Since the discovery that enhancers can support transcription, the roles of enhancer RNAs have remained largely elusive. We identified that enhancer RNAs interact with and augment bromodomain engagement with acetylated chromatin. Here, we discuss our recent findings and the potential mechanisms underlying the regulation and functions of enhancer RNA-bromodomain associations.

Neurofibromatosis type 1 is a rare neurogenetic syndrome, characterized by pigmentary abnormalities, learning and social deficits, and a predisposition for benign and malignant tumor formation caused by germline mutations in the NF1 gene. With the cloning of the NF1 gene and the recognition that the encoded protein, neurofibromin, largely functions as a negative regulator of RAS activity, attention has mainly focused on RAS and canonical RAS effector pathway signaling relevant to disease pathogenesis and treatment. However, as neurofibromin is a large cytoplasmic protein the RAS regulatory domain of which occupies only 10% of its entire coding sequence, both canonical and non-canonical RAS pathway modulation, as well as the existence of potential non-RAS functions, are becoming apparent. In this Special article, we discuss our current understanding of neurofibromin function.

Cardiac functions can be altered by changes in the microstructure of the heart, i.e., remodeling of the cardiac tissue, which may activate pathologies such as hypertrophy, dilation, or cardiac fibrosis. Cardiac fibrosis can develop due to an excessive deposition of extracellular matrix proteins, which are products of the activation of fibroblasts. In this context, the anatomical-histological change may interfere with the functioning of the cardiac tissue, which requires specialized cells for its operation. The purpose of the present study was to determine the cellular interactions and morphological changes in cocultures of 3T3 fibroblasts and RL-14 cardiomyocytes via the generation of a platform an in vitro model. For this purpose, a platform emulating the biological characteristics of endomyocardial fibrosis was generated using a cell patterning technique to study morphological cellular changes in compact and irregular patterns of fibrosis. It was found that cellular patterns emulating the geometrical distributions of endomyocardial fibrosis generated morphological changes after interaction of the RL-14 cardiomyocytes with the 3T3 fibroblasts. Through this study, it was possible to evaluate biological characteristics such as cell proliferation, adhesion, and spatial distribution, which are directly related to the type of emulated endomyocardial fibrosis. This research concluded that fibroblasts inhibited the proliferation of cardiomyocytes via their interaction with specific microarchitectures. This behavior is consistent with the histopathological distribution of cardiac fibrosis; therefore, the platform developed in this research could be useful for the in vitro assessment of cellular microdomains. This would allow for the experimental determination of interactions with drugs, substrates, or biomaterials within the engineering of cardiac tissues.

The Iglesia basin, in the San Juan Province, is the northern part of a Cenozoic piggy-back basin (the Iglesia-Calingasta-Uspallata basin), located above of the active flat-slab subduction zone of western Argentina. This basin is located between two mountain ranges, the Cordillera Frontal to the west and the Precordillera to the east, affected by thin and thick skinned tectonics, respectively. It is elongated in a north-south direction (70 km) and has a maximum width of 35 km. We have analyzed 17 seismic reflection lines corresponding to more than 500 km of interpreted sections. A strong reflection at 0.5-2 s is interpreted as indicative of shales and sandstones in the upper part of the Agua Negra Formation (Carboniferous); this represents a seismic basement for the Iglesia basin clearly separating stratified (shallower) from chaotic (deeper) reflectors. Several high angle faults have been recognized in the interpreted seismic lines affecting the Neogene fill and even the basement; some of them correlate with structures observed at the surface such us El Tigre Fault System. A 3D model shows the seismic top of basement smoothly deepening down to 3,650 m beneath the Pismanta area. The basement continues upward to the east with a steeper slope clearly defining an asymmetrical shape for the basin. Moreover, there are three depocenters of similar maximum depths around the geothermal hot spring of the Pismanta center. Some of the interpreted faults may be helping in the outflow process of meteoric water heated by a normal geothermal gradient. Considering earthquake data framework, our observations correlate with transpressive deformation likely associated with El Tigre Fault System, which affects Neogene and Pleistocene strata of the Iglesia Group.

No abstract