This work shows that
Plasmodium falciparum merozoite surface protein-6 (MSP-6) peptides specifically bind to membrane surface receptor on human erythrocytes. Three high activity binding peptides ...(HABPs) were found: peptides 31175 (
41MYNNDKILSKNEVDTNIESN
60) and 31178 (
101YDIQATYQFPSTSGGNNVIP
120) in the amino terminal region and 31191 (
361EIDSTINNLVQEMIHLFSNNY
380) at the carboxy terminal. Their binding to erythrocytes was saturable. HABPs 31191 and 31178 recognized 56 and 26
kDa receptors on erythrocyte membrane and inhibited in vitro
Plasmodium falciparum merozoite invasion of erythrocytes by between 27% and 46% at 200
μg
ml
−1 concentration, suggesting that these MSP-6 protein peptides play a possible role in the invasion process.
Summary
The arrival of bone marrow T‐cell progenitors to the thymus, and the directed migration of thymocytes, are thought to be regulated by the expression of chemokines and their receptors. Recent ...data has shown that the Jak\Stat signalling pathway is involved in chemokine receptor signalling. We have investigated the role of Jak 3 in chemokine‐mediated signalling in the thymus using Jak 3–\– mice. These mice show defects in T‐cell development, as well as in peripheral T‐cell function, resulting in a hypoplastic thymus and an altered T‐cell homeostasis. Here we demonstrate, for the first time, that bone marrow progenitors and thymocytes from Jak 3–\– mice have decreased chemotactic responses to CXCL12 and CCL25. We also show that Jak 3 is involved in signalling through CCR9 and CXCR4, and that specific inhibition of Jak 3 in wild‐type progenitors and thymocytes decreases their chemotactic responses towards CCL25 and CXCL12. Finally, quantitative reverse transcription–polymerase chain reaction analysis showed that thymocytes from Jak 3–\– mice express similar levels of CXCR4 and CCR9 compared to wild‐type mice. Altogether, deficient CCL25‐ and CXCL12‐induced migration could result in a homing defect of T‐cell progenitors to the thymus, as well as in a deficient thymocyte migration through the thymic stroma. Our results strongly suggest that the absence of Jak 3 affects T‐cell development, not only through an impaired interleukin‐7 receptor (IL‐7R)‐mediated signalling, but also through impaired chemokine‐mediated responses, which are crucial for thymocyte migration and differentiation.
Intoxications are a frequent cause for consultation and admission in emergency medical services. Treating these patients is a challenge both diagnostically and therapeutically, where some critical ...circumstances may determine the prognosis. A structured search was conducted in the PubMed/Medline database, for articles discussing how intoxications were handled in emergency medical services published between March 2005 and December 2023. A combination of the following keywords was used to perform the search: “intoxication”, “poisoning”, “management”, “emergency”, and “patient”. All reviews, clinical trials, observational studies, and case reports related to handling intoxicated patients were considered. Lastly, articles in the authors’ databases were included, as well as reference books and gray literature. 42 articles that met the selection criteria were chosen. Upon review of the literature, a Toxicological Chain of Survival (TCS) was devised, a basic diagnostic and therapeutic algorithm that can be useful for the first responder.
Plasmodium falciparum rhoptry-associated proteins 1 (RAP1) and 2 (RAP2) are antigens presenting themselves as candidates for a subunit malaria vaccine. RAP2 protein, non-overlapping, consecutive ...peptides were synthesised and tested in red blood cell (RBC) binding assays to identify their receptor–ligand interaction in recognising RAP2 regions involved in the in vitro merozoite invasion process. Four high activity binding peptides (HABPs) were identified in the resulting 20 peptides. Peptides 26220 (
61NHFSSADE
LIKYLEKTNINT
80), 26225 (
161IKKN
PFLRV
LNKA
STTTH
AT
180) and 26229 (
241RSVNNV
ISKN
KTLG
LRKRSS
260) were located in the amino terminal and central part of the protein and HABP 26235 (
361FLAEDFVELFDVTMDCYSRQ
380) was located at the carboxy terminal. All these HABPs showed saturable binding and presented dissociation constants between 500 and 950 nM; the number of binding sites per RBC ranged from 48 000 to 160 000. High binding peptides’ critical amino acids involved in RBC binding were determined by competition binding assays; their amino acids appear in bold in the sequences shown above. SDS-PAGE results showed that peptides 26220, 26225 and 26229 had at least two different sets of 62 and 42 kDa HABP receptors on RBCs and that peptide 26235 had at least two different sets of 77 and 62 kDa. HABPs inhibited in vitro merozoite invasion by between 54% and 94% at 200 μM, suggesting that these RAP2 peptides are involved in the in vitro
P. falciparum invasion process.
PDF
