Do Cockatiels Choose Their Favourite Tunes? Use of Touchscreen for Animal Welfare Enhancement and Insights into Musical Preferences.

Music may be one of the oldest forms of art, and its appreciation is thought to be universal among humans. Music could also represent a useful tool to improve captive animals' welfare, especially if individuals can choose the music they prefer. The ability to discriminate between different kinds of music or composers has been demonstrated in numerous non-human species.

AXL receptor as an emerging molecular target in colorectal cancer.

AXL receptor tyrosine kinase (AXL) is a receptor tyrosine kinase whose aberrant expression has recently been associated with colorectal cancer (CRC), contributing to tumor growth, epithelial-mesenchymal transition (EMT), increased invasiveness, metastatic spreading, and the development of drug resistance. In this review we summarize preclinical data, the majority of which are limited to recent years, convincingly linking the AXL receptor to CRC. These findings support the value of targeting AXL with molecules in drug discovery, offering novel and advanced therapeutic or diagnostic tools for CRC management.

Molecular Characterization of the Recombinant Ig1 Axl Receptor Domain: An Intriguing Bait for Screening in Drug Discovery.

Axl receptor tyrosine kinase and its ligand Gas6 regulate several biological processes and are involved in both the onset and progression of tumor malignancies and autoimmune diseases. Based on its key role in these settings, Axl is considered a promising target for the development of molecules with therapeutic and diagnostic purposes. In this paper, we describe the molecular characterization of the recombinant Ig1 domain of Axl (Ig1 Axl) and its biochemical properties.

Structure-Based Design of Peptides Targeting VEGF/VEGFRs.

Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) play a main role in the regulation of angiogenesis and lymphangiogenesis. Furthermore, they are implicated in the onset of several diseases such as rheumatoid arthritis, degenerative eye conditions, tumor growth, ulcers and ischemia. Therefore, molecules able to target the VEGF and its receptors are of great pharmaceutical interest.

Switching the N-Capping Region from all-L to all-D Amino Acids in a VEGF Mimetic Helical Peptide.

The N-capping region of an α-helix is a short N-terminal amino acid stretch that contributes to nucleate and stabilize the helical structure. In the VEGF mimetic helical peptide QK, the N-capping region was previously demonstrated to be a key factor of QK helical folding. In this paper, we explored the effect of the chiral inversion of the N-capping sequence on QK folding, performing conformational analysis in solution by circular dichroism and NMR spectroscopy.

How's my kitty? Acoustic parameters of cat-directed speech in human-cat interactions.

In Western cultures, humans tend to use a specific kind of speech when talking to their pets, characterised, from an acoustical point of view, by elevated pitch and greater pitch modulation. Pet-directed speech (PDS), which has been mainly studied in dogs, shares some acoustic features with infant-directed speech (IDS), used when talking to young children. The purpose of this study was to test the hypothesis that adult humans also modify characteristics of their voice when talking to a cat.

Structural characterization of the thermal unfolding pathway of human VEGFR1 D2 domain.

Folding stability is a crucial feature of protein evolution and is essential for protein functions. Thus, the comprehension of protein folding mechanisms represents an important complement to protein structure and function, crucial to determine the structural basis of protein misfolding. In this context, thermal unfolding studies represent a useful tool to get a molecular description of the conformational transitions governing the folding/unfolding equilibrium of a given protein.

Probing the helical stability in a VEGF-mimetic peptide.

The analysis of the forces governing helix formation and stability in peptides and proteins has attracted considerable interest in order to shed light on folding mechanism. We analyzed the role of hydrophobic interaction, steric hindrance and chain length on i, i + 3 position in QK peptide, a VEGF mimetic helical peptide. We focused on position 10 of QK, occupied by a leucine, as previous studies highlighted the key role of the Leu7-Leu10 interaction in modulating the helix formation and inducing an unusual thermodynamic stability.

Exploiting Protein N-Terminus for Site-Specific Bioconjugation.

Although a plethora of chemistries have been developed to selectively decorate protein molecules, novel strategies continue to be reported with the final aim of improving selectivity and mildness of the reaction conditions, preserve protein integrity, and fulfill all the increasing requirements of the modern applications of protein conjugates. The targeting of the protein N-terminal alpha-amine group appears a convenient solution to the issue, emerging as a useful and unique reactive site universally present in each protein molecule. Herein, we provide an updated overview of the methodologies developed until today to afford the selective modification of proteins through the targeting of the N-terminal alpha-amine.

Metabolic and conformational stabilization of a VEGF-mimetic beta-hairpin peptide by click-chemistry.

HPLW is a Vascular Endothelial Growth Factor (VEGF)-mimicking beta-hairpin peptide endowed of proangiogenic effect and showing valuable biomedical application in the proangiogenic therapy. However, the translational potential of HPLW is limited by its low metabolic stability, which would shorten the in vivo efficacy of the molecule. Here, we developed a peptide analog of HPLW, named HPLW2, that retains the structural and biological properties of the original peptide but features an impressive resistance to degradation by human serum proteases.

Therapeutic aspects of the Axl/Gas6 molecular system.

Axl receptor tyrosine kinase (RTK) and its ligand, growth arrest-specific protein 6 (Gas6), are involved in several biological functions and participate in the development and progression of a range of malignancies and autoimmune disorders. In this review, we present this molecular system from a drug discovery perspective, highlighting its therapeutic implications and challenges that need to be addressed. We provide an update on Axl/Gas6 axis biology, exploring its role in fields ranging from angiogenesis, cancer development and metastasis, immune response and inflammation to viral infection.

Water Quality Assessment: A Quali-Quantitative Method for Evaluation of Environmental Pressures Potentially Impacting on Groundwater, Developed under the M.I.N.O.Re. Project.

At global level, the vulnerability of aquifers is deteriorating at an alarming rate due to environmental pollution and intensive human activities. In this context, Local Health Authority ASL Lecce has launched the M.I.

Biochemical and Conformational Characterization of Recombinant VEGFR2 Domain 7.

Angiogenesis is a biological process finely tuned by a plethora of pro- and anti-angiogenic molecules, among which vascular endothelial growth factors (VEGFs). Their biological activity is expressed through the interaction with three cognate receptor tyrosine kinases, VEGFR1, 2, and 3. VEGFR2 is the primary regulator of angiogenesis.

Labeling of VEGFR1D2 through oxime ligation.

We reported an useful protocol for the labeling of the second domain of the Vascular Endothelial Growth Factor Receptor 1 (VEGFR1D2), a small protein ligand able to bind VEGF, the main regulator of angiogenesis. We developed a bioconjugation strategy based on the use of oxime-ligation reaction conjugating an aldehyde derivative of the VEGFR1D2 to a molecular probe harboring an alkoxyamine functional group. We applied the synthetic protocol to prepare a biotinylated conjugate of VEGFR1D2 and we demonstrate that the bioconjugate retains its ability to specifically bind its natural ligand, VEGF, with high affinity.

Human Recombinant VEGFR2D4 Biochemical Characterization to Investigate Novel Anti-VEGFR2D4 Antibodies for Allosteric Targeting of VEGFR2.

VEGF-A/VEGFR2 complex is the major signaling pathway involved in angiogenesis and the inhibition of this axis retards tumor growth and inflammatory disorders progression, reducing vessel sprouting. Signaling by VEGFR2 requires receptor dimerization and a well-defined orientation of monomers in the active dimer. The extracellular portion of receptor is composed of seven Ig-like domains, of which D2-3 are the ligand binding domains, while D4 and D7, establishing homotypic contacts, allosterically regulate receptor activity.

Phosphate uptake by the phosphonate transport system PhnCDE.

Background: Phosphate is a fundamental nutrient for all creatures. It is thus not surprising that a single bacterium carries different transport systems for this molecule, each usually operating under different environmental conditions. The phosphonate transport system of E.

Structural studies of the binding of an antagonistic cyclic peptide to the VEGFR1 domain 2.

Physiological and pathological angiogenesis is mainly regulated by the binding of the vascular endothelial growth factor (VEGF) to its receptors (VEGFRs). Antagonists of VEGFR are very attractive for the treatment of diseases related to excessive angiogenesis. Our previously designed C-terminal alkylated cyclic peptides [YKDEGLEE]-NHR (R = alkyl, arylalkyl) disrupt the interaction between VEGF and VEGFRs in biological assays.

VEGFR Recognition Interface of a Proangiogenic VEGF-Mimetic Peptide Determined In Vitro and in the Presence of Endothelial Cells by NMR Spectroscopy.

QK peptide is a vascular endothelial growth factor (VEGF)-mimetic molecule with significant proangiogenic activity. In particular, QK is able to bind and activate VEGF receptors (VEGFRs) to stimulate a functional response in endothelial cells. To characterize the peptide bioactivity and its molecular recognition properties, a detailed picture of the interaction between peptide QK and VEGF receptors is reported.

Unveiling a VEGF-mimetic peptide sequence in the IQGAP1 protein.

The ability to modulate angiogenesis by chemical tools has several important applications in different scientific fields. With the perspective of finding novel proangiogenic molecules, we searched peptide sequences with a chemical profile similar to that of the QK peptide, a well described VEGF mimetic peptide. We found that residues 1617-1627 of the IQGAP1 protein show molecular features similar to those of the QK peptide sequence.

Miniaturizing VEGF: Peptides mimicking the discontinuous VEGF receptor-binding site modulate the angiogenic response.

The angiogenic properties of VEGF are mediated through the binding of VEGF to its receptor VEGFR2. The VEGF/VEGFR interface is constituted by a discontinuous binding region distributed on both VEGF monomers. We attempted to reproduce this discontinuous binding site by covalently linking into a single molecular entity two VEGF segments involved in receptor recognition.

Mycophenolate mofetil therapy for severe immune thrombocytopenia.

Severe immune thrombocytopenia purpura (ITP) presents a clinical challenge. Second-line treatment options are variable without a precise protocol. We present 46 severe ITP patients treated with mycophenolate mofetil (MMF), retrospectively identified from three London teaching hospitals.

Functional binding surface of a β-hairpin VEGF receptor targeting peptide determined by NMR spectroscopy in living cells.

In this study, the functional interaction of HPLW peptide with VEGFR2 (Vascular Endothelial Growth Factor Receptor 2) was determined by using fast (15)N-edited NMR spectroscopic experiments. To this aim, (15)N uniformly labelled HPLW has been added to Porcine Aortic Endothelial Cells. The acquisition of isotope-edited NMR spectroscopic experiments, including (15)N relaxation measurements, allowed a precise characterization of the in-cell HPLW epitope recognized by VEGFR2.