bluuebunny/crossref_metadata_2025 huggingface dataset:
miR-15b-5p REGULATES THE NLRP3 INFLAMMASOME SIGNAL THROUGH TARGETING SIRT3 TO REGULATE HYPOXIA/REOXYGENATION-INDUCED CARDIOMYOCYTE PYROPTOSIS PROCESS
Authors: Xu Jiawei , Chen Xuexia , Nie Wenhong
Published: August 2022

Hypoxia/reoxygenation (H/R) induces pyroptosis in the setting of acute myocardial infarction (AMI). Previous studies have shown that the expression of the miR-15 family is stimulated in myocardial ischemia–reperfusion injury or H/R-induced cardiomyocyte injury, and miR-15 is a promoter of cardiac ischemia–reperfusion or H/R injury. However, whether miR-15b-5p regulates H/R injury and cardiomyocyte pyroptosis and its mechanism still need to be further clarified. Bioinformatics analysis elicited that SIRT3 was the downstream regulatory target gene of miR-15b-5p. SIRT3 has been shown to participate in the regulation of pyroptosis by negatively regulating the NLRP3 inflammasome pathway. Therefore, we hypothesized that miR-15b-5p targets SIRT3 and activated the NLRP3 inflammasome pathway to promote H/R-induced cardiomyocyte pyroptosis. We first show that H/R increases miR-15b-5p in rat cardiomyocytes H9C2. Next, we tested the effects of inhibition of miR-15b-5p or overexpression of SIRT3. We found that miR-15b-5p downregulation or SIRT3 overexpression could reverse the H/R-induced pyroptosis. Furthermore, silencing SIRT3 antagonized the protective effect of miR-15b-5p downregulation on H9C2 cells. NLRP3 inhibitor MCC950 annulled the previously mentioned antagonistic effect of silencing SIRT3 on the protection of miR-15b-5p downregulation against pyroptosis. We then used a rat AMI model to analyze myocardial infarction area by triphenyl tetrazolium chloride staining and assess serum cardiac troponin T level by ELISA and found that miR-15b-5p silencing reduced AMI injury in rats. Collectively, these results suggest that miR-15b-5p increase H/R-induced pyroptosis in cardiomyocytes by targeting SIRT3 and activating the NLRP3 inflammasome.
EFFECTS OF SHENFU INJECTION ON SUBLINGUAL MICROCIRCULATION IN SEPTIC SHOCK PATIENTS: A RANDOMIZED CONTROLLED TRIAL
Authors: Wang Shiwei , Liu Guoxiang , Chen Li , Xu Xinhui , Jia Tianyuan , Zhu Changqing , Xiong Jianfei
Published: August 2022

Background and Objective: The optimization of macrocirculatory hemodynamics is recommended by current sepsis guidelines. However, microcirculatory dysfunction is considered the cause of severe sepsis. In the present study, we designed to verify whether the application of Shenfu injection (SFI) restores microcirculation, thereby improving tissue perfusion and inhibiting organ dysfunction, resulting in improved outcomes. Design: We conducted a prospective, single-center, randomized, double-blind, placebo-controlled clinical trial. Intervention: Patients were randomly assigned to group receiving SFI (n = 20) or placebo (n = 20) for 5 days. We administered SFI or glucose injection for 5 days and blinded the investigators and clinical staff by applying light-proof infusion equipment that concealed therapy allocation. Measurements and Results: We measured the systemic dynamics and lactate levels, biomarkers of endothelial dysfunction, and inflammatory cytokines in the plasma. The parameters of sublingual microcirculation were assessed using side-stream dark-field imaging. Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACHE) score, total dose, and duration of vasopressor use, emergency intensive care unit (EICU) stay, and 28-day mortality were evaluated. After treatment with SFI, the disturbance of the sublingual microcirculation was considerably alleviated, as indicated by the significant increase in total vessel density, perfused vessel density, and microvascular flow index. Moreover, the plasma biomarker levels of endothelial dysfunction, including Ang-2, Syn-1, and ET-1, were reversed after SFI treatment. Importantly, the SFI group had a more favorable prognosis than the control group in terms of the APACHE-II score, SOFA score, duration of vasopressor administration, and length of EICU stay. However, the difference in mortality at day 28 was not statistically different between the SFI (15%, 3/20) and placebo (25%, 5/20) groups (P = 0.693). Conclusions: Shenfu injection provided apparent effects in improving sublingual microcirculatory perfusion in patients with septic shock, and this protection may be related with the inhibition of endothelial dysfunction and vasodilatory effects.
Therapeutic Effects of 4 Surgical Approaches for Small Gastrointestinal Stromal Tumors: A Network Meta-analysis
Authors: Yu Zhiyuan , Tu Huaiyu , Liang Chen , Qiu Shuzhong , Dong Xiaoyu , Zhang Yonghui , Ma Chao , Li Peiyu
Published: August 2022

This study aims to systematically evaluate the efficacy of endoscopic resection (ER), laparoscopic resection (LR), laparoscopic endoscopic cooperative surgery (LECS), and open surgery (OpS) for gastrointestinal stromal tumors with small diameters (≤5 cm). Relevant studies were collected through Pubmed, Cochrane Library, and Embase databases. Operative time, hospital stays, time to liquid diet, intraoperative bleeding, and complications were used as outcome indicators for meta-analysis. Twenty-four retrospective cohort studies with 2406 participants were analyzed. LR and OpS groups had longer operating time than the ER group. ER, LECS, and LR groups had decreased lengths of hospital stay than the OpS group. Moreover, patients in LR and LECS groups had fewer complications than those in the OpS group. Endoscopic operation for small gastrointestinal stromal tumors contributes to shortened lengths of surgery and hospital stay. This reduces intraoperative blood loss and promotes gastroenteric functional recovery without increasing the risk of complications or tumor recurrence.
‘Cloudbuster’: a Python-based open source application for three-dimensional reconstruction and quantification of stacked biological imaging samples
Authors: Rohwedder A. , Knipp S. , Esteves F. O. , Hale M. , Ketchen S. E. , Treanor D. , Brüning-Richardson A.
Published: August 2022

Three-dimensional (3D) spheroid cultures are generating increasing interest in cancer research, e.g. for the evaluation of pharmacological effects of novel small molecule inhibitors. This is mainly due to the fact that such 3D structures reflect physiological characteristics of tumours and the cellular microenvironments they reside in more faithfully than two-dimensional (2D) cell cultures; in addition, they allow the reduction of animal experiments while providing significantly relevant human-based models. Quantification of such organoid structures as well as the mainly slice-based acquisition and thus forced 2D representation of 3D spheroids provide a challenge for the interpretation of the associated generated data. Here, we provide a novel open-source workflow to reconstruct a 3D entity from slice-recorded microscopical images with or without treatment with anti-migratory small molecule inhibitors. This reconstruction produces distinct point clouds as basis for subsequent comparison of basic readout parameters using average computer processor, memory and graphics resources within an acceptable time frame. We were able to validate the usefulness of this workflow using 3D data generated by various imaging techniques, including
z
-stacks from confocal microscopy and histochemically labelled spheroid sectioning, and demonstrate the possibility to accurately characterize inhibitor effects in great detail.
Potential of stem cell seeded three-dimensional scaffold for regeneration of full-thickness skin wounds
Authors: Khan Irfan , Siddiqui Marium Naz , Jameel Fatima , Qazi Rida-e-Maria , Salim Asmat , Aslam Shazmeen , Zaidi Midhat Batool
Published: August 2022

Hypoxic wounds are tough to heal and are associated with chronicity, causing major healthcare burden. Available treatment options offer only limited success for accelerated and scarless healing. Traditional skin substitutes are widely used to improve wound healing, however, they lack proper vascularization. Mesenchymal stem cells (MSCs) offer improved wound healing; however, their poor retention, survival and adherence at the wound site negatively affect their therapeutic potential. The aim of this study is to enhance skin regeneration in a rat model of full-thickness dermal wound by transplanting genetically modified MSCs seeded on a three-dimensional collagen scaffold. Rat bone marrow MSCs were efficiently incorporated in the acellular collagen scaffold. Skin tissues with transplanted subcutaneous scaffolds were histologically analysed, while angiogenesis was assessed both at gene and protein levels. Our findings demonstrated that three-dimensional collagen scaffolds play a potential role in the survival and adherence of stem cells at the wound site, while modification of MSCs with jagged one gene provides a conducive environment for wound regeneration with improved proliferation, reduced inflammation and enhanced vasculogenesis. The results of this study represent an advanced targeted approach having the potential to be translated in clinical settings for targeted personalized therapy.
Current strategies with implementation of three-dimensional cell culture: the challenge of quantification
Authors: Temple Jonathan , Velliou Eirini , Shehata Mona , Lévy Raphaël , Gupta Priyanka
Published: August 2022

From growing cells in spheroids to arranging them on complex engineered scaffolds, three-dimensional cell culture protocols are rapidly expanding and diversifying. While these systems may often improve the physiological relevance of cell culture models, they come with technical challenges, as many of the analytical methods used to characterize traditional two-dimensional (2D) cells must be modified or replaced to be effective. Here we review the advantages and limitations of quantification methods based either on biochemical measurements or microscopy imaging. We focus on the most basic of parameters that one may want to measure, the number of cells. Precise determination of this number is essential for many analytical techniques where measured quantities are only meaningful when normalized to the number of cells (e.g. cytochrome p450 enzyme activity). Thus, accurate measurement of cell number is often a prerequisite to allowing comparisons across different conditions (culturing conditions or drug and treatment screening) or between cells in different spatial states. We note that this issue is often neglected in the literature with little or no information given regarding how normalization was performed, we highlight the pitfalls and complications of quantification and call for more accurate reporting to improve reproducibility.
An insight into the iPSCs-derived two-dimensional culture and three-dimensional organoid models for neurodegenerative disorders
Authors: Bhargava Anushka , Sandoval Castellanos Ana M. , Shah Sonali , Ning Ke
Published: August 2022

The use of induced pluripotent stem cells (iPSCs) is a promising approach when used as models to study neurodegenerative disorders (NDDs)
in vitro
. iPSCs have been used in
in vitro
two-dimensional cultures; however, these two-dimensional cultures do not mimic the physiological three-dimensional cellular environment. The use of iPSCs-derived three-dimensional organoids has risen as a powerful alternative to using animal models to study NDDs. These iPSCs-derived three-dimensional organoids can resemble the complexity of the tissue of interest, making it an approachable, cost-effective technique, to study NDDs in an ethical manner. Furthermore, the use of iPSCs-derived organoids will be an important tool to develop new therapeutics and pharmaceutics to treat NDDs. Herein, we will highlight how iPSCs-derived two-dimensional cultures and three-dimensional organoids have been used to study NDDs, as well as the advantages and disadvantages of both techniques.
Parallel Networks to simulate complex multicellular dynamics - A proof of concept with intervertebral disc cell systems
Authors: Baumgartner Laura , Gonzalez Ballester Miguel Angel , Noailly Jerome
Published: August 2022

Background: Network models are convenient to represent in a mechanistic way the complexity of cell biological activity. Dynamic simulations of such networks might require approximations of equation parameters through reverse engineering, numerous and costly experimental research, and/or have limited capacity to explore cell responses to chronic, dose-dependent stimulus exposure. Here we present a mechanistic methodology allowing the simulation of interrelated cell responses of multicellular systems to multifactorial stimuli with dose-and time dependent network links. Methods: a mathematical framework to approach systems biology research questions is presented, the Parallel Networks (PN)-Methodology. It consists of a novel concept, where multicellular systems are described as many relatively small feed-forward networks acting in parallel. Each parallel network is calculated through a specifically designed ordinary differential equation (ODE). Through a unique approach to feed the ODE with interrelated parameters, a system of decoupled, analytically resolvable ODE was obtained. Results: Applied to intervertebral disc multicellular systems, virtual environments of multifactorial stimuli and multiple cell responses simulating daily moving activities, and to microgravity could successfully be created. Conclusions: The PN-Methodology stands for a one-of-a-kind mathematical methodology to approximate dynamics of complex multicellular systems over long periods of time at low computational costs.
Predator feeding rates may often be unsaturated under typical prey densities
Authors: Coblentz Kyle E. , Novak Mark , DeLong John P.
Published: August 2022

Predator feeding rates (described by their functional response) must saturate at high prey densities. Although thousands of manipulative functional response experiments show feeding rate saturation at high densities under controlled conditions, it is unclear how saturated feeding rates are at natural prey densities. The general degree of feeding rate saturation has important implications for the processes determining feeding rates and how they respond to changes in prey density. To address this, we linked two databases – one of functional response parameters and one on mass-abundance scaling – through prey mass to calculate a feeding rate saturation index. We find that: 1) feeding rates may commonly be unsaturated and 2) the degree of saturation varies with predator and prey taxonomic identities and body sizes, habitat, interaction dimension, and temperature. These results reshape our conceptualization of predator-prey interactions in nature and suggest new research on the ecological and evolutionary implications of unsaturated feeding rates.
Assessing the accuracy of paired and random sampling for quantifying plant–plant interactions in natural communities
Authors: Michalet Richard , Losapio Gianalberto , Kikvidze Zaal , Brooker Rob W. , Butterfield Bradley J. , Callaway Ragan M. , Cavieres Lohengrin A. , Lortie Christopher J. , Pugnaire Francisco I. , Schöb Christian
Published: August 2022

Interactions among plant species in extreme ecological systems are often inferred from spatial associations and quantified by means of paired sampling. Yet, this method might be confounded by habitat-sharing effects, in particular when microenvironmental heterogeneity and stress are high. Here, we address whether paired and random sampling methods provide similar results at varying levels of environmental heterogeneity. Furthermore, we investigate how the relationship between species preferences and abiotic severity influences the outcome of these two methods. We quantified spatial associations with the two methods at three sites that encompass different micro-environmental heterogeneity and stress levels: semi-arid environments in Canary Islands, Spain and Sardinia, Italy and a cold alpine environment in Hokkaido (Japan). Then, we simulated plant communities with different levels of species micro-habitat preferences, environmental heterogeneity and stress levels. We found that differences in species associations between paired and random sampling were indistinguishable from zero in our model simulations. At each site, there were strong differences between beneficiary species in their spatial association with benefactor species, and associations became more positive with increasing stress in Spain. Most importantly, there were no differences in the results yielded by the two methods at any of the different stress levels at the Spanish and Japanese sites. At the Italian site, although micro-environmental heterogeneity was low, we found weakly significant differences between methods that were unlikely due to habitat-sharing effects. We conclude that the paired sampling method can provide significant insights into net, long-term effects of plant interactions in spatially conspicuous environments.
MONI-k: An index for efficient pangenome-to-pangenome comparison
Authors: Gagie Travis
Published: August 2022

Maximal exact matches (MEMs) are widely used in bioinformatics, originally for genome-to-genome comparison but especially for DNA alignment ever since Li (2013) presented BWA-MEM. Building on work by Bannai, Gagie and I (2018) and again targeting alignment, Rossi et al. (2022) recently built an index called MONI that is based on the run-length compressed Burrows-Wheeler Transform and can find MEMs efficiently with respect to pangenomes.

In this paper we define k-MEMs to be maximal substrings of a pattern that each occur exactly at least k times in a text (so a MEM is a 1-MEM) and briefly explain why computing k-MEMs could be useful for pangenome-to-pangenome comparison. We then show that, when k is given at construction time, MONI can easily be extended to find k-MEMs efficiently as well.
Grazers and predators mediate the post-settlement bottleneck in Caribbean octocoral forests
Authors: Wells Christopher D. , Benz Joseph , Tonra Kaitlyn J. , Anderson Emily R. , Lasker Howard R.
Published: August 2022

Caribbean octocorals have not suffered the decades long decline in abundance that has plagued reef-building scleractinian corals. Their success and the formation of octocoral forests has been attributed to their continuing recruitment to reef habitats. Assessing the processes controlling recruitment is essential to understanding the success of octocorals and predicting their future. Benthic grazers on coral reefs can facilitate the growth and recruitment of corals by reducing the abundance of competitive algal turfs and macroalgae or hinder corals through predation of coral tissue and recruits. We assessed the effects of grazing by fishes and the sea urchinDiadema antillarumand mesofaunal predation on octocoral recruitment in a series of manipulative experiments using varying grazer/predator exclusion and inclusion conditions inin situandex situexperiments. Exposure to fish and urchin grazing significantly reduced survival and recruitment of single-polyp octocorals, while turf-associated mesofauna did not significantly affect neither recruitment nor survival. We also found a positive relationship between octocoral recruitment and turf algae, a potential related response to the deleterious effect of grazing exposure. These data suggest that grazers and predators mediate the mortality bottleneck characteristic of recruitment. Thus, the declines in the abundance of grazing fishes and urchins throughout the Caribbean may have contributed to the increase in abundance of octocorals in the Caribbean, concurrent with the loss of scleractinians.
The cosmopolitan appendicularian Oikopleura dioica reveals hidden genetic diversity around the globe
Authors: Masunaga Aki , Mansfield Michael J , Tan Yongkai , Liu Andrew W , Bliznina Aleksandra , Barzaghi Paolo , Hodgetts Tamara L , Ferrández-Roldán Alfonso , Cañestro Cristian , Onuma Takeshi A , Plessy Charles , Luscombe Nicholas M
Published: August 2022

Appendicularian tunicates are some of the most abundant mesozooplankton organisms with key roles in marine trophic webs and global carbon flux. Like most appendicularians with cosmopolitan distributions, Oikopleura dioica Fol, 1872 is considered a single species worldwide based on morphological features that distinguish them from other appendicularians. Despite their abundance however, there are still only ∼70 described appendicularian species, compared with over 2,800 ascidian tunicates. Here we perform a molecular phylogenetic, morphological, and reproductive assessment of O. dioica specimens collected from the Ryukyu Archipelago, mainland Japan, and Europe. The specimens are morphologically very similar, with only detailed examination of the oikoplastic epithelium and quantitative measurements revealing minor distinguishing characteristics. Phylogenetic analyses of the ribosomal gene loci and mitochondrial cytochrome oxidase I (COI) gene strongly indicate that they form three separate genetic clades despite their morphological similarities. Finally, in vitro crosses between the Ryukyu and mainland Japanese specimens show total prezygotic reproductive isolation. Our results reveal that the current taxonomic O. dioica classification likely hides multiple cryptic species, highlighting the genetic diversity and complexity of their population structures. Cryptic organisms are often hidden under a single species name because their morphological similarities make them difficult to disinguish and their correct identification is fundamental to understanding Earth’s biodiversity. O. dioica is an attractive model to understand how morphological conservation can be maintained despite pronounced genetic divergence.
CRISPR/Cas9 mutants delineate roles ofPopulus FTandTFL1/CEN/BFTfamily members in growth, dormancy release and flowering
Authors: Sheng Xiaoyan , Mahendra R. Ayeshan , Wang Chieh-Ting , Brunner Amy M.
Published: August 2022

Vegetative and reproductive phase change and phenology are economically and ecologically important traits. Trees typically require several years of growth before flowering and once mature, seasonal control of the transition to flowering and flower development is necessary to maintain vegetative meristems and for reproductive success. Members of two related gene subfamilies,FLOWERING LOCUST (FT)andTERMINAL FLOWER1 (TFL1)/CENTRORADIALIS (CEN)/BROTHER OF FT AND TFL1 (BFT), have antagonistic roles in flowering in diverse species and roles in vegetative phenology in trees, but many details of their functions in trees have yet to be resolved. Here, we used CRISPR/Cas9 to generate single and double mutants involving the fivePopulus FTandTFL1/CEN/BFTgenes.ft1mutants exhibited wild-type-like phenotypes in long days and short days, but after chilling to release dormancy showed delayed bud flush and GA3could compensate for theft1mutation. After rooting and generating some phytomers in tissue culture, bothcen1andcen1ft1mutants produced terminal as well as axillary flowers, indicating that thecen1flowering phenotype is independent ofFT1. Some axillary meristems initially generated phytomers and in potted plants, the timing of flowering in these shoots correlated with upregulation ofFT2in maturing leaves, suggesting that, in long days,CEN1antagonizesFT2promotion of flowering but enablesFT2promotion of shoot growth by maintaining indeterminacy of the shoot apical meristem.CEN1showed distinct circannual expression patterns in vegetative and reproductive tissues and comparison with the expression patterns ofFT1andFT2suggest that the relative levels ofCEN1compared toFT1andFT2regulate multiple phases of vegetative and reproductive seasonal development.
Synergistic action of the Arabidopsis spliceosome components PRP39a and SmD1 in promoting post-transcriptional transgene silencing
Authors: Bazin Jérémie , Elvira-Matelot Emilie , Blein Thomas , Jauvion Vincent , Bouteiller Nathalie , Cao Jun , Crespi Martin D. , Vaucheret Hervé
Published: August 2022

Besides regulating splicing, the conserved spliceosome component SmD1 was shown to promote posttranscriptional silencing of sense transgenes (S-PTGS). Here, we show that the conserved spliceosome component PRP39a also plays a role in S-PTGS. However, PRP39a and SmD1 actions appear distinct in both splicing and S-PTGS. Indeed, RNA-seq analysis of prp39a and smd1 mutants identified different sets of deregulated mRNAs and non-coding RNAs, both at expression level and alternative splicing genome-wide. Moreover, double mutant analyses involving prp39a or smd1 and RNA quality control (RQC) mutants revealed genetic interactions of SmD1 and PRP39a with distinct nuclear RQC machineries, suggesting synergistic rather than redundant roles in the RQC/PTGS interplay. Supporting this hypothesis, a prp39a smd1 double mutant exhibited enhanced suppression of S-PTGS compared with single mutants. Because no major changes in the expression of PTGS or RQC components or in small RNA production were identified in prp39a and smd1 mutants, and because prp39a and smd1 mutations do not alter PTGS triggered by inverted-repeat transgenes directly producing dsRNA (IR-PTGS), PRP39a and SmD1 seem to synergistically promote a step specific to S-PTGS. We propose that, independent of their specific roles in splicing, PRP39a and SmD1 limit 3’-to-5’ and 5’-to-3’ degradation of transgene aberrant RNAs, respectively, thus favoring the export of aberrant RNAs to the cytoplasm where their transformation into dsRNA initiates S-PTGS.
Distantly related hepaciviruses share common entry factor, Claudin-1
Authors: Toon Kamilla , Kalemera Mphatso D , Palor Machaela , Rose Nicola J. , Takeuchi Yasuhiro , Grove Joe , Mattiuzzo Giada
Published: August 2022

Due to increased and broadened screening efforts, the last decade has seen a rapid expansion in the number of viral species classified into the Hepacivirus genus. Conserved genetic features of hepaciviruses suggest they have undergone specific adaptation and evolved to hijack similar host proteins for efficient propagation in the liver. Here, we developed pseudotyped viruses to elucidate the entry factors of GB virus-B (GBV-B), the first hepacivirus described in an animal, closely related to hepatitis C virus (HCV). GBV-B pseudotyped viruses (GBVBpp) were shown to be uniquely sensitive to the serum of tamarins infected with GBV-B, validating their usefulness as a surrogate for GBV-B entry studies. We screened GBVBpp infection of hepatoma cell lines CRISPR/Cas9-engineered to ablate expression of individual HCV receptors/entry factors and found that claudin-1 is essential for GBV-B infection, indicating GBV-B and HCV share a common entry factor. Our data suggest that claudin-1 facilitates HCV and GBV-B entry through distinct mechanisms since the former requires the first extracellular loop and the latter is reliant on the second extracellular loop. The implication of this sharing of claudin-1 as an entry factor between these two hepaciviruses on their tissue tropism and evolutionary relationships will be discussed.

Importance

Hepatitis C virus (HCV) is a major public health burden; approximately 58 million individuals have chronic HCV infection which could lead to cirrhosis and liver cancer. To achieve the World Health Organisation target of eliminating hepatitis by 2030, new therapeutics and vaccines are needed. Understanding how HCV enters the cells will inform the design of new vaccines and treatments, targeting the first stage of HCV infection. However, the entry mechanism is complex and sparsely described. Studying the entry of related hepaciviruses will increase the knowledge of the molecular mechanisms of the first stages of HCV infection, such as the membrane fusion, and inform structure-guided HCV vaccine design; in this work we have identified a protein, Claudin-1, which facilitates the entry of HCV-related hepacivirus, but with a mechanism not described for HCV. Similar work on other hepaciviruses may unveil commonality of entry factors and possibly new mechanisms.
In silico discovery of repetitive elements as key sequence determinants of 3D genome folding
Authors: Gunsalus Laura M. , Keiser Michael J. , Pollard Katherine S.
Published: August 2022

Natural and experimental genetic variants can modify DNA loops and insulating boundaries to tune transcription, but it is unknown how sequence perturbations affect chromatin organization genome-wide. We developed an in silico deep-learning strategy to quantify the effect of any insertion, deletion, inversion, or substitution on chromatin contacts and systematically scored millions of synthetic variants. While most genetic manipulations have little impact, regions with CTCF motifs and active transcription are highly sensitive, as expected. However, our analysis also points to noncoding RNA genes and several families of repetitive elements as CTCF motif-free DNA sequences with particularly large effects on nearby chromatin interactions, sometimes exceeding the effects of CTCF sites and explaining interactions that lack CTCF. We anticipate that our available disruption tracks may be of broad interest and utility as a measure of 3D genome sensitivity and our computational strategies may serve as a template for biological inquiry with deep learning.
Effects of early life stress and subsequent re-exposure to stress on neuronal activity in the lateral habenula
Authors: Webster Jack F. , Beerens Sanne , Wozny Christian
Published: August 2022

Early life stress can result in depression in humans and depressive-like behaviour in rodents. In various animal models of depression, the lateral habenula (LHb) has been shown to become hyperactive immediately after early life stress. However, whether these pathological changes persist into adulthood is less well understood. Hence, we utilised the maternal separation (MS) model of depression to study how early life stress alters LHb physiology and depressive behaviour in adult mice. We find that only a weak depressive phenotype persists into adulthood which surprisingly is underpinned by LHb hypoactivity in acute slices, accompanied by alterations in both excitatory and inhibitory signalling. However, while we find the LHb to be less active at rest, we report that the neurons reside in a sensitised state where they are more responsive to re-exposure to stress in adulthood in the form of acute restraint, thus priming them to respond to aversive events with an increase in neuronal activity mediated by changes in glutamatergic transmission. These findings thus suggest that in addition to LHb hyperactivity, hypoactivity likely also promotes an adverse phenotype. Re-exposure to stress results in the reappearance of LHb hyperactivity offering a possible mechanism to explain how depression relapses occur following previous depressive episodes.
SARS-CoV-2 specific plasma cells acquire the phenotype of long-lived plasma cells in the human bone marrow
Authors: Schulz Axel R. , Hirseland Heike , Diekmann Lisa-Marie , Reinke Simon , Hardt Sebastian , Niedobitek Antonia , Mei Henrik E.
Published: August 2022

Establishment of long-lived plasma cells (PC) in the bone marrow (BM) is important for the development of long-term specific humoral immunity. While SARS-CoV-2-specific, resting, affinity-matured, IgG-secreting plasma cells were described in human bone marrow approx. 6-7 months after infection or vaccination, the long-term durability of these PC remains unclear. We here show that approximately 20% of SARS-CoV-2-specific human BM plasma cells, including RBD-specific PC accommodate the phenotype of long-lived plasma cells, characterized by the lack of CD19 and/or CD45. This result provides evidence in support of the emergence of persistent SARS-CoV-2 specific plasma cells in humans sustaining the durable production of specific serum IgG protecting against severe courses of COVID-19.
Functional dissociation of the language network and other cognition in early childhood
Authors: Hiersche K.J. , Schettini E. , Li J. , Saygin Z.M.
Published: August 2022

Is language distinct from other cognition during development? Does neural machinery for language emerge from general-purpose neural mechanisms, becoming tuned for language after years of experience and maturation? Answering these questions will shed light on the origins of domain-specificity in the brain. We address these questions using precision fMRI and found young children (35 months-9 years) show domain-specific, left-lateralized language activation, and the language network is not responsive to domain-general cognitive load. Additionally, the cortically adjacent multiple demand network is selective to cognitive load, but not to language. These networks show higher within vs. between-network functional connectivity. This connectivity is stable across ages (examined cross-sectionally and longitudinally), whereas language responses increase with age and across-time within subject, reflecting a domain-specific developmental change. Overall, these findings suggest that domain-specificity, even for uniquely human cognition like language, develops early and distinctly from mechanisms that presumably support other human cognition.

Significance Statement

This study provides evidence of a double dissociation between neural processors for language and domain-general cognition (specifically, cognitive load) in young children. These results refute previous claims that linguistic function emerges from domain-general mechanisms supporting non-linguistic, higher-order cognition, and with both cross-sectional and longitudinal analyses, show that the continued development of linguistic specialization is also unrelated to domain-general mechanisms that support cognitive flexibility and executive function. This work emphasizes the importance of single-subject fMRI analyses with multiple tasks to explicitly dissociate cognitive constructs, and the importance of longitudinal research for scientific rigor, even in toddlers and preschoolers who are difficult to image with fMRI.
TheSolanum americanumpangenome and effectoromics reveal new resistance genes against potato late blight
Authors: Lin Xiao , Jia Yuxin , Heal Robert , Prokchorchik Maxim , Sindalovskaya Maria , Olave-Achury Andrea , Makechemu Moffat , Fairhead Sebastian , Noureen Azka , Heo Jung , Witek Kamil , Smoker Matthew , Taylor Jodie , Shrestha Ram-Krishna , Lee Yoonyoung , Zhang Chunzhi , Park Soon Ju , Sohn Kee Hoon , Huang Sanwen , Jones Jonathan D. G.
Published: August 2022

Late blight caused by the oomycete pathogenPhytophthora infestanscontinues to cause major worldwide losses in potato and tomato. Most accessions ofSolanum americanum, a globally distributed, wild Solanaceae plant, are highly resistant to late blight. We generated high-quality reference genomes of fourS. americanumaccessions, re-sequenced 52 accessions, and we defined variation in the NLR immune receptor genes (theS. americanumNLRome). We further screened for variation in recognition of ∼315P. infestansRXLR effectors in 52S. americanumaccessions. Using these genotypic and phenotypic data, we cloned three novel NLR-encoding genesRpi-amr4, Rpi-amr16andRpi-amr17, and determined their corresponding RXLR effector genesAvramr4(PITG_22825),Avramr16(PITG_02860) andAvramr17(PITG_04373) fromP. infestans. These genomic resources and methodology will support efforts to convert potato into a “nonhost” of late blight and can be applied to diseases of other crops.
Overlapping and specialized roles of tomato phytoene synthase isoforms PSY1 and PSY2 in carotenoid and ABA production
Authors: Ezquerro Miguel , Burbano Esteban , Rodriguez-Concepcion Manuel
Published: August 2022

Carotenoids are plastidial isoprenoids required for photosynthesis and production of hormones such as abscisic acid (ABA) in all plants. In tomato (Solanum lycopersicum), carotenoids also provide color to flowers and ripe fruit. Phytoene synthase (PSY) catalyzes the first and main flux-controlling step of the carotenoid pathway. Three PSY isoforms are present in tomato, PSY1 to 3. Mutants have shown that PSY1 is the isoform providing carotenoids for fruit pigmentation but it is dispensable in photosynthetic tissues. No mutants are available for PSY2 or PSY3, but their expression profiles suggest a main role for PSY2 in leaves and PSY3 in roots. To further investigate isoform specialization with genetic tools, we created tomato edited lines defective in PSY1 and PSY2 in the MicroTom background. The albino phenotype of lines lacking both PSY1 and PSY2 confirmed that PSY3 does not contribute to carotenoid biosynthesis in shoot tissues. Our work further shows that carotenoid production in tomato shoots relies on both PSY1 and PSY2 but with different contributions in different tissues. PSY2 is the main isoform for carotenoid biosynthesis in leaf chloroplasts, but the supporting role of PSY1 is particularly important under high light. PSY2 also contributes to the production of carotenoids in flower petals and, to a lower extent, fruit chromoplasts. Most interestingly, our results demonstrate that fruit growth and ripening is controlled by ABA produced in the pericarp from PSY1-derived precursors whereas PSY2 provides precursors for ABA synthesis in seeds to control germination.
Cytoplasmic tail of the putative polycystin channel Pkd2 regulates its clustering in the fission yeast eisosomes
Authors: Malla Mamata , Sinha Debatrayee , Chowdhury Pritha , Bisesi Benjamin Thomas , Chen Qian
Published: August 2022

Polycystins are a family of conserved ion channels, mutations of which lead to human genetic disorder Autosomal Dominant Polycystic Kidney Disease. The unicellular model organism fission yeast Schizosacchromyces pombe possesses single essential polycystin Pkd2 that localizes to the plasma membrane and is required for cell proliferation. Here, we carried out a functional analysis of Pkd2 based on its Alphafold predicted structure. It consisted of N-terminal lipid-binding (LBD), central transmembrane (TMD) and C-terminal cytoplasmic (CCD) domains. LBD assumes a unique immunoglobulin-fold, while TMD contains nine transmembrane helices. Both were essential. Although the mostly disordered CCD was not, its removal led to clustering of Pkd2 in eisosomes, a microdomain of the plasma membrane. Inhibiting eisosome assembly prevented the clustering but disrupting ER-PM contacts further increased it. Pkd2 shared similar structure with two other putative channels Trp663 and Trp1322, but their intracellular localization and function diverged from each other. Replacing LBD with that of Trp663 partially restored the function of Pkd2, but TMD could not be replaced by either that of Trp663 or human polycystins. We concluded that both the plasma membrane microdomains and cytoplasmic tail of Pkd2 regulate the cell surface clustering of this putative ion channel.
Crystal structure, Hirshfeld surface analysis and geometry optimization of 2-hydroxyimino-N-[1-(pyrazin-2-yl)ethylidene]propanohydrazide
Authors: Plutenko Maksym O. , Shishkina Svitlana V. , Shishkin Oleg V. , Potaskalov Vadim A. , Kalibabchuk Valentina A.
Published: August 2022

In the molecule of the title compound, C9H11N5O2, the oxime and hydrazide groups are situated in a cis-position in relation to the C—C bond linking the two functional groups. The CH3C(=NOH)C(O)NH fragment deviates from planarity because of a twist between the oxime and amide groups. In the crystal, molecules are linked by O—H...O hydrogen bonds, forming zigzag chains in the [013] and [0\overline{1}3] directions.
Bis[(4-methylphenyl)diphenylphosphine-κP](nitrito-κ2
O,O′)silver(I)
Authors: Potgieter Kariska , Malan Frederick P. , Alimi Oyekunle Azeez , Meijboom Reinout
Published: August 2022

The title AgI complex, [Ag(NO2)(C19H17P)2], reveals a distorted pseudo-trigonal–planar shape around the AgI atom geometry resulting from the coordination of two phosphine ligands, as well as a nitrito-O,O′ ligand coordinating to the silver(I) atom through the oxygen atoms; in this description, the two oxygen atoms are assumed to occupy one position, forming an acute O—Ag—O angle of 51.44 (9)°. The plane resulting from the NO2 coordination to Ag is nearly perpendicular to the plane from the coordination of the phosphine-P atoms to Ag [dihedral angle = 86.43 (9)°].
Pandemic uncertainty and sectoral stock returns predictability in South Africa
Authors: Fasanya Ismail Olaleke
Published: August 2022

Purpose

In this paper, the author examines the role of uncertainty due to pandemic on the predictability of sectoral stock returns in South Africa. This is motivated by the ongoing global pandemic, COVID-19, in predicting sector stock returns.

Design/methodology/approach

The study considers estimation of dynamic panel data with dynamic common correlated effects estimator and two pair-wise forecast measures, namely Campbell and Thompson (2008) and Clark and West (2007) tests in dealing with the nested predictive models.

Findings

The results show that pandemic uncertainty has a negative and statistically significant effect on the different sector returns, implying that sector stock returns decline as the pandemic outbreak becomes more pronounced. While the single predictor model consistently outperforms the historical average model both for in-sample and out-of-sample, controlling for other macroeconomic variables effect improves the forecast accuracy of infectious diseases uncertainty. These results are consistently robust to both the in-sample and out-of-sample forecast periods, outliers and heterogeneity. These results have implications for portfolio diversification strategies, which we set aside for future research.

Originality/value

The empirical literature is satiated with studies on how news can predict economic and financial variables, however, the role of uncertainty due to infectious diseases in the stock return predictability especially at the sectoral level is less understudied, this is the main contribution of the study.
Dual solutions of unsteady two-dimensional electro-magneto-hydrodynamics (EMHD) axisymmetric stagnation-point flow of a hybrid nanofluid past a radially stretching/shrinking Riga surface with radiation effect
Authors: Khashi’ie Najiyah Safwa , Waini Iskandar , Arifin Norihan Md , Pop Ioan
Published: August 2022

Purpose

This paper aims to analyse numerically the unsteady stagnation-point flow of Cu-Al2O3/H2O hybrid nanofluid towards a radially shrinking Riga surface with thermal radiation.

Design/methodology/approach

The governing partial differential equations are transformed into a set of ordinary (similar) differential equations by applying appropriate transformations. The numerical computation of these equations including the stability analysis is conducted using the bvp4c solver.

Findings

Two solutions are possible within the allocated interval: shrinking parameter, unsteadiness decelerating parameter, electro-magneto-hydrodynamics (EMHD) parameter, nanoparticles volumetric concentration, radiation parameter and width parameter, whereas the stability analysis certifies that the first (upper branch) solution, which fulfills the boundary conditions is the physical/real solution. The EMHD parameter generated from the application of Riga plate enhances the skin friction coefficient as well as the heat transfer process. The width parameter d is also one of the factors in the deterioration of the skin friction coefficient and heat transfer rate. It is crucial to control the width parameter of the magnets and electrodes to obtain the desired outcome. The radiation parameter is not affecting the boundary layer separation because the critical values are unchanged. However, the addition of radiation and unsteadiness decelerating parameters boosts the thermal rate.

Originality/value

The results are novel and contribute to the discovery of the flow and thermal performance of the hybrid nanofluid subjected to a radially shrinking Riga plate. Besides, this work is beneficial to the other researchers and general audience from industries regarding the factors which contribute to the thermal enhancement of the working fluid.
The impact of exploitative leadership on hospitality employees’ proactive customer service performance: a self-determination perspective
Authors: Sun Zhuanzhuan , Wu Long-Zeng , Ye Yijiao , Kwan Ho Kwong
Published: August 2022

Purpose

Based on self-determination theory, this research paper aims to explore the implication of exploitative leadership for hospitality employees’ proactive customer service performance (PCSP) via harmonious passion for work (HPFW) and the moderating mechanism of power distance.

Design/methodology/approach

The authors’ sample included a total of 207 leader–follower dyads from three Chinese hotels. Hierarchical multiple regression and the PROCESS macro were used to analyze the data.

Findings

The results indicated that exploitative leadership has a negative indirect relationship with hospitality employees’ PCSP through decreased HPFW, and power distance plays a protective role of alleviating the negative implications of exploitative leadership for hospitality employees’ HPFW and PCSP.

Practical implications

Hotels are suggested to develop strict codes of conduct and adopt zero-tolerance policies for exploitative leadership. Additionally, hotels should also act to improve employees’ HPFW and pay attention to low-power-distance employees.

Originality/value

This research enriches exploitative leadership literature by investigating its effect on PCSP. Further, this research investigates HPFW as a mechanism linking exploitative leadership to PCSP. Finally, this research establishes the relationships among exploitative leadership, HPFW and PCSP by investigating the contingent impact of power distance.
Daily hotel demand forecasting with spatiotemporal features
Authors: Huang Liyao , Li Cheng , Zheng Weimin
Published: August 2022

Purpose

Given the importance of spatial effects in improving the accuracy of hotel demand forecasting, this study aims to introduce price and online rating, two critical factors influencing hotel demand, as external variables into the model, and capture the spatial and temporal correlation of hotel demand within the region.

Design/methodology/approach

For high practical implications, the authors conduct the case study in Xiamen, China, where the hotel industry is prosperous. Based on the daily demand data of 118 hotels before and during the COVID-19 period (from January to June 2019 and from January to June 2021), the authors evaluate the prediction performance of the proposed innovative model, that is, a deep learning-based model, incorporating graph convolutional networks (GCN) and gated recurrent units.

Findings

The proposed model simultaneously predicts the daily demand of multiple hotels. It effectively captures the spatial-temporal characteristics of hotel demand. In addition, the features, price and online rating of competing hotels can further improve predictive performance. Meanwhile, the robustness of the model is verified by comparing the forecasting results for different periods (during and before the COVID-19 period).

Practical implications

From a long-term management perspective, long-term observation of market competitors’ rankings and price changes can facilitate timely adjustment of corresponding management measures, especially attention to extremely critical factors affecting forecast demand, such as price. While from a short-term operational perspective, short-term demand forecasting can greatly improve hotel operational efficiency, such as optimizing resource allocation and dynamically adjusting prices. The proposed model not only achieves short-term demand forecasting, but also greatly improves the forecasting accuracy by considering factors related to competitors in the same region.

Originality/value

The originalities of the study are as follows. First, this study represents a pioneering attempt to incorporate demand, price and online rating of other hotels into the forecasting model. Second, integrated deep learning models based on GCN and gated recurrent unit complement existing predictive models using historical data in a methodological sense.