Gene Expression Signaling Pathways Research Articles

Oncogene-specific inhibition in the treatment of advanced pediatric thyroid cancer.

Papillary thyroid cancer (PTC) is the most common form of differentiated thyroid cancer in the pediatric population and represents the second most common malignancy in adolescent females. Historically, PTC has been classified on the basis of histology, however, accumulating data indicate that molecular subtyping based on somatic oncogenic alterations along with gene expression profiling can better predict clinical behavior and may provide opportunities to incorporate oncogene-specific inhibitory therapy to improve the response to radioactive iodine (RAI). In this issue of the JCI, Y.A. Lee, H. Lee, and colleagues showed that oncogenic fusions were more commonly associated with invasive disease, increased expression of MAPK signaling pathway genes (ERK score), and decreased expression of the sodium-iodine symporter, which was restored by RET- and NTRK-inhibitory therapy. These findings lend credence to the idea of reclassifying pediatric thyroid cancers using a three-tiered system, rather than the two-tiered adult system, and open avenues for the treatment of progressive, RAI-refractory PTC in patients.

Role of ethylene in effective establishment of the peanut-bradyrhizobia symbiotic interaction.

Ethylene has been implicated in nitrogen fixing symbioses in legumes, where rhizobial invasion occurs via infection threads (IT). In the symbiosis between peanut (Arachis hypogaea L.) and bradyrhizobia, the bacteria penetrate the root cortex intercellularly and IT are not formed. Little attention has been paid to the function of ethylene in the establishment of this symbiosis. The aim of this article is to evaluate whether ethylene plays a role in the development of this symbiotic interaction and the participation of Nod Factors (NF) in the regulation of ethylene signalling. Manipulation of ethylene in peanut was accomplished by application of 1-aminocyclopropane-1-carboxylic acid (ACC), which mimics applied ethylene, or AgNO3, which blocks ethylene responses. To elucidate the participation of NF in the regulation of ethylene signalling, we inoculated plants with a mutant isogenic rhizobial strain unable to produce NF and evaluated the effect of AgNO3 on gene expression of NF and ethylene responsive signalling pathways. Data revealed that ethylene perception is required for the formation of nitrogen-fixing nodules, while addition of ACC does not affect peanut symbiotic performance. This phenotypic evidence is in agreement with transcriptomic data from genes involved in symbiotic and ethylene signalling pathways. NF seem to modulate the expression of ethylene signalling genes. Unlike legumes infected through IT formation, ACC addition to peanut does not adversely affect nodulation, but ethylene perception is required for establishment of this symbiosis. Evidence for the contribution of NF to the modulation of ethylene-inducible defence gene expression is provided.

Phenotypes of STAT3 gain-of-function variant related to disruptive regulation of CXCL8/STAT3, KIT/STAT3, and IL-2/CD25/Treg axes.

STAT3 is a cytokine-signaling transcription factor critical for gene regulation. Gain-of-function (GOF) mutations in STAT3 are associated with lymphoproliferation, autoimmune cytopenias, increased susceptibility to infection, early-onset solid-organ autoimmunity, short stature, and eczema. We studied the JAK/STAT signaling pathway gene expression and the cytokine profile in two families carrying STAT3-GOF variants to shed light on the STAT3-GOF-associated variable expressivity, including the identification of disease markers. Considering 92 target genes, KIT and IL2RA were downregulated only in patients with high clinical penetrance, while CXCL8 was markedly downregulated for all of them. Unlike previous studies, SOCS3-a STAT3 inhibitor-was not upregulated in patients. In addition, low levels of IL-2 and a reduced numbers of Tregs cells were strikingly prevalent in patients. This study shows a disruptive role of STAT3-GOF variants in the regulatory axis activities CXCL8/STAT3, KIT/STAT3, IL2/CD25/Treg, which, by slightly different mechanisms, underlie the broad clinical spectrum seen in the studied patients. In addition, we suggest the investigation of CXCL8 as a biomarker for identifying STAT3-GOF mutation.

Wolfberry-derived zeaxanthin dipalmitate delays retinal degeneration in a mouse model of retinitis pigmentosa through modulating STAT3, CCL2 and MAPK pathways.

Retinitis pigmentosa (RP) is a group of inherited photoreceptor degeneration diseases that causes blindness without effective treatment. The pathogenesis of retinal degeneration involves mainly oxidative stress and inflammatory responses. Zeaxanthin dipalmitate (ZD), a wolfberry-derived carotenoid, has anti-inflammatory and anti-oxidative stress effects. Here we investigated whether these properties of ZD can delay the retinal degeneration in rd10 mice, a model of RP, and explored its underlying mechanism. One shot of ZD or control vehicle was intravitreally injected into rd10 mice on postnatal day 16 (P16). Retinal function and structure of rd10 mice were assessed at P25, when rods degenerate substantially, using a visual behavior test, multi-electrode-array recordings and immunostaining. Retinal pathogenic gene expression and regulation of signaling pathways by ZD were explored using transcriptome sequencing and western blotting. Our results showed that ZD treatment improved the visual behavior of rd10 mice and delayed the degeneration of retinal photoreceptors. It also improved the light responses of photoreceptors, bipolar cells and retinal ganglion cells. The expression of genes that are involved in inflammation, apoptosis and oxidative stress were up-regulated in rd10 mice, and were reduced by ZD. ZD further reduced the activation of two key factors, signal transducer and activator of transcription 3 and chemokine (C-C motif) ligand 2, down-regulated the expression of the inflammatory factor GFAP, and inhibited extracellular signal regulated protein kinases and P38, but not the JNK pathways. In conclusion, ZD delays the degeneration of the rd10 retina both morphologically and functionally. Its anti-inflammatory function is mediated primarily through the signal transducer and activator of transcription 3, chemokine (C-C motif) ligand 2 and MAPK pathways. Thus, ZD may serve as a potential clinical candidate to treat RP.

Enhanced Iron Uptake in Plants by Volatile Emissions of Rahnella aquatilis JZ-GX1.

Iron deficiency in soil has crucially restricted agricultural and forestry production. Volatile organic compounds (VOCs) produced by beneficial microorganisms have been proven to play an important role in inducing abiotic stress tolerance in plants. We investigated the effects of VOCs released by the rhizobacterium Rahnella aquatilis JZ-GX1 on the growth and root parameters of Arabidopsis thaliana under iron deficiency. The effect of the rhizobacterial VOCs on the gene expression in iron uptake and hormone signaling pathways were detected by RT-qPCR. Finally, the VOCs of the JZ-GX1 strain that could promote plant growth under iron deficiency stress were screened. The results showed that the JZ-GX1 strain could induce A. thaliana tolerance to iron deficiency stress by promoting the development of lateral roots and root hairs and increasing the activities of H+ ATPase and Fe3+ reductase. In addition, the AHA2, FRO2, and IRT1 genes of A. thaliana exposed to JZ-GX1-emitted VOCs were upregulated 25-, 1. 81-, and 1.35-fold, respectively, and expression of the abscisic acid (ABA) synthesis gene NCED3 was upregulated on both the 3rd and 5th days. Organic compounds were analyzed in the headspace of JZ-GX1 cultures, 2-undecanone and 3-methyl-1-butanol were found to promote Medicago sativa and A. thaliana growth under iron-limited conditions. These results demonstrated that the VOCs of R. aquatilis JZ-GX1 have good potential in promoting iron absorption in plants.

Insulin signaling pathway assessment by enhancing antioxidant activity due to morin using in vitro rat skeletal muscle L6 myotubes cells.

Plant-derived phytochemicals such as flavonoids have been explored to be powerful antioxidants that protect against oxidative stress-related diseases. In the present study, Morin, a flavonoid compound was studied for its antioxidant and antidiabetic properties in relation to oxidative stress in insulin resistant models conducted in rat skeletal muscle L6 cell line model. Evaluation of antioxidant property of morin was assayed using in vitro methods such as cell viability by MTT assay, estimation of SOD and CAT activity and NO scavenging activity. The anti-oxidative nature of morin on L6 cell line was conducted by the DCF-DA fluorescent activity. Glucose uptake in morin treated L6 myotubes are accessed by 2-NBDG assay in the presence or absence of IRTK and PI3K inhibitors. Further glycogen content estimation due to the morin treatment in L6 myotubes was performed. Antioxidant and insulin signaling pathway gene expression was examined over RT-PCR analysis. Morin has a negligible cytotoxic effect at doses of 20, 40, 60, 80, and 100µM concentration according to cell viability assay. Morin revealed that the levels of the antioxidant enzymes SOD and CAT in L6 myotubes had increased. When the cells were subjected to the nitro blue tetrazolium assay, morin lowered reactive oxygen species (ROS) formation at 60µM concentration displaying 39% ROS generation in oxidative stress condition. Lesser NO activity and a drop in green fluorescence emission in the DCFDA assay, demonstrating its anti-oxidative nature by reducing ROS formation in vitro. Glucose uptake by the L6 myotube cells using 2-NBDG, and with IRTK and PI3K inhibitors (genistein and wortmannin) showed a significant increase in glucose uptake by the cells which shows the up regulated GLUT-4 movement from intracellular pool to the plasma membrane. Morin (60µM) significantly enhanced the expression of antioxidant genes GPx, GST and GCS as well as insulin signalling genes IRTK, IRS-1, PI3K, GLUT-4, GSK-3β and GS in L6 myotubes treated cells. Morin has the ability to act as an anti-oxidant by lowering ROS levels and demonstrating insulin mimetic activity by reversing insulin resistance associated with oxidative stress.

Abstract LB018: Cloud-based biological domain knowledge derived gene expression classifier to predict the cancer clinical outcome

Abstract We report the advances of a cloud-based software utilizing advanced algorithms to identify the molecular cancer drivers and its signal transduction. To test, a classifier based on the NFκB signaling pathway gene expression profiles that predicts the clinical therapeutic response to chemo-radiation therapy of Squamous Cell Carcinomas of the Head and Neck (SCCHN) patients are described here. Expression of HPV16, p16 and 84 NFκB signaling pathway genes were determined using real time RT PCR in SCCHN patient samples and SCCHN cell lines. Gene expression was correlated to chemo-radiation response in cell lines and the model was blindly tested in SCCHN patients to predict their clinical outcome to chemo-radiation. This tool intends to fuse biological domain knowledge by way of integrating disease targets, cell line experiments towards creating a gene expression classifier for clinical outcome. The gene expression-based predicted clinical outcome compared with patients actual observed clinical outcome correctly identified the clinical response in 73% of the cases. Such work will allow design of tailored individualized clinical treatment strategies to target NFκB inhibition using biological modifying agents with or without chemo/radiation therapy. This will help to develop several targets to directly inhibit the NFκB activity or inhibit the downstream pivotal targets. The significance of the classifier would be the ability to use the biologic attributes of a tumor to tailor specific treatment protocols for each individual patient. This would not only spare the chemo-radiation resistant patients the ill effects of the therapy but will also decrease the delay in effective treatment among the resistant patients. The long-term objective is to use such pro-survival driver genes in other cancers; SMAD, TGFβ in pancreatic cancer, and AR in prostate cancer. This tool (MeghaOncomine) intends to fuse biological domain knowledge by way of integrating cancer targets, cell line experiments towards creating a gene expression classifier for clinical outcome. Citation Format: Rao V. Papineni, Seema Gupta, Aravindan Natarajan, Ram Papineni, Chandra Kasinathan. Cloud-based biological domain knowledge derived gene expression classifier to predict the cancer clinical outcome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB018.

What's New in Shock, July 2021?

What's New in Shock, July 2021?

Increased expression of autophagy and Nrf2-dependent signaling pathway genes by new monophenolic antioxidants depends on their structure

Under certain conditions, both activators and inhibitors of Nrf2-dependent signaling and autophagy can serve as potential agents for the prevention, treatment, and maintenance therapy of cancer, as well as overcoming chemoresistance. We are developing a panel of structurally related synthetic monophenolic compounds, in addition to a direct antioxidant effect, having the ability to affect intracellular signaling pathways and processes, including the above mentioned. Aim of the study was to investigate the relationship between its structure and the ability to influence the expression of autophagy and Nrf2 pathway genes.Material and methods. Five original hydrophilic phenolic structurally related compounds were synthesized; the prototypical inductor of the Keap1/Nrf2/ARE system, monosubstituted phenol tert-butylhydro-quinone (tBHQ), served as a reference substance. We used cultures of murine Lewis lung carcinoma (LLC) and human breast adenocarcinoma MCF-7 cells, with the test compounds at a concentration of 20 gM cells were incubated for 24 hours. Changes in mRNA expression of Nrf2, Nqo1, LC3b, and Sqstm1 genes encoding Nrf2, NAD(P)H:quinone oxidoreductase-1, LC3B, p62/sequestosome-1, respectively, were determined by TaqMan real-time PCR.Results and discussion. Structurally related synthetic monophenols effectively induced the Keap1/Nrf2/ARE system in LLC and MCF-7 cells, increasing the expression of the Nrf2-driven Nqo1 gene, and ambiguously affected the transcription of genes of proteins mediating autophagy: the content of mRNA of the LC3B protein did not change, while the expression of mRNA of the p62 protein, which affects the operation of both systems (processes), is increased only by the action of ortho-monosubstituted phenol with an «active» sulfur atom in the para-propyl substituent TS-13 and its structural analogue TS-12 with a para-substituent shortened by one methylene. It can be assumed that the observed effect either indicates the ability of TS-13 and TS-12 both to induce the Keap1/Nrf2/ARE system and to stimulate autophagy, or reflects a compound-mediated mutually reinforcing cross-activation of these processes.

Anti-Diabetic Effects of Metformin Nanoemulsion and Cell-Based Therapy on the Insulin Signaling Pathway (IRS1/AKT) and Apoptotic Related Genes in Type 2 Diabetic Rat Model

Restoration of the normoglycemic state is the basic tenet of diabetes research. Nowadays, using nanoemulsion drug delivery systems represent an alternative effective tool in Type 2 diabetes mellitus management. We aimed to investigate the anti-diabetic potential of metformin nanoemulsion and mesenchymal stem cells (MSCs) therapy on streptozotocin (STZ)-induced diabetic rat model. Nanoemulsion formulation was prepared with oil phase (5%v/v), 1gm metformin with a hydrophilic surfactant, then characterized for particle size and zeta potential.Adult male albino rats were induced for diabetes with 60 mg/kg STZ and were classified into 4 groups: STZ control group; STZ+MET group (orally administered daily dose of metformin 18 mg/200 g b.wt.); STZ+MSCs group (mono-therapeutic dose of BM-MSCs 1×106 cells/rat) and STZ+Nano-MET group (daily intraperitoneal dose of metformin nanoemulsion 18 mg/kg b.wt.). After 8 weeks, relative expression levels of hepatic IRS-1, AKT, Bcl-2, and Bax were assessed by qPCR. Also, histopathological investigations were performed. We reported cytoplasmic vacuolation, tissue necrosis, dilated blood sinusoid and congested hepatic vein in STZ group. Experimental animals either treated with metformin nanoemulsion or the mono-therapeutic dose of MSCs exhibited significant up-regulation in IRS-1/AKT pathway and Bcl-2 gene expression levels, as well as significant repression in Bax mRNA levels, besides a remarkable amelioration in a hepatic histological organization.Conclusion: Nano-MET holds an anti-diabetic potential that clearly surpasses metformin via affecting the insulin signaling pathway and apoptotic gene expression.

The Notch receptor-ligand Delta is involved in the immune response of Penaeus vannamei

In the Notch signaling pathway in vertebrates and invertebrates, the ligand Delta plays crucial roles in cell proliferation, differentiation, and immunity. Although the Notch signaling pathway has recently been implicated in the immune defense of Penaeus vannamei, the association of Delta with this immune response remains unclear. Here, we cloned and characterized the Delta homolog in P. vannamei (designated as PvDelta). PvDelta has a 2493 bp open reading frame (ORF) encoding a putative protein of 830 amino acids. Bioinformatics analysis revealed that PvDelta contains an N-terminal signal peptide, a conserved Notch ligand (MNNL) domain, a Delta/Serrate/Lag-2 segment, 9 epidermal growth factors segments, a transmembrane domain, and shares high homology with other Delta family members. Transcripts of PvDelta were detected in all shrimp tissues tested and were induced by Vibrio parahaemolyticus, white spot syndrome virus (WSSV), and lipopolysaccharide (LPS), indicating its involvement in shrimp immune response. Moreover, after PvDelta knockdown followed by LPS stimulation, the expression of Notch signaling pathway genes (i.e., PvNotch, PvCSL, and PvHey) was downregulated. Finally, shrimp depleted of PvDelta showed a lower survival rate in response to V. parahaemolyticus challenge. In sum, our data reveal that PvDelta is involved in the innate immunity of shrimp by positively modulating the Notch signaling pathway.

WNT signaling pathway genes expression profile in isolated hypodontia

WNT signaling pathway genes expression profile in isolated hypodontia

METTL3 regulates viral m6A RNA modification and host cell innate immune responses during SARS-CoV-2 infection.

It is urgent and important to understand the relationship of the widespread severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) with host immune response and study the underlining molecular mechanism. N6-methylation of adenosine (m6A) in RNA regulates many physiological and disease processes. Here, we investigate m6A modification of the SARS-CoV-2 gene in regulating the host cell innate immune response. Our data show that the SARS-CoV-2 virus has m6A modifications that are enriched in the 3′ end of the viral genome. We find that depletion of the host cell m6A methyltransferase METTL3 decreases m6A levels in SARS-CoV-2 and host genes, and m6A reduction in viral RNA increases RIG-I binding and subsequently enhances the downstream innate immune signaling pathway and inflammatory gene expression. METTL3 expression is reduced and inflammatory genes are induced in patients with severe coronavirus disease 2019 (COVID-19). These findings will aid in the understanding of COVID-19 pathogenesis and the design of future studies regulating innate immunity for COVID-19 treatment.

Bifenthrin reduces pregnancy potential via induction of oxidative stress in porcine trophectoderm and uterine luminal epithelial cells

Exposure to pesticides has become a serious concern for the environment and human health. Bifenthrin, a synthetic pyrethroid pesticide, is one of the most frequently used pesticides worldwide. Despite the toxic potential of bifenthrin, no studies have elucidated the cytotoxic response of bifenthrin in maternal and fetal cells that are involved in the implantation process. In this study, the cytotoxic effect of bifenthrin was investigated using porcine trophectoderm (pTr) and uterine luminal epithelial (pLE) cells. The results showed that bifenthrin suppressed cell proliferation and viability in pTr and pLE cells. In particular, bifenthrin induced cell cycle arrest, resulting in apoptosis in both cell lines. We found that bifenthrin damaged the mitochondria and induced the production of reactive oxygen species, causing endoplasmic reticulum stress and calcium dysregulation in pTr and pLE cells. Finally, bifenthrin altered the MAPK/PI3K signaling pathway and pregnancy-related gene expression. Collectively, our results suggest that bifenthrin reduces the implantation potential of embryos and may help elucidate the mechanisms underlying toxin-derived cytotoxicity in maternal and fetal cells.

Postnatal Catch-Up Growth Programs Telomere Dynamics and Glucose Intolerance in Low Birth Weight Mice.

Low birth weight and rapid postnatal weight gain are independent predictors of obesity and diabetes in adult life, yet the molecular events involved in this process remain unknown. In inbred and outbred mice, this study examines natural intrauterine growth restriction (IUGR) in relation to body weight, telomere length (TL), glucose tolerance, and growth factor gene (Igf1, Igf2, Insr, Igf1r, and Igf2r) mRNA expression levels in the brain, liver, and muscle at 2- and 10 days of age and then at 3- and 9 months of age. At birth, ~15% of the animals showed IUGR, but by 3 and 9 months, half of these animals had regained the same weight as controls without IUGR (recuperated group). At 10 days, there was no difference in TL between animals undergoing IUGR and controls. However, by 3 and 9 months of age, the recuperated animals had shorter TL than the control and IUGR-non recuperated animals and also showed glucose intolerance. Further, compared to controls, Igf1 and Igf2 growth factor mRNA expression was lower in Day 2-IUGR mice, while Igf2r and Insr mRNA expression was higher in D10-IUGR animals. Moreover, at 3 months of age, only in the recuperated group were brain and liver Igf1, Igf2, Insr, and Igf2r expression levels higher than in the control and IUGR-non-recuperated groups. These data indicate that catch-up growth but not IUGR per se affects TL and glucose tolerance, and suggest a role in this latter process of insulin/insulin-like growth signaling pathway gene expression during early development.

Gut microbial taxa elevated by dietary sugar disrupt memory function

Emerging evidence highlights a critical relationship between gut microbiota and neurocognitive development. Excessive consumption of sugar and other unhealthy dietary factors during early life developmental periods yields changes in the gut microbiome as well as neurocognitive impairments. However, it is unclear whether these two outcomes are functionally connected. Here we explore whether excessive early life consumption of added sugars negatively impacts memory function via the gut microbiome. Rats were given free access to a sugar-sweetened beverage (SSB) during the adolescent stage of development. Memory function and anxiety-like behavior were assessed during adulthood and gut bacterial and brain transcriptome analyses were conducted. Taxa-specific microbial enrichment experiments examined the functional relationship between sugar-induced microbiome changes and neurocognitive and brain transcriptome outcomes. Chronic early life sugar consumption impaired adult hippocampal-dependent memory function without affecting body weight or anxiety-like behavior. Adolescent SSB consumption during adolescence also altered the gut microbiome, including elevated abundance of two species in the genus Parabacteroides (P. distasonis and P. johnsonii) that were negatively correlated with hippocampal function. Transferred enrichment of these specific bacterial taxa in adolescent rats impaired hippocampal-dependent memory during adulthood. Hippocampus transcriptome analyses revealed that early life sugar consumption altered gene expression in intracellular kinase and synaptic neurotransmitter signaling pathways, whereas Parabacteroides microbial enrichment altered gene expression in pathways associated with metabolic function, neurodegenerative disease, and dopaminergic signaling. Collectively these results identify a role for microbiota “dysbiosis” in mediating the detrimental effects of early life unhealthy dietary factors on hippocampal-dependent memory function.

Critical role of the BAF chromatin remodeling complex during murine neural crest development.

The BAF complex plays an important role in the development of a wide range of tissues by modulating gene expression programs at the chromatin level. However, its role in neural crest development has remained unclear. To determine the role of the BAF complex, we deleted BAF155/BAF170, the core subunits required for the assembly, stability, and functions of the BAF complex in neural crest cells (NCCs). Neural crest-specific deletion of BAF155/BAF170 leads to embryonic lethality due to a wide range of developmental defects including craniofacial, pharyngeal arch artery, and OFT defects. RNAseq and transcription factor enrichment analysis revealed that the BAF complex modulates the expression of multiple signaling pathway genes including Hippo and Notch, essential for the migration, proliferation, and differentiation of the NCCs. Furthermore, we demonstrated that the BAF complex is essential for the Brg1-Yap-Tead-dependent transcription of target genes in NCCs. Together, our results demonstrate an important role of the BAF complex in modulating the gene regulatory network essential for neural crest development.

The Diverse Cellular Functions of Inner Nuclear Membrane Proteins.

The nuclear compartment is delimited by a specialized expanded sheet of the endoplasmic reticulum (ER) known as the nuclear envelope (NE). Compared to the outer nuclear membrane and the contiguous peripheral ER, the inner nuclear membrane (INM) houses a unique set of transmembrane proteins that serve a staggering range of functions. Many of these functions reflect the exceptional position of INM proteins at the membrane-chromatin interface. Recent research revealed that numerous INM proteins perform crucial roles in chromatin organization, regulation of gene expression, genome stability, and mediation of signaling pathways into the nucleus. Other INM proteins establish mechanical links between chromatin and the cytoskeleton, help NE remodeling, or contribute to the surveillance of NE integrity and homeostasis. As INM proteins continue to gain prominence, we review these advancements and give an overview on the functional versatility of the INM proteome.

Bumble bee queens activate dopamine production and gene expression in nutritional signaling pathways in the brain

To explore the neuroendocrine mechanisms underlying caste-specific behavior and its evolution from primitive to advanced eusocial bees, the monoamine levels and expression of genes involved in monoamine production and signaling in the brain were compared between the castes of Bombus ignitus. Higher levels of dopamine and its related substances were found in the brains of newly emerged queens than in the brains of emerged workers. The degree of caste differences in B. ignitus was smaller than that reported in Apis mellifera, indicating a link to different social stages in the two species. There was no differential expression in genes involved in dopamine biosynthesis between castes, suggesting that the high dopamine production in queens was not largely influenced by the expression of these genes at emergence, rather it might be influenced by tyrosine supply. Genome-wide analyses of gene expression by RNA-sequencing indicated that a greater number of genes involved in nutrition were actively expressed in the brains of newly emerged queens in comparison to the emerged workers. Some of the expression was confirmed by real-time quantitative PCR. The signaling pathways driven by the expression of these genes may be associated with dopamine signaling or the parallel activation of dopamine production.

High Glucose Causes Distinct Expression Patterns of Primary Human Skin Cells by RNA Sequencing.

Diabetes-related skin problems represent the most common long-term complications in diabetes mellitus patients. These complications, which include diabetic dermopathy, diabetic blisters, necrobiosis lipoidica diabeticorum, and eruptive xanthomatosis, may dramatically impair patients’ quality of life and cause long-lasting disability. However, the cellular and molecular mechanisms linking diabetes-related hyperglycemia and skin complications are still incompletely understood. To assess the role of the various skin-cell types in hyperglycemia-induced skin disorders, we performed RNA sequencing-based transcriptome analysis, measuring gene expression patterns in biological replicates in normal- and high glucose-stimulated skin cells. Three primary human skin-cell types were examined, i.e., epidermal keratinocytes, dermal fibroblasts, and dermal microvascular endothelial cells. For each separate cell type, we identified gene expression. Comparing gene abundances and expression levels revealed that transcription profiles exhibit distinct patterns in the three skin-cell types exposed to normal (i.e., physiological) glucose treatment and high (i.e., supraphysiological) glucose treatment. The obtained data indicate that high glucose induced differential gene expression and distinct activity patterns in signaling pathways in each skin-cell type. We are adding these data to the public database in the hope that they will facilitate future studies to develop novel targeted interventions for diabetic skin complications.