No abstract

Most protein in hair and wool is of two broad types: keratin intermediate filament-forming proteins (commonly known as keratins) and keratin-associated proteins (KAPs). Keratin nomenclature was reviewed in 2006, but the KAP nomenclature has not been revised since 1993. Recently there has been an increase in the number of KAP genes (KRTAPs) identified in humans and other species, and increasingly reports of variation in these genes. We therefore propose that an updated naming system is needed to accommodate the complexity of the KAPs. It is proposed that the system is founded in the previous nomenclature, but with the abbreviation sp-KAPm-nL*x for KAP proteins and sp-KRTAPm-n(p/L)*x for KAP genes. In this system “sp” is a unique letter-based code for different species as described by the protein knowledge-based UniProt. “m” is a number identifying the gene or protein family, “n” is a constituent member of that family, “p” signifies a pseudogene if present, “L” if present signifies “like” and refers to a temporary “place-holder” until the family is confirmed and “x” signifies a genetic variant or allele. We support the use of non-italicised text for the proteins and italicised text for the genes.This nomenclature is not that different to the existing system, but it includes species information and also describes genetic variation if identified, and hence is more informative. For example, GenBank sequence JN091630 would historically have been named KRTAP7-1 for the gene and KAP7-1 for the protein, but with the proposed nomenclature would be SHEEP-KRTAP7-1*A and SHEEP-KAP7-1*A for the gene and protein respectively. This nomenclature will facilitate more efficient storage and retrieval of data and define a common language for the KAP proteins and genes from all mammalian species.

Tibetan is a valuable Himalayan sheep breed classified as endangered. Knowledge of the level and distribution of genetic diversity in Tibetan sheep is important for designing conservation strategies for their sustainable survival and to preserve their evolutionary potential. Thus, for the first time, genetic variability in the Tibetan population was accessed with twenty five inter-simple sequence repeat markers. All the microsatellites were polymorphic and a total of 148 alleles were detected across these loci. The observed number of alleles across all the loci was more than the effective number of alleles and ranged from 3 (BM6506) to 11 (BM6526) with 5.920 ± 0.387 mean number of alleles per locus. The average observed heterozygosity was less than the expected heterozygosity. The observed and expected heterozygosity values ranged from 0.150 (BM1314) to 0.9 (OarCP20) with an overall mean of 0.473 ± 0.044 and from 0.329 (BM8125) to 0.885 (BM6526) with an overall mean 0.672 ± 0.030, respectively. The lower heterozygosity pointed towards diminished genetic diversity in the population. Thirteen microsatellite loci exhibited significant (P < 0.05) departures from the Hardy–Weinberg proportions in the population. The estimate of heterozygote deficiency varied from − 0.443 (OarCP20) to 0.668 (OarFCB128) with a mean positive value of 0.302 ± 0.057. A normal ‘L’ shaped distribution of mode-shift test and non-significant heterozygote excess on the basis of different models suggested absence of recent bottleneck in the existing Tibetan population. In view of the declining population of Tibetan sheep (less than 250) in the breeding tract, need of the hour is immediate scientific management of the population so as to increase the population hand in hand with retaining the founder alleles to the maximum possible extent.

The highly co-evolved relationship of parasites and their hosts appears to include modulation of host immune signals, although the molecular mechanisms involved in the host-parasite interplay remain poorly understood. Characterization of these key genes and their cognate proteins related to the host-parasite interplay should lead to a better understanding of this intriguing biological phenomenon. The malaria agent Plasmodium falciparum is predicted to export a cohort of several hundred proteins to remodel the host erythrocyte. However, proteins actively exported by the asexual intracellular parasite beyond the host red blood cell membrane (before merozoite egress) have been poorly investigated so far. Here we used two complementary methodologies, two-dimensional gel electrophoresis/MS and LC-MS/MS, to examine the extracellular secreted antigens at asexual blood stages of P. falciparum. We identified 27 novel antigens exported by P. falciparum in the culture medium of which some showed clustering with highly polymorphic genes on chromosomes, suggesting that they may encode putative antigenic determinants of the parasite. Immunolocalization of four novel secreted proteins confirmed their export beyond the infected red blood cell membrane. Of these, preliminary functional characterization of two novel (Sel1 repeat-containing) parasite proteins, PfSEL1 and PfSEL2 revealed that they down-regulate expression of cell surface Notch signaling molecules in host cells. Also a novel protein kinase (PfEK) and a novel protein phosphatase (PfEP) were found to, respectively, phosphorylate/dephosphorylate parasite-specific proteins in the extracellular culture supernatant. Our study thus sheds new light on malaria parasite extracellular secreted antigens of which some may be essential for parasite development and could constitute promising new drug targets. Molecular & Cellular Proteomics 8:2102-2118, 2009.

Genetic diversity of Magra -a lustrous carpet wool breed of India, was investigated by means of 25 ovine microsatellite markers proposed by the Food and Agriculture Organization and the International Society for Animal Genetics (FAO-ISAG). All used microsatellites amplified well and exhibited polymorphisms. A wide range of genetic variability was observed as allele number from 3 (BM6506, OarCP20) to 10 (CSSM31), observed heterozygosity from 0.200 (BM6506) to 0.947 (OarHH35), expected heterozygosity from 0.368 (CSSM47) to 0.864 (BM1314) and Polymorphism Information Content (PIC) from 0.347 (CSSM47) to 0.849 (BM1314). This supported the utility of these microsatellite loci in the measurement of genetic diversity indices in Indian sheep too. Various average genetic variability measures viz., allele diversity (5.7), observed heterozygosity (0.597), expected heterozygosity (0.694) and mean PIC (0.648) values showed high genetic variability despite accumulated inbreeding as reflected by the high average inbreeding coefficient (F IS = 0.159) due to the unequal sex ratio of the breeding animals.

The genetic diversity in two buffalo populations of northern India, the Bhadawari and the Tarai was assessed using a set of 22 heterologous (bovine) microsatellite markers. The average number of alleles across all loci in both populations was found to be 4.7, indicating that this set of 22 bovine microsatellite markers could be used to study genetic variation in buffalo species also. The overall polymorphic information content (PIC) value for these markers was 0.54. The average observed and expected heterozygosities for both populations were 0.59 and 0.64, respectively. Common alleles with varying allele frequencies in both populations also represented the genetic variability existing between Bhadawari and Tarai buffaloes. However the h estimates for population differentiation indicated low levels of differentiation between the two populations. This was further supported by the low genetic distance (0.155) between Bhadawari and Tarai, which was calculated using Nei's standard genetic distance method. The present study on Bhadawari and Tarai populations represents a much-needed preliminary effort that could be extended to other local buffalo populations of India as well. Zusammenfassung Genetische Diversita¨tsstudie von zwei nordindischen Büffelpopulationen mit MikrosatellitenmarkernDie genetische Diversität in zwei nordindischen Bü ffelpopulationen, Bhadawari und Tarai wurde mit 22 heterologen-(bovinen) Mikrosatellitenmarkern geschätzt. Die durchschnittlich geschätzte Allelzahl ü ber alle Genorte in beiden Populationen betrug 4,7 und zeigt, dass diese 22 bovine Mikrosatellitenmarker auch benutzt werden kö nnen, um die genetische Variabilität von Bü ffeln zu studieren. Der gesamte ÔÔPolymorphic Information ContentÕÕ (PIC) fü r diese Marker war 0,54. Die durchschnittlichen beobachteten und erwarteten Heterozygotiewerte fü r beide Populationen waren 0,59 beziehungsweise 0,64. Gemeinsame Allele mit unterschiedlichen Frequenzen in beiden Populationen stellten auch die genetische Variabilität dar, die zwischen Bhadawari und Tarai Bü ffeln besteht. Jedoch zeigten die Schätzungen fü r die Populationsdifferenzierung (h) niedrige Werte zwischen den zwei Populationen an. Dies wird auch gestü tzt durch den niedrigen genetischen Abstand (0,155) zwischen Bhadawari und Tarai, der mit Nei's-Standard genetischer Distanzmethode (Ds) berechnet wurde. Die vorliegenden Untersuchungen anhand von Bhadawari-und Tarai-Populationen stellen eine dringend benö tigte Basis dar, die auch auf andere lokale indische Bü ffelpopulationen ausgeweitet werden kö nnte.

The expression of genes and their regulation during lactation in buffaloes remains less understood. To understand the interplay of various genes and pathways, the milk transcriptome from three lactation stages of Murrah buffalo was analyzed by RNA sequencing. The filtered reads were mapped to the Bubalus bubalis as well as Bos taurus reference assemblies. The average mapping rate to water buffalo and Btau 4.6 reference sequence, was 75.5% and 75.7% respectively. Highly expressed genes (RPKM > 3000), throughout lactation included CSN2, CSN1S1, CSN3, LALBA, SPP1 and TPT1. A total of 12833 transcripts were common across all the stages, while 271, 205 and 418 were unique to early, mid and late lactation respectively. Majority of the genes throughout lactation were linked to biological functions like protein metabolism, transport and immune response. A discernible shift from metabolism in early stage to metabolism and immune response in mid stage, and an increase in immune response functions in late lactation was observed. The results provide information of candidate genes and pathways involved in the different stages of lactation in buffalo. The study also identified 14 differentially expressed and highly connected genes across the three lactation stages, which can be used as candidates for future research.

A new class of potent PI3Kα inhibitors is identified based on aryl substituted morpholino-triazine scaffold. The identified compounds showed not only a high level of enzymatic and cellular potency in nanomolar range but also high oral bioavailability. The three lead molecules (based on their in vitro potency) when evaluated further for in vitro metabolic stability as well as pharmacokinetic profile led to the identification of 26, as a candidate for further development. The IC50 and EC50 value of 26 is 60 and 500 nM, respectively, for PI3Kα enzyme inhibitory activity and ovarian cancer (A2780) cell line. The identified lead also showed a high level of microsomal stability and minimal inhibition activity for CYP3A4, CYP2C19, and CYP2D6 at 10 μM concentrations. The lead compound 26, demonstrated excellent oral bioavailability with an AUC of 5.2 μM at a dose of 3 mpk in mice and found to be well tolerated in mice when dosed at 30 mpk BID for 5 days.