement Therapy, Cognitive‐Behavioral Therapy, or Twelve‐Step Facilitation. Participants completed the 24‐item URICA for assessing the stages of change in relation to drinking at baseline and post‐treatment (3 months after baseline).

Results

A 4‐factor ESEM provided a good fit to the data and a better fit to the data than a conventional 4‐factor confirmatory factor analysis model. Further, the URICA demonstrated scalar invariance across each patient subgroup at baseline (sex, ethnicity, marital status, education, and parental history of AUD) and treatment condition at follow‐up. However, the URICA was not longitudinally invariant as the metric model resulted in a significant decrement in model fit.

Conclusions

Measurement invariance of the URICA over time was not supported. Longitudinally invariant measures of the stages of change are needed to test the proposal that progression through the stages explains treatment effects.
Stability and change in the interpretation of facial emotions in fetal alcohol spectrum disorders from childhood to adolescence
Authors: Lindinger Nadine M. , Jacobson Joseph L. , Dodge Neil C. , Malcolm‐Smith Susan , Molteno Christopher D. , Meintjes Ernesta M. , Jacobson Sandra W.
Published: May 2022

Background

The ability to identify and interpret facial emotions plays a critical role in effective social functioning, which may be impaired in individuals with fetal alcohol spectrum disorders (FASD). We previously reported deficits in children with fetal alcohol syndrome (FAS) and partial FAS (PFAS) on the “Reading the Mind in the Eyes” (RME) test, which assesses the interpretation of facial emotion. This follow‐up study in adolescents was designed to determine whether this impairment persists or represents a developmental delay; to classify the RME stimuli by valence (positive, negative, or neutral) and determine whether RME deficits differ by affective valence; and to explore how components of executive function mediate these associations.

Methods

The RME stimuli were rated and grouped according to valence. Sixty‐two participants who had been administered the RME in late childhood (mean ± SD = 11.0 ± 0.4 years) were re‐administered this test during adolescence (17.2 ± 0.6 years). Overall and valence‐specific RME accuracy was examined in relation to prenatal alcohol exposure (PAE) and FASD diagnosis.

Results

Children with FAS (n = 8) and PFAS (n = 15) performed more poorly on the RME than non‐syndromal heavily exposed (HE; n = 19) and control individuals (n = 20). By adolescence, the PFAS group performed similarly to HE and controls, whereas the FAS group continued to perform more poorly. No deficits were seen for positively valenced items in any of the groups. For negative and neutral items, in late childhood individuals with FAS and PFAS performed more poorly than HE and controls, but by adolescence only the FAS group continued to perform more poorly. Test–retest reliability was moderate across the two ages. At both timepoints, the effects in the FAS group were partially mediated by Verbal Fluency but not by other aspects of executive function.

Conclusions

Individuals with full FAS have greater difficulty interpreting facial emotions than those with non‐syndromal HE and healthy controls in both childhood and adolescence. By contrast, RME deficits in individuals with PFAS in childhood represent developmental delay.
Performance of PCR‐based syndromic testing compared to bacterial culture in patients with suspected pneumonia applying microscopy for quality assessment
Authors: Andrews Vigith , Pinholt Mette , Schneider Uffe Vest , Schønning Kristian , Søes Lillian Marie , Lisby Gorm
Published: May 2022

Syndromic testing for lower respiratory tract infections with BioFire® FilmArray® Pneumonia Panel Plus (BF) detects 27 pathogens with a turn‐around‐time of one hour. We compared the performance of BF with culture. Samples from 298 hospitalized patients with suspected pneumonia routinely sent for culture were also analyzed using BF. Retrospectively, patients were clinically categorized as having “pneumonia” or “no pneumonia.” BF and culture were compared by analytical performance, which was evaluated by pathogen concordance, and by clinical performance by comparing pathogen detections in patients with and without pneumonia. The BF results for viruses and atypical bacteria were not included in the performance analysis. In 298 patient samples, BF and culture detected 285 and 142 potential pathogens, respectively. Positive percent agreement (PPA) was 88% (125/142). In patients with community‐acquired pneumonia (CAP), clinical sensitivity was 70% and 51%, and specificity was 43% and 71% for BF and culture, respectively. In patients with hospital‐acquired pneumonia, the corresponding numbers were 55% and 23%, and 47% and 68%. There was no significant improvement of performance, when only high‐quality sputum samples were considered. Efficacy of both BF and culture was low. Both tests are best used in CAP patients for whom the diagnosis has already been clinically established. Indiscriminate use may be clinically misleading and a cause of improper use of antibiotics.
Electrochemical methods to discriminate technology and provenance of Apulian red‐figured pottery. I. VIMP and SECM
Authors: Doménech‐Carbó Antonio , Giannuzzi Michele , Mangone Annarosa , Giannossa Lorena Carla
Published: April 2022

Voltammetry of immobilized particles (VIMP) and scanning electrochemical microscopy techniques are combined to study nanosamples from 60 Apulian red‐figured pottery objects from six Apulian archaeological sites (Altamura, Arpi, Conversano, Egnazia, Monte Sannace, Taranto) and three Attic samples from Pella. The VIMP signatures corresponding to the electrocatalytic effect of microparticulate deposits of the clay body and the black gloss on the oxygen evolution reaction and the oxygen reduction reaction are obtained. These signatures provide information on the reducing/oxidizing conditions of firing. The combination of the above voltammetric data permits us to distinguish between Apulian production and Attic importations as well as to discriminate the productions from different archaeological sites or even within different technologies in samples from the same site.
Environmental justice and climate change policies
Authors: Resnik David B.
Published: April 2022

Climate change is an environmental justice issue because it is likely to cause disproportionate harm to low‐income countries and low‐income populations in higher‐income countries. While climate change mitigation and adaptation policies may be able to minimize these harms, they could make them worse unless they are developed and implemented with an eye toward promoting justice and fairness. Those who view climate change as an environmental justice issue should be wary of endorsing policies that sound like they promote the cause of social and economic justice, but in fact do not. While climate change policies may help to mitigate the effects of climate change on poor people, there is no guarantee that they will be just at the local, national, or global level. Those who care about global climate justice must remain actively engaged in policy formation and implementation to ensure that justice does not get shortchanged in the response to global warming.
Do we need repeat transurethral resection after en bloc resection for pathological T1 bladder cancer?
Authors: Yanagisawa Takafumi , Sato Shun , Hayashida Yasushi , Okada Yohei , Iwatani Kosuke , Matsukawa Akihiro , Kimura Takahiro , Takahashi Hiroyuki , Egawa Shin , Shariat Shahrokh F. , Miki Jun
Published: April 2022

Objectives

To assess the clinical significance of repeat transurethral resection (reTUR) and surgical margin status after en bloc resection of bladder tumour (ERBT) for pathological T1 (pT1) bladder cancer.

Patients and Methods

We retrospectively analysed the record of 106 patients with pT1 high‐grade bladder cancer who underwent ERBT between April 2013 and February 2021 at multiple institutions. All specimens were reviewed by a genitourinary pathologist. The primary outcome measures were recurrence‐free survival (RFS) and progression‐free survival (PFS) between patients with and those without reTUR. We also analysed the predictive value of surgical margin on the likelihood of residual tumour on reTUR.

Results

A reTUR was performed in 50 of the 106 patients. The 2‐year RFS and 3‐year PFS were comparable between patients who underwent reTUR and those who did not (55.1% vs 59.9%, P = 0.6, 80.6% vs 82.6%, P = 0.6, respectively). No patient was upstaged to pT2 on reTUR. Regarding the surgical margin status, there were no recurrences at the original site in 51 patients with negative horizontal margins. Cox proportional hazard analysis revealed that a positive vertical margin was an independent prognostic factor of worse PFS. On reTUR, six pTa/is residues were detected in patients with a positive horizontal margin, and three pT1 residues were detected in one patient with a positive vertical margin or other adverse pathological features.

Conclusions

A reTUR after ERBT for pT1 bladder cancer appears not to improve either recurrence or progression. Surgical margin status affects prognosis and reTUR outcomes. A reTUR can be omitted after ERBT in patients with pT1 bladder cancer and negative margins; for those with positive horizontal or vertical margins, reTUR should remain the standard until proven otherwise.