Targeting Aquaporin Function:Potent Inhibition of Aquaglyceroporin-3 by a Gold-Based Compound

Aquaporins (AQPs) are membrane channels that conduct water and small solutes such as glycerol and are involved in many physiological functions. Aquaporin-based modulator drugs are predicted to be of broad potential utility in the treatment of several diseases. Until today few AQP inhibitors have been described as suitable candidates for clinical development. Here we report on the potent inhibition of AQP3 channels by gold(III) complexes screened on human red blood cells (hRBC) and AQP3-transfected PC12 cells by a stopped-flow method. Among the various metal compounds tested, Auphen is the most active on AQP3 (IC(50) = 0.8±0.08 µM in hRBC). Interestingly, the compound poorly affects the water permeability of AQP1. The mechanism of gold inhibition is related to the ability of Au(III) to interact with sulphydryls groups of proteins such as the thiolates of cysteine residues. Additional DFT and modeling studies on possible gold compound/AQP adducts provide a tentative description of the system at a molecular level. The mapping of the periplasmic surface of an homology model of human AQP3 evidenced the thiol group of Cys40 as a likely candidate for binding to gold(III) complexes. Moreover, the investigation of non-covalent binding of Au complexes by docking approaches revealed their preferential binding to AQP3 with respect to AQP1. The high selectivity and low concentration dependent inhibitory effect of Auphen (in the nanomolar range) together with its high water solubility makes the compound a suitable drug lead for future in vivo studies. These results may present novel metal-based scaffolds for AQP drug development

Gauge invariant definition of the jet quenching parameter

In the framework of Soft-Collinear Effective Theory, the jet quenching parameter, $\hat{q}$, has been evaluated by adding the effect of Glauber gluon interactions to the propagation of a highly-energetic collinear parton in a medium. The result, which holds in covariant gauges, has been expressed in terms of the expectation value of two Wilson lines stretching along the direction of the four-momentum of the parton. In this paper, we show how that expression can be generalized to an arbitrary gauge by the addition of transverse Wilson lines. The transverse Wilson lines are explicitly computed by resumming interactions of the parton with Glauber gluons that appear only in non-covariant gauges. As an application of our result, we discuss the contribution to $\hat{q}$ coming from transverse momenta of order $g^2T$ in a medium that is a weakly-coupled quark-gluon plasma.Comment: 31 pages, 7 figures; journal versio

Factorizing the hard and soft spectator scattering contributions for the nucleon form factor F_1 at large Q^2

We investigate the soft spectator scattering contribution for the FF $F_{1}$. We focus our attention on factorization of the hard-collinear scale $\sim Q\Lambda$ corresponding to transition from SCET-I to SCET-II. We compute the leading order jet functions and find that the convolution integrals over the soft fractions are logarithmically divergent. This divergency is the consequence of the boost invariance and does not depend on the model of the soft correlation function describing the soft spectator quarks. Using as example a two-loop diagram we demonstrated that such a divergency corresponds to the overlap of the soft and collinear regions. As a result one obtains large rapidity logarithm which must be included in the correct factorization formalism. We conclude that a consistent description of the factorization for $F_{1}$ implies the end-point collinear divergencies in the hard and soft spectator contributions, i.e. convolution integrals with respect to collinear fractions are not well-defined. Such scenario can only be realized when the twist-3 nucleon distribution amplitude has specific end-point behavior which differs from one expected from the evolution of the nucleon distribution amplitude. Such behavior leads to the violation of the collinear factorization for the hard spectator scattering contribution. We suggest that the soft spectator scattering and chiral symmetry breaking provide the mechanism responsible for the violation of collinear factorization in case of form factor $F_{1}$.Comment: 25 pages, 6 figures, text is improved, few typos corrected, one figure added, statement about end-point behavior of the nucleon DA is formulated more accuratel

Spectroscopic Discovery of the Supernova 2003dh Associated with GRB 030329

We present early observations of the afterglow of the Gamma-Ray Burst (GRB) 030329 and the spectroscopic discovery of its associated supernova SN 2003dh. We obtained spectra of the afterglow of GRB 030329 each night from March 30.12 (0.6 days after the burst) to April 8.13 (UT) (9.6 days after the burst). The spectra cover a wavelength range of 350 nm to 850 nm. The early spectra consist of a power-law continuum (F_nu ~ nu^{-0.9}) with narrow emission lines originating from HII regions in the host galaxy, indicating a low redshift of z=0.1687. However, our spectra taken after 2003 Apr. 5 show broad peaks in flux characteristic of a supernova. Correcting for the afterglow emission, we find the spectrum of the supernova is remarkably similar to the type Ic `hypernova' SN 1998bw. While the presence of supernovae have been inferred from the light curves and colors of GRB afterglows in the past, this is the first direct, spectroscopic confirmation that a subset of classical gamma-ray bursts originate from supernovae.Comment: published by ApJ Letters; additional material avilable at http://cfa-www.harvard.edu/cfa/oir/Research/GRB

A Policy Maker’s Guide to Designing Payments for Ecosystem Services

Over the past five years, there has been increasing interest around the globe in payment schemes for the provision of ecosystem services, such as water purification, carbon sequestration, flood control, etc. Written for an Asian Development Bank project in China, this report provides a user-friendly guide to designing payments for the provision of ecosystem services. Part I explains the different types of ecosystem services, different ways of assessing their value, and why they are traditionally under-protected by law and policy. This is followed by an analysis of when payments for services are a preferable approach to other policy instruments. Part II explains the design issues underlying payments for services. These include identification of the service as well as potential buyers and sellers, the level of service needed, payment timing, payment type, and risk allocation. Part II contains a detailed analysis of the different types of payment mechanisms, ranging from general subsidy and certification to mitigation and offset payments. Part III explores the challenges to designing a payment scheme. These include the ability to monitor service provision, secure property rights, perverse incentives, supporting institutions, and poverty alleviation

Characterization of semi-arid Chadian sweet sorghum accessions as potential sources for sugar and ethanol production

Sweet sorghum (Sorghum bicolor (L.) Moench) is an important crop in Chad that plays an economic role in the countryside were stalks are produced mainly for human consumption without any processing. Unfortunately, very little information exists on its genetic diversity and brix content. Studies performed in 2014 and 2015 showed that there were significant variations (p < 0.001) for all assessed quantitative traits. Potential grain yield (0.12–1.67 t ha−1), days to 50% flowering (68.3–126.3 days), and plant height (128.9–298.3 cm) were among traits that exhibited broader variability. Brix content range from 5.5 to 16.7% across accessions, was positively correlated to stalk diameter and plant height, but negatively correlated to moisture content in fresh stalk and potential grain yield. Fresh stalk yield range from 16.8 to 115.7 Mg ha−1, with a mean value of 58.3 Mg ha−1 across accession. Moisture content in fresh stalk range from 33.7 to 74.4% but was negatively correlated to fresh stalk yield. Potential sugar yield range from 0.5 to 5.3 Mg ha−1 across accession with an average of 2.2 Mg ha−1. Theoretical ethanol yield range from 279.5 to 3,101.2 L ha−1 across accession with an average of 1,266.3 L ha−1 which is significantly higher than values reported under similar semiarid conditions. Overall, grain yields were comparatively low. However, two accessions had grain yield of more than 1.5 t ha−1; which is greater than the average 1.0 t ha−1 for local grain sorghum varieties in Chad. These could have multi-purpose uses; grains, sugar and bioenergy production

Photometry and Spectroscopy of GRB 030329 and Its Associated Supernova 2003dh: The First Two Months

We present extensive optical and infrared photometry of the afterglow of gamma-ray burst (GRB) 030329 and its associated supernova (SN) 2003dh over the first two months after detection (2003 March 30-May 29 UT). Optical spectroscopy from a variety of telescopes is shown and, when combined with the photometry, allows an unambiguous separation between the afterglow and supernova contributions. The optical afterglow of the GRB is initially a power-law continuum but shows significant color variations during the first week that are unrelated to the presence of a supernova. The early afterglow light curve also shows deviations from the typical power-law decay. A supernova spectrum is first detectable ~7 days after the burst and dominates the light after ~11 days. The spectral evolution and the light curve are shown to closely resemble those of SN 1998bw, a peculiar Type Ic SN associated with GRB 980425, and the time of the supernova explosion is close to the observed time of the GRB. It is now clear that at least some GRBs arise from core-collapse SNe.Comment: 57 pages, 13 figures, accepted by ApJ, revised per referee's comments, includes full photometry table. Data available at ftp://cfa-ftp.harvard.edu/pub/kstanek/GRB030329 or through WWW at http://cfa-www.harvard.edu/cfa/oir/Research/GRB

A Global Forum on Ultramafic Ecosystems: From Ultramafic Ecology to Rehabilitation of Degraded Environments

The 9th International Conference on Serpentine Ecology (ICSE) was held in Tirana and Pogradec (Albania) from June 5 to 9, 2017. More than 100 delegates from 29 countries around the world gathered to present their research on recent advances in: (i) ultramafic soils, (ii) biogeochemistry, (iii) diversity of ultramafic flora, microflora and fauna, (iv) ecophysiology of ultramafic-adapted organisms, (v) interactions between ultramafic organisms and their ecology, (vi) nature rehabilitation of degraded ultramafic environments (resulting from mining activities), and (vii) the production of bio-based metals through agromining technology. Additionally, the ICSE featured the first symposium on ultramafic aquatic ecology and ecotoxicology. Albania has one of the most diverse ultramafic floras in Europe. During the conference delegates visited some of the most emblematic ultramafic sites in Albania as well as the first agromining field trial in Europe. Here, we present the major topics and provide some highlights of the 25 contributions in this Special Issue (Vol. 33 no.3 and 4)