Thiazole-substituted benzenesulfonamides as inhibitors of 12 human carbonic anhydrases

Four series of para or meta - substituted thiazolylbenzenesulfonamides bearing Cl substituents were designed, synthesized, and evaluated as inhibitors of all 12 catalytically active recombinant human carbonic anhydrase (CA) isoforms. Observed affinities were determined by the fluorescent thermal shift assay and the intrinsic affinities were calculated based on the fractions of binding-ready deprotonated sulfonamide and CA bearing protonated hydroxide bound to the catalytic Zn(II) in the active site. Several compounds exhibited selectivity towards CA IX, an anticancer target. Intrinsic affinities reached 30 pM, while the observed affinities - 70 nM. The structure-intrinsic affinity relationship map of the compounds showed the energetic contributions of the thiazole ring and its substituents.     

Does a long‐term shift in Wood Stork diet foreshadow adaptability to human‐induced rapid environmental change?

To preserve biodiversity, identifying at‐risk populations and developing conservation plans to mitigate the effects of human‐induced rapid environmental change (HIREC) are essential. Changes in diet, especially for food‐limited species, can aid in detecting populations being impacted by HIREC, and characterizing the quality, abundance, and temporal and spatial consistency of newly consumed food items may provide insight concerning the likelihood of a species persisting in a changing environment. We used Wood Storks (Mycteria americana) nesting in the Florida Everglades as a model system to study the possible effects of HIREC on a food‐limited population. We compared the diets of Wood Storks in 2013 and 2014 with those reported during the 1970s before major anthropogenic activities affected the Everglades system and prey availability. Wood Storks in our study consumed more large‐bodied sunfish species (Lepomis spp.), fewer native marsh fishes, and more non‐native fish species than during the 1970s. Large sunfish and non‐native fish are relatively rare in the drying pools of Everglades marshes where storks traditionally forage, suggesting that Wood Storks may be using novel foraging habitats such as created wetlands (i.e., canals and stormwater ponds). Although created wetlands have long hydroperiods conducive to maintaining large‐bodied fishes and could provide alternative foraging habitat when prey availability is reduced in natural marshes, additional studies are needed to determine the extent to which these wetlands are used by Wood Storks and, importantly, the quality of prey items potentially available to foraging Wood Storks in created wetlands.     

Thermal tolerance and recovery behaviour of Thorectes lusitanicus (Coleoptera,Geotrupidae)

1. Population differences in physiological responses are examined in Thorectes lusitanicus, an endemic Iberian dung beetle species, by submitting individuals of different populations to the same experimental and acclimation conditions. 2. An infrared thermography protocol was used, consisting of three assays: start of activity, cold response, and heat response. Individuals of 12 populations were studied and the comparative explanatory capacities of several environmental factors in relation to the observed inter‐population differences were examined. 3. The heating rate from chill coma to the beginning of activity was the variable with the highest discrimination power among the studied populations, accounting for 94% of the observed variance. Regarding the heat response, only six of the 16 thermal variables reached significance (inter‐population differences accounted for 52–74% in these six thermal parameters). 4. From the three considered environmental factors (Mediterranean climate, land cover, and trophic characteristics) only land cover characteristics remain statistically significant, affecting the cold response of individuals. 5. Thorectes lusitanicus is a species characterised by a high diversity of thermotolerance and recovery traits across populations with a low degree of association with broad environmental factors. Finally, it is suggested that the apterous character of this species could be a determinant factor explaining the high diversity of ecophysiological traits related to thermal stress tolerance and the recovery time.     

RUNAWAY COEVOLUTION: ADAPTATION TO HERITABLE AND NONHERITABLE ENVIRONMENTS

Populations evolve in response to the external environment, whether abiotic (e.g., climate) or biotic (e.g., other conspecifics). We investigated how adaptation to biotic, heritable environments differs from adaptation to abiotic, nonheritable environments. We found that, for the same selection coefficients, the coadaptive process between genes and heritable environments is much faster than genetic adaptation to an abiotic nonheritable environment. The increased rate of adaptation results from the positive association generated by reciprocal selection between the heritable environment and the genes responding to it. These associations result in a runaway process of adaptive coevolution, even when the genes creating the heritable environment and genes responding to the heritable environment are unlinked. Although tightening the degree of linkage accelerates the coadaptive process, the acceleration caused by a comparable amount of inbreeding is greater, because inbreeding has a cumulative effect on reducing functional recombination over generations. Our results suggest that that adaptation to local abiotic environmental variation may result in the rapid diversification of populations and subsequent reproductive isolation not directly but rather via its effects on heritable environments and the genes responding to them.     

Pituitary Secretory Granule Topography: Influence of Different Electron Microscopic Preparation Procedures on the Surface of Epon Sections

Human, rat and mouse pituitary tissues have been examined electron microscopically in transmission (TEM), scanning-transmission (STEM) and scanning (SEM) modes for the surface appearance of the secretory granules in tissue sections. Cryofixed and cryosectioned tissue showed only slightly protruding granule profiles which had a smooth surface. Cryofixed, freeze-dried and Epon embedded pituitaries, on the other hand, demonstrated swollen and furrowed surfaces over the granules after contact with water. This topography could also be seen after glutaraldehyde fixation but less after post-fixation in OsO₄. The surface alterations in the sections of pituitary secretory granules are thought to be due to differences in the homogeneity of the resin infiltration, leaving resin-free openings where water can enter. It also seems probable that the Epon resin is more influenced by water than has been previously assumed, based on the findings of efficient elimination of osmium from the granules after incubation of tissue sections in water for only 10 min.     

Purification of Neuronal Cell Surface Proteins and Generation of Epitope-Specific Monoclonal Antibodies Against Cell Adhesion Molecules

To establish a procedure for the purification of a broad spectrum of cell surface proteins, three separate methods based on different principles were compared with the aid of four marker proteins. Membrane preparation by sedimentation-flotation centrifugation, temperature-induced phase separation with Triton X-114, and lectin affinity chromatography were used separately as well as in combination. The two-step procedure of membrane preparation and lectin affinity chromatography provided by far the best enrichment of cell surface marker proteins. This result was further substantiated by screening greater than 6,600 hybridoma cultures that originated from mice that had been immunized with protein fractions obtained by different purification protocols. In addition, it was found that solubilized glycoproteins used as immunogens led to many more cell surface-specific monoclonal antibodies than glycoproteins immobilized on lectin-agarose beads. Three monoclonal antibodies that recognize distinct epitopes of cell adhesion molecules (CAMs) were isolated. Monoclonal antibody C4 bound to a detergent-labile epitope of G4 (neuron-glia CAM). Monoclonal antibody D1 recognized specifically nonreduced neural CAM (N-CAM) with intact disulfide bridges, and monoclonal antibody D3 recognized only the 180-kilodalton isoform of N-CAM. Because of these specificities, these monoclonal antibodies promise to be useful tools for the elucidation of the structural organization of adhesion molecules.     

Preventing Ultimate Harm as the Justification for Biomoral Modification

Most advocates of biogenetic modification hope to amplify existing human traits in humans in order to increase the value of such traits as intelligence and resistance to disease. These advocates defend such enhancements as beneficial for the affected parties. By contrast, some commentators recommend certain biogenetic modifications to serve social goals. As Ingmar Persson and Julian Savulescu see things, human moral psychology is deficient relative to the most important risks facing humanity as a whole, including the prospect of Ultimate Harm, the point at which worthwhile life is forever impossible on the planet. These risks can be mitigated, they say, by enhancing moral psychology in novel ways. Persson and Savulescu argue that some parents should modify the underlying biogenetics of their children's moral psychology, if such measures were safe and effective, but they admit these interventions may not decouple humanity from Ultimate Harm. Neither are these modifications the only options, they concede, for addressing risks to humanity. Even with these concessions, saving humanity from itself is a fairly poor reason to modify the moral psychology of children. In most ways, adults would be better candidates, morally speaking, for modifications of psychology. Even then, there is no direct link between morally enhanced human beings and the hoped‐for effect of better protection from Ultimate Harm. Asserting a general duty of all to contribute to the avoidance of Ultimate Harm is a better moral strategy than intervening in the moral psychology of some, even though meeting that duty may involve substantial interference with the free exercise of one's interests.     

CELL SURFACE ALTERATIONS BY TAXOL ASSOCIATED WITH ABNORMAL MORPHOGENESIS IN THE CHICK EMBRYO

The anticancer drug taxol brings about its biological effects by altering the stability of microtubules. We have examined the effects of taxol on early morphogenesis in chick embryos culturedin vitro. Taxol induced various abnormalities in the developing nervous system, heart and somites as well as general retardation of development. SEM studies revealed that taxol treatment leads to dramatic alterations in the embryonic cell surfaces. Time-course experiments demonstrated that the action of taxol is very rapid and becomes evident within a few minutes at the ultrastructural level. Taxol thus throws embryonic cell adhesion and motility out of balance. This appears to be the major cause of abnormal morphogenesis in taxol-treated embryos.     

Zosteric acid and salicylic acid bound to a low density polyethylene surface successfully control bacterial biofilm formation

The active moieties of the anti-biofilm natural compounds zosteric (ZA) and salicylic (SA) acids have been covalently immobilized on a low density polyethylene (LDPE) surface. The grafting procedure provided new non-toxic eco-friendly materials (LDPE-CA and LDPE-SA) with anti-biofilm properties superior to the conventional biocide-based approaches and with features suitable for applications in challenging fields where the use of antimicrobial agents is limited. Microbiological investigation proved that LDPE-CA and LDPE-SA: (1) reduced Escherichia coli biofilm biomass by up to 61% with a mechanism that did not affect bacterial viability; (2) significantly affected biofilm morphology, decreasing biofilm thickness, roughness, substratum coverage, cell and matrix polysaccharide bio-volumes by >80% and increasing the surface to bio-volume ratio; (3) made the biofilm more susceptible to ampicillin and ethanol. Since no molecules were leached from the surface, they remained constantly effective and below the lethal level; therefore, the risk of inducing resistance was minimized.