Poliovirus mutant that contains a cold-sensitive defect in viral RNA synthesis

By manipulating an infectious cDNA clone of poliovirus, we have introduced a single-codon insertion into the 3A region of the viral genome which has been proposed to encode a functional precursor of the virion-linked protein VPg. The resulting mutant was cold sensitive in monkey kidney cells. Viral RNA synthesis was poor at 32.5 degrees C, although no other function of the virus was obviously affected. The synthesis of both positive and negative strands was severely depressed. Temperature shift experiments suggest that a normal level of production of the affected function was required only during the early (exponential) phase of RNA synthesis. Analysis of viral polyprotein processing at the nonpermissive temperature revealed that some of the normal cleavages were not made, most likely as a consequence of the defect in RNA synthesis or as a result of the concomitant reduction in the level of virally encoded proteases

The Role of DNA Repair and the Epigenetic Markers Left after Repair in Neurologic Functions, Including Memory and Learning

In eukaryotic cell nuclei, DNA is wrapped around and firmly associated with histone proteins, forming chromatin. When DNA is damaged, the chromatin structure needs to be loosened to allow repair enzymes to gain access to the damage. This requires modifying the histone proteins. These modifications, called epigenetic alterations, do not alter the base-pair sequence. Repair-associated epigenetic alterations are usually transient, removed when no longer needed for repair. However, some remain after repair. In the human brain, long-lasting novel epigenetic alterations appear to account for the persistence of addictions to such substances as alcohol, nicotine and cocaine. Certain neurodegenerative diseases are caused by inherited mutations in genes necessary for DNA repair. Deficient DNA repair in these diseases is associated with extensive epigenetic alterations that likely have a role in the disease phenotype. Persistent epigenetic alterations due to DNA repair processes, both histone modifications and methylations of DNA, can also have positive consequences. Stimulation of brain activity (e.g. learning and memory formation) is often accompanied by the generation of DNA damage in neuronal DNA, followed by repair associated with persistent epigenetic alterations. In particular, recent research has shown the need for non-homologous end joining and base excision repair in memory formation

Sexual Processes in Microbial Eukaryotes

Two principal ideas have been proposed to explain the primary adaptive function of the sexual process of meiosis: (1) meiosis, and particularly meiotic recombination, is a process for repairing DNA and (2) meiosis, by means of meiotic recombination, is a process for generating beneficial genetic variation among progeny. We review the sexual processes of a number of well-studied microbial eukaryotes: Saccharomyces cerevisiae, Saccharomyces paradoxus, Schizosaccharomyces pombe, Candida albicans, Ustilago maydis, Paramecium tetraurelia, Volvox carteri, Trypanosoma brucei, Neurospora crassa, and Amoebozoa. We indicate aspects of the sexual processes of these microbial eukaryotes, where they have been established, that support the idea that meiosis is primarily a process for repairing DNA. In addition, we review the likely origin of meiotic sex among the microbial eukaryotes. A prokaryotic archaeon is the likely ancestor of eukaryotes. Extant archaea are capable of a sexual process involving syngamy and recombinational repair of genome damage, suggesting that the precursor of eukaryotic meiotic sex may already have been present in the archaeal ancestor of eukaryotes. We believe that attainment of an understanding of the adaptive function of meiotic sex in microbial eukaryotes is of considerable importance since it will likely apply to meiotic sex in eukaryotes generally

Demethylation in Early Embryonic Development and Memory

DNA repair processes arose early in evolution. During evolution, DNA base excision repair apparently acquired additional roles in demethylation of cytosines in DNA. Demethylation is central to two mammalian fundamental processes. Embryonic reprogramming and neuronal memory require rapid gene expression alterations depending in part on demethylations. The active demethylation reactions in both processes primarily depend, first, on the family of 5-methylcytosine oxidases sharing the acronym ten-eleven translocation (TET methylcytosine dioxygenases) and, second, on DNA base excision repair enzymes. In mice, within 6 h of fertilization, the paternal chromosomes are close to 100% actively demethylated through TET and repair activity. (Methylation of maternal DNA is blocked during subsequent cycles of replication, so methyl groups on maternal DNA, passively, becomes highly diluted over the next 4 days.) Rats subjected to one instance of contextual fear conditioning create an especially strong long-term memory. At 24 h after training, 9.2% of the genes in the rat genomes of hippocampus neurons are differentially methylated, including over 500 genes with demethylation. The emergence of embryonic development in evolution depended on preexisting DNA methylation/demethylation pathways to modify gene expression. The further emergence of memory likely evolved from the earlier set of methylation/demethylation capabilities associated with embryonic development

Measurements of B → D(∗)−,0D(∗)+,0K+π− Branching Fractions in the K∗0 Mass Window

This thesis presents measurements of 11 branching fractions of the form B →D(∗)−,0D(∗)+,0K+π− within the K∗0 mass window using LHCb data taken in 2016, 2017 and 2018. All 11 branching fractions are measured simultaneously and are reported alongside the covariance and correlation matrices for the final measurement

Level structures on the Weierstrass family of cubics

Let W -> A^2 be the universal Weierstrass family of cubic curves over C. For each N >= 2, we construct surfaces parametrizing the three standard kinds of level N structures on the smooth fibers of W. We then complete these surfaces to finite covers of A^2. Since W -> A^2 is the versal deformation space of a cusp singularity, these surfaces convey information about the level structure on any family of curves of genus g degenerating to a cuspidal curve. Our goal in this note is to determine for which values of N these surfaces are smooth over (0,0). From a topological perspective, the results determine the homeomorphism type of certain branched covers of S^3 with monodromy in SL_2(Z/N).Comment: LaTeX, 12 pages; added section giving a topological interpretation of the result

Analytical and experimental investigation of a 1/8-scale dynamic model of the shuttle orbiter. Volume 3A: Supporting data

For abstract, see N75-15681