Ecomorphology and Morphological Disparity of Caquetaia Kraussii (Perciformes: Cichlidae) in Colombia.

Understanding the interspecific morphological variability of Caquetaia kraussii (Perciformes: Cichlidae) between different localities in its distribution range is becoming essential, as this species constitutes a valuable resource for the economy and subsistence of the local human communities where it is endemic in Colombia and Venezuela. In order to develop efficient farming and handling plans for this species, a deep understanding of the factors and mechanisms generating morphological variability is crucial. This study analyzes the morphological variability of by using geometric morphometrics in four localities distributed between the Dique and North channels, which are part of the Bolívar department in Colombia.

Stereo electronic principles for selecting fully-protective, chemically-synthesised malaria vaccines.

Major histocompatibility class II molecule-peptide-T-cell receptor (MHCII-p-TCR) complex-mediated antigen presentation for a minimal subunit-based, multi-epitope, multistage, chemically-synthesised antimalarial vaccine is essential for inducing an appropriate immune response. Deep understanding of this MHCII-p-TCR complex's stereo-electronic characteristics is fundamental for vaccine development. This review encapsulates the main principles for achieving such epitopes' perfect fit into MHC-II human (HLADRβ̞1*) or (Aona DR) molecules.

SM-COLSARSPROT: Highly Immunogenic Supramutational Synthetic Peptides Covering the World's Population.

Fifty ~20-amino acid (aa)-long peptides were selected from functionally relevant SARS-CoV-2 S, M, and E proteins for trial and another 53 common ones, plus some new ones derived from the virus' main genetic variants for complementary trial . Peptide selection was based on tremendous SARS-CoV-2 genetic variability for analysing them concerning vast human immunogenetic polymorphism for developing the first supramutational, Colombian SARS-protection (SM-COLSARSPROT), peptide mixture. Specific physicochemical rules were followed, i.

evaluation of the toxic activity and genotoxicity of the L.'s resin in .

Due to the negative consequences carried by the usage of synthetic insecticides, a global interest into finding substitutes for these chemical compounds through natural products has arisen. When yielded to external attacks, plants generally produce metabolites to defend themselves. The physicochemical characteristics of this kind of compounds have allowed their usage as potential bioinsecticides.

The First Chemically-Synthesised, Highly Immunogenic Anti-SARS-CoV-2 Peptides in DNA Genotyped Monkeys for Human Use.

Thirty-five peptides selected from functionally-relevant SARS-CoV-2 spike (S), membrane (M), and envelope (E) proteins were suitably modified for immunising MHC class II (MHCII) DNA-genotyped monkeys and matched with HLA-DRβ1* molecules for use in humans. This was aimed at producing the first minimal subunit-based, chemically-synthesised, immunogenic molecules (COLSARSPROT) covering several HLA alleles. They were predicted to cover 48.

Specific β-Turns Precede PPII Structures Binding to Allele-Specific HLA-DRβ1 PBRs in Fully-Protective Malaria Vaccine Components.

The 3D structural analysis of 62 peptides derived from highly pathogenic malaria parasite proteins involved in host cell invasion led to finding a striking association between particular β-turn types located in the N-terminal peripheral flanking residue region (preceding the polyproline II left-handed structures fitting into the HLA-DRβ allele family) and modified mmune protection-inducing protein structure induced long-lasting protective immunity. This is the first time association between two different secondary structures associated with a specific immunological function has been described: full, long-lasting protective immunity.

Conserved Binding Regions Provide the Clue for Peptide-Based Vaccine Development: A Chemical Perspective.

Synthetic peptides have become invaluable biomedical research and medicinal chemistry tools for studying functional roles, i.e., binding or proteolytic activity, naturally-occurring regions' immunogenicity in proteins and developing therapeutic agents and vaccines.

A Large Size Chimeric Highly Immunogenic Peptide Presents Multistage Plasmodium Antigens as a Vaccine Candidate System against Malaria.

Rational strategies for obtaining malaria vaccine candidates should include not only a proper selection of target antigens for antibody stimulation, but also a versatile molecular design based on ordering the right pieces from the complex pathogen molecular puzzle towards more active and functional immunogens. Classical antigens regarded as vaccine candidates have been selected as model targets in this study. Among all possibilities we have chosen epitopes of CSP, STARP; MSA1 and 155/RESA from pre- and erythrocyte stages respectively for designing a large 82-residue chimeric immunogen.

Functionally relevant proteins in Plasmodium falciparum host cell invasion.

A totally effective, antimalarial vaccine must involve sporozoite and merozoite proteins (or their fragments) to ensure complete parasite blocking during critical invasion stages. This Special Report examines proteins involved in critical biological functions for parasite survival and highlights the conserved amino acid sequences of the most important proteins involved in sporozoite invasion of hepatocytes and merozoite invasion of red blood cells. Conserved high activity binding peptides are located in such proteins' functionally strategic sites, whose functions are related to receptor binding, nutrient and protein transport, enzyme activity and molecule-molecule interactions.

TCR-contacting residues orientation and HLA-DRβ* binding preference determine long-lasting protective immunity against malaria.

Fully-protective, long-lasting, immunological (FPLLI) memory against Plasmodium falciparum malaria regarding immune protection-inducing protein structures (IMPIPS) vaccinated into monkeys previously challenged and re-challenged 60 days later with a lethal Aotus monkey-adapted P. falciparum strain was found to be associated with preferential high binding capacity to HLA-DRβ1* allelic molecules of the major histocompatibility class II (MHC-II), rather than HLA-DRβ3*, β4*, β5* alleles. Complete PPIIL 3D structure, a longer distance (26.

IMPIPS: the immune protection-inducing protein structure concept in the search for steric-electron and topochemical principles for complete fully-protective chemically synthesised vaccine development.

Determining immune protection-inducing protein structures (IMPIPS) involves defining the stereo-electron and topochemical characteristics which are essential in MHC-p-TCR complex formation. Modified high activity binding peptides (mHABP) were thus synthesised to produce a large panel of IMPIPS measuring 26.5 ±3.

Protecting capacity against malaria of chemically defined tetramer forms based on the Plasmodium falciparum apical sushi protein as potential vaccine components.

Developing novel generations of subunit-based antimalarial vaccines in the form of chemically-defined macromolecule systems for multiple antigen presentation represents a classical problem in the field of vaccine development. Many efforts involving synthesis strategies leading to macromolecule constructs have been based on dendrimer-like systems, the condensation of large building blocks and conventional asymmetric double dimer constructs, all based on lysine cores. This work describes novel symmetric double dimer and condensed linear constructs for presenting selected peptide multi-copies from the apical sushi protein expressed in Plasmodium falciparum.

Gauche(+) side-chain orientation as a key factor in the search for an immunogenic peptide mixture leading to a complete fully protective vaccine.

Topological and stereo-electron characteristics are essential in major histocompability class II-peptide-T-cell receptor (MHC-p-TCR) complex formation for inducing an appropriate immune response. Modified high activity binding peptides (mHABPs) were synthesised for complete full protection antimalarial vaccine development producing a large panel of individually fully protection-inducing protein structures (FPIPS) and very high long-lasting antibody-inducing (VHLLAI) mHABPs. Most of those which did not interfere, compete, inhibit or suppress their individual VHLLAI or FPIPS activity contained or displayed a polyproline II-like (PPIIL) structure when mixed.

Towards the development of a fully protective Plasmodium falciparum antimalarial vaccine.

If ever there were a truism then it would be that a completely protective Plasmodium falciparum malaria vaccine is desperately needed. Our institute has devoted all its efforts during the last 30 years to developing a fully protective, minimal subunit-based, multiepitope, multistage (targeting sporozoite and merozoite proteins), chemically synthesized antimalarial vaccine, given that peptides with high binding activity to their corresponding host cells (liver cells or red blood cells) form the springboard for vaccine design. However, such conserved high activity binding peptides have to be specifically modified to render them into highly immunogenic and protection-inducing peptides since they are immunologically silent.

Phi (Φ) and psi (Ψ) angles involved in malarial peptide bonds determine sterile protective immunity.

Modified HABP (mHABP) regions interacting with HLA-DRβ1(∗) molecules have a more restricted conformation and/or sequence than other mHABPs which do not fit perfectly into their peptide binding regions (PBR) and do not induce an acceptable immune response due to the critical role of their Φ and Ψ torsion angles. These angle's critical role was determined in such highly immunogenic, protection-inducing response against experimental malaria using the conformers (mHABPs) obtained by (1)H-NMR and superimposed into HLA-DRβ1(∗)-like Aotus monkey molecules; their phi (Φ) and psi (Ψ) angles were measured and the H-bond formation between these molecules was evaluated. The aforementioned mHABP propensity to assume a regular conformation similar to a left-handed polyproline type II helix (PPII(L)) led to suggesting that favouring these conformations according to their amino acid sequence would lead to high antibody titre production and sterile protective immunity induction against malaria, thereby adding new principles or rules for vaccine development, malaria being one of them.

The high immunogenicity induced by modified sporozoites' malarial peptides depends on their phi (ϕ) and psi (ψ) angles.

The importance of CSP- and STARP-derived ϕ and ψ dihedral angles in mHABP structure was analysed by (1)H NMR in the search for molecules which can be included as components of a first-line-of-defence Plasmodium falciparum sporozoite multi-epitope vaccine against the most lethal form of human malaria. Most of the aforementioned dihedral angles were left-hand-like polyproline type II (PPII(L)) structures whilst others had right-hand-like α-helix (α(R)), thus allowing mHABPS to fit better into MHCII molecules and thereby form an appropriate pMHCII complex and also establish the H-bonds which stabilise such complex and by this means induce an appropriate immune response. This information has great implications for vaccine development, malaria being one of them.

A single amino acid change in the Plasmodium falciparum RH5 (PfRH5) human RBC binding sequence modifies its structure and determines species-specific binding activity.

Identifying the ligands or regions derived from them which parasites use to invade their target cells has proved to be an excellent strategy for identifying targets for vaccine development. Members of the reticulocyte-binding homologue family (PfRH), including RH5, have been implicated in invasion as adhesins binding to specific receptors on erythrocyte surface. The regions mediating PfRH5-RBC specific interactions have been identified here by fine mapping the whole PfRH5 protein sequence.

Binding activity, structure, and immunogenicity of synthetic peptides derived from Plasmodium falciparum CelTOS and TRSP proteins.

Several sporozoite proteins have been associated with Plasmodium falciparum cell traversal and hepatocyte invasion, including the cell-traversal protein for ookinetes and sporozoites (CelTOS), and thrombospondin-related sporozoite protein (TRSP). CelTOS and TRSP amino acid sequences have been finely mapped to identify regions specifically binding to HeLa and HepG2 cells, respectively. Three high-activity binding peptides (HABPs) were found in CelTOS and one HABP was found in TRSP, all of them having high α-helical structure content.

Protective immunity provided by a new modified SERA protein peptide: its immunogenetic characteristics and correlation with 3D structure.

The serine repeat antigen (SERA) protein is a leading candidate molecule for inclusion as a component in a multi-antigen, multi-stage, minimal subunit-based, chemically synthesised anti-malarial vaccine. Peptides having high red blood cell binding affinity (known as HABPs) have been identified in this protein. The 6733 HABP was located in the C-terminal portion of the 47-kDa fragment while HABP 6754 was located in the C-terminal region of the 56-kDa fragment.

3D structure determination of STARP peptides implicated in P. falciparum invasion of hepatic cells.

To block the different stages of Plasmodium falciparum invasion into human hepatocytes and red blood cells, we have focused on those proteins belonging to the pre-erythrocytic stage. One of these proteins is Sporozoite Threonine and Asparagine Rich Protein (STARP), which is a ligand used by P. falciparum parasites to bind Hepatic cells (HepG2).

3D analysis of the TCR/pMHCII complex formation in monkeys vaccinated with the first peptide inducing sterilizing immunity against human malaria.

T-cell receptor gene rearrangements were studied in Aotus monkeys developing high antibody titers and sterilizing immunity against the Plasmodium falciparum malaria parasite upon vaccination with the modified synthetic peptide 24112, which was identified in the Merozoite Surface Protein 2 (MSP-2) and is known to bind to HLA-DRbeta1*0403 molecules with high capacity. Spectratyping analysis showed a preferential usage of Vbeta12 and Vbeta6 TCR gene families in 67% of HLA-DRbeta1*0403-like genotyped monkeys. Docking of peptide 24112 into the HLA-DRbeta1*0401-HA peptide-HA1.

Structural and immunological analysis of circumsporozoite protein peptides: a further step in the identification of potential components of a minimal subunit-based, chemically synthesised antimalarial vaccine.

The Plasmodium falciparum circumsporozoite protein is considered a major antimalarial-vaccine target due to its involvement in sporozoite invasion of mosquito's salivary glands and human hepatocytes. The 4383, 4388 and 4389 CSP-conserved high activity hepatocyte binding peptides and their modified analogues were synthesised and their immunogenicity was tested in Aotus monkeys. Peptide 4388 modified analogues induced higher and more permanent antibody titers against sporozoites in approximately 40% of immunised monkeys; whilst peptides 4383 and 4389 modified analogues elicited high, long-lasting antibody titers as well as short-lived antibodies.