bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of TSS on anti-CVB3 through TLR3 pathway
Authors: Zheng Xiao-han , Yuan Ming-ming , Wang Yuan , Zhou Jing , Zhang Lei
Published: March 2022

Toll-like receptors (TLRs) can recognize molecular patterns associated with microorganisms and induce immune responses. TLR3 is responsible for recognizing viruses and making hosts resistant to Coxsackie B3 (CVB3) infection. In this study, we found that Tectorigenin Sodium Sulfonate (TSS) has a TLR3 inhibitory effect and exerts strong anti-CVB3 activity through the TLR3 pathway both in vivo and in vitro. Balb/c mice were infected by ip injection of CVB3 virus, and subcutaneously injected with TSS at 264mg·Kg-1·d-1 for 7 d. The life extension rate of CVB3-infected mice was up to 46.67%, and the mean time to death was prolonged from 6.00 ± 0.47 d to 8.80 ± 2.78 d (P < 0.01). TSS was also able to reduce the level of weight loss in mice, significantly reduce the symptoms of myocarditis caused by CVB3, reduce the virus titer in the heart, improve the spleen and thymus index, and enhance immune function. We further explored the underlying mechanism of TSS in CVB3-infected HT-29 cells and mice: TSS reduced TLR3 expression and downregulated its downstream TRIF, TRAF6, IRF3, NF-κ B. MAPK, AP1 expression, reduced expression of IFN-β、IL-6、TNF-α. TSS has strong anti-CVB3 activity in vitro and in vivo and has the effect of inhibiting the activation of TLR3 pathway.

IMPORTANCE

TSS is expected to be an antiviral drug for the treatment of CVB3 infection. Its regulatory effect on the immune system provides a new approach for antiviral research.
Vomocytosis ofCryptococcus neoformanscells from murine, bone marrow-derived dendritic cells
Authors: Pacifici Noah , Cruz-Acuña Melissa , Diener Agustina , Senthil Neeraj , Han Hyunsoo , Lewis Jamal S.
Published: March 2022

Cryptococcus neoformans(CN) cells survive within the acidic phagolysosome of macrophages for extended times, then escape without impacting the viability of the host cell via a phenomenon that has been coined ‘vomocytosis’. Through this mechanism, CN disseminate throughout the body, sometimes resulting in a potentially fatal condition - Cryptococcal Meningitis (CM). Justifiably, vomocytosis studies have focused primarily on macrophages, as alveolar macrophages within the lung act as first responders that ultimately expel this fungal pathogen. Herein, we hypothesize that dendritic cells (DCs), an innate immune cell with attributes that include phagocytosis and antigen presentation, can also act as ‘vomocytes’. Presciently, this report shows that vomocytosis of CN indeed occurs from DCs. Primarily through time-lapse microscopy imaging, we show that rates of vomocytosis events from DCs are comparable to those seen from macrophages and further, are independent of the presence of the CN capsule and infection ratios. Moreover, phagosome-altering drugs such as chloroquine and bafilomycin A, as well as the actin-modifying drug, cytochalasin B inhibit this phenomenon from DCs. Although DC immunophenotype does not affect the total number of vomocytic events, we observed differences in the numbers of CN per phagosome and expulsion times. Interestingly, these observations were similar in primary, murine macrophages. Understanding the vomocytic behavior of different phagocytes and their phenotypic subtypes is needed to help elucidate the full picture of the dynamic interplay between CN and the immune system. Critically, deeper insight into vomocytosis could reveal novel approaches to treat CM, as well as other immune-related conditions.
Sleep spindles favor emotion regulation over memory consolidation of stressors in PTSD
Authors: Natraj Nikhilesh , Neylan T.C. , Yack L.M. , Metzler T.J. , Woodward S.H. , Hubachek S.Q. , Dukes C. , Udupa N.S. , Mathalon D.H. , Richards A.
Published: March 2022

Posttraumatic stress disorder (PTSD) is a trauma-induced debilitating condition, with symptoms that revolve around a declarative memory of a severe stressor. How does the brain process declarative and emotional information of stressors in PTSD? We evaluated the role of NREM sleep spindles in this process after exposure to laboratory stress, in a cohort of human subjects with different levels of PTSD symptoms. Subjects performed two laboratory visits: 1) a stress visit which involved exposure to negatively-valent images in the morning and 2) a control visit. In both visits subjects had a sleep/nap opportunity in the afternoon monitored via electroencephalography (EEG). In the stress visit, self-reported anxiety confirmed elevated stress immediately after stressor exposure (pre-sleep) that decayed to control levels post-sleep. An image recall session took place in the late afternoon. Overall, NREM2 spindle rates were elevated in the stress visit as compared to the control visit. This increase in NREM2 spindle rates, especially over occipital cortex, was significantly greater in subjects with high vs. low PTSD symptoms. However in high-PTSD subjects, NREM2 spindle rates correlated with poorer recall accuracy of stressor images as compared to lower symptomatic individuals while surprisingly correlating with a greater reduction in anxiety levels across sleep. Thus although NREM2 spindles are known to play a role in declarative memory processes, our findings highlight an important role of NREM sleep in favoring sleep-dependent anxiety regulation over memory consolidation after exposure to stressors in PTSD and shed new light on the function of NREM2 spindles in PTSD.
Single-cell dissection of a collective behaviour in honeybees
Authors: Traniello Ian M. , Bukhari Syed Abbas , Dibaeinia Payam , Serrano Guillermo , Avalos Arian , Ahmed Amy Cash , Sankey Alison L. , Hernaez Mikel , Sinha Saurabh , Zhao Sihai Dave , Catchen Julian , Robinson Gene E.
Published: March 2022

Understanding how genotypic variation results in phenotypic variation, a major challenge in biology, is especially difficult for collective behaviour because collective group phenotypes arise from complex interactions between group members1. Honeybees aggressively defend their colony from attacks with highly integrated collective behaviour in which different groups of bees play specific roles, giving rise to distinct colony-level differences in aggression. A previous genome-wide association study of a population of Africanized honeybees (Apis mellifera scutellata) from Puerto Rico that recently evolved decreased aggression identified hundreds of genes with single nucleotide polymorphisms (SNPs) that associated with colony-level variation in aggression2. Many of these SNPs also showed strong signals of selection for decreased aggression2,3, but their influence on brain function was unknown. Using brain single-cell (sc) transcriptomics and sc gene regulatory network analysis, we show here that variants of these genes give rise to genetic differences in transcription factor-target gene relationships. These differences involved the activity of several TFs, some that have been previously associated with aggression, likesingle stranded-binding protein c31A, and some that have been associated with tissue morphogenesis but not behaviour, likeapontic. The activity of these and other TFs was located in specific brain cell populations related to olfaction and vision, the two sensory modalities that bees use in colony defence. They also implicate metabolism of serotonin, a neurochemical already known to influence honeybee aggression, but not from a genetic perspective. Surprisingly, genetic differences were more pronounced in the brains of forager bees than in similarly aged but more aggressive soldier bees, pointing to an evolutionary change in division of labour for colony defence. Our results demonstrate how group genetics can shape a collective phenotype by modulating individual brain gene regulatory network architecture.
Reproducible and sensitive micro-tissue RNA-sequencing from formalin-fixed paraffin-embedded tissue for spatial gene expression analysis
Authors: Matsunaga Hiroko , Arikawa Koji , Yamazaki Miki , Wagatsuma Ryota , Ide Keigo , Zachariah Samuel Ashok , Takamochi Kazuya , Suzuki Kenji , Hayashi Takuo , Hosokawa Masahito , Kambara Hideki , Takeyama Haruko
Published: March 2022

Spatial transcriptome analysis of formalin-fixed paraffin-embedded (FFPE) tissues using RNA-sequencing (RNA-seq) provides interactive information on morphology and gene expression, which is useful for clinical applications. However, despite the advantages of long-term storage at room temperature, FFPE tissues may be severely damaged by methylene crosslinking and provide less gene information than fresh-frozen tissues. In this study, we proposed a sensitive FFPE micro-tissue RNA-seq method that combines the punching of tissue sections (diameter: 100 μm) and the direct construction of RNA-seq libraries. We evaluated a method using mouse liver tissues at 2 years after fixation and embedding and detected approximately 7,000 genes in micro-punched tissue-spots (thickness: 10 μm), similar to that detected with purified total RNA (2.5 ng) equivalent to the several dozen cells in the spot. We applied this method to clinical FFPE specimens of lung cancer that had been fixed and embedded 6 years prior, and found that it was possible to determine characteristic gene expression in the microenvironment containing tumor and non-tumor cells of different morphologies. This result indicates that spatial gene expression analysis of the tumor microenvironment is feasible using FFPE tissue sections stored for extensive periods in medical facilities.
DNA methylation in human gastric epithelial cells allows cell type-related plasticity and defines regional identity
Authors: Fritsche Kristin , Boccellato Francesco , Schlaermann Philipp , Koeppel Max , Denecke Christian , Gut Ivo , Meyer Thomas F. , Berger Hilmar
Published: March 2022

Background

Epigenetic modifications in mammalian DNA are commonly manifested by DNA methylation. In the stomach, altered DNA methylation patterns have been observed following chronic Helicobacter pylori infections and in gastric cancer. In the context of epigenetic regulation, the regional nature of the stomach has been rarely considered in detail.

Results

Here, we describe the DNA methylation landscape across the phenotypically different regions of the healthy human stomach (i.e., antrum, corpus, fundus) together with the corresponding transcriptomes. We show that stable regional DNA methylation differences translate to a limited extent into regulation of the transcriptomic phenotype, indicating a largely permissive epigenetic regulation. We identify a small number of transcription factors with novel region-specific activity and likely epigenetic impact in the stomach, including GATA4, IRX5, IRX2, PDX1, and CDX2. Detailed analysis of the Wnt pathway reveals differential regulation along the craniocaudal axis, which involves non-canonical Wnt signaling in determining cell fate in the proximal stomach.

Conclusions

By extending our analysis to pre-neoplastic lesions and gastric cancers, we conclude that epigenetic dysregulation already characterizes intestinal metaplasia as a founding basis for functional changes in gastric cancer. Finally, our study provides a well-defined resource of regional stomach transcription and epigenetics as a starting point for further studies.
Glia-neuron coupling via a bipartite sialylation pathway promotes neural transmission and stress tolerance in Drosophila
Authors: Scott Hilary , Novikov Boris , Ugur Berrak , Allen Brooke , Mertsalov Ilya , Monagas-Valentin Pedro , Koff Melissa , Robinson Sarah Baas , Aoki Kazuhiro , Veizaj Raisa , Lefeber Dirk , Tiemeyer Michael , Bellen Hugo , Panin Vlad
Published: March 2022

Modification by sialylated glycans can affect protein functions, underlying mechanisms that control animal development and physiology. Sialylation relies on a dedicated pathway involving evolutionarily conserved enzymes, including CMP-sialic acid synthetase (CSAS) and sialyltransferase (SiaT) that mediate the activation of sialic acid and its transfer onto glycan termini, respectively. In Drosophila, CSAS and DSiaT genes function in the nervous system, affecting neural transmission and excitability. We found that these genes function in different cells: the function of CSAS is restricted to glia, while DSiaT functions in neurons. This partition of the sialylation pathway allows for regulation of neural functions via a glia-mediated control of neural sialylation. The sialylation genes were shown to be required for tolerance to heat and oxidative stress and for maintenance of the normal level of voltage-gated sodium channels. Our results uncovered a unique bipartite sialylation pathway that mediates glia-neuron coupling and regulates neural excitability and stress tolerance.

Graphical Abstract
Patient-derived recombinant autoantibodies reveal the subcellular neuroglial distribution and heterogeneous interactome of leucine-rich glioma-inactivated 1
Authors: Ramirez-Franco Jorge , Debreux Kévin , Extremet Johanna , Maulet Yves , Belghazi Maya , Villard Claude , Sangiardi Marion , Youssouf Fahamoe , Far Lara El , Lévêque Christian , Debarnot Claire , Marchot Pascale , Paneva Sofija , Debanne Dominique , Russier Michael , Seagar Michael , Irani Sarosh R , Far Oussama El
Published: March 2022

Autoantibodies against leucine-rich glioma-inactivated 1 (LGI1) occur in patients with encephalitis who present with frequent focal seizures and a pattern of amnesia consistent with focal hippocampal damage. To investigate whether the cellular and subcellular distribution of LGI1 may explain the localisation of these features, and gain broader insights into LGI1 neurobiology, we analysed the detailed localisation of LGI1, and the diversity of its protein interactome, in mouse brains using recombinant monoclonal LGI1-antibodies derived from encephalitis patients. Combined immunofluorescence and mass spectrometry analyses showed that LGI1 is enriched in excitatory and inhibitory synaptic contact sites, most densely within CA3 regions of the hippocampus. LGI1 is secreted in both neuronal somatodendritic and axonal compartments, and occurs in oligodendrocytic, neuro- oligodendrocytic and astro-microglial protein complexes. Proteomic data support the hypothesis that destabilization of Kv1 / MAGUK complexes by autoantibodies could promote excitability, but did not reveal LGI1 complexes with postsynaptic glutamate receptors. Our results extend our understanding of regional, cellular and subcellular LGI1 expression profiles and reveal novel LGI1-associated complexes, thus providing insights into the complex biology of LGI1 and its relationship to seizures and memory loss.
Generation of raptor diversity in Europe: linking speciation with climate changes and the ability to migrate
Authors: Negro Juan J. , Rodríguez-Rodríguez Eduardo , Rodríguez Airam , Bildstein Keith
Published: March 2022

Aim

Europe should be considered as a diversity hotspot for diurnal raptors, but just during the breeding season, as it holds the higher proportion of transcontinental migratory species of any landmass, and the area becomes depleted during the winter period. This study will test the hypothesis that the high diversification of the raptor assemblage in Europe is a recent event, occurring mainly during the Quaternary, and that closely related species sharing the same trophic niches can only coexist in sympatry during the breeding period, when food availability is higher.

Location

Continental Europe.

Taxon

Diurnal birds of prey (Accipitriformes and Falconiformes).

Methods

A consensus molecular phylogeny for the 38 regular breeding species of raptors in Europe was obtained from BirdTree. For the same species, a trophic niche cluster dendrogram was constructed. Size and migratory strategy were introduced in the resulting phylogeny, where trophic groups were also identified.

Results

A total of 16 trophic groups were identified. Multispecific trophic groups tended to be composed of reciprocal sister species, while monospecific groups (only three) were composed of highly specialized species. According to time calibrated phylogenies, the speciation events took place during the glacial cycles of the Quaternary period in a majority of cases. During the non-breeding season, the smaller species in every trophic group migrate to sub-Saharan Africa, whereas larger species are either non-migratory or perform shorter migrations within Europe and/or northern Africa.

Main conclusions

This investigation illustrates how the rich assemblage of diurnal birds of prey in Europe, more diverse and more migratory than the North American assemblage at equivalent latitudes, has emerged recently due to the multiplication of look-alike species with similar trophic ecologies, mainly in climate refugia during cold periods. In the non-breeding season, when shared food resources are limited, smaller species migrate to Africa and alleviate competition.
PPAR-γ activation promotes xenogenic bioroot regeneration by attenuating the xenograft induced-oxidative stress
Authors: Lan Tingting , Bi Fei , Xu Yuchan , Yin Xiaoli , Chen Jie , Han Xue , Guo Weihua
Published: March 2022

Objective

xenogenic organ transplantation has been considered the most promising strategy in providing possible subtitutes with physiological function of the failing organs as well as solving the problem of insufficient donor sources. However, the xenograft, suffered from immune rejection and ischemia-reperfusion injury (IRI), causes massive ROS expression and the subsequent cell apoptosis, leading to the xenograft failure. Our previous study found a positive role of PPAR-γ in anti-inflammation through its immunomodulation effects, which inspires us to apply PPAR-γ agonist rosiglitazone (RSG) to address survival issue of xenograft with the potential to eliminate the excessive ROS.

Methods

Xenogenic bioroot was constructed by wrapping the dental follicle cells (DFC) with porcine extracellular matrix (pECM). The hydrogen peroxide (H2O2)-induced DFC was pretreated with RSG to observe its protection on the damaged biological function. Immunoflourescence staining and transmission electron microscope were used to detect the intracellular ROS level. SD rat orthotopic transplantation model and SOD1 knockout mice subcutaneous transplantation model were applied to explore the regenerative outcome of the xenograft.

Results

RSG pretreatment significantly reduced the adverse effects of H2O2 on DFC with decreased intracellular ROS expression and alleviated mitochondrial damage. In vivo results confirmed RSG administration substantially enhanced the host’s antioxidant capacity with reduced osteoclasts formation and increased periodontal ligament like tissue regeneration efficiency, maximumly maintaining the xenograft function.

Conclusions

RSG preconditioning could preserve the biological properties of the transplanted stem cells under OS microenvironment and promote organ regeneration by attenuating the inflammatory reaction and OS injury.
Repeated ethanol exposure and withdrawal alters ACE2 expression in discrete brain regions: Implications for SARS-CoV-2 infection
Authors: Balasubramanian Nagalakshmi , James Thomas D , Pushpavathi Selvakumar Govindhasamy , Marcinkiewcz Catherine A.
Published: March 2022

Emerging evidence suggests that people with alcohol use disorders are at higher risk for SARS-CoV-2. SARS-CoV-2 engages angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) receptors for cellular entry. While ACE2 and TMPRSS2 genes are upregulated in the cortex of alcohol-dependent individuals, information on expression in specific brain regions and neural populations implicated in SARS-CoV-2 neuroinvasion, particularly monoaminergic neurons, is limited. We sought to clarify how chronic alcohol exposure affects ACE2 and TMPRSS2 expression in monoaminergic brainstem circuits and other putative SARS-CoV-2 entry points. C57BL/6J mice were exposed to chronic intermittent ethanol (CIE) vapor for 4 weeks and brains were examined using immunofluorescence. We observed increased ACE2 levels in the olfactory bulb and hypothalamus following CIE, which are known to mediate SARS-CoV-2 neuroinvasion. Total ACE2 immunoreactivity was also elevated in the raphe magnus (RMG), raphe obscurus (ROB), and locus coeruleus (LC), while in the dorsal raphe nucleus (DRN), ROB, and LC we observed increased colocalization of ACE2 with monoaminergic neurons. ACE2 also increased in the periaqueductal gray (PAG) and decreased in the amygdala. Whereas ACE2 was detected in most brain regions, TMPRSS2 was only detected in the olfactory bulb and DRN but was not significantly altered after CIE. Our results suggest that previous alcohol exposure may increase the risk of SARS-CoV-2 neuroinvasion and render brain circuits involved in cardiovascular and respiratory function as well as emotional processing more vulnerable to infection, making adverse outcomes more likely. Additional studies are needed to define a direct link between alcohol use and COVID-19 infection.
A Quantitative Modelling Approach for DNA Repair on a Population Scale
Authors: Zeitler Leo , Wilkes Cyril Denby , Goldar Arach , Soutourina Julie
Published: March 2022

Despite intensive research of DNA repair after UV in eukaryotes, a framework to quantitatively describe the dynamics in vivo is still lacking. We developed a new data-driven approach to analyse CPD repair kinetics over time in Saccharomyces cerevisiae. In contrast to other studies that consider sequencing signals as an average behaviour, we introduce a hidden axis representing independent cells where loci can transition from damaged to repaired. This permits the application of the Kolmogorov-Johnson–Mehl–Avrami model to find a region-specific and continuous representation of the entire temporal process. We correlated the parameters via a k-nearest neighbour approach to a variety of genomic features, including transcription rate and nucleosome density. The clearest link was found for the gene size, which has been unreported for budding yeast to our knowledge. The framework hence allows a comprehensive analysis of nuclear processes on a population scale.

Author Summary

As DNA encodes our very identity, it has been subject to a plethora of studies over the last century. The advent of new technologies that permit rapid sequencing of large DNA and RNA samples opened doors to before unknown mechanisms and interactions on a genomic scale. This led to an in-depth analysis of several nuclear processes, including transcription of genes and lesion repair. However, the applied protocols do mostly not allow a high temporal resolution. Quite the contrary, the experiments yield often only some few data signals over several hours. Missing dynamics between time points are chiefly ignored, implicitly assuming that they straightforwardly transition from one to another. Here, we show that such an understanding can be flawed. We use the repair process of UV-induced DNA damage as an example to present a quantitative analysis framework that permits the representation of the entire temporal process with only three parameters. We subsequently describe how they can be linked to other heterogeneous data sets. Consequently, we evaluate a correlation to the whole kinetic process rather than to a single time point. Although the approach is exemplified using DNA repair, it can be readily applied to any other mechanism and sequencing data that represents a state transition between two states, such as damaged and repaired.
MultiHeadGAN: A Deep Learning Method for Low Contrast Retinal Pigment Epithelium Cells Segmentation in Fluorescent Flatmount Microscopy Images
Authors: Yu Hanyi , Wang Fusheng , Theodoro George , Nickerson John , Kong Jun
Published: March 2022

Background

Retinal pigment epithelium (RPE) aging is an important cause of vision loss. As RPE aging is accompanied by changes in cell morphological features, an accurate segmentation of RPE cells is a prerequisite to such morphology analyses. Due the overwhelmingly large cell number, manual annotations of RPE cell borders are time-consuming. Computer based methods do not work well on cells with weak or missing borders in the impaired RPE sheet regions.

Method

To address such a challenge, we develop a semi-supervised deep learning approach, namely MultiHeadGAN, to segment low contrast cells from impaired regions in RPE flatmount images. The developed deep learning model has a multi-head structure that allows model training with only a small scale of human annotated data. To strengthen model learning effect, we further train our model with RPE cells without ground truth cell borders by generative adversarial networks. Additionally, we develop a new shape loss to guide the network to produce closed cell borders in the segmentation results.

Results

In this study, 155 annotated and 1,640 unlabeled image patches are included for model training. The testing dataset consists of 200 image patches presenting large impaired RPE regions. The average RPE segmentation performance of the developed model MultiHeadGAN is 85.4 (correct rate), 88.8 (weighted correct rate), 87.3 (precision), and 80.1 (recall), respectively. Compared with other state-of-the-art deep learning approaches, our method demonstrates superior qualitative and quantitative performance.

Conclusions

Suggested by our extensive experiments, our developed deep learning method can accurately segment cells from RPE flatmount microscopy images and is promising to support large scale cell morphological analyses for RPE aging investigations.
Multi-Layered Maps of Neuropil with Segmentation-Guided Contrastive Learning
Authors: Dorkenwald Sven , Li Peter H. , Januszewski Michał , Berger Daniel R. , Maitin-Shepard Jeremy , Bodor Agnes L. , Collman Forrest , Schneider-Mizell Casey M. , da Costa Nuno Maçarico , Lichtman Jeff W. , Jain Viren
Published: March 2022

Maps of the nervous system that identify individual cells along with their type, subcellular components, and connectivity have the potential to reveal fundamental organizational principles of neural circuits. Volumetric nanometer-resolution imaging of brain tissue provides the raw data needed to build such maps, but inferring all the relevant cellular and subcellular annotation layers is challenging. Here, we present Segmentation-Guided Contrastive Learning of Representations (“SegCLR”), a self-supervised machine learning technique that produces highly informative representations of cells directly from 3d electron microscope imagery and segmentations. When applied to volumes of human and mouse cerebral cortex, SegCLR enabled the classification of cellular subcompartments (axon, dendrite, soma, astrocytic process) with 4,000-fold less labeled data compared to fully supervised approaches. Surprisingly, SegCLR also enabled inference of cell types (neurons, glia, and subtypes of each) from fragments with lengths as small as 10 micrometers, a task that can be difficult for humans to perform and whose feasibility greatly enhances the utility of imaging portions of brains in which many neuron fragments terminate at a volume boundary. These predictions were further augmented via Gaussian process uncertainty estimation to enable analyses restricted to high confidence subsets of the data. Finally, SegCLR enabled detailed exploration of layer-5 pyramidal cell subtypes and automated large-scale statistical analysis of upstream and downstream synaptic partners in mouse visual cortex.
The sugarless grape trait characterized by single berry phenotyping
Authors: Bigard Antoine , Romieu Charles , Ojeda Hernán , Torregrosa Laurent
Published: March 2022

For grape production, an important driver for the selection of varieties better adapted to climate fluctuations, especially warming, is the balance between fruit sugars and acidity. Since the past decades, temperature during ripening has constantly raised causing excessive sugars concentrations and insufficient acidity of the wine grapes in warmest regions. There is thus an increasing interest in breeding new cultivars, able to ripen at lower sugar concentration while preserving fruit acidity. However, the phenotyping of berry composition challenges both methodological and conceptual issues. Indeed, most authors predetermine either average harvest date, ripening duration, thermal time or even hexoses concentration threshold itself, to compare accessions at an hopefully similar ripe stage. Here, we have phenotyped the fruit development and composition of 6 genotypes, including 3 new disease-tolerant varieties known to produce wines with low alcoholic contents. The study was performed at single berry level from the end of green growth stage to the arrest of phloem unloading, when water and solute contents reach a maximum per berry. The results confirmed that sugarless genotypes achieve fruit ripening with 20-30% less hexoses than classical varieties, Grenache N and Merlot N, without impacting berry growth, total acidity or cations accumulation. Sugarless genotypes displayed a higher malic acid/tartaric acid balance than other genotypes with similar sucrose/H+ exchanges at the onset of ripening. Data suggest that sugarless phenotype results from a specific plasticity in the relationship between growth and the turgor imposed by organic acid accumulation and sugar loading. This opens interesting perspectives to understand the mechanism of grapevine berry growth and to breed varieties better coping with climate warming.
Female directors and environmental innovation: is stakeholder orientation a missing link?
Authors: Wang Yu , Chang Xiaoying , Wang Tienan , Wang Shanshan
Published: March 2022

Purpose

The purpose of this study is to examine the effect of stakeholder orientation in mediating the impact of female directors on environmental innovation. The authors argue that female directors are eco-friendly and more concerned with multi-stakeholder interests and demands. Thus, they promote environmental innovation by including more stakeholder-oriented values and beliefs in firm decision-making.

Design/methodology/approach

As the dependent variable in this study is a nonnegative count variable, the authors use a count data model based on Poisson regression. A sample of Chinese listed firms between 2010 and 2020 is used to test the hypotheses.

Findings

The results of this study show that female directors can enhance environmental innovation. Further, stakeholder orientation represents an intermediate channel that accounts for the effects of female directors on environmental innovation. This suggests that having women on a board can lead to better stakeholder management, which, in turn, positively affects environmental innovation. The authors also reveal that female directors contribute more to stakeholder orientation with the presence of female chairpersons.

Originality/value

A significant limitation in the literature is that little attention has been paid to the mechanisms linking female directors to firm outcomes. In the context of environmental innovation, while previous studies have investigated the influence of female directors on environmental innovation, the underlying channels of that influence remain largely unexplored. Therefore, the findings of this study advance the understanding of the effects of female directors on environmental innovation by revealing an important underlying channel – stakeholder orientation.
Enhancing in-store picking for e-grocery: an empirical-based model
Authors: Seghezzi Arianna , Siragusa Chiara , Mangiaracina Riccardo
Published: March 2022

Purpose

This paper identifies, configures and analyses a solution aimed at increasing the efficiency of in-store picking for e-grocers and combining the traditional store-based option with a warehouse-based logic (creating a back area dedicated to the most required online items).

Design/methodology/approach

The adopted methodology is a multi-method approach combining analytical modelling and interviews with practitioners. Interviews were performed with managers, whose collaboration allowed the development and application of an empirically-grounded model, aimed to estimate the performances of the proposed picking solution in its different configurations. Various scenarios are modelled and different policies are evaluated.

Findings

The proposed solution entails time benefits compared to traditional store-based picking for three main reasons: lower travel time (due to the absence of offline customers), lower retrieval time (tied to the more efficient product allocation in the back) and lower time to manage stock-outs (since there are no missing items in the back). Considering the batching policies, order picking is always outperformed by batch and zone picking, as they allow for the reduction of the average travelled distance per order. Conversely, zone picking is more efficient than batch picking when demand volumes are high.

Originality/value

From an academic perspective, this work proposes a picking solution that combines the store-based and warehouse-based logics (traditionally seen as opposite/alternative choices). From a managerial perspective, it may support the definition of the picking process for traditional grocers that are offering – or aim to offer – e-commerce services to their customers.
Survey of non‐native small mammals traded in South Africa
Authors: Shivambu Ndivhuwo , Shivambu Tinyiko C. , Downs Colleen T.
Published: March 2022

The sale of live non‐native animals has become a social norm and is of global concern. The pet trade industry has become one of the main pathways where non‐native small mammals are introduced worldwide. We conducted a questionnaire survey in South African pet shops from September 2018 to September 2019 to gain insights into non‐native small mammalian species trade in South Africa. We also investigated whether the pet shop owners were aware of the South African National Environmental Management: Biodiversity Act (NEM: BA; No. 10 of 2004), which regulates and provides management and conservation of the country's biodiversity. A total of 111 pet shop owners/managers responded to the survey, with 26.6% of the owners reporting the sale of birds, 25.1% of fish and 22.5% of mammals. A total of 16 non‐native small mammalian species were reported sold, with European rabbits (Oryctolagus cuniculus), Norwegian rats (Rattus norvegicus) and house mice (Mus musculus) being the most commonly sold pets. We found that breeders, animal rescues and pet shops were the major suppliers of small mammal pets, and in terms of the regulation, most respondents (67.8%) were aware of NEM: BA. However, despite the knowledge of the regulations, some of the traded species pose a serious invasion threat. As a result, we recommend increased regulation, monitoring and public awareness to prevent the potential negative impacts associated with non‐native mammal species in South Africa.
Comparison of aquatic macroinvertebrate communities of Lake Ahémé (Benin, West Africa) across the short and long wet seasons
Authors: Odountan Olaniran Hamed , Sidi O. I. Massara Nadjib , Janssens de Bisthoven Luc , Bird Matthew S. , Abou Youssouf
Published: March 2022

Seldom investigated for its biodiversity, the biomonitoring of Lake Ahémé is expected to increase in future and a prerequisite is the design of an appropriate sampling strategy. Here, we assessed macroinvertebrate assemblages in relation to environmental conditions in Lake Ahémé during the short and long wet seasons (SWS and LWS, respectively). This will help optimise sampling strategies for the future, when sampling only during the SWS or the LWS. A total of 4049 macroinvertebrates from 28 families and 32 genera were collected. Abundance was significantly higher at sites sampled during the SWS. Molluscs were the most dominant taxon and accounted for 92.8% of individuals collected during this study. This was followed by annelids, insects and crustaceans representing 3.7%, 3.2% and 0.3% of the total abundance, respectively. Biodiversity indices showed a significantly higher diversity in the SWS and higher spatial variation in the macroinvertebrate community. The first three axes of the non‐metric multidimensional scaling revealed spatial changes in the macroinvertebrate community during the SWS and LWS. These changes were driven by salinity, conductivity, pH, temperature, dissolved oxygen and water depth. No taxa could be assigned as indicators in the LWS whereas diverse brackish and freshwater species characterised the SWS. As a result, when considering sampling during the wet seasons, SWS sampling should suffice for a qualitative study whereas an accurate ecological investigation requires both SWS and LWS.
The smile curve: Evolving sources of value added in manufacturing
Authors: Baldwin Richard , Ito Tadashi
Published: March 2022

A dramatic disordering of global manufacturing has been seen in recent years. Production processes have fragmented, and many production stages have been offshored to developing nations. Organization of this new global supply chain has evolved into what are often called global value chains (GVCs). Less studied, but no less important, is the shift in the sectoral source of value added in manufactured exports. This phenomenon, often called the “smile curve,” involves a swing in the share of value added in manufactured exports that is generated in the manufacturing sector itself instead of, for example, in the pre‐ and post‐fabrication stages. Our paper presents new evidence quantifying the magnitude of the smile curve notion. Using international input–output databases, we find evidence supporting the smile curve at the aggregate level. Specifically, for almost all exporting sectors and nations, we find that the value added to exports has shifted decisively from the manufacturing sector to service sectors. We also find that developing countries reduced their own‐sourcing service value‐added share, while developed countries maintained their relatively high levels of own‐sourcing service value‐added share.
Presidential Address: The orca conjecture
Authors: Taylor M. Scott
Published: March 2022

In this address, I argue that the Southern Resident Killer Whale (SRKW) population has been negatively affected by commercial vessel traffic, tied to international trade, in the post‐1998 period. I present new data showing a dramatic increase in both the volume of kilometres travelled and the composition of vessel traffic in the Salish Sea. By exploiting recent work in biology linking vessel noise to changes in foraging and socializing behaviour, I argue that these changes have degraded their habitat significantly. Moreover, because SRKWs and Northern Resident Killer Whales (NRKWs) share prey, this negative vessel disturbance shock to the SRKW is magnified by the existence of across‐population competition. Vessel disturbance magnified by competition for prey has placed the SRKW on a slow‐motion path towards extinction.
Imaging of the nail unit in psoriatic patients:A systematic scoping review of techniques and terminology
Authors: Ortner Vinzent Kevin , Mandel Victor Desmond , Bertugno Serena , Philipsen Peter Alshede , Haedersdal Merete
Published: March 2022

Background

The growing interest in the visualization of psoriatic nail unit changes has led to the discovery of an abundance of image characteristics across various modalities.

Objective

To identify techniques for non‐invasive imaging of nail unit structures in psoriatic patients and review extracted image features to unify the diverse terminology.

Methods

For this systematic scoping review, we included studies available on PubMed and Embase, independently extracted image characteristics, and semantically grouped the identified features to suggest a preferred terminology for each technique.

Results

After screening 753 studies, 67 articles on the visualization of clinical and subclinical psoriatic changes in the nail plate, matrix, bed, folds and hyponychium were included. We identified 4 optical and 3 radiological imaging techniques for the assessment of surface (dermoscopy [n = 16], capillaroscopy [n = 12]), sub‐surface (ultrasound imaging [n = 36], optical coherence tomography [n = 4], fluorescence optical imaging [n = 3]), and deep‐seated psoriatic changes (magnetic resonance imaging [n = 2], positron emission tomography‐computed tomography [n = 1]). By condensing 244 image feature descriptions into a glossary of 82 terms, overall redundancy was cut by 66.4% (37.5%–77.1%). More than 75% of these image features provide additional disease‐relevant information that is not captured using conventional clinical assessment scales.

Conclusions

This review has identified, unified, and contextualized image features and related terminology for non‐invasive imaging of the nail unit in patients with psoriatic conditions. The suggested glossary could facilitate the integrative use of non‐invasive imaging techniques for the detailed examination of psoriatic nail unit structures in research and clinical practice.
Shrinkage versus fragmentation response in neoadjuvantly treated oesophageal adenocarcinoma: significant prognostic relevance
Authors: Graham Martinez Cristina , Kus Öztürk Sonay , Al‐Kaabi Ali , Valkema Maria J , Bokhorst John‐Melle , Rosman Camiel , Rütten Heidi , Wauters Carla A P , Doukas Michail , van Lanschot Joseph Jan‐Baptist , Siersema Peter D , Nagtegaal Iris D , van der Post Rachel Sofia
Published: March 2022

Aims

No consensus exists on the clinical value of tumour regression grading (TRG) systems for therapy effects of neoadjuvant chemoradiotherapy (nCRT) in oesophageal adenocarcinoma. Existing TRG systems lack standardization and reproducibility, and do not consider the morphological heterogeneity of tumour response. Therefore, we aim to identify morphological tumour regression patterns of oesophageal adenocarcinoma after nCRT and their association with survival.

Methods and results

Patients with oesophageal adenocarcinoma, who underwent nCRT followed by surgery and achieved a partial response to nCRT, were identified from two Dutch upper‐gastrointestinal (GI) centres (2005–18; test cohort). Resection specimens were scored for regression patterns by two independent observers according to a pre‐defined three‐step flowchart. The results were validated in an external cohort (2001–17). In total, 110 patients were included in the test cohort and 115 in the validation cohort. In the test cohort, two major regression patterns were identified: fragmentation (60%) and shrinkage (40%), with an excellent interobserver agreement (κ = 0.87). Here, patients with a fragmented pattern had a significantly higher pathological stage (stages III/IV: 52 versus 16%; P < 0.001), less downstaging (48 versus 91%; P < 0.001), a higher risk of recurrence [risk ratio (RR) = 2.9, 95% confidence interval (CI) = 1.5–5.6] and poorer 5‐year overall survival (30 versus 80% respectively, P = 0.001).

Conclusions

The validation cohort confirmed these findings, although had more advanced cases (case‐stages = III/IV 91 versus 73%, P = 0.005) and a higher prevalence of fragmented‐pattern cases (80 versus 60%, P = 0.002). When combining the cohorts in multivariate analysis, the pattern of response was an independent prognostic factor [hazard ratio (HR) = 1.76, 95% CI = 1.0–3.0]. In conclusion, we established an externally validated, reproducible and clinically relevant classification of tumour response.
Research Review: A guide to computing and implementing polygenic scores in developmental research
Authors: Allegrini Andrea G. , Baldwin Jessie R. , Barkhuizen Wikus , Pingault Jean‐Baptiste
Published: March 2022

The increasing availability of genotype data in longitudinal population‐ and family‐based samples provides opportunities for using polygenic scores (PGS) to study developmental questions in child and adolescent psychology and psychiatry. Here, we aim to provide a comprehensive overview of how PGS can be generated and implemented in developmental psycho(patho)logy, with a focus on longitudinal designs. As such, the paper is organized into three parts: First, we provide a formal definition of polygenic scores and related concepts, focusing on assumptions and limitations. Second, we give a general overview of the methods used to compute polygenic scores, ranging from the classic approach to more advanced methods. We include recommendations and reference resources available to researchers aiming to conduct PGS analyses. Finally, we focus on the practical applications of PGS in the analysis of longitudinal data. We describe how PGS have been used to research developmental outcomes, and how they can be applied to longitudinal data to address developmental questions.
Maternal and fetal outcomes of COVID‐19 infection in pregnant women with chronic rheumatic heart disease in a South Asian population: A case series
Authors: Rajan Mamta , Sachan Shikha , Abhinay Abhishek , Verma Bhupendra
Published: March 2022

Rheumatic heart disease (RHD) is associated with an increased risk of adverse maternal, fetal, and neonatal outcomes, particularly in developing countries. The current COVID‐19 pandemic has also affected pregnant women, probably increasing the adverse effects. It is speculated that COVID‐19 infection in pregnant women would further increase the risk of complications. However, factual data is still lacking, especially from resource‐constrained countries. We conducted a case series of 20 pregnant women with RHD and COVID‐19 infection and compared their outcomes with 40 with RHD but without COVDI‐19. We observed a high risk of adverse cardiac and pregnancy effects across the whole cohort of 60 patients. However, the comparative study between the two groups failed to show any incremental risk of complications due to COVID‐19 infection. Although the sample size was limited; the results are encouraging, particularly for developing countries.
Case report: Vaccine Brigade Chicago, Illinois: From founding February to July, 2021
Authors: Blacksin Beth A.
Published: March 2022

The COVID 19 epidemic disrupted every aspect of American life and imposed severe trauma as a result of lockdown, fears of disease or death, separation from and death of loved ones, and daily media coverage of the unfolding pandemic. The following case report describes the experiences of the Vaccine Brigade, a group of Public Health Nurses (PHNs) and other professionals, mostly retired, who organized themselves to provide assistance with vaccine administration in the city of Chicago and Cook County, Illinois. The report describes the founding of their organization in February, 2021 and their work to support vaccine administration in communities of color and other underserved communities. This case report presents a successful model of volunteerism, built on foundational principals of collective decision making, democracy and social justice. Its members developed existing social networks and skills they had learned during their careers as PHNs and activists to create a functional organization that could assist with the task of getting shots into arms.
Development of the healthy airway smooth muscle bundles: The basis to understand airway wall remodelling
Authors: Roth Michael
Published: March 2022

See related article
Viscosity of bridgmanite determined by in situ stress and strain measurements in uniaxial deformation experiments
Authors: Tsujino Noriyoshi , Yamazaki Daisuke , Nishihara Yu , Yoshino Takashi , Higo Yuji , Tange Yoshinori
Published: March 2022

To understand mantle dynamics, it is important to determine the rheological properties of bridgmanite, the dominant mineral in Earth’s mantle. Nevertheless, experimental data on the viscosity of bridgmanite are quite limited due to experimental difficulties. Here, we report viscosity and deformation mechanism maps of bridgmanite at the uppermost lower mantle conditions obtained through in situ stress-strain measurements of bridgmanite using deformation apparatuses with the Kawai-type cell. Bridgmanite would be the hardest among mantle constituent minerals even under nominally dry conditions in the dislocation creep region, consistent with the observation that the lower mantle is the hardest layer. Deformation mechanism maps of bridgmanite indicate that grain size of bridgmanite and stress conditions at top of the lower mantle would be several millimeters and ~10
5
Pa to realize viscosity of 10
21–22
Pa·s, respectively. This grain size of bridgmanite suggests that the main part of the lower mantle is isolated from the convecting mantle as primordial reservoirs.