Lipid complexes with cationic peptides and OAKs; their role in antimicrobial action and in the delivery of antimicrobial agents

Antimicrobial agents are toxic to bacteria by a variety of mechanisms. One mechanism that is very dependent on the lipid composition of the bacterial membrane is the clustering of anionic lipid by cationic antimicrobial agents. Certain species of oligo-acyl-lysine (OAK) antimicrobial agents are particularly effective in clustering anionic lipids in mixtures mimicking the composition of bacterial membranes. The clustering of anionic lipids by certain cationic antimicrobial agents contributes to the anti-bacterial action of these agents. Bacterial membrane lipids are a determining factor, resulting in some species of bacteria being more susceptible than others. In addition, lipids can be used to increase the effectiveness of antimicrobial agents when administered in vivo. Therefore, we review some of the structures in which lipid mixtures can assemble, to more effectively be utilized as antimicrobial delivery systems. We describe in more detail the complexes formed between mixtures of lipids mimicking bacterial membranes and an OAK and their usefulness in synergizing with antibiotics to overcome bacterial multidrug resistance.     

Altered expression of securin (Pttg1) and serpina3n in the auditory system of hearing-impaired Tff3-deficient mice

Introduction

Tff3 peptide exerts important functions in cytoprotection and restitution of the gastrointestinal (GI) tract epithelia. Moreover, its presence in the rodent inner ear and involvement in the hearing process was demonstrated recently. However, its role in the auditory system still remains elusive. Our previous results showed a deterioration of hearing with age in Tff3-deficient animals.

Results

Present detailed analysis of auditory brain stem response (ABR) measurements and immunohistochemical study of selected functional proteins indicated a normal function and phenotype of the cochlea in Tff3 mutants. However, a microarray-based screening of tissue derived from the auditory central nervous system revealed an alteration of securin (Pttg1) and serpina3n expression between wild-type and Tff3 knock-out animals. This was confirmed by qRT-PCR, immunostaining and western blots.

Conclusions

We found highly down-regulated Pttg1 and up-regulated serpina3n expression as a consequence of genetically deleting Tff3 in mice, indicating a potential role of these factors during the development of presbyacusis.     

SecA,a remarkable nanomachine

Biological cells harbor a variety of molecular machines that carry out mechanical work at the nanoscale. One of these nanomachines is the bacterial motor protein SecA which translocates secretory proteins through the protein-conducting membrane channel SecYEG. SecA converts chemically stored energy in the form of ATP into a mechanical force to drive polypeptide transport through SecYEG and across the cytoplasmic membrane. In order to accommodate a translocating polypeptide chain and to release transmembrane segments of membrane proteins into the lipid bilayer, SecYEG needs to open its central channel and the lateral gate. Recent crystal structures provide a detailed insight into the rearrangements required for channel opening. Here, we review our current understanding of the mode of operation of the SecA motor protein in concert with the dynamic SecYEG channel. We conclude with a new model for SecA-mediated protein translocation that unifies previous conflicting data.     

Beta-carotene affects gene expression in lungs of male and female <Emphasis Type="Italic">Bcmo1</Emphasis><Superscript>−/−</Superscript> mice in opposite directions

Molecular mechanisms triggered by high dietary beta-carotene (BC) intake in lung are largely unknown. We performed microarray gene expression analysis on lung tissue of BC supplemented beta-carotene 15,15′-monooxygenase 1 knockout (Bcmo1 ^−/−) mice, which are—like humans—able to accumulate BC. Our main observation was that the genes were regulated in an opposite direction in male and female Bcmo1 ^−/− mice by BC. The steroid biosynthetic pathway was overrepresented in BC-supplemented male Bcmo1 ^−/− mice. Testosterone levels were higher after BC supplementation only in Bcmo1 ^−/− mice, which had, unlike wild-type (Bcmo1 ^+/+) mice, large variations. We hypothesize that BC possibly affects hormone synthesis or metabolism. Since sex hormones influence lung cancer risk, these data might contribute to an explanation for the previously found increased lung cancer risk after BC supplementation (ATBC and CARET studies). Moreover, effects of BC may depend on the presence of frequent human BCMO1 polymorphisms, since these effects were not found in wild-type mice.     

Highly reactive oxygen species: detection, formation, and possible functions

The so-called reactive oxygen species (ROS) are defined as oxygen-containing species that are more reactive than O(2) itself, which include hydrogen peroxide and superoxide. Although these are quite stable, they may be converted in the presence of transition metal ions, such as Fe(II), to the highly reactive oxygen species (hROS). hROS may exist as free hydroxyl radicals (HO·), as bound ("crypto") radicals or as Fe(IV)-oxo (ferryl) species and the somewhat less reactive, non-radical species, singlet oxygen. This review outlines the processes by which hROS may be formed, their damaging potential, and the evidence that they might have signaling functions. Since our understanding of the formation and actions of hROS depends on reliable procedures for their detection, particular attention is given to procedures for hROS detection and quantitation and their applicability to in vivo studies.     

Distribution of Brechmorhoga clubskimmers (Odonata: Libellulidae) in the Grand Canyon region, southwestern USA

We examined the distribution of Brechmorhoga mendax and B. pertinax (Libellulidae) in northern Arizona and southern Nevada. Brechmorhoga mendax occurs widely throughout the Southwest and in Arizona up to the Mogollon Rim, and up the Colorado River from the west to at least River Mile 132 (downstream from Lees Ferry, Arizona) at elevations of 110-1460 m. In Grand Canyon it occurs along small to large tributaries and on the mainstream at elevations below 650 m. The only previously reported locality for B. pertinax in the United States is in southeastern Arizona, where it was presumed to be accidental. We report B. pertinax along 5 small, perennial tributaries emanating from Redwall Formation aquifer springs on the south side of central Grand Canyon. Those springs habitats may be threatened by regional groundwater depletion. Brechmorhoga pertinax appears to be somewhat more stenotolerant in its habitat requirements than B. mendax , a finding in keeping with these differences in range. The presence of isolated populations of B. pertinax in Grand Canyon is an example of a Neotropical influence on the fauna and indicates biogeographic corridor and refuge functions of this large, deep canyon.     

Temperature and high salinity effects in germinating dimorphic seeds of Atriplex rosea

Atriplex rosea L. (Chenopodiaceae; tumbling orach), an annual herb, is a widely established weedy species of disturbed sites in all counties of Utah. Seeds of Atriplex rosea were collected from a salt marsh in Faust, Utah, and are dimorphic, light brown, and 2-2.5 mm wide, or black and 1-2 mm wide. Seed germination responses of the black and brown seeds were studied over a range of salinity and temperature. Both brown and black seeds germinated at 1000 mM NaCl, and the optimal temperature for germination of both types was 20°-30°C. Variation in temperature, however, affected germination of black seeds more than brown seeds. At lower thermoperiod only 40%-50% black seeds germinated in nonsaline control, and germination was almost completely inhibited with the inclusion of salinity. However, all brown seeds germinated in control at temperatures above 5°-15°C, and inhibition caused by salinity was comparatively lower. Brown seeds had a higher germination rate than black seeds at all temperature and salinity treatments. The highest rate of germination of both seeds occurred at the temperature regime of 5°-15°C. Recovery of germination for black seeds when transferred to distilled water after being in various salinity treatments for 20 days was quite variable. Recovery decreased with increase in salinity at lower temperature regimes, increased with salinity at optimal thermoperiod, and had no effect at 20°-30°C. Brown seeds recovered poorly from salinity at all thermoperiods except 5°-15°C, where recovery decreased with an increase in salinity. Brown seeds are adapted to germination in the early part of the growing season, whereas black seeds are capable of surviving harsher conditions and can germinate in later time periods. Characteristics of the dimorphic seeds increase chances for survival in the harsh saline desert environment.     

Biogeographic and taxonomic relationships among the mountain snails (Gastropoda: Oreohelicidae) of the central Great Basin

Described here are 4 species of mountain snails, Oreohelix , isolated on mountains in the central Great Basin of Nevada and Utah since the end of the Pleistocene. Forty-three mountains were searched during an 18-year period, resulting in 24 mountains found with no oreohelicids present. One population, Oreohelix loisae (19 mm to 23 mm in shell diameter), is described here as a new species related to, but geographically isolated from, the species Oreohelix nevadensis (17 mm to 22 mm diameter). Oreohelix loisae is present only in the Goshute Mountains while O. nevadensis is represented in 3 geographically adjacent ranges in the central Great Basin. These 2 species are possibly related to the Oreohelix haydeni group from the northern Wasatch Range. The subspecies Oreohelix strigosa depressa (15 mm to 21 mm diameter) is present on 11 ranges from western Utah west to east central Nevada. This subspecies is closely related to populations found today in the northern Wasatch Mountains of Utah. The smallest species in diameter (8 mm to 14 mm), Oreohelix hemphilli , is centered in the central Great Basin and found on 16 ranges often in sympatry with 1 or 2 of the larger conspecifics. Both qualitative and quantitative information on shell characters and soft anatomy is provided here for these 4 species. Shell characters, soft anatomy, geographical isolation, and statistical analysis suggest that 4 distinct species inhabit the central Great Basin today. Xeric and calciphilic species include O. hemphilli and O. loisae , while O. strigosa and O. nevadensis typically are associated with permanent water and both metamorphic and limestone mountains.     

Recurrence of Mexican long-tongued bats ( Choeronycteris mexicana ) at historical sites in Arizona and New Mexico

The Mexican long-tongued bat ( Choeronycteris mexicana ) is a nectar-eating species that seasonally inhabits the southwestern United States. Since 1906, fewer than 1500 individuals of C. mexicana have been documented throughout the range of the species. We conducted a field survey in Arizona and New Mexico during summer 1999 to check historically occupied areas for recurrence of C. mexicana . We observed C. mexicana occupying a majority (75%, n = 18) of visited sites. Multiple individuals were observed at many sites, including young-of-year. Choeronycteris mexicana roosted in lighted areas close to entrances within mine adits, abandoned buildings, wide rock crevices, and caves. All occupied sites in Madrean evergreen woodlands or semidesert grasslands where species of Agave were present. Most sites were located near a water source and, with the exception of a single site, near areas of riparian vegetation. Sites at which we did not encounter C. mexicana were frequently disturbed, difficult to search, or historically occupied by single individuals. Based on the relatively high rate of bat recurrence, we do not believe that populations of C. mexicana in the region have declined dramatically over the past several decades.     

Pygmy rabbits in the Colorado River drainage

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