MicroRNA regulation of BAG3

B-cell lymphoma 2 (Bcl-2)-associated athanogene 3 (BAG3) protein is a member of BAG family of co-chaperones that modulates major biological processes, including apoptosis, autophagy, and development to promote cellular adaptive responses to stress stimuli. Although BAG3 is constitutively expressed in several cell types, its expression is also inducible and is regulated by microRNAs (miRNAs). miRNAs are small non-coding RNAs that mostly bind to the 3′-UTR (untranslated region) of mRNAs to inhibit their translation or to promote their degradation. miRNAs can potentially regulate over 50% of the protein-coding genes in a cell and therefore are involved in the regulation of all major functions, including cell differentiation, growth, proliferation, apoptosis, and autophagy. Dysregulation of miRNA expression is associated with pathogenesis of numerous diseases, including peripheral artery disease (PAD). BAG3 plays a critical role in regulating the response of skeletal muscle cells to ischemia by its ability to regulate autophagy. However, the biological role of miRNAs in the regulation of BAG3 in biological processes has only been elucidated recently. In this review, we discuss how miRNA may play a key role in regulating BAG3 expression under normal and pathological conditions.

Quantitative Proteome and Transcriptome Dynamics Analysis Reveals Iron Deficiency Response Networks and Signature in Neuronal Cells

Iron and oxygen deficiencies are common features in pathophysiological conditions, such as ischemia, neurological diseases, and cancer. Cellular adaptive responses to such deficiencies include repression of mitochondrial respiration, promotion of angiogenesis, and cell cycle control. We applied a systematic proteomics analysis to determine the global proteomic changes caused by acute hypoxia and chronic and acute iron deficiency (ID) in hippocampal neuronal cells. Our analysis identified over 8600 proteins, revealing similar and differential effects of each treatment on activation and inhibition of pathways regulating neuronal development. In addition, comparative analysis of ID-induced proteomics changes in cultured cells and transcriptomic changes in the rat hippocampus identified common altered pathways, indicating specific neuronal effects. Transcription factor enrichment and correlation analysis identified key transcription factors that were activated in both cultured cells and tissue by iron deficiency, including those implicated in iron regulation, such as HIF1, NFY, and NRF1. We further identified MEF2 as a novel transcription factor whose activity was induced by ID in both HT22 proteome and rat hippocampal transcriptome, thus linking iron deficiency to MEF2-dependent cellular signaling pathways in neuronal development. Taken together, our study results identified diverse signaling networks that were differentially regulated by hypoxia and ID in neuronal cells.

Features of the Bioconversion of Pentacyclic Triterpenoid Oleanolic Acid Using Rhodococcus Actinobacteria

The ability of actinobacteria of the genus Rhodococcus to transform oleanolic acid (OA), a plant pentacyclic triterpenoid, was shown for the first time using bioresources of the Regional Specialized Collection of AlkanotrophicMicroorganisms (IEGM; WDCM #768;www.iegmcol.ru). The most promising strains (R.opacus IEGM 488 and R.rhodochrousIEGM 285) were selected, and these catalyzed80% bioconversion of OA (0.5 g/L) in the presence of n-hexadecane (0.1% v/v) for seven days. The process of OA bioconversion was accompanied by a gradual decrease in the culture medium pH. Adaptive responses of bacterial cells to the OA effects included the formation of compact cellular aggregates, a marked change in the surface-to-volume ratio of cells, and a significant increase in the Zeta potential values. The results demonstrated that the process of OA bioconversion was catalyzed by membrane-bound enzyme complexes. Participation of cytochrome P450-dependent monooxygenases in the oxidation of the OA moleculewas confirmedusing specific inhibitors. The obtained data expand our knowledge on the catalytic activity of actinobacteria of the genus Rhodococcus and their possible use as biocatalysts for the bioconversion of complex hydrophobic compounds. The results can also be used inthe searchfor promising OA derivatives to be used in the synthesis of biologically active agents. Keywords: bioconversion, oleanolic acid, Rhodococcus, biologically active compounds

High-altitude erythrocytosis: mechanisms of adaptive and mal-adaptive responses

Erythrocytosis, or increased production of red blood cells, is one of the most well-documented physiological traits that varies within and among in high-altitude populations. Although a modest increase in blood O2-carrying capacity may be beneficial for life in highland environments, erythrocytosis can also become excessive and lead to maladaptive syndromes such as Chronic Mountain Sickness (CMS).

Culture or Context: a Qualitative Approach Investigating the Relationship of Scheduling Styles and Situational Context in Uganda and Germany

Previous literature suggested that different countries and regions are associated with different temporal cultures resulting in according scheduling styles: people in anglo-european countries supposedly plan and structure their life predominantly according to the clock (clock time orientation) while people in some other parts of the world are more prone to live their lives in disregard of clock time but follow inner needs and/or the structure given by the events that happen in their lives (event time orientation). However, recent research shows that scheduling styles are also adaptive responses to situational demands and event and clock timing are associated with different experiences of control. Transferring these findings to a cross-cultural setting, we investigated whether situational context is the predominant factor explaining the application of different scheduling styles. To this end, we used a mixed-methods approach with semi-structured interviews exploring whether participants from Uganda and Germany (employees with fixed working hours) differ in the level to which they structure their narratives of daily routines of time associated with work primarily in reference to the clock while recounting free time predominantly in reference to events and/or inner needs. Our data, processed using qualitative content analysis, show this pattern for the participants from both countries. Overall interviewees from Germany do not refer to the clock more often than their Ugandan counterparts. This suggests that individuals’ scheduling styles reflect intersituational adaptations to a given demand for synchronization rather than being kind of a strong cultural imprint on individuals.

Intermittent administration of peracetic acid is a mild environmental stressor that elicits mucosal and systemic adaptive responses from Atlantic salmon post-smolts

Background Fish encounter oxidative stress several times during their lifetime, and it has a pervasive influence on their health and welfare. One of the triggers of oxidative stress in fish farming is the use of oxidative disinfectants to improve rearing conditions, especially in production systems employing recirculation technology. Here we report the physiological and morphological adaptive responses of Atlantic salmon (Salmo salar L.) post-smolts to intermittent exposure to a potent oxidative agent peracetic acid (PAA). Fish reared in semi-commercial scale brackish water recirculating aquaculture system (RAS) were exposed to 1 ppm PAA every 3 days over 6 weeks. Mucosal and systemic responses were profiled before exposure, 22 and 45 days during the intermittent PAA administration. Results Oxidative stress was likely triggered as plasma antioxidant capacity increased significantly during the exposure period. Adaptive stress response to the periodic oxidant challenge was likewise demonstrated in the changes in plasma glucose and lactate levels. PAA-induced alterations in the transcription of antioxidants, cytokines, heat shock proteins and mucin genes showed a tissue-specific pattern: downregulation was observed in the gills and olfactory rosette, upregulation occurred in the skin, and no substantial changes in the liver. Further, PAA exposure resulted in histological changes in key mucosal organs (i.e. olfactory rosette, skin and gills); pathological alterations were predominant in the gills where cases of epithelial lifting, hypertrophy and clubbing were prevalent. In addition, intermittent PAA administration resulted in an apparent overproduction of mucus in the nasal mucosa. Lastly, PAA did not dramatically alter the ability of salmon to mount a physiological stress response in the presence of a secondary stressor, though some subtle interference was documented in the kinetics and magnitude of plasma cortisol and glucose response post-stress. Conclusions The present study collectively demonstrated that intermittent oxidant exposure was a mild environmental stressor that salmon could mount strong adaptive responses at systemic and mucosal levels. The results will be valuable in optimising the rearing conditions of post-smolts in RAS, especially in adopting water treatment strategies that do not considerably interfere with fish health and welfare.

Climate Change Situation in Kenya and Measures Towards Adaptive Management in the Water Sector

Climate change is a growing challenge to socio-economic development and sustainable environmental management worldwide. Developing countries with low adaptive capacity and high vulnerability to the phenomena are affected severely. This study assessed the climate change situation in a developing country, its effects on the water sector and adaptive responses to improve climate change resilience using Kenya as a case study. Findings showed that Kenya is experiencing temperature and rainfall rises currently, and future projections showed an even worse situation. Climate variability and change however differed based on time and space. Highlighted effects on the water sector included fluctuations in its quantities and deterioration of its quality. Adaptive responses such as infrastructural modifications of water body environments, forecasting using models to predict climate change uncertainties and disseminating early warnings are discussed. Their success relies on strong policy and institutions to steer their implementation in Kenya.

ADAPTIVE STRATEGIES EMPLOYED BY THE MICE SECTOR IN RESPONSE TO COVID-19

COVID-19 has brought to the fore drastic and transformative changes to MICE tourism. The current study therefore sought to examine the adaptive responses employed by the MICE sector of South Africa to survive and maintain business continuity during the COVID-19 pandemic. Adopting a qualitative research design, 19 representatives of various subsectors of the MICE industry (including organisers, suppliers, and associations) were interviewed. The data reveals that the immediate strategies implemented by many MICE organisations involved the reevaluation of their operational costs. Moreover, the study found that the sector has readjusted its business models to include virtual events in order to ensure recovery and resilience in light of the pandemic. The study argues the importance of understanding adaptive strategies as broadening theory on tourism and crises (specifically to the MICE sector) as well as understanding the process of sector resilience post-COVID-19.

Sequestration of histidine kinases by non-cognate response regulators establishes a threshold level of stimulation for bacterial two-component signaling

Two-component signaling systems (TCSs) in bacteria are often positively auto-regulated, where the histidine kinase (HK) and response regulator (RR) proteins comprising a TCS are expressed downstream of the signal they transduce. This auto-regulation improves the sensitivity of the TCS to stimuli and amplifies adaptive responses. The downside, however, is that the TCS may mount disproportionately large responses to weak or fleeting signals. How bacteria prevent such disproportionate responses is not known. Here, we show that sequestration of phosphorylated HKs by non-cognate RRs serves as a design to prevent such disproportionate responses. Using TCSs of M. tuberculosis as model systems, we found that with every one of the five HKs we studied, there was at least one non-cognate RR with higher affinity than that of the cognate RR for the HK. Phosphorylated HKs would thus preferentially bind the non-cognate RRs, suppressing signal transduction through the cognate pathways, which we demonstrated in vitro. Using mathematical modeling of TCS signaling in vivo, we predicted that this sequestration would introduce a threshold level of stimulation for a significant response, preventing responses to signals below this threshold. Finally, we showed in vivo using tunable expression systems in M. bovis that upregulation of a higher affinity non-cognate RR substantially suppressed the output from the cognate TCS pathway, presenting strong evidence of sequestration by non-cognate RRs as a design to regulate TCS signaling. Blocking this sequestration may be a novel intervention strategy, as it would compromise bacterial fitness by letting it respond unnecessarily to signals.