A herpes simplex virus DNA polymerase mutation that specifically attenuates neurovirulence in mice

Herpes simplex virus can infect the mammalian brain causing lethal encephalitis (neurovirulence). Previously, herpes simplex virus mutants that are attenuated for neurovirulence have exhibited defects in replication in brain and/or blocks to replication in neuronal cells. We investigated the attenuation of neurovirulence of mutant PAAr5, which exhibits resistance to antiviral drugs due to altered viral DNA polymerase. Following intracerebral inoculation of 7-week-old CD1 mice, PAAr5 was 30-fold attenuated for neurovirulence compared to its wild-type parent. A drug-sensitive virus derived by marker rescue with DNA polymerase gene sequences exhibited neurovirulence that was essentially indistinguishable from that of wild-type virus, demonstrating that attenuation was due to a polymerase mutation. PAAr5 replicated in brain similarly to wild-type virus unlike another polymerase mutant, 615.8, that exhibited a similar degree of attenuation. The attenuation of PAAr5 was not associated with altered particle to PFU ratios nor with any obvious reductions in viral antigen expression in neurons, spread, histopathology, or TUNEL staining suggestive of apoptotic cells. Thus PAAr5 differs from other mutants that are attenuated for neurovirulence. Understanding how a polymerase mutation specifically attenuates neurovirulence may shed light on how herpes simplex virus can cause lethal encephalitis.     

How ciliates manipulate their own DNA – A splendid example of natural computing

DNA computing is a novel and vivid researcharea which is genuinely interdisciplinary –computer scientists and molecular scientistscollaborate to investigate the use of DNAmolecules for the purpose of computing. DNAcomputing in vivo is the investigation ofcomputations taking place naturally in a livingcell, with the goal of understandingcomputational properties of DNA molecules intheir native environment. Gene assembly inciliates (single cell organisms) is perhaps themost involved process of DNA manipulation yetknown in living organisms. The computationalnature of this process has attracted muchattention in recent years. The resultsobtained so far demonstrate that this processof gene assembly is a splendid example ofcomputing taking place in nature, i.e., NaturalComputing. Indeed, DNA computing in vivomay be far more widespread in nature than wecurrently recognize. This paper is a tutorialon (computational nature of the) gene assemblyin ciliates, which is intended for a broadaudience of researchers interested in NaturalComputing. In particular, no knowledge ofmolecular biology is assumed on the part of themotivated reader.     

Developmental systems with locally catenative formulas

Summary A locally catenative sequence of strings of letters is such that each string in the sequence, after an initial stretch, is formed by concatenating strings which occurred at some specified distances previously in the sequence. These kinds of structures are frequently encountered in biological development, particularly in the case of compound branching structures or compound leaves. Developmental systems have been formally defined in previous publications. One of the present results is that dependent PDOL systems can produce sequences for every locally catenative formula (PDOL systems are propagating, deterministic developmental systems without interactions). Every dependent PDOL system produces a sequence which satisfies an infinite class of locally catenative formulas. Some of these formulas can be derived from a minimum formula, but a sequence may satisfy more than one minimum formulas.     

Representation theorems using DOS languages

It is demonstrated that every context-free language is a homomorphic image of the intersection of two DOS languages and that every recursively enumerable language is the homomorphic image of the intersection of three DOS languages. It is also proved that by increasing the number of components in the intersections of DOS languages one gets an infinite hierarchy of classes of languages within the class of context-sensitive languages.     

Educating patients about the benefits and drawbacks of hormone replacement therapy

Transthoracic Doppler echocardiography was used to evaluate the technique of measuring and normal patterns of pulmonary venous flow in fourteen normal dogs. Polyphasic pulmonary venous flow profiles were obtained in all dogs, consisting of one (S) or two (SE and SL) systolic forward flow waves, one early diastolic forward flow wave (D), one reverse flow wave (R) related to atrial contraction, and one reverse flow wave (R2) observed after cessation of systolic flow. Pulmonary venous flow was laminar in 9 dogs (65%). Maximal flow velocity during systole (0.39 +/- 0.14 m/sec) was significantly lower (P < 0.01) than in early diastole (0.56 +/- 0.14 m/sec). During late diastole peak flow velocity was 0.20 +/- 0.08 m/sec and maximum R2 velocity was 0.17 +/- 0.05 m/sec. Duration of mitral A-wave was significantly greater (P < 0.05) than R-wave duration in all dogs (0.075 +/- 0.010 vs 0.058 +/- 0.012 sec). These results can be used for comparison with patterns found in disease states.