In vertebrates, cytosine-guanine (CpG) dinucleotides are predominantly methylated, with ∼80% of all CpG sites containing 5-methylcytosine (5mC), a repressive mark associated with long-term gene silencing. The exceptions to such a globally hypermethylated state are CpG-rich DNA sequences called CpG islands (CGIs), which are mostly hypomethylated relative to the bulk genome. CGIs overlap promoters from the earliest vertebrates to humans, indicating a concerted evolutionary drive compatible with CGI retention. CGIs are characterised by DNA sequence features that include DNA hypomethylation, elevated CpG and GC content and the presence of transcription factor binding sites. These sequence characteristics are congruous with the recruitment of transcription factors and chromatin modifying enzymes, and transcriptional activation in general. CGIs colocalize with sites of transcriptional initiation in hypermethylated vertebrate genomes, however, a growing body of evidence indicates that CGIs might exert their gene regulatory function in other genomic contexts. In this review, we discuss the diverse regulatory features of CGIs, their functional readout, and the evolutionary implications associated with CGI retention in vertebrates and possibly in invertebrates.Protein-protein interactions (PPIs) orchestrate nearly all biological processes. They are also considered attractive drug targets for treating many human diseases, including cancers and neurodegenerative disorders. Protein-fragment complementation assays (PCAs) provide a direct and straightforward way to study PPIs in living cells or multicellular organisms. Importantly, PCAs can be used to detect the interaction of proteins expressed at endogenous levels in their native cellular environment. In this review, we present the principle of PCAs and discuss some of their advantages and limitations. We describe their application in large-scale experiments to investigate PPI networks and to screen or profile PPI targeting compounds.Alzheimer’s disease (AD) is a common neurodegenerative condition that involves the extracellular accumulation of amyloid plaques predominantly consisting of Aβ peptide aggregates. The amyloid plaques and soluble oligomeric species of Aβ are believed to be the major cause of synaptic dysfunction in AD brain and their cytotoxic mechanisms have been proposed to involve interactions with cell membranes. In this review, we discuss our solid-state nuclear magnetic resonance (ssNMR) studies of Aβ interactions with model membranes.

To demonstrate the applicability of a growth modeling framework for quantifying spatial variations in geographic atrophy (GA) lesion kinetics.

Thirty-eight eyes from 27 patients with GA secondary to age-related macular degeneration were imaged with a commercial swept source optical coherence tomography instrument at two visits separated by 1 year. Local GA growth rates were computed at 6-µm intervals along each lesion margin using a previously described growth model. Corresponding margin eccentricities, margin angles, and growth angles were also computed. The average GA growth rates conditioned on margin eccentricity, margin angle, growth angle, and fundus position were estimated via kernel regression.

A total of 88,356 GA margin points were analyzed. The average GA growth rates exhibited a hill-shaped dependency on eccentricity, being highest in the 0.5 mm to 1.6 mm range and lower on either side of that range. Average growth rates were also found to be higher for growth trajectories oriented away from (smaller growth angle), rather than toward (larger growth angle), the foveal center. The dependency of average growth rate on margin angle was less pronounced, although lesion segments in the superior and nasal aspects tended to grow faster.

Our proposed growth modeling framework seems to be well-suited for generating accurate, spatially resolved GA growth rate atlases and should be confirmed on larger datasets.

Our proposed growth modeling framework may enable more accurate measurements of spatial variations in GA growth rates.

Our proposed growth modeling framework may enable more accurate measurements of spatial variations in GA growth rates.

Many recent studies emphasize that mixed species is a promising silvicultural option for sustainable ecosystem management under uncertain and risky future environmental conditions. However, compared with monocultures, knowledge of mixed stands is still rather fragmentary. This comprehensive study analysed the most common Central European tree species combinations to determine the extent to which mono-layered species mixing (i) can increase stand productivity and stem diameter growth, (ii) increase stand density or growth efficiency, and (iii) reduce competition and attenuate the relationship between stand density and stem diameter growth compared with mono-specific stands.

The study was based on 63 long-term experimental plots in Germany with repeated spatially explicit stand inventories. They covered mono-specific and mixed species stands of Norway spruce (Picea abies), silver fir (Abies alba), Scots pine (Pinus sylvestris), European beech (Fagus sylvatica), sessile oak (Quercus petraea), European ash (Friptions for mixed-species stands.Polycystic Kidney Disease (PKD) refers to a group of disorders, driven by the formation of cysts in renal tubular cells and is currently one of the leading causes of end-stage renal disease. The range of symptoms observed in PKD is due to mutations in cilia-localising genes, resulting in changes in cellular signalling. AZD9291 molecular weight As such, compounds that are currently in preclinical and clinical trials target some of these signalling pathways that are dysregulated in PKD. In this review, we highlight these pathways including cAMP, EGF and AMPK signalling and drugs that target them and may show promise in lessening the disease burden of PKD patients. At present, tolvaptan is the only approved therapy for ADPKD, however, it carries several adverse side effects whilst comparatively, no pharmacological drug is approved for ARPKD treatment. Aside from this, drugs that have been the subject of multiple clinical trials such as metformin, which targets AMPK signalling and somatostatins, which target cAMP signalling have shown great promise in reducing cyst formation and cellular proliferation.