Environmentally constrained mutation and adaptive evolution in Salmonella

The relationship between environment and mutation is complex [1]. Claims of Lamarkian mutation [2] have proved unfounded [3], [4] and [5]; it is apparent, however, that the external environment can influence the generation of heritable variation, through either direct effects on DNA sequence [6] or DNA maintenance and copying mechanisms [7], [8], [9] and [10], or as a consequence of evolutionary processes [11], [12], [13], [14], [15] and [16]. The spectrum of mutational events subject to environmental influence is unknown [6] and precisely how environmental signals modulate mutation is unclear. Evidence from bacteria suggests that a transient recombination-dependent hypermutational state can be induced by starvation [5]. It is also apparent that chnages in the mutability of specific loci can be influenced by alterations in DNA topology [10] and [17]. Here we describe a remarkable instance of adaptive evolution in Salmonella which is caused by a mutation that occurs in intermediate-strength osmotic environments. We show that the mutation is not ‘directed’ and describe its genetic basis. We also present compelling evidence in support of the hypothesis that the mutational event is constrained by signals transmitted from the external environment via changes in the activity of DNA gyrase.     

Galectin 9 is the sugar-regulated urate transporter/channel UAT

UAT, also designated galectin 9, is a multifunctional protein that can function as a urate channel/transporter, a regulator of thymocyte-epithelial cell interactions, a tumor antigen, an eosinophil chemotactic factor, and a mediator of apoptosis. We review the evidence that UAT is a transmembrane protein that transports urate, describe our molecular model for this protein, and discuss the evidence from epitope tag and lipid bilayer studies that support this model of the transporter. The properties of recombinant UAT are compared with those of urate transport into membrane vesicles derived from proximal tubule cells in rat kidney cortex. In addition, we review channel functions predicted by our molecular model that resulted in the novel finding that the urate channel activity is regulated by sugars and adenosine. Finally, the presence and possible functions of at least 4 isoforms of UAT and a closely related gene hUAT2 are discussed. Published in 2004.     

Pinocytic uptake and intracellular degradation of N-(2-hydroxypropyl)methacrylamide copolymers a potential drug delivery system

Synthetic ¹²⁵I-labelled N-(2-hydroxypropyl)methacrylamide copolymers containing four different, potentially degradable peptidyl side chains were incubated with rat visceral yolk sacs cultured in vitro. All copolymers were captured by fluid-phase pinocytosis and three of the side chains were susceptible to lysosomal hydrolysis, resulting in release of [¹²⁵I]iodotyrosine back into the culture medium. Uptake and degradation was completely inhibited by 2,4-dinitrophenol. The thiol-proteinase inhibitor leupeptin did not affect the rate of pinocytosis, but caused different degrees of inhibition of hydrolysis depending on side chain composition.     

The karyotype of Alligator mississippiensis,and chromosomal mapping of the ZFY/X homologue,Zfc

Comparative mapping studies of X-linked genes in mammals have provided insights into the evolution of the X chromosome. Many reptiles including the American alligator, Alligator mississippiensis, do not appear to possess heteromorphic sex chromosomes, and sex is determined by the incubation temperature of the egg during embryonic development. Mapping of homologues of mammalian X-linked genes in reptiles could lead to a greater understanding of the evolution of vertebrate sex chromosomes. One of the genes used in the mammalian mapping studies was ZFX, an X-linked copy of the human ZFY gene which was originally isolated as a candidate for the mammalian testis-determining factor (TDF). ZFX is X-linked in eutherians, but maps to two autosomal locations in marsupials and monotremes, close to other genes associated with the eutherian X. The alligator homologue of the ZFY/ZFX genes, Zfc, has been isolated and described previously. A detailed karyotype of A. mississippiensis is presented, together with chromosomal in situ hybridisation data localising the Zfc gene to chromosome 3. Further chromosomal mapping studies using eutherian X-linked genes may reveal conserved chromosomal regions in the alligator that have become part of the eutherian X chromosome during evolution.     

Extracellular potassium can simulate the role of serum as an activator of uridine uptake by quiescent hamster cells in culture

Replacement of ~100 mM of sodium chloride in the extracellular medium of quiescent hamster fibroblasts (Nil 8 and BHK cells) by potassium chloride causes an increase in the rate of uridine uptake. This increase is identical with that achieved by addition of 10% serum to the same cultures. The effects of serum and KCl are not additive. The dependence of the rate of uridine uptake on extracellular KCl concentration is of a sigmoid nature. The time course of the activation process is similar to that of serum activation of uridine uptake in the same cells. The high rate of uridine uptake persists for at least 30 min after return to an extracellular medium containing a high concentration of sodium.     

Treatment of burns casualties after fire at Bradford City football ground.

On 11 May 1985 the main stand of Bradford City Football Club caught fire. Within four minutes the stand was alight from end to end. Fifty three people were burnt to death and about 250 injured; 83 required admission to hospital, and 55 of these were treated by primary excision of their burns and skin grafting. In such disasters the help of staff from other hospitals and areas is essential. Patients should be assessed to see whether they have burns that will ultimately be fatal; if they have they should not be sent to regional burns units, where they would take up beds that could be used for patients with treatable burns. All districts should ensure that their plans for accidents in which burns injuries predominate are adequate.     

Effects of urbanization on streams of the Melbourne region, Victoria, Australia. I. Benthic macroinvertebrate communities

1. Macroinvertebrate community composition was assessed in small streams of the Melbourne region to test the effects of (a) urban density (catchment imperviousness 0–51%) and (b) stormwater drainage intensity (comparing the intensively drained metropolitan area with urban areas of the hinterland, which had open drains and some localized stormwater drainage).
2. Hinterland communities separated into two groups of sites correlating strongly with patterns of electrical conductivity (EC), basalt geology and annual rainfall. Community composition varied little in the high-EC, western group (imperviousness 0.2–1.2%), but in the eastern group it was strongly correlated with catchment imperviousness (0–12%), with lower taxon richness in more impervious catchments.
3. Metropolitan communities (imperviousness 1–51%) were all severely degraded, with high abundances of a few tolerant taxa. Community composition was poorly correlated with patterns of geology, rainfall or imperviousness. Differences between metropolitan and hinterland communities were well explained by patterns of biochemical oxygen demand and electrical conductivity, which were postulated to indicate the more efficient transport of pollutants to receiving streams by the metropolitan stormwater drainage system.
4. Degradation of macroinvertebrate community composition was well explained by urban density but intensive urban drainage increased degradation severely at even low urban densities. Quantification of relationships between imperviousness, drainage intensity and stream degradation can better inform the assessment, conservation and restoration of urban streams.