The SARS-CoV-2 Delta-Omicron Recombinant Lineage (XD) Exhibits Immune-Escape Properties Similar to the Omicron (BA.1) Variant

Recently, a recombinant SARS-CoV-2 lineage, XD, emerged that harbors a spike gene that is largely derived from the Omicron variant BA.1 in the genetic background of the Delta variant. This finding raised concerns that the recombinant virus might exhibit altered biological properties as compared to the parental viruses and might pose an elevated threat to human health. Here, using pseudotyped particles, we show that ACE2 binding and cell tropism of XD mimics that of BA.1. Further, XD and BA.1 displayed comparable sensitivity to neutralization by antibodies induced upon vaccination with BNT162b2/Comirnaty (BNT) or BNT vaccination followed by breakthrough infection. Our findings reveal important biological commonalities between XD and Omicron BA.1 host cell entry and its inhibition by antibodies.     

Autoimmune Neutropenia and Immune-Dysregulation in a Patient Carrying a TINF2 Variant

In recent years, the knowledge about the immune-mediated impairment of bone marrow precursors in immune-dysregulation and autoimmune disorders has increased. In addition, immune-dysregulation, secondary to marrow failure, has been reported as being, in some cases, the most evident and early sign of the disease and making the diagnosis of both groups of disorders challenging. Dyskeratosis congenita is a disorder characterized by premature telomere erosion, typically showing marrow failure, nail dystrophy and leukoplakia, although incomplete genetic penetrance and phenotypes with immune-dysregulation features have been described. We report on a previously healthy 17-year-old girl, with a cousin successfully treated for acute lymphoblastic leukemia, who presented with leukopenia and neutropenia. The diagnostic work-up showed positive anti-neutrophil antibodies, leading to the diagnosis of autoimmune neutropenia, a slightly low NK count and high TCR-αβ+-double-negative T-cells. A next-generation sequencing (NGS) analysis showed the 734C>A variant on exon 6 of the TINF2 gene, leading to the p.Ser245Tyr. The telomere length was short on the lymphocytes and granulocytes, suggesting the diagnosis of an atypical telomeropathy showing with immune-dysregulation. This case underlines the importance of an accurate diagnostic work-up of patients with immune-dysregulation, who should undergo NGS or whole exome sequencing to identify specific disorders that deserve targeted follow-up and treatment.     

Perinatal Obesity Induces Hepatic Growth Restriction with Increased DNA Damage Response,Senescence, and Dysregulated Igf-1-Akt-Foxo1 Signaling in Male Offspring of Obese Mice

Maternal obesity predisposes for hepato-metabolic disorders early in life. However, the underlying mechanisms causing early onset dysfunction of the liver and metabolism remain elusive. Since obesity is associated with subacute chronic inflammation and accelerated aging, we test the hypothesis whether maternal obesity induces aging processes in the developing liver and determines thereby hepatic growth. To this end, maternal obesity was induced with high-fat diet (HFD) in C57BL/6N mice and male offspring were studied at the end of the lactation [postnatal day 21 (P21)]. Maternal obesity induced an obese body composition with metabolic inflammation and a marked hepatic growth restriction in the male offspring at P21. Proteomic and molecular analyses revealed three interrelated mechanisms that might account for the impaired hepatic growth pattern, indicating prematurely induced aging processes: (1) Increased DNA damage response (γH2AX), (2) significant upregulation of hepatocellular senescence markers (Cdnk1a, Cdkn2a); and (3) inhibition of hepatic insulin/insulin-like growth factor (IGF)-1-AKT-p38-FoxO1 signaling with an insufficient proliferative growth response. In conclusion, our murine data demonstrate that perinatal obesity induces an obese body composition in male offspring with hepatic growth restriction through a possible premature hepatic aging that is indicated by a pathologic sequence of inflammation, DNA damage, senescence, and signs of a possibly insufficient regenerative capacity.     

Genetic Dissection of Light-Regulated Adventitious Root Induction in Arabidopsis thaliana Hypocotyls

Photomorphogenic responses of etiolated seedlings include the inhibition of hypocotyl elongation and opening of the apical hook. In addition, dark-grown seedlings respond to light by the formation of adventitious roots (AR) on the hypocotyl. How light signaling controls adventitious rooting is less well understood. Hereto, we analyzed adventitious rooting under different light conditions in wild type and photomorphogenesis mutants in Arabidopsis thaliana. Etiolation was not essential for AR formation but raised the competence to form AR under white and blue light. The blue light receptors CRY1 and PHOT1/PHOT2 are key elements contributing to the induction of AR formation in response to light. Furthermore, etiolation-controlled competence for AR formation depended on the COP9 signalosome, E3 ubiquitin ligase CONSTITUTIVELY PHOTOMORPHOGENIC (COP1), the COP1 interacting SUPPRESSOR OF PHYA-105 (SPA) kinase family members (SPA1,2 and 3) and Phytochrome-Interacting Factors (PIF). In contrast, ELONGATED HYPOCOTYL5 (HY5), suppressed AR formation. These findings provide a genetic framework that explains the high and low AR competence of Arabidopsis thaliana hypocotyls that were treated with dark, and light, respectively. We propose that light-induced auxin signal dissipation generates a transient auxin maximum that explains AR induction by a dark to light switch.     

Enzymatic Formation and Physico-Chemical Behaviour of Uncommon Monoglycerides

Results on the enzymatic monoacylation of glycerol by aid of phenylboronic acid in organic solvents are presented. The comparison of two alternative methods indicates that the ?2-step-method”? (synthesis in one batch unit without isolation of intermediates) is in total more favourable than the ?3-step-method”? (synthesis in two batch units including isolation of intermediates), although yields are somewhat lower. Probably this disadvantage originates from an enzyme inhibition caused by residual free phenylboronic acid in the reaction system. Several varying uncommon fatty acids like (S)-17-hydroxyoctadecanoic acid, 12-hydroxyoctadecanoic acid and 2-hydroxyhexadecanoic acid have been used as oleo-components. As far as no steric hindrance is caused by these substrates, product formation is about 80% (basis ?2-step-method”?). Investigations at the Langmuir film balance showed different film states with specific transition phases for the 1(3)-(17-hydroxy)-octadecanoyl and the 1(3)-(12-hydroxy)-octadecanoyl glycerol. The monoglyceride of the 2-hydroxyhexadecanoic acid proved to be a good emulsifier. Its qualities in this respect were confirmed by the data of the surface and interfacial tension versus n-hexadecane and also by the outcome of the emulsification tests. The enzymatic acylation of a diol like 1,3-propanediol led to the 1-(17-hydroxy)-octadecanoyl-3-propanol (yield: 50%). The film behaviour of this ester was similar to that of the corresponding monoglyceride.     

Method and simulation program informed decisions in the early stages of building design

The early stages of building design include a number of decisions which have a strong influence on the performance of the building throughout the rest of the process. It is therefore important that designers are aware of the consequences of these design decisions. This paper presents a method for making informed decisions in the early stages of building design to fulfil performance requirements with regard to energy consumption and indoor environment. The method is operationalised in a program that utilises a simple simulation program to make performance predictions of user-defined parameter variations. The program then presents the output in a way that enables designers to make informed decisions. The method and the program reduce the need for design iterations, reducing time consumption and construction costs, to obtain the intended energy performance and indoor environment.     

Stochastic collocation-based nonlinear analysis of concrete bridges with uncertain parameters

This paper focuses on the stochastic response of concrete bridges considering uncertainty in bearing and abutment stiffness. A multi-span simply supported bridge with concrete girders is selected. A 3D-dimensional model is prepared, and nonlinear response history analyses are performed. For the numerical dynamic simulation, the non-sampling stochastic method based on generalized polynomial chaos (gPC) expansion is utilised. The uncertain parameters include the vertical and shear stiffness of bearings and the lateral stiffness of abutments are presented by the truncated gPC expansions. Furthermore, the system response such as base shear, acceleration, velocity and displacement in different columns is presented by gPC expansion with unknown deterministic coefficients. The stochastic Galerkin projection is employed to calculate a set of deterministic equations. A non-intrusive solution, as a set of collocation points, determines the unknown gPC coefficients of the system response and the results are compared with Monte Carlo simulations. The key advantage of spectral discretization is the combination of the mentioned method with the spatial discretization, e.g. finite element model. This study also emphasises the accuracy in results and time efficiency of the proposed non-sampling method for uncertainty quantification of stochastic systems comparing to sampling procedure (e.g. Monte Carlo simulation).