Indigenous and Community Conserved Areas (ICCA) and the Batak Cultural Minorities of Northern Palawan, Philippines

This nascent study examines the current state of the Batak indigenous people in So. Tinitian, Brgy. Tagnipa, Roxas, Palawan as they engage with external institutions in the process of ICCA declaration of their ancestral domain in the midst that legal land and resources rights recognition had been elusive in the past[1]. The Batak indigenous people are termed a

Lipids modulate the conformational dynamics of a secondary multidrug transporter

Direct interactions with lipids have emerged as key determinants of the folding, structure and function of membrane proteins, but an understanding of how lipids modulate protein dynamics is still lacking. Here, we systematically explored the effects of lipids on the conformational dynamics of the proton-powered multidrug transporter LmrP from Lactococcus lactis, using the pattern of distances between spin-label pairs previously shown to report on alternating access of the protein. We uncovered, at the molecular level, how the lipid headgroups shape the conformational-energy landscape of the transporter. The model emerging from our data suggests a direct interaction between lipid headgroups and a conserved motif of charged residues that control the conformational equilibrium through an interplay of electrostatic interactions within the protein. Together, our data lay the foundation for a comprehensive model of secondary multidrug transport in lipid bilayers

INNODIA Master Protocol for the evaluation of investigational medicinal products in children, adolescents and adults with newly diagnosed type 1 diabetes

Background The INNODIA consortium has established a pan-European infrastructure using validated centres to prospectively evaluate clinical data from individuals with newly diagnosed type 1 diabetes combined with centralised collection of clinical samples to determine rates of decline in beta-cell function and identify novel biomarkers, which could be used for future stratification of phase 2 clinical trials. Methods In this context, we have developed a Master Protocol, based on the “backbone” of the INNODIA natural history study, which we believe could improve the delivery of phase 2 studies exploring the use of single or combinations of Investigational Medicinal Products (IMPs), designed to prevent or reverse declines in beta-cell function in individuals with newly diagnosed type 1 diabetes. Although many IMPs have demonstrated potential efficacy in phase 2 studies, few subsequent phase 3 studies have confirmed these benefits. Currently, phase 2 drug development for this indication is limited by poor evaluation of drug dosage and lack of mechanistic data to understand variable responses to the IMPs. Identification of biomarkers which might permit more robust stratification of participants at baseline has been slow. Discussion The Master Protocol provides (1) standardised assessment of efficacy and safety, (2) comparable collection of mechanistic data, (3) the opportunity to include adaptive designs and the use of shared control groups in the evaluation of combination therapies, and (4) benefits of greater understanding of endpoint variation to ensure more robust sample size calculations and future baseline stratification using existing and novel biomarkers

Preparation and structure of [iiii] tetraphosphonatocavitands bearing long chain functionality at the lower rim: Metal picrates extraction studies

The stereoselective synthesis of the iiii stereoisomer of novel tetraphosphonato-cavitands derived from resorc [4]arene is reported. o-Nitrophenyl-n-octyl ether and n-undecyl-n-decanyl thioether functionalities were introduced in the lower rim of 1 and 2, respectively, to develop new molecular devices. The crystal structure of the solvated cavitand 1.6CH(3)CN was elucidated by X-ray crystallography. C104H104O24N4P4.6CH(3)CN crystallizes in the monoclinic space group P2(1)/c, a = 20.574(4), b = 16.591(4), c = 33.973(7) Angstrom, beta = 92.09(2)degrees, V = 11589(4) Angstrom(3), Z = 4, R = 0.065. The host molecule has the iiii configuration with the four P=O bonds oriented towards the molecular cavity. The affinity of molecules 1 and 2 for metal cations was investigated by the liquid-liquid extraction method: among the investigated metal picrates, Ag+, Ba2+ and Eu3+ were the best-extracted cations

A new supramolecular assembly obtained from the combination of silver(I) cations with a thiophosphorylated cavitand

The new tetra-thiophosphonatocavitand 1 in its iiii configuration extracts quantitatively Ag+ ions from aqueous solutions; the tetranuclear complex [1(2).Ag(4)Pic(4)] was selectively formed and characterized in the solid state by X-ray diffraction which revealed the formation of a new dimeric assembly through Ag+ coordination

Thiophosphorylated cavitand: structure and affinity towards soft metal ions

The iiii stereoisomer of the tetrathiophosphonate-calix[4]resorcinarene host 1 exhibited excellent extraction properties towards soft metal ions, with a better affinity for Ag+ (91%), than for Tl+ (38%) and Hg2+ (16%). The extraction of other picrate salts (Cu2+, Ni2+, Co2+, Zn2+, Cd2+, Pb2+) was not detected. The stoichiometry and the structure of the Hg2+, Tl+ and Ag+ complexes were studied by NMR in solution and gave respectively 1:1, 1:1 and 1:2 host-guest complexes. The formation of the self-assembled 1(2).(AgPic)(4) complex was independent on the anion and only observed with silver(l) ion. (C) 2003 Elsevier Ltd. All rights reserved

Design of differently P-substituted 4iPO fluorescent tetraphosphonate cavitands

Experimental approaches to tetraphosphonate cavitands bearing fluorenyl-phosphonate bridges are reported. Different routes are described depending on the substitution on the cavitand structure. Tetra-, tri- and di-bridged phosphonate cavitands have been prepared as precursors of fluorescent hosts, for which the stereochemistry is highly dependent on the substitution at the wide rim of the resorcin[4]arene scaffold. The conformational change in 3io tetraphosphonate cavitands has been characterised by X-ray diffraction. These new molecular receptors have been used for the recognition of acetylcholine. © 2013 Copyright Taylor and Francis Group, LLC