Validation of the French ADNM-20 in the assessment of emotional difficulties resulting from COVID-19 quarantine and outbreak

Background: Multiple psychological consequences of the COVID-19 outbreak and quarantine have been described. However, there is a lack of global conceptualization. We argue that the stressful aspects of the situation, the multiple environmental consequences of the outbreak, and the diversity of symptoms observed in such a situation, suggest that Adjustment disorder (AD) is a promising way to conceptualize the psychological consequences of the outbreak and quarantine. The first aim of the study was to validate the French version of the ADNM. The second aim was to set out adjustment difficulties resulting from COVID-19 outbreak and quarantine. Method: We recruited 1010 (840 women, 170 men) who consented online to participate. They filled out the French ADNM, visual analogic scales, HADS, IES, and the COPE, to evaluate coping strategies. Results: We confirmed the factor structure of the ADNM and we found good psychometric properties. We found that 61.3% of participants presented an adjustment disorder related to COVID-19 outbreak. We found multiple risk factors and protective factors to AD due to quarantine and outbreak. We also identified the coping strategies negatively and positively associated with AD. Conclusion: Adjustment disorder is a relevant concept to understand psychological manifestations caused by quarantine and outbreak. The French ANDM has good psychometric properties to evaluate such manifestations. The association between coping strategies and AD symptoms suggest that CBT may be the best intervention to help people suffering from AD

Genome sequence and analysis of the tuber crop potato

Potato (Solanum tuberosum L.) is the world’s most important non-grain food crop and is central to global food security. It is clonally propagated, highly heterozygous, autotetraploid, and suffers acute inbreeding depression. Here we use a homozygous doubled-monoploid potato clone to sequence and assemble 86% of the 844-megabase genome. We predict 39,031 protein-coding genes and present evidence for at least two genome duplication events indicative of a palaeopolyploid origin. As the first genome sequence of an asterid, the potato genome reveals 2,642 genes specific to this large angiosperm clade. We also sequenced a heterozygous diploid clone and show that gene presence/absence variants and other potentially deleterious mutations occur frequently and are a likely cause of inbreeding depression. Gene family expansion, tissue-specific expression and recruitment of genes to new pathways contributed to the evolution of tuber development. The potato genome sequence provides a platform for genetic improvement of this vital cro

Integrin-interleukin-4 mechanotransduction pathways in human chondrocytes

INTRODUCTION Low intensity ultrasound (LIUS) is a special type of sonic pressure that can generate radiation forces, shear stresses and cavitation MATERIALS AND METHODS C-28/I2 cells (human chondrocyte cell line) were cultured in monolayer and treated with LIUS at an intensity of 200 mW/cm 2 using Noblelife TM (Duplogen Inc., Suwon, Korea). The role of stretchactivated channels (SAC) and integrins was first examined in mediating the LIUS effects on the expression of type II collagen and aggrecan by RT-PCR and Western blot analysis. Inhibitors for SACs (gadolinium) and integrins (GRGDSP peptide or anti-integrin α1 antibody) were used to confirm their specificity. The involvement of three MPAKs signal pathways in the LIUS-mediated phenotypic changes of chondrocytes and its mechanotrnsduction pathways was also investigated using the phospho-specific antibodies. Similar approaches are currently undergoing using rabbit primary chondrocytes in three-dimensional alginate culture. RESULTS Effect of LIUS on the expression of cartilage matrix proteins C-28/I2 cells were stimulated with LIUS, and the optimal conditions for incubation and treatment times were examined in terms of type II collagen and aggrecan expression by RT-PCR. The mRNA level of type II collagen was the highest after 3 hr and that of aggrecan was gradually increasing by time, when cells were treated with LIUS for 15 min. Role of SACs in the LIUS signal When examined at 1, 3 and 6 hr after stimulation by RT-PCR, the LIUS effects on the mRNA levels of type II collagen and aggrecan were reduced by gadolinium treatment depending on time Role of integrins in the LIUS signal C-28/I2 cells were pre-incubated with the inhibitor (GRGDSP) or a control peptide (GRADSP) for 10 min before LIUS treatment. The mRNA levels of type II collagen and aggrecan were clearly induced by LIUS in the presence of GRADSP but were lower than the untreated control (0 hr) when GRGDSP was co-treated. MAPKs as downstream mediators of LIUS signal The phosphorylation of ERK and JNK was induced by LIUS but that of p38 kinase was not CONCLUSION These results suggest that the LIUS signal might be mediated via canonical mechanoreceptors of SACs and integrins and subsequently through JNK and ERK pathways. Further studies are necessary to understand more details of the LIUS signaling network and regulation mechanisms. In addition, our ongoing studies in a 3-D culture of chondrocytes would give more important information about the cellular and molecular mechanism(s) of LIUS effects on development of chondrogenic phenotypes. REFERENCES 1. Feril, L.B. Jr. and Kondo, T. Biological effects of low intensity ultrasound: the mechanism involved and its implications on therapy and on biosafety of ultrasound

Superior antigen cross-presentation and XCR1 expression define human CD11c+CD141+ cells as homologues of mouse CD8+ dendritic cells

In recent years, human dendritic cells (DCs) could be subdivided into CD304+ plasmacytoid DCs (pDCs) and conventional DCs (cDCs), the latter encompassing the CD1c+, CD16+, and CD141+ DC subsets. To date, the low frequency of these DCs in human blood has essentially prevented functional studies defining their specific contribution to antigen presentation. We have established a protocol for an effective isolation of pDC and cDC subsets to high purity. Using this approach, we show that CD141+ DCs are the only cells in human blood that express the chemokine receptor XCR1 and respond to the specific ligand XCL1 by Ca2+ mobilization and potent chemotaxis. More importantly, we demonstrate that CD141+ DCs excel in cross-presentation of soluble or cell-associated antigen to CD8+ T cells when directly compared with CD1c+ DCs, CD16+ DCs, and pDCs from the same donors. Both in their functional XCR1 expression and their effective processing and presentation of exogenous antigen in the context of major histocompatibility complex class I, human CD141+ DCs correspond to mouse CD8+ DCs, a subset known for superior antigen cross-presentation in vivo. These data define CD141+ DCs as professional antigen cross-presenting DCs in the human

Deterministic approach to microscopic three-phase traffic theory

Two different deterministic microscopic traffic flow models, which are in the context of the Kerner's there-phase traffic theory, are introduced. In an acceleration time delay model (ATD-model), different time delays in driver acceleration associated with driver behaviour in various local driving situations are explicitly incorporated into the model. Vehicle acceleration depends on local traffic situation, i.e., whether a driver is within the free flow, or synchronized flow, or else wide moving jam traffic phase. In a speed adaptation model (SA-model), vehicle speed adaptation occurs in synchronized flow depending on driving conditions. It is found that the ATD- and SA-models show spatiotemporal congested traffic patterns that are adequate with empirical results. In the ATD- and SA-models, the onset of congestion in free flow at a freeway bottleneck is associated with a first-order phase transition from free flow to synchronized flow; moving jams emerge spontaneously in synchronized flow only. Differences between the ATD- and SA-models are studied. A comparison of the ATD- and SA-models with stochastic models in the context of three phase traffic theory is made. A critical discussion of earlier traffic flow theories and models based on the fundamental diagram approach is presented.Comment: 40 pages, 14 figure

The Ukraine-Russia war : a symptoms network of complex posttraumatic stress disorder during continuous traumatic stress

Objective: This study is aimed to test the symptoms network of ICD-11 Complex Post-traumatic Stress Disorder (CPTSD) symptoms, using data collected from Ukrainian civilians during the 2022 Russia-Ukraine war. Findings can inform our understanding of the stress response in individuals exposed to continuous trauma and give insight into the nature of CPTSD during war. Methods: A network analysis was conducted on CPTSD symptoms as assessed by the International Trauma Questionnaire using data from a nationally representative sample of 2000 Ukrainians. Results: While Post-traumatic Stress Disorder (PTSD) and Disturbances in Self Organization (DSO) clusters did not enmesh, several communities within these clusters were merged. Results highlight that in terms of strength centrality, emotional dysregulation (emotional numbing) and a heightened sense of threat were most prominent. Conclusion: The results confirm the ICD-11 structure of CPTSD but suggest that continuous traumatic stress manifests in more condensed associations between CPTSD symptoms and that emotional regulation may play a vital role in activating the CPTSD network. War-exposed populations could be provided with scalable, brief self-help materials focused on fostering emotion regulation and sense of threat

Found in translation: the human equivalent of mouse CD8+ dendritic cells

The murine dendritic cell network comprises multiple subsets with distinct functions, but few of their human counterparts have been described. New data now reveals the likely human equivalent of the mouse DC subset specialized in cross-presentation

A remote secondary binding pocket promotes heteromultivalent targeting of DC-SIGN

Dendritic cells (DC) are antigen-presenting cells coordinating the interplay of the innate and the adaptive immune response. The endocytic C-type lectin receptors DC-SIGN and Langerin display expression profiles restricted to distinct DC subtypes and have emerged as prime targets for next-generation immunotherapies and anti-infectives. Using heteromultivalent liposomes copresenting mannosides bearing aromatic aglycones with natural glycan ligands, we serendipitously discovered striking cooperativity effects for DC-SIGN+ but not for Langerin+ cell lines. Mechanistic investigations combining NMR spectroscopy with molecular docking and molecular dynamics simulations led to the identification of a secondary binding pocket for the glycomimetics. This pocket, located remotely of DC-SIGN’s carbohydrate bindings site, can be leveraged by heteromultivalent avidity enhancement. We further present preliminary evidence that the aglycone allosterically activates glycan recognition and thereby contributes to DC-SIGN-specific cell targeting. Our findings have important implications for both translational and basic glycoscience, showcasing heteromultivalent targeting of DCs to improve specificity and supporting potential allosteric regulation of DC-SIGN and CLRs in general

Recruitment and Activation of Pancreatic Stellate Cells from the Bone Marrow in Pancreatic Cancer: A Model of Tumor-Host Interaction

BACKGROUND AND AIMS: Chronic pancreatitis and pancreatic cancer are characterised by extensive stellate cell mediated fibrosis, and current therapeutic development includes targeting pancreatic cancer stroma and tumor-host interactions. Recent evidence has suggested that circulating bone marrow derived stem cells (BMDC) contribute to solid organs. We aimed to define the role of circulating haematopoietic cells in the normal and diseased pancreas. METHODS: Whole bone marrow was harvested from male β-actin-EGFP donor mice and transplanted into irradiated female recipient C57/BL6 mice. Chronic pancreatitis was induced with repeat injections of caerulein, while carcinogenesis was induced with an intrapancreatic injection of dimethylbenzanthracene (DMBA). Phenotype of engrafted donor-derived cells within the pancreas was assessed by immunohistochemistry, immunofluorescence and in situ hybridisation. RESULTS: GFP positive cells were visible in the exocrine pancreatic epithelia from 3 months post transplantation. These exhibited acinar morphology and were positive for amylase and peanut agglutinin. Mice administered caerulein developed chronic pancreatitis while DMBA mice exhibited precursor lesions and pancreatic cancer. No acinar cells were identified to be donor-derived upon cessation of cerulein treatment, however rare occurrences of bone marrow-derived acinar cells were observed during pancreatic regeneration. Increased recruitment of BMDC was observed within the desmoplastic stroma, contributing to the activated pancreatic stellate cell (PaSC) population in both diseases. Expression of stellate cell markers CELSR3, PBX1 and GFAP was observed in BMD cancer-associated PaSCs, however cancer-associated, but not pancreatitis-associated BMD PaSCs, expressed the cancer PaSC specific marker CELSR3. CONCLUSIONS: This study demonstrates that BMDC can incorporate into the pancreas and adopt the differentiated state of the exocrine compartment. BMDC that contribute to the activated PaSC population in chronic pancreatitis and pancreatic cancer have different phenotypes, and may play important roles in these diseases. Further, bone marrow transplantation may provide a useful model for the study of tumor-host interactions in cancer and pancreatitis