Avian biodiversity in the coastal wetlands of the Okahukura Peninsula

The Tapora Landcare Group, operating on the Okahukura Peninsula, has the long-term goal of making this region predator fenced. The aim of this study was to obtain information on the current status of avian biodiversity and the bird community across the band of coastal wetlands on the Okahukura Peninsula. Bird counts were conducted and playback lures used to detect three cryptic wetland species: fernbirds (Bowdleria punctata); spotless crakes (Porzana tabuensis); and banded rails (Gallirallus philippensis). Fernbirds and banded rails were detected at seven of the eight wetland sites sampled whereas spotless crakes were detected at two sites. The native species with the highest relative abundance across the eight sites were silvereyes (Zosterops lateralis) and South Island pied oystercatchers (Haematopus finschi). Changes in avian biodiversity over time in the region can now be monitored, and comprehensive long-term data on the status of avian biodiversity over time obtained.     

The varied nature of women's sexuality: unresolved issues and a theoretical approach

During the 20th century there were clear indications that the socio-cultural suppression of women's sexuality had lessened, revealing a marked variability of women's sexual expression. In this article we review the recent literature to explore explanations for this variability. It is clear that we know little about the nature of sexual desire, and in particular, what it is that is desired. There is also now substantial evidence that vaginal response, as measured by vaginal pulse amplitude, is a relatively automatic response to perception of sexual stimuli, regardless of whether these stimuli are perceived positively or result in subjective arousal. This is considered as a possible mechanism that allows vaginal intercourse without pain, even when the woman is not sexually aroused. The roles of androgens and estrogen in women's sexuality remain uncertain. The evidence is, however, consistent with there being a testosterone-dependent component of women's sexuality that is more important for some women than others. Finally, a new theoretical model is presented that aims to resolve these uncertainties and that proposes different types of women's sexuality. Once we have a better understanding of “normal” female sexuality, in its various forms, our ability to develop effective treatments for women's sexual problems should improve.     

Hormonal regulation of IGFBP-2 proteolysis is attenuated with progression to androgen insensitivity in the LNCaP progression model

The identification of molecular determinants involved in the promotion of metastasis and development of androgen insensitive prostate cancer (AI-PCa) is necessary to discriminate aggressive from indolent disease and to identify therapeutic targets for advanced disease. Overexpression of one particular member of the insulin like growth factor (IGF) axis, IGFBP-2, is implicated in the development of AI-PCa and other cancers. Using the LNCaP human PCa progression model, we show that the AI and metastatic prostate cancer cell line C4-2B4 expresses greater amounts of secreted IGFBP-2 than the androgen sensitive (AS), non-metastatic LNCaP progenitor cell line. Further, the ability of androgens to decrease extracellular IGFBP-2 levels is attenuated in the AI and metastatic C4-2 cell line. The ability of androgen to negatively regulate extracellular IGFBP-2 levels was blocked by Casodex in a dose-dependent manner. The mechanism underlying the androgen-induced downregulation of secreted IGFBP-2 appears to involve extracellular proteolysis, resulting in the production of IGFBP-2 fragments lacking the ability to bind IGF-I and IGF-II. As C4-2 cells have an attenuated ability to proteolyze IGFBP-2 in response to androgen and C4-2B4 cells express greater amounts of IGFBP-2, our data implies that the diminished regulation of IGFBP-2 and loss of associated proteolytic fragments play a role in the increased metastatic behavior of these cells in vivo. Furthermore, our results suggest that either increased levels of intact IGFBP-2 or decreased levels of IGFBP-2 proteolytic fragments could serve as a biomarker to monitor for progression to AI-PCa.     

Genome‐wide selection footprints and deleterious variations in young Asian allotetraploid rapeseed

Brassica napus (AACC, 2n = 38) is an important oilseed crop grown worldwide. However, little is known about the population evolution of this species, the genomic difference between its major genetic groups, such as European and Asian rapeseed, and the impacts of historical large‐scale introgression events on this young tetraploid. In this study, we reported the de novo assembly of the genome sequences of an Asian rapeseed (B. napus), Ningyou 7, and its four progenitors and compared these genomes with other available genomic data from diverse European and Asian cultivars. Our results showed that Asian rapeseed originally derived from European rapeseed but subsequently significantly diverged, with rapid genome differentiation after hybridization and intensive local selective breeding. The first historical introgression of B. rapa dramatically broadened the allelic pool but decreased the deleterious variations of Asian rapeseed. The second historical introgression of the double‐low traits of European rapeseed (canola) has reshaped Asian rapeseed into two groups (double‐low and double‐high), accompanied by an increase in genetic load in the double‐low group. This study demonstrates distinctive genomic footprints and deleterious SNP (single nucleotide polymorphism) variants for local adaptation by recent intra‐ and interspecies introgression events and provides novel insights for understanding the rapid genome evolution of a young allopolyploid crop.     

The control of seed oil polyunsaturate content in the polyploid crop species Brassica napus

Many important plant species have polyploidy in their recent ancestry, complicating inferences about the genetic basis of trait variation. Although the principal locus controlling the proportion of polyunsaturated fatty acids (PUFAs) in seeds of Arabidopsis thaliana is known (fatty acid desaturase 2; FAD2), commercial cultivars of a related crop, oilseed rape (Brassica napus), with very low PUFA content have yet to be developed. We showed that a cultivar of oilseed rape with lower than usual PUFA content has non-functional alleles at three of the four orthologous FAD2 loci. To explore the genetic basis further, we developed an ethyl methanesulphonate mutagenised population, JBnaCAB_E, and used it to identify lines that also carried mutations in the remaining functional copy. This confirmed the hypothesised basis of variation, resulting in an allelic series of mutant lines showing a spectrum of PUFA contents of seed oil. Several lines had PUFA content of ~6 % and oleic acid content of ~84 %, achieving a long-standing industry objective: very high oleic, very low PUFA rapeseed without the use of genetic modification technology. The population contains a high rate of mutations and represents an important resource for research in B. napus.     

Synovial phenotypes in rheumatoid arthritis correlate with response to biologic therapeutics

Introduction

Rheumatoid arthritis (RA) is a complex and clinically heterogeneous autoimmune disease. Currently, the relationship between pathogenic molecular drivers of disease in RA and therapeutic response is poorly understood.

Methods

We analyzed synovial tissue samples from two RA cohorts of 49 and 20 patients using a combination of global gene expression, histologic and cellular analyses, and analysis of gene expression data from two further publicly available RA cohorts. To identify candidate serum biomarkers that correspond to differential synovial biology and clinical response to targeted therapies, we performed pre-treatment biomarker analysis compared with therapeutic outcome at week 24 in serum samples from 198 patients from the ADACTA (ADalimumab ACTemrA) phase 4 trial of tocilizumab (anti-IL-6R) monotherapy versus adalimumab (anti-TNFα) monotherapy.

Results

We documented evidence for four major phenotypes of RA synovium – lymphoid, myeloid, low inflammatory, and fibroid - each with distinct underlying gene expression signatures. We observed that baseline synovial myeloid, but not lymphoid, gene signature expression was higher in patients with good compared with poor European league against rheumatism (EULAR) clinical response to anti-TNFα therapy at week 16 (P =0.011). We observed that high baseline serum soluble intercellular adhesion molecule 1 (sICAM1), associated with the myeloid phenotype, and high serum C-X-C motif chemokine 13 (CXCL13), associated with the lymphoid phenotype, had differential relationships with clinical response to anti-TNFα compared with anti-IL6R treatment. sICAM1-high/CXCL13-low patients showed the highest week 24 American College of Rheumatology (ACR) 50 response rate to anti-TNFα treatment as compared with sICAM1-low/CXCL13-high patients (42% versus 13%, respectively, P =0.05) while anti-IL-6R patients showed the opposite relationship with these biomarker subgroups (ACR50 20% versus 69%, P =0.004).

Conclusions

These data demonstrate that underlying molecular and cellular heterogeneity in RA impacts clinical outcome to therapies targeting different biological pathways, with patients with the myeloid phenotype exhibiting the most robust response to anti-TNFα. These data suggest a path to identify and validate serum biomarkers that predict response to targeted therapies in rheumatoid arthritis and possibly other autoimmune diseases.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01119859","term_id":"NCT01119859"}}NCT01119859     

Telomere Length Shows No Association with BRCA1 and BRCA2 Mutation Status

This study aimed to determine whether telomere length (TL) is a marker of cancer risk or genetic status amongst two cohorts of BRCA1 and BRCA2 mutation carriers and controls. The first group was a prospective set of 665 male BRCA1/2 mutation carriers and controls (mean age 53 years), all healthy at time of enrolment and blood donation, 21 of whom have developed prostate cancer whilst on study. The second group consisted of 283 female BRCA1/2 mutation carriers and controls (mean age 48 years), half of whom had been diagnosed with breast cancer prior to enrolment. TL was quantified by qPCR from DNA extracted from peripheral blood lymphocytes. Weighted and unweighted Cox regressions and linear regression analyses were used to assess whether TL was associated with BRCA1/2 mutation status or cancer risk. We found no evidence for association between developing cancer or being a BRCA1 or BRCA2 mutation carrier and telomere length. It is the first study investigating TL in a cohort of genetically predisposed males and although TL and BRCA status was previously studied in females our results don''t support the previous finding of association between hereditary breast cancer and shorter TL.