Aerobic Interval Training Partly Reverse Contractile Dysfunction and Impaired Ca2+ Handling in Atrial Myocytes from Rats with Post Infarction Heart Failure

Background

There is limited knowledge about atrial myocyte Ca²⁺ handling in the failing hearts. The aim of this study was to examine atrial myocyte contractile function and Ca²⁺ handling in rats with post-infarction heart failure (HF) and to examine whether aerobic interval training could reverse a potential dysfunction.

Methods and results

Post-infarction HF was induced in Sprague Dawley rats by ligation of the left descending coronary artery. Atrial myocyte shortening was depressed (p<0.01) and time to relaxation was prolonged (p<0.01) in sedentary HF-rats compared to healthy controls. This was associated with decreased Ca²⁺ amplitude, decreased SR Ca²⁺ content, and slower Ca²⁺ transient decay. Atrial myocytes from HF-rats had reduced sarcoplasmic reticulum Ca²⁺ ATPase activity, increased Na⁺/Ca²⁺-exchanger activity and increased diastolic Ca²⁺ leak through ryanodine receptors. High intensity aerobic interval training in HF-rats restored atrial myocyte contractile function and reversed changes in atrial Ca²⁺ handling in HF.

Conclusion

Post infarction HF in rats causes profound impairment in atrial myocyte contractile function and Ca²⁺ handling. The observed dysfunction in atrial myocytes was partly reversed after aerobic interval training.     

Single cell time-resolved quorum responses reveal dependence on cell density and configuration

Bacterial communication via quorum sensing has been extensively investigated in recent years. Bacteria communicate in a complex manner through the production, release, and reception of diffusible low molecular weight chemical signaling molecules. Much work has focused on understanding the basic mechanisms of quorum sensing. As more and more bacteria grow resistant to conventional antibiotics, the development of drugs that do not kill bacteria but instead interrupt their communication is of increasing interest. This study presents a method for analyzing bacterial communication by investigating single cell responses. Most conventional analysis methods for bacterial communication are based on the averaged response from many bacteria, masking how individual cells respond to their immediate environment. We applied a fiber-optic microarray to record cellular communication from single cells. Single cell quorum sensing systems have previously been employed, but the highly ordered array reported here is an improvement because it allows us to simultaneously investigate cellular communication in many different environments with known cellular densities and configurations. We employed this method to detect how genes under quorum regulation are induced or repressed over time on the single cell level and to determine whether cellular density and configuration are indicative of the single cell temporal patterns of gene expression.     

Taking practical learning in STEM education home: Examples from do‐it‐yourself experiments in plant biology

Practical teaching can give authentic learning experiences and teach valuable skills for undergraduate students in the STEM disciplines. One of the main ways of giving students such experiences, laboratory teaching, is met with many challenges such as budget cuts, increased use of virtual learning, and currently the university lockdowns due to the COVID‐19 pandemic. We highlight how at‐home do‐it‐yourself (DIY) experiments can be a good way to include physical interaction with your study organism, system, or technique to give the students a practical, authentic learning experience. We hope that by outlining the benefits of a practical, at‐home, DIY experiment we can inspire more people to design these teaching activities in the current remote teaching situation and beyond. By contributing two examples in the field of plant biology we enrich the database on experiments to draw inspiration from for these teaching methods.     

Next‐generation field courses: Integrating Open Science and online learning

As Open Science practices become more commonplace, there is a need for the next generation of scientists to be well versed in these aspects of scientific research. Yet, many training opportunities for early career researchers (ECRs) could better emphasize or integrate Open Science elements. Field courses provide opportunities for ECRs to apply theoretical knowledge, practice new methodological approaches, and gain an appreciation for the challenges of real‐life research, and could provide an excellent platform for integrating training in Open Science practices. Our recent experience, as primarily ECRs engaged in a field course interrupted by COVID‐19, led us to reflect on the potential to enhance learning outcomes in field courses by integrating Open Science practices and online learning components. Specifically, we highlight the opportunity for field courses to align teaching activities with the recent developments and trends in how we conduct research, including training in: publishing registered reports, collecting data using standardized methods, adopting high‐quality data documentation, managing data through reproducible workflows, and sharing and publishing data through appropriate channels. We also discuss how field courses can use online tools to optimize time in the field, develop open access resources, and cultivate collaborations. By integrating these elements, we suggest that the next generation of field courses will offer excellent arenas for participants to adopt Open Science practices.     

Human cytomegalovirus infection increases mitochondrial biogenesis

Fibroblasts infected by Human Cytomegalovirus (CMV) undergo a robust increase in mitochondrial biogenesis with a corresponding increase in mitochondrial activity that is partly dependent on the viral anti-apoptotic pUL37x1 protein (vMIA). The increased respiration activity is blocked by the mitochondrial translation inhibitor chloramphenicol, which additionally suppresses viral production. Intriguingly, chloramphenicol and pUL37x1 depletion have different effects on respiration capacity but similar effects on CMV production, suggesting that pUL37x1 promotes viral replication by efficient utilization of new mitochondria. These results argue for a role of pUL37x1 beyond controlling apoptosis.     

The chromatin remodeling factor SMARCB1 forms a complex with human cytomegalovirus proteins UL114 and UL44

Background

Human cytomegalovirus (HCMV) uracil DNA glycosylase, UL114, is required for efficient viral DNA replication. Presumably, UL114 functions as a structural partner to other factors of the DNA-replication machinery and not as a DNA repair protein. UL114 binds UL44 (HCMV processivity factor) and UL54 (HCMV-DNA-polymerase). In the present study we have searched for cellular partners of UL114.

Methodology/Principal Findings

In a yeast two-hybrid screen SMARCB1, a factor of the SWI/SNF chromatin remodeling complex, was found to be an interacting partner of UL114. This interaction was confirmed in vitro by co-immunoprecipitation and pull-down. Immunofluorescence microscopy revealed that SMARCB1 along with BRG-1, BAF170 and BAF155, which are the core SWI/SNF components required for efficient chromatin remodeling, were present in virus replication foci 24–48 hours post infection (hpi). Furthermore a direct interaction was also demonstrated for SMARCB1 and UL44.

Conclusions/Significance

The core SWI/SNF factors required for efficient chromatin remodeling are present in the HCMV replication foci throughout infection. The proteins UL44 and UL114 interact with SMARCB1 and may participate in the recruitment of the SWI/SNF complex to the chromatinized virus DNA. Thus, the presence of the SWI/SNF chromatin remodeling complex in replication foci and its association with UL114 and with UL44 might imply its involvement in different DNA transactions.     

Non-genomic effects of progestins--inhibition of cell growth and increased intracellular levels of cyclic nucleotides

The anti-proliferative effect of progestins was studied in human transformed cell lines from the uterine cervix (C-4I, C33A and Me-180). Progestins caused a concentration-dependent inhibition of proliferation. The maximum tested concentration (2.6-3.2 microM) inhibited C-4I cell growth by the following order of potency: progesterone (56%) > medroxyprogesterone (38%) > megestrol acetate (25%). The sensitivity, expressed as I(25) (the concentration that caused 25% inhibition of growth), showed the same order: progesterone (7.7 nM) > medroxyprogesterone (78 nM) > megestrol acetate (570 nM). The intracellular levels of cGMP and cAMP were elevated and the cellular export of these cyclic nucleotides was inhibited by a similar order of potency. The C-4I cell line was devoid of progesterone-, estrogen-, androgen- and glucocorticoid-receptors. In addition, the antiprogestins mifepristone, onapristone and ZK-112993 did not block the anti-proliferative effect of progesterone. On the other hand, antiprogestins (2.3 nM) appeared to have some progesterone-like ("mimetic") activity with inhibition of C-4I cell growth; mifepristone (11%), onapristone (12%) and ZK-112993 (16%). The observed effects of progestins and antiprogestins on C-4I cells were also presented in C33A cells (16% androgen receptor positive) and Me-180 cells (22% progesterone receptor positive, 9% androgen receptor positive and 17% glucocorticoid receptor positive). This study suggests that a non-genomic mechanism contributes to the anti-proliferative effect of progestins.     

Mound building termites contribute to savanna vegetation heterogeneity

With biomass densities comparable to large ungulates and megaherbivores, termites play a key functional role in many tropical savanna ecosystems. This study focuses on vegetated termite mounds (termitaria) constructed by the Termitidae species Macrotermes herus. We studied how resource rich termitaria affect graminoid herbs (Poaceae and Cyperaceae), forbs and woody species composition and diversity. The density of termitaria explained 89% of the variation in dense thickets in the area. Fire tolerant Acacia species dominated the open savanna while fire sensitive species like Grewia spp. and the succulent Euphorbia candelabrum were restricted to termite mounds. Termitaria plots had four times the mean number of woody species and supported three times as many forb species as the adjacent savanna. For woody species, both the Shannon–Wiener index and the Shannon evenness index were higher on temitaria than on the savanna. There were no differences for graminoid herbs, except for the Shannon evenness index which was higher on termitaria. Our results indicate that graminoid herb richness peaks at lower productivity levels than trees and forbs in savanna ecosystems, as also recently found in temperate areas.     

Bioreactor design for propagation of somatic embryos

Six identical bioreactors were constructed and built at the Agricultural University of Norway to provide optimal conditions for plant cell regeneration from cells into somatic embryos (clonal or somatic seeds). This was made possible through cooperation in COST87 by a European network in a working group on regeneration from plant cell cultures. The bioreactor design provides gentle stirring through a slow-speed stirrer that regularly changes direction of rotation to prevent quiet zones in the suspension in which cells can settle and grow. In addition, the oxygen is provided, bubble-free, through thin silicone tubing loops that are hanging loose, moving with the liquid to prevent cell growth on these tubes. We used off-the-shelf components whenever possible, to reduce the costs to a minimum, which was another aim of the construction. The result was a suite of relatively inexpensive computer-controlled bioreactors that could control temperature, oxygen, pH, stirrer speed and stirrer direction. In addition, we have provided different light spectral qualities by simple means of filtering the light. Using the present software, the parameters can be set up to alter every hour during the 24-h day/night cycle. All our cultures have improved growth in the bioreactors compared to identical cultures in Erlenmeyer flasks. The cultures used are: embryogenic cultures of carrot (Daucus carota), Norway spruce (Picea abies), birch (Betula pendula), cyclamen (Cyclamen persicum) and shoot cultures of Christmas begonia (Begonia x cheimantha). The paper also discusses recommendations for improvements of the current system for future revisions.