Purpose
Type 2 diabetes is associated with a higher risk of cardiovascular diseases, lowering the quality of life and increasing mortality rates of affected individuals. Circulating monocytes are ...tightly involved in the atherosclerosis process leading to cardiovascular diseases (CVD), and their inflammatory profile can be modified by exercise. The objective was to exploratory identify genes associated with CVD that could be regulated by high-intensity interval training (HIIT) in monocytes of type 2 diabetes patients.
Methods
Next-generation RNA sequencing (RNA-seq) analyses were conducted on isolated circulating monocytes (CD14
+
) of six women aged 60 and over with type 2 diabetes who completed a 12-week supervised HIIT intervention on a treadmill.
Results
Following the intervention, a reduction of resting diastolic blood pressure was observed. Concomitant with this result, 56 genes were found to be downregulated following HIIT intervention in isolated monocytes. A large proportion of the regulated genes was involved in cellular adhesion, migration and differentiation into an “atherosclerosis-specific” macrophage phenotype.
Conclusion
The downregulation of transcripts in monocytes globally suggests a favorable cardiovascular effect of the HIIT in older women with type 2 diabetes. In the context of precision medicine and personalized exercise prescription, shedding light on the fundamental mechanisms underlying HIIT effects on the gene profile of immune cells is essential to develop efficient nonpharmacological strategies to prevent CVD in high-risk population.
This paper presents the first investigation of the solubility of iron in mineral dust aerosols collected at the Henties Bay Aerosol Observatory (HBAO), in Namibia, from April to December 2017. During ...the study period, 10 intense dust events occurred. Elemental iron reached peak concentrations as high as 1.5 µg m.sup.-3, significantly higher than background levels. These events are attributed to wind erosion of natural soils from the surrounding gravel plains of the Namib desert. The composition of the sampled dust is found to be overall similar to that of aerosols from northern Africa but is characterized by persistent and high concentrations of fluorine which are attributed to local fugitive dust.
Alternative splicing (AS) constitutes a mechanism by which protein-coding genes and long non-coding RNA (lncRNA) genes produce more than a single mature transcript. From plants to humans, AS is a ...powerful process that increases transcriptome complexity. Importantly, splice variants produced from AS can potentially encode for distinct protein isoforms which can lose or gain specific domains and, hence, differ in their functional properties. Advances in proteomics have shown that the proteome is indeed diverse due to the presence of numerous protein isoforms. For the past decades, with the help of advanced high-throughput technologies, numerous alternatively spliced transcripts have been identified. However, the low detection rate of protein isoforms in proteomic studies raised debatable questions on whether AS contributes to proteomic diversity and on how many AS events are really functional. We propose here to assess and discuss the impact of AS on proteomic complexity in the light of the technological progress, updated genome annotation, and current scientific knowledge.
The Sahara is a major source of mineral particles for the Mediterranean Sea. The air-suspended particles alter the radiative transfer of solar and terrestrial radiation and the input of nutrients ...resulting from the deposition of mineral dust into the surface waters is thought to be essential for the development of marine ecosystems. In order to document the spatial and temporal variabilities of the dust atmospheric content and deposition flux close to the North-African coast where the impacts are expected to be the largest but where experimental stations are cruelly lacking, we use the MERRA-2 monthly reanalysis data of the 1980–2018 period. We have extracted the dust optical depth (AODdust), surface concentrations (Cdust), precipitations (Prcp), and deposition fluxes (Fdry, Fwet, and Ftot) of 14 areas (7 coastal and 7 offshore) regularly spaced from the Straights of Gibraltar in the west to Egypt and Cyprus in the east. The principal Component Analysis (PCA) shows that 86% of the variability of AODdust can be explained by two factors only: F1 whose influence is dominant in the Central Mediterranean and peaks in spring, and F2 whose importance decreases from Morocco to Egypt and peaks in summer. The variability of the surface concentration is more complex than that of the optical depth. AODdust and Cdust are maximal downwind of the main Algerian and Libyan dust sources, which is to say on and off the coast of the Central Mediterranean (south-Tunisia, Libya, Malta …). In spite of the climate change already underway, no long-term trend of Cdust or AODdust can yet be evidenced for any of the 14 areas between 1980 and 2018.
Along the coast of the eastern basin, the low precipitations (from 6.1 to 10.5 mm month−1 on average) explain that dry deposition accounts for a significant (45–53%) proportion of the total deposition. Everywhere else, wet deposition dominates and particularly in the marine areas where it represents about 90% of the total. From 1980 to 2018, the monthly averaged Ftot did not increase significantly. It varies from 0.24 (eastern Egypt) to 0.63 g m−2 month−1 (south-Tunisia) along the North-African coast, and from 0.26 (Baleares) to 0.48 g m−2 month−1 (Malta) in the marine areas. Because of the spatial variability of the precipitations, the largest deposition fluxes do not necessarily coincide with the regions of largest atmospheric dust content.
•The eastern basin is dustier than the western, based on average levels of dust on the surface and columns in the atmosphere.•The total deposition flux is maximal and relatively homogeneous in the north-Algerian, Tunisian, and west-Libyan coasts.•The largest deposition fluxes do not necessarily coincide with the regions of largest atmospheric dust content.
Most pseudogenes are generated when an RNA transcript is reverse-transcribed and integrated into the genome at a new location. Pseudogenes are often considered as an imperfect and silent copy of a ...functional gene because of the accumulation of numerous mutations in their sequence. Here we report the presence of
, a
retrotransposed pseudogene in the mouse genome, which has no disruptions in its coding sequence. We show that this pseudogene is mainly transcribed in testis and can produce a PHF8-PS protein in vivo. As the PHF8-PS protein has a well-conserved JmjC domain, we characterized its enzymatic activity and show that PHF8-PS does not have the intrinsic capability to demethylate H3K9me2 in vitro compared to the parental PHF8 protein. Surprisingly, PHF8-PS does not localize in the nucleus like PHF8, but rather is mostly located at the cytoplasm. Finally, our proteomic analysis of PHF8-PS-associated proteins revealed that PHF8-PS interacts not only with mitochondrial proteins, but also with prefoldin subunits (PFDN proteins) that deliver unfolded proteins to the cytosolic chaperonin complex implicated in the folding of cytosolic proteins. Together, our findings highlighted PHF8-PS as a new pseudogene-derived protein with distinct molecular functions from PHF8.
Histone demethylation is known to regulate transcription, but its role in other processes is largely unknown. We report a role for the histone demethylase LSD1/KDM1A in the DNA damage response (DDR). ...We show that LSD1 is recruited directly to sites of DNA damage. H3K4 dimethylation, a major substrate for LSD1, is reduced at sites of DNA damage in an LSD1-dependent manner. The E3 ubiquitin ligase RNF168 physically interacts with LSD1 and we find this interaction to be important for LSD1 recruitment to DNA damage sites. Although loss of LSD1 did not affect the initial formation of pH2A.X foci, 53BP1 and BRCA1 complex recruitment were reduced upon LSD1 knockdown. Mechanistically, this was likely a result of compromised histone ubiquitylation preferentially in late S/G2. Consistent with a role in the DDR, knockdown of LSD1 resulted in moderate hypersensitivity to γ-irradiation and increased homologous recombination. Our findings uncover a direct role for LSD1 in the DDR and place LSD1 downstream of RNF168 in the DDR pathway.
The RNA-binding protein Musashi-1 (MSI1) exerts essential roles in multiple cellular functions, such as maintenance of self-renewal and pluripotency of stem cells. MSI1 overexpression has been ...observed in several tumor tissues, including glioblastoma (GBM), and is considered as a well-established marker for tumor metastasis and recurrence. However, the molecular mechanisms by which MSI1 regulates cell migration are still undetermined. Here we reported that MSI1 alters cell morphology, promotes cell migration, and increases viscoelasticity of GBM cells. We also found that MSI1 directly binds to the 3'UTR of Tensin 3 (TNS3) mRNA, a negative regulator of cell migration, to inhibit its translation. Additionally, we identified that RhoA-GTP could be a potential regulator in MSI1/TNS3-mediated cell migration and morphological changes. In a xenograft animal model, high expression ratio of MSI1 to TNS3 enhanced GBM tumor migration. We also confirmed that MSI1 and TNS3 expressions are mutually exclusive in migratory tumor lesions, and GBM patients with MSI1
/TNS3
pattern tend to have poor clinical outcome. Taken together, our findings suggested a critical role of MSI1-TNS3 axis in regulating GBM migration and highlighted that the ratio of MSI1/TNS3 could predict metastatic and survival outcome of GBM patients.
Previous studies have provided some insight into the Saharan dust deposition at a few specific locations from observations over long time periods or intensive field campaigns. However, no assessment ...of the dust deposition temporal variability in connection with its regional spatial distribution has been achieved so far from network observations over more than 1 year. To investigate dust deposition dynamics at the regional scale, five automatic deposition collectors named CARAGA (Collecteur Automatique de Retombées Atmosphériques insolubles à Grande Autonomie in French) have been deployed in the western Mediterranean region during 1 to 3 years depending on the station. The sites include, from south to north, Lampedusa, Majorca, Corsica, Frioul and Le Casset (southern French Alps). Deposition measurements are performed on a common weekly period at the five sites. The mean dust deposition fluxes are higher close to the northern African coasts and decrease following a south–north gradient, with values from 7.4 g m−2 year−1 in Lampedusa (35°31′ N, 12°37′ E) to 1 g m−2 year−1 in Le Casset (44°59′ N, 6°28′ E). The maximum deposition flux recorded is of 3.2 g m−2 wk−1 in Majorca with only two other events showing more than 1 g m−2 wk−1 in Lampedusa, and a maximum of 0.5 g m−2 wk−1 in Corsica. The maximum value of 2.1 g m−2 year−1 observed in Corsica in 2013 is much lower than existing records in the area over the 3 previous decades (11–14 g m−2 year−1). From the 537 available samples, 98 major Saharan dust deposition events have been identified in the records between 2011 and 2013. Complementary observations provided by both satellite and air mass trajectories are used to identify the dust provenance areas and the transport pathways from the Sahara to the stations for the studied period. Despite the large size of African dust plumes detected by satellites, more than 80 % of the major dust deposition events are recorded at only one station, suggesting that the dust provenance, transport and deposition processes (i.e. wet vs. dry) of dust are different and specific for the different deposition sites in the Mediterranean studied area. The results tend to indicate that wet deposition is the main form of deposition for mineral dust in the western Mediterranean basin, but the contribution of dry deposition (in the sense that no precipitation was detected at the surface) is far from being negligible, and contributes 10 to 46 % to the major dust deposition events, depending on the sampling site.
Alzheimer's disease (AD) is the most common form of dementia and aging is the most common risk factor for developing the disease. The etiology of AD is not known but AD may be considered as a ...clinical syndrome with multiple causal pathways contributing to it. The amyloid cascade hypothesis, claiming that excess production or reduced clearance of amyloid-beta (Aβ) and its aggregation into amyloid plaques, was accepted for a long time as the main cause of AD. However, many studies showed that Aβ is a frequent consequence of many challenges/pathologic processes occurring in the brain for decades. A key factor, sustained by experimental data, is that low-grade infection leading to production and deposition of Aβ, which has antimicrobial activity, precedes the development of clinically apparent AD. This infection is chronic, low grade, largely clinically silent for decades because of a nearly efficient antimicrobial immune response in the brain. A chronic inflammatory state is induced that results in neurodegeneration. Interventions that appear to prevent, retard or mitigate the development of AD also appear to modify the disease. In this review, we conceptualize further that the changes in the brain antimicrobial immune response during aging and especially in AD sufferers serve as a foundation that could lead to improved treatment strategies for preventing or decreasing the progression of AD in a disease-modifying treatment.
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