Computational protein design and large-scale assessment by I-TASSER structure assembly simulations

Protein design aims at designing new protein molecules of desired structure and functionality. One of the major obstacles to large-scale protein design are the extensive time and manpower requirements for experimental validation of designed sequences. Recent advances in protein structure prediction have provided potentials for an automated assessment of the designed sequences via folding simulations. We present a new protocol for protein design and validation. The sequence space is initially searched by Monte Carlo sampling guided by a public atomic potential, with candidate sequences selected by the clustering of sequence decoys. The designed sequences are then assessed by I-TASSER folding simulations, which generate full-length atomic structural models by the iterative assembly of threading fragments. The protocol is tested on 52 nonhomologous single-domain proteins, with an average sequence identity of 24% between the designed sequences and the native sequences. Despite this low sequence identity, three-dimensional models predicted for the first designed sequence have an RMSD of < 2 Å to the target structure in 62% of cases. This percentage increases to 77% if we consider the three-dimensional models from the top 10 designed sequences. Such a striking consistency between the target structure and the structural prediction from nonhomologous sequences, despite the fact that the design and folding algorithms adopt completely different force fields, indicates that the design algorithm captures the features essential to the global fold of the target. On average, the designed sequences have a free energy that is 0.39 kcal/(mol residue) lower than in the native sequences, potentially affording a greater stability to synthesized target folds.     

Seromucous anal gland in a New World hystricognath rodent Thrichomys apereoides (Lund, 1839)

New World species of the Hystricognathi comprise a group of rodents that exhibit poorly understood social behaviour. One such species, the echimyid Thrichomys apereoides, has a behavioural and social repertoire which suggests the use of its eversible anal gland in communication between individuals; however, no information on the morphology of this gland is available. In this study, the anal gland of nineteen adult individuals (11 males and 8 females) was analysed through histological and histochemical techniques. The gland was located in the submucosal of the anal region, cranial to the anus, and had an opening located dorsally in the rectum mucosa at approximately 1 mm from the anus. The gland was characterized as seromucous, secreting neutral glycoprotein. Not all individuals studied presented secretion in the glandular ducts, indicating a possible functional variation in the gland. This was the first record of an anal gland of the seromucous type in rodents.     

Impact of the Três Marias dam on the reproduction of the forage fish Astyanax bimaculatus and A. fasciatus from the São Francisco River,downstream from the dam,southeastern Brazil

Alterations to the hydrologic regime downstream from hydroelectric dams include thermal disturbances which may have an impact on the reproductive success of fish. In order to make a comparative analysis of forage fish reproduction in two sections of the São Francisco River downstream from the Três Marias hydroelectric power plant, we captured 606 specimens of Astyanax fasciatus (n?=?465) and A. bimaculatus (n?=?141) at 2-month intervals between November 2009 and October 2010. Fish were captured in two sections of the São Francisco River: section 1, encompassing the first 34 km immediately downstream from the dam; section 2, after the confluence with the Abaeté River, 34–54 km downstream from the dam. The canonical correlation test indicated that for both species, female reproduction is more dependent on environmental factors than male reproduction. Compared to section 1, the specimens captured in section 2 were more abundant and the females of both species presented larger total length, body weight, gonadosomatic index and fecundity values. Higher values of water temperature, dissolved oxygen and turbidity during the rainy season (September to February) were also recorded for section 2, when compared to section 1 where the physical–chemical conditions of the water do not favour reproduction. Based on this analysis of reproductive parameters, this study shows, for the first time, that the reproductive activity of two species of forage fishes, A. fasciatus and A. bimaculatus, from the section of the São Francisco River immediately downstream from the Três Marias dam is disrupted and that the Abaeté River is an important tributary for the reproductive success of these species.     

Male reproductive system in the South American catfish Conorhynchus conirostris

The testes of the catfish Conorhynchus conirostris ( n  = 67) from the São Francisco River, Minas Gerais, Brazil were of the fringed type, similar to those of some Pimelodidae. The germ, Sertoli and Leydig cells showed characteristics which are general for all vertebrates although the spermatozoa had a peculiar morphology, with an ovoid head without an acrosome, inverted U‐shaped nucleus, a short midpiece and a long tail, typical of teleosts showing external fertilization. The spermatic duct and genital papilla performed a secretory function.     

Ultrasound promoted synthesis of 2-imidazolines in water: A greener approach toward monoamine oxidase inhibitors

A series of sixteen 2-substituted-2-imidazolines (where the substituent R = Ph, Me-4-Ph; MeO-4-Ph; (MeO)₂-3,4-Ph; (MeO)₃-3,4,5-Ph; Ph-4-O-C(O)-Ph; Cl-4-Ph; Cl-2-Ph; Cl₂-2,4-Ph; NO₂-4-Ph; NO₂-3-Ph; Naphth-2-yl; Fur-2-yl; Benzofur-2-yl; Pyridin-2-yl; Quinolin-2-yl) has been synthesized from the reaction of the substituted-aldehydes and ethylenediamine by ultrasound irradiation with NBS in an aqueous medium in high yields (80–99%). The 2-imidazoline ability to inhibit the activity of the A and B isoforms of monoamine oxidase (MAO) was investigated and some of them showed potent and selective MAO inhibitory activity especially for the MAO-B isoform and could become promising candidates for future development.