Selective G-quadruplex ligands: The significant role of side chain charge density in a series of perylene derivatives

The human telomeric G-quadruplex structure is a promising target for the design of cancer drugs. The selectivity of G-quadruplex ligands with respect to duplex genomic DNA is of especial importance. The high selectivity of polyamine conjugated perylene derivatives appears to be regulated by side-chain charge density, as indicated by data from a FRET melting assay and induced CD spectroscopy.     

Wilsonosiphonia gen. nov. (Rhodomelaceae,Rhodophyta) based on molecular and morpho‐anatomical characters

Morphological, anatomical, and molecular sequence data were used to assess the establishment and phylogenetic position of the genus Wilsonosiphonia gen. nov. Phylogenies based on rbcL and concatenated rbcL and cox1 loci support recognition of Wilsonosiphonia gen. nov., sister to Herposiphonia. Diagnostic features for Wilsonosiphonia are rhizoids located at distal ends of pericentral cells and taproot‐shaped multicellular tips of rhizoids. Wilsonosiphonia includes three species with diagnostic rbcL and cox1 sequences, Wilsonosiphonia fujiae sp. nov. (the generitype), W. howei comb. nov., and W. indica sp. nov. These three species resemble each other in external morphology, but W. fujiae is distinguished by having two tetrasporangia per segment rather than one, W. indica by having abundant and persistent trichoblasts, and W. howei by having few and deciduous trichoblasts.     

Changes in the reproductive biology of Biomphalaria glabrata experimentally infected with the nematode Angiostrongylus cantonensis

This study showed for the first time changes in the reproductive biology of Biomphalaria glabrata experimentally infected with Angiostrongylus cantonensis. The values of all the parameters analyzed (total number of eggs, number of egg masses, number of eggs/mass, number of eggs/snail, percentage of viable eggs and galactogen content in albumen gland) changed with progressive infection. The results indicate the occurrence of partial parasitic castration of B. glabrata by A. cantonensis larvae, probably in response to the depletion of energy reserves, with no injuries to the gonadal tissues.     

Lipid levels in Biomphalaria glabrata infected with different doses of Echinostoma paraensei miracidia

The effect of experimental exposure of Biomphalaria glabrata to different doses (5 and 50) of Echinostoma paraensei miracidia on the total levels of cholesterol and triglycerides circulating in the hemolymph and the neutral lipids in the digestive gland–gonad (DGG) complex were studied. The snails were dissected one, two, three and four weeks after infection to collect the hemolymph and DGG tissue, to measure the levels of cholesterol and triglycerides in the hemolymph and neutral lipids in the tissue. The results for the hemolymph showed a similar order of variation for both substrates tested in the first week after infection. The reduced levels of these lipids in the infected snails indicate intense use of these substrates both by the intermediate host and the parasite, suggesting its probable participation in the energy metabolism and structural construction of the developing larval stages. Alterations in the profile of neutral lipids in the DGG were also found. The results obtained indicate that in this model, the lipid metabolism depends on the miracidial dose used.     

Spatially explicit models as tools for implementing effective management strategies for invasive alien mammals

1. Invasive alien species are major drivers of global change that can have severe impacts on biodiversity and human well-being. Management strategies implemented to mitigate these impacts are based on a hierarchical approach, from prevention of invasion, via early warning and rapid response, to invasive species management.
2. We evaluated how different classes of spatially explicit models have been used as predictive tools to improve the effectiveness of management strategies. A review of literature published between 2000 and 2019 was undertaken to retrieve studies addressing alien mammal species through these models.
3. We collected 62 studies, dealing with 70 (27%) of the 261 mammal species that are considered to be introduced worldwide. Most of the studies dealt with species from the orders Rodentia (34%), Artiodactyla and Carnivora (both 24%); the most commonly studied families were Sciuridae (13%) and Muridae (12%).
4. Most of the studies (73%) provided spatial predictions of potential species spread, while only ca. 15% of the studies included evaluations of management options. About 29% of the studies were considered useful in risk assessment procedures, but only because they presented climatic suitability predictions worldwide, while studies modelling suitability before a species was introduced locally are still lacking for mammals. With some exceptions, spatially explicit population models are still little used, probably because of the perceived need for detailed information on life history parameters.
5. Spatially explicit models have been used in relatively few studies dealing with invasive mammals, and most of them covered a restricted pool of species. Most of the studies used climate matching to evaluate the suitability of geographic areas worldwide or the possibility of species that were already established spreading further. Modelling procedures could be a useful tool to assess the risk of establishment for species not yet present in an area but likely to arrive; however, such studies are lacking for mammals.

     

The targeting of the plasma membrane calcium pump in the cell

The information on the structural determinants that control the cellular distribution of P-type pumps is very scarce. However, recent experiments on the membrane targeting of the plasma membrane Ca²⁺ pump (PMCA) have provided interesting leads on the problem: they will be discussed in this succinct review. A general introduction on the biochemical properties of the PMCA pump will preface the discussion of the specific findings on the role of three distinct regions of the molecule in the targeting process.     

Is preoperative fasting necessary?

The effects of fasting and of histamine (H2) antagonists on gastric volume and acidity were studied in 56 baboons undergoing various surgical procedures under general anesthesia and randomly allocated into 4 groups; group A--fasted for 14 hours; group B--given 100-120 ml of water 3 hours before surgery; groups C and D--also given 100-120 ml of water 3 hours before surgery; in addition, the former received cimetidine 10 mg/kg IM and the latter ranitidine 1.5 mg/kg IM 30-40 minutes before anesthesia. There were no significant differences between groups A and B with respect to the gastric volume and pH. Both ranitidine and cimetidine significantly (P < 0.02) reduced gastric volume and increased gastric pH. Thus, prolonged withholding of oral fluids does not reduce the gastric volume or increase gastric pH. H2-antagonists are effective in reducing both gastric residual volume and pH.     

Kinetics of muscle deoxygenation are accelerated at the onset of heavy-intensity exercise in patients with COPD: relationship to central cardiovascular dynamics.

Patients with chronic obstructive pulmonary disease (COPD) have slowed pulmonary O(2) uptake (Vo(2)(p)) kinetics during exercise, which may stem from inadequate muscle O(2) delivery. However, it is currently unknown how COPD impacts the dynamic relationship between systemic and microvascular O(2) delivery to uptake during exercise. We tested the hypothesis that, along with slowed Vo(2)(p) kinetics, COPD patients have faster dynamics of muscle deoxygenation, but slower kinetics of cardiac output (Qt) following the onset of heavy-intensity exercise. We measured Vo(2)(p), Qt (impedance cardiography), and muscle deoxygenation (near-infrared spectroscopy) during heavy-intensity exercise performed to the limit of tolerance by 10 patients with moderate-to-severe COPD and 11 age-matched sedentary controls. Variables were analyzed by standard nonlinear regression equations. Time to exercise intolerance was significantly (P < 0.05) lower in patients and related to the kinetics of Vo(2)(p) (r = -0.70; P < 0.05). Compared with controls, COPD patients displayed slower kinetics of Vo(2)(p) (42 +/- 13 vs. 73 +/- 24 s) and Qt (67 +/- 11 vs. 96 +/- 32 s), and faster overall kinetics of muscle deoxy-Hb (19.9 +/- 2.4 vs. 16.5 +/- 3.4 s). Consequently, the time constant ratio of O(2) uptake to mean response time of deoxy-Hb concentration was significantly greater in patients, suggesting a slower kinetics of microvascular O(2) delivery. In conclusion, our data show that patients with moderate-to-severe COPD have impaired central and peripheral cardiovascular adjustments following the onset of heavy-intensity exercise. These cardiocirculatory disturbances negatively impact the dynamic matching of O(2) delivery and utilization and may contribute to the slower Vo(2)(p) kinetics compared with age-matched controls.     

Molecular dynamics simulation of the docking of substrates to proteins

A simple method is described to perform docking of subtrates to proteins or probes to receptor molecules by a modification of molecular dynamics simulations. The method consists of a separation of the center-of-mass motion of the substrate from its internal and rotational motions, and a separate coupling to different thermal baths for both types of motion of the substrate and for the motion of the receptor. Thus the temperatures and the time constants of coupling to the baths can be arbitrarily varied for these three types of motion, allowing either a frozen or a flexible receptor and allowing control of search rate without disturbance of internal structure. In addition, an extra repulsive term between substrate and protein was applied to smooth the interaction. The method was applied to a model substrate docking onto a model surface, and to the docking of phosphocholine onto immunoglobulin McPC603, in both cases with a frozen receptor. Using transrational temperatures of the substrate in the range of 1300–1700 K and room temperature for the internal degrees of freedom of the substrate, an efficient nontrapping exploratory search (“helicopter view”) is obtained, which visits the correct binding sites. Low energy conformations can then be further investigated by separate search or by dynamic simulated annealing. In both cases the correct minima were identified. The possibility to work with flexible receptors is discussed. © 1994 Wiley-Liss, Inc.     

Thermodynamics and kinetics of the thermal unfolding of plastocyanin

The thermal denaturation of plastocyanin in aqueous solution was investigated by means of DSC, ESR and absorbance techniques, with the aim of determining the thermodynamic stability of the protein and of characterizing the thermally induced conformational changes of its active site. The DSC and absorbance experiments indicated an irreversible and kinetically controlled denaturation path. The extrapolation of the heat capacity and optical data at infinite scan rate made it possible to calculate the kinetic and thermodynamic parameters associated with the denaturation steps. The denaturation pathway proposed, and the parameters found from the calorimetric data, were checked by computer simulation using an equation containing the information necessary to describe the denaturation process in detail. ESR and absorbance measurements have shown that structural changes of the copper environment occur during the protein denaturation. In particular, the geometry of the copper-ligand atoms changes from being tetrahedral to square planar and the disruption of the active site precedes the global protein denaturation. The thermodynamic enthalpic change, the half-width transition temperature, and the value of ΔCp, were used to calculate the thermodynamic stability, ΔG, of the reversible process over the entire temperature range of denaturation. The low thermal stability found for plastocyanin, is discussed in connection with structural factors stabilizing the native state of a protein. Received: 17 July 1997 / Revised version: 22 November 1997 / Accepted: 15 January 1998