Broad and potent neutralizing human antibodies to tick-borne flaviviruses protect mice from disease

Tick-borne encephalitis virus (TBEV) is an emerging human pathogen that causes potentially fatal disease with no specific treatment. Mouse monoclonal antibodies are protective against TBEV, but little is known about the human antibody response to infection. Here, we report on the human neutralizing antibody response to TBEV in a cohort of infected and vaccinated individuals. Expanded clones of memory B cells expressed closely related anti-envelope domain III (EDIII) antibodies in both groups of volunteers. However, the most potent neutralizing antibodies, with IC₅₀s below 1 ng/ml, were found only in individuals who recovered from natural infection. These antibodies also neutralized other tick-borne flaviviruses, including Langat, louping ill, Omsk hemorrhagic fever, Kyasanur forest disease, and Powassan viruses. Structural analysis revealed a conserved epitope near the lateral ridge of EDIII adjoining the EDI–EDIII hinge region. Prophylactic or early therapeutic antibody administration was effective at low doses in mice that were lethally infected with TBEV.     

CD27 costimulation contributes substantially to the expansion of functional memory CD8+ T cells after peptide immunization

Naive T cells require signals from multiple costimulatory receptors to acquire full effector function and differentiate to long‐lived memory cells. The costimulatory receptor, CD27, is essential for optimal T‐cell priming and memory differentiation in a variety of settings, although whether CD27 is similarly required during memory CD8⁺ T‐cell reactivation remains controversial. We have used OVA and anti‐CD40 to establish a memory CD8⁺ T‐cell population and report here that their secondary expansion, driven by peptide and anti‐CD40, polyI:C, or LPS, requires CD27. Furthermore, antigenic peptide and a soluble form of the CD27 ligand, CD70 (soluble recombinant CD70 (sCD70)), is sufficient for secondary memory CD8⁺ T‐cell accumulation at multiple anatomical sites, dependent on CD80/86. Prior to boost, resting effector‐ and central‐memory CD8⁺ T cells both expressed CD27 with greater expression on central memory cells. Nonetheless, both populations upregulated CD27 after TCR engagement and accumulated in proportion after boosting with Ag and sCD70. Mechanistically, sCD70 increased the frequency of divided and cytolytic memory T cells, conferred resistance to apoptosis and enabled retardation of tumor growth in vivo. These data demonstrate the central role played by CD27/70 during secondary CD8⁺ T‐cell activation to a peptide Ag, and identify sCD70 as an immunotherapeutic adjuvant for antitumor immunity.     

Relationship between children physical activity,inflammatory mediators and lymphocyte activation: possible impact of social isolation (COVID-19)

Sport Sciences for Health - Lifestyle and body composition may be simultaneously responsible for immune response modulation. This study aimed to compare plasmatic adipokines concentration and...     

Child Sexual Abuse and Age at Onset of Psychotic Disorders: A Matched-cohort Study: L’âge d’apparition des troubles psychotiques chez les victimes d’agression sexuelle à l’enfance: Une étude prospective de cohortes appariées

Objective:Victims of child sexual abuse (CSA) present with a higher risk of psychotic disorders. However, the developmental course of psychosis following CSA, such as the age at onset, remains unknown. This study aimed to determine whether the age at onset of psychotic disorders was influenced by sexual abuse, sex, and confounding factors (substance misuse, intellectual disability, and socioeconomic status).Method:A prospective matched-cohort design was used, with administrative databases from a child protection agency (CPA) and a public health system. Children who received a substantiated report of CSA at the CPA and whose health data could be retrieved were selected (n = 882) and matched with children from the general population using their date of birth, sex, and geographical area. Survival analysis was performed to estimate the association between sexual abuse, sex, and confounding factors and the age at onset of psychotic disorders.Results:Sexual abuse and substance misuse are significantly associated with the age at onset of psychotic disorders. In the sexually abused group, only substance misuse is associated with the age at onset of psychotic disorders, but this was not significant for the general population.Conclusions:These findings highlight the importance of prevention of psychotic disorders among sexually abused youth, especially those with a substance misuse diagnosis.     

Differential in vitro pathogenicity of Photorhabdus bacterial species against two distinct insect cell lines

Understanding the mode of action of pathogenic bacteria through in vitro studies can provide additional insight into their infection strategies. Here we have characterized the effect of Photorhabdus luminescens and Photorhabdus asymbiotica on two distinct insect cell lines. We report that insect cell survival and metabolism as well as bacterial proliferation differ between infection with two Photorhabdus species. These findings reinforce the notion that P. luminescens and P. asymbiotica deploy diverse tactics to infect insect cells. This knowledge might lead to better appreciation of the interaction between pathogenic bacteria and different types of insect cells.     

Impact of income and perceived stress on engagement and weight loss outcomes in an online behavioral weight loss program

Journal of Behavioral Medicine - Lower income is associated with greater stress, and stress has been shown to undermine treatment engagement and weight loss outcomes in face-to-face interventions....     

Metacognitive beliefs in obsessive-compulsive patients: A comparison with healthy and schizophrenia participants

Introduction. Distorted metacognitive beliefs are increasingly considered in theoretical models of obsessive-compulsive disorder (OCD). However, so far no consensus has emerged regarding the specific metacognitive profile of OCD.

Methods. Participants with OCD (n=55), schizophrenia (n=39), and nonclinical controls (n=49) were assessed with the Metacognitions Questionnaire (MCQ-30).

Results. Except for positive beliefs about worry, both patient samples exceeded nonclinical controls on all MCQ subscales. The MCQ “need to control thoughts” and “negative beliefs about uncontrollability and danger” subscales showed strong correlations with obsessions, and scores in the former scale were elevated in hallucinators. In contrast to several prior studies, “cognitive confidence” was related neither to core OCD nor to schizophrenia symptomatology.

Conclusions. Notwithstanding large pathogenetic differences between OCD and schizophrenia, findings suggest that obsessions and hallucinations may share a common metacognitive pathway. Need to control thoughts and dysfunctional beliefs about the malleability of worries may represent critical prerequisites for the two phenomena to emerge.