piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans

Transgenerational effects have wide-ranging implications for human health, biological adaptation, and evolution; however, their mechanisms and biology remain poorly understood. Here, we demonstrate that a germline nuclear small RNA/chromatin pathway can maintain stable inheritance for many generations when triggered by a piRNA-dependent foreign RNA response in C. elegans. Using forward genetic screens and candidate approaches, we find that a core set of nuclear RNAi and chromatin factors is required for multigenerational inheritance of environmental RNAi and piRNA silencing. These include a germline-specific nuclear Argonaute HRDE1/WAGO-9, a HP1 ortholog HPL-2, and two putative histone methyltransferases, SET-25 and SET-32. piRNAs can trigger highly stable long-term silencing lasting at least 20 generations. Once established, this long-term memory becomes independent of the piRNA trigger but remains dependent on the nuclear RNAi/chromatin pathway. Our data present a multigenerational epigenetic inheritance mechanism induced by piRNAs.     

Adherence to a treat-to-target strategy in early rheumatoid arthritis: results of the DREAM remission induction cohort

Introduction

Clinical trials have demonstrated that treatment-to-target (T2T) is effective in achieving remission in early rheumatoid arthritis (RA). However, the concept of T2T has not been fully implemented yet and the question is whether a T2T strategy is feasible in daily clinical practice. The objective of the study was to evaluate the adherence to a T2T strategy aiming at remission (Disease Activity Score in 28 joints (DAS28) < 2.6) in early RA in daily practice. The recommendations regarding T2T included regular assessment of the DAS28 and advice regarding DAS28-driven treatment adjustments.

Methods

A medical chart review was performed among a random sample of 100 RA patients of the DREAM remission induction cohort. At all scheduled visits, it was determined whether the clinical decisions were compliant to the T2T recommendations.

Results

The 100 patients contributed to a total of 1,115 visits. The DAS28 was available in 97.9% (1,092/1,115) of the visits, of which the DAS28 was assessed at a frequency of at least every three months in 88.3% (964/1,092). Adherence to the treatment advice was observed in 69.3% (757/1,092) of the visits. In case of non-adherence when remission was present (19.5%, 108/553), most frequently medication was tapered off or discontinued when it should have been continued (7.2%, 40/553) or treatment was continued when it should have been tapered off or discontinued (6.2%, 34/553). In case of non-adherence when remission was absent (42.1%, 227/539), most frequently medication was not intensified when an intensification step should have been taken (34.9%, 188/539). The main reason for non-adherence was discordance between disease activity status according to the rheumatologist and DAS28.

Conclusions

The recommendations regarding T2T were successfully implemented and high adherence was observed. This demonstrates that a T2T strategy is feasible in RA in daily clinical practice.     

Isolation and characterization of 11 microsatellite primers for a temperate reef fish, the California sheephead (Semicossyphus pulcher)

Eleven microsatellites were characterized for Semicossyphus pulcher (California sheephead) using an enrichment protocol. The number of alleles varied from three to 14 for a sample of 40 individuals from two populations. Expected heterozygosities ranged from 0.311 to 0.891. All loci but one were in Hardy-Weinberg equilibrium. No evidence for linkage disequilibrium was observed. These polymorphic microsatellites will be useful for genetic diversity and connectivity analyses of S. pulcher.     

Tree diversity,composition, forest structure and aboveground biomass dynamics after single and repeated fire in a Bornean rain forest

Forest fires remain a devastating phenomenon in the tropics that not only affect forest structure and biodiversity, but also contribute significantly to atmospheric CO2. Fire used to be extremely rare in tropical forests, leaving ample time for forests to regenerate to pre-fire conditions. In recent decades, however, tropical forest fires occur more frequently and at larger spatial scales than they used to. We studied forest structure, tree species diversity, tree species composition, and aboveground biomass during the first 7 years since fire in unburned, once burned and twice burned forest of eastern Borneo to determine the rate of recovery of these forests. We paid special attention to changes in the tree species composition during burned forest regeneration because we expect the long-term recovery of aboveground biomass and ecosystem functions in burned forests to largely depend on the successful regeneration of the pre-fire, heavy-wood, species composition. We found that forest structure (canopy openness, leaf area index, herb cover, and stem density) is strongly affected by fire but shows quick recovery. However, species composition shows no or limited recovery and aboveground biomass, which is greatly reduced by fire, continues to be low or decline up to 7 years after fire. Consequently, large amounts of the C released to the atmosphere by fire will not be recaptured by the burned forest ecosystem in the near future. We also observed that repeated fire, with an inter-fire interval of 15 years, does not necessarily lead to a huge deterioration in the regeneration potential of tropical forest. We conclude that burned forests are valuable and should be conserved and that long-term monitoring programs in secondary forests are necessary to determine their recovery rates, especially in relation to aboveground biomass accumulation.     

The human La (SS-B) autoantigen interacts with DDX15/hPrp43, a putative DEAH-box RNA helicase

The human La (SS-B) autoantigen is an abundantly expressed putative RNA chaperone, functioning in various intracellular processes involving RNA. To further explore the molecular mechanisms by which La functions in these processes, we performed large-scale immunoprecipitations of La from HeLa S100 extracts using the anti-La monoclonal antibody SW5. La-associated proteins were subsequently identified by sequence analysis. This approach allowed the identification of DDX15 as a protein interacting with La. DDX15, the human ortholog of yeast Prp43, is a member of the superfamily of DEAH-box RNA helicases that appeared to interact with La both in vivo and in vitro. The region needed for the interaction with La partly overlaps the DEAH-box domain of DDX15. Immunofluorescence data indicated that endogenous DDX15 accumulates in U snRNP containing nuclear speckles in HEp-2 cells. Surprisingly DDX15 also accumulates in the nucleoli of HEp-2 cells. Moreover, DDX15 and La seem to colocalize in the nucleoli. Regions of DDX15 involved in nuclear, nuclear speckle, and nucleolar localization are located within the N- and C-terminal regions flanking the DEAH-box. RNA coprecipitation experiments indicated that DDX15 is associated with spliceosomal U small nuclear RNAs in HeLa cell extracts. The possible functional implications of the interaction between La and DDX15 are discussed.     

Enzymatic glycan remodeling–metal free click (GlycoConnect™) provides homogenous antibody-drug conjugates with improved stability and therapeutic index without sequence engineering

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Scaling Relationships in Life Cycle Assessment

Life cycle assessment (LCA) studies include a vast amount of different products. Often, extrapolations are necessary to obtain the life cycle inventory of a specific product. This article provides quantitative scaling factors with power (heat output) for product properties and life cycle impact assessment results of heat pump and biomass furnace technologies. Included in the study are 508 heat pumps and furnaces with differences in power over three orders of magnitude per product group. The key properties of the heat pump system were defined as mass, refrigerant use, and coefficient of performance. For the biomass furnaces, the key properties analyzed were mass, electrical input, and efficiency. The results indicated that both the mass and the refrigerant use increased subproportionally to power. For coefficient of performance and furnace efficiency, no scaling effect was found. Subproportional growth was found between two environmental impacts (global warming and ozone depletion) and power for the production phase. This scaling behavior was similar to conventional cost scaling. The results of our study imply that in LCA, scaling factors can be applied to estimate key properties and corresponding life cycle impact assessment results. This is particularly useful for prospective technology assessments with limited data available.     

Pathogenicity,characterization and comparative virulence of Rhizoctonia spp. from insect-galled roots of Lepidium draba in Europe

The association of Rhizoctonia spp. with insect-damaged and diseased tissue of the invasive perennial Lepidium draba was documented throughout the range of L. draba that was surveyed in Europe, including Hungary, Austria, Switzerland and France. Samples that could be both maintained under cooled conditions after collection and promptly processed consistently yielded Rhizoctonia solani, 11 isolates of which anastomosed with AG-4, one with AG-2-1 and one isolate was determined to be binucleate. Comparative virulence among the isolates was analyzed using nonparametric survival analysis for interval-censored data. This analysis indicated that there were significant differences among the isolates. These findings provide further evidence that both root-attacking insects and soilborne pathogens are associated with the lower density of a perennial invasive species in its native range. Prioritization of prospective biocontrol agents should include the ability to engage in insect/plant pathogen synergisms. The application of nonparametric maximum likelihood estimation to interval-censored data for the assessment of comparative virulence among several strains of a plant pathogen is more accessible than calculation of the area under the disease progress curve.