A comparison of populations of island and adjacent mainland species of Caribbean Selenops (Araneae: Selenopidae) spiders

The role of the landscape in structuring populations has been the focus of numerous studies, in particular, the extent to which islands provide opportunities for isolation, and the consistency of such an effect across lineages. The current study examines this phenomenon using a series of relatively widespread taxa, all within a single genus of spiders, Selenops. We focus on the Caribbean Islands and adjacent Mesoamerican mainland to examine how the islands per se dictate structure across lineages. We use molecular genetic data from mitochondrial and nuclear genes to examine the population structure of seven species of Selenops. Comparisons are made between species found in the Greater Antilles, Lesser Antilles, and adjacent mainland. Results indicate that geography has little effect on the population structure of mainland species. In contrast, population structure appears to be partitioned by island in the insular Caribbean. Within islands, the amount of population structure for each species is variable and may be dictated more by ecological or demographic parameters, rather than geographic location. The overall conclusion is that the extent to which a given lineage is structured is highly variable across species, with this variability overwhelming any general signal of geographical isolation.     

Total synthesis and biological evaluation of tambjamine K and a library of unnatural analogs

Herein we disclose the first total synthesis of tambjamine K and a library of unnatural analogs. Unnatural analogs were shown to be more potent in viability, proliferation, and invasion assays than the natural product in multiple cancer cell lines, with minimal to no cytotoxicity on non-transformed cell lines.     

Discovery of platelet-type 12-human lipoxygenase selective inhibitors by high-throughput screening of structurally diverse libraries

Human lipoxygenases (hLO) have been implicated in a variety of diseases and cancers and each hLO isozyme appears to have distinct roles in cellular biology. This fact emphasizes the need for discovering selective hLO inhibitors for both understanding the role of specific lipoxygenases in the cell and developing pharmaceutical therapeutics. To this end, we have modified a known lipoxygenase assay for high-throughput (HTP) screening of both the National Cancer Institute (NCI) and the UC Santa Cruz marine extract library (UCSC-MEL) in search of platelet-type 12-hLO (12-hLO) selective inhibitors. The HTP screen led to the characterization of five novel 12-hLO inhibitors from the NCI repository. One is the potent but non-selective michellamine B, a natural product, anti-viral agent. The other four compounds were selective inhibitors against 12-hLO, with three being synthetic compounds and one being alpha-mangostin, a natural product, caspase-3 pathway inhibitor. In addition, a selective inhibitor was isolated from the UCSC-MEL (neodysidenin), which has a unique chemical scaffold for a hLO inhibitor. Due to the unique structure of neodysidenin, steady-state inhibition kinetics were performed and its mode of inhibition against 12-hLO was determined to be competitive (K(i)=17microM) and selective over reticulocyte 15-hLO-1 (K(i) 15-hLO-1/12-hLO>30).     

A revision of the spider genus Selenops Latreille, 1819 (Arachnida, Araneae, Selenopidae) in North America, Central America and the Caribbean

The spider genus Selenops Latreille, 1819 occurs in both the Old World and New World tropics and subtropics and contains nearly half of the species in the family Selenopidae Simon, 1897. In this paper the members of the genus Selenops found in North America, Central America, and on islands of the Caribbean are revised, excluding Cuban endemics. No taxonomic changes are currently made to the species from the southwestern United States. In total, 21 new species are described, including Selenops arikoksp. n., Selenops chamelasp. n., Selenops amonasp. n., Selenops bawekasp. n., Selenops bocacanadensissp. n., Selenops enriquillosp. n, Selenops ixchelsp. n., Selenops huetocatlsp. n., Selenops kalinagosp. n., Selenops oviedosp. n., Selenops morrosp. n., Selenops deniasp. n., Selenops duansp. n., Selenops malinalxochitlsp. n., Selenops oricuajosp. n., Selenops petenajtoysp. n., Selenops guerrerosp. n., Selenops makimakisp. n., Selenops souligasp. n., Selenops wilmotorumsp. n., and Selenops wilsonisp. n. Six species names were synonymized: Selenops lunatus Muma, 1953 syn. n. =Selenops candidus Muma, 1953; Selenops tehuacanus Muma 1953 syn. n., Selenops galapagoensis Banks, 1902 syn. n. and Selenops vagabundus Kraus, 1955 syn. n. = Selenops mexicanus Keyserling, 1880; Selenops santibanezi Valdez-Mondragón, 2010 syn. n. = Selenops nigromaculatus Keyserling, 1880; and Selenops salvadoranus Chamberlin, 1925 syn. n. = Selenops bifurcatus Banks, 1909. Lectotypes are designated for the following three species: Selenops marginalis F. O. Pickard-Cambridge, 1900 (♂), Selenops morosus Banks, 1898 (♂), and Selenops mexicanus Keyserling, 1880 (♀). The female neotype is designated for Selenops aissus Walckenaer, 1837. The males of Selenops bani Alayón-García, 1992 and Selenops marcanoi Alayón-García, 1992 are described for the first time, and the females of Selenops phaselus Muma, 1953 and Selenops geraldinae Corronca, 1996 are described for the first time. Almost all species are redescribed, barring Cuban endemics and a few species recently described. New illustrations are provided, including those of the internal female copulatory organs, many of which are illustrated for the first time. A key to species is also provided as are new distributional records.     

Indolyl esters and amides related to indomethacin are selective COX-2 inhibitors

Previous studies from our laboratory have revealed that esterification/amidation of the carboxylic acid moiety in the nonsteroidal anti-inflammatory drug, indomethacin, generates potent and selective COX-2 inhibitors. In the present study, a series of reverse ester/amide derivatives were synthesized and evaluated as selective COX-2 inhibitors. Most of the reverse esters/amides displayed time-dependent COX-2 inhibition with IC₅₀ values in the low nanomolar range. Replacement of the 4-chlorobenzoyl group on the indole nitrogen with a 4-bromobenzyl moiety resulted in compounds that retained selective COX-2 inhibitory potency. In addition to inhibiting COX-2 activity in vitro, the reverse esters/amides also inhibited COX-2 activity in the mouse macrophage-like cell line, RAW264.7. Overall, this strategy broadens the scope of our previous methodology of neutralizing the carboxylic acid group in NSAIDs as a means of generating COX-2-selective inhibitors and is potentially applicable to other NSAIDs.     

Sex chromosomes and sex determination in reptiles

Reptiles occupy a crucial position with respect to vertebrate phylogeny, having roamed the earth for more than 300 million years and given rise to both birds and mammals. To date, this group has been largely ignored by contemporary genomics technologies, although the green anole lizard was recently recommended for whole genome sequencing. Future experiments using flow-sorted chromosome libraries and high-throughout genomic sequencing will help to discover important findings regarding sex chromosome evolution, early events in sex determination, and dosage compensation. This information should contribute extensively toward a general understanding of the genetic control of development in amniotes.     

New dual inhibitors of EGFR and HER2 protein tyrosine kinases

A novel series of dual EGFR and HER2 inhibitors based on the pyrrolo[2,1-f][1,2,4]triazine nucleus is described. A general route toward their synthesis, which enables functionalization at multiple sites, has been developed. Biological evaluation in enzymatic and cell-based assays has identified a series of C-6 carbamates with potent biochemical and cellular activities.     

Effects of alpha-synuclein immunization in a mouse model of Parkinson's disease

Abnormal folding of alpha-synuclein (alpha-syn) is thought to lead to neurodegeneration and the characteristic symptoms of Lewy body disease (LBD). Since previous studies suggest that immunization might be a potential therapy for Alzheimer's disease, we hypothesized that immunization with human (h)alpha-syn might have therapeutic effects in LBD. For this purpose, halpha-syn transgenic (tg) mice were vaccinated with halpha-syn. In mice that produced high relative affinity antibodies, there was decreased accumulation of aggregated halpha-syn in neuronal cell bodies and synapses that was associated with reduced neurodegeneration. Furthermore, antibodies produced by immunized mice recognized abnormal halpha-syn associated with the neuronal membrane and promoted the degradation of halpha-syn aggregates, probably via lysosomal pathways. Similar effects were observed with an exogenously applied FITC-tagged halpha-syn antibody. These results suggest that vaccination is effective in reducing neuronal accumulation of halpha-syn aggregates and that further development of this approach might have a potential role in the treatment of LBD.