Unusual chromatographic behavior of oligonucleotide sequence isomers on two different anion exchange HPLC columns

The retention behavior of the unmodified phosphodiester oligonucleotide sequence isomers was investigated on two different anion exchange columns: Biospher GMB 1000Q (based on DEAE-modified glycidyl methacrylate) and PolyWAX LP (based on silica with a crosslinked coating of linear polyethyleneimine). There was a notable difference in retention of oligonucleotides of the same composition but differing in the position of a single base. The most pronounced difference was observed between the oligonucleotides with the variable base in the end and in the center of the sequence. The use of either acetonitrile or 2-propanol as a mobile phase organic modifier did not markedly affect the retention time patterns. Prediction of the retention times of oligonucleotides must take into account the base position as well as identity. This is the first report of such a "same composition different sequence" effect, described for the short peptides, for synthetic oligonucleotides.     

Structural analysis of RecA protein-DNA complexes by fluorescence-detected linear dichroism: absence of structural change of filament for pairing of complementary DNA strands

We have developed a simple measuring system for fluorescence-detected linear dichroism and applied it to the structural analysis of the RecA-DNA complex filaments, which are intermediates of the homologous recombination reaction. Taking advantage of the selectivity of fluorescence signals, we distinguished the linear dichroism signals of ethidium bromide and tryptophan residues in the RecA-DNA-ethidium bromide complex, whereas the conventional (absorption-detected) linear dichroism measurement provides only the sum of the signals because signals overlap each other and that of DNA. We further observed that the tryptophan residue at position 290 of RecA in the RecA-DNA-adenosine-5'-O-(3-thiotriphosphate) complex was oriented parallel to the long axis of the filament, in good agreement with the previous site-specific linear dichroism analysis, and that this orientation was not significantly modified by the pairing of the complementary DNA strand. These results suggest that the pairing reaction occurs without a large structural change of the RecA filament.     

Meta-analysis for surrogacy: accelerated failure time models and semicompeting risks modeling

There has been great recent interest in the medical and statistical literature in the assessment and validation of surrogate endpoints as proxies for clinical endpoints in medical studies. More recently, authors have focused on using metaanalytical methods for quantification of surrogacy. In this article, we extend existing procedures for analysis based on the accelerated failure time model to this setting. An advantage of this approach relative to proportional hazards model is that it allows for analysis in the semicompeting risks setting, where we model the region where the surrogate endpoint occurs before the true endpoint. Several estimation methods and attendant inferential procedures are presented. In addition, between- and within-trial methods for evaluating surrogacy are developed; a novel principal components procedure is developed for quantifying trial-level surrogacy. The methods are illustrated by application to data from several studies in colorectal cancer.     

C-type Natriuretic Peptide: a novel biomarker of steroid induced bone toxicity in children with acute lymphoblastic leukemia (ALL)

Impaired bone growth and mineralization, and osteonecrosis are significant and common long-term sequelae of chemotherapy for childhood acute lymphoblastic leukemia (ALL). Here we have evaluated the relationship between linear bone growth during chemotherapy for ALL and bone derived C-type Natriuretic Peptide (CNP). CNP is known to be critical to normal endochondral bone growth in both rodents and humans, and plasma concentration of the amino terminal pro CNP (NTproCNP) is strongly correlated with concurrent height velocity in children. Plasma NTproCNP and CNP were measured by radio-immunoassay in 12 children aged 2-9 years during induction and maintenance chemotherapy for children with ALL. Height velocity was calculated from stadiometer readings at intervals of 3-12 months and related to plasma NTproCNP during each growth interval. Plasma NTproCNP was markedly suppressed in all subjects during induction chemotherapy. Brief periods of NTproCNP decline and rapid rebound during maintenance treatment coincided with the use of dexamethasone but not with other chemotherapeutics. Height velocity was markedly reduced during ALL induction but unaffected in maintenance phase, and these changes in growth were strongly correlated with plasma NTproCNP concentration. Plasma NTproCNP has potential use as a biomarker of glucocorticoid-induced bone toxicity.     

SORL1 and SIRT1 mRNA expression and promoter methylation levels in aging and Alzheimer’s Disease

Alzheimer’s Disease (AD) is a neurodegenerative disorder and the most common cause of dementia among the elderly. Efforts have been made to understand the genetic and epigenetic mechanisms involved in the development of this disease. As SORL1 (sortilin-related receptor) and SIRT1 (sirtuin 1) genes have been linked to AD pathogenesis, we aimed to investigate their mRNA expression and promoter DNA methylation in post mortem brain tissues (entorhinal and auditory cortices and hippocampus) from healthy elderly subjects and AD patients. We also evaluated these levels in peripheral blood leukocytes from young, healthy elderly and AD patients, investigating whether there was an effect of age on these profiles. The comparative CT method by Real Time PCR and MALDI-TOF mass spectrometry were used to analyze gene expression and DNA methylation, respectively. SORL1 gene was differently expressed in the peripheral blood leukocytes and might act as a marker of aging in this tissue. Furthermore, we found that SORL1 promoter DNA methylation might act as one of the mechanisms responsible for the differences in expression observed between blood and brain for both healthy elderly and AD patients groups. The impact of these studied genes on AD pathogenesis remains to be better clarified.     

中国植物志、Flora of China和维管植物新系统中科的比较

《中国植物志》和“Flora of China”是目前世界上最大型、记录植物种类最多的植物志,它为有效保护和合理利用我国的植物资源提供了极为重要的基础信息和科学依据。近年来,基于分子系统学研究提出的APG系统被广泛接受,相应方法得到的系统也相继应用于整个维管植物中。以APG系统为代表的维管植物新系统为全面和系统地修订植物志提供了新的系统框架。本文依据最新的分子系统学“线性排列”成果与《中国植物志》和“Flora of China”在科级水平上进行对比,确定了以APG系统为代表的分子系统框架下中国维管植物为309科,其中石松类和蕨类植物38科,裸子植物10科和被子植物261科。尽管中国维管植物不少科的界限发生了较大的变化,其总数却变化不大,在《中国植物志》中为300科,“Flora of China”为309科。此外,还重点介绍了一些主要科的变动情况。     

Fine-scale spatial genetic structure of Dalbergia nigra (Fabaceae), a threatened and endemic tree of the Brazilian Atlantic Forest

The Atlantic Forest is one of the most diverse ecosystems in the world and considered a hotspot of biodiversity conservation. Dalbergia nigra (Fabaceae) is a tree endemic to the Brazilian Atlantic Forest, and has become threatened due to overexploitation of its valuable timber. In the present study, we analyzed the genetic diversity and fine-scale spatial genetic structure of D. nigra in an area of primary forest of a large reserve. All adult individuals (N = 112) were sampled in a 9.3 ha plot, and genotyped for microsatellite loci. Our results indicated high diversity with a mean of 8.6 alleles per locus, and expected heterozygosity equal to 0.74. The co-ancestry coefficients were significant for distances among trees up to 80 m. The Sp value was equal to 0.017 and indirect estimates of gene dispersal distances ranged from 89 to 144 m. No strong evidence of bottleneck or effects of human-disturbance was found. This study highlights that long-term efforts to protect a large area of Atlantic Forest have been effective towards maintaining the genetic diversity of D. nigra. The results of this study are important towards providing a guide for seed collection for ex-situ conservation and reforestation programmes of this threatened species.     

Spatio-temporal population genetics of the Danish pine marten (Martes martes)

A spatio-temporal study of genetic variation in the Danish pine marten ( Martes martes ) populations from the Jutland peninsula and from the island of Sealand was performed using 11 microsatellite markers. Samples obtained from 1892 to 2003 were subdivided into historical (prior to 1970) and recent (from 1970) groups. As compared with the historical samples, there was a significant loss of genetic variation in the recent Jutland population, but not in Sealand. Effective population sizes were estimated using Bayesian-based software (TMVP). Historical effective population sizes were 5897 (90% highest probability density, HPD, limits: 1502–6849) in Jutland and 1300 (90% HPD limits: 224–5929) in Sealand, whereas recent effective population sizes were 14.7 (90% HPD limits: 10.9–23.5) in Jutland and 802 (90% HPD limits: 51.8–5510) in Sealand. Significant genetic differentiation ( F _ST) was found between the two historical samples, between the two recent samples, and between the historical and the recent sample in Jutland; whereas the F _ST value between the historical and the recent sample in Sealand was not significant. The significant genetic differentiation between the historical and the recent samples indicates changes in the genetic compositions over time, and the higher F _ST values between the two recent samples, as compared with the two historical samples, indicates that the populations in Sealand and Jutland have drifted apart within a short time span. No deviation from Hardy–Weinberg equilibrium was found within populations, indicating no further substructuring.  © 2008 The Linnean Society of London, Biological Journal of the Linnean Society , 2008, 93 , 457–464.     

The functions of the "Greeting Ceremony" among male mantled howlers (Alouatta palliata) on Agaltepec Island, Mexico

Nonhuman primates use greeting behaviors as nonaggressive communicatory signals in multiple social contexts. Adult male mantled howlers (Alouatta palliata) perform a ritual greeting that has been associated with bond-strengthening functions. The aim of this study is to explore the greeting patterns of male howlers living on Agaltepec Island, Mexico. Specifically, we analyzed the relationships between greetings and several individual, relational, and contextual variables, such as the expression of affiliation and agonism, dominance rank, age, kinship relationships, spatial organization, activity patterns, and subgrouping patterns. Greetings were more frequent between males with closer dominance ranks. Among those dyads that greeted at least once, dominant males initiated greetings more frequently than less-dominant males. On the other hand, more greetings were observed when one of the participants had recently returned to a subgroup and during locomotion. On the basis of these results, we propose that on Agaltepec greetings are a conflict management mechanism used between males of similar ranks. The fission-fusion social system of this group of howlers allows males with conflicting interests to remain separated, and greetings may reduce tension during fusion events.     

Innovative social behavior in chimpanzees (Pan troglodytes)

We present evidence of agonistic buffering in captive chimpanzees, recorded from 1993 until 2005, mainly from ad libitum sampling in over 2000 hr of observation. A total of 33 agonistic buffering episodes were analyzed for context and effects of this complex social behavior. Agonistic buffering was directed at the whole chimpanzee colony as they supported an individual who initially received aggression from the alpha male, independently of the victim's age, sex or social rank. Chimpanzee agonistic buffering behavior is compared with that in other nonhuman primate species, and we describe some particularities of chimpanzee agonistic buffering: the status of the buffers used-socially important offspring such as those from the alpha female-and the social rank of the adult male responsible for the buffering episode-alpha male. Possible functions for this behavior in chimpanzees are suggested as appeasement of group members in a particularly crowded captive setting, and/or as a "forced reconciliation" mechanism. Chimpanzees exhibit behavioral flexibility by adapting themselves to new social and physical situations and use novel behavior to achieve social benefits.