Membrane Disruptive Action of Cationic Antibacterial Peptide B1CTcu3.

A twenty-two-residue peptide Brevinin1 Clinotarsus curtipus-3 (B1CTcu3), identified from the skin secretion of frog Clinotarsus curtipes of the Western Ghats, exhibited a broad range of antibacterial activity against Gram-negative and Gram-positive bacteria, including the methicillin-resistant Staphylococcus aureus (MRSA). It showed anti-biofilm activity even at sub-minimum inhibitory concentration (sub-MIC) against Pseudomonas aeruginosa and Staphylococcus aureus. Analysis of the scanning electron microscopic (SEM) images, confocal images, flow cytometric data and the effect of salt concentration on antibacterial potency suggests that the killing action of the peptide is through the membranolytic process.

Novel small synthetic HIV-1 V3 crown variants: CCR5 targeting ligands.

The CC chemokine receptor 5 (CCR5) antagonism represents a promising pharmacological strategy for therapeutic intervention as it plays a significant role in reducing the severity and progression of a wide range of pathological conditions. Here we designed and generated peptide ligands targeting the chemokine receptor, CCR5, that were derived from the critical interaction sites of the V3 crown domain of envelope protein glycoprotein gp120 (TRKSIHIGPGRAFYTTGEI) of HIV-1 using computational biology approach and the peptide sequence corresponding to this region was taken as the template peptide, designated as TMP-1. The peptide variants were synthesized by employing Fmoc chemistry using polymer support and were labelled with rhodamine B to study their interaction with the CCR5 receptor expressed on various cells.

Poly-Lysine Dendritic Nanocarrier to Target Epidermal Growth Factor Receptor Overexpressed Breast Cancer for Methotrexate Delivery.

A fourth generation poly-lysine dendritic nanocarrier (PLDN)-based targeted chemotherapy for breast cancer is attempted by incorporating an epidermal growth factor receptor (EGFR)-specific short peptide E2 (ARSHVGYTGAR) and the drug methotrexate (MTX) into a nanocarrier system. The drug is incorporated into the nanocarrier using a cathepsin B cleavable spacer: glycine-phenylalanine-leucine-glycine (GFLG). The in vitro analysis of the time-dependent drug release, binding and internalization ability, and the cytotoxic nature showed that this drug delivery system (DDS) is highly effective.

Generation of hiPSC-derived low threshold mechanoreceptors containing axonal termini resembling bulbous sensory nerve endings and expressing Piezo1 and Piezo2.

Somatosensory low threshold mechanoreceptors (LTMRs) sense innocuous mechanical forces, largely through specialized axon termini termed sensory nerve endings, where the mechanotransduction process initiates upon activation of mechanotransducers. In humans, a subset of sensory nerve endings is enlarged, forming bulb-like expansions, termed bulbous nerve endings. There is no in vitro human model to study these neuronal endings.

Maturational Changes in Mouse Cutaneous Touch and Piezo2-Mediated Mechanotransduction.

The age of studied animals has a profound impact on experimental outcomes in animal-based research. In mice, age influences molecular, morphological, physiological, and behavioral parameters, particularly during rapid postnatal growth and maturation until adulthood (at 12 weeks of age). Despite this knowledge, most biomedical studies use a wide-spanning age range from 4 to 12 weeks, raising concerns about reproducibility and potential masking of relevant age differences.

Myotubularin related protein-2 and its phospholipid substrate PIP control Piezo2-mediated mechanotransduction in peripheral sensory neurons.

Piezo2 ion channels are critical determinants of the sense of light touch in vertebrates. Yet, their regulation is only incompletely understood. We recently identified myotubularin related protein-2 (Mtmr2), a phosphoinositide (PI) phosphatase, in the native Piezo2 interactome of murine dorsal root ganglia (DRG).

Nocistatin sensitizes TRPA1 channels in peripheral sensory neurons.

The ability of sensory neurons to detect potentially harmful stimuli relies on specialized molecular signal detectors such as transient receptor potential (TRP) A1 ion channels. TRPA1 is critically implicated in vertebrate nociception and different pain states. Furthermore, TRPA1 channels are subject to extensive modulation and regulation - processes which consequently affect nociceptive signaling.

Native Piezo2 Interactomics Identifies Pericentrin as a Novel Regulator of Piezo2 in Somatosensory Neurons.

The ability of somatosensory neurons to perceive mechanical stimuli relies on specialized mechanotransducing proteins and their molecular environment. Only recently has the identity of a major transducer of mechanical forces in vertebrates been revealed by the discovery of Piezo2. Further work has established its pivotal role for innocuous touch in mice.

Alternatively Spliced Isoforms of KV10.1 Potassium Channels Modulate Channel Properties and Can Activate Cyclin-dependent Kinase in Xenopus Oocytes.

KV10.1 is a voltage-gated potassium channel expressed selectively in the mammalian brain but also aberrantly in cancer cells. In this study we identified short splice variants of KV10.

Modulation of nociceptive ion channels and receptors via protein-protein interactions: implications for pain relief.

In the last 2 decades biomedical research has provided great insights into the molecular signatures underlying painful conditions. However, chronic pain still imposes substantial challenges to researchers, clinicians and patients alike. Under pathological conditions, pain therapeutics often lack efficacy and exhibit only minimal safety profiles, which can be largely attributed to the targeting of molecules with key physiological functions throughout the body.

Annexin A2 regulates TRPA1-dependent nociception.

The transient receptor potential A1 (TRPA1) channel is essential for vertebrate pain. Even though TRPA1 activation by ligands has been studied extensively, the molecular machinery regulating TRPA1 is only poorly understood. Using an unbiased proteomics-based approach we uncovered the physical association of Annexin A2 (AnxA2) with native TRPA1 in mouse sensory neurons.