Localisation of nucleolus-organising regions in interphase cells

Summary A technique based on the use of silver solutions, which selectively stains the nucleolus-organising regions (NORs) in chromosomes, was applied to interphase Ehrlich tumour cells. The results indicate that nucleolar fibrillar centres correspond to the NORs.     

Ultrastructural cytochemistry of the mammalian cell nucleolus

In the present review on the organization of the mammalian cell nucleolus, we report and discuss data obtained during the past 10 years by means of cytochemical and immunocytochemical ultrastructural techniques. Particular emphasis is placed on the following topics: location of the nucleolus organizer regions in interphasic nucleolar components, structure of nucleolar chromatin in situ, and the structure-function relationship of the nucleolar components. The cytochemical and immunocytochemical results are compared and the concordant data are stressed for each topic.     

The importance of plant–soil interactions,soil nutrients,and plant life history traits for the temporal dynamics of Jacobaea vulgaris in a chronosequence of old‐fields

We examined to what extent temporal dynamics of Jacobaea vulgaris cover in old‐fields were related to plant–soil feedback, soil nutrients, seed availability and performance, and seedling establishment. Long‐term measurements at an experimental field and in ten old‐fields representing a chronosequence following land abandonment revealed a remarkably similar hump‐shaped temporal pattern of J. vulgaris cover, which peaked at about five years after abandonment. In a plant–soil feedback study, J. vulgaris biomass of plants grown in soil from all chronosequence fields was lower than in sterilized control soil. However, biomass of J. vulgaris in the feedback study was lower when grown in soil collected from fields with a high density of J. vulgaris plants than in soil from fields with a low density of J. vulgaris. When plants were grown again in the conditioned soil, a strong negative plant–soil feedback response was observed for soils from all fields. These results indicate that soils from all stages of the chronosequence can develop a strong negative soil feedback to J. vulgaris, and that there is a positive relationship between J. vulgaris density and the subsequent level of control by the soil community. In a common‐garden experiment with turfs collected from the chronosequence fields in which J. vulgaris was seeded, seedling establishment was significantly lower in turfs from older than from young fields. In a seed bank study the number of emerging seedlings declined with time since abandonment of the field. In conclusion, negative plant–soil feedback is an important factor explaining the hump‐shaped population development of J. vulgaris. However, it is not operating alone, as propagule availability and characteristics, and competition may also be important. Thus, in order to explain its contribution to plant population dynamics, the role of biotic plant–soil interactions, soil nutrients and life history characteristics along successional gradients should be considered from a community perspective.     

Dispelling myths about rare disease registry system development

Rare disease registries (RDRs) are an essential tool to improve knowledge and monitor interventions for rare diseases. If designed appropriately, patient and disease related information captured within them can become the cornerstone for effective diagnosis and new therapies. Surprisingly however, registries possess a diverse range of functionality, operate in different, often-times incompatible, software environments and serve various, and sometimes incongruous, purposes. Given the ambitious goals of the International Rare Diseases Research Consortium (IRDiRC) by 2020 and beyond, RDRs must be designed with the agility to evolve and efficiently interoperate in an ever changing rare disease landscape, as well as to cater for rapid changes in Information Communication Technologies. In this paper, we contend that RDR requirements will also evolve in response to a number of factors such as changing disease definitions and diagnostic criteria, the requirement to integrate patient/disease information from advances in either biotechnology and/or phenotypying approaches, as well as the need to adapt dynamically to security and privacy concerns. We dispel a number of myths in RDR development, outline key criteria for robust and sustainable RDR implementation and introduce the concept of a RDR Checklist to guide future RDR development.     

Gut-Microbiota-Metabolite Axis in Early Renal Function Decline

Introduction

Several circulating metabolites derived from bacterial protein fermentation have been found to be inversely associated with renal function but the timing and disease severity is unclear. The aim of this study is to explore the relationship between indoxyl-sulfate, p-cresyl-sulfate, phenylacetylglutamine and gut-microbial profiles in early renal function decline.

Results

Indoxyl-sulfate (Beta(SE) = -2.74(0.24); P = 8.8x10^-29), p-cresyl-sulfate (-1.99(0.24), P = 4.6x10^-16), and phenylacetylglutamine(-2.73 (0.25), P = 1.2x10^-25) were inversely associated with eGFR in a large population base cohort (TwinsUK, n = 4439) with minimal renal function decline. In a sub-sample of 855 individuals, we analysed metabolite associations with 16S gut microbiome profiles (909 profiles, QIIME 1.7.0). Three Operational Taxonomic Units (OTUs) were significantly associated with indoxyl-sulfate and 52 with phenylacetylglutamine after multiple testing; while one OTU was nominally associated with p-cresyl sulfate. All 56 microbial members belong to the order Clostridiales and are represented by anaerobic Gram-positive families Christensenellaceae, Ruminococcaceae and Lachnospiraceae. Within these, three microbes were also associated with eGFR.

Conclusions

Our data suggest that indoxyl-sulfate, p-cresyl-sulfate and phenylacetylglutamine are early markers of renal function decline. Changes in the intestinal flora associated with these metabolites are detectable in early kidney disease. Future efforts should dissect this relationship to improve early diagnostics and therapeutics strategies.