Discovery of transferable distal genetic elements capable of activating gene transcription was a milestone in the study of transcriptional control. These genetic elements were termed “enhancers” because of their ability to enhance proximal coding gene transcription. Since then, it was believed that the activation potential of enhancers is entirely intrinsic. However, most prior studies of enhancer elements have removed them from their native genomic context, transplanting them onto plasmids or artificial chromosomes, thereby removing any potential effects of other elements in the genome. We sought to ask the question of whether the strongest E2 regulated enhancers on human chromosome 21 might interact, even when located on opposite ends of the chromosome q arm. These interactions play a functional role in allowing all interacting enhancers to have synergistically high levels of robustness. We have found that a cohort of the most highly active “first tier” ERα bound enhancers on chromosome 21, distributed across a linear distance of over 30 mega-bases, exhibit induced proximity when treated with the ligand agonist estradiol-17β (E2). Using CRISPR-Cas9 technology to delete some of these enhancers, we found, these enhancers seem to confer additional robustness onto other interacting enhancers. We believe that this occurs due to the physical proximity between “first tier” enhancers gained in response to E2, and that these interactions are dependent upon eRNA and a host of protein factors. These individual first tier enhancers in effect form a previously unappreciated “spatially distributed super-enhancer network”. These interaction events reflect physical constraints placed upon chromosome 21 imposed by a very large heterochromatic “B” compartment, which seems to predominantly localize to the surface of the nucleolus arising from the ribosomal DNA repeat rich p-arm of the acrocentric chromosome 21. The euchromatin “A” compartments on either side of the “B” compartment are thus allowed to interact dynamically. These sorts of dynamic interactions between regions of the chromosome constitute, in part, the overall structure of the chromosome. Therefore, the robustness of individual enhancers in a chromosome cannot be disentangled from the contributions of all interacting enhancers and the subnuclear structures in which these interactions can occur.

Recent evidence indicates that insulin resistance in skeletal muscle may be related to reduce mitochondrial number and oxidation capacity. However, it is not known whether increasing mitochondrial number and function improves insulin resistance. In the present study, we investigated the effects of a combination of nutrients on insulin resistance and mitochondrial biogenesis/function in skeletal muscle of type 2 diabetic Goto–Kakizaki rats.

We demonstrated that defect of glucose and lipid metabolism is associated with low mitochondrial content and reduced mitochondrial enzyme activity in skeletal muscle of the diabetic Goto-Kakizaki rats. The treatment of combination of R-α-lipoic acid, acetyl-L-carnitine, nicotinamide, and biotin effectively improved glucose tolerance, decreased the basal insulin secretion and the level of circulating free fatty acid (FFA), and prevented the reduction of mitochondrial biogenesis in skeletal muscle. The nutrients treatment also significantly increased mRNA levels of genes involved in lipid metabolism, including peroxisome proliferator–activated receptor-α (Pparα), peroxisome proliferator–activated receptor-δ (Pparδ), and carnitine palmitoyl transferase-1 (Mcpt-1) and activity of mitochondrial complex I and II in skeletal muscle. All of these effects of mitochondrial nutrients are comparable to that of the antidiabetic drug, pioglitazone. In addition, the treatment with nutrients, unlike pioglitazone, did not cause body weight gain.

These data suggest that a combination of mitochondrial targeting nutrients may improve skeletal mitochondrial dysfunction and exert hypoglycemic effects, without causing weight gain.

To evaluate the efficacy and safety of a novel sutureless AMT (amniotic membrane transplantation) or CAT (conjunctivolimbal autograft transplantation) using fibrin glue for reconstructing corneoconjunctival surfaces for primary pterygium associated with cysts.

A prospective descriptive study was made of the period 1 January 2006-1 May 2009. Nine patients with primary pterygium associated with cysts underwent pterygium and cyst excision followed by sutureless AMT or CAT using fibrin glue.

During a mean follow-up of 8.00±0.67 months, all eyes maintained a smooth and stable corneal epithelial surface without recurrent erosion or persistent epithelial defect. The limbal donor site showed the presence of mild depressions without the formation of pseudopterygium. All eyes have good tear secretion function, tear film stability and ocular motility.

Sutureless transplantation using fibrin glue is safe and effective for restoring a stable corneoconjunctival epithelium in primary pterygium associated with cysts.