Linkage to chromosome 2q32.2-q33.3 in familial serrated neoplasia (Jass syndrome)

Causative genetic variants have to date been identified for only a small proportion of familial colorectal cancer (CRC). While conditions such as Familial Adenomatous Polyposis and Lynch syndrome have well defined genetic causes, the search for variants underlying the remainder of familial CRC is plagued by genetic heterogeneity. The recent identification of families with a heritable predisposition to malignancies arising through the serrated pathway (familial serrated neoplasia or Jass syndrome) provides an opportunity to study a subset of familial CRC in which heterogeneity may be greatly reduced. A genome-wide linkage screen was performed on a large family displaying a dominantly-inherited predisposition to serrated neoplasia genotyped using the Affymetrix GeneChip Human Mapping 10 K SNP Array. Parametric and nonparametric analyses were performed and resulting regions of interest, as well as previously reported CRC susceptibility loci at 3q22, 7q31 and 9q22, were followed up by finemapping in 10 serrated neoplasia families. Genome-wide linkage analysis revealed regions of interest at 2p25.2-p25.1, 2q24.3-q37.1 and 8p21.2-q12.1. Finemapping linkage and haplotype analyses identified 2q32.2-q33.3 as the region most likely to harbour linkage, with heterogeneity logarithm of the odds (HLOD) 2.09 and nonparametric linkage (NPL) score 2.36 (P = 0.004). Five primary candidate genes (CFLAR, CASP10, CASP8, FZD7 and BMPR2) were sequenced and no segregating variants identified. There was no evidence of linkage to previously reported loci on chromosomes 3, 7 and 9

A role for the endometrial microbiome in dysfunctional menstrual bleeding

This study aimed to characterise the microbial community within the endometrial cavity and endocervix in women with menorrhagia or dysmenorrhea. Paired endocervical and endometrial biopsy samples were collected from women undergoing operative hysteroscopy and/or laparoscopy. Samples were cohorted based on pathology, indications for surgery, and histological dating of the endometrium. Samples were interrogated for the presence of microbial DNA using a two-step next generation sequencing technology approach to exploit the V5-V8 regions of the 16S rRNA gene. Pyrosequencing revealed that the endocervix and endometrium share a minor microbial community, but that each site harbours a separate and distinct microbial population (p\ua0=\ua00.024). This was also the case for women with menorrhagia and dysmenorrhea (p\ua0=\ua00.017). Lactobacillus spp. were the most abundant microbial taxa present in 50% of the cohorts, and across all endocervical groups. Members of the genera Prevotella, Fusobacterium and Jonquetella were the most abundant taxa identified in samples collected from nulliparous women. It can be concluded that the female upper genital tract is not sterile. Microbial community profiling revealed differences in the endometrial microbial community profiles for: (1) the endocervix compared to the endometrium, and (2), women with menorrhagia versus dysmenorrhea. The distinct microbial community profiles in these women may offer insight into the pathology and clinical management of dysfunctional menstrual bleeding

Fallopian tube microbiota: evidence beyond DNA

Aim: To determine whether cultivation-dependent and -independent analyses identifying fallopian tube bacteria were associated with visually observable microbial cells in situ using scanning electron microscopy. Patients: Fallopian tubes were collected from pre- and postmenopausal women undergoing salpingectomies for benign disease or as prophylaxis. Materials & methods: Fresh fallopian tube samples were processed for scanning electron microscopy to characterize fallopian tube ultrastructure. Histopathology was used to exclude fallopian tube abnormalities and for menstrual cycle staging of the endometrium. Results: Scanning electron microscopy revealed observable microbial cells in fallopian tube samples. Conclusion: In the absence of inflammatory pathology, the fallopian tube harbors a visually observable microbial population, which correlates with cultivation-dependent and -independent data, further refuting the sterility of this anatomical niche

IFPA meeting 2015 workshop report IV: placenta and obesity; stem cells of the feto-maternal interface; placental immunobiology and infection

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialised topics. At the 2015 IFPA annual meeting there were 12 themed workshops, three of which are summarized in this report. These workshops related to various aspects of placental biology and collectively covered areas of obesity and the placenta, stem cells of the feto-maternal interface, and placental immunobiology and infection

Design, assessment and feasibility of legume-based cropping systems in three European regions

International audienceGrain legumes in cropping systems result in agronomic and environmental benefits. Nevertheless, their areas in Europe have strongly decreased over the past decades. Our aim was to design locally adapted innovative cropping systems including grain legumes for three European local pedoclimatic contexts, to assess their sustainability, and to discuss their feasibility with stakeholders. The methodology included an initial diagnosis of the most frequent cropping systems and local improvement targets in each local context (e.g. improve legume profitability, limit diseases of legumes, reduce intensive use of chemical inputs in cropping systems), the design of innovative legume-based cropping systems during a common workshop, focusing on three aims ((i) decrease pesticide use, (ii) reduce mineral N fertiliser dependency, and (iii) increase yield stability of grain legume crops and other crops of the crop sequence), and their multicriteria sustainability assessment. Stakeholders meetings were organised in each local context to discuss the feasibility of implementing the innovative cropping systems in farmers' fields (technical implementation of cropping systems and possibility of development of legume sectors). Four to five cropping systems were designed in each local context, with crop sequences longer than references. They included at least two grain legumes (pea, faba bean, chickpea, lentil or lupine), as sole crops or intercropped with cereals. Overall sustainability was similar or improved in 71% of the legume-based cropping systems compared with their corresponding references. Among the designed cropping systems, stakeholders identified feasible ones considering both technical issues and development of legume sectors. The results indicate that reintegrating more grain legumes in the three European local contexts tested will contribute to more sustainable farming systems

Modulation of placental gene expression in small-for-gestational-age infants

Small-for-gestational-age (SGA) infants are fetuses that have not reached their genetically programmed growth potential. Low birth weight predisposes these infants to an increased risk of developing cardiovascular, metabolic and neurodevelopmental conditions in later life. However, our understanding of how this pathology occurs is currently incomplete. Previous research has focused on understanding the transcriptome, epigenome and bacterial signatures separately. However, we hypothesise that interactions between moderators of gene expression are critical to understanding fetal growth restriction. Through a review of the current literature, we identify that there is evidence of modulated expression/methylation of the placental genome and the presence of bacterial DNA in the placental tissue of SGA infants. We also identify that despite limited evidence of the interactions between the above results, there are promising suggestions of a relationship between bacterial signatures and placental function. This review aims to summarise the current literature concerning fetal growth from multiple avenues and propose a novel relationship between the placental transcriptome, methylome and bacterial signature that, if characterised, may be able to improve our current understanding of the placental response to stress and the aetiology of growth restriction

Hormone-dependent bacterial growth, persistence and biofilm formation - a pilot study investigating human follicular fluid collected during IVF cycles

Human follicular fluid, considered sterile, is aspirated as part of an in vitro fertilization (IVF) cycle. However, it is easily contaminated by the trans-vaginal collection route and little information exists in its potential to support the growth of microorganisms. The objectives of this study were to determine whether human follicular fluid can support bacterial growth over time, whether the steroid hormones estradiol and progesterone (present at high levels within follicular fluid) contribute to the in vitro growth of bacterial species, and whether species isolated from follicular fluid form biofilms. We found that bacteria in follicular fluid could persist for at least 28 weeks in vitro and that the steroid hormones stimulated the growth of some bacterial species, specifically Lactobacillus spp., Bifidobacterium spp. Streptococcus spp. and E. coli. Several species, Lactobacillus spp., Propionibacterium spp., and Streptococcus spp., formed biofilms when incubated in native follicular fluids in vitro (18/24, 75%). We conclude that bacteria aspirated along with follicular fluid during IVF cycles demonstrate a persistent pattern of growth. This discovery is important since it can offer a new avenue for investigation in infertile couples