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ABSTRACT: Streptococcus pyogenes is an important human pathogen, commonly spread by airborne droplets but also by ingestion of contaminated food. Apart from causing infection, this pathogen produces 13 distinct types of streptococcal pyrogenic exotoxins (SPE). The current method for detection cannot distinguish between the biologically active form of SPE that has been reported to cause foodborne outbreaks and the inactivated toxin that poses no health risk. To measure the biological activity of SPE type C (SPE-C), one such toxin that was linked to foodborne outbreaks associated with milk and milk products, we developed a cell-based assay that can discern between biologically active and inactive SPE-C. To the best of our knowledge, this is the first showing that SPE-C activates T-cells expressing Vβ8. With this finding, we used a T-cell line natively expressing Vβ8 that was genetically engineered to also express the luciferase reporter gene under the regulation of nuclear factor of activated T-cells response element in combination with a B-cell line to present the recombinant SPE-C (rSPE-C) toxin via major histocompatibility complex (MHC) class II to the Vβ8 T-cell receptor (TCR) in an assay to detect and to discern between biologically active and inactive rSPE-C. By using this system, we demonstrated that SPE-C induced significant IL-2 secretion after 72 h and visible light emission after only 5 h, doubling by 24 h. We utilize this finding to assess the specificity of the assay and the effect of pasteurization on SPE-C activity. We observed no cross-reactivity with SPE-B and significant loss of SPE-C biological activity in spiked phosphate-buffered saline while SPE-C spiked into milk is heat stable. Once SPE-C has formed, it is infeasible to eliminate it from milk by thermal treatment.

Abstract The humoral response after the fourth dose of a mRNA vaccine against COVID-19 has not been adequately described in elderly recipients, particularly those not exposed previously to SARS-CoV-2. Serum anti-RBD IgG levels (Abbott SARS-CoV-2 IgG II Quant assay) and neutralizing capacities (spike SARS-CoV-2 pseudovirus Wuhan and Omicron BA.1 variant) were measured after the third and fourth doses of a COVID-19 mRNA vaccine among 46 elderly residents (median age 85 years [IQR 81; 89]) of an assisted living facility. Among participants never infected by SARS-CoV-2, the mean serum IgG levels against RBD (2025 BAU/ml), 99 days after the fourth vaccine, was as high as 76 days after the third vaccine (1987 BAU/ml), and significantly higher (p = 0.030) when the latter were corrected for elapsed time. Neutralizing antibody levels against the historical Wuhan strain were significantly higher (Mean 1046 vs 1573; p = 0.002) and broader (against Omicron) (Mean 170 vs 375; p = 0.018), following the fourth vaccine. The six individuals with an Omicron breakthrough infection mounted strong immune responses for anti-RBD and neutralizing antibodies against the Omicron variant indicating that the fourth vaccine dose did not prevent a specific adaptation of the immune response. These findings point out the value of continued vaccine boosting in the elderly population

This study presents the development and application of a prototype decision support system (DSS) for tree selection specifically for Punjab, India, a region facing challenges of low forest cover and an increasing demand for sustainable land use practices. The DSS developed using the R Shiny framework integrates ecological, social, and agro-commercial criteria to facilitate scientific knowledge decision making in tree plantation. The modules in this DSS include a tree selection tool based on comprehensive species attributes, a GIS-based tree suitability map module utilizing an Analytical Hierarchical Process (AHP), and a silviculture practice information module sourced from authoritative databases. Combining sophisticated statistical and spatial analysis, such as NMDS and AHP-GIS, this DSS mitigates data redundancy in SDM while incorporating extensive bibliographic research in dataset processing. The study highlights the necessity of fundamental niche-based suitability in comparison to realized niche suitability. It emphasizes on the importance of addressing ecosystem services, agro-commercial aspects, and enhancing silvicultural knowledge. Additionally, the study underscores the significance of local stakeholder engagement in tree selection, particularly involving farmers and other growers, to ensure community involvement and support. The DSS supports agroforestry initiatives and finds applications in urban tree management and governmental programs, emphasizing the use of scientific literature at each step, in contrast to relying solely on local knowledge.

We present the first comprehensive review of 62 migratory shorebird species in Mongolia, covering their ecological status, IUCN assessments at regional or national levels, population trends, threats, and conservation measures. Mongolia hosts a total of 62 shorebird species from twenty-two genera and seven families, with six species classified as globally threatened: the Critically Endangered Sociable Lapwing, the Endangered Siberian Sandplover, the Far Eastern Curlew, the Great Knot, and the Vulnerable Sharp-Tailed Sandpiper. Both national and global IUCN Red List assessments highlight Mongolia’s significance as a breeding and passage migrating site for globally threatened and Near-Threatened shorebirds. Species richness is higher in northern regions compared to the south, with the highest diversity found in areas with complex aquatic ecosystems. Global population trends indicate a decline in 61% of species, with 18% remaining stable, 16% of unknown status, and 5% increasing. At the national level, most species are stable (61%), 34% status is unknown, and 5% are decreasing. Anthropogenic-induced threats, including habitat loss and degradation, pollution, disturbance, and harvesting, pose significant risks to 69% of species, while natural disasters affect 11%. Additionally, 8% of species are impacted by accidental mortality and intrinsic factors, and 5% by changes in native species. Despite these threats, no specific conservation action plans exist for shorebirds in Mongolia. However, general conservation measures are in place, such as environmental and fauna protection laws, regulations on foreign trade in endangered species, and the establishment of protected areas under governmental resolutions. Mongolia also participates in international conventions like the Convention on Biological Diversity (CBD), Ramsar, and Migratory Species (CMS), and has developed national red lists, red books, and publications such as “A Summary Conservation Action Plan for Mongolian Birds”, “Important Bird Areas” to support conservation efforts.

Ovarian cancer (OC) is one of the most lethal gynecologic cancers that is typically diagnosed at the very late stage of disease progression. Thus, there is an unmet need to develop diagnostic probes for early detection of OC. One approach may rely on RNA as a molecular biomarker. In this regard, FLJ22447 lncRNA is an RNA biomarker that is over-expressed in ovarian cancer (OC) and in cancer-associated fibroblasts (CAFs). CAFs appear early on in OC as they provide a metastatic niche for OC progression. FIT-PNAs (forced intercalation-peptide nucleic acids) are DNA analogs that are designed to fluoresce upon hybridization to their complementary RNA target sequence. In recent studies, we have shown that the introduction of cyclopentane PNAs into FIT-PNAs (cpFIT-PNA) results in superior RNA sensors. Herein, we report the design and synthesis of cpFIT-PNAs for the detection of this RNA biomarker in living OC cells (OVCAR8) and in CAFs. cpFIT-PNA was compared to FIT-PNA and the cell-penetrating peptide (CPP) of choice was either a simple one (four L-lysines) or a CPP with enhanced cellular uptake (CLIP6). The combination of CLIP6 with cpFIT-PNA resulted in a superior sensing of FLJ22447 lncRNA in OVCAR8 cells as well as in CAFs. Moreover, incubation of CLIP6-cpFIT-PNA in OVCAR8 cells leads to a significant decrease (ca. 60%) in FLJ22447 lncRNA levels and in cell viability, highlighting the potential theranostic use of such molecules.

Kohelet: A Map to Eden--An Intertextual Journey (Maggid Books, 2023), by David Curwin. 254 pp. Reviewed by Reuven Chaim Klein. This work is a highly enjoyable and refreshingly original exploration [...]

Abstract Background Cancer immunotherapy is implemented by identifying antigens that are presented on the cell surface of cancer cells and illicit T-cell response (Schumacher and Schreiber, Science 348:69–74, 2015; Waldman et al., Nat Rev Immunol 20:651–668, 2020; Zhang et al., Front Immunol 12:672,356, 2021b). Classical candidates of such antigens are the peptides resulting from genetic alterations and are named “neoantigen" (Schumacher and Schreiber, Science 348:69–74, 2015). Neoantigens have been widely catalogued across several human cancer types (Tan et al., Database (Oxford) 2020;2020b; Vigneron et al., Cancer Immun 13:15, 2013; Yi et al., iScience 24:103,107, 2021; Zhang et al., BMC Bioinformatics 22:40, 2021a). Recently, a new class of inducible antigens has been identified, namely Substitutants, that are produced as a result of aberrant protein translation (Pataskar et al., Nature 603:721–727, 2022). Main Catalogues of Substitutant expression across human cancer types, their specificity and association to gene expression signatures remain elusive for the scientific community's access. As a solution, we present ABPEPserver, an online database and analytical platform that can visualize a large-scale tumour proteomics analysis of Substitutant expression across eight tumour types sourced from the CPTAC database (Edwards et al., J Proteome Res 14:2707–2713, 2015). Functionally, ABPEPserver offers the analysis of gene-association signatures of Substitutant peptides, a comparison of enrichment between tumour and tumour-adjacent normal tissues, and a list of peptides that serve as candidates for immunotherapy design. ABPEPserver will significantly enhance the exploration of aberrant protein production in human cancer, as exemplified in a case study. Conclusion ABPEPserver is designed on an R SHINY platform to catalogue Substitutant peptides in human cancer. The application is available at https://rhpc.nki.nl/sites/shiny/ABPEP/ . The code is available under GNU General public license from GitHub ( https://github.com/jasminesmn/ABPEPserver ).