Ecological and evolutionary drivers of phenotypic and genetic variation in the European crabapple [Malus sylvestris (L.) Mill.], a wild relative of the cultivated apple.

BACKGROUND AND AIMS: Studying the relationship between phenotypic and genetic variation in populations distributed across environmental gradients can help us to understand the ecological and evolutionary processes involved in population divergence. We investigated the patterns of genetic and phenotypic diversity in the European crabapple, Malus sylvestris, a wild relative of the cultivated apple (Malus domestica) that occurs naturally across Europe in areas subjected to different climatic conditions, to test for divergence among populations. METHODS: Growth rates and traits related to carbon uptake in seedlings collected across Europe were measured in controlled conditions and associated with the genetic status of the seedlings, which was assessed using 13 microsatellite loci and the Bayesian clustering method. Isolation-by-distance, isolation-by-climate and isolation-by-adaptation patterns, which can explain genetic and phenotypic differentiation among M. sylvestris populations, were also tested. KEY RESULTS: A total of 11.6 % of seedlings were introgressed by M. domestica, indicating that crop-wild gene flow is ongoing in Europe. The remaining seedlings (88.4 %) belonged to seven M. sylvestris populations. Significant phenotypic trait variation among M. sylvestris populations was observed. We did not observe significant isolation by adaptation; however, the significant association between genetic variation and the climate during the Last Glacial Maximum suggests that there has been local adaptation of M. sylvestris to past climates. CONCLUSIONS: This study provides insight into the phenotypic and genetic differentiation among populations of a wild relative of the cultivated apple. This might help us to make better use of its diversity and provide options for mitigating the impact of climate change on the cultivated apple through breeding.

Genomic signature of successful colonization of Eurasia by the allopolyploid shepherd's purse (Capsella bursa-pastoris).

Polyploidization is a dominant feature of flowering plant evolution. However, detailed genomic analyses of the interpopulation diversification of polyploids following genome duplication are still in their infancy, mainly because of methodological limits, both in terms of sequencing and computational analyses. The shepherd's purse (Capsella bursa-pastoris) is one of the most common weed species in the world. It is highly self-fertilizing, and recent genomic data indicate that it is an allopolyploid, resulting from hybridization between the ancestors of the diploid species Capsella grandiflora and Capsella orientalis. Here, we investigated the genomic diversity of C. bursa-pastoris, its population structure and demographic history, following allopolyploidization in Eurasia. To that end, we genotyped 261 C. bursa-pastoris accessions spread across Europe, the Middle East and Asia, using genotyping-by-sequencing, leading to a total of 4274 SNPs after quality control. Bayesian clustering analyses revealed three distinct genetic clusters in Eurasia: one cluster grouping samples from Western Europe and Southeastern Siberia, the second one centred on Eastern Asia and the third one in the Middle East. Approximate Bayesian computation (ABC) supported the hypothesis that C. bursa-pastoris underwent a typical colonization history involving low gene flow among colonizing populations, likely starting from the Middle East towards Europe and followed by successive human-mediated expansions into Eastern Asia. Altogether, these findings bring new insights into the recent multistage colonization history of the allotetraploid C. bursa-pastoris and highlight ABC and genotyping-by-sequencing data as promising but still challenging tools to infer demographic histories of selfing allopolyploids.

Hyperthermic intraperitoneal chemotherapy leads to an anticancer immune response via exposure of cell surface heat shock protein 90.

The occurrence of peritoneal carcinomatosis is a major cause of treatment failure in colorectal cancer and is considered incurable. However, new therapeutic approaches have been proposed, including cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Although HIPEC has been effective in selected patients, it is not known how HIPEC prolongs a patient's lifespan. Here, we have demonstrated that HIPEC-treated tumor cells induce the activation of tumor-specific T cells and lead to vaccination against tumor cells in mice. We have established that this effect results from the HIPEC-mediated exposure of heat shock protein (HSP) 90 at the plasma membrane. Inhibition or blocking of HSP90, but not HSP70, prevented the HIPEC-mediated antitumoral vaccination. Our work raises the possibility that the HIPEC procedure not only kills tumor cells but also induces an efficient anticancer immune response, therefore opening new opportunities for cancer treatment.

[Surgical site infections in vaginal prolapse surgery]. / Infections du site opératoire en chirurgie du prolapsus par voie vaginale.

INTRODUCTION: Vaginal prolapse surgery is at high risk of surgical site infections (SSI) because it's a "clean-contaminated surgery" and it's frequently associated with implantation of meshes. OBJECTIVES: To evaluate the rate of SSI and associated risk factors in vaginal prolapse surgery with mesh support. METHODS: In a retrospective unicenter study, two groups of patients were operated by vaginal route for a pelvic floor reconstructive surgery with mesh support. Colporraphy was made by classic surgical sutures non-coated (Monosyn(®) 3/0, B-Braun) in the first group, and surgical sutures coated with triclosan in the second group. We collected risk factors of SSIs using the procedure of the CCLIN and analyzed the occurrence of SSIs with a statistical comparative univariate analysis. RESULTS: Study included 78 patients in the first group and 72 in the second group. SSIs total rate was 2.6 % (4 of 150), as part of 3 in the group with surgical sutures non-coated and one in the group with surgical sutures coated with triclosan (P=0.62). CONCLUSION: In our study, SSIs rate in vaginal prolapse surgery was twice higher than classic gynecologic surgery. As the interest of using a surgical suture coated with triclosan to reduce SSI has not been demonstrated statistically, we can't recommend it.

GAPDH binds to active Akt, leading to Bcl-xL increase and escape from caspase-independent cell death.

Increased glucose catabolism and resistance to cell death are hallmarks of cancers, but the link between them remains elusive. Remarkably, under conditions where caspases are inhibited, the process of cell death is delayed but rarely blocked, leading to the occurrence of caspase-independent cell death (CICD). Escape from CICD is particularly relevant in the context of cancer as apoptosis inhibition only is often not sufficient to allow oncogenic transformation. While most glycolytic enzymes are overexpressed in tumors, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is of particular interest as it can allow cells to recover from CICD. Here, we show that GAPDH, but no other glycolytic enzymes tested, when overexpressed could bind to active Akt and limit its dephosphorylation. Active Akt prevents FoxO nuclear localization, which precludes Bcl-6 expression and leads to Bcl-xL overexpression. The GAPDH-dependent Bcl-xL overexpression is able to protect a subset of mitochondria from permeabilization that are required for cellular survival from CICD. Thus, our work suggests that GAPDH overexpression could induce Bcl-xL overexpression and protect cells from CICD-induced chemotherapy through preservation of intact mitochondria that may facilitate tumor survival and chemotherapeutic resistance.

Comparison between trans-obturator trans-vaginal mesh and traditional anterior colporrhaphy in the treatment of anterior vaginal wall prolapse: results of a French RCT.

INTRODUCTION AND HYPOTHESIS: To compare the efficacy of a collagen-coated polypropylene mesh and anterior colporrhaphy in the treatment of stage 2 or more anterior vaginal wall prolapse. METHODS: Prospective, randomized, multicenter study conducted between April 2005 and December 2009. The principal endpoint was the recurrence rate of stage 2 or more anterior vaginal wall prolapse 12 months after surgery. Secondary endpoints consisted of functional results and mesh-related morbidity. RESULTS: One hundred and forty-seven patients were included, randomized and analyzed: 72 in the anterior colporrhaphy group and 75 in the mesh group. The anatomical success rate was significantly higher in the mesh group (89%) than in the colporrhaphy group (64%) (p = 0.0006). Anatomical and functional recurrence was also less frequent in the mesh group (31.3% vs 52.2%, p = 0.007). Two patients (2.8%) were reoperated on in the colporrhaphy group for anterior vaginal wall prolapse recurrence. No significant difference was noted regarding minor complications. An erosion rate of 9.5% was noted. De novo dyspareunia occurred in 1/14 patients in the colporrhaphy group and in 3/13 patients in the mesh group. An analysis of the quality of life questionnaires showed an overall improvement in both groups, with no statistical difference between them. Satisfaction rates were high in both groups (92% in the colporrhaphy group and 96% in the mesh group). CONCLUSION: Trans-obturator Ugytex mesh used to treat anterior vaginal wall prolapse gives better 1-year anatomical results than traditional anterior colporrhaphy, but with small a increase in morbidity in the mesh group.

Postglacial recolonization history of the European crabapple (Malus sylvestris Mill.), a wild contributor to the domesticated apple.

Understanding the way in which the climatic oscillations of the Quaternary Period have shaped the distribution and genetic structure of extant tree species provides insight into the processes driving species diversification, distribution and survival. Deciphering the genetic consequences of past climatic change is also critical for the conservation and sustainable management of forest and tree genetic resources, a timely endeavour as the Earth heads into a period of fast climate change. We used a combination of genetic data and ecological niche models to investigate the historical patterns of biogeographic range expansion of a wild fruit tree, the European crabapple (Malus sylvestris), a wild contributor to the domesticated apple. Both climatic predictions for the last glacial maximum and analyses of microsatellite variation indicated that M. sylvestris experienced range contraction and fragmentation. Bayesian clustering analyses revealed a clear pattern of genetic structure, with one genetic cluster spanning a large area in Western Europe and two other genetic clusters with a more limited distribution range in Eastern Europe, one around the Carpathian Mountains and the other restricted to the Balkan Peninsula. Approximate Bayesian computation appeared to be a powerful technique for inferring the history of these clusters, supporting a scenario of simultaneous differentiation of three separate glacial refugia. Admixture between these three populations was found in their suture zones. A weak isolation by distance pattern was detected within each population, indicating a high extent of historical gene flow for the European crabapple.

Floral volatiles, pollinator sharing and diversification in the fig-wasp mutualism: insights from Ficus natalensis, and its two wasp pollinators (South Africa).

Combining biogeographic, ecological, morphological, molecular and chemical data, we document departure from strict specialization in the fig-pollinating wasp mutualism. We show that the pollinating wasps Elisabethiella stuckenbergi and Elisabethiella socotrensis form a species complex of five lineages in East and Southern Africa. Up to two morphologically distinct lineages were found to co-occur locally in the southern African region. Wasps belonging to a single lineage were frequently the main regional pollinators of several Ficus species. In South Africa, two sister lineages, E. stuckenbergi and E. socotrensis, pollinate Ficus natalensis but only E. stuckenbergi also regularly pollinates Ficus burkei. The two wasp species co-occur in individual trees of F. natalensis throughout KwaZulu-Natal. Floral volatile blends emitted by F. natalensis in KwaZulu-Natal were similar to those emitted by F. burkei and different from those produced by other African Ficus species. The fig odour similarity suggests evolutionary convergence to attract particular wasp species. The observed pattern may result from selection for pollinator sharing among Ficus species. Such a process, with one wasp species regionally pollinating several hosts, but several wasp species pollinating a given Ficus species across its geographical range could play an important role in the evolutionary dynamics of the Ficus-pollinating wasp association.

[Colpocleisis without mid-urethral sling: A valid concept in the elderly with vault vaginal prolapse and stress urinary incontinence?]. / Colpocléisis sans soutènement sous-urétral : un concept valide chez la femme âgée ayant un prolapsus génital associé à une incontinence urinaire d'effort ?

OBJECTIVES: Estimate the urinary impact of vaginal occlusion without mid-urethral sling in the elderly with vault vaginal prolapse and stress urinary incontinence. PATIENTS AND METHODS: Retrospective case series of 22 women who underwent a vaginal closure between May 2005 and April 2009. Postoperating evaluation of the impact on the urinary tract of this surgery and of the satisfaction of the patients to a phone investigation. RESULTS: Seventeen patients with mean age 80 years answered the phone questionnaire. With a mean follow up of 23.9 months, the rate of satisfaction amounts to 88%. The rate of recurrence is 11%. Urge incontinence decreases from 36 to 24% and there is no stress urinary incontinence postoperatively. CONCLUSION: Colpocleisis is a surgical technique which meets high rates of satisfaction and which seems effective in the treatment of urinary incontinence associated with vaginal vault prolapse in the elderly.

A comparative immunohistochemical study of cytokeratin and vimentin expression in middle ear mucosa and cholesteatoma, and in epidermis.

Cytokeratin expression was studied in human middle ear cholesteatoma lesions, using a variety of immunohistological techniques and a wide range of polyclonal antisera and monoclonal antibodies against cytokeratin (CK) subgroups or individual CK polypeptides. The expression of the other cytoskeletal proteins, vimentin and desmin, was also investigated. Middle ear mucosa and epidermal tissues were used as reference tissues. Our investigations also included epithelial structures present in the cholesteatoma perimatrix and in dermal tissues. The results indicate that, compared with epidermal tissues, the expression profile of CKs in cholesteatoma matrix is representative of a hyperproliferative disease. Evaluating the presence of a marker of terminal keratinization - the 56.5 kD acidic CK n degrees 10 - we found supportive evidence of a pronounced retardation of its expression, which did not parallel histological differentiation. In epidermal tissues, the first prickle cell layers are CK10 positive whereas in many cholesteatomas this finding was observed near the stratum granulosum only. Probing the early stages of keratinization - the 58 kD basic CK n degrees 5 and the 50 kD acidic CK n degrees 14 - we regularly observed an extended staining area in the cholesteatoma matrix. In epidermal reference tissues, only the basal and nearest suprabasal layers were convincingly labeled. As a rule, non-epidermal CKs did not belong to the cholesteatoma CK set. However, exceptions to that rule were noticed as a focal or more extended expression of one or more non-epidermal CKs in about half of the cases. Together with the extended CK5 topography, this is further evidence that CK expression is seriously affected by the diseased state. CK expression in the perimatrix is limited to mucous glands, either normal, atrophic or hyperplastic. CKs n degrees 4, 5, 7, 14, 18 and 19, also displayed by middle ear mucosa, were consistently observed. Where ductal arrangements were present, CK10 was also detected, in analogy with the CK10 registration in ductal portions of mucous glands in the external ear canal skin. The absence of CK8 in mucous glands of the perimatrix, however, strongly differentiates these structures from the mucous gland acini and ducti in the external ear canal, where CK8 is systematically expressed. Vimentin staining was restricted to dendritic cells of the matrix (Langerhans cells) and to perimatrix fibroblasts, blood cells and vascular endothelium. Coexpression of CK and vimentin was not observed.

[Technics for the study of a total leukocyte dialysate and its fractions]. / Techniques d'étude d'un dialysat leucocytaire total et de ses fractions.

The crude dialysate extracted from human white blood cells from a thousand unselected donors were studied by leukocyte migration inhibition test with measles antigen. This dialysate and its fractions eluted from Biogel P4 and P6 chromatography were compared towards rosette restoration test and nucleotide composition.