Identification of mongoose (genus: Herpestes) species from hair through band pattern studies using discriminate functional analysis (DFA) and microscopic examination.

India is home to seven species of mongoose (Herpestes sp). Mongooses are being poached primarily for their hair, which is used in the production of painting and shaving brushes. Prior to September 2002, mongooses were listed under Schedule-IV of the Wildlife (Protection) Act 1972 (India). Indiscriminate poaching of the mongoose created an immediate threat to their survival and hence mongooses have now been placed under Schedule-II of the Wildlife (Protection) Act-1972 (India). In order to convict a person under this legislation, species identification of case related samples is necessary. Four species of mongoose i.e. H. edwardsii, H. smithii, H. palustris and H. urva were characterised by performing discriminate functional analysis (DFA) on measurements of their dorsal guard hair banding pattern and by microscopic hair characteristics (Cuticular, medullar and cross section). It was possible to distinguish between the four species studied, based on both these methods.

Synthesis and pharmacological characterization of ethylenediamine synthetic opioids in human µ-opiate receptor 1 (OPRM1) expressing cells.

Opioids are powerful analgesics acting via the human µ-opiate receptor (hMOR). Opioid use is associated with adverse effects such as tolerance, addiction, respiratory depression, and constipation. Two synthetic opioids, AH-7921 and U-47700 that were developed in the 1970s but never marketed, have recently appeared on the illegal drug market and in forensic toxicology reports. These agents were initially characterized for their analgesic activity in rodents; however, their pharmacology at hMOR has not been delineated. Thus, we synthesized over 50 chemical analogs based on core AH-7921 and U-47700 structures to assess for their ability to couple to Gαi signaling and induce hMOR internalization. For both the AH-7921 and U-47700 analogs, the 3,4-dichlorobenzoyl substituents were the most potent with comparable EC50 values for inhibition of cAMP accumulation; 26.49 ± 11.2 nmol L-1 and 8.8 ± 4.9 nmol L-1, respectively. Despite similar potencies for Gαi coupling, these two compounds had strikingly different hMOR internalization efficacies: U-47700 (10 µmol L-1) induced ~25% hMOR internalization similar to DAMGO while AH-7921 (10 µmol L-1) induced ~5% hMOR internalization similar to morphine. In addition, the R, R enantiomer of U-47700 is significantly more potent than the S, S enantiomer at hMOR. In conclusion, these data suggest that U-47700 and AH-7921 analogs have high analgesic potential in humans, but with divergent receptor internalization profiles, suggesting that they may exhibit differences in clinical utility or abuse potential.

Hair characteristics of four Indian bear species.

Dorsal guard hairs of four species of bear (family: Ursidae) found in India were characterized using light microscopy by studying features including colour, hair thickness, cuticle pattern, medulla pattern, medullary index, cross-section and scale count index. The gross cuticular pattern was quite similar for the four species but a distinct difference was observed in the scale count index. Medulla type was narrow and amorphous with a very low medullary index (< 0.15) except for brown bear which showed a comparatively higher medullary index (0.38) and a vacuolated medulla. By combining together the parameters mentioned above it was possible to characterize bear species on the basis of their hair characteristics.

The effect of Pro(2) modifications on the structural and pharmacological properties of endomorphin-2.

Endomorphins (EM-1 and EM-2) are selective, high affinity agonists of the µ-opioid (MOP) receptor, an important target in pain regulation. Their clinical use is impeded by their poor metabolic stability and limited entry to the central nervous system. In this study, the Pro(2) residue of EM-2 was modified systematically through substitution by hydroxyproline (Hyp), (S)-ß-homoproline (ßPro), 2-aminocyclopentene-1-carboxylic acid (ΔAcpc), or 2-aminocyclohexene-1-carboxylic acid (ΔAchc) to obtain stable MOP active compounds. Both Hyp(2) and ßPro(2) substitution decreased receptor affinity. Analogues incorporating alicyclic ß-amino acids exhibited diverse receptor binding properties, depending on the configuration of the substituent side-chain. (1S,2R)ΔAcpc(2)-EM-2 was shown to have MOP affinity and selectivity comparable to those of EM-2 and proved to act as agonist while being resistant to proteolysis. NMR and molecular dynamics (MD) studies revealed that bent backbone structures are predominant in the most potent analogues, while their presence is less pronounced in ligands of lower receptor affinity.

Asymmetric synthesis and conformational analysis by NMR spectroscopy and MD of Aba- and α-MeAba-containing dermorphin analogues.

Dermorphin analogues, containing a (S)- and (R)-4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one scaffold (Aba) and the α-methylated analogues as conformationally constrained phenylalanines, were prepared. Asymmetric phase-transfer catalysis was unable to provide the (S)-α-Me-o-cyanophenylalanine precursor for (S)-α-MeAba in acceptable enantiomeric purity. However, by using a Schöllkopf chiral auxiliary, this intermediate was obtained in 88 % ee. [(S)-Aba 3-Gly 4]dermorphin retained µ-opioid affinity but displayed an increased δ-affinity. The corresponding R epimer was considerably less potent. In contrast, the [(R)-α-MeAba 3-Gly 4]dermorphin isomer was more potent than its S epimer. Tar-MD simulations of both non-methylated [Aba 3-Gly 4]dermorphin analogues showed a degree of folding at the C-terminal residues toward the N terminus of the peptide, without however, adopting a stabilized ß-turn conformation. The α-methylated analogues, on the other hand, exhibited a type I/I' ß-turn conformation over the α-MeAba 3 and Gly 4 residues, which was stabilized by a hydrogen bond involving Tyr 5-HN and D-Ala 2-CO.

Microscopic hair characteristics of a few bovid species listed under Schedule-I of Wildlife (Protection) Act 1972 of India.

Dorsal guard hairs of 10 bovid species of India, listed under Schedule-I of Wildlife (Protection) Act 1972 of India and some of them quite frequently encountered in illegal trade, were studied using light microscopy. We discuss characteristics including colour, hair thickness, cuticular pattern, medulla pattern, medulla index, cross-section and scale count index for species characterisation/identification to deal wildlife offence cases. Although some species could be identified very easily based on one or few microscopic hair characteristics, however there were some overlaps of few hair characteristics among some species. Species like Pantholops hodgsonii could be characterised most easily, just based on cuticular pattern and similarly Capricornis sumatraensis could be characterised simply by medulla pattern. For species showing overlaps in some of the microscopic hair characteristics, a combination of all the characteristics was most useful. We suggest the use of maximum number of parameters for distinguishing sympatric and closely related species. In addition to wild species, hair characteristics of three domestic species have been examined and compared with the selected wild species.