Marine macroalgae as food for earthworms: Growth and selection experiments across ecotypes

Historically, subsistence farmers around the Atlantic coast of NW Europe utilised marine algae as a fertiliser in agroecosystems, a practice that continued in small areas and is now considered to have real potential for re-establishing sustainable food production systems on marginal soils. Earthworms form a significant component of soil fauna and their ecosystem services are well documented. Therefore, palatability of marine organic amendments to faunal detritivores of terrestrial systems is of interest. This work aimed to assess the potential for growth of Aporrectodea caliginosa, Lumbricus rubellus and Aporrectodea longa fed with two common macroalgae (seaweeds), Laminaria digitata and Fucus serratus. In addition, choice chambers were constructed to permit earthworm selection of these macroalgae with more conventional organic materials, horse manure (HM) and birch leaves (BL). Over a period of two months, earthworm species showed significantly greater mass gain with conventional food (p<0.05). Laminaria outperformed Fucus, which in turn was superior to soil alone. Similarly, when given a choice, a significant preference (p<0.001) was shown for the more nitrogen-rich HM and BL over the seaweeds. No removal was recorded for A. caliginosa when offered seaweeds only. By contrast, L. rubellus and A. longa showed significant preferences (p<0.001) for Laminaria over Fucus and fresh material over degraded. These results underline an interest to profit from natural resources (seaweeds) to maintain or improve soil biological quality in marginal coastal areas

Redundant and Specific Roles of the ARGONAUTE Proteins AGO1 and ZLL in Development and Small RNA-Directed Gene Silencing

The Arabidopsis ARGONAUTE1 (AGO1) and ZWILLE/PINHEAD/AGO10 (ZLL) proteins act in the miRNA and siRNA pathways and are essential for multiple processes in development. Here, we analyze what determines common and specific function of both proteins. Analysis of ago1 mutants with partially compromised AGO1 activity revealed that loss of ZLL function re-establishes both siRNA and miRNA pathways for a subset of AGO1 target genes. Loss of ZLL function in ago1 mutants led to increased AGO1 protein levels, whereas AGO1 mRNA levels were unchanged, implicating ZLL as a negative regulator of AGO1 at the protein level. Since ZLL, unlike AGO1, is not subjected to small RNA-mediated repression itself, this cross regulation has the potential to adjust RNA silencing activity independent of feedback dynamics. Although AGO1 is expressed in a broader pattern than ZLL, expression of AGO1 from the ZLL promoter restored transgene PTGS and most developmental defects of ago1, whereas ZLL rescued only a few AGO1 functions when expressed from the AGO1 promoter, suggesting that the specific functions of AGO1 and ZLL are mainly determined by their protein sequence. Protein domain swapping experiments revealed that the PAZ domain, which in AGO1 is involved in binding small RNAs, is interchangeable between both proteins, suggesting that this common small RNA-binding domain contributes to redundant functions. By contrast, the conserved MID and PIWI domains, which are involved in 5′-end small RNA selectivity and mRNA cleavage, and the non-conserved N-terminal domain, to which no function has been assigned, provide specificity to AGO1 and ZLL protein function

A phase I and II study of 2-weekly irinotecan with capecitabine in advanced gastroesophageal adenocarcinoma

We investigated 2-weekly intravenous irinotecan combined with oral capecitabine in patients with advanced gastroesophageal adenocarcinoma. In phase I, doses were escalated in chemotherapy naïve or pretreated patients to establish maximum tolerated doses (MTD). In phase II, patients were treated at MTD as first-line therapy with the primary end point of RECIST response. Dose levels in phase I were as follows: Level 1: irinotecan 150 mg m−2 on day 1; capecitabine 850 mg m−2 12-hourly on days 1–9. Level 2: as level 1 but capecitabine 1000 mg m−2. Level 3: as level 2 but irinotecan 180 mg m−2. Level 4: as level 3 but capecitabine 1250 mg m−2. In phase I, 21 patients were entered. Maximum tolerated dose was level 3. Dose-limiting toxicities were lethargy, diarrhoea, vomiting and mucositis. In phase II, 31 patients were entered at level 3. During the first six cycles, 13 of these patients underwent dose reduction and three patients stopped treatment for toxicity. A further six patients stopped for progressive disease. The commonest grade 3–4 toxicities were lethargy (20%), diarrhoea (17%), nausea (10%) and anorexia (10%). There were no treatment-related deaths. The response rate was 32% (95% CI 16–52%). Median overall survival was 10 months. This regimen is active in gastroesophageal adenocarcinoma. However, using the MTD defined in phase I, fewer than 50% patients tolerated six cycles without modification in phase II; therefore, modification of these doses is recommended for further study

Clamp loader ATPases and the evolution of DNA replication machinery

Clamp loaders are pentameric ATPases of the AAA+ family that operate to ensure processive DNA replication. They do so by loading onto DNA the ring-shaped sliding clamps that tether the polymerase to the DNA. Structural and biochemical analysis of clamp loaders has shown how, despite differences in composition across different branches of life, all clamp loaders undergo the same concerted conformational transformations, which generate a binding surface for the open clamp and an internal spiral chamber into which the DNA at the replication fork can slide, triggering ATP hydrolysis, release of the clamp loader, and closure of the clamp round the DNA. We review here the current understanding of the clamp loader mechanism and discuss the implications of the differences between clamp loaders from the different branches of life

Earthworm burrowing activity of two non-Lumbricidae earthworm species incubated in soils with contrasting organic carbon content (Vertisol vs. Ultisol)

International audienceThe aim of this study was to investigate the burrowing activity of two earthworm species: the endogeic Drawida sinica and one undescribed Amynthas species incubated inVertisol and Ultisol presenting different soil organic C content. Because of their contrasting feeding behaviours, we hypothesised that soil type would have a bigger influence on the burrowing activity of the endogeic than the anecic species. Repacked soil columns inoculated with earthworms for 30 days were scanned using X-ray tomography and the compiled images used to characterise the burrow systems. After scanning, the saturated hydraulic conductivity (K-sat) was also measured. The Amynthas species burrows were less numerous (30 vs. 180), more vertically oriented (57 vs. 37 degrees), more connected from the surface to the bottom of the columns (73 vs. 5 cm(3)) and had a higher global connectivity index (83 vs. 28%) than those of D. sinica. The K-sat was threefold faster in columns incubated with Amynthas and was linked to the volume of percolating burrows (R-2 = 0.81). The soil type did not influence Amynthas burrow characteristics. In contrast, there were 30% more D. sinica burrows in the Vertisol than in the Ultisol while other burrow characteristics were not affected. This result suggests that these burrows were more refilled with casts leading to shorter and discontinuous burrows. The K-sat was negatively related to the number of burrows (R-2 = 0.44) but was not statistically different between the Vertisol and the Ultisol, suggesting a constant impact of this species on the K-sat. We found that a decrease in the amount of soil organic C by 50% had only a small influence on earthworm burrowing activity and no effect on the K-sat

Primary localized rectal/pararectal gastrointestinal stromal tumors: results of surgical and multimodal therapy from the French Sarcoma group.

BACKGROUND: Rectal and pararectal gastrointestinal stromal tumors (GISTs) are rare. The optimal management strategy for primary localized GISTs remains poorly defined. METHODS: We conducted a retrospective analysis of 41 patients with localized rectal or pararectal GISTs treated between 1991 and 2011 in 13 French Sarcoma Group centers. RESULTS: Of 12 patients who received preoperative imatinib therapy for a median duration of 7 (2-12) months, 8 experienced a partial response, 3 had stable disease, and 1 had a complete response. Thirty and 11 patients underwent function-sparing conservative surgery and abdominoperineal resection, respectively. Tumor resections were mostly R0 and R1 in 35 patients. Tumor rupture occurred in 12 patients. Eleven patients received postoperative imatinib with a median follow-up of 59 (2.4-186) months. The median time to disease relapse was 36 (9.8-62) months. The 5-year overall survival rate was 86.5%. Twenty patients developed local recurrence after surgery alone, two developed recurrence after resection combined with preoperative and/or postoperative imatinib, and eight developed metastases. In univariate analysis, the mitotic index (≤5) and tumor size (≤5 cm) were associated with a significantly decreased risk of local relapse. Perioperative imatinib was associated with a significantly reduced risk of overall relapse and local relapse. CONCLUSIONS: Perioperative imatinib therapy was associated with improved disease-free survival. Preoperative imatinib was effective. Tumor shrinkage has a clear benefit for local excision in terms of feasibility and function preservation. Given the complexity of rectal GISTs, referral of patients with this rare disease to expert centers to undergo a multidisciplinary approach is recommended