A high-affinity antibody against the CSP N-terminal domain lacks Plasmodium falciparum inhibitory activity

Malaria is a global health concern and research efforts are ongoing to develop a superior vaccine to RTS,S/AS01. To guide immunogen design, we seek a comprehensive understanding of the protective humoral response against Plasmodium falciparum circumsporozoite protein (PfCSP). In contrast to the well-studied responses to the repeat region and the C-terminus, the antibody response against the N-terminal domain of PfCSP (N-CSP) remains obscure. Here, we characterized the molecular recognition and functional efficacy of the N-CSP-specific monoclonal antibody 5D5. The crystal structure at 1.85 Åresolution revealed that 5D5 binds an α-helical epitope in N-CSP with high affinity through extensive shape and charge complementarity, and the unusual utilization of an N-linked glycan. Nevertheless, functional studies indicated low 5D5 binding to live Pf sporozoites, and lack of sporozoite inhibition in vitro and in mosquitoes. Overall, our data on low recognition and inhibition of sporozoites do not support the inclusion of the 5D5 epitope into the next generation of CSP-based vaccines.Summary Statement The Plasmodium falciparum sporozoite surface protein, PfCSP, is an attractive vaccine target, but the antibody response against the CSP N-terminal domain has remained understudied. Here, to guide immunogen design, Thai et al. provide insights into the binding motif and functional efficacy of the N-terminal domain-specific monoclonal antibody, 5D5

'The show must go on': Event dramaturgy as consolidation of community

Event dramaturgy and cultural performance have not been examined in the literature from a strategic standpoint of fostering the social value of events. Thus, the purpose of this study was to explore the case of the Water Carnival, a celebratory event in a rural community of Southwest Texas, demonstrating the essence of this event as a symbolic social space, wherein event participants instantiate a shared and valued sense of community. A hermeneutical approach was employed, interpreting the event and its symbolisms as a text, combined with findings from ethnographic fieldwork, including participant observation, in-depth interviews and analysis of archival documents. The study examines the ways that dramaturgy in the Water Carnival helps frame the ongoing public discourse for community improvement and enhances social capital. The implications of the study for social leverage of events are discussed. It is suggested that a foundation for strategic social planning is the understanding of events as symbolic social spaces and their embeddedness in community development, which can be accomplished when events are pertinent to public discourse, address community issues, represent an inclusive range of stakeholders, and promote cooperation

Phytoene synthase 1 (Psy-1) and lipoxygenase 1 (Lpx-1) Genes Influence on Semolina Yellowness in Wheat Mediterranean Germplasm

Phytoene synthase 1 (Psy1) and lipoxygenase 1 (Lpx-1) are key genes involved in the synthesis and catalysis of carotenoid pigments in durum wheat, regulating the increase and decrease in these compounds, respectively, resulting in the distinct yellow color of semolina and pasta. Here, we reported new haplotype variants and/or allele combinations of these two genes significantly affecting yellow pigment content in grain and semolina through their effect on carotenoid pigments. To reach the purpose of this work, three complementary approaches were undertaken: the identification of QTLs associated to carotenoid content on a recombinant inbred line (RIL) population, the characterization of a Mediterranean panel of accessions for Psy1 and Lpx-1 genes, and monitoring the expression of Psy1 and Lpx-1 genes during grain filling on two genotypes with contrasting yellow pigments. Our data suggest that Psy1 plays a major role during grain development, contributing to semolina yellowness, and Lpx-1 appears to be more predominant at post-harvest stages and during pasta making.info:eu-repo/semantics/publishedVersio

Lenalidomide Maintenance and Measurable Residual Disease in a Real-World Multiple Myeloma Transplanted Population Receiving Different Treatment Strategies Guided by Access to Novel Drugs in Brazil

Despite recent advances in multiple myeloma (MM), the incorporation of novel agents and measurable residual disease (MRD) monitoring in low-income countries remains a challenge. Although lenalidomide maintenance (M-Len) after autologous stem cell transplantation (ASCT) has been associated with improved outcomes and MRD has refined the prognosis of complete response (CR) cases, until now, there have been no data on the benefits of these approaches in Latin America. Here, we evaluate the benefits of M-Len and MRD using next-generation flow cytometry (NGF-MRD) at Day + 100 post-ASCT (n = 53). After ASCT, responses were evaluated based on the International Myeloma Working Group criteria and NGF-MRD. MRD was positive in 60% of patients with a median progression-free survival (PFS) of 31 months vs. not reached (NR) for MRD-negative cases (p = 0.05). The patients who received M-Len continuously had a significantly better PFS and overall survival (OS) than those without M-Len (median PFS: NR vs. 29 months, p = 0.007), with progression in 11% vs. 54% of cases after a median follow-up of 34 months, respectively. In a multivariate analysis, MRD status and M-Len therapy emerged as independent predictors of PFS (median PFS of M-Len/MRD− vs. no M-Len/MRD+ of NR vs. 35 months, respectively; p = 0.01). In summary, M-Len was associated with improved survival outcomes in our real-world MM cohort in Brazil, with MRD emerging as a useful reproducible tool to identify patients at an earlier risk of relapse. The inequity in drug access remains a hurdle in countries with financial constraints, with a negative impact on MM survival.This work was supported by from Coordenação de Aperfeiçomento de Pessoal de Nível Superior—Brazil (CAPES) Finance code 001-8888.331795/2010-01; Programa de Oncobiologia 001/2017 and 004/2017; Centro Investigación Biomédica em Red—Cáncer (CIBERONC code CB//00400) of Instituto de Salud Carlos III, Ministry of Science and Innovation (Madrid, Spain), number CB16/12/00400; The International Myeloma Foundation-Black Swan Research Initiative (Los Angeles, CA) (Grant: LSHB-CT-2006-018708). A.B.S.S. was supported by a grant from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior CAPES/PROEX, number: 88887.688096/2022-00. R.M.P. was supported by a grant from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/DGPU), number: 000281/2016-06 and CAPES/PROEX 641/2018, Brazil, and Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro of Brazil (FAPERJ), number: E01/200/537/2018. E.S.B. was supported by a grant from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior CAPES/PROEX, number: 88887.335769/2019-00 and Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), number: E-26/200.192/2020, Brazil

Estudo da prevalência de anticorpos para o vírus da síndrome reprodutiva e respiratória dos suínos (PRRS) em granjas de suínos no Brasil.

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Semi-Analytic Modelling of Galaxy Formation: The Local Universe

Using semi-analytic models of galaxy formation, we investigate galaxy properties such as the Tully-Fisher relation, the B and K-band luminosity functions, cold gas contents, sizes, metallicities, and colours, and compare our results with observations of local galaxies. We investigate several different recipes for star formation and supernova feedback, including choices that are similar to the treatment in Kauffmann, White & Guiderdoni (1993) and Cole et al. (1994) as well as some new recipes. We obtain good agreement with all of the key local observations mentioned above. In particular, in our best models, we simultaneously produce good agreement with both the observed B and K-band luminosity functions and the I-band Tully-Fisher relation. Improved cooling and supernova feedback modelling, inclusion of dust extinction, and an improved Press-Schechter model all contribute to this success. We present results for several variants of the CDM family of cosmologies, and find that models with values of $\Omega_0 \simeq 0.3$--0.5 give the best agreement with observations.Comment: 26 pages, LaTeX, MNRAS format, 23 inlined postscript figures. Accepted for publication in MNRAS. Revised version contains substantial changes including improved models. High resolution figures, original version, and summary of changes may be found at http://www.fiz.huji.ac.il/~rachels/papers/sp.htm