Inhibiting SLC26A4 reverses cardiac hypertrophy in H9C2 cells and in rats
Background It has been confirmed that mutations in solute carrier family 26 member 4 (SLC26A4) contribute to pendred syndrome. However, the role of SLC26A4 in cardiac hypertrophy and the signaling pathways remain unclear. Methods Cardiomyocytes were treated by 200 µM phenylephrine (PE) to induce cardiac hypertrophy. Also, the expression of SLC26A4, GSK3, cardiac hypertrophy markers including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was detected through real-time quantitative polymerase chain reaction (RT-qPCR). Flow cytometry assay was used to test the apoptosis of PE-induced cardiomyocytes transfected by small interfere RNA (siRNA)-SLC26A4. Furthermore, we detected the expression of autophagy-related markers including light chain 3 (LC3) and P62. Finally, we established a rat model of abdominal aortic constriction (AAC)-induced cardiac hypertrophy in vivo. Results RT-qPCR results showed that the mRNA expression of SLC26A4 was significantly up-regulated in PE-induced cardiac hypertrophy. After inhibiting SLC26A4, the release of ANP and BNP was significantly decreased and GSK3β was elevated in vivo and in vitro. Furthermore, inhibiting SLC26A4 promoted apoptosis of cardiac hypertrophy cells. In addition, LC3 was down-regulated and P62 was enhanced after transfection of siRNA-SLC26A4. Conclusion Our findings revealed that SLC26A4 increases cardiac hypertrophy, and inhibiting SLC26A4 could decrease the release of ANP/BNP and promote the expression of GSK-3β in vitro and in vivo. Moreover, SLC26A4 silencing inhibits autophagy of cardiomyocytes and induces apoptosis of cardiomyocytes. Therefore, SLC26A4 possesses potential value to be a therapeutic target of cardiac hypertrophy, and our study provides new insights into the mechanisms of cardiac hypertrophy.
Tang et al. (2020) Inhibiting SLC26A4 reverses cardiac hypertrophy in H9C2 cells and in rats. PeerJ 8:e8253 https://doi.org/10.7717/peerj.8253
Variability of soil carbon and nitrogen stocks after conversion of natural forest to plantations in Eastern China
Forest plantation, either through afforestation or reforestation, has been suggested to reverse and mitigate the process of deforestation. However, uncertainties remain in the potential of plantation forest (PF) to sequestrate carbon (C) and nitrogen (N) compared to natural forest (NF). Soil C and N stocks require a critical and updated look at what is happening especially in the context of increasing rate of land use change and climate change. The current study was conducted in China’s Eastern forest to estimate soil C and N stocks in six depth layers (0–10, 10–20, 20–40, 40–60, 60–80 and 80–100 cm) and two forest types (NF and PF) at four sites along climate factors gradient. The results showed that the overall mean soil C and N amounts to a depth of 20 cm ranged from 2.6 ± 1.1 Mg ha−1 to 38.6 ± 23.1 Mg ha−1, and soil nitrogen stock ranged from 0.2 ± 0.1 Mg ha−1 to 3.3 ± 1.5 Mg ha−1. Moreover, a loss of C stock was observed at Qingyuan (QY) by −7%, Dinghushan (DH) by −26%, Jianfengling (JF) by −13% while that of N stock was observed at QY (−8%), DH (−19%) and JF (−12%) at both depth layers. These results indicate that NFs have a better capacity to accumulate soil C and N. The soil C and N decreased from the southeast to the northeast and increased from tropical to temperate mixed forests zone in the eastern part of the study area. The C and N stock mainly occurred in the topsoil and decreased significantly with depth. Moreover, soil C and N stocks increased with age of plantation. This study provides an overview of the current spatial distribution and soil stocks of C and N, as well as the effects of environmental factors on soil C and N stocks. It also indicated that, although mean annual temperature and mean annual precipitation are the key factors affecting the variations in soil C and N, their vertical and horizontal distribution differed in various aspects.
Ngaba et al. (2020) Variability of soil carbon and nitrogen stocks after conversion of natural forest to plantations in Eastern China. PeerJ 8:e8377 https://doi.org/10.7717/peerj.8377
Soil temperatures and active carbon components as key drivers of C stock dynamics between two different stand ages of Larix principis-rupprechtii plantation
Forest soils sequester a large amount of carbon (C) and have a significant effect on the global C balance. Forests are commonly managed to maintain certain age structures but the effects of this management on soil C pools (kg C m−2) is still uncertain. We compared 40-year-old (1GF) and 24-year-old (2GF) plantations of Larix principis-rupprechtii in North China. Specifically, we measured environmental factors (e.g., soil temperature, moisture, and pH), the active C and nitrogen (N) pools (e.g., soil organic C, soil total N, dissolved organic C and N, microbial biomass C and N), and soil processes (e.g., C mineralization and microbial activity in different seasons) in five soil layers (0–50 cm, 10 cm for each soil layer) across the growing seasons in three 25 m × 25 m plots in each age class (1GF and 2GF). Findings indicated that the soil organic C pool in the older 1GF forest (12.43 kg C m−2) was significantly higher than 2GF forests (9.56 kg C m−2), and that soil temperature in 1GF forests was 9.8 °C, on average, 2.9% warmer than temperature in 2GF forests. The C lost as carbon dioxide (CO2) as a result of mineralization in the 2GF plots may partly explain the lower soil organic C pool in these younger forests; microorganisms likely drive this process.
Ma et al. (2020) Soil temperatures and active carbon components as key drivers of C stock dynamics between two different stand ages of Larix principis-rupprechtii plantation. PeerJ 8:e8384 https://doi.org/10.7717/peerj.8384
Differentially expressed genes and key molecules of BRCA1/2-mutant breast cancer: evidence from bioinformatics analyses
Background BRCA1 and BRCA2 genes are currently proven to be closely related to high lifetime risks of breast cancer. To date, the closely related genes to BRCA1/2 mutations in breast cancer remains to be fully elucidated. This study aims to identify the gene expression profiles and interaction networks influenced by BRCA1/2 mutations, so as to reflect underlying disease mechanisms and provide new biomarkers for breast cancer diagnosis or prognosis. Methods Gene expression profiles from The Cancer Genome Atlas (TCGA) database were downloaded and combined with cBioPortal website to identify exact breast cancer patients with BRCA1/2 mutations. Gene set enrichment analysis (GSEA) was used to analyze some enriched pathways and biological processes associated BRCA mutations. For BRCA1/2-mutant breast cancer, wild-type breast cancer and corresponding normal tissues, three independent differentially expressed genes (DEGs) analysis were performed to validate potential hub genes with each other. Protein–protein interaction (PPI) networks, survival analysis and diagnostic value assessment helped identify key genes associated with BRCA1/2 mutations. Results The regulation process of cell cycle was significantly enriched in mutant group compared with wild-type group. A total of 294 genes were identified after analysis of DEGs between mutant patients and wild-type patients. Interestingly, by the other two comparisons, we identified 43 overlapping genes that not only significantly expressed in wild-type breast cancer patients relative to normal tissues, but more significantly expressed in BRCA1/2-mutant breast patients. Based on the STRING database and cytoscape software, we constructed a PPI network using 294 DEGs. Through topological analysis scores of the PPI network and 43 overlapping genes, we sought to select some genes, thereby using survival analysis and diagnostic value assessment to identify key genes pertaining to BRCA1/2-mutant breast cancer. CCNE1, NPBWR1, A2ML1, EXO1 and TTK displayed good prognostic/diagnostic value for breast cancer and BRCA1/2-mutant breast cancer. Conclusion Our research provides comprehensive and new insights for the identification of biomarkers connected with BRCA mutations, availing diagnosis and treatment of breast cancer and BRCA1/2-mutant breast cancer patients.
Li et al. (2020) Differentially expressed genes and key molecules of BRCA1/2-mutant breast cancer: evidence from bioinformatics analyses. PeerJ 8:e8403 https://doi.org/10.7717/peerj.8403
Population genetics of swamp eel in the Yangtze River: comparative analyses between mitochondrial and microsatellite data provide novel insights
The swamp eel (Monopterus albus) is a typical sex reversal fish with high economic value. Several phylogeographic studies have been performed using various markers but comparative research between mitochondrial and nuclear markers is rare. Here, a fine-scale study was performed across six sites along the Yangtze River including three sites on the main stem and three sites from tributaries. A total of 180 swamp eel individuals were collected. Genetic structure and demographic history were explored using data from two mitochondrial genes and eight microsatellite loci. The results revealed the samples from tributary sites formed three separate clades which contained site-specific lineages. Geographic isolation and the habitat patchiness caused by seasonal cutoff were inferred to be the reasons for this differentiation. Strong gene flow was detected among the sites along the main stem. Rapid flow of the river main stem may provide the dynamic for the migration of swamp eel. Interestingly, the comparative analyses between the two marker types was discordant. Mitochondrial results suggested samples from three tributary sites were highly differentiated. However, microsatellite analyses indicated the tributary samples were moderately differentiated. We conclude this discordance is mainly caused by the unique life history of sex reversal fish. Our study provides novel insights regarding the population genetics of sex reversal fish.
Zhou et al. (2020) Population genetics of swamp eel in the Yangtze River: comparative analyses between mitochondrial and microsatellite data provide novel insights. PeerJ 8:e8415 https://doi.org/10.7717/peerj.8415
Global transcriptome analysis of alfalfa reveals six key biological processes of senescent leaves
Leaf senescence is a complex organized developmental stage limiting the yield of crop plants, and alfalfa is an important forage crop worldwide. However, our understanding of the molecular mechanism of leaf senescence and its influence on biomass in alfalfa is still limited. In this study, RNA sequencing was utilized to identify differentially expressed genes (DEGs) in young, mature, and senescent leaves, and the functions of key genes related to leaf senescence. A total of 163,511 transcripts and 77,901 unigenes were identified from the transcriptome, and 5,133 unigenes were differentially expressed. KEGG enrichment analyses revealed that ribosome and phenylpropanoid biosynthesis pathways, and starch and sucrose metabolism pathways are involved in leaf development and senescence in alfalfa. GO enrichment analyses exhibited that six clusters of DEGs are involved in leaf morphogenesis, leaf development, leaf formation, regulation of leaf development, leaf senescence and negative regulation of the leaf senescence biological process. The WRKY and NAC families of genes mainly consist of transcription factors that are involved in the leaf senescence process. Our results offer a novel interpretation of the molecular mechanisms of leaf senescence in alfalfa.
Yuan et al. (2020) Global transcriptome analysis of alfalfa reveals six key biological processes of senescent leaves. PeerJ 8:e8426 https://doi.org/10.7717/peerj.8426
Toward a clinical real time tissue ablation technology: combining electroporation and electrolysis (E2)
Background Percutaneous image-guided tissue ablation (IGA) plays a growing role in the clinical management of solid malignancies. Electroporation is used for IGA in several modalities: irreversible electroporation (IRE), and reversible electroporation with chemotoxic drugs, called electrochemotherapy (ECT). It was shown that the combination of electrolysis and electroporation—E2—affords tissue ablation with greater efficiency, that is, lower voltages, lower energy and shorter procedure times than IRE and without the need for chemotoxic additives as in ECT. Methods A new E2 waveform was designed that delivers optimal doses of electroporation and electrolysis in a single waveform. A series of experiments were performed in the liver of pigs to evaluate E2 in the context of clinical applications. The goal was to find initial parameter boundaries in terms of electrical field, pulse duration and charge as well as tissue behavior to enable real time tissue ablation of clinically relevant volumes. Results Histological results show that a single several hundred millisecond long E2 waveform can ablate large volume of tissue at relatively low voltages while preserving the integrity of large blood vessels and lumen structures in the ablation zone without the use of chemotoxic drugs or paralyzing drugs during anesthesia. This could translate clinically into much shorter treatment times and ease of use compared to other techniques that are currently applied.
Guenther et al. (2020) Toward a clinical real time tissue ablation technology: combining electroporation and electrolysis (E2). PeerJ 8:e7985 https://doi.org/10.7717/peerj.7985
Experimental evaluation of genomic DNA degradation rates for the pathogen Pseudogymnoascus destructans (Pd) in bat guano
Pseudogymnoascus destructans (Pd), the causative agent of white-nose syndrome in bats (WNS), has led to dramatic declines of bat populations in eastern North America. In the spring of 2016, WNS was first detected at several locations in Washington State, USA, which has prompted the need for large scale surveillance efforts to monitor the spread of Pd. Pd is typically detected in bats using invasive methods requiring capturing and swabbing individual bats. However, Pd can also be detected in guano, which may provide an efficient, affordable, and noninvasive means to monitor Pd in bats across North America. The widespread implementation of Pd surveillance in guano is hindered by substantial uncertainty about the probability of detecting Pd when present, and how this probability is influenced by the time since defecation, local environmental conditions, the amount of guano sampled, and the original concentration of DNA shed in the guano. In addition, the expected degradation rate of Pd DNA depends on whether the Pd DNA found in guano represents extracellular DNA fragments, intracellular DNA from dead Pd fungal cells, or from intracellular and viable Pd cells. While this is currently unknown, it has been posited that most environmental DNA, such as Pd found in guano long after defecation, is fragmented extracellular DNA. Using non-viable isolated DNA at precise quantities, we experimentally characterized the degradation rates of Pd DNA in guano samples. We spiked 450 guano samples with Pd gDNA in a 10-fold dilution series from 1 million to 1,000 fg and placed them in variable environmental conditions at five sites at Mount Rainier National Park in Washington State, which is a priority location for Pd surveillance. We evaluated DNA degradation over 70 days by quantifying the amount of DNA in samples collected every 14 days using real-time quantitative PCR (qPCR). Our sampling period was from July 10th to September 17th 2018 which overlaps with bat movement between summer roosts as well as movement from maternity colonies fall swarms. We detected Pd DNA in guano 56 and 70 days after inoculation with 1 million and 100,000 fg respectively, while the lowest quantity (1,000 fg) was detected until 42 days. Detection probability was variable among sites and lower where samples were left exposed without overhead cover. If Pd is shed as extracellular DNA in guano at quantities above 1,000 fg, then guano collection is likely to provide an effective tool for environmental screening of Pd that can be employed in an early detection and rapid response framework throughout Washington and other regions where this disease is rapidly emerging.
Urbina et al. (2020) Experimental evaluation of genomic DNA degradation rates for the pathogen Pseudogymnoascus destructans (Pd) in bat guano. PeerJ 8:e8141 https://doi.org/10.7717/peerj.8141
TRANSPARENT TESTA GLABRA 1 participates in flowering time regulation in Arabidopsis thaliana
Pleiotropic regulatory factors mediate concerted responses of the plant’s trait network to endogenous and exogenous cues. TRANSPARENT TESTA GLABRA 1 (TTG1) is such a factor that has been predominantly described as a regulator of early developmental traits. Although its closest homologs LIGHT-REGULATED WD1 (LWD1) and LWD2 affect photoperiodic flowering, a role of TTG1 in flowering time regulation has not been reported. Here we reveal that TTG1 is a regulator of flowering time in Arabidopsis thaliana and changes transcript levels of different targets within the flowering time regulatory pathway. TTG1 mutants flower early and TTG1 overexpression lines flower late at long-day conditions. Consistently, TTG1 can suppress the transcript levels of the floral integrators FLOWERING LOCUS T and SUPPRESSOR OF OVEREXPRESSION OF CO1 and can act as an activator of circadian clock components. Moreover, TTG1 might form feedback loops at the protein level. The TTG1 protein interacts with PSEUDO RESPONSE REGULATOR (PRR)s and basic HELIX-LOOP-HELIX 92 (bHLH92) in yeast. In planta, the respective pairs exhibit interesting patterns of localization including a recruitment of TTG1 by PRR5 to subnuclear foci. This mechanism proposes additional layers of regulation by TTG1 and might aid to specify the function of bHLH92. Within another branch of the pathway, TTG1 can elevate FLOWERING LOCUS C (FLC) transcript levels. FLC mediates signals from the vernalization, ambient temperature and autonomous pathway and the circadian clock is pivotal for the plant to synchronize with diurnal cycles of environmental stimuli like light and temperature. Our results suggest an unexpected positioning of TTG1 upstream of FLC and upstream of the circadian clock. In this light, this points to an adaptive value of the role of TTG1 in respect to flowering time regulation.
Paffendorf et al. (2020) TRANSPARENT TESTA GLABRA 1 participates in flowering time regulation in Arabidopsis thaliana. PeerJ 8:e8303 https://doi.org/10.7717/peerj.8303
A revised Holocene coral sea-level database from the Florida reef tract, USA
The coral reefs and mangrove habitats of the south Florida region have long been used in sea-level studies for the western Atlantic because of their broad geographic extent and composition of sea-level tracking biota. The data from this region have been used to support several very different Holocene sea-level reconstructions (SLRs) over the years. However, many of these SLRs did not incorporate all available coral-based data, in part because detailed characterizations necessary for inclusion into sea-level databases were lacking. Here, we present an updated database comprised of 303 coral samples from published sources that we extensively characterized for the first time. The data were carefully screened by evaluating and ranking the visual taphonomic characteristics of every dated sample within the database, which resulted in the identification of 134 high-quality coral samples for consideration as suitable sea-level indicators. We show that our database largely agrees with the most recent SLR for south Florida over the last ∼7,000 years; however, the early Holocene remains poorly characterized because there are few high-quality data spanning this period. Suggestions to refine future Holocene SLRs in the region are provided including filling spatial and temporal data gaps of coral samples, particularly from the early Holocene, as well as constructing a more robust peat database to better constrain sea-level variability during the middle to late Holocene. Our database and taphonomic-ranking protocol provide a framework for researchers to evaluate data-selection criteria depending on the robustness of their sea-level models.
Stathakopoulos et al. (2020) A revised Holocene coral sea-level database from the Florida reef tract, USA. PeerJ 8:e8350 https://doi.org/10.7717/peerj.8350