Mitochondrial DNA variations associated with recurrent pregnancy loss among Indian women

Several genetic factors have been found to be associated with recurrent pregnancy loss (RPL). However, not many attempts have been made to associate the mitochondrial DNA (mtDNA) variations with RPL. Therefore, we have analyzed the complete mtDNA of 100 women with RPL and 12 aborted fetal tissues. Our analysis revealed a total of 681 variations, most of which were in NADH Dehydrogenase (ND) genes that encode mitochondrial enzyme Complex I. Presence of T4216C variation (ND1 gene) in 9% of the RPL women and several pathogenic, and novel mutations suggest the role of mtDNA variations in RPL.     

Conservatism and Adaptability during Squirrel Radiation: What Is Mandible Shape Telling Us?

Both functional adaptation and phylogeny shape the morphology of taxa within clades. Herein we explore these two factors in an integrated way by analyzing shape and size variation in the mandible of extant squirrels using landmark-based geometric morphometrics in combination with a comparative phylogenetic analysis. Dietary specialization and locomotion were found to be reliable predictors of mandible shape, with the prediction by locomotion probably reflecting the underlying diet. In addition a weak but significant allometric effect could be demonstrated. Our results found a strong phylogenetic signal in the family as a whole as well as in the main clades, which is in agreement with the general notion of squirrels being a conservative group. This fact does not preclude functional explanations for mandible shape, but rather indicates that ancient adaptations kept a prominent role, with most genera having diverged little from their ancestral clade morphologies. Nevertheless, certain groups have evolved conspicuous adaptations that allow them to specialize on unique dietary resources. Such adaptations mostly occurred in the Callosciurinae and probably reflect their radiation into the numerous ecological niches of the tropical and subtropical forests of Southeastern Asia. Our dietary reconstruction for the oldest known fossil squirrels (Eocene, 36 million years ago) show a specialization on nuts and seeds, implying that the development from protrogomorphous to sciuromorphous skulls was not necessarily related to a change in diet.     

Middle Miocene tragulid remains from Abocador de Can Mata: The earliest record of Dorcatherium naui from Western Europe

In the past, the tragulid species Dorcatherium crassum has been considered a synonym of Dorcatherium naui, although they are currently considered distinct species. The former has an exclusively Aragonian (MN4 to MN6) stratigraphic range, whereas D. naui is considered a typically Vallesian species (MN9 and MN10) that survives until the Turolian (MN11). There are only a few previous citations of Dorcatherium from the European latest Aragonian (MN7+8), and only that of Przeworno (Poland) can be securely attributed to D. naui. Here we describe dentognathic and postcranial remains of Dorcatherium from several localities from the stratigraphic series of the Abocador de Can Mata (ACM), in els Hostalets de Pierola (Vallès-Penedès Basin, Catalonia, Spain). These Dorcatherium remains, from both the lower (ca. 11.9-12.5 Ma, MN7) and upper (ca. 11.6 Ma, MN8) portions of the ACM series, constitute the earliest record of D. naui from the Iberian Peninsula and Western Europe. They most closely resemble D. naui from the Vallesian, but still share several features with D. crassum. On the basis of the unique combination of features displayed by the ACM material, a new subspecies, D. naui meini is erected. Its distinct status from the nominotypical subspecies, D. naui naui, is reinforced by the chronological differences between the two taxa. The morphological similarities between Dorcatherium and the extant water chevrotain (Hyemoschus aquaticus) tentatively suggest the presence of forested and humid paleoenvironments in this area of the Vallès-Penedès Basin during the latest Aragonian. Nevertheless, Dorcatherium is very rare in ACM and displays a very patchy chronological distribution. Together with the similarly spotty distribution of both primates and castorids along the ACM series, this suggests that very humid conditions might have been only intermittently present in this area throughout the latest Aragonian.     

Biochronological, taphonomical, and paleoenvironmental background of the fossil great ape Pierolapithecus catalaunicus (Primates, Hominidae)

The Late Aragonian (late middle Miocene) stratigraphic sequence of Abocador de Can Mata (ACM) from Els Hostalets de Pierola (Vallès-Penedès Basin, Catalonia, Spain), rich in fossil vertebrate localities, provides a unique opportunity to study the evolution of western Eurasian hominoids. Among these sites, Barranc de Can Vila 1 (BCV1) recently delivered a well-preserved hominoid partial skeleton of a new genus and species, Pierolapithecus catalaunicus. On the basis of the small-mammal fauna recovered at BCV1, we infer an early MN 7+8 age, between 12.5 and 12Ma, for this site. The spatial distribution of macromammal fossils, the relative abundances of skeletal elements, and their state of preservation suggest that different agents were involved in the accumulation of the P. catalaunicus individual and the remaining taxa. Carnivore marks occur on some bones of the P. catalunicus skeleton, documenting the action of predators and/or scavengers in this case. In contrast, carnivore marks are extremely rare on other macromammal remains, which seem to be derived from adjacent alluvial-fan plain areas. The small-mammal fauna from BCV1 and the large-mammal fauna from the ACM series, indicate the presence of considerably humid and warm forest environments. The compositions of the small-mammal fauna from BCV1 and from other Late Aragonian sites from the Vallès-Penedès area are similar to those from France and central Europe. The former are clearly distinct from those of Iberian inner basins, where the environment appears to have been drier, thus precluding the dispersal of hominoids into that area.     

Predicting allergenic proteins using wavelet transform

MOTIVATION: With many transgenic proteins introduced today, the ability to predict their potential allergenicity has become an important issue. Previous studies were based on either sequence similarity or the protein motifs identified from known allergen databases. The similarity-based approaches, although being able to produce high recalls, usually have low prediction precisions. Previous motif-based approaches have been shown to be able to improve the precisions on cross-validation experiments. In this study, a system that combines the advantages of similarity-based and motif-based prediction is described. RESULTS: The new prediction system uses a clustering algorithm that groups the known allergenic proteins into clusters. Proteins within each cluster are assumed to carry one or more common motifs. After a multiple sequence alignment, proteins in each cluster go through a wavelet analysis program whereby conserved motifs will be identified. A hidden Markov model (HMM) profile will then be prepared for each identified motif. The allergens that do not appear to carry detectable allergen motifs will be saved in a small database. The allergenicity of an unknown protein may be predicted by comparing it against the HMM profiles, and, if no matching profiles are found, against the small allergen database by BLASTP. Over 70% of recall and over 90% of precision were observed using cross-validation experiments. Using the entire Swiss-Prot as the query, we predicted about 2000 potential allergens. AVAILABILITY: The software is available upon request from the authors.     

2-Hydroxy-4-methoxybenzaldehyde from Hemidesmus indicus is antagonistic to Staphylococcus epidermidis biofilm formation

Abstract

Staphylococcus epidermidis (SE) is an opportunistic nosocomial pathogen that accounts for recalcitrant device-related infections worldwide. Owing to the growing interest in plants and their secondary metabolites targeting bacterial adhesion, this study was intended to uncover the anti-biofilm potential of Hemidesmus indicus and its major constituent 2-hydroxy-4-methoxybenzaldehyde (HMB) against SE. The minimum biofilm inhibitory concentration (MBIC) of H. indicus root extract and HMB were found to be 500 and 250?µg ml^?1, respectively. The results of time-dependent biofilm inhibition and mature biofilm disruption assays confirmed that HMB targets initial cell adhesion. Furthermore, interference by HMB in the expression of adhesin genes (icaA, aap and bhp) and biofilm components was associated with an increased susceptibility of SE to oxidative stress and antibiotics. To conclude, this study reports for the first time HMB as a potential drug against SE biofilms.     

Human tumor cells, modified by a novel pressure/crosslinking methodology, promote autologous lymphocyte proliferation and modulate cytokine secretion

 Hydrostatic pressure (P) combined with membrane protein crosslinking (CL) by adenosine dialdehyde (AdA) can render tumor cells immunogenic. We have recently shown that PCL treatment of murine tumor cells augmented the presentation of MHC-restricted tumor-associated antigens and enhanced cell-mediated immunity. In cancer patients inoculated with autologous PCL-modified tumor cells, a significant delayed-type hypersensitivity response was elicited. Since the balance between cell-mediated immunity and humoral immunity is reciprocally controlled by immunoregulatory cytokines, we have examined the proliferative response and cytokine secretion pattern in cultures of human peripheral blood mononuclear cells (PBMC) stimulated by autologous PCL-modified and unmodified tumor cells. These tumor cells were obtained from freshly resected tumor tissue of 16 patients with colon (8), lung (4) and renal (4) carcinomas. The results demonstrated that PCL-modified tumor cells promoted an increase in PBMC proliferation in 5 out of 8 (63%), 1 out of 4 (25%) and 4 out of 4 (100%) colon, lung and renal cell carcinomas. Fourteen of the above cultures were also analyzed for the secretion of interleukin-10 and interferon-γ. Overall, a substantial decrease in IL-10 secretion was detected in 9 out of 14 (64%) cultures while a reciprocal increase in interferon-γ secretion was noted in 8 out of 14 (57%) cultures. Our results confirmed that PCL-modified human tumor cells of different etiologies can modulate the pattern of cytokines released from stimulated autologous lymphocytes. Such a procedure could prove valuable in the production of autologous tumor vaccines. Received: 8 January 1998 / Accepted: 9 April 1998