The two pathogenic species of Neisseria, N. meningitidis and N. gonorrhoeae, have evolved resistance to penicillin by alterations in chromosomal genes encoding the high molecular weight penicillin-binding proteins, or PBPs. The PBP 2 gene (penA) has been sequenced from over 20 Neisseria isolates, including susceptible and resistant strains of the two pathogenic species, and five human commensal species. The genes from penicillin-susceptible strains of N. meningitidis and N. gonorrhoeae are very uniform, whereas those from penicillin-resistant strains consist of a mosaic of regions resembling those in susceptible strains of the same species, interspersed with regions resembling those in one, or in some cases, two of the commensal species. The mosaic structure is interpreted as having arisen from the horizontal transfer, by genetic transformation, of blocks of DNA, usually of a few hundred base pairs. The commensal species identified as donors in these interspecies recombinational events (N. flavescens and N. cinerea) are intrinsically more resistant to penicillin than typical isolates of the pathogenic species. Transformation has apparently provided N. meningitidis and N. gonorrhoeae with a mechanism by which they can obtain increased resistance to penicillin by replacing their penA genes (or the relevant parts of them) with the penA genes of related species that fortuitously produce forms of PBP 2 that are less susceptible to inhibition by the antibiotic. The ends of the diverged blocks of DNA in the penA genes of different penicillin-resistant strains are located at the same position more often than would be the case if they represent independent crossovers at random points along the gene. Some of these common crossover points may represent common ancestry, but reasons are given for thinking that some may represent independent events occurring at recombinational hotspots.

An F 2 population (n = 151) derived from Dahl salt-sensitive (S) and Lewis rats was raised on a 8% NaCl diet for 9 weeks and analyzed for blood pressure quantitative trait loci (QTL) by use of a whole genome scan. Chromosomes 5 and 10 yielded lod scores for linkage to blood pressure that were significant; chromosomes 1, 2, 3, 8, 16, 17, and 18 gave lod scores suggestive for linkage. Chromosome 7 gave a significant signal for heart weight with a lesser effect on blood pressure. Congenic strains were constructed by introgressing Lewis low-blood-pressure QTL alleles for chromosomes 1, 5, 10, and 17 into the S genetic background. Congenic strains for chromosomes 1, 5, and 10 had significantly lower blood pressure than S, proving the existence of QTL on these chromosomes, but the chromosome 17 congenic strain failed to trap a contrasting QTL allele. The QTL allele increasing blood pressure originated from S rats for all QTL except those on chromosomes 2 and 7 in which the Lewis allele increased blood pressure. Interactions between each QTL and every other locus in the genome scan yielded significant interactions between chromosomes 10 and 4, and between chromosomes 2 and 3.More than 30 years ago, Dahl et al. (1963) selectively bred rats for sensitivity (S rats) and resistance (R rats) to the hypertensive effect of a high-salt (NaCl) diet. Inbred strains of S and R rats were subsequently developed from Dahl's selectively bred lines (Rapp and Dene 1985). These strains are the prototypic animal model for studying salt-induced hypertension.S rats develop hypertension even on a low-salt diet, but this is markedly exacerbated by increased salt intake (Dahl et al. 1963;Rapp and Dene 1985). Chromosomal regions containing blood pressure quantitative trait loci (QTL) have been detected by the candidate gene approach starting in 1972 with a biochemical genetic marker for steroid 11␤-hydroxylase Dahl 1972a, 1976), and then in 1989 when restriction fragment-length polymorphisms first became available (Rapp et al. 1989). More recently, additional chromosomal regions containing blood pressure QTL were identified around candidate genes by use of Dahl rats and more modern genetic markers

Non-f8-lactamase-producing, penicillin-resistant strains of Neisseria meningildis produce altered forms of penicillin-binding protein 2 that have decreased affinity for penicillin. The sequence of the penicillin-binding protein 2 gene (penA) from a penicillin-resistant strain of N. meningitidis was compared to the sequence of the same gene from penicillinsensitive strains and from penicillin-sensitive and penicillinresistant strains of Neisseria gonorrhoeae. The penA genes from penicillin-sensitive strains ofN. gonorrhoeae and N. meningitdis were 98% identical. The gene from the penicillin-resistant strain ofN. meningitis consisted of regions that were almost identical to the corresponding regions in the penicillin-sensitive strains (<0.2% divergence) and two regions that were very different from them (-22% divergence). The two blocks of altered sequence have arisen by the replacement of meningococcal sequences with the corresponding regions from thepenA gene of Neisseria flavescens and result in an altered form of penicillinbinding protein 2 that contains 44 amino acid substitutions and 1 amino acid insertion compared to penicillin-binding protein 2 of penicillin-sensitive strains of N. meningitddis. A similar introduction of part of the penA gene of N. flavescens, or a very similar commensal Neisseria species, appears to have occurred independently during the development of altered penA genes in non-,B-lactamase-producing penicillin-resistant strains of N. gonorrhoeae.The nucleotide sequences of the PBP-2 gene (penA) from two penicillin-sensitive, and three penicillin-resistant, non-

When a granular material is impacted by a sphere, its surface deforms like a liquid yet it preserves a circular crater like a solid. Although the mechanism of granular impact cratering by solid spheres is well explored, our knowledge on granular impact cratering by liquid drops is still very limited. Here, by combining high-speed photography with high-precision laser profilometry, we investigate liquid-drop impact dynamics on granular surface and monitor the morphology of resulting impact craters. Surprisingly, we find that despite the enormous energy and length difference, granular impact cratering by liquid drops follows the same energy scaling and reproduces the same crater morphology as that of asteroid impact craters. Inspired by this similarity, we integrate the physical insight from planetary sciences, the liquid marble model from fluid mechanics, and the concept of jamming transition from granular physics into a simple theoretical framework that quantitatively describes all of the main features of liquid-drop imprints in granular media. Our study sheds light on the mechanisms governing raindrop impacts on granular surfaces and reveals a remarkable analogy between familiar phenomena of raining and catastrophic asteroid strikes.liquid impacts | granular impact cratering | jamming | liquid marble G ranular impact cratering by liquid drops is likely familiar to all of us who have watched raindrops splashing in a backyard or on a beach. It is directly relevant to many important natural, agricultural, and industrial processes such as soil erosion (1, 2), drip irrigation (3), dispersion of microorganisms in soil (4), and spray-coating of particles and powders. The vestige of raindrop imprints in fossilized granular media has even been used to infer air density on Earth 2.7 billion years ago (5). Hence, understanding the dynamics of liquid-drop impacts on granular media and predicting the morphology of resulting impact craters are of great importance for a wide range of basic research and practical applications.Directly related to two long-standing problems in fluid and granular physics research, i.e., drop impact on solid/liquid surfaces (6-9) and granular impact cratering by solid spheres (10-16), liquid-drop impact on granular surfaces is surely more complicated. Although several recent experiments have been attempted to investigate the morphology of liquid-drop impact craters (17-21), a coherent picture for describing various features of the impact craters is still lacking. Even for the most straightforward impact-energy (E) dependence of the size of liquid-drop impact craters, the results remain controversial and incomplete (17,19,20). Katsuragi (17) and Delon et al. (19) reported that the diameter of liquid-drop impact craters D c scales as the 1/4 power of the Weber number of liquid drops, which yields D c ∼ E 1=4 , quantitatively similar to the energy scaling for low-speed solid-sphere impact cratering (10, 11). However, because the energy balance of liquid-drop impacts is different from that of solid...

The penicillin-binding protein 2 genes (penA) of penicillin-resistant Neisseria meningitidis have a mosaic structure that has arisen by the introduction of regions from the penA genes of Neisseria flavescens or Neisseria cinerea. Chromosomal DNA from both N. cinerea and N. flavescens could transform a penicillin-susceptible isolate of N. meningitidis to increased resistance to penicillin. With N. flavescens DNA, transformation to resistance was accompanied by the introduction of the N. flavescens penA gene, providing a laboratory demonstration of the interspecies recombinational events that we believe underlie the development of penicillin resistance in many meningococci in nature. Surprisingly, with N. cinerea DNA, the penicillin-resistant transformants did not obtain the N. cinerea penA gene. However, the region of the penA gene derived from N. cinerea in N. meningitidis K196 contained an extra codon (Asp-345A) which was not found in any of the four N. cinerea isolates that we examined and which is known to result in a decrease in the affinity of PBP 2 in gonococci.