Analysis of insecticides in long-lasting insecticidal nets using X-ray fluorescence spectroscopy and correlation with bioefficacy.

Background: Long-lasting insecticidal nets (LLINs) are a key vector control tool used for the prevention of malaria. Active ingredient (AI) measurements in LLINs are essential for evaluating their quality and efficacy. The main aim of the present study was to determine the utility of X-ray fluorescence (XRF) spectroscopy as a suitable field-deployable tool for total AI quantification in LLINs.

A Modular Self-Assembling and Self-Adjuvanting Multiepitope Peptide Nanoparticle Vaccine Platform to Improve the Efficacy and Immunogenicity of BCG.

After more than a century since its initial development, Bacille Calmette-Guérin (BCG) remains the only licensed vaccine against tuberculosis (TB). Subunit boosters are considered a viable strategy to enhance BCG efficacy, which often wanes in adolescence. While many studies on booster subunit vaccines have concentrated on recombinant proteins, here we developed a novel modular peptide-based subunit vaccine platform that is flexible, cold-chain independent and customizable to diverse circumstances and populations.

Structural analysis of an Asterias rubens peptide indicates the presence of a disulfide-directed β-hairpin fold.

Sea stars are an abundant group of marine invertebrates that display remarkably robust regenerative capabilities throughout all life stages. Numerous proteins and peptides have been identified in a proteome study on the coelomic fluid (biofluid) of the common sea star Asterias rubens, which appear to be involved with the wound-healing response in the organism. However, the three-dimensional structure and function of several of these injury-responsive peptides, including the peptide KASH2, are yet to be investigated.

Structural analysis of a U-superfamily conotoxin containing a mini-granulin fold: Insights into key features that distinguish between the ICK and granulin folds.

We are entering an exciting time in structural biology where artificial intelligence can be used to predict protein structures with greater accuracy than ever before. Extending this level of accuracy to the predictions of disulfide-rich peptide structures is likely to be more challenging, at least in the short term, given the tight packing of cysteine residues and the numerous ways that the disulfide bonds can potentially be linked. It has been previously shown in many cases that several disulfide bond connectivities can be accommodated by a single set of NMR-derived structural data without significant violations.

In silico design of potential Mcl-1 peptide-based inhibitors.

Context: BIM (Bcl-2 interacting mediator of apoptosis)-derived peptides that specifically target over-expressed Mcl-1 (myeloid cell leukemia-1) protein and induce apoptosis are potentially anti-cancer agents. Since the helicity of BIM-derived peptides has a crucial role in their functionality, a range of strategies have been used to increase the helicity including the introduction of unnatural residues and stapling methods that have some drawbacks such as the accumulation in the liver. To avoid these drawbacks, this study aimed to design a more helical peptide by utilizing bioinformatics algorithms and molecular dynamics simulations without exploiting unnatural residues and stapling methods.

Structure-function and rational design of a spider toxin Ssp1a at human voltage-gated sodium channel subtypes.

The structure-function and optimization studies of Na-inhibiting spider toxins have focused on developing selective inhibitors for peripheral pain-sensing Na1.7. With several Na subtypes emerging as potential therapeutic targets, structure-function analysis of Na-inhibiting spider toxins at such subtypes is warranted.

Solution structure of the N-terminal extension domain of a asparaginyl-tRNA synthetase.

Several secreted proteins from helminths (parasitic worms) have been shown to have immunomodulatory activities. Asparaginyl-tRNA synthetases are abundantly secreted in the filarial nematode (AsnRS) and the parasitic flatworm (AsnRS), indicating a possible immune function. The suggestion is supported by AsnRS alleviating disease symptoms in a T-cell transfer mouse model of colitis.

Pmu1a, a novel spider toxin with dual inhibitory activity at pain targets hNa 1.7 and hCa 3 voltage-gated channels.

Venom-derived peptides targeting ion channels involved in pain are regarded as a promising alternative to current, and often ineffective, chronic pain treatments. Many peptide toxins are known to specifically and potently block established therapeutic targets, among which the voltage-gated sodium and calcium channels are major contributors. Here, we report on the discovery and characterization of a novel spider toxin isolated from the crude venom of Pterinochilus murinus that shows inhibitory activity at both hNa 1.

ApInAPDB: a database of apoptosis-inducing anticancer peptides.

ApInAPDB (Apoptosis-Inducing Anticancer Peptides Database) consists of 818 apoptosis-inducing anticancer peptides which are manually collected from research articles. The database provides scholars with peptide related information such as function, binding target and affinity, IC50 and etc. In addition, GRAVY (grand average of hydropathy), net charge at pH 7, hydrophobicity and other physicochemical properties are calculated and presented.

Peptides derived from hookworm anti-inflammatory proteins suppress inducible colitis in mice and inflammatory cytokine production by human cells.

A decline in the prevalence of parasites such as hookworms appears to be correlated with the rise in non-communicable inflammatory conditions in people from high- and middle-income countries. This correlation has led to studies that have identified proteins produced by hookworms that can suppress inflammatory bowel disease (IBD) and asthma in animal models. Hookworms secrete a family of abundant netrin-domain containing proteins referred to as AIPs (Anti-Inflammatory Proteins), but there is no information on the structure-function relationships.

Anti-inflammatory properties of novel galloyl glucosides isolated from the Australian tropical plant Uromyrtus metrosideros.

Two new galloyl glucosides, galloyl-lawsoniaside A (4) and uromyrtoside (6), were isolated from the polar fraction of Uromyrtus metrosideros leaf extract along with another four previously identified phytochemicals (1, 2, 3, and 5). The structures of these six compounds were characterised using low and high-resolution mass spectrometry (L/HRMS) and 1D and 2D Nuclear Magnetic Resonance (NMR) spectroscopy. These compounds were not toxic to human peripheral blood mononuclear cells (PBMCs) at 10 μg/mL over 24 h, yet showed significant in vitro suppression of proinflammatory cytokines involved in the pathogenesis of inflammatory bowel disease (IBD).

Newly Discovered Peptides from the Coral Show Structural and Functional Diversity.

Scleractinian corals are crucially important to the health of some of the world's most biodiverse, productive, and economically important marine habitats. Despite this importance, analysis of coral peptidomes is still in its infancy. Here we show that the tentacle extract from the stony coral is rich in peptides with diverse and novel structures.

Voltage-Gated Sodium Channel Modulation by a New Spider Toxin Ssp1a Isolated From an Australian Theraphosid.

Given the important role of voltage-gated sodium (Na) channel-modulating spider toxins in elucidating the function, pharmacology, and mechanism of action of therapeutically relevant Na channels, we screened the venom from Australian theraphosid species against the human pain target hNa1.7. Using assay-guided fractionation, we isolated a 33-residue inhibitor cystine knot (ICK) peptide (Ssp1a) belonging to the NaSpTx1 family.

Plant derived cyclic peptides.

Cyclic peptides are widespread throughout the plant kingdom, and display diverse sequences, structures and bioactivities. The potential applications attributed to these peptides and their unusual biosynthesis has captivated the attention of researchers for many years. Several gene sequences for plant cyclic peptides have been discovered over the last two decades but it is only recently that we are beginning to understand the intricacies associated with their biosynthesis.

Synthesis, Structural and Pharmacological Characterizations of CIC, a Novel α-Conotoxin with an Extended N-Terminal Tail.

Cone snails are venomous marine predators that rely on fast-acting venom to subdue their prey and defend against aggressors. The conotoxins produced in the venom gland are small disulfide-rich peptides with high affinity and selectivity for their pharmacological targets. A dominant group comprises α-conotoxins, targeting nicotinic acetylcholine receptors.

A netrin domain-containing protein secreted by the human hookworm Necator americanus protects against CD4 T cell transfer colitis.

The symbiotic relationships shared between humans and their gastrointestinal parasites present opportunities to discover novel therapies for inflammatory diseases. A prime example of this phenomenon is the interaction of humans and roundworms such as the hookworm, Necator americanus. Epidemiological observations, animal studies and clinical trials using experimental human hookworm infection show that hookworms can suppress inflammation in a safe and well-tolerated way, and that the key to their immunomodulatory properties lies within their secreted proteome.

Gastrointestinal Helminth Infection Improves Insulin Sensitivity, Decreases Systemic Inflammation, and Alters the Composition of Gut Microbiota in Distinct Mouse Models of Type 2 Diabetes.

Type 2 diabetes (T2D) is a major health problem and is considered one of the top 10 diseases leading to death globally. T2D has been widely associated with systemic and local inflammatory responses and with alterations in the gut microbiota. Microorganisms, including parasitic worms and gut microbes have exquisitely co-evolved with their hosts to establish an immunological interaction that is essential for the formation and maintenance of a balanced immune system, including suppression of excessive inflammation.

IgE and IgG epitopes revealed on the major fish allergen Lat c 1.

Background: The IgE- and IgG-binding patterns of the major fish allergen parvalbumins are not clearly understood. IgE antibody-binding to parvalbumin from Asian seabass, Lat c 1.01, is implicated in up to 90 % of allergic reactions, although the region of IgE or IgG4 epitopes are unknown.

Backbone Cyclization Turns a Venom Peptide into a Stable and Equipotent Ligand at Both Muscle and Neuronal Nicotinic Receptors.

Venom peptides are promising drug leads, but their therapeutic use is often limited by stability and bioavailability issues. In this study, we designed cyclic analogues of α-conotoxin CIA, a potent muscle nicotinic acetylcholine receptor (nAChR) blocker with a significantly lower affinity at the neuronal α3β2 subtype. Remarkably, all analogues retained the low nanomolar activity of native CIA toward muscle-type nAChRs but showed greatly improved resistance to degradation in human serum and, surprisingly, displayed up to 52-fold higher potency for the α3β2 neuronal nAChR subtype (IC 1.

The NK cell granule protein NKG7 regulates cytotoxic granule exocytosis and inflammation.

Immune-modulating therapies have revolutionized the treatment of chronic diseases, particularly cancer. However, their success is restricted and there is a need to identify new therapeutic targets. Here, we show that natural killer cell granule protein 7 (NKG7) is a regulator of lymphocyte granule exocytosis and downstream inflammation in a broad range of diseases.

Folding of Truncated Granulin Peptides.

Granulins are a family of unique protein growth factors which are found in a range of species and have several bioactivities that include cell proliferation and wound healing. They typically contain six disulfide bonds, but the sequences, structures and bioactivities vary significantly. We have previously shown that an N-terminally truncated version of a granulin from the human liver fluke, , can fold independently into a "mini-granulin" structure and has potent wound healing properties in vivo.

Small Molecules in the Venom of the Scorpion .

Despite scorpion stings posing a significant public health issue in particular regions of the world, certain aspects of scorpion venom chemistry remain poorly described. Although there has been extensive research into the identity and activity of scorpion venom peptides, non-peptide small molecules present in the venom have received comparatively little attention. Small molecules can have important functions within venoms; for example, in some spider species the main toxic components of the venom are acylpolyamines.