A new moradisaurine captorhinid reptile (Amniota: Eureptilia) from the upper Permian of India.

Upper Permian rocks of the former supercontinent Gondwana record climax late Paleozoic terrestrial vertebrate faunas that were dominated numerically and ecologically by therapsid synapsids. Older faunal elements of earlier Paleozoic faunas, such as captorhinid reptiles, are rare and scattered components of the first amniote faunas to inhabit high-latitude regions. Here we describe a new genus and species of moradisaurine captorhinid that represents an archaic faunal element of the high-fibre herbivore fauna of the late Permian of what is now peninsular India.

The osteology of Shuvosaurus inexpectatus, a shuvosaurid pseudosuchian from the Upper Triassic Post Quarry, Dockum Group of Texas, USA.

A vast array of pseudosuchian body plans evolved during the diversification of the group in the Triassic Period, but few can compare to the toothless, long-necked, and bipedal shuvosaurids. Members of this clade possess theropod-like character states mapped on top of more plesiomorphic pseudosuchian character states, complicating our understanding of the evolutionary history of the skeleton. One taxon in this clade, Shuvosaurus inexpectatus has been assigned to various theropod dinosaur groups based on a partial skull and referred material and its postcranium was assigned to a different taxon in Pseudosuchia.

Osteology of the sauropodomorph dinosaur Jaklapallisaurus asymmetricus from the Late Triassic of central India.

The Gondwana formations exposed in the Pranhita-Godavari Valley of central India include Middle Triassic to Lower Jurassic continental deposits that provide essential information about the tetrapod assemblages of that time, documenting some of the oldest known dinosaurs and the first faunas numerically dominated by this group. The Upper Maleri Formation of the Pranhita-Godavari Basin preserves an early-middle Norian dinosaur assemblage that provides information about the early evolutionary history of this group in central-south Gondwana. This assemblage comprises sauropodomorph dinosaurs and an herrerasaurian, including two nominal species.

Cranial anatomy of Libognathus sheddi Small, 1997 (Parareptilia, Procolophonidae) from the Upper Triassic Dockum Group of West Texas, USA.

Libognathus sheddi, a leptopleuronine procolophonid from the Upper Triassic Cooper Canyon Formation, Dockum Group, West Texas, was based on an isolated left dentary and partial coronoid. New material referable to Libognathus sheddi, from the Cooper Canyon Formation, provides new information on the cranial anatomy. This new cranial material includes the antorbital portion of a skull, a left maxilla and premaxilla, quadratojugals, and dentaries, including intact tooth rows in the upper and lower jaws.

The Coevolution of Biomolecules and Prebiotic Information Systems in the Origin of Life: A Visualization Model for Assembling the First Gene.

Prebiotic information systems exist in three forms: analog, hybrid, and digital. The Analog Information System (AIS), manifested early in abiogenesis, was expressed in the chiral selection, nucleotide formation, self-assembly, polymerization, encapsulation of polymers, and division of protocells. It created noncoding RNAs by polymerizing nucleotides that gave rise to the Hybrid Information System (HIS).

A remarkable group of thick-headed Triassic Period archosauromorphs with a wide, possibly Pangean distribution.

The radiation of archosauromorph reptiles in the Triassic Period produced an unprecedented collection of diverse and disparate forms with a mix of varied ecologies and body sizes. Some of these forms were completely unique to the Triassic, whereas others were converged on by later members of Archosauromorpha. One of the most striking examples of this is with Triopticus primus, the early dome-headed form later mimicked by pachycephalosaurid dinosaurs.

The Origin of Prebiotic Information System in the Peptide/RNA World: A Simulation Model of the Evolution of Translation and the Genetic Code.

Information is the currency of life, but the origin of prebiotic information remains a mystery. We propose transitional pathways from the cosmic building blocks of life to the complex prebiotic organic chemistry that led to the origin of information systems. The prebiotic information system, specifically the genetic code, is segregated, linear, and digital, and it appeared before the emergence of DNA.

A new sauropodiform dinosaur with a 'sauropodan' skull from the Lower Jurassic Lufeng Formation of Yunnan Province, China.

The Early Jurassic Lufeng Formation of Yunnan Province in southwestern China is one of the best fossil localities in the world for understanding the early radiation of sauropodomorph dinosaurs. It has yielded a rich assemblage of complete and three-dimensionally preserved skeletons of herbivorous dinosaurs that provide crucial morphological information for systematic and evolutionary studies. Here we describe a new taxon, Yizhousaurus sunae gen.

Vegaviidae, a new clade of southern diving birds that survived the K/T boundary.

The fossil record of Late Cretaceous-Paleogene modern birds in the Southern Hemisphere includes the Maastrichtian Neogaeornis wetzeli from Chile, Polarornis gregorii and Vegavis iaai from Antarctica, and Australornis lovei from the Paleogene of New Zealand. The recent finding of a new and nearly complete Vegavis skeleton constitutes the most informative source for anatomical comparisons among Australornis, Polarornis, and Vegavis. The present contribution includes, for the first time, Vegavis, Polarornis, and Australornis in a comprehensive phylogenetic analysis.

Fossil evidence of the avian vocal organ from the Mesozoic.

From complex songs to simple honks, birds produce sounds using a unique vocal organ called the syrinx. Located close to the heart at the tracheobronchial junction, vocal folds or membranes attached to modified mineralized rings vibrate to produce sound. Syringeal components were not thought to commonly enter the fossil record, and the few reported fossilized parts of the syrinx are geologically young (from the Pleistocene and Holocene (approximately 2.

A symbiotic view of the origin of life at hydrothermal impact crater-lakes.

Submarine hydrothermal vents are generally considered as the likely habitats for the origin and evolution of early life on Earth. The theory suffers from the 'concentration problem' of cosmic and terrestrial biomolecules because of the vastness of the Eoarchean global ocean. An attractive alternative site would be highly sequestered, small, hydrothermal crater-lakes that might have cradled life on early Earth.

In search of next generation antimalarials.

Compounds 7-10 displayed potency without any apparent toxicity, in animal models of both relapsing and non-relapsing forms of malaria offering hope of a single molecule that can cure both relapsing and non relapsing forms of malaria.

Lactam and oxazolidinone derived potent 5-hydroxytryptamine 6 receptor antagonists.

Lactam and oxazolidinone derived potent 5-hydroxytryptamine 6 (5-HT6) receptor antagonists have been disclosed. One potent member from the lactam series, racemic compound 14 (Ki of 2.6 nM in binding assay, IC50 of 15 nM in functional cAMP antagonism assay) was separated into corresponding enantiomers that displayed the effect of chirality on binding potency (Ki of 1.

In search of potent 5-HT6 receptor inverse agonists.

A series of non-sulfonamide/non-sulfone derived potent 5-HT6 receptor inverse agonists has been disclosed. Representative compound 9 (Ki  = 14 nm) displayed selectivity against a set of family members as well as brain permeability 6 h post-oral administration. In addition, the separated enantiomers of compound 9 displayed difference in activity indicating the influence of chirality on potency.

1-Thia-4,7-diaza-spiro[4.4]nonane-3,6-dione: a structural motif for 5-hydroxytryptamine 6 receptor antagonism.

A series of potent 5-hydroxytryptamine 6 (5-HT₆) receptor antagonists based on 1-thia-4,7-diaza-spiro[4.4]nonane-3,6-dione motif has been disclosed. Enantiomers of potent racemate compound 8a (K(i) = 26 nM) displayed difference in activity (K(i) of 15 nM versus 855 nM) signaling the influence of the stereochemistry of the chiral center on potency.

Serendipitous discovery of a prodrug of a PARP-1 inhibitor.

During SAR development of previously reported pyrrolocarbazole 1, a potent PARP-1 inhibitor, compound 14, was discovered serendipitously to be a prodrug of compound 1.

Synthesis and activity of proteasome inhibitors.

Among its various catalytic activities, "chymotrypsin-like" activity of proteasome, a large multicatalytic proteinase complex has emerged as the focus of drug discovery efforts in cancer therapy. Herein, we report results from our investigation on a series of peptidomimetic inhibitors.

From an atypical wake-promoting agent to potent histamine-3 receptor inverse agonists.

Utilizing atypical wake-promoting agent modafinil (inactive in both rH(3) and hH(3) binding assays) as a launching pad, a series of sulfinyl- and sulfone-derived H(3) receptor inverse agonists were developed. Brain-permeable compound 27, a potent member of the series displayed excellent selectivity against related family members (H(1), H(2), and H(4) receptors).

Aryl-heteroaryl derivatives as novel wake-promoting agents.

In search of a next generation molecule to the novel wake-promoting agent modafinil, a series of aryl-heteroayl-derived wakefulness enhancing agents (in rats) was developed. From this work, compound 16 was separated into its enantiomers to profile them individually.

Wake-promoting agents: search for next generation modafinil: part IV.

In search of a next generation molecule to the novel wake promoting agent modafinil, a series of diphenyl ether derived wakefulness enhancing agents (in rat) was developed. From this work, racemic compound 16 was separated into its chiral enantiomers to profile them individually.

Wake promoting agents: search for next generation modafinil, lessons learned: part III.

In searching for a next generation molecule to the novel wake promoting agent modafinil (compound 1), a series of fluorene-derived wakefulness enhancing agents were developed and evaluated in rat. Extensive pharmacokinetic studies of a potent member of the series (compound 15) revealed that the wake promotion activity of the analog was likely due to an active metabolite (compound 3).

Serendipity in discovery of proteasome inhibitors.

Among its various catalytic activities, the 'chymotrypsin-like' activity of the proteasome, a large multicatalytic proteinase complex has emerged as the focus of drug discovery efforts in cancer therapy. Herein, a series of first generation (2S, 3R)-2-amino-3-hydroxybutyric acid derived proteasome inhibitors that were discovered serendipitously en route to original goal of generating a series of sterically constrained oxazoline derivatives has been reported.

Proteasome inhibitors for cancer therapy.

Proteasome, a large multicatalytic proteinase complex that plays an important role in processing of proteins, has been shown to possess multiple catalytic activities. Among its various activities, the 'chymotrypsin-like' activity of proteasome has emerged as the focus of drug discovery efforts in cancer therapy. Herein we report chiral boronate derived novel, potent, selective and cell-permeable peptidomimetic inhibitors 6 and 7 that displayed activity against various rodent and human tumor cell lines (in vitro).

Wake-promoting agents: search for next generation modafinil: part II.

In search of a next generation molecule to modafinil, a novel wake promoting agent, we previously disclosed bi-phenyl derived racemate compound (±)-2 as a new generation of wake-promoting agent. Here we describe the profiles of the individual enantiomers (-)-2 and (+)-2, respectively.

Novel morpholine ketone analogs as potent histamine H3 receptor inverse agonists with wake activity.

Structure-activity relationship on a novel ketone class of H(3)R antagonists/inverse agonists is disclosed. Compound 4 showed excellent target potency, selectivity and brain penetration. Evaluation of antagonist 4 in the rat EEG/EMG model demonstrated robust wake activity thereby establishing preclinical proof of concept.