Gene Regulation In Response Research Articles

Genome-Wide Identification and Expression Analysis of Cytokinin Response Regulator (RR) Genes in the Woody Plant Jatropha curcas and Functional Analysis of JcRR12 in Arabidopsis.

The cytokinin (CK) response regulator (RR) gene family plays a pivotal role in regulating the developmental and environmental responses of plants. Axillary bud outgrowth in the perennial woody plant Jatropha curcas is regulated by the crosstalk between CK and gibberellins (GA). In this study, we first analyzed the effects of gibberellin A3 (GA3), lovastatin (a CK synthesis inhibitor), decapitation, and their interaction, on the outgrowth of axillary buds. The results indicate that lovastatin completely inhibited GA-promoted axillary bud outgrowth and partially weakened the decapitation-promoted axillary bud outgrowth. To further characterize and understand the role of CK signaling in promoting the development of female flowers and branches, we performed bioinformatics and expression analyses to characterize the CK RR gene (JcRR) family in J. curcas. A total of 14 members of the JcRR family were identified; these genes were distributed on 10 chromosomes. Phylogenetic analysis indicated that the corresponding RR proteins are evolutionarily conserved across different plant species, and the Myb-like DNA-binding domain divides the 14 members of the JcRR family into type-A and type-B proteins. Further analysis of cis-acting elements in the promoter regions of JcRRs suggests that JcRRs are expressed in response to phytohormones, light, and abiotic stress factors; thus, JcRRs may be involved in some plant development processes. Genomic sequence comparison revealed that segmental duplication may have played crucial roles in the expansion of the JcRR gene family, and five pairs of duplicated genes were all subjected to purifying selection. By analyzing RNA sequencing (RNA-seq) and quantitative reverse transcription-polymerase chain reaction (qRT–PCR) data, we characterized that the temporospatial expression patterns of JcRRs during the development of various tissues and the response of these genes to phytohormones and abiotic stress. The JcRRs were mainly expressed in the roots, while they also exhibited differential expression patterns in other tissues. The expression levels of all six type-A and one type-B JcRRs increased in response to 6-benzylaminopurine (6-BA), while the four type-B JcRRs levels decreased. The expression levels of two type-B JcRRs increased in response to exogenous GA3 treatment, while those of three type-A and three type-B JcRRs decreased. We found that type-A JcRRs may play a positive role in the continuous growth of axillary buds, while the role of type-B JcRRs might be the opposite. In response to abiotic stress, the expression levels of two type-A and three type-B JcRRs strongly increased. The overexpression of JcRR12 in Arabidopsis thaliana slightly increased the numbers of rosette branches after decapitation, but not under normal conditions. In conclusion, our results provide detailed knowledge of JcRRs for further analysis of CK signaling and JcRR functions in J. curcas.

Characterizing gene expression in an in vitro biomechanical strain model of joint health

Background: Both genetic and environmental factors appear to contribute to joint health and disease. For example, pathological levels of biomechanical stress on joints play a notable role in initiation and progression of osteoarthritis (OA), a common chronic degenerative joint disease affecting articular cartilage and underlying bone. Population-level gene expression studies of cartilage cells experiencing biomechanical stress may uncover gene-by-environment interactions relevant to human joint health. Methods: To build a foundation for population-level gene expression studies in cartilage, we applied differentiation protocols to develop an in vitro system of chondrogenic cell lines (iPSC-chondrocytes). We characterized gene regulatory responses of three human iPSC-chondrocyte lines to cyclic tensile strain treatment. We measured the contribution of biological and technical factors to gene expression variation in this system. Results: We identified patterns of gene regulation that differ between strain-treated and control iPSC-chondrocytes. Differentially expressed genes between strain and control conditions are enriched for gene sets relevant to joint health and OA. Furthermore, even in this small sample, we found several genes that exhibit inter-individual expression differences in response to mechanical strain, including genes previously implicated in OA. Conclusions: Expanding this system to include iPSC-chondrocytes from a larger number of individuals will allow us to characterize and better understand gene-by-environment interactions related to joint health.

Repeated turnovers keep sex chromosomes young in willows

BackgroundSalicaceae species have diverse sex determination systems and frequent sex chromosome turnovers. However, compared with poplars, the diversity of sex determination in willows is poorly understood, and little is known about the evolutionary forces driving their turnover. Here, we characterized the sex determination in two Salix species, S. chaenomeloides and S. arbutifolia, which have an XY system on chromosome 7 and 15, respectively.ResultsBased on the assemblies of their sex determination regions, we found that the sex determination mechanism of willows may have underlying similarities with poplars, both involving intact and/or partial homologs of a type A cytokinin response regulator (RR) gene. Comparative analyses suggested that at least two sex turnover events have occurred in Salix, one preserving the ancestral pattern of male heterogamety, and the other changing heterogametic sex from XY to ZW, which could be partly explained by the “deleterious mutation load” and “sexually antagonistic selection” theoretical models. We hypothesize that these repeated turnovers keep sex chromosomes of willow species in a perpetually young state, leading to limited degeneration.ConclusionsOur findings further improve the evolutionary trajectory of sex chromosomes in Salicaceae species, explore the evolutionary forces driving the repeated turnovers of their sex chromosomes, and provide a valuable reference for the study of sex chromosomes in other species.

The cytokinin type-B response regulator PeRR12 is a negative regulator of adventitious rooting and salt tolerance in poplar

Adventitious root (AR) development is an ecologically and economically important biological process that maintains ecological balance, improves plant survivability, and allows for massive vegetative propagation, but its genetic mechanisms are not well understood. Here, eight Arabidopsis response regulator (ARR) genes were cloned and identified in poplar, most of which were detected in the AR, phloem, and xylem and showed remarkable induction at different time points during AR development. Subcellular localization indicated that most of these PeRR genes are in the nucleus. Based on qRT-PCR expression analysis of some genes related to AR development, we inferred that overexpression of PeRR12 (OE_PeRR12) may inhibited AR formation by suppressing the transcription of PeWOX11, PeWOX5, PePIN1 and PePIN3 in poplar while promoting type-A RR transcripts. Correspondingly, exogenous auxin partially restored the rooting of OE_PeRR12 poplar by inhibiting PeRR12 expression. Moreover, the activities of the antioxidant systems of OE_PeRR12 poplars were lower than those of wild-type poplars under salt stress conditions, indicating that PeRR12 may acts as a repressor that mediates salt tolerance by suppressing the expression of PeHKT1;1. Altogether, these results suggest that PeRR12 plays essential roles in mediating AR formation and salinity tolerance in poplar.

Epigenomic profiling of glucocorticoid responses identifies cis-regulatory disruptions impacting steroid resistance in childhood acute lymphoblastic leukemia

Glucocorticoids (GCs) are a mainstay of contemporary, multidrug chemotherapy in the treatment of childhood acute lymphoblastic leukemia (ALL), and resistance to GCs remains a major clinical concern. Resistance to GCs is predictive of ALL relapse and poor clinical outcome, and therefore represents a major hurdle limiting further improvements in survival rates. While advances have been made in identifying genes implicated in GC resistance, there remains an insufficient understanding of the impact of cis-regulatory disruptions in resistance. To address this, we mapped the gene regulatory response to GCs in two ALL cell lines using functional genomics and high-throughput reporter assays and identified thousands of GC-responsive changes to chromatin state, including the formation of over 250 GC-responsive super-enhancers and a depletion of AP-1 bound cis-regulatory elements implicated in cell proliferation and anti-apoptotic processes. By integrating our GC response maps with genetic and epigenetic datasets in primary ALL cells from patients, we further uncovered cis-regulatory disruptions at GC-responsive genes that impact GC resistance in childhood ALL. Overall, these data indicate that GCs initiate pervasive effects on the leukemia epigenome, and that alterations to the GC gene regulatory network contribute to GC resistance.

Structure and character analysis of cotton response regulator genes family reveals that GhRR7 responses to draught stress

BackgroundCytokinin signal transduction is mediated by a two-component system (TCS). Two-component systems are utilized in plant responses to hormones as well as to biotic and abiotic environmental stimuli. In plants, response regulatory genes (RRs) are one of the main members of the two-component system (TCS).MethodFrom the aspects of gene structure, evolution mode, expression type, regulatory network and gene function, the evolution process and role of RR genes in the evolution of the cotton genome were analyzed.ResultA total of 284 RR genes in four cotton species were identified. Including 1049 orthologous/paralogous gene pairs were identified, most of which were whole genome duplication (WGD). The RR genes promoter elements contain phytohormone responses and abiotic or biotic stress-related cis-elements. Expression analysis showed that RR genes family may be negatively regulate and involved in salt stress and drought stress in plants. Protein regulatory network analysis showed that RR family proteins are involved in regulating the DNA-binding transcription factor activity (COG5641) pathway and HP kinase pathways. VIGS analysis showed that the GhRR7 gene may be in the same regulatory pathway as GhAHP5 and GhPHYB, ultimately negatively regulating cotton drought stress by regulating POD, SOD, CAT, H2O2 and other reactive oxygen removal systems.ConclusionThis study is the first to gain insight into RR gene members in cotton. Our research lays the foundation for discovering the genes related to drought and salt tolerance and creating new cotton germplasm materials for drought and salt tolerance.

Transcriptional regulation of ergosterol biosynthesis genes in response to iron deficiency.

Iron participates as an essential cofactor in the biosynthesis of critical cellular components, including DNA, proteins and lipids. The ergosterol biosynthetic pathway, which is an important target of antifungal treatments, depends on iron in four enzymatic steps. Our results in the model yeast Saccharomyces cerevisiae show that the expression of ergosterol biosynthesis (ERG) genes is tightly modulated by iron availability probably through the iron-dependent variation of sterol and heme levels. Whereas the transcription factors Upc2 and Ecm22 are responsible for the activation of ERG genes upon iron deficiency, the heme-dependent factor Hap1 triggers their Tup1-mediated transcriptional repression. The combined regulation by both activating and repressing regulatory factors allows for the fine-tuning of ERG transcript levels along the progress of iron deficiency, avoiding the accumulation of toxic sterol intermediates and enabling efficient adaptation to rapidly changing conditions. The lack of these regulatory factors leads to changes in the yeast sterol profile upon iron-deficient conditions. Both environmental iron availability and specific regulatory factors should be considered in ergosterol antifungal treatments.

Upregulation of proto-oncogene ski by thyroid hormone in the intestine and tail during Xenopus metamorphosis

Thyroid hormone (T3) is important for adult organ function and vertebrate development, particularly during the postembryonic period when many organs develop/mature into their adult forms. Amphibian metamorphosis is totally dependent on T3 and can be easily manipulated, thus offering a unique opportunity for studying how T3 controls postembryonic development in vertebrates. Numerous early studies have demonstrated that T3 affects frog metamorphosis through T3 receptor (TR)-mediated regulation of T3 response genes, where TR forms a heterodimer with RXR (9-cis retinoic acid receptor) and binds to T3 response elements (TREs) in T3 response genes to regulate their expression. We have previously identified many candidate direct T3 response genes in Xenopus tropicalis tadpole intestine. Among them is the proto-oncogene Ski, which encodes a nuclear protein with complex function in regulating cell fate. We show here that Ski is upregulated in the intestine and tail of premetamorphic tadpoles upon T3 treatment and its expression peaks at stage 62, the climax of metamorphosis. We have further discovered a putative TRE in the first exon that can bind to TR/RXR in vitro and mediate T3 regulation of the promoter in vivo. These data demonstrate that Ski is activated by T3 through TR binding to a TRE in the first exon during Xenopus tropicalis metamorphosis, implicating a role of Ski in regulating cell fate during metamorphosis.

Transcriptional regulation of secondary metabolism and autophagy genes in response to DNA replication stress in Setosphaeria turcica

The fungal pathogen Setosphaeria turcica causes northern corn leaf blight (NCLB), which leads to considerable crop losses. Setosphaeria turcica elaborates a specialized infection structures called appressorium for maize infection. Previously, we demonstrated that the S. turcica triggers an S-phase checkpoint and ATR (Ataxia Telangiectasia and Rad3 related)-dependent self-protective response to DNA genotoxic insults during maize infection. However, how the regulatory mechanism works was still largely unknown. Here, we report a genome wide transcriptional profile analysis during appressorium formation in the present of DNA replication stress. We performed RNA-Seq analysis to identify S. tuicica genes responsive to DNA replication stress. In the current work, we found that appressorium-mediated maize infection by S. turcica is significantly blocked by S-phase checkpoint. A large serial of secondary metabolite and melanin biosynthesis genes were blocked in appressorium formation of S. turcica during the replication stress. The secondary metabolite biosynthesis genes including alcohol dehydrogenase GroES-like domain, multicopper oxidase, ABC-transporter families, cytochrome P450 and FAD-containing monooxygenase were related to plant pathogen infection. In addition, we demonstrated that autophagy in S. turcica is up-regulated by ATR as a defense response to stress. We identified StATG3, StATG4, StATG5, StATG7 and StATG16 genes for autophagy were induced by ATR-mediated S-phase checkpoint. We therefore propose that in response to genotoxic stress, S. turcica utilizes ATR-dependent pathway to turn off transcription of genes governing appressorium-mediated infection, and meanwhile inducing transcription of autophagy genes likely as a mechanism of self-protection, aside from the more conservative responses in eukaryotes.

ABCG11 modulates cytokinin responses in Arabidopsis thaliana.

The Arabidopsis ABC transporter ABCG11 transports lipidic precursors of surface coating polymers at the plasma membrane of epidermal cells. Mutants in ABCG11 exhibit severe developmental defects, suggesting that ABCG11 might also participate in phytohormone-mediated development. Here, we report that ABCG11 is involved in cytokinin-mediated development. The roots of abcg11 mutant seedlings failed to respond to cytokinins and accumulated more cytokinins than wild-type roots. When grown under short-day conditions, abcg11 exhibited longer roots and shorter hypocotyls compared to wild type, similar to abcg14, a knockout mutant in a cytokinin transporter. Treatment with exogenous trans-zeatin, which inhibits primary root elongation in the wild type, enhanced abcg11 primary root elongation. It also increased the expression of cytokinin-responsive Arabidopsis response regulator (ARR) genes, and the signal of the TCS::GFP reporter in abcg11 roots compared to wild-type roots, suggesting that cytokinin signaling was enhanced in abcg11 roots. When we treated only the roots of abcg11 with trans-zeatin, their shoots showed lower ARR induction than the wild type. The abcg14 abcg11 double mutant did not have additional root phenotypes compared to abcg11. Together, these results suggest that ABCG11 is necessary for normal cytokinin-mediated root development, likely because it contributes to cytokinin transport, either directly or indirectly.

Gene expression patterns in Atlantic salmon (Salmo salar) with severe nephrocalcinosis.

Nephrocalcinosis is a common disorder in farmed Atlantic salmon, but the consequences for the fish physiology are not well understood. We performed a transcriptome study in kidneys of Atlantic salmon (Salmo salar) smolts without and with severe chronic nephrocalcinosis (NC). The study revealed that numerous genes are differentially expressed in fish with NC compared with healthy salmon. The most evident changes in gene expression patterns in the NC group were a massive downregulation of metabolism and energy production, upregulation of signalling pathways important for tissue repair and function maintenance and upregulation of inflammatory responses. Overall, the extensive tissue damage and the gene regulation responses that affect salmon with severe nephrocalcinosis are highly likely to have dramatic consequences on fish survival.

Plasma-Derived Exosomal SncRNA as a Promising Diagnostic Biomarker for Early Detection of HBV-Related Acute-on-Chronic Liver Failure.

ObjectivesThe small noncoding RNAs (sncRNAs) including microRNAs and the noncanonical sncRNAs [i.e., tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNAs)] are a vital class of gene regulators in response to a variety of diseases. We focus on an sncRNA signature enriched in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) to develop a plasma exosome-based noninvasive biomarker for human ACLF.MethodsIn this work, sncRNAs related to HBV-ACLF were identified by small RNA sequencing (RNA-seq) in plasma exosomes collected from 3 normal subjects, 4 chronic hepatitis B (CHB) patients with flare, and 6 HBV-ACLF patients in the discovery cohort. Thereafter, the differentially expressed sncRNAs were further verified in a validation cohort (n = 313) using the newly developed molecular signature incorporating different mi/ts/rsRNAs (named as MTR-RNAs) through qRT-PCR assays. Subsequently, using the least absolute shrinkage and selection operator (LASSO) logistic regression (LR) model analysis, we developed an MTR-RNA classifier for early detection of ACLF.ResultsThe identified sncRNAs (hsa-miR-23b-3p, hsa-miR-223-3p, hsa-miR-339-5p, tsRNA-20, tsRNA-46, and rsRNA-249) were specifically differentially expressed in plasma exosomes of HBV-ACLF. The MTR-RNA signature (AUC = 0.787) containing the above sncRNAs distinguished HBV-ACLF cases among normal subjects with 71.67% specificity and 74.29% sensitivity, CHB patients with flare (AUC = 0.694, 85.71% sensitivity/59.5% specificity), and patients with CHB/cirrhosis (AUC = 0.785, 57.14% sensitivity/94.59% specificity). Notably, it revealed 100% specificity/94.80% sensitivity in detecting patients or normal people.ConclusionsOur as-constructed plasma-derived exosomal sncRNA signature can serve as a reliable biomarker for ACLF detection and also be adopted to be the pre−triage biomarker for selecting cases that can gain benefits from adjuvant treatment.

A chromosome-level Populus qiongdaoensis genome assembly provides insights into tropical adaptation and a cryptic turnover of sex determination.

Populus species have long been used as model organisms to study the adaptability of trees and the evolution of sex chromosomes. As a species belonging to the section Populus and limited to tropical areas, the P. qiongdaoensis genome contains important information for tropical poplar studies and protection. Here, we report a chromosome-level genome assembly and annotation of a female P. qiongdaoensis. Gene family clustering, positive selection detection and historical reconstruction of population dynamics revealed the tropical adaptation of P. qiongdaoensis, and showed convergent evolution with another tropical poplar, P. ilicifolia, at the molecular level, especially on some functional genes (e.g., PIF3 and PIL1). In addition, we also identified a ZW sex determination system on chromosome 19 of P. qiongdaoensis, and inferred that it seems to have a similar sex determination mechanism to other poplars, controlled by a type-A cytokinin response regulator (RR) gene. However, comparison and phylogenetic analysis of the sex determination regions confirmed a cryptic sex turnover event in the section Populus, which may be caused by the translocation and duplication of the RR gene driven by Helitron-like transposable elements. Our study provides new insights into the environmental adaptation and sex chromosome evolution of poplars, and emphasizes the importance of using long read sequencing in ecological and evolutionary inferences of plants.

Identification of genetic loci in lettuce mediating quantitative resistance to fungal pathogens

Key messageWe demonstrate genetic variation for quantitative resistance against important fungal pathogens in lettuce and its wild relatives, map loci conferring resistance and predict key molecular mechanisms using transcriptome profiling.Lactuca sativa L. (lettuce) is an important leafy vegetable crop grown and consumed globally. Chemicals are routinely used to control major pathogens, including the causal agents of grey mould (Botrytis cinerea) and lettuce drop (Sclerotinia sclerotiorum). With increasing prevalence of pathogen resistance to fungicides and environmental concerns, there is an urgent need to identify sources of genetic resistance to B. cinerea and S. sclerotiorum in lettuce. We demonstrated genetic variation for quantitative resistance to B. cinerea and S. sclerotiorum in a set of 97 diverse lettuce and wild relative accessions, and between the parents of lettuce mapping populations. Transcriptome profiling across multiple lettuce accessions enabled us to identify genes with expression correlated with resistance, predicting the importance of post-transcriptional gene regulation in the lettuce defence response. We identified five genetic loci influencing quantitative resistance in a F6 mapping population derived from a Lactuca serriola (wild relative) × lettuce cross, which each explained 5–10% of the variation. Differential gene expression analysis between the parent lines, and integration of data on correlation of gene expression and resistance in the diversity set, highlighted potential causal genes underlying the quantitative trait loci.

Single-cell RNA-sequencing of peripheral blood mononuclear cells reveals widespread, context-specific gene expression regulation upon pathogenic exposure

The host’s gene expression and gene regulatory response to pathogen exposure can be influenced by a combination of the host’s genetic background, the type of and exposure time to pathogens. Here we provide a detailed dissection of this using single-cell RNA-sequencing of 1.3M peripheral blood mononuclear cells from 120 individuals, longitudinally exposed to three different pathogens. These analyses indicate that cell-type-specificity is a more prominent factor than pathogen-specificity regarding contexts that affect how genetics influences gene expression (i.e., eQTL) and co-expression (i.e., co-expression QTL). In monocytes, the strongest responder to pathogen stimulations, 71.4% of the genetic variants whose effect on gene expression is influenced by pathogen exposure (i.e., response QTL) also affect the co-expression between genes. This indicates widespread, context-specific changes in gene expression level and its regulation that are driven by genetics. Pathway analysis on the CLEC12A gene that exemplifies cell-type-, exposure-time- and genetic-background-dependent co-expression interactions, shows enrichment of the interferon (IFN) pathway specifically at 3-h post-exposure in monocytes. Similar genetic background-dependent association between IFN activity and CLEC12A co-expression patterns is confirmed in systemic lupus erythematosus by in silico analysis, which implies that CLEC12A might be an IFN-regulated gene. Altogether, this study highlights the importance of context for gaining a better understanding of the mechanisms of gene regulation in health and disease.

A role for the mitotic proteins Bub3 and BuGZ in transcriptional regulation of catalase-3 expression.

The spindle assembly checkpoint factors Bub3 and BuGZ play critical roles in mitotic process, but little is known about their roles in other cellular processes in eukaryotes. In aerobic organisms, transcriptional regulation of catalase genes in response to developmental or environmental stimuli is necessary for redox homeostasis. Here, we demonstrate that Bub3 and BuGZ negatively regulate cat-3 transcription in the model filamentous fungus Neurospora crassa. The absence of Bub3 caused a significant decrease in BuGZ protein levels. Our data indicate that BuGZ and Bub3 interact directly via the GLEBS domain of BuGZ. Despite loss of the interaction, the amount of BuGZ mutant protein negatively correlated with the cat-3 expression level, indicating that BuGZ amount rather than Bub3-BuGZ interaction determines cat-3 transcription level. Further experiments demonstrated that BuGZ binds directly to the cat-3 gene and responses to cat-3 overexpression induced by oxidative stresses. However, the zinc finger domains of BuGZ have no effects on DNA binding, although mutations of these highly conserved domains lead to loss of cat-3 repression. The deposition of BuGZ along cat-3 chromatin hindered the recruitment of transcription activators GCN4/CPC1 and NC2 complex, thereby preventing the assembly of the transcriptional machinery. Taken together, our results establish a mechanism for how mitotic proteins Bub3 and BuGZ functions in transcriptional regulation in a eukaryotic organism.

Constant light exposure in early life induces m6A-mediated inhibition of IGF gene family in the chicken.

Insulin-like growth factor (IGF) family plays important roles in regulating the development of various organ systems through stimulating cell proliferation and differentiation. Photoperiod is an important factor affecting growth and development in the chicken, yet the effect of constant light exposure in early life on IGF1 and IGF2 expression in the chicken remains unclear. In this study, one-day-old chickens were kept in either constant light (24L:0D, LL) or natural photoperiod (12L:12D, LD) for the first week of life and then maintained in constant light from 8 to 21 d of age. Constant light exposure in early life reduced mRNA expression of IGF gene family, including mRNA expression of IGF1, IGF2, and IGF2 binding proteins, in the hippocampus, hypothalamus, and liver of chickens at both 7 and 21 d of age. Moreover, constant light exposure increased mRNA expression of genes involved in RNA methylation N6-methyladenosine (m6A) in a tissue-specific manner. Interestingly, higher m6A on 3'UTR of IGF2 mRNA coincides with lower IGF2 mRNA, indicating a possible role of m6A in the post-transcriptional regulation of IGF2 expression in the hippocampus, hypothalamus, and liver of chickens. These findings suggest a m6A-mediated gene regulation of IGF gene family in different organs of chicken and expand our knowledge on mechanism of gene regulation in response to early life experience.

First report on molecular characterization and in silico analysis of caprine TCIM gene

Goats are used as animal models in physiological and biological studies since they can adapt to any harsh climate. The TCIM (transcriptional and immune response regulator) gene was highly expressed in thyroid cancer. The Wnt/-catenin, mitogen-activated ERK1/2, transforming growth factor, and NF-B signaling pathways were all regulated by TC1 protein. Heat shock response is upregulated by the TCIM gene. The caprine TC1 (Thyroid cancer 1) protein is a relatively new gene in livestock, and its different roles in carcinogenesis, cell stress, and heat shock warranted to be investigated. The present study was carried with the aim of molecular characterization of the caprine TCIM gene for the first time. In the present study, an allelic variant at the c.A300T that leads to an amino acid change in p.N100K was observed when compared with the reference sequence from the NCBI Genbank. The goat nucleotide sequence was 89.41% similar to the human TCIM gene. Intrinsically disordered regions of TC1 protein that are predicted in the current study may be important for transcriptional, translational regulation, and cell cycle control. The HSP (heat shock protein) inhibitor geldanamycin (anti-thyroid cancer drug) was used for docking study to find the interacting amino residues with the caprine TC1 protein. Further extensive studies on their association characters, as well as the experimental studies at the protein level, may be useful in the selection of the TCIM gene as a biomarker for carcinogenesis and heat stress in goats.

Neuronal Polarity Pathways as Central Integrators of Cell-Extrinsic Information During Interactions of Neural Progenitors With Germinal Niches.

Germinal niche interactions and their effect on developing neurons have become the subject of intense investigation. Dissecting the complex interplay of cell-extrinsic and cell-intrinsic factors at the heart of these interactions reveals the critical basic mechanisms of neural development and how it goes awry in pediatric neurologic disorders. A full accounting of how developing neurons navigate their niches to mature and integrate into a developing neural circuit requires a combination of genetic characterization of and physical access to neurons and their supporting cell types plus transformative imaging to determine the cell biological and gene-regulatory responses to niche cues. The mouse cerebellar cortex is a prototypical experimental system meeting all of these criteria. The lessons learned therein have been scaled to other model systems and brain regions to stimulate discoveries of how developing neurons make many developmental decisions. This review focuses on how mouse cerebellar granule neuron progenitors interact with signals in their germinal niche and how that affects the neuronal differentiation and cell polarization programs that underpin lamination of the developing cerebellum. We show how modeling of these mechanisms in other systems has added to the growing evidence of how defective neuronal polarity contributes to developmental disease.

Role of the type-B authentic response regulator gene family in fragrant rice under alkaline salt stress.

Globally, rice is being consumed as a main staple food and faces different kinds of biotic and abiotic stresses such drought, salinity, and pest attacks. Through the cytokinin signaling, Type-B authentic response regulators (ARR-Bs) respond positively towards the environmental stimuli. ARR-Bs are involved in abiotic stress tolerance and plant development but their molecular mechanisms in fragrant rice are still not fully explored. The current study showed the genome-wide characterization of OsARR-B genes under alkaline salt stress. Results showed that in total, 24 OsARR-B genes were found and divided into four subgroups on the basis of a phylogenetic analysis. These genes were located on all rice chromosomes except 8 and 10. Analysis of gene duplications, gene structure, cis-elements, protein-protein interactions, and miRNA were performed. Gene ontology analysis showed that OsARR-B genes are involved in plant development through the regulation of molecular functions, biological processes, and cellular components. Furthermore, 117 and 192 RNA editing sites were detected in chloroplast and mitochondrial genes, respectively, encoding proteins of OsARR-B. In chloroplast and mitochondrial genes, six and nine types of amino acid changes, respectively, were caused by RNA editing, showing that RNA editing has a role in the alkaline salt stress tolerance in fragrant rice. We also used a comparative transcriptome approach to study the gene expression changes in alkaline tolerant and susceptible genotypes. Under alkaline salt stress, OsARR-B5, OsARR-B7, OsARR-B9, OsARR-B10, OsARR-B16, OsARR-B22, and OsARR-B23 showed higher transcript levels in alkaline salt tolerant genotypes as compared to susceptible ones. Quantitative RT-PCR showed upregulation of gene expression in the alkaline tolerant genotypes under alkaline stress. Our study explored the gene expression profiling and RESs of two rice contrasting genotypes, which will help to understand the molecular mechanisms of alkaline salt tolerance in fragrant rice.