Phenotypic suppression caused by resonance with light-dark cycles indicates the presence of a 24-hours oscillator in yeast and suggests a new role of intrinsically disordered protein regions as internal mediators

The mutual interaction between environment and life is a main topic of biological sciences. An interesting aspect of this interaction is the existence of biological rhythms spanning all the levels of organisms from bacteria to humans. On the other hand, the existence of a coupling between external oscillatory stimuli and adaptation and evolution rate of biological systems is a still unexplored issue. Here we give the demonstration of a substantial increase of heritable phenotypic changes in yeast, an organism lacking a photoreception system, when growing at 12 h light/dark cycles, with respect to both stable dark (or light) or non-12 + 12 h cycling. The model system was a yeast strain lacking a gene whose product is at the crossroad of many different physiological regulations, so ruling out any simple explanation in terms of increase in reverse gene mutations. The abundance of intrinsically disordered protein regions (IDPRs) in both deleted gene product and in its vast ensemble of interactors supports the hypothesis that resonance with the environmental cycle might be mediated by intrinsic disorder-driven interactions of protein molecules. This result opens to the speculation of the effect of environment/biological resonance phenomena in evolution and of the role of protein intrinsically disordered regions as internal mediators. Communicated by Ramaswamy H. Sarma

Analysis of Detection of Delaminations in Fiber Reinforced Composite Tubes Using Axially Symmetric Guided Waves

The current and proposed use of fiber reinforced composite tubes in a number of aerospace structural applications is well established. The most serious hindrance to acceptance of composites, in general, is the need to certify non-destructively the integrity of the material [1]. The modes of damage in a composite are varied and complex. Delaminations are particularly important, representing an advanced state of damage in the material [2,3]

Dual stimulation by autoantigen and CpG fosters the proliferation of exhausted rheumatoid factor-specific CD21low B cells in hepatitis C virus-cured mixed cryoglobulinemia

Hepatitis C virus (HCV) causes mixed cryoglobulinemia (MC) by driving clonal expansion of B cells expressing B cell receptors (BCRs), often encoded by the VH1-69 variable gene, endowed with both rheumatoid factor (RF) and anti-HCV specificity. These cells display an atypical CD21low phenotype and functional exhaustion evidenced by unresponsiveness to BCR and Toll-like receptor 9 (TLR9) stimuli. Although antiviral therapy is effective on MC vasculitis, pathogenic B cell clones persist long thereafter and can cause virus-independent disease relapses. MethodsClonal B cells from patients with HCV-associated type 2 MC or healthy donors were stimulated with CpG or heath-aggregated IgG (as surrogate immune complexes) alone or in combination; proliferation and differentiation were then evaluated by flow cytometry. Phosphorylation of AKT and of the p65 NF-kB subunit were measured by flow cytometry. TLR9 was quantified by qPCR and by intracellular flow cytometry, and MyD88 isoforms were analyzed using RT-PCR. DiscussionWe found that dual triggering with autoantigen and CpG restored the capacity of exhausted VH1-69pos B cells to proliferate. The signaling mechanism for this BCR/TLR9 crosstalk remains elusive, since TLR9 mRNA and protein as well as MyD88 mRNA were normally expressed and CpG-induced phosphorylation of p65 NF-kB was intact in MC clonal B cells, whereas BCR-induced p65 NF-kB phosphorylation was impaired and PI3K/Akt signaling was intact. Our findings indicate that autoantigen and CpG of microbial or cellular origin may unite to foster persistence of pathogenic RF B cells in HCV-cured MC patients. BCR/TLR9 crosstalk might represent a more general mechanism enhancing systemic autoimmunity by the rescue of exhausted autoreactive CD21low B cells

Recovering or Persisting: The Immunopathological Features of SARS-CoV-2 Infection in Children

Background. The profile of cellular immunological responses of children across the spectrum of COVID-19, ranging from acute SARS-CoV-2 infection to full recovery or Long COVID, has not yet been fully investigated. Methods. We examined and compared cytokines in sera and cell subsets in peripheral blood mononuclear cells (B and regulatory T lymphocytes) collected from four distinct groups of children, distributed as follows: younger than 18 years of age with either acute SARS-CoV-2 infection (n = 49); fully recovered from COVID-19 (n = 32); with persistent symptoms (Long COVID, n = 51); and healthy controls (n = 9). Results. In the later stages after SARS-CoV-2 infection, the cohorts of children, both with recovered and persistent symptoms, showed skewed T and B subsets, with remarkable differences when compared with children at the onset of the infection and with controls. The frequencies of IgD+CD27− naïve B cells, IgD+IgM+ and CD27−IgM+CD38dim B cells were higher in children with recent infection than in those with an older history of disease (p < 0.0001 for all); similarly, the total and natural Tregs compartments were more represented in children at onset when compared with Long COVID (p < 0.0001 and p = 0.0005, respectively). Despite the heterogeneity, partially due to age, sex and infection incidence, the susceptibility of certain children to develop persistent symptoms after infection appeared to be associated with the imbalance of the adaptive immune response. Following up and comparing recovered versus Long COVID patients, we analyzed the role of circulating naïve and switched B and regulatory T lymphocytes in counteracting the evolution of the symptomatology emerged, finding an interesting correlation between the amount and ability to reconstitute the natural Tregs component with the persistence of symptoms (linear regression, p = 0.0026). Conclusions. In this study, we suggest that children affected by Long COVID may have a compromised ability to switch from the innate to the adaptive immune response, as supported by our data showing a contraction of naïve and switched B cell compartment and an unstable balance of regulatory T lymphocytes occurring in these children. However, further prospective immunological studies are needed to better clarify which factors (epigenetic, diet, environment, etc.) are involved in the impairment of the immunological mechanisms in the Long COVID patients

The same ELA class II risk factors confer equine insect bite hypersensitivity in two distinct populations

Insect bite hypersensitivity (IBH) is a chronic allergic dermatitis common in horses. Affected horses mainly react against antigens present in the saliva from the biting midges, Culicoides ssp, and occasionally black flies, Simulium ssp. Because of this insect dependency, the disease is clearly seasonal and prevalence varies between geographical locations. For two distinct horse breeds, we genotyped four microsatellite markers positioned within the MHC class II region and sequenced the highly polymorphic exons two from DRA and DRB3, respectively. Initially, 94 IBH-affected and 93 unaffected Swedish born Icelandic horses were tested for genetic association. These horses had previously been genotyped on the Illumina Equine SNP50 BeadChip, which made it possible to ensure that our study did not suffer from the effects of stratification. The second population consisted of 106 unaffected and 80 IBH-affected Exmoor ponies. We show that variants in the MHC class II region are associated with disease susceptibility (praw = 2.34 × 10−5), with the same allele (COR112:274) associated in two separate populations. In addition, we combined microsatellite and sequencing data in order to investigate the pattern of homozygosity and show that homozygosity across the entire MHC class II region is associated with a higher risk of developing IBH (p = 0.0013). To our knowledge this is the first time in any atopic dermatitis suffering species, including man, where the same risk allele has been identified in two distinct populations

Evolutionary Descent of Prion Genes from the ZIP Family of Metal Ion Transporters

In the more than twenty years since its discovery, both the phylogenetic origin and cellular function of the prion protein (PrP) have remained enigmatic. Insights into a possible function of PrP may be obtained through the characterization of its molecular neighborhood in cells. Quantitative interactome data demonstrated the spatial proximity of two metal ion transporters of the ZIP family, ZIP6 and ZIP10, to mammalian prion proteins in vivo. A subsequent bioinformatic analysis revealed the unexpected presence of a PrP-like amino acid sequence within the N-terminal, extracellular domain of a distinct sub-branch of the ZIP protein family that includes ZIP5, ZIP6 and ZIP10. Additional structural threading and orthologous sequence alignment analyses argued that the prion gene family is phylogenetically derived from a ZIP-like ancestral molecule. The level of sequence homology and the presence of prion protein genes in most chordate species place the split from the ZIP-like ancestor gene at the base of the chordate lineage. This relationship explains structural and functional features found within mammalian prion proteins as elements of an ancient involvement in the transmembrane transport of divalent cations. The phylogenetic and spatial connection to ZIP proteins is expected to open new avenues of research to elucidate the biology of the prion protein in health and disease

Study of the effects of Lemna minor extracts on human immune cell populations

OBJECTIVE: Lemna minor is a plant with a huge repertoire of secondary metabolites. The literature indicates that extracts of Lemna minor have antioxidant, antiradical, immunomodulatory and anti-inflammatory properties. The objective of the present study was to find a suitable technique to extract active compounds from this plant and verify whether these extracts have immunomodulatory activity. MATERIALS AND METHODS: We grew L. minor on a standard medium with Gamborg B5 and vitamins. We extracted compounds from the plant by maceration and decoction. The phytochemical profile of the extracts was characterized by chromatography, spectrophotometry, and spectroscopy. The extracts were tested on cultures of mononuclear cells from four human subjects. These cells were pulsed with carboxyfluorescein succinimidyl ester, grown in triplicate in standard culture medium without (control) and with increasing concentrations of Lemna extracts. Flow cytometry was used to evaluate cell death and proliferation of the total mononuclear cell population and of CD4+, CD8+, B cell and monocyte populations. RESULTS: The Lemna extracts were not cytotoxic and did not cause cell necrosis or apoptosis in immune cells. At low concentrations, they induced very limited proliferation of CD4+ cells within 48 hours. At high concentrations, they induced proliferation of CD8+ cells and B lymphocytes within 48 hours. CONCLUSIONS: Unfortunately, we failed to confirm any immunomodulatory activity of Lemna extracts. Growth and death rates of human immune cells were not significantly affected by adding Lemna extracts to the culture medium

Addressing strategic challenges on mega cities through MS2G

Abstract This paper proposes the combination of modeling and simulation and serious games in order to create an effective framework to address crowdsourcing. Indeed interoperable simulation, intelligent agents and serious games have great potential and a new architecture is proposed in this paper. Such architecture that is based on modern technologies and standards allow today to develop an effective cloud solution that could deliver simulation as a service (SaaS). This approach is defined as MS2G (Modeling, Simulation and Serious Games) and could be used to address also other areas such as capability development, training, etc. In this paper MS2G is proposed to adopt it in order to face the strategic challenges related to future scenarios involving megacities; hence, the large metropolitan areas are expected to require simulation as support tool to address complex aspects such as energy, logistics, food, safety, security. Crowdsourcing in this framework provide a great chance for both policy makers and citizens to work together evaluating new solutions

The B-Side of B Cells

No abstract availabl

Gambling disorder and dissociative features: A systematic review and meta-analysis

OBJECTIVE: Multilevel consequences related to gambling disorder (GD) are glaring enough to make gambling a worldwide public health issue. Dissociation has been pointed out in clinical, empirical, and theoretical contributions as a key variable accounting for the development and maintenance of GD. However, we still lack a systematization of available empirical data that may facilitate further accurate conclusions. METHOD: A systematic review and meta-analysis were performed with the goal to answer to open questions. We followed the PRISMA guidelines conducting a systematic search of 5 scientific databases (PsycINFO, PsycARTICLES, MEDLINE, Scopus, Web of Science, and PubMed) including grey literature. RESULTS: A total of 843 records were screened, and 20 studies were included in the qualitative and quantitative analyses. A systematic review of selected studies outlines the high heterogeneity in the operationalization of the dissociation construct as well as the absence of studies examining the role played by the specific dimensions of the pathological dissociative feature in GD. A significant, positive, and moderate effect size (r = .37) was found linking GD to dissociation. Moreover, this effect appears to not be moderated by the quality of studies, age, and gender of participants nor measures used to evaluate dissociation. CONCLUSIONS: Despite empirical evidences supporting the theoretical assertions toward the relationship between GD and dissociation, few studies have reached an articulated understanding of this topic, mostly failing to identify specific dissociative features involved in GD. Furthermore, the existence of the current gap in the literature are discussed to delineate future lines of research. (PsycInfo Database Record (c) 2021 APA, all rights reserved)