Peptide delivery of a multivalent mRNA SARS-CoV-2 vaccine.

Lipid nanoparticles (LNP) have been instrumental in the success of mRNA vaccines and have opened up the field to a new wave of therapeutics. However, what is ahead beyond the LNP? The approach herein used a nanoparticle containing a blend of Spike, Membrane and Envelope antigens complexed for the first time with the RALA peptide (RALA-SME). The physicochemical characteristics and functionality of RALA-SME were assessed. With >99% encapsulation, RALA-SME was administered via intradermal injection in vivo, and all three antigen-specific IgG antibodies were highly significant. The IgG2a:IgG1 ratio were all >1.2, indicating a robust TH1 response, and this was further confirmed with the T-Cell response in mice. A complete safety panel of markers from mice were all within normal range, supported by safety data in hamsters. Vaccination of Syrian Golden hamsters with RALA-SME derivatives produced functional antibodies capable of neutralising SARS-CoV-2 from both Wuhan-Hu-1 and Omicron BA.1 lineages after two doses. Antibody levels increased over the study period and provided protection from disease-specific weight loss, with inhibition of viral migration down the respiratory tract. This peptide technology enables the flexibility to interchange and add antigens as required, which is essential for the next generation of adaptable mRNA vaccines.

Reasoning biases and delusional ideation in the general population: A longitudinal study.

BACKGROUND: Reasoning biases have been suggested as risk factors for delusional ideation in both patients and non-clinical individuals. Still, it is unclear how these biases are longitudinally related to delusions in the general population. We hence aimed to investigate longitudinal associations between reasoning biases and delusional ideation in the general population. METHODS: We conducted an online cohort study with 1184 adults from the German and Swiss general population. Participants completed measures on reasoning biases (jumping-to-conclusion bias [JTC], liberal acceptance bias [LA], bias against disconfirmatory evidence [BADE], possibility of being mistaken [PM]) and delusional ideation at baseline, and delusional ideation 7 to 8 months later. RESULTS: A greater JTC bias was associated with a greater increase in delusional ideation over the following months. This association was better described by a positive quadratic relationship. Neither BADE, LA nor PM were associated with subsequent changes in delusional ideation. CONCLUSIONS: This study suggests that jumping-to-conclusions predicts delusional ideation in the general population but that this association may follow a quadratic trajectory. While no other associations turned significant, future studies with shorter temporal distances may shed further light on the role of reasoning biases as risk factors for delusional ideation in non-clinical samples.

Is intuition allied with jumping to conclusions in decision-making? An intensive longitudinal study in patients with delusions and in non-clinical individuals.

Research suggests that a jumping-to-conclusions (JTC) bias, excessive intuition, and reduced analysis in information processing may favor suboptimal decision-making, both in non-clinical and mentally disordered individuals. The temporal relationship between processing modes and JTC bias, however, remains unexplored. Therefore, using an experience sampling methodology (ESM) approach, this study examines the temporal associations between intuitive/analytical information processing, JTC bias, and delusions in non-clinical individuals and patients with schizophrenia. Specifically, we examine whether a high use of intuitive and/or a low use of analytical processing predicts subsequent JTC bias and paranoid conviction. In a smartphone-based ESM study, participants will be prompted four times per day over three consecutive days to answer questionnaires designed to measure JTC bias, paranoid conviction, and preceding everyday-life intuition/analysis. Our hierarchical data will be analyzed using multilevel modelling for hypothesis testing. Results will further elucidate the role of aberrant human reasoning, particularly intuition, in (non-)clinical delusions and delusion-like experiences, and also inform general information processing models.

Coronavirus conspiracy beliefs in the German-speaking general population: endorsement rates and links to reasoning biases and paranoia.

BACKGROUND: Coronavirus-related conspiracy theories (CT) have been found to be associated with fewer pandemic containment-focused behaviors. It is therefore important to evaluate associated cognitive factors. We aimed to obtain first endorsement rate estimates of coronavirus-related conspiracy beliefs in a German-speaking general population sample and investigate whether delusion-related reasoning biases and paranoid ideation are associated with such beliefs. METHODS: We conducted a cross-sectional non-probability online study, quota-sampled for age and gender, with 1684 adults from Germany and German-speaking Switzerland. We assessed general and specific coronavirus conspiracy beliefs, reasoning biases [jumping-to-conclusions bias (JTC), liberal acceptance bias (LA), bias against disconfirmatory evidence (BADE), possibility of being mistaken (PM)], and paranoid ideation, using established experimental paradigms and self-report questionnaires. RESULTS: Around 10% of our sample endorsed coronavirus-related CT beliefs at least strongly, and another 20% to some degree. Overall endorsement was similar to levels observed in a UK-based study (Freeman et al., 2020b). Higher levels of conspiracy belief endorsement were associated with greater JTC, greater LA, greater BADE, higher PM, and greater paranoid ideation. Associations were mostly small to moderate and best described by non-linear relationships. CONCLUSIONS: A noticeable proportion of our sample recruited in Germany and German-speaking Switzerland endorsed coronavirus conspiracy beliefs strongly or to some degree. These beliefs are associated with reasoning biases studied in delusion research. The non-probability sampling approach limits the generalizability of findings. Future longitudinal and experimental studies investigating conspiracy beliefs along the lines of reasoning are encouraged to validate reasoning aberrations as risk factors.

Oomycete small RNAs bind to the plant RNA-induced silencing complex for virulence.

The exchange of small RNAs (sRNAs) between hosts and pathogens can lead to gene silencing in the recipient organism, a mechanism termed cross-kingdom RNAi (ck-RNAi). While fungal sRNAs promoting virulence are established, the significance of ck-RNAi in distinct plant pathogens is not clear. Here, we describe that sRNAs of the pathogen Hyaloperonospora arabidopsidis, which represents the kingdom of oomycetes and is phylogenetically distant from fungi, employ the host plant's Argonaute (AGO)/RNA-induced silencing complex for virulence. To demonstrate H. arabidopsidis sRNA (HpasRNA) functionality in ck-RNAi, we designed a novel CRISPR endoribonuclease Csy4/GUS reporter that enabled in situ visualization of HpasRNA-induced target suppression in Arabidopsis. The significant role of HpasRNAs together with AtAGO1 in virulence was revealed in plant atago1 mutants and by transgenic Arabidopsis expressing a short-tandem-target-mimic to block HpasRNAs, that both exhibited enhanced resistance. HpasRNA-targeted plant genes contributed to host immunity, as Arabidopsis gene knockout mutants displayed quantitatively enhanced susceptibility.

Oligodendrocytes in Development, Myelin Generation and Beyond.

Oligodendrocytes are the myelinating cells of the central nervous system (CNS) that are generated from oligodendrocyte progenitor cells (OPC). OPC are distributed throughout the CNS and represent a pool of migratory and proliferative adult progenitor cells that can differentiate into oligodendrocytes. The central function of oligodendrocytes is to generate myelin, which is an extended membrane from the cell that wraps tightly around axons. Due to this energy consuming process and the associated high metabolic turnover oligodendrocytes are vulnerable to cytotoxic and excitotoxic factors. Oligodendrocyte pathology is therefore evident in a range of disorders including multiple sclerosis, schizophrenia and Alzheimer's disease. Deceased oligodendrocytes can be replenished from the adult OPC pool and lost myelin can be regenerated during remyelination, which can prevent axonal degeneration and can restore function. Cell population studies have recently identified novel immunomodulatory functions of oligodendrocytes, the implications of which, e.g., for diseases with primary oligodendrocyte pathology, are not yet clear. Here, we review the journey of oligodendrocytes from the embryonic stage to their role in homeostasis and their fate in disease. We will also discuss the most common models used to study oligodendrocytes and describe newly discovered functions of oligodendrocytes.

Protein arginine methylation: a prominent modification and its demethylation.

Arginine methylation of histones is one mechanism of epigenetic regulation in eukaryotic cells. Methylarginines can also be found in non-histone proteins involved in various different processes in a cell. An enzyme family of nine protein arginine methyltransferases catalyses the addition of methyl groups on arginines of histone and non-histone proteins, resulting in either mono- or dimethylated-arginine residues. The reversibility of histone modifications is an essential feature of epigenetic regulation to respond to changes in environmental factors, signalling events, or metabolic alterations. Prominent histone modifications like lysine acetylation and lysine methylation are reversible. Enzyme family pairs have been identified, with each pair of lysine acetyltransferases/deacetylases and lysine methyltransferases/demethylases operating complementarily to generate or erase lysine modifications. Several analyses also indicate a reversible nature of arginine methylation, but the enzymes facilitating direct removal of methyl moieties from arginine residues in proteins have been discussed controversially. Differing reports have been seen for initially characterized putative candidates, like peptidyl arginine deiminase 4 or Jumonji-domain containing protein 6. Here, we review the most recent cellular, biochemical, and mass spectrometry work on arginine methylation and its reversible nature with a special focus on putative arginine demethylases, including the enzyme superfamily of Fe(II) and 2-oxoglutarate-dependent oxygenases.

The serotonin transporter polymorphism (5-HTTLPR) and coping strategies influence successful emotion regulation in an acute stress situation: Physiological evidence.

INTRODUCTION: Emotion regulation is an important everyday-life skill to reduce harm and stress. Consequently, research shows associations between psychopathologies and emotional dysregulation. The serotonin transporter polymorphism (5-HTTLPR) has repeatedly been associated to phenotypes and syndromes related to emotional dysregulation. However, there is no study showing any direct effects of 5-HTTLPR genotype and emotion regulation. Hence, the aim of the present study was to draw a link between 5-HTTLPR to emotion regulation. METHOD: N=91 healthy participants filled in a coping questionnaire, provided gene samples and participated in an emotion regulation experiment. In a within-subject design they viewed emotional pictures and were either instructed to suppress their emotions or not. During the emotion regulation task, skin conductance responses (SCR) were recorded. RESULTS: Emotion regulation abilities measured by SCR were influenced by 5-HTTLPR and coping strategies, together explaining 30% of variance. S-allele carriers showed increased SCRs when watching aversive stimuli in the uninstructed condition. However, when receiving an emotion regulation instruction, they were able to downregulate their arousal resulting in comparable SCRs as observed in LL-carriers. DISCUSSION: This is the first study showing an impact of 5-HTTLPR on physiological emotion regulation. Results show that S-allele carriers have the same emotional arousal as L-allele carriers, when they get a supportive instruction to suppress unwanted feelings. These findings have implications for psychotherapeutic treatments.

Does drywall installers' innovative idea reduce the ergonomic exposures of ceiling installation: A field case study.

OBJECTIVE: The study was conducted to assess an intervention suggested by the workers to reduce the physical or ergonomic exposures of the drywall installation task. METHODS: The drywall installers were asked to brainstorm on innovative ideas that could reduce their ergonomic exposures during the drywall installation work. The workers proposed the idea of using a 'deadman' (narrow panel piece) to hold the panels to the ceiling while installing them. The researcher collected quantitative exposure data (PATH, 3DSSPP) at the baseline and intervention phases and compared the phases to find out any change in the exposure while using the 'deadman'. RESULTS: Results showed that ergonomic exposures (such as overhead arm and awkward trunk postures and heavy load handling) were reduced at the intervention phase while using the 'deadman' with an electrically operated lift. CONCLUSION: The concept of the 'deadman', which was shown to help reduce musculoskeletal exposures during ceiling installation, can be used to fabricate a permanent ergonomic tool to support the ceiling drywall panel.