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Wisniewska, M.

Publications and source records attributed to Wisniewska, M..

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Simulated poaching affects connectedness and efficiency in social networks of African savanna elephants

Selective harvest, such as poaching, impacts group-living animals directly through mortality of individuals with desirable traits, and indirectly by altering the structure of their social networks. Understanding the relationship between the structural network changes and group performance in wild animals remains an outstanding problem. To address this knowledge gap, we evaluate the immediate effect of disturbance on group sociality in African savanna elephants -- an example, group-living species threatened by poaching. Drawing on static association data from one free ranging population, we constructed 100 virtual networks; performed a series of experiments poaching the oldest, socially central or random individuals; and quantified the immediate change in the theoretical indices of network connectivity and efficiency of social diffusion. Although the virtual networks never broke down, targeted elimination of the socially central conspecifics, regardless of age, decreased network connectivity and efficiency. These findings hint at the need to further study resilience by modeling network reorganization and interaction-mediated socioecological learning, empirical data permitting. Our work is unique in quantifying connectivity together with global efficiency in multiple virtual networks that represent the sociodemographic diversity of elephant populations likely found in the wild. The basic design of our simulation platform makes it adaptable for hypothesis testing about the consequences of anthropogenic disturbance or lethal management on social interactions in a variety of group-living species with limited, real-world data. Author SummaryWe consider the immediate response of animal groups to human disturbance by using the African savanna elephant as an example of a group-living species threatened by poaching. Previous research in one elephant population showed that poaching-induced mortality reduced social interaction among distantly related elephants, but not among close kin. Whether this type of resilience indicates that affected populations function similarity before and after poaching is an open problem. Understanding it is important because poaching often targets the largest and most socially and ecologically experienced group members. Drawing on empirical association data, we simulated poaching in 100 virtual elephant populations and eliminated the most senior or sociable members. Targeted poaching of sociable conspecifics was more impactful. Although it did not lead to population breakdown, it hampered theoretical features of interspecific associations that in other systems have been associated with group cohesion and the efficiency of transferring social information. Our findings suggest that further inquiry into the relationship between resilience to poaching and group performance is warranted. In addition, our simulation platform offers a generalizable basis for hypothesis testing in other social species, wild or captive, subject to exploitation by humans.

animal behavior and cognition

SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 elicits immunogenicity in baboons and protection in mice

The COVID-19 pandemic continues to spread throughout the world with an urgent need for a safe and protective vaccine to effectuate herd immunity to control the spread of SARS-CoV-2. Here, we report the development of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) produced from the full-length spike (S) protein, stabilized in the prefusion conformation. Purified NVX-CoV2373 S form 27.2nm nanoparticles that are thermostable and bind with high affinity to the human angiotensin-converting enzyme 2 (hACE2) receptor. In mice and baboons, low-dose NVX-CoV2373 with saponin-based Matrix-M adjuvant elicits high titer anti-S IgG that is associated with blockade of hACE2 receptor binding, virus neutralization, and protection against SARS-CoV-2 challenge in mice with no evidence of vaccine-associated enhanced respiratory disease (VAERD). NVX-CoV2373 vaccine also elicits multifunctional CD4+ and CD8+ T cells, CD4+ T follicular helper T cells (Tfh), and the generation of antigen-specific germinal center (GC) B cells in the spleen. These results support the ongoing phase 1/2 clinical evaluation of the safety and immunogenicity of NVX-CoV2327 with Matrix-M (NCT04368988).

microbiology

Kallikrein-related peptidase 14 activates zymogens of membrane type matrix metalloproteinases (MT-MMPs) - a CleavEx library-based analysis

Kallikrein-related peptidases (KLKs) and matrix metalloproteinases (MMPs) are secretory proteinases known to proteolytically process components of the extracellular matrix (ECM), thus modulating the pericellular environment in physiology and excessively in pathologies like cancer. However, the interconnection between these groups of proteases remains elusive. To test this hypothesis, we have developed a peptide library-based exposition system (Cleavage of exposed amino acid sequences, CleavEx) aiming at investigating the potential of KLK14 to recognize and hydrolyze proMMP sequences specifically. Initial assessment of the library identified a total of ten MMP activation domain sequences which were validated by Edman degradation. The CleavEx analysis revealed that membrane-type (MT) MMPs are likely targeted by KLK14 for activation. Correspondingly, commercially available proMT-MMPs, namely proMMP14-17 were investigated in vitro and found to be effectively processed by KLK14. Again, the expected neo-N-termini of the activated MT MMPs were yielded and confirmed by Edman degradation. In addition, the productivity of proMMP activation was analyzed by gelatin zymography, which indicated the release of fully active, mature MT-MMPs upon KLK14 treatment. Lastly, MMP14 was shown to be processed on the cell surface by KLK14 using murine fibroblasts stably overexpressing human MMP14. Herein, we propose KLK14-mediated selective activation of cell-membrane located MT-MMPs as an additional layer of their regulation within the ECM. As both, KLKs and MT-MMPs are implicated in cancer, the activation described herein may constitute an important factor in tumor progression and metastasis.

biochemistry