Effect Of Zinc Cations On The Kinetics Of Supramolecular Assembly And The Chirality Of Porphyrin J-Aggregates

Dilute aqueous solutions of anionic meso-4-sulfonatophenyl-porphyrin (TPPS) extract zinc(ii) ions from glass or quartz surfaces at room temperature and efficiently form the corresponding metal complex (ZnTPPS). The partial or complete formation of ZnTPPS has been probed by UV/Vis spectroscopy and both static and time-resolved fluorescence. The source of zinc(ii) ions has been clearly identified through inductively coupled plasma optical emission spectrometry. The presence of increasing amounts of ZnTPPS slows down the rate of TPPS J-aggregate formation in acid solution. This influences the nucleation step and has a profound impact on the onset of chirality in these species. This evidence indicates the important role of this adventitious metal ion in the interpretation of various spectroscopic and kinetic data for the self-assembly of the TPPS porphyrin and provides some insights into controversial findings on their chirality. The use of this metal derivative as the starting compound for in situ formation of monomeric TPPS is suggested

Mechanism For Copper(II)-Mediated Disaggregation Of A Porphyrin J-Aggregate

J-aggregates of anionic meso-tetrakis(4-sulfonatophenyl)porphyrin form at intermediate pH (2.3–3.1) in the presence of NiSO₄ or ZnSO₄ (ionic strength, I.S. = 3.2 M). These aggregates convert to monomeric porphyrin units via metallation with copper(II) ions. The kinetics for the disassembly process, as monitored by UV/vis spectroscopy, exhibits zeroth-order behavior. The observed zeroth-order rate constants show a two-term dependence on copper(II) ion concentrations: linear and second order. Also observed is an inverse dependence on hydrogen ion concentration. Activation parameters have been determined for the disassembly process leading to ΔH^≠ = (+163 ± 15) kJ·mol⁻¹ and ΔS^≠ = (+136 ± 11) J·K⁻¹. A mechanism is proposed in which copper(II) cation is in pre-equilibrium with a reactive site at the rim of the J-aggregate. An intermediate copper species is thus formed that eventually leads to the final metallated porphyrin either through an assisted attack of a second metal ion or through a direct insertion of the metal cation into the macrocycle core

Posttranscriptional regulation of PARG mRNA by HuR facilitates DNA repair and resistance to PARP inhibitors

The majority of pancreatic ductal adenocarcinomas (PDAC) rely on the mRNA stability factor HuR (ELAV-L1) to drive cancer growth and progression. Here, we show that CRISPR-Cas9–mediated silencing of the HuR locus increases the relative sensitivity of PDAC cells to PARP inhibitors (PARPi). PDAC cells treated with PARPi stimulated translocation of HuR from the nucleus to the cytoplasm, specifically promoting stabilization of a new target, poly (ADP-ribose) glycohydrolase (PARG) mRNA, by binding a unique sequence embedded in its 30 untranslated region. HuR-dependent upregulation of PARG expression facilitated DNA repair via hydrolysis of polyADP-ribose on related repair proteins. Accordingly, strategies to inhibit HuR directly promoted DNA damage accumulation, inefficient PAR removal, and persistent PARP-1 residency on chromatin (PARP-1 trapping). Immunoprecipitation assays demonstrated that the PARP-1 protein binds and posttranslationally modifies HuR in PARPi-treated PDAC cells. In a mouse xenograft model of human PDAC, PARPi monotherapy combined with targeted silencing of HuR significantly reduced tumor growth compared with PARPi therapy alone. Our results highlight the HuR–PARG axis as an opportunity to enhance PARPi-based therapies. ©2017 AACR

Characterization of DNA Sequences that Confer Complement Resistance in \u3ci\u3eLeishmania chagasi\u3c/i\u3e

Serial passage of axenically cultured Leishmania chagasi promastigotes results in a progressive diminution in resistance to complement-mediated lysis (CML), whereas high CML resistance is seen in infectious metacyclic promastigotes from the sandfly vector as well as metacyclic-like promastigotes within low-passage cultures at stationary growth phase. As we previously reported, in a screen seeking to identify novel genes involved in CML resistance: (1) a genomic cosmid library derived from DNA of CML-resistant L. chagasi promastigotes was transfected into highpassage (constitutively CML-sensitive) L. chagasi promastigotes; (2) transformants were screened for acquisition of CML-resistance; (3) multiple cosmid-transfectants exhibited partial CML resistance; and (4) the sequence for one of the cosmids (Cosmid 51) was determined. This report extends the analysis of Cosmid 51, and identifies by deletion analysis a subregion of the cosmid insert that is critical to the CML-resistance phenotype of Cosmid 51 transformants. We also report the sequence determination and initial CML-resistance activity of another cosmid that also confers partial resistance to CML

Characterization of DNA Sequences that Confer Complement Resistance in \u3ci\u3eLeishmania chagasi\u3c/i\u3e

Serial passage of axenically cultured Leishmania chagasi promastigotes results in a progressive diminution in resistance to complement-mediated lysis (CML), whereas high CML resistance is seen in infectious metacyclic promastigotes from the sandfly vector as well as metacyclic-like promastigotes within low-passage cultures at stationary growth phase. As we previously reported, in a screen seeking to identify novel genes involved in CML resistance: (1) a genomic cosmid library derived from DNA of CML-resistant L. chagasi promastigotes was transfected into highpassage (constitutively CML-sensitive) L. chagasi promastigotes; (2) transformants were screened for acquisition of CML-resistance; (3) multiple cosmid-transfectants exhibited partial CML resistance; and (4) the sequence for one of the cosmids (Cosmid 51) was determined. This report extends the analysis of Cosmid 51, and identifies by deletion analysis a subregion of the cosmid insert that is critical to the CML-resistance phenotype of Cosmid 51 transformants. We also report the sequence determination and initial CML-resistance activity of another cosmid that also confers partial resistance to CML

Biomass and Productivity of Thalassia testudinum in Estuaries of the Florida Panhandle

Thalassia testudinum often dominates seagrass meadows of the Florida panhandle but few measurements of productivity, biomass, density, turnover or leaf area index in this region have been made. We targeted 5 estuaries located at similar latitudes, 30⁰ ± 0.3⁰N: Big Lagoon, Santa Rosa Sound, St. Andrew Bay, St. Joseph Bay, and St. George Sound. This study was one component of a collaborative partnership of state and local researchers examining factors preventing recovery in panhandle estuarine areas that had historically contained seagrass in the 1940s and 1950s. Measurements were made twice in 2016, once in June and then again in summer or fall, except in Santa Rosa Sound where measurements were made 3 times. In the estuaries sampled for the second time in July or August, aboveground productivity was greater than in June. St. Joseph Bay had the highest aboveground productivity (4.3 g/m2/d) and 1—sided leaf area index (4.2) while St. George Sound had the lowest values (0.41 g/m2/d and 1.0). Principal component analysis suggested that St. Andrew Bay, Big Lagoon and Santa Rosa Sound were the most similar, with higher values for shoot densities and leaf turnover and lower salinities and watershed:water ratios. St. Joseph Bay had high aboveground productivity and salinity, and low turbidity. St. George Sound had low aboveground productivity, high total suspended solids and the highest watershed:water ratio. These baseline productivity estimates will be useful to assess the success of restoration efforts targeting seagrasses in the Florida panhandle and evaluate impacts of climate change on seagrasses

CAMBIOS TEMPORALES EN LA DIETA DEL PLAYERO ROJIZO (CALIDRIS CANUTUS RUFA) EN UN HUMEDAL DE PENÍNSULA VALDÉS, PATAGONIA ARGENTINA

Temporal variation in the diet of the Red Knot (Calidris canutus rufa) in a wetland from Península Valdés, Patagonia Argentina. – During their northward migration, Red Knots forage extensively in intertidal areas of Península Valdés (Patagonia, Argentina). This species has a small population and declines have been linked to reduced prey availability in migratory stopover sites. Thus, knowing the temporal variation in prey availability and diet is essential to understand population dynamics in the Red Knot. We studied temporal variation in the diet of the Red Knot at Colombo Beach (northeastern Nuevo Gulf, Península Valdés). To evaluate prey availability, we sampled benthic invertebrates in March every study year. We collected 292 feces during April in 2002, 2003, 2006, and 2007. Prey items were identified by using key hard structures. The clam Darina solenoides was the most common prey positively selected every year (Savage index), although in some years the polychaete Travisia olens was also selected. Other, less important prey items were seeds, mussels, insects, crustaceans, isopods, amphipods, ostracods, the snail Buccinanops globulosus, and the clam Tellina petitiana. Red Knots selected clams in variable size ranges depending on the year (10–18 mm in 2002, 8–22 mm in 2003, 10–20 in 2006, and 18–26 mm in 2007 mm). In the years where the contribution to biomass by the clam D. solenoids was lower, knots had a higher trophic diversity. Diet composition varied between years mainly due to differences in the intake of polychaetes