Changes In RNA Expression Research Articles

Changes in the Messenger RNA Expression of Toll-Like Receptors 2 and 4 in Healthy Infants According to Age.

Toll-like receptors (TLRs) are potentially useful indicators of several pediatric disease states. Here, we explore the mechanisms by which inflammation is regulated by interactions between microbiota and the host. Little data are available regarding the expression of TLRs in postnatal healthy infants. TLR 2 and TLR4 are extracellular TLRs that act as innate immune receptors by recognizing a wide range of endogenous ligands and microorganisms. The aim of this study was to use real-time polymerase chain reaction to investigate the expression of the messenger RNAs (mRNAs) of TLR2 and TLR4 in blood samples obtained from healthy full-term infants and toddlers. We analyzed the mRNA expression levels of TLRs in 88 healthy term children separated according to age. The median expression level of TLR2 was 1.49 ± 1.10 arbitrary units (AU) (n = 25) in infants younger than 3 months, 0.67 ± 0.72 AU (n = 25) in infants aged between 3 and 12 months, and 0.03 ± 0.02 AU (n= 38) in infants older than 12 months. The median expression level of TLR4 was 1.25 ± 0.79 AU (n = 25) in infants younger than 3 months, 0.75 ± 0.54 AU (n = 25) in infants aged 3 to 12 months, and 0.44 ± 0.28 AU (n = 38) in infants older than 12 months. There was difference in the mRNA expression level of TLR2 and TLR4 between infants aged 0 to 3 and 3 to 12 months and those aged more than 1 year (p < 0.0001 and p < 0.0001, respectively) CONCLUSION: We found that the expression levels of TLR2 and TLR4 were associated with age. In particular, we observed that their expression increased during the suckling period and then clearly decreased once the infants reached 1 year of age (p < 0.001). These findings could be related to microbial colonization and the immune system.

Assessment of myoblast circular RNA dynamics and its correlation with miRNA during myogenic differentiation.

Myoblast differentiation is a highly complex process that is regulated by proteins as well as by non-coding RNAs. Circular RNAs have been identified as an emerging new class of non-coding RNA in the modulation of skeletal muscle development, whereas their expression profiles and functional regulation in myoblast differentiation remain unknown. In the present study, we performed deep RNA-sequencing of C2C12 myoblasts during cell differentiation and uncovered 37,751 unique circular RNAs derived from 6943 hosting genes. The ensuing qRT-PCR and RNA fluorescence in situ hybridization verification were carried out to confirm the RNA-sequencing results. An unbiased analysis demonstrated dynamic circular RNA expression changes in the process of myoblast differentiation, and the circular RNA abundances were independent from their cognate linear RNAs. Gene ontology analysis showed that many down-regulated circular RNAs were exclusive to cell division and the cell cycle, whereas up-regulated circular RNAs were related to the cell development process. Furthermore, interaction networks of circular RNA-microRNA were constructed. Several microRNAs well-known for myoblast regulation, such as miR-133, miR-24 and miR-23a, were in this network. In summary, this study showed that circular RNA expression dynamics changed during myoblast differentiation. Circular RNAs play a role in regulating the myoblast cell cycle and development by acting as microRNA binding sites to facilitate their regulation of gene expression during myoblast differentiation. These findings open a new avenue for future investigation of this emerging RNA class in skeletal muscle growth and development.

Single-walled and multi-walled carbon nanotubes induce sequence-specific epigenetic alterations in 16 HBE cells.

Recent studies have identified carbon nanotube (CNT)-induced epigenetic changes as one of the key players in patho-physiological response. In the present study, we investigated whether CNT exposure is associated with epigenetic changes in human bronchial epithelial cells (16 HBE), in vitro. We focused on global DNA methylation, methylation of LINE-1 elements and promoter sequence of twelve functionally important genes (SKI, DNMT1, HDAC4, NPAT, ATM, BCL2L11, MAP3K10, PIK3R2, MYO1C, TCF3, FGFR 1 and AGRN). Additionally, we studied the influence of CNT exposure on miRNA expression. Using a LC-MS/MS method and pyrosequencing for LINE-1, we observed no significant changes in global DNA methylation (%) between the concentrations of multi-walled and single-walled CNT (MWCNT and SWCNT, respectively). Significant changes in sequence-specific methylation was observed in at least one CpG site for DNMT1 (SWCNT), HDAC4 (MWCNT), NPAT/ATM (MWCNT and SWCNT), MAP3K10 (MWCNT), PIK3R2 (MWCNT and SWCNT) and MYO1C (SWCNT). While changes in DNA methylation of the genes were relatively small, these changes were associated with changes in RNA expression, especially for MWCNT. However, the study did not reveal any significant alteration in the miRNA expression, associated with MWCNT and SWCNT exposure. Based on our results, mainly MWCNT influence DNA methylation and expression of the studied genes and could have significant impact on several critical cellular processes.

Bacteria, Brains, and Behavior: gut microbes and their effects on regulation of gene expression in the brain

The purpose of this research is to investigate the relationship between the microbiota of the gastrointestinal (GI) system, behavioral characteristics related to Autism Spectrum Disorder (ASD), and relative gene expression of miRNAs in the brain. This research utilizes BALB/c mice (a mouse strain that demonstrates low sociability) as a prototype for ASD and C57BL/6 as a control group of mice. Each mouse strain is fed either Bifidiobacterium longum, Lactobacillus rhamnosus, both bacteria, or only the bacterial media as a negative control. These bacterial strains are both well characterized probiotics shown to change behavior and improve sociability. Behavioral characteristics throughout the 10‐week feeding period for both mouse strains, and each probiotic condition, are compared using Crawley's Sociability and Preference for Social Novelty protocol. Upon completion of the 10‐week study, the mice are sacrificed, the brains are harvested, and the RNA is extracted from the brains of the mice. PCR arrays (Qiagen) are performed to determine changes in the gene expression of brain‐specific miRNAs. Preliminary results from a 3‐week feeding study indicated several miRNAs of interest. For example, these results revealed that relative gene expression of mmi‐488‐3c in the BALB/c mice was substantially more similar to the miRNA's expression in C57BL/6 only following the Bifidobacterium probiotic treatment. The data set from the extended 10‐week probiotic treatment will provide more significant evidence that these GI bacterial probiotics cause changes in expression of important regulatory RNAs. The resultant consequences for target brain mRNAs will also be demonstrated. As this study continues, it aims to further close the gap of understanding between causal relationships between the gut microbiota, neurological changes, and social behavior of animals.Support or Funding InformationTrinity Christian College, Vander Velde Research Fellowship.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Epigenetics of inflammatory arthritis.

Aberrant epigenetic changes in DNA methylation, histone marks, and noncoding RNA expression regulate the pathogenesis of many rheumatic diseases. The present article will review the recent advances in the epigenetic profile of inflammatory arthritis and discuss diagnostic biomarkers and potential therapeutic targets. Methylation signatures of fibroblast-like synoviocytes not only distinguish rheumatoid arthritis (RA) and osteoarthritis (OA), but also early RA from late RA or juvenile idiopathic arthritis. Methylation patterns are also specific to individual joint locations, which might explain the distribution of joint involvement in some rheumatic diseases. Hypomethylation in systemic lupus erythematosus (SLE) T cells is, in part, because of active demethylation and 5-hydroxymethylation. The methylation status of some genes in SLE is associated with disease severity and has potential as a diagnostic marker. An integrative analysis of OA methylome, transcriptome, and proteome in chondrocytes has identified multiple-evidence genes that might be evaluated for therapeutic potential. Class-specific histone deacetylase inhibitors are being evaluated for therapy in inflammatory arthritis. Disease pathogenesis is regulated by the interplay of genetics, environment, and epigenetics. Understanding how these mechanisms regulate cell function in health and disease has implications for individualized therapy.

Continuous hypergravity alters the cytoplasmic elasticity of MC3T3-E1 osteoblasts via actin filaments

Osteoblasts are sensitive to altered gravity conditions, displaying changes in RNA and protein expression, proliferation, and differentiation; however, the effect of hypergravity on the mechanical properties of osteoblasts remains unclear. In this study, atomic force microscopy (AFM) was used to evaluate the effect of hypergravity on the elasticity of osteoblasts. We demonstrate that a continuous hypergravitational environment increased the elasticity of the cytoplasm, but not the nuclei zone, of MC3T3-E1 osteoblasts. Actin filaments, but not microtubules, dominated in the increased elasticity. These findings provide new insights on cellular gravity-sensing mechanisms.

Klinefelter Syndrome: Integrating Genetics, Neuropsychology, and Endocrinology.

Although first identified over 70 years ago, Klinefelter syndrome (KS) continues to pose substantial diagnostic challenges, as many patients are still misdiagnosed, or remain undiagnosed. In fact, as few as 25% of patients with KS are accurately diagnosed and most of these diagnoses are not made until adulthood. Classic characteristics of KS include small testes, infertility, hypergonadothropic hypogonadism, and cognitive impairment. However, the pathophysiology behind KS is not well understood, although genetic effects are also thought to play a role. For example, recent developments in genetics and genomics point to a fundamental change in our understanding of KS, with global epigenetic and RNA expression changes playing a central role for the phenotype. KS is also associated with more general health markers, including higher morbidity and mortality rates and lower socioeconomic status (which likely affect both morbidity and mortality). In addition, hypogonadism is associated with greater risk of metabolic syndrome, type 2 diabetes, cardiovascular disease, breast cancer, and extragonadal germ cell tumors. Medical treatment typically focuses on testosterone replacement therapy (TRT), although the effects of this therapy have not been studied rigorously, and future studies need to evaluate the effects of TRT on metabolic risk and neurocognitive outcomes. This review presents a comprehensive interdisciplinary examination of recent developments in genetic, endocrine, and neurocognitive science, including the study of animal models. It provides a number of recommendations for improving the effectiveness of research and clinical practice, including neonatal KS screening programs, and a multidisciplinary approach to KS treatment from childhood until senescence.

Effects of Luteinizing Hormone‐releasing Hormone Analog Injection on Intestinal Transcriptome in Grass Carp, Ctenopharyngodon idella

AbstractThe present study aimed to detect the changes in gene expression by luteinizing hormone‐releasing hormone analog (LHRH‐A) stimulation in the intestine of grass carp. LHRH‐A has been widely used for inducing ovulation of teleosts. The transcriptome changes induced by LHRH‐A are not fully understood, especially in intestines. To understand the changes of RNA expression after intraperitoneal injection of LHRH‐A, two cDNA libraries of intestines from grass carps, including LHRH‐A injection group and control group, were sequenced using Illumina HiSeq 4000 (Illumina, San Diego, CA, USA). In total, 13,581,225,000 nucleotides were obtained and 66,127 unigenes were generated by de novo assembly. The differentially expressed genes were identified by comparing the Fragments Per Kilobase Of Exon Per Million of the unigenes between the two groups. The results indicated that 255 and 212 unigenes were upregulated and downregulated, respectively, in the LHRH‐A injection group. Furthermore, the protein digestion and absorption pathways as well as fat digestion and absorption pathways tended to be upregulated by LHRH‐A injection. These findings provide a valuable resource for understanding the response of intestinal transcriptome levels to hormones.

Mid-to-Late Gestational Changes in Inflammatory Gene Expression in the Rat Placenta.

The placenta plays an important role during pregnancy providing maternal blood supply from the uterus to the developing fetus. The structure and function of the placenta changes with gestation, as the fetus develops and its demands change. This study aims to elucidate changes in cytokine and chemokine gene expression throughout mid-to-late gestation in rat placenta. Sprague Dawley rats were time-mated, and placentae were obtained from 6 pregnant dams at 4 different gestational periods: E14.25, E15.25, E17.25, and E20. Changes in placental gene expression were measured by microarray analysis. Differentially expressed inflammatory genes were functionally categorized by pathway analysis. To validate the microarray results, a subset of genes was analyzed by quantitative real-time polymerase chain reaction (qPCR) in a validation cohort of 22 rats. Changes in messenger RNA (mRNA) expression of various cytokines, chemokines, and genes of the tumor growth factor β and tumor necrosis factor family were analyzed in rat placentae at E14.25, E15.25, E17.25, and E20. Forty-six genes were differentially expressed, and of these 21 genes had increased expression in late gestation (E20). The gestational age pattern of gene expression was confirmed by qPCR in the validation cohort. The observed acute, prelabor changes in the expression of these genes during gestation warrant further investigation to elucidate their role in pregnancy and parturition.

Inhibitory effects of candesartan on KCa3.1 potassium channel expression and cell culture and proliferation in peripheral blood CD4+T lymphocytes in Kazakh patients with hypertension from the Xinjiang region

ABSTRACTBackground and aim: Increasing evidence confirms that potassium channels are essential for lymphocyte activation, suggesting an involvement in the development of hypertension. Moreover, chronic inflammation is regarded as a direct or indirect manifestation of hypertension, highlighting the theoretical mechanisms. In this study, we investigated changes in KCa3.1 potassium channel expression in the blood of hypertensive and healthy Kazakh people in north-west China.Methods: Flow cytometry technology was used for T-lymphocyte subtype analysis. Changes in the messenger RNA and protein expression of the KCa3.1 potassium channel in CD4+ T lymphocytes were detected using real-time quantitative polymerase chain reaction and western blots, using CD4+ T-cell samples from hypertensive Kazakh patients divided into candesartan and TRAM-34 treatment groups, and healthy case controls. Peripheral blood CD4+ T lymphocytes were activated and proliferated in vitro and then incubated for 0, 24, and 48 h under various treatment conditions. Changes in CD4+ T-lymphocytic proliferation were determined using Cell Counting Kit-8 and electron microscope photography.Results: Expression of KCa3.1 was significantly higher in the hypertensive patients than in the controls (p < 0.05). Compared with the healthy group, Kazakh hypertensive patients had a reduced proportion of CD4+ T lymphocytes (p < 0.05).Candesartan and TRAM-34 intervention for 24 h and 48 h inhibited the expression of Kv1.3 and KCa3.1 at mRNA and protein level (p < 0.05).Conclusions: Increase in functional KCa3.1 channels expressed in CD4+ T lymphocytes of Kazakh patients with hypertension was blocked by candesartan, providing theoretical support for hypertension treatment at the cellular ion channel level. Candesartan may potentially regulate hypertensive inflammatory responses by inhibiting T-lymphocytic proliferation and KCa3.1 potassium channel expression in CD4 + T lymphocytes.

Long Noncoding RNA-Associated Transcriptomic Changes in Resiliency or Susceptibility to Depression and Response to Antidepressant Treatment.

BackgroundRecent emergence of long noncoding RNAs in regulating gene expression and thereby modulating physiological functions in brain has manifested their possible role in psychiatric disorders. In this study, the roles of long noncoding RNAs in susceptibility and resiliency to develop stress-induced depression and their response to antidepressant treatment were examined.MethodsMicroarray-based transcriptome-wide changes in long noncoding RNAs were determined in hippocampus of male Holtzman rats who showed susceptibility (learned helplessness) or resiliency (nonlearned helplessness) to develop depression. Changes in long noncoding RNA expression were also ascertained after subchronic administration of fluoxetine to learned helplessness rats. Bioinformatic and target prediction analyses (cis- and trans-acting) and qPCR-based assays were performed to decipher the functional role of altered long noncoding RNAs.ResultsGroup-wise comparison showed an overrepresented class of long noncoding RNAs that were uniquely associated with nonlearned helplessness or learned helplessness behavior. Chromosomal mapping within the 5-kbp flank region of the top 20 dysregulated long noncoding RNAs in the learned helplessness group showed several target genes that were regulated through cis- or trans-actions, including Zbtb20 and Zfp385b from zinc finger binding protein family. Genomic context of differentially expressed long noncoding RNAs showed an overall blunted response in the learned helplessness group regardless of the long noncoding RNA classes analyzed. Gene ontology exhibited the functional clustering for anatomical structure development, cellular architecture modulation, protein metabolism, and cellular communications. Fluoxetine treatment reversed learned helplessness-induced changes in many long noncoding RNAs and target genes.ConclusionsThe involvement of specific classes of long noncoding RNAs with distinctive roles in modulating target gene expression could confer the role of long noncoding RNAs in resiliency or susceptibility to develop depression with a reciprocal response to antidepressant treatment.

Enhanced skeletal muscle ribosome biogenesis, yet attenuated mTORC1 and ribosome biogenesis-related signalling, following short-term concurrent versus single-mode resistance training

Combining endurance training with resistance training (RT) may attenuate skeletal muscle hypertrophic adaptation versus RT alone; however, the underlying mechanisms are unclear. We investigated changes in markers of ribosome biogenesis, a process linked with skeletal muscle hypertrophy, following concurrent training versus RT alone. Twenty-three males underwent eight weeks of RT, either performed alone (RT group, n = 8), or combined with either high-intensity interval training (HIT+RT group, n = 8), or moderate-intensity continuous training (MICT+RT group, n = 7). Muscle samples (vastus lateralis) were obtained before training, and immediately before, 1 h and 3 h after the final training session. Training-induced changes in basal expression of the 45S ribosomal RNA (rRNA) precursor (45S pre-rRNA), and 5.8S and 28S mature rRNAs, were greater with concurrent training versus RT. However, during the final training session, RT further increased both mTORC1 (p70S6K1 and rps6 phosphorylation) and 45S pre-rRNA transcription-related signalling (TIF-1A and UBF phosphorylation) versus concurrent training. These data suggest that when performed in a training-accustomed state, RT induces further increases mTORC1 and ribosome biogenesis-related signalling in human skeletal muscle versus concurrent training; however, changes in ribosome biogenesis markers were more favourable following a period of short-term concurrent training versus RT performed alone.

Transcriptomic profiling of interacting nasal staphylococci species reveals global changes in gene and non-coding RNA expression.

Interspecies interactions between bacterial pathogens and the commensal microbiota can influence disease outcome. In the nasal cavities, Staphylococcus epidermidis has been shown to be a determining factor for Staphylococcus aureus colonization and biofilm formation. However, the interaction between S. epidermidis and S. aureus has mainly been described by phenotypic analysis, and little is known about how this interaction modulates gene expression. This study aimed to determine the interactome of nasal S. aureus and S. epidermidis isolates to understand the molecular effect of interaction. After whole-genome sequencing of two nasal staphylococcal isolates, an agar-based RNA sequencing setup was utilized to identify interaction-induced transcriptional alterations in surface-associated populations. Our results revealed differential expression of several virulence genes in both species. We also identified putative non-coding RNAs (ncRNAs) and, interestingly, detected a putative ncRNA transcribed antisense to esp, the serine protease of S. epidermidis, that has previously been shown to inhibit nasal colonization of S. aureus. In our study, the gene encoding Esp and the antisense ncRNA are both downregulated during interaction with S. aureus. Our findings contribute to a better understanding of pathogen physiology in the context of interactions with the commensal microbiota, and may provide targets for future therapeutics.

Practical implications of mineral and vitamin imbalance in grazing sheep

Rapid progress in research on mineral functions in biological systems over the past 20 years has provided new and unexplored implications for health and production in grazing livestock. The strong interaction among calcium (Ca), magnesium (Mg), phosphorus (P), sodium (Na), potassium (K) and vitamin D influences the absorption, utilisation and status of these nutrients, particularly Ca and Mg. An imbalanced intake of Ca, Mg, P, Na, K and vitamin D is common in ruminants grazing pastures and vegetative crops. The interaction may modify susceptibility to clinical hypocalcaemia, hypomagnesaemia and pregnancy toxaemia, or to subclinical and chronic deficiencies of Ca, Mg and Na. However, hypocalcaemia is also associated with endocrine failure. Whether this failure is susceptible to nutritional modulation or even whether supplements of Ca, Mg, Na and vitamin D reduce or exacerbate the risk of metabolic disease in sheep is unclear. Selenium, manganese, zinc, copper, sulfur, vitamin E and vitamin A play synergistic roles in the antioxidant defence mechanism and modulate the consequences of oxidative stress. In extensive grazing systems combined low intakes of these antioxidants are not unusual, particularly in seasonally dry environments and at a time coinciding with the increased oxidative stress that naturally occurs through the reproductive cycle. This oxidative stress is accentuated by heat stress and parasite infection. Oxidative stress in the short-term influences growth, reproduction, offspring survival and health. Long-term, oxidative damage to embryo DNA and changes in RNA expression, may influence lifetime performance of offspring. The high cost of providing mineral supplements to grazing sheep is a deterrence to addressing the implications of multiple mineral deficiencies. New herbaceous and shrub options to increase the botanical and nutritional diversity within pasture and crop-grazing systems may allow livestock to select a heterogeneous diet providing a more balanced mineral intake.

Метаболомное профилирование больных с сердечно-сосудистыми заболеваниями

Cardiovascular diseases (CVD) are the main cause of death worldwide. A broad study of the pathogenetic mechanisms of the CVD onset and progression has led to understanding of the importance of endothelial dysfunction (ED) in these processes. During recent years intensive work has been conducted in the direction of searching for markers of ED. Metabolomics is an intensively advancing approach to early diagnostics of diseases. Metabolomic analysis based on mass spectrometry allows to study complete metabolic profiles and their deviations resulting from changes in expression of genes and RNA, protein activity, or environmental factors. Metabolomic analysis has already demonstrated significant results in the solving of different scientific and clinical problems. It appears to be a promising method for detecting early biomarkers of CVD. Various aspects of application of metabolomic profiling in the field of cardiovascular diseases are discussed in this article.

Folic acid modulates cancer-associated micro RNAs and inflammatory mediators in neoplastic and non-neoplastic colonic cells in a different way.

Scientific evidence suggests that folic acid (FA) supplementation protects the healthy colonic mucosa from neoplastic transformation but may promote the progression of precancerous lesions. The underlying molecular mechanisms are not fully understood. Therefore, we explored, if high physiological FA doses provoke changes in (i) promoter-specific DNA methylation (ii) expression of cancer-associated micro RNAs (miRNAs) and (iii) inflammatory mediators in human neoplastic and non-neoplastic colonic cell lines. The malignant and the non-malignant colonic cell lines HT29 and HCEC were adapted to different near-physiological FA concentrations. Using DNA methylation and pathway specific PCR arrays, high-physiological FA concentrations revealed no relevant impact on promoter methylation but a number of differences between the cell lines in the expression of miRNAs and inflammatory mediators. In the HCEC cell line pro-inflammatory genes were repressed and the miRNA expression remained nearly unaffected. In contrast, in the HT29 cell line tumour-suppressive miRNAs were predominantly down-regulated and the expression of genes involved in chemotaxis and immunity were modulated. The different effects of high-physiological FA concentrations in malignant and non-malignant colonic cell lines regarding cancer-associated miRNAs and inflammatory mediators may contribute to the different effects of FA supplementation on colonic carcinogenesis.

Prostate Cancer: An Update on Molecular Pathology with Clinical Implications

Abstract Recent advances in sequencing technologies, proteomics, and metabolomics have led to the identification of numerous molecular alterations across solid tumors including prostate cancer. The delineation of various genetic and epigenetic events involved in tumor progression have facilitated the development of novel diagnostic tests and the successful therapeutic targeting of key oncogenic events in prostate cancer. The most common genomic aberrations in prostate cancer include gene fusions, amplification, deletion, and mutations. In addition, up and down regulation of gene expression in critical cellular pathways is also at play. A series of long noncoding RNA expression changes have been also unveiled from transcriptome sequencing data. They play a regulatory role in prostate cancer and are promising diagnostic and potentially prognostic markers. In this review, we summarize recent advances in molecular pathology of prostate cancer and their emerging clinical utility.

Integration of lncRNA-miRNA-mRNA reveals novel insights into oviposition regulation in honey bees.

BackgroundThe honey bee (Apis mellifera) is a highly diverse species commonly used for honey production and pollination services. The oviposition of the honey bee queen affects the development and overall performance of the colony. To investigate the ovary activation and oviposition processes on a molecular level, a genome-wide analysis of lncRNAs, miRNAs and mRNA expression in the ovaries of the queens was performed to screen for differentially expressed coding and noncoding RNAs. Further analysis identified relevant candidate genes or RNAs.ResultsThe analysis of the RNA profiles in different oviposition phase of the queens revealed that 740 lncRNAs, 81 miRNAs and 5,481 mRNAs were differently expressed during the ovary activation; 88 lncRNAs, 13 miRNAs and 338 mRNAs were differently expressed during the oviposition inhibition process; and finally, 100 lncRNAs, four miRNAs and 497 mRNAs were differently expressed during the oviposition recovery process. In addition, functional annotation of differentially expressed RNAs revealed several pathways that are closely related to oviposition, including hippo, MAPK, notch, Wnt, mTOR, TGF-beta and FoxO signaling pathways. Furthermore, in the QTL region for ovary size, 73 differentially expressed genes and 14 differentially expressed lncRNAs were located, which are considered as candidate genes affecting ovary size and oviposition. Moreover, a core set of genes served as bridges among different miRNAs were identified through the integrated analysis of lncRNA-miRNA-mRNA network.ConclusionThe observed dramatic expression changes of coding and noncoding RNAs suggest that they may play a critical role in honey bee queens’ oviposition. The identified candidate genes for oviposition activation and regulation could serve as a resource for further studies of genetic markers of oviposition in honey bees.

Understanding and Resetting Radiation Sensitivity in Rectal Cancer.

The aim of the study was to explore specific microRNAs (miRs) in rectal cancer that would predict response to radiation and identify target pathways that may be exploited for neoadjuvant therapies. Chemoradiotherapy (CRT) response is a predictor of survival in rectal cancer. Studies have demonstrated changes in RNA expression correlate with chemoradiation sensitivity across cancers. Forty-five rectal cancer patients, partial responders (PR = 18), nonresponders (NR = 13), and complete responders (CR = 14) to CRT, as defined by a tumor regression score, were examined. miRs differentially expressed, using NanoString microArray profiling, were validated with qPCR. We quantified 1 miR and its downstream targets in patient samples. Chemosensitivity was measured in HCT-116, a human colorectal carcinoma cell line, using inhibitors of SHP2 and RAF. miR-451a, 502-5p, 223-3p, and 1246 were the most upregulated miRs (>1.5-fold change) in a NanoString profiling miR panel. qPCR revealed a decrease in expression of miR-451a in NRs. EMSY and CAB39, both downstream targets of miR-451a and involved in carcinogenesis (shown in TCGA) were increased in NRs (qPCR). Both targets are associated with worse survival in colorectal cancer. Inhibition of miR-451a in HCT-116 cells significantly decreased cell proliferation with treatment of SHP2 and RAF inhibitors. An integrated analysis of rectal cancer miRs may yield biomarkers of radioresistance and offer treatment targets for resensitization.

Combinatorial effects of zinc deficiency and arsenic exposure on zebrafish (Danio rerio) development.

Zinc deficiency and chronic low level exposures to inorganic arsenic in drinking water are both significant public health concerns that affect millions of people including pregnant women. These two conditions can co-exist in the human population but little is known about their interaction, and in particular, whether zinc deficiency sensitizes individuals to arsenic exposure and toxicity, especially during critical windows of development. To address this, we utilized the Danio rerio (zebrafish) model to test the hypothesis that parental zinc deficiency sensitizes the developing embryo to low-concentration arsenic toxicity, leading to altered developmental outcomes. Adult zebrafish were fed defined zinc deficient and zinc adequate diets and were spawned resulting in zinc adequate and zinc deficient embryos. The embryos were treated with environmentally relevant concentrations of 0, 50, and 500 ppb arsenic. Arsenic exposure significantly reduced the amount of zinc in the developing embryo by ~7%. The combination of zinc deficiency and low-level arsenic exposures did not sensitize the developing embryo to increased developmental malformations or mortality. The combination did cause a 40% decline in physical activity of the embryos, and this decline was significantly greater than what was observed with zinc deficiency or arsenic exposure alone. Significant changes in RNA expression of genes that regulate zinc homeostasis, response to oxidative stress and insulin production (including zip1, znt7, nrf2, ogg1, pax4, and insa) were found in zinc deficient, or zinc deficiency and arsenic exposed embryos. Overall, the data suggests that the combination of zinc deficiency and arsenic exposure has harmful effects on the developing embryo and may increase the risk for developing chronic diseases like diabetes.