scholarly journals MO049FUNCTIONAL IMPORTANCE OF MAPKBP1 PROTEIN DOMAINS IN NEPHRONOPHTHISIS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Christin Hartig ◽  
Ria Schönauer ◽  
Sebastian Sewerin ◽  
Anastasia Ertel ◽  
Wenjun Jin ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Expression Profiles ◽  
Intracellular Localization ◽  
Significant Proportion ◽  
Protein Domains ◽  
Binding Domain ◽  
Protein Domain ◽  
Rna Seq ◽  
Wild Type ◽  
Wd40 Domain

Abstract Background and Aims Nephronophthisis is an autosomal-recessive kidney disease that accounts for a significant proportion of end-stage renal disease (ESRD) in childhood, adolescence and early adulthood. Biallelic pathogenic variants in MAPKBP1, encoding the c-Jun N-terminale kinase (JNK)-binding protein 1, are associated with development of Nephronophthisis and subsequent chronic kidney disease (CKD) (Macia et al, AJHG, 2017). We recently characterized MAPKBP1 as microtubule-associated protein that is able to localize to centrioles and the base of primary cilia depending on dimerization via its C-terminal coiled-coil domain (Schönauer et al, Kidney Int, 2020). However, the physiological function of its N-terminal WD40 and intermediate JNK-binding domain is still poorly understood. By in vitro comparison of artificial domain deletions with known and novel patient variants, we aim at pinpointing functional consequences of pathogenic MAPKBP1 in cilia and cell cycle control. Method N-terminally GFP-tagged MAPKBP1 constructs with either full-domain deletions or patient-derived variants were expressed in non-ciliated HeLa and ciliated H69 cells for fluorescence microscopy studies. Furthermore, RNA-seq analysis using primary patient cells was conducted to investigate differentially regulated molecular pathways compared to healthy control individuals. Results Immunofluorescence microscopy revealed inappropriate intracellular localization upon single or combined deletion of any MAPKBP1 protein domain. Compared to wild type, all deletion variants showed reduced intensity at the centrosome and ciliary base. Despite preserved dimerization ability, loss of the intermediate JNK-binding domain (JBD) most effectively abolished centrosomal or ciliary targeting, whereas loss of the N-terminal WD40-domain induced strongest mitotic aberrations. Unlike wild type, both, artificial and patient-derived truncating variants were able to enter the nucleus. RNA-seq analysis using primary patient fibroblasts with varying C-terminal truncations will allow important insights into common gene expression profiles unveiling consequences of aberrant intracellular trafficking. Conclusion In the present work, we demonstrate that all protein domains are indispensable for appropriate MAPKBP1 intracellular localization and function. Most of clinically reported patient variants exhibiting C-terminal truncation of varying lengths resulted in comparable intracellular behavior in presence of an intact N-terminal WD40 domain. Surprisingly, deletion of the JNK-binding domain alone aggravated functional disturbances hinting at a prominent regulatory role of this protein part interdepending with dimerization. Further insights into domain-specific functions will explain molecular disease mechanisms of MAPKBP1.

scholarly journals RNA-seq analysis of gene expression profiles in isolated stria vascularis from wild-type and Alport mice reveals key pathways underling Alport strial pathogenesis

PLoS ONE ◽  
2020 ◽  
Vol 15 (8) ◽  
pp. e0237907
Author(s):  
Brianna Dufek ◽  
Daniel T. Meehan ◽  
Duane Delimont ◽  
Kevin Wilhelm ◽  
Gina Samuelson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Stria Vascularis ◽  
Gene Expression Profiles ◽  
Rna Seq ◽  
Wild Type ◽  
Key Pathways

scholarly journals TFIIA Plays a Role in the Response to Oxidative Stress

2006 ◽  
Vol 5 (7) ◽  
pp. 1081-1090 ◽  
Author(s):  
Susan M. Kraemer ◽  
David A. Goldstrohm ◽  
Ann Berger ◽  
Susan Hankey ◽  
Sherry A. Rovinsky ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Rna Polymerase Ii ◽  
Expression Profiles ◽  
Intracellular Localization ◽  
Regulation Of Gene Expression ◽  
Wild Type ◽  
Mutant Strains

ABSTRACT To characterize the role of the general transcription factor TFIIA in the regulation of gene expression by RNA polymerase II, we examined the transcriptional profiles of TFIIA mutants of Saccharomyces cerevisiae using DNA microarrays. Whole-genome expression profiles were determined for three different mutants with mutations in the gene coding for the small subunit of TFIIA, TOA2. Depending on the particular mutant strain, approximately 11 to 27% of the expressed genes exhibit altered message levels. A search for common motifs in the upstream regions of the pool of genes decreased in all three mutants yielded the binding site for Yap1, the transcription factor that regulates the response to oxidative stress. Consistent with a TFIIA-Yap1 connection, the TFIIA mutants are unable to grow under conditions that require the oxidative stress response. Underexpression of Yap1-regulated genes in the TFIIA mutant strains is not the result of decreased expression of Yap1 protein, since immunoblot analysis indicates similar amounts of Yap1 in the wild-type and mutant strains. In addition, intracellular localization studies indicate that both the wild-type and mutant strains localize Yap1 indistinguishably in response to oxidative stress. As such, the decrease in transcription of Yap1-dependent genes in the TFIIA mutant strains appears to reflect a compromised interaction between Yap1 and TFIIA. This hypothesis is supported by the observations that Yap1 and TFIIA interact both in vivo and in vitro. Taken together, these studies demonstrate a dependence of Yap1 on TFIIA function and highlight a new role for TFIIA in the cellular mechanism of defense against reactive oxygen species.

MEF2D-BCL9 Fusion Gene Is Associated With High-Risk Acute B-Cell Precursor Lymphoblastic Leukemia in Adolescents

2016 ◽  
Vol 34 (28) ◽  
pp. 3451-3459 ◽  
Author(s):  
Kyogo Suzuki ◽  
Yusuke Okuno ◽  
Nozomu Kawashima ◽  
Hideki Muramatsu ◽  
Tatsuya Okuno ◽  
...  
Keyword(s):  
B Cell ◽  
Expression Profiles ◽  
Lymphoblastic Leukemia ◽  
Significant Proportion ◽  
Gene Fusions ◽  
Rna Seq ◽  
Cell Precursor ◽  
Sensitivity Testing ◽  
Exogenous Expression

Purpose Acute lymphoblastic leukemia (ALL) makes up a significant proportion of all pediatric cancers, and relapsed ALL is a leading cause of cancer-associated deaths in children. Identification of risk factors and druggable molecular targets in ALL can lead to a better stratification of treatments and subsequent improvement in prognosis. Patients and Methods We enrolled 59 children with relapsed or primary refractory ALL who were treated in our institutions. We primarily performed RNA sequencing (RNA-seq) using patients’ leukemic cells to comprehensively detect gene fusions and analyze gene expression profiles. On the basis of results obtained by RNA-seq, we performed genetic validation, functional analysis, and in vitro drug sensitivity testing using patients’ samples and an exogenous expression model. Results We identified a total of 26 gene fusions in 22 patients by RNA-seq. Among these, 19 were nonrandom gene fusions already described in ALL, and four of the remaining seven involved identical combination of MEF2D and BCL9. All MEF2D-BCL9–positive patients had B-cell precursor immunophenotype and were characterized as being older in age, being resistant to chemotherapy, having very early relapse, and having leukemic blasts that mimic morphologically mature B-cell leukemia with markedly high expression of HDAC9. Exogenous expression of MEF2D-BCL9 in a B-cell precursor ALL cell line promoted cell growth, increased HDAC9 expression, and induced resistance to dexamethasone. Using a primary culture of leukemic blasts from a patient, we identified several molecular targeted drugs that conferred inhibitory effects in vitro. Conclusion A novel MEF2D-BCL9 fusion we identified characterizes a novel subset of pediatric ALL, predicts poor prognosis, and may be a candidate for novel molecular targeting.

Mutations In The Zinc Finger Domain Of Human and Mouse KLF1 Cause Congenital Dyserythropoietic Anemia (CDA) Via Promiscuous DNA Binding and Ectopic Target Gene Expression

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 11-11
Author(s):  
Kevin R Gillinder ◽  
Mathieu Lajoie ◽  
Melissa Ilsley ◽  
Michael R Tallack ◽  
Graham Magor ◽  
...  
Keyword(s):  
Dna Binding ◽  
Zinc Finger ◽  
De Novo ◽  
Binding Domain ◽  
Erythroid Cell ◽  
Dna Binding Domain ◽  
Rna Seq ◽  
Wild Type ◽  
Congenital Dyserythropoietic Anemia ◽  
Cell Biol

Abstract Krûppel-like factor-1 (KLF1) is an essential erythroid-specific transcription factor1, 2. A number of studies have shown up to ∼700 genes are poorly expressed when KLF1 is absent3-6. This global loss of expression is responsible for failure of effective red blood cell production in KLF1 knockout mice, and partly responsible for congenital dyserythropoietic anemia type IV (CDA-IV) observed in humans with dominant mutations in the DNA-binding domain of KLF17. Recently an ENU-generated mouse model of neonatal anemia, ‘nan’, was also reported to harbour a mutation in the second zinc-finger of KLF18. Remarkably, the ‘nan’ mutation (E339D) resides at exactly the same amino acid which results in human CDA IV (i.e. E325 in humans). Unlike loss of function point mutations in KLF1, this mutation leads to a more severe phenotype than the KLF1 null allele, suggesting it is an unusual dominant mutation9. To investigate how this mutation might cause disease, we introduced tamoxifen-inducible versions of KLF1 and KLF1nan into an erythroid cell line derived from Klf1-/- fetal liver cells10. We performed ChIP-seq to determine genome occupancy site preferences for KLF1 and KLF1nan. We identified about 4-fold the number of binding sites within the genome for KLF1nan versus KLF1; many of these are ectopic or promiscuous. Using de novo motif discovery11, we find KLF1nan binds a slightly degenerate CACC box element (CCMNGCCC) in comparison with wild type KLF1 (CCMCRCCC). This specificity is novel with respect to known TFs, so we think it represents specificity not normally present in mammals. The degenerate motif is consistent with models of how the second zinc finger of KLF1 specifically interacts with the 9bp consensus binding site12,13. We also isolated nascent RNA from wild type and mutant cells, to identify primary transcriptional targets of KLF1 and aberrant targets of the KLF1nanmutation. We performed primary transcript RNA-seq and validation using RT-PCR of pre-processed nuclear transcripts. Together the RNA-seq and ChIP-seq studies have provided a novel explanation for how mutations in KLF1 result in dominant anemia in mice and man. This mechanism, whereby a transcription factor DNA-binding domain mutation leads to promiscuous binding, activation of an aberrant transcriptional program and subsequent derailing of co-ordinated differentiation, is novel. References: 1. Perkins, A.C., A.H. Sharpe, and S.H. Orkin. Nature, 1995. 375(6529): p. 318-22. 2. Nuez, B., et al., Nature, 1995. 375(6529): p. 316-8. 3. Pilon, A.M., et al., Mol Cell Biol, 2006. 26(11): p. 4368-77. 4. Drissen, R., et al., Mol Cell Biol, 2005. 25(12): p. 5205-14. 5. Hodge, D., et al., Blood, 2006. 107(8): p. 3359-70. 6. Tallack, M.R., et al., Genome Res, 2012. 22(12):2385-98 7. Arnaud, L., et al., Am J Hum Genet. 87(5): p. 721-7. 8. Siatecka, M., et al., Proc Natl Acad Sci U S A. 2010. 107(34):15151-6 9. Heruth, D.P., et al., Genomics, 2010. 96(5): p. 303-7. 10. Coghill, E., et al., Blood, 2001. 97(6): p. 1861-1868. 11. Bailey, T.L., et al., Nucleic Acids Res, 2009. 37(Web Server issue): p. W202-8. 12. Schuetz, A., et al., Cell Mol Life Sci, 2011. 68(18): p. 3121-31. 13. Oka, S., et al., Biochemistry, 2004. 43(51): p. 16027-35. Disclosures: Perkins: Novartis Oncology: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees.

New Insights into the Mechanism of Dominant Anemia Caused By Zinc Finger Mutations in KLF1

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 740-740
Author(s):  
Andrew C Perkins ◽  
Kevin R Gillinder ◽  
Graham Magor ◽  
Mathieu Lajoie ◽  
Timothy L Bailey ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Zinc Finger ◽  
Fetal Liver ◽  
Binding Domain ◽  
Erythroid Cell ◽  
Dna Binding Domain ◽  
Rna Seq ◽  
Wild Type ◽  
Cell Biol

Abstract Krûppel-like factor-1 (KLF1) is an essential erythroid-specific transcription factor [1, 2]. A number of studies have shown up to ~700 genes are poorly expressed when KLF1 is absent [3-6]. This global loss of expression is responsible for failure of effective red blood cell production in KLF1 knockout mice, and partly responsible for congenital dyserythropoietic anemia type IV (CDA-IV) observed in humans with dominant mutations in the DNA-binding domain of KLF1 [7]. Recently an ENU-generated mouse model of neonatal anemia, ‘nan’, was also reported to harbour a mutation in the second zinc-finger of KLF1 [8]. Remarkably, the ‘nan’ mutation (E339D) resides at exactly the same amino acid which results in human CDA IV (= E325 in humans). Unlike loss of function point mutations in KLF1, this mutation leads to a more severe phenotype than the KLF1 null allele, suggesting it is an unusual dominant mutation [9]. To investigate how this mutation might cause disease, we introduced tamoxifen-inducible versions of KLF1 and KLF1nan into an erythroid cell line derived from Klf1-/- fetal liver cells [10]. We performed ChIP-seq to determine differences in genome occupancy in vivo, and identified novel sites occupied by EKLF-E339D but not by wild type KLF1. Using de novo motif discovery [11], we find KLF1nan binds a slightly degenerate CACC box element (CCMNGCCC) in comparison with wild type KLF1 (CCMCRCCC). This specificity is novel with respect to any known TFs, so we think it represents a sequence specificity not normally encoded in mammals. Ectopic binding to non-erythroid gene promoters is accompanied by aberrant gene expression as determined by 4sU labelling and deep sequencing of tamoxifen-induced primary nuclear RNAs. We find a 4-fold greater number of genes induced by KLF1-nan compared with wild type KLF1 which is consistent with degenerate genome occupancy. We compared the KLF1-nan dependent genes with RNA-seq performed in primary fetal liver for KLF1+/nan versus KLF1+/- mice. We confirmed aberrant binding using EMSA and surface plasmon resonance (SPR) using recombinant GST-Klf1 zinc finger domains expressed in E.coli. The degenerate motif is consistent with structural models of how the second zinc finger of KLF1 specifically interacts with its binding site [12, 13]. We are undertaking structural studies to confirm this modelling. Together RNA-seq, ChIP-seq and SPR studies have provided a novel explanation for how mutations in KLF1 result in dominant anemia in mice and man. To our knowledge this mechanism, whereby a transcription factor DNA-binding domain mutation leads to promiscuous binding, activation of an aberrant transcriptional program and subsequent derailing of co-ordinated differentiation, is novel. References: 1.Perkins, A.C., A.H. Sharpe, and S.H. Orkin. Nature, 1995. 375(6529): p. 318-22. 2.Nuez, B., et al., Nature, 1995. 375(6529): p. 316-8. 3.Pilon, A.M., et al., Mol Cell Biol, 2006. 26(11): p. 4368-77. 4.Drissen, R., et al., Mol Cell Biol, 2005. 25(12): p. 5205-14. 5.Hodge, D., et al., Blood, 2006. 107(8): p. 3359-70. 6.Tallack, M.R., et al., Genome Res, 2012. 22(12):2385-98 7.Arnaud, L., et al., Am J Hum Genet. 87(5): p. 721-7. 8.Siatecka, M., et al., Proc Natl Acad Sci U S A. 2010. 107(34):15151-6 9.Heruth, D.P., et al., Genomics, 2010. 96(5): p. 303-7. 10.Coghill, E., et al., Blood, 2001. 97(6): p. 1861-1868. 11.Bailey, T.L., et al., Nucleic Acids Res, 2009. 37(Web Server issue): p. W202-8. 12.Schuetz, A., et al., Cell Mol Life Sci, 2011. 68(18): p. 3121-31. 13.Oka, S., et al., Biochemistry, 2004. 43(51): p. 16027-35. Disclosures No relevant conflicts of interest to declare.

scholarly journals Exploring the genes involved in biosynthesis of dihydroquercetin and dihydromyricetin in Ampelopsis grossedentata

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zheng-Wen Yu ◽  
Ni Zhang ◽  
Chun-Yan Jiang ◽  
Shao-Xiong Wu ◽  
Xia-Yu Feng ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Differentially Expressed Gene ◽  
Rna Seq ◽  
Illumina Hiseq ◽  
Genetic Studies ◽  
Sequencing Platform ◽  
Protein Databases ◽  
Helix Loop Helix ◽  
Wd40 Domain ◽  
Ampelopsis Grossedentata

AbstractDihydroquercetin (DHQ), an extremely low content compound (less than 3%) in plants, is an important component of dietary supplements and used as functional food for its antioxidant activity. Moreover, as downstream metabolites of DHQ, an extremely high content of dihydromyricetin (DHM) is up to 38.5% in Ampelopsis grossedentata. However, the mechanisms involved in the biosynthesis and regulation from DHQ to DHM in A. grossedentata remain unclear. In this study, a comparative transcriptome analysis of A. grossedentata containing extreme amounts of DHM was performed on the Illumina HiSeq 2000 sequencing platform. A total of 167,415,597 high-quality clean reads were obtained and assembled into 100,584 unigenes having an N50 value of 1489. Among these contigs, 57,016 (56.68%) were successfully annotated in seven public protein databases. From the differentially expressed gene (DEG) analysis, 926 DEGs were identified between the B group (low DHM: 210.31 mg/g) and D group (high DHM: 359.12 mg/g) libraries, including 446 up-regulated genes and 480 down-regulated genes (B vs. D). Flavonoids (DHQ, DHM)-related DEGs of ten structural enzyme genes, three myeloblastosis transcription factors (MYB TFs), one basic helix–loop–helix (bHLH) TF, and one WD40 domain-containing protein were obtained. The enzyme genes comprised three PALs, two CLs, two CHSs, one F3’H, one F3’5’H (directly converts DHQ to DHM), and one ANS. The expression profiles of randomly selected genes were consistent with the RNA-seq results. Our findings thus provide comprehensive gene expression resources for revealing the molecular mechanism from DHQ to DHM in A. grossedentata. Importantly, this work will spur further genetic studies about A. grossedentata and may eventually lead to genetic improvements of the DHQ content in this plant.

Distinct Modulation of Wild-Type and Selective Gene Mutated Vitamin D Receptor by Essential Poly Unsaturated Fatty Acids

2021 ◽  
Vol 21 ◽  
Author(s):  
Hari Balaji ◽  
Selvaraj Ayyamperuma ◽  
Niladri Saha ◽  
Shyam Sundar Pottabathula ◽  
Jubie Selvaraj ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Vitamin D ◽  
Ligand Binding ◽  
Vitamin D Deficiency ◽  
Binding Affinity ◽  
Unsaturated Fatty Acids ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Binding Energies ◽  
Wild Type

: Vitamin-D deficiency is a global concern. Gene mutations in the vitamin D receptor’s (VDR) ligand binding domain (LBD) variously alter the ligand binding affinity, heterodimerization with retinoid X receptor (RXR) and inhibit coactivator interactions. These LBD mutations may result in partial or total hormone unresponsiveness. A plethora of evidence report that selective long chain polyunsaturated fatty acids (PUFAs) including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) bind to the ligand-binding domain of VDR and lead to transcriptional activation. We therefore hypothesize that selective PUFAs would modulate the dynamics and kinetics of VDRs, irrespective bioactive of vitamin-D binding. The spatial arrangements of the selected PUFAs in VDR active site were examined by in-silico docking studies. The docking results revealed that PUFAs have fatty acid structure-specific binding affinity towards VDR. The calculated EPA, DHA & AA binding energies (Cdocker energy) were lesser compared to vitamin-D in wild type of VDR (PDB id: 2ZLC). Of note, the DHA has higher binding interactions to the mutated VDR (PDB id: 3VT7) when compared to the standard Vitamin-D. Molecular dynamic simulation was utilized to confirm the stability of potential compound binding of DHA with mutated VDR complex. These findings suggest the unique roles of PUFAs in VDR activation and may offer alternate strategy to circumvent vitamin-D deficiency.

scholarly journals Putative transmembrane transporter modulates higher-level aggression in Drosophila

2017 ◽  
Vol 114 (9) ◽  
pp. 2373-2378 ◽  
Author(s):  
Budhaditya Chowdhury ◽  
Yick-Bun Chan ◽  
Edward A. Kravitz
Keyword(s):  
Causal Effect ◽  
Nerve Terminals ◽  
Rna Seq ◽  
Wild Type ◽  
Temperature Dependent ◽  
Number Of Genes ◽  
Interesting Family ◽  
Solute Carrier ◽  
Transmembrane Transporter ◽  
Selection Of

By selection of winners of dyadic fights for 35 generations, we have generated a hyperaggressive Bully line of flies that almost always win fights against the parental wild-type Canton-S stock. Maintenance of the Bully phenotype is temperature dependent during development, with the phenotype lost when flies are reared at 19 °C. No similar effect is seen with the parent line. This difference allowed us to carry out RNA-seq experiments and identify a limited number of genes that are differentially expressed by twofold or greater in the Bullies; one of these was a putative transmembrane transporter, CG13646, which showed consistent and reproducible twofold down-regulation in Bullies. We examined the causal effect of this gene on the phenotype with a mutant line for CG13646, and with an RNAi approach. In all cases, reduction in expression of CG13646 by approximately half led to a hyperaggressive phenotype partially resembling that seen in the Bully flies. This gene is a member of a very interesting family of solute carrier proteins (SLCs), some of which have been suggested as being involved in glutamine/glutamate and GABA cycles of metabolism in excitatory and inhibitory nerve terminals in mammalian systems.

scholarly journals Transcriptomal dissection of soybean circadian rhythmicity in two geographically, phenotypically and genetically distinct cultivars

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yanlei Yue ◽  
Ze Jiang ◽  
Enoch Sapey ◽  
Tingting Wu ◽  
Shi Sun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Circadian Clock ◽  
Chromosome Structure ◽  
Clock Genes ◽  
Expression Profiles ◽  
Circadian Rhythmicity ◽  
Rna Seq ◽  
Night Time ◽  
Time Points ◽  
Circadian Clock Genes

Abstract Background In soybean, some circadian clock genes have been identified as loci for maturity traits. However, the effects of these genes on soybean circadian rhythmicity and their impacts on maturity are unclear. Results We used two geographically, phenotypically and genetically distinct cultivars, conventional juvenile Zhonghuang 24 (with functional J/GmELF3a, a homolog of the circadian clock indispensable component EARLY FLOWERING 3) and long juvenile Huaxia 3 (with dysfunctional j/Gmelf3a) to dissect the soybean circadian clock with time-series transcriptomal RNA-Seq analysis of unifoliate leaves on a day scale. The results showed that several known circadian clock components, including RVE1, GI, LUX and TOC1, phase differently in soybean than in Arabidopsis, demonstrating that the soybean circadian clock is obviously different from the canonical model in Arabidopsis. In contrast to the observation that ELF3 dysfunction results in clock arrhythmia in Arabidopsis, the circadian clock is conserved in soybean regardless of the functional status of J/GmELF3a. Soybean exhibits a circadian rhythmicity in both gene expression and alternative splicing. Genes can be grouped into six clusters, C1-C6, with different expression profiles. Many more genes are grouped into the night clusters (C4-C6) than in the day cluster (C2), showing that night is essential for gene expression and regulation. Moreover, soybean chromosomes are activated with a circadian rhythmicity, indicating that high-order chromosome structure might impact circadian rhythmicity. Interestingly, night time points were clustered in one group, while day time points were separated into two groups, morning and afternoon, demonstrating that morning and afternoon are representative of different environments for soybean growth and development. However, no genes were consistently differentially expressed over different time-points, indicating that it is necessary to perform a circadian rhythmicity analysis to more thoroughly dissect the function of a gene. Moreover, the analysis of the circadian rhythmicity of the GmFT family showed that GmELF3a might phase- and amplitude-modulate the GmFT family to regulate the juvenility and maturity traits of soybean. Conclusions These results and the resultant RNA-seq data should be helpful in understanding the soybean circadian clock and elucidating the connection between the circadian clock and soybean maturity.

scholarly journals Altered Emotional Phenotypes in Chronic Kidney Disease Following 5/6 Nephrectomy

2021 ◽  
Vol 11 (7) ◽  
pp. 882
Author(s):  
Yeon Hee Yu ◽  
Seong-Wook Kim ◽  
Dae-Kyoon Park ◽  
Ho-Yeon Song ◽  
Duk-Soo Kim ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Local Field ◽  
Smooth Muscle Actin ◽  
Local Field Potentials ◽  
Renal Tissue ◽  
Field Potentials ◽  
Wild Type ◽  
Sprague Dawley ◽  
Rat Models

Increased prevalence of chronic kidney disease (CKD) and neurological disorders including cerebrovascular disease, cognitive impairment, peripheral neuropathy, and dysfunction of central nervous system have been reported during the natural history of CKD. Psychological distress and depression are serious concerns in patients with CKD. However, the relevance of CKD due to decline in renal function and the pathophysiology of emotional deterioration is not clear. Male Sprague Dawley rats were divided into three groups: sham control, 5/6 nephrectomy at 4 weeks, and 5/6 nephrectomy at 10 weeks. Behavior tests, local field potentials, and histology and laboratory tests were conducted and investigated. We provided direct evidence showing that CKD rat models exhibited anxiogenic behaviors and depression-like phenotypes, along with altered hippocampal neural oscillations at 1–12 Hz. We generated CKD rat models by performing 5/6 nephrectomy, and identified higher level of serum creatinine and blood urea nitrogen (BUN) in CKD rats than in wild-type, depending on time. In addition, the level of α-smooth muscle actin (α-SMA) and collagen I for renal tissue was markedly elevated, with worsening fibrosis due to renal failures. The level of anxiety and depression-like behaviors increased in the 10-week CKD rat models compared with the 4-week rat models. In the recording of local field potentials, the power of delta (1–4 Hz), theta (4–7 Hz), and alpha rhythm (7–12 Hz) was significantly increased in the hippocampus of CKD rats compared with wild-type rats. Together, our findings indicated that anxiogenic behaviors and depression can be induced by CKD, and these abnormal symptoms can be worsened as the onset of CKD was prolonged. In conclusion, our results show that the hippocampus is vulnerable to uremia.

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