Exploration of a Possible Partnership among Orphan Two-Component System Proteins in Cyanobacterium Synechococcus elongatus PCC 7942

To understand the induction of the adaptive response under various stress conditions, it is important to determine the partnership between histidine kinase and response regulators in the bacterial two-component system (TCS). The genes encoding TCS partners are usually comprised of an operon in the genome, but many of them are orphans in the cyanobacterial genome. There is little information on their partnerships in Synechococcus elongatus PCC 7942. Our comprehensive analysis of protein-protein interactions among all 37 full-length proteins and the truncated domains of 24 orphans revealed a number of specific interactions. They involved evolutionarily well-conserved orphan proteins among cyanobacterial species such as Synpcc7942_0453/Ycf29, NblS/RpaB, NblS/SrrA, SasA/RpaA, and SasA/Synpcc7942_2466. Our investigation of the transphosphorylation of interaction partners indicates that orphan TCSs comprise a complex signaling network.     

Inhibitors of human 2,3-oxidosqualene cyclase (OSC) discovered by virtual screening

Five human 2,3-oxidosqualnene cyclase (OSC) inhibitors were discovered using the combination of a virtual screening based on a docking study and an isotope-free assay system. All of these inhibitors were revealed to have activities comparable or superior to that of LDAO, a known OSC inhibitor. The computational study of the newly identified inhibitors suggested that CH/π interactions with F444 and W581 contribute to the binding, and these interactions are candidates for additional structural filters in the next generation of virtual screening.     

Boundary zone between northern and southern pig-tailed macaques and their morphological differences

Based on previous conflicting reports that the two forms of pig-tailed macaque (northern and southern) exist as separate species, subspecies, or forms, and that their boundary zone lies in Thailand, a survey of the distribution range and morphology of pig-tailed macaques in Thailand was conducted during 2003–2010. We first conducted a questionnaire survey. Questionnaires were sent to 7,410 subdistricts throughout Thailand. We then traveled to 72 of the 123 subdistricts reporting the presence of pig-tailed macaques. However, due to a lack of reports of the presence of free-ranging pig-tailed macaques living south of the Isthmus of Kra, a survey of pet pig-tailed macaques was also conducted during 16–24 September 2011. Furthermore, 35 wild northern pig-tailed macaques inhabiting northern Thailand (13°13′N, 101°03′E) were temporarily caught and their morphological characters were measured and then compared to those of the southern form captured from Sumatra, Indonesia. Although largely allopatric, the ranges of the northern and southern pig-tailed macaques in Thailand were found to have a partially sympatric boundary at the Surat Thani–Krabi depression (8–9°30′N). Morphologically, these two forms were very distinctive, with different morphological characters such as the crown patch, the white color of the triangle above the eyes, the red streak at the external rim of the eyes, pelage color, ischial callosity, tail length and carriage, facial height, and limb length in both sexes, and patterns of sex skin swelling and reddening in females. These differences in morphological characters between the northern and southern forms should help settle the problems of their taxonomy.     

Morphological and Body Color Variation in Thai <Emphasis Type="Italic">Macaca fascicularis fascicularis</Emphasis> North and South of the Isthmus of Kra

Long-tailed macaques (Macaca fascicularis fascicularis) are widely distributed in Southeast Asia and are morphologically and genetically (Tosi et al. in International Journal of Primatology 23:161–178, 2002) distinguishable on either side of the Isthmus of Kra (ca. 10.5°N). We compared the somatometry and body color of 15 local populations of long-tailed macaques in Thailand distributed over areas from 6.5°N to 16.3°N and also a Thai rhesus macaque population at 17.2°N. Limb proportions and body color variation follow the geographical trend. However, contrary to a previous report, body size does not decrease with latitude in the northern group and also in the southern (southerly distributed) rhesus macaque. Relative tail length (RTL) and color contrast in yellow between the back and thigh are the sole traits that distinctively separate the 2 groups: the southern group has a long relative tail length (RTL >125%) and small color contrast, whereas the northern group has a short RTL (<120%) and large color contrast. The southern rhesus macaques appear to have somatometric and body color traits that follow the geographical trend in long-tailed macaques, though they maintain their distinctive species-specific traits of shorter RTL (ca. 55%), shorter relative facial length, and a bipartite body color pattern. Researchers assume that the northern group of long-tailed macaques and the southern rhesus macaques had undergone partial introgression with each other. Montane refugia present during the glacial period are localities in which introgression occurred in long-tailed macaques.     

Pelage Color Variation of Macaca arctoides and Its Evolutionary Implications

Stump-tailed macaques (Macaca arctoides) exhibit significant intraspecific variation in pelage color. Based on their pelage color and geographical distribution, they are classified into 2 subspecies: northern bright brown Macaca arctoides arctoides and southern black Macaca arctoides melanota. However, studies on the natural population are extremely scarce, and researchers have occasionally questioned the subspecific classification. We quantitatively examined pelage color variation of Macaca arctoides in 3 free-ranging populations in Thailand. Pelage color difference between populations is significant. The population distributed south of the Isthmus of Kra showed wide intrapopulational variation, including bright brown, dark brown, and completely black, whereas the northern populations primarily had dark brown hairs. Thus, we conclude that one cannot classify the color variants into subspecies. Further, we hypothesize that the distinctive polymorphism in southern Thailand resulted from geographical isolation caused by the Pleistocene eustatic fluctuations and subsequent recovery of land connection and subsequent gene flow.     

Functional cooperation among Ras, STAT5, and phosphatidylinositol 3-kinase is required for full oncogenic activities of BCR/ABL in K562 cells.

BCR/ABL tyrosine kinase generated from the chromosomal translocation t(9;22) causes chronic myelogenous leukemia and acute lymphoblastic leukemia. To examine the roles of BCR/ABL-activated individual signaling molecules and their cooperation in leukemogenesis, we inducibly expressed a dominant negative (DN) form of Ras, phosphatidylinositol 3-kinase, and STAT5 alone or in combination in p210 BCR/ABL-positive K562 cells. The inducibly expressed DN Ras (N17), STAT5 (694F), and DN phosphatidylinositol 3-kinase (Delta p85) inhibited the growth by 90, 55, and 40%, respectively. During the growth inhibition, the expression of cyclin D2 and cyclin D3 was suppressed by N17, 694F, or Delta p85; that of cyclin E by N17; and that of cyclin A by Delta p85. In addition, N17 induced apoptosis in a small proportion of K562, whereas 694F and Delta p85 were hardly effective. In contrast, coexpression of two DN mutants in any combinations induced severe apoptosis. During these cultures, the expression of Bcl-2 was suppressed by N17, 694F, or Delta p85, and that of Bcl-XL by N17. Furthermore, although K562 was resistant to interferon-alpha- and dexamethasone-induced apoptosis, disruption of one pathway by N17, 694F, or Delta p85 sensitized K562 to these reagents. These results suggested that cooperation among these molecules is required for full leukemogenic activities of BCR/ABL.