Smaller,Stronger, More Stable: Peptide Variants of a SARS-CoV-2 Neutralizing Miniprotein

Based on the structure of a de novo designed miniprotein (LCB1) in complex with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, we have generated and characterized truncated peptide variants of LCB1, which present only two of the three LCB1 helices, and which fully retained the virus neutralizing potency against different SARS-CoV-2 variants of concern (VOC). This antiviral activity was even 10-fold stronger for a cyclic variant of the two-helix peptides, as compared to the full-length peptide. Furthermore, the proteolytic stability of the cyclic peptide was substantially improved, rendering it a better potential candidate for SARS-CoV-2 therapy. In a more mechanistic approach, the peptides also served as tools to dissect the role of individual mutations in the RBD for the susceptibility of the resulting virus variants to neutralization by the peptides. As the peptides reported here were generated through chemical synthesis, rather than recombinant protein expression, they are amenable to further chemical modification, including the incorporation of a wide range of non-proteinogenic amino acids, with the aim to further stabilize the peptides against proteolytic degradation, as well as to improve the strength, as well the breadth, of their virus neutralizing capacity.     

Tumor Infiltration with CD20+CD73+ B Cells Correlates with Better Outcome in Colorectal Cancer

Immunotherapy has become increasingly important in the treatment of colorectal cancer (CRC). Currently, CD73, also known as ecto-5′-nucleotidase (NT5E), has gained considerable interest as a potential therapeutic target. CD73 is one of the key enzymes catalyzing the conversion of extracellular ATP into adenosine, which in turn exerts potent immune suppressive effects. However, the role of CD73 expression on various cell types within the CRC tumor microenvironment remains unresolved. The expression of CD73 on various cell types has been described recently, but the role of CD73 on B-cells in CRC remains unclear. Therefore, we analyzed CD73 on B-cells, especially on tumor-infiltrating B-cells, in paired tumor and adjacent normal tissue samples from 62 eligible CRC patients. The highest expression of CD73 on tumor-infiltrating B-cells was identified on class-switched memory B-cells, followed by naive B-cells, whereas no CD73 expression was observed on plasmablasts. Clinicopathological correlation analysis revealed that higher CD73⁺ B-cells infiltration in the CRC tumors was associated with better overall survival. Moreover, metastasized patients showed a significantly decreased number of tumor-infiltrating CD73⁺ B-cells. Finally, neoadjuvant therapy correlated with reduced CD73⁺ B-cell numbers and CD73 expression on B-cells in the CRC tumors. As promising new immune therapies are being developed, the role of CD73⁺ B-cells and their subsets in the development of colorectal cancer should be further explored to find new therapeutic options.     

Absolute characterization of high numerical aperture microscope objectives utilizing a dipole scatterer

Measuring the aberrations of optical systems is an essential step in the fabrication of high precision optical components. Such a characterization is usually ba...     

Simulating the emergence of norms in different scenarios

This paper deals with EMIL-S, a software tool box which was designed during the EMIL project for the simulation of processes during which norms emerged in an agent society. This tool box implements the cognitive architecture of normative agents which was designed during the EMIL project which is also discussed in other papers in this issue. This implementation is described in necessary detail, and two examples of its application to several different scenarios are given, namely a scenario in which persons involved in micro finance are simulated and learn how to sanction free riders and how to learn from these sanctions, and a scenario in which simulated persons move through a simulated airport where they more often than not have to wait in queues and learn how to behave properly in queues.     

Phase equilibria in the Al–Si–V system: The vanadium rich part

The V-rich part of the Al–Si–V phase diagram was determined by a combination of optical microscopy, powder X-ray diffraction (XRD), differential thermal analysis (DTA) and electron probe microanalysis (EPMA). Phase equilibria were investigated at two isothermal sections at 850 and 1300 °C. High temperature DTA was performed to identify the ternary invariant reactions yielding a ternary reaction scheme and the vertical section at 50 at.% V. As cast samples were investigated in order to gain additional information about primary crystallization fields. A liquidus surface projection was constructed for the entire ternary system by combining our experimental data with those from literature.     

Deficits in emotion-regulation skills predict alcohol use during and after cognitive–behavioral therapy for alcohol dependence.

Objective: As emotion regulation is widely considered to be a primary motive in the misuse of alcohol, our aim in the study was to investigate whether deficits in adaptive emotion-regulation skills maintain alcohol dependence (AD). Method: A prospective study investigated whether emotion-regulation skills were associated with AD and whether these skills predicted alcohol use during and after treatment for AD. Participants were 116 individuals treated for AD with cognitive–behavioral therapy. Emotion regulation and severity of AD symptoms were assessed by self-report. Alcohol use during treatment was assessed by Breathalyzer and urine analysis for ethyl glucuronide; alcohol use during the 3-month follow-up interval was assessed by self-report. Results: Pretreatment emotion-regulation skills predicted alcohol use during treatment, and posttreatment emotion-regulation skills predicted alcohol use at follow-up, even when controlling for other predictors potentially related to emotion regulation. Among a broad range of specific emotion-regulation skills, the ability to tolerate negative emotions was the only skill that negatively predicted subsequent alcohol consumption when controlling for the other skills. Individuals in the AD sample reported significantly larger deficits in emotion-regulation skills than did those in a nonclinical control sample but significantly less than did those in a sample of individuals exclusively meeting criteria for major depressive disorder. Conclusions: Enhancement of general emotion-regulation skills, especially the ability to tolerate negative emotions, appears to be an important target in the treatment of AD. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Examining infants' preferences for tempo in lullabies and playsongs.

Caregivers around the world sing to their infants. Infants not only prefer to listen to infant-directed singing over adult-directed singing, but infant-directed singing also serves a function, communicating affective information to preverbal infants to aid in adjusting arousal levels. Pitch variation has previously been identified as one performance feature that may help to convey the message. Earlier research has indicated that infants' pitch preferences are context dependent, suggesting that infants are tuned in to the communicative intent of infant-directed singing. However, there are several other performance-based features present in infant-directed singing that may also contribute to the affective message. The current study examined the role of context on infants' tempo preferences in sung playsongs and lullabies. Using a head-turn preference procedure, we measured 24 preverbal infants' natural preferences for foreign language playsongs and lullabies as a function of tempo. Infants showed a preference for fast over slow tempo playsongs, but no such context dependent preference was found within lullabies. Results partially support the role of tempo as a communicative feature of infant directed singing. (PsycINFO Database Record (c) 2011 APA, all rights reserved)