How to Build a Library Bookmas Tree

Step by step instructions on how to build a Christmas tree out of library books. A Bookmas tree!

CHROMOSOMAL MAPPING, LINKAGE RELATIONSHIPS, AND EVOLUTIONARY STUDIES OF THE HUMAN ANONYMOUS DNA CLONE D1S1 (IN SITU HYBRIDIZATION, PRIMATES, GENE MAPPING, AUTOSOMAL DOMINANT RETINITIS PIGMENTOSA, GENE DUPLICATION)

D1S1, an anonymous human DNA clone originally called (lamda)Ch4-H3 or (lamda)H3, was the first single copy mapped to a human chromosome (1p36) by in situ hybridization. The chromosomal assignment has been confirmed in other laboratories by repeating the in situ hybridization but not by another method. In the present study, hybridization to a panel of hamster-human somatic cell hybrids revealed copies of D1S1 on both chromosomes 1 and 3. Subcloning D1S1 showed that the D1S1 clone itself is from chromosome 3, and the sequence detected by in situ hybridization is at least two copies of part of the chromosome 3 copy. This finding demonstrates the importance of verifying gene mapping with two methods and questions the accuracy of in situ hybridization mapping.^ Non-human mammals have only one copy of D1S1, and the non-human primate D1S1 map closely resembles the human chromosome 3 copy. Thus, the human chromosome 1 copies appear to be part of a very recent duplication that occurred after the divergence between humans and the other great apes.^ A moderately informative HindIII D1S1 RFLP was mapped to chromosome 3. This marker and 12 protein markers were applied to a linkage study of autosomal dominant retinitis pigmentosa (ADRP). None of the markers proved linkage, but adding the three families examined to previously published data raises the ADRP:Rh lod score to 1.92 at (THETA) = 0.30. ^

Roles of IkappaB kinase alpha in centrosome duplication and skin carcinogenesis

IκB kinase α (IKKα) is one kinase subunit of the IKK complex that is responsible for NF-κB activation. Previous studies have shown that IKKα determines mouse keratinocyte terminal differentiation independent of the NF-κB pathway. Accumulating evidence suggests that IKKα functions as a tumor suppressor in skin carcinogenesis; however, the downstream pathways mediating this function are largely unknown. By using primary cultured keratinocytes, we found that Ikkα-/- cells developed aneuploidy and underwent spontaneous immortalization and transformation while wild type cells underwent terminal differentiation in the same culture condition. Using proteomic analysis we identified nucleophosmin (NPM), a centrosome duplication regulator, as an IKKα substrate. We further demonstrated that IKKα interacted with NPM and colocalized with NPM on the centrosome, suggesting that NPM is a physiological substrate of IKKα. Loss of IKKα reduced centrosome-bound NPM and promoted abnormal centrosome amplification, which contributed to aneuploidy development. Detailed analysis revealed that ablation of IKKα target site serine-125 of NPM induced destabilization of NPM hexamers, disrupted NPM association with centrosomes, and resulted in abnormal centrosome amplification. Re-introduction of IKKα rescued the defect in Ikkα-/- keratinocytes. Thus, IKKα is required for maintaining proper centrosome duplication by phosphorylating NPM. ^ UV is the major etiological agent for human skin cancer and UV-induced mouse skin carcinogenesis is one of the most relevant experimental models for human skin carcinogenesis. Thus, we further evaluated IKKα function in UV-induced skin carcinogenesis in Ikkα+/- mice. We demonstrated that IKKα is also critical in UV skin carcinogenesis, as evidenced by increased tumor multiplicity and reduced tumor latency in Ikkα+/- mice after chronic UVB treatment. Reduced expression of IKKα decreased UV-induced apoptosis and promoted accumulation of P53 mutations in the epidermis. This indicates that IKKα is critical for UV-induced apoptosis in vivo and thus prevents mutation accumulation that is important for tumor development. ^ Together, these findings uncover previously unknown in vivo functions of IKKα in centrosome duplication and apoptosis, thus providing a possible mechanism of how loss of IKKα may contribute to skin carcinogenesis. ^

Molecular and evolutionary genetics of the X -linked visual pigment genes in humans and New World monkeys

Normal humans have one red and at least one green visual pigment genes. These genes are tightly linked as tandem repeats on the X chromosome and each of them has six exons. There is only one X-linked visual pigment gene in New World monkeys (NWMs) but the locus has three polymorphic alleles encoding red, yellow and green visual pigments, respectively. The spectral properties of the squirrel monkey and the marmoset (both NWMs) have been studied and partial sequences of the three alleles are available. To study the evolutionary history of these X-linked opsin genes in humans and NWMs, coding and intron sequences of the three squirrel monkey alleles and the three marmoset alleles were amplified by PCR followed by subcloning and sequencing. Introns 2 and 4 of the human red and green pigment genes were also sequenced. The results obtained are as follows: (1) The sequences of introns 2 and 4 of the human red and green opsin genes are significantly more similar between the two genes than are coding sequences, contrary to the usual situation where coding regions are better conserved in evolution than are introns. The high similarities in the two introns are probably due to recent gene conversion events during evolution of the human lineage. (2) Phylogenetic analysis of both intron and exon sequences indicates that the phylogenetic tree of the available primate opsin genes is the same as the species tree. The two human genes were derived from a gene duplication event after the divergence of the human and NWM lineages. The three alleles in each of the two NWM species diverged after the split of the two NWMs but have persisted in the population for at least 5 million years. (3) Allelic gene conversion might have occurred between the three squirrel monkey alleles. (4) A model of additive effect of hydroxyl-bearing amino acids on spectral tuning is proposed by treating some unknown variables as groups. Under the assumption that some residues have no effect, it is found that at least five amino acid residues, at positions 178 (3 nm), 180 (5 nm), 230 ($-$4 nm), 277 (9 nm) and 285 (13 nm), have linear spectral tuning effects. (5) Adaptive evolution of the opsin genes to different spectral peaks was observed at four residues that are important for spectral tuning. ^