MicroRNAs, Heart Failure, and Aging: Potential Interactions with Skeletal Muscle

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by targeting mRNAs for degradation or translational repression. MiRNAs can be expressed tissue specifically and are altered in response to various physiological conditions. It has recently been shown that miRNAs are released into the circulation, potentially for the purpose of communicating with distant tissues. This manuscript discusses miRNA alterations in cardiac muscle and the circulation during heart failure, a prevalent and costly public health issue. A potential mechanism for how skeletal muscle maladaptations during heart failure could be mediated by myocardium-derived miRNAs released to the circulation is presented. An overview of miRNA alterations in skeletal muscle during the ubiquitous process of aging and perspectives on miRNA interactions during heart failure are also provided

Characterization of the infectious reservoir of malaria with an agent-based model calibrated to age-stratified parasite densities and infectiousness

Background Elimination of malaria can only be achieved through removal of all vectors or complete depletion of the infectious reservoir in humans. Mechanistic models can be built to synthesize diverse observations from the field collected under a variety of conditions and subsequently used to query the infectious reservoir in great detail. Methods The EMOD model of malaria transmission was calibrated to prevalence, incidence, asexual parasite density, gametocyte density, infection duration, and infectiousness data from 9 study sites. The infectious reservoir was characterized by diagnostic detection limit and age group over a range of transmission intensities with and without case management and vector control. Mass screen-and-treat drug campaigns were tested for likelihood of achieving elimination. Results The composition of the infectious reservoir by diagnostic threshold is similar over a range of transmission intensities, and higher intensity settings are biased toward infections in children. Recent ramp-ups in case management and use of insecticide-treated bednets reduce the infectious reservoir and shift the composition toward submicroscopic infections. Mass campaigns with antimalarial drugs are highly effective at interrupting transmission if deployed shortly after ITN campaigns. Conclusions Low density infections comprise a substantial portion of the infectious reservoir. Proper timing of vector control, seasonal variation in transmission intensity, and mass drug campaigns allows lingering population immunity to help drive a region toward elimination.Comment: submitted to Malaria Journal on March 31, 201

Myonuclear Domain Flexibility Challenges Rigid Assumptions on Satellite Cell Contribution to Skeletal Muscle Fiber Hypertrophy

Satellite cell-mediated myonuclear accretion is thought to be required for skeletal muscle fiber hypertrophy, and even drive hypertrophy by preceding growth. Recent studies in humans and rodents provide evidence that challenge this axiom. Specifically, Type 2 muscle fibers reliably demonstrate a substantial capacity to hypertrophy in the absence of myonuclear accretion, challenging the notion of a tightly regulated myonuclear domain (i.e., area that each myonucleus transcriptionally governs). In fact, a “myonuclear domain ceiling”, or upper limit of transcriptional output per nucleus to support hypertrophy, has yet to be identified. Satellite cells respond to muscle damage, and also play an important role in extracellular matrix remodeling during loading-induced hypertrophy. We postulate that robust satellite cell activation and proliferation in response to mechanical loading is largely for these purposes. Future work will aim to elucidate the mechanisms by which Type 2 fibers can hypertrophy without additional myonuclei, the extent to which Type 1 fibers can grow without myonuclear accretion, and whether a true myonuclear domain ceiling exists

Translocation as a strategy to rehabilitate the queen conch (Strombus gigas) population in the Florida Keys

Queen conch (Strombus gigas) stocks in the Florida Keys once supported commercial and recreational fisheries, but overharvesting has decimated this once abundant snail. Despite a ban on harvesting this species since 1985, the local conch population has not recovered. In addition, previous work has reported that conch located in nearshore Keys waters are incapable of spawning because of poor gonadal condition, although reproduction does occur offshore. Queen conch in other areas undergo ontogenetic migrations from shallow, nearshore sites to offshore habitats, but conch in the Florida Keys are prevented from doing so by Hawk Channel. The present study was initiated to determine the potential of translocating nonspawning nearshore conch to offshore sites in order to augment the spawning stock. We translocated adult conch from two nearshore sites to two offshore sites. Histological examinations at the initiation of this study confirmed that nearshore conch were incapable of reproduction, whereas offshore conch had normal gonads and thus were able to reproduce. The gonads of nearshore females were in worse condition than those of nearshore males. However, the gonadal condition of the translocated nearshore conch improved, and these animals began spawning after three months offshore. This finding suggests that some component of the nearshore environment (e.g., pollutants, temperature extremes, poor food or habitat quality) disrupts reproduction in conch, but that removal of nearshore animals to suitable offshore habitat can restore reproductive viability. These results indicate that translocations are preferable to releasing hatchery-reared juveniles because they are more cost-effective, result in a more rapid increase in reproductive output, and maintain the genetic integrity of the wild stock. Therefore, translocating nearshore conch to offshore spawning aggregations may be the key to expediting the recovery of queen conch stocks in the Florida Keys

Myonuclear Transcriptional Dynamics in Response to Exercise Following Satellite Cell Depletion

Skeletal muscle is composed of post-mitotic myofibers that form a syncytium containing hundreds of myonuclei. Using a progressive exercise training model in the mouse and single nucleus RNA-sequencing (snRNA-seq) for high-resolution characterization of myonuclear transcription, we show myonuclear functional specialization in muscle. After 4 weeks of exercise training, snRNA-seq reveals that resident muscle stem cells, or satellite cells, are activated with acute exercise but demonstrate limited lineage progression while contributing to muscle adaptation. In the absence of satellite cells, a portion of nuclei demonstrates divergent transcriptional dynamics associated with mixed-fate identities compared with satellite cell replete muscles. These data provide a compendium of information about how satellite cells influence myonuclear transcription in response to exercise