Development of antiviral fusion inhibitors: short modified peptides derived from the transmembrane glycoprotein of feline immunodeficiency virus

Feline immunodeficiency virus (FIV) is a naturally occurring pathogen that causes an AIDS-like syndrome in domestic cats and is a valuable model system by which criteria for antiviral vaccines and drugs development can be tested. The cell-entry step of the lentivirus life cycle is regarded as a promising target for the development of new generation inhibitors. We have previously described potent in vitro anti-FIV activity associated with a synthetic octapeptide, termed C8 (Ac-Trp-Glu-Asp-Trp-Val-Gly-Trp-Ile-NH2), containing the Trp-rich motif of FIV transmembrane glycoprotein, which shares a common structural framework with the corresponding molecule of HIV and appears to play a similar role in cell entry. In this report, in an attempt to develop simpler potential fusion inhibitors to be tested in vivo, we describe further studies focused on synthetic peptide analogues of C8. Since C8 inhibitory activity is dependent upon the Trp motif, we systematically replaced these residues with bulky and/or aromatic natural and unnatural amino acids, in order to develop a rational structure-activity relationship. Furthermore, the amino acids located between the Trp residues, which are not crucial for inhibitory activity, were replaced by simple alkyl spacers of appropriate length. Design, NMR structural analysis, in vitro anti-FIV activity in lymphoid cell cultures, and serum stability of these new analogues are reported. The final results indicate that a simpler hexapeptide (Ac-Nal2-Ape-Nal2-Ape-Nal2-Ile-NH2; Nal2 = 3-naphthalen-2-yl-L-alanine, Ape = 5-aminopentanoic acid), almost entirely made up of unnatural amino acid residues, has markedly increased enzymatic stability, while maintaining strong antiviral potency in vitro.     

Adsorption of carotenes and phosphorus from palm oil onto acid activated bleaching earth: Equilibrium,kinetics and thermodynamics

In this work, the adsorption of carotenes and phosphorus from crude palm oil onto acid activated bleaching earth was investigated under bleaching conditions, i.e. high temperature (90, 105 and 115 °C) and low pressure (less than 50 mbar). Bleaching earth was added to palm oil in a range of 0.5–3.0 wt%. Results presented in this work suggest that adsorption of β-carotene increases with temperature, while phosphorus adsorption was less affected. Both the pseudo-first-order and the pseudo-second-order kinetic model describe efficiently the β-carotene experimental data. Intra-particle diffusion is involved in β-carotene adsorption mechanism, although it is not the sole rate limiting step in the adsorption onto acid activated bleaching earth. Phosphorus adsorption was too fast resulting in a lack of kinetic data. The equilibrium data were described better by Langmuir and Freundlich models, for β-carotene and phosphorus, respectively. A multi-component Freundlich type isotherm was tested. Its competition coefficients were too low, and it assumed the same form as the monocomponent Freundlich. A thermodynamic study demonstrated that β-carotene and phosphorus adsorption is spontaneous, endothermic and an entropy-driven process. Isosteric heat values suggest that the interactions between adsorbate and adsorbent are heterogeneous.     

Application of a Synthetic Ferredoxin-Inspired [4Fe4S]-Peptide Maquette as the Redox Partner for an [FeFe]-Hydrogenase

‘Bacterial-type’ ferredoxins host a cubane [4Fe4S]^2+/+ cluster that enables these proteins to mediate electron transfer and facilitate a broad range of biological processes. Peptide maquettes based on the conserved cluster-forming motif have previously been reported and used to model the ferredoxins. Herein we explore the integration of a [4Fe4S]-peptide maquette into a H₂-powered electron transport chain. While routinely formed under anaerobic conditions, we illustrate by electron paramagnetic resonance (EPR) analysis that these maquettes can be reconstituted under aerobic conditions by using photoactivated NADH to reduce the cluster at 240 K. Attempts to tune the redox properties of the iron-sulfur cluster by introducing an Fe-coordinating selenocysteine residue were also explored. To demonstrate the integration of these artificial metalloproteins into a semi-synthetic electron transport chain, we utilize a ferredoxin-inspired [4Fe4S]-peptide maquette as the redox partner in the hydrogenase-mediated oxidation of H₂.     

The hydromorphology index IHM based on fish requirements

Stream ecosystems are diverse and dynamic habitats that are strongly influenced by the direct and indirect consequences of human interventions. Several initiatives have been started all over Europe to satisfy the European guidelines for the protection of local water bodies, but a standardised procedure across national borders fulfilling all relevant aspects and parameters of the Water Framework Directive (WFD) does not exist. In this context, we propose a new methodical approach based on salmonid fish populations to assess stream quality to increase the comparability of individual assessments due to standardized survey and evaluation methods for hydromorphology. Our approach is based on the Austrian and Italian methods, which account for the European standards, and it has been tested in 81 stream sections representative of different site and anthropogenic use conditions in the European Alps. The assessment procedure is composed of a set of 11 indicators, which were selected to evaluate longitudinal and lateral morphological and temporal dynamics of morphological and hydrological conditions. The indicators were combined into three indices, the morphology (I_M), hydrology (I_H), and hydromorphology indices (I_HM), to obtain a holistic picture with as few parameters as possible. The definition of indicators and indices, their methodical implementation and practical testing in the field, were carried out by an interdisciplinary team of international experts. The resulting and tested field manual is included with this publication as Supplementary material. The applicability, strengths, and weaknesses of the approach are discussed in the present paper.     

3D Generative Model Latent Disentanglement via Local Eigenprojection

Designing realistic digital humans is extremely complex. Most data-driven generative models used to simplify the creation of their underlying geometric shape do not offer control over the generation of local shape attributes. In this paper, we overcome this limitation by introducing a novel loss function grounded in spectral geometry and applicable to different neural-network-based generative models of 3D head and body meshes. Encouraging the latent variables of mesh variational autoencoders (VAEs) or generative adversarial networks (GANs) to follow the local eigenprojections of identity attributes, we improve latent disentanglement and properly decouple the attribute creation. Experimental results show that our local eigenprojection disentangled (LED) models not only offer improved disentanglement with respect to the state-of-the-art, but also maintain good generation capabilities with training times comparable to the vanilla implementations of the models. Our code and pre-trained models are available at github.com/simofoti/LocalEigenprojDisentangled .