Conformationally constrained CCK8 analogues obtained from a rationally designed peptide library as ligands for cholecystokinin type B receptor

A library of 14 cyclic peptide analogues derived from the octapeptide C-terminal sequence of the human cholecystokinin hormone (CCK(26-33), or CCK8) was designed, synthesized, and characterized. The 14 peptide analogues were rationally designed to specifically interact with the CCK type B receptor (CCK(B)-R) on the basis of the structure of the bimolecular complex between CCK8 and the third extracellular loop of CCK(B)-R, namely CCK(B)-R(352-379). The rational design of new ligands for CCK(B)-R has relied on stabilization by cyclic constraints of the structural motifs that bring the key residues of the ligand (especially Trp 30, Met 31, and Phe 33) in the proper spatial orientation for optimal interaction with the receptor. The binding affinity of the new ligands for CCK(B)-R was assessed by displacement experiments of (111)In-radiolabeled CCK8 in cells that overexpress the CCK(B) receptor. The new ligands generally showed binding affinities lower than that of parent CCK8, with the best compounds having IC50 values around 10 microM. Structure-activity relationship data show that preservation of the Trp 30-Met 31 motif is essential and that the Phe 33 side chain must be present. NMR conformational studies of the compound with maximal binding affinity (cyclo-B11, IC50=11 microM) in DPC micelles shows that this compound presents a turn-like conformation centered at the Trp 30-Met 31 segment, as planned by rational design. Such a conformation is stabilized by its interaction with the micelle rather than by the cyclic constraint.     

Effect of atmosphere composition on the quality of ready‐to‐use broccoli raab (Brassica rapa L.)

BACKGROUND: Many leafy brassicas are widely used for ready‐to‐use salads. Broccoli raab (Brassica rapa L.), also called turnip top, or rapini, is extensively cultivated in southern Italy. The edible portion is made up of the green, immature inflorescences and the stem with its most tender leaves. Recently, interest in this crop has increased among European consumers; moreover, a substantial increase in consumption could come from the ready‐to‐use product. RESULTS: The effects of four different atmosphere compositions (air, 3% O₂ in nitrogen, 3% O₂ + 10% CO₂ in air, and 10% CO₂ in air) on quality attributes of ready‐to‐use broccoli raab were studied. Controlled atmosphere affected appearance, composition, respiration rate, weight loss, and presence of off‐odours. Storage of broccoli raab florets under low oxygen conditions delayed post‐cutting deterioration during storage at 5 °C and preserved appearance and typical odour, up to 17 days. Moreover, respiration rate as well as loss of green colour, chlorophyll and vitamin C were also slowed down in this condition. Finally, in this study no effect of controlled atmosphere storage was found on total phenols content and antioxidant activity. CONCLUSION: Results showed that cold storage in 3% O₂ can be beneficial in order to maintain quality of ready‐to‐use, broccoli raab for up to 17 days. Copyright © 2010 Society of Chemical Industry     

Effects of free fatty acids on the oxidative processes in purified olive oil

Several studies have investigated the interaction of free fatty acids with the oxidative phenomena involving oils during processing and storage. Nevertheless, the available information is insufficient and, in some cases, contradictory.The aim of this work was to throw light upon this matter, by evaluating – by means of different analytical approaches – the effect of adding increasing amounts of free fatty acids (0.25%, 0.5%, 1%, 3%) on the oxidative processes occurring in purified olive oil during oxidation at 60 °C.The results obtained showed that oxidized forms of triglycerides and polar oligopolymers of triglycerides increased during oxidation. Low amounts of added FFA caused a further increase of the levels of oxidized triglycerides and triglyceride oligopolymers – pointing out a pro-oxidant activity – while higher doses of added free fatty acids lead to lower amounts of oxidized forms of triglycerides respect to the purified oil. This could be due to an increase in peroxide decomposition exerted by free fatty acids when present in higher amounts.     

Shear and longitudinal ultrasonic measurements of solid fat dispersions

Dispersions of coating fat in corn oil (2.5–12.5 wt%) were prepared following two different protocols: Type A dispersions had an average crystal size of 30–36 μm, whereas type B dispersions were less than 1 μm. In both dispersions the fat crystals were aggregated into larger structures (up to 80 μm). The longitudinal ultrasonic properties (i.e., velocity, attenuation, and reflectance) were linearly related to the solid fat content, but only attenuation was sensitive to the different microstructures. The velocity and reflectance measurements were modeled using the Urick equation. Shear ultrasonic reflectance and oscillatory viscometry were used to measure the dynamic viscosity of all dispersions. According to both methods, type B samples were always more viscous than type A at a similar solids content. The correlation between the two techniques was good (r ²>0.99), but the numeric agreement was different for both systems.     

Structure-based drug design to the discovery of new 2-aminothiazole CDK2 inhibitors

N-(5-Bromo-1,3-thiazol-2-yl)butanamide (compound 1) was found active (IC50=808 nM) in a high throughput screening (HTS) for CDK2 inhibitors. By exploiting crystal structures of several complexes between CDK2 and inhibitors and applying structure-based drug design (SBDD), we rapidly discovered a very potent and selective CDK2 inhibitor 4-[(5-isopropyl-1,3-thiazol-2-yl)amino] benzenesulfonamide (compound 4, IC50=20 nM). The syntheses, structure-based analog design, kinases inhibition data and X-ray crystallographic structures of CDK2/inhibitor complexes are reported.     

Virtual reality as a communication process

In this work, we consider immersive Virtual Reality (VR) as a communication process between humans, mediated by computer systems, which uses interaction, visualization, and other sensory stimuli to convey information. From this viewpoint, it is relevant to understand how VR can solve a given communication problem, what is therefore the expressive power of VR system, i.e., its ability in establishing the communication, what are the guidelines to design an effective system, and what are the more relevant models of VR applications. Firstly, we try to clarify the notion of reality in Virtual Reality systems and conclude that reality is not an intrinsic characteristic of VR, rather the result of a conventional way of coding information. The purpose of coding is to lead the observer to the conclusion that the VR set is what is called in italian as verisimile (from Latin veri similis), i.e., ??similar-to-the-real-thing??. So the creation of an effective VR application is an artifice or an illusion. But in order to avoid an over-reliance on the creativity of the VR designer, we intend to identify a solid ground on which different kinds of VR solutions can be considered in terms of their ability to solve the desired communication objective. To this aim, we will rely on methods derived from rhetoric to semiotics.     

Switched nonlinear systems with state-dependent dwell-time

The asymptotic convergence of a switched nonlinear system in the presence of disturbances is studied. The system switches among a family of integral input-to-state stable systems. The time between two consecutive switchings is not less than a value τ_D. This dwell-time τ_D is allowed to take different values according to a function whose argument is the state of the system at the switching times. We propose a dwell-time function which depends on the comparison functions which characterize the integral input-to-state stability property and guarantees the state of the switched system to converge to zero under the action of disturbances with “bounded energy”. The main feature of the analysis is that it does not rely on the property for the switching to stop in finite time. The two important cases of locally exponentially stable and feedforward systems are analyzed in detail.     

Multigram-scale production of aliphatic carboxylic acids by oxidation of alcohols with Acetobacter pasteurianus NCIMB 11664

Acetobacter pasteurianus NCIMB 11664 was selected for multigram-scale production of different aliphatic carboxylic acids through oxidation of the corresponding alcohols after screening different acetic acid bacteria. Continuous production was carried out using an air-lift reactor, with overall yields of 1-propionic, 1-butyric, 2-methyl-1-butyric and 3-methyl-1-butyric acids ranging from 45 to 61 g dm⁻³. ©1997 SCI     

Therapeutic Acellular Scaffolds for Limiting Left Ventricular Remodelling-Current Status and Future Directions

Myocardial infarction (MI) is one of the leading causes of heart-related deaths worldwide. Following MI, the hypoxic microenvironment triggers apoptosis, disrupts the extracellular matrix and forms a non-functional scar that leads towards adverse left ventricular (LV) remodelling. If left untreated this eventually leads to heart failure. Besides extensive advancement in medical therapy, complete functional recovery is never accomplished, as the heart possesses limited regenerative ability. In recent decades, the focus has shifted towards tissue engineering and regenerative strategies that provide an attractive option to improve cardiac regeneration, limit adverse LV remodelling and restore function in an infarcted heart. Acellular scaffolds possess attractive features that have made them a promising therapeutic candidate. Their application in infarcted areas has been shown to improve LV remodelling and enhance functional recovery in post-MI hearts. This review will summarise the updates on acellular scaffolds developed and tested in pre-clinical and clinical scenarios in the past five years with a focus on their ability to overcome damage caused by MI. It will also describe how acellular scaffolds alone or in combination with biomolecules have been employed for MI treatment. A better understanding of acellular scaffolds potentialities may guide the development of customised and optimised therapeutic strategies for MI treatment.