Timely expression of PGAM5 and its cleavage control mitochondrial homeostasis during neurite re-growth after traumatic brain injury.

BACKGROUND: Patients suffered from severe traumatic brain injury (TBI) have twice the risk of developing into neurodegenerative diseases later in their life. Thus, early intervention is needed not only to treat TBI but also to reduce neurodegenerative diseases in the future. Physiological functions of neurons highly depend on mitochondria. Thus, when mitochondrial integrity is compromised by injury, neurons would initiate a cascade of events to maintain homeostasis of mitochondria. However, what protein senses mitochondrial dysfunction and how mitochondrial homeostasis is maintained during regeneration remains unclear. RESULTS: We found that TBI-increased transcription of a mitochondrial protein, phosphoglycerate mutase 5 (PGAM5), during acute phase was via topological remodeling of a novel enhancer-promoter interaction. This up-regulated PGAM5 correlated with mitophagy, whereas presenilins-associated rhomboid-like protein (PARL)-dependent PGAM5 cleavage at a later stage of TBI enhanced mitochondrial transcription factor A (TFAM) expression and mitochondrial mass. To test whether PGAM5 cleavage and TFAM expression were sufficient for functional recovery, mitochondrial oxidative phosphorylation uncoupler carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) was used to uncouple electron transport chain and reduce mitochondrial function. As a result, FCCP triggered PGAM5 cleavage, TFAM expression and recovery of motor function deficits of CCI mice. CONCLUSIONS: Findings from this study implicate that PGAM5 may act as a mitochondrial sensor for brain injury to activate its own transcription at acute phase, serving to remove damaged mitochondria through mitophagy. Subsequently, PGAM5 is cleaved by PARL, and TFAM expression is increased for mitochondrial biogenesis at a later stage after TBI. Taken together, this study concludes that timely regulation of PGAM5 expression and its own cleavage are required for neurite re-growth and functional recovery.

Epicardial delivery of a conductive membrane synchronizes conduction to reduce atrial fibrillation.

Conductive polymers have been investigated as a medium for the transmission of electrical signals in biological tissues, but their capacity to rewire cardiac tissue has not been evaluated. Myocardial tissue is unique in being able to generate an electrical potential at a fixed rate; this potential spreads rapidly among cells to trigger muscle contractions. Tissue injuries result in myocardial fibrosis and subsequent non-uniform conductivity, leading to arrhythmia. Atrial fibrillation (AF) is the most common sustained arrhythmia, associated with disruption of atrial electrical signaling, which can potentially be restored by the epicardial delivery of conductive polymers. In this work, poly-3-amino-4-methoxybenzoic acid, conjugated to gelatin, is fabricated as a membrane (PAMB-G) to support conductive velocities that are close to that of the myocardium. A cross-linked gelatin membrane (Gelatin) is used as a control. The as-fabricated PAMB-G has similar tensile elasticities, determined using the Young's modulus, as contracting myocardium; it can also transmit electrical signals to initiate cardiac cell and tissue excitation. Delivering PAMB-G onto the atrium of a rat AF model shortens AF duration and improves post-AF recovery for the duration of a 28-day-long study. Atrial tissue in the PAMB-G-implanted group has lower impedance, higher conduction velocity, and higher field potential amplitude than that in the Gelatin-implanted group. Therefore, the as-proposed PAMB-G is a suitable medium for restoring proper cardiac electrical signaling in AF hearts.

A fast and facile platform for fabricating phase-change materials-based drug carriers powered by chemical Marangoni effect.

Emulsions of oil droplets as drug carriers are typically formulated by emulsification, which is complex and time-consuming and requires high energy input. To address these concerns, a fast and facile method for fabricating lipid-based oil droplets, using propulsive forces that arise from the chemical Marangoni effect, is developed for the oral delivery of lipophilic drugs, such as vitamin D. The oil droplets are prepared by solubilizing vitamin D in a phase-changeable fatty acid with the addition of ethanol as an oil phase, which is then deposited on a water bath. As a result of the differing surface tensions of water and ethanol (chemical energy), propulsive Marangoni forces are generated (kinetic energy), rapidly spreading the oil phase into many tiny oil droplets. To prevent their coalescence, the generated oil droplets are solidified by reducing their environmental temperature. Following oral administration, the fluidity of the solidified droplets increases at body temperature; they can be further emulsified into the vitamin D-containing micelles by intestinal bile salts. The micelles are then taken up by the intestinal epithelial cells, enabling their contained vitamin D to be absorbed into systemic circulation, improving its oral bioavailability.

Cloudy with a Chance of Insights: Context Dependent Gene Regulation and Implications for Evolutionary Studies.

Research in various fields of evolutionary biology has shown that divergence in gene expression is a key driver for phenotypic evolution. An exceptional contribution of cis-regulatory divergence has been found to contribute to morphological diversification. In the light of these findings, the analysis of genome-wide expression data has become one of the central tools to link genotype and phenotype information on a more mechanistic level. However, in many studies, especially if general conclusions are drawn from such data, a key feature of gene regulation is often neglected. With our article, we want to raise awareness that gene regulation and thus gene expression is highly context dependent. Genes show tissue- and stage-specific expression. We argue that the regulatory context must be considered in comparative expression studies.

PCR-RFLP of mitochondrial DNA reveals two origins of Apis mellifera in Taiwan.

Beekeeping has been a highly valued industry in Taiwan. As a result, many subspecies of Apis mellifera have been introduced to Taiwan since 1911, leading to the hybridization of different subspecies. In order to know the matrilineal origins of Taiwan A. mellifera, a total of 280 samples collected from 33 apiaries throughout the island were examined. Using PCR-RFLP of four mitochondrial gene fragments, i.e., the non-coding region between tRNAleu and cytochrome c oxidase subunit II (intergenic tRNAleu-COII), cytochrome b (Cyt b), large subunit rRNA (Ls rRNA) and cytochrome c oxidase subunit I (COI), we only found two haplotypes exist in 280 samples. Haplotypes ababa and bbbaa account for 87% of these Western bees belonged to the Eastern European (C) lineage and 13% belonged to the Middle East (Z) lineage, respectively, with the latter being totally absent in northern Taiwan. African (A) and Mellifera (M) lineages, officially imported once in 1990s and 1930s respectively, were not detected. The identification of subspecies of A. mellifera and survey of their distribution on the island are expected to facilitate efficient breeding programs and establish a more booming beekeeping industry.