Pre-Omicron Vaccine Breakthrough Infection Induces Superior Cross-Neutralization against SARS-CoV-2 Omicron BA.1 Compared to Infection Alone

SARS-CoV-2 variants raise concern because of their high transmissibility and their ability to evade neutralizing antibodies elicited by prior infection or by vaccination. Here, we compared the neutralizing abilities of sera from 70 unvaccinated COVID-19 patients infected before the emergence of variants of concern (VOCs) and of 16 vaccine breakthrough infection (BTI) cases infected with Gamma or Delta against the ancestral B.1 strain, the Gamma, Delta and Omicron BA.1 VOCs using live virus. We further determined antibody levels against the Nucleocapsid (N) and full Spike proteins, the receptor-binding domain (RBD) and the N-terminal domain (NTD) of the Spike protein. Convalescent sera featured considerable variability in the neutralization of B.1 and in the cross-neutralization of different strains. Their neutralizing capacity moderately correlated with antibody levels against the Spike protein and the RBD. All but one convalescent serum failed to neutralize Omicron BA.1. Overall, convalescent sera from patients with moderate disease had higher antibody levels and displayed a higher neutralizing ability against all strains than patients with mild or severe forms of the disease. The sera from BTI cases fell into one of two categories: half the sera had a high neutralizing activity against the ancestral B.1 strain as well as against the infecting strain, while the other half had no or a very low neutralizing activity against all strains. Although antibody levels against the spike protein and the RBD were lower in BTI sera than in unvaccinated convalescent sera, most neutralizing sera also retained partial neutralizing activity against Omicron BA.1, suggestive of a better cross-neutralization and higher affinity of vaccine-elicited antibodies over virus-induced antibodies. Accordingly, the IC50: antibody level ratios were comparable for BTI and convalescent sera, but remained lower in the neutralizing convalescent sera from patients with moderate disease than in BTI sera. The neutralizing activity of BTI sera was strongly correlated with antibodies against the Spike protein and the RBD. Together, these findings highlight qualitative differences in antibody responses elicited by infection in vaccinated and unvaccinated individuals. They further indicate that breakthrough infection with a pre-Omicron variant boosts immunity and induces cross-neutralizing antibodies against different strains, including Omicron BA.1.     

Getting a Grip on the Undrugged: Targeting β-Catenin with Fragment-Based Methods

Aberrant WNT pathway activation, leading to nuclear accumulation of β-catenin, is a key oncogenic driver event. Mutations in the tumor suppressor gene APC lead to impaired proteasomal degradation of β-catenin and subsequent nuclear translocation. Restoring cellular degradation of β-catenin represents a potential therapeutic strategy. Here, we report the fragment-based discovery of a small molecule binder to β-catenin, including the structural elucidation of the binding mode by X-ray crystallography. The difficulty in drugging β-catenin was confirmed as the primary screening campaigns identified only few and very weak hits. Iterative virtual and NMR screening techniques were required to discover a compound with sufficient potency to be able to obtain an X-ray co-crystal structure. The binding site is located between armadillo repeats two and three, adjacent to the BCL9 and TCF4 binding sites. Genetic studies show that it is unlikely to be useful for the development of protein–protein interaction inhibitors but structural information and established assays provide a solid basis for a prospective optimization towards β-catenin proteolysis targeting chimeras (PROTACs) as alternative modality.     

Modulation of Transaminase Activity by Encapsulation in Temperature-Sensitive Poly(N-acryloyl glycinamide) Hydrogels

Smart hydrogels hold much potential for biocatalysis, not only for the immobilization of enzymes, but also for the control of enzyme activity. We investigated upper critical solution temperature-type poly N-acryloyl glycinamide (pNAGA) hydrogels as a smart matrix for the amine transaminase from Bacillus megaterium (BmTA). Physical entrapment of BmTA in pNAGA hydrogels results in high immobilization efficiency (>89 %) and high activity (97 %). The temperature-sensitiveness of pNAGA is preserved upon immobilization of BmTA and shows a gradual deswelling upon temperature reduction. While enzyme activity is mainly controlled by temperature, deactivation tended to be higher for immobilized BmTA (≈62–68 %) than for free BmTA (≈44 %), suggesting a deactivating effect due to deswelling of the pNAGA gel. Although the deactivation in response to hydrogel deswelling is not yet suitable for controlling enzyme activity sufficiently, it is nevertheless a good starting point for further optimization.     

Lignin and lignin derivatives as components in biobased hot melt adhesives

Hot melt adhesives (HMAs) are formulated for the first time with different lignins as major components, and the developed HMA formulations were tested for gluing paperboard. The best formulations showed equal or even better bond strength compared to a commercial HMA reference. A maximum bond strength of 16.1 N was achieved with a formulation of oxidized cellulose acetate, organosolv lignin, and triethyl citrate, whereas the bond strength of the commercial HMA reference was 10.5 N. The performance was adjusted via the selection of lignin, the formulation, and chemical modification. Lignin modification was not necessary but provided further possibilities for adjusting the properties for different products (reversible vs irreversible adhesive seams) and also for producing plasticizer-free formulations. Modification with tall oil fatty acids enabled the formulation of fully biobased HMAs without any external plasticizer and provided a bond strength as high as high as 8.9 N. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47983.     

Hydrolysis of intralipid by pancreatic lipase and phospholipase A2-gel filtration studies

Intralipid was incubated with pancreatic lipase (EC 3.1.1.3) and/or phospholipase A₂ (EC 3.1.1.4) at two bile salts/phosphatidylcholine molar ratios and at two different triglyceride hydrolysis rates using various amounts of lipase. Incubations were studied by gel filtration. Results show: (i) During lipase action, three phases of lipids coexist: an emulsified phase, a micellar phase and an intermediate heavy phase sized between the two others. The equilibrium between each phase is dependent upon the bile salts concentration. (ii) Under these conditions, pancreatic lipase was at 60% bound to the emulsified phase, whereas pancreatic phospholipase A₂ was bound at 94% to the micellar phase.     

Transition from subcritical to supercritical bifurcation in penetrative convection in a vertical cylinder

The stability of a vertical cylindrical column of water with the horizontal bottom boundary maintained at 0°C and the temperature of the top boundary varying between 4 and 8°C is considered. A weakly non-linear analysis shows that the bifurcation is either supercritical or subcritical depending upon the values of two parameters: the aspect ratio of the cylinder (height/radius) which is varied between 2 and 4, and the penetration parameter μ defined as the ratio of the whole height over the height of the 4°C isotherm. For a given value of the aspect ratio, the bifurcation is supercritical when the whole height is unstable (μ = 1) and becomes subcritical above a particular value of μ when penetration occurs (μ > 1).     

Detection of β‐Amyloid by Sialic Acid Coated Bovine Serum Albumin Magnetic Nanoparticles in a Mouse Model of Alzheimer's Disease

The accumulation and formation of β‐amyloid (Aβ) plaques in the brain are distinctive pathological hallmarks of Alzheimer's disease (AD). Designing nanoparticle (NP) contrast agents capable of binding with Aβ highly selectively can potentially facilitate early detection of AD. However, a significant obstacle is the blood brain barrier (BBB), which can preclude the entrance of NPs into the brain for Aβ binding. In this work, bovine serum albumin (BSA) coated NPs are decorated with sialic acid (NP‐BSA_x‐Sia) to overcome the challenges in Aβ imaging in vivo. The NP‐BSA_x‐Sia is biocompatible with high magnetic relaxivities, suggesting that they are suitable contrast agents for magnetic resonance imaging (MRI). The NP‐BSA_x‐Sia binds with Aβ in a sialic acid dependent manner with high selectivities toward Aβ deposited on brains and cross the BBB in an in vitro model. The abilities of these NPs to detect Aβ in vivo in human AD transgenic mice by MRI are evaluated without the need to coinject mannitol to increase BBB permeability. T₂*‐weighted MRI shows that Aβ plaques in mouse brains can be detected as aided by NP‐BSA_x‐Sia, which is confirmed by histological analysis. Thus, NP‐BSA_x‐Sia is a promising new tool for noninvasive in vivo detection of Aβ plaques.     

Generating and exploiting customer insights from social media data

Previous research has emphasized the virtues of customer insights as a key source of competitive advantage. The rise of customers’ social media use allows firms to collect customer data in an ever-increasing volume and variety. However, to date, little is known about the capabilities required of firms to turn social media data into valuable customer insights and exploit these insights to create added value for customers. Based on the dynamic capabilities perspective, in particular the concept of absorptive capacity (ACAP), the authors conducted multiple case studies of seven mid-sized and large B2C firms in Switzerland and Germany. The results provide an in-depth analysis of the underlying processes of ACAP as well as contingent factors – that is, physical, human and organizational resources that underpin the firms’ ACAP.     

Emergent vegetation in Netley-Libau Marsh: Temporal changes (1990–2013) in cover in relation to Lake Winnipeg level and Red River flow

A time-series (1990–2013) of classified vegetation cover maps was produced for Netley-Libau Marsh, a 26,000 ha coastal wetland on Lake Winnipeg, to assess its current status and verify earlier trends of emergent vegetation loss. Open water area in the marsh was measured from late-summer Landsat images for 20 years; three classes of vegetation types (emergents, wet meadows, upland) could also be identified for 12 images covering the same period. Temporal changes in area and distribution of marsh vegetation were related to adjoining Lake Winnipeg water-level and Red River discharge, as well as marsh connectivity and bathymetry. From 1990 to 2002, an increase in open-water areas and decrease in emergent vegetation coincided with rising levels and flows. The year 2003 marked major wetland regeneration and a decrease of open-water area under extremely low water-levels and flows. From 2005 to 2013, open-water area remained consistent, under high but variable levels and flows. A strong negative correlation was found between area of emergent vegetation and mean Red River discharge in the previous June-July. Superimposition of the limit of new emergent vegetation observed in 2003 with depth contours surveyed in 2010 revealed the dynamic nature of marsh bathymetry. Periods of extremely low water as short as one year (2003) induced a marked expansion in emergent vegetation cover that persisted over the next ten years despite higher water-levels. Rather than being gradual, changes in the spatial extent of Netley-Libau Marsh vegetation appeared to proceed by fits and starts, wherein periods of relative stasis were disrupted by major changes in abundance.