The Drosophila melanogaster Levodopa-Induced Depression Model Exhibits Negative Geotaxis Deficits and Differential Gene Expression in Males and Females

More than 320 million people live with depression in the world, a disorder that severely limits psychosocial functioning and diminishes quality of life. The prevalence of major depression is almost two times higher in women than in men. However, the molecular mechanisms of its sex-specific pathophysiology are still poorly understood. Drosophila melanogaster is an established model for neurobiological research of depression-like states, as well as for the study of molecular and genetic sex differences in the brain. Here, we investigated sex-specific effects on forced-climbing locomotion (negative geotaxis) and gene expression of a fly model of depression-like phenotypes induced by levodopa administration, which was previously shown to impair normal food intake, mating frequency, and serotonin concentration. We observed that both males and females show deficits in the forced-climbing paradigm; however, modulated by distinct gene expression patterns after levodopa administration. Our results suggest that Drosophila models can be a valuable tool for identifying the molecular mechanisms underlying the difference of depressive disorder prevalence between men and women.

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Sex-specific longitudinal association of DNA methylation with lung function

ERJ Open Research ◽

10.1183/23120541.00127-2021 ◽

2021 ◽

pp. 00127-2021

Author(s):

Shadia Khan Sunny ◽

Hongmei Zhang ◽

Caroline L. Relton ◽

Susan Ring ◽

Latha Kadalayil ◽

...

Keyword(s):

Gene Expression ◽

Lung Function ◽

Mixed Models ◽

Enrichment Analysis ◽

Expression Data ◽

Specific Effects ◽

Parents And Children ◽

Longitudinal Association ◽

Males And Females ◽

Avon Longitudinal Study

Investigating whether DNA-M at an earlier age is associated with lung function at a later age and whether this relationship differs by sex could enable prediction of future lung function deficit.A training/testing-based technique was used to screen 402 714 cytosine-phosphate-guanine dinucleotide sites (CpGs) to assess the longitudinal association of blood-based DNA-M at ages 10 and 18-years with lung function at 18 and 26-years, respectively, in the Isle of Wight birth cohort (IOWBC). Multivariable linear mixed models were applied to the CpGs that passed screening. To detect differentially methylated regions (DMRs), DMR enrichment analysis was conducted. Findings were further examined in the Avon Longitudinal Study of Parents and Children (ALSPAC). Biological relevance of the identified CpGs was assessed utilizing gene expression data.DNA-M at 8 CpGs (FEV1: 5 and FEV1/FVC: 3 CpGs) at an earlier age was associated with lung function at a later age regardless of sex, while at 13 CpGs (FVC: 5, FEV1:3, and FEV1/FVC: 5 CpGs), the associations were sex-specific (pFDR<0.05) in IOWBC with consistent directions of association in ALSPAC (IOWBC-ALSPAC consistent CpGs). cg16582803 (WNT10A) and cg14083603 (ZGPAT) were replicated in ALSPAC for main and sex-specific effects, respectively. Among IOWBC-ALSPAC consistent CpGs, DNA-M at cg01376079 (SSH3) and cg07557690 (TGFBR3) was associated with gene expression both longitudinally and cross-sectionally. In total, 57 and 170 DMRs were linked to lung function longitudinally in males and females, respectively.CpGs showing longitudinal associations with lung function have the potential to serve as candidate markers in future studies on lung function deficit prediction.

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Integrative Transcriptomics Reveals Activation of Innate Immune Responses and Inhibition of Inflammation During Oral Immunotherapy for Egg Allergy in Children

Frontiers in Immunology ◽

10.3389/fimmu.2021.704633 ◽

2021 ◽

Vol 12 ◽

Author(s):

Piia Karisola ◽

Kati Palosuo ◽

Victoria Hinkkanen ◽

Lukas Wisgrill ◽

Terhi Savinko ◽

...

Keyword(s):

Gene Expression ◽

Clinical Outcome ◽

Immune Responses ◽

Molecular Mechanisms ◽

Expression Patterns ◽

Oral Immunotherapy ◽

Innate Immune ◽

Egg Allergy ◽

Innate Immune Responses ◽

Open Label

We previously reported the results of a randomized, open-label trial of egg oral immunotherapy (OIT) in 50 children where 44% were desensitized and 46% were partially desensitized after 8 months of treatment. Here we focus on cell-mediated molecular mechanisms driving desensitization during egg OIT. We sought to determine whether changes in genome-wide gene expression in blood cells during egg OIT correlate with humoral responses and the clinical outcome. The blood cell transcriptome of 50 children receiving egg OIT was profiled using peripheral blood mononuclear cell (PBMC) samples obtained at baseline and after 3 and 8 months of OIT. We identified 467 differentially expressed genes (DEGs) after 3 or 8 months of egg OIT. At 8 months, 86% of the DEGs were downregulated and played a role in the signaling of TREM1, IL-6, and IL-17. In correlation analyses, Gal d 1–4-specific IgG4 antibodies associated positively with DEGs playing a role in pathogen recognition and antigen presentation and negatively with DEGs playing a role in the signaling of IL-10, IL-6, and IL-17. Desensitized and partially desensitized patients had differences in their antibody responses, and although most of the transcriptomic changes were shared, both groups had also specific patterns, which suggest slower changes in partially desensitized and activation of NK cells in the desensitized group. OIT for egg allergy in children inhibits inflammation and activates innate immune responses regardless of the clinical outcome at 8 months. Changes in gene expression patterns first appear as posttranslational protein modifications, followed by more sustained epigenetic gene regulatory functions related to successful desensitization.

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crooked legs encodes a family of zinc finger proteins required for leg morphogenesis and ecdysone-regulated gene expression during Drosophila metamorphosis

Development ◽

10.1242/dev.125.9.1733 ◽

1998 ◽

Vol 125 (9) ◽

pp. 1733-1745 ◽

Cited By ~ 13

Author(s):

P.P. D'Avino ◽

C.S. Thummel

Keyword(s):

Gene Expression ◽

Molecular Mechanisms ◽

Genetic Locus ◽

Regulatory Genes ◽

Protein Isoforms ◽

Sequence Motif ◽

Specific Effects ◽

Insect Metamorphosis ◽

Adult Head ◽

Regulated Gene Expression

Drosophila imaginal discs undergo extensive pattern formation during larval development, resulting in each cell acquiring a specific adult fate. The final manifestation of this pattern into adult structures is dependent on pulses of the steroid hormone ecdysone during metamorphosis, which trigger disc eversion, elongation and differentiation. We have defined genetic criteria that allow us to screen for ecdysone-inducible regulatory genes that are required for this transformation from patterned disc to adult structure. We describe here the first genetic locus isolated using these criteria: crooked legs (crol). crol mutants die during pupal development with defects in adult head eversion and leg morphogenesis. The crol gene is induced by ecdysone during the onset of metamorphosis and encodes at least three protein isoforms that contain 12–18 C2H2 zinc fingers. Consistent with this sequence motif, crol mutations have stage-specific effects on ecdysone-regulated gene expression. The EcR ecdysone receptor, and the BR-C, E74 and E75 early regulatory genes, are submaximally induced in crol mutants in response to the prepupal ecdysone pulse. These changes in gene activity are consistent with the crol lethal phenotypes and provide a basis for understanding the molecular mechanisms of crol action. The genetic criteria described here provide a new direction for identifying regulators of adult tissue development during insect metamorphosis.

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An ABA-flavonoid relationship contributes to the differences in drought resistance between different sea buckthorn subspecies

Tree Physiology ◽

10.1093/treephys/tpaa155 ◽

2020 ◽

Author(s):

Guori Gao ◽

Zhongrui Lv ◽

Guoyun Zhang ◽

Jiayi Li ◽

Jianguo Zhang ◽

...

Keyword(s):

Drought Stress ◽

Rna Sequencing ◽

Drought Resistance ◽

Molecular Mechanisms ◽

Expression Patterns ◽

Normal Growth ◽

Carotenoid Biosynthesis ◽

Sea Buckthorn ◽

Mutual Regulation ◽

The Difference

Abstract Drought is the most severe abiotic stress and hinders the normal growth and development of plants. Sea buckthorn (Hippophae rhamnoides Linn.) is a typical drought-resistant tree species. In this study, the leaves of the H. rhamnoides ssp. sinensis (“FN”) and H. rhamnoides ssp. mongolica (“XY”) were selected during drought-recovery cycles for RNA sequencing, and physiological and biochemical analyses. The results revealed that drought stress significantly decreased leaf water potential, net photosynthetic rate, and stomatal conductance in both sea buckthorn subspecies. Similarly, the contents of flavone, flavonol, isoflavone and flavanone significantly decreased under drought stress in “XY.” Conversely, in “FN,” the flavone and abscisic acid (ABA) contents were significantly higher under drought stress and recovered after rehydration. Meanwhile, 4,618 and 6,100 differentially expressed genes (DEGs) were identified under drought stress in “FN” and “XY,” respectively. In total, 5,164 DEGs were observed in the comparison between “FN” and “XY” under drought stress. This was more than the 3,821 and 3,387 DEGs found when comparing the subspecies under control and rehydration conditions, respectively. These DEGs were mainly associated with carotenoid biosynthesis, flavonoid biosynthesis, photosynthesis, and plant hormone signal transduction. Six hub DEGs (ABCG5, ABCG22, ABCG32, ABCG36, ABF2 and PYL4) were identified to respond to drought stress based on WGCNA and BLAST analysis using DroughtDB. These six DEGs were annotated to play roles in the ABA-dependent signaling pathway. Sixteen RNA sequencing results involving eight genes and similar expression patterns (12/16) were validated using quantitative real-time PCR. The biochemical and molecular mechanisms underlying the regulation of drought responses by ABA and flavonoids in sea buckthorn were clarified. In this study, gene co-expression networks were constructed, and the results suggested that the mutual regulation of ABA and flavonoid signaling contributed to the difference in drought resistance between the different sea buckthorn subspecies.

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An animal model study on the gene expression profile of meniscal degeneration

Scientific Reports ◽

10.1038/s41598-020-78349-4 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Yehan Fang ◽

Hui Huang ◽

Gang Zhou ◽

Qinghua Wang ◽

Feng Gao ◽

...

Keyword(s):

Gene Expression ◽

Pathway Analysis ◽

Molecular Mechanisms ◽

Expression Patterns ◽

Control Group ◽

Ion Binding ◽

Endoplasmic Reticulum Membrane ◽

Rt Pcr ◽

Go Analysis ◽

Meniscal Degeneration

AbstractMeniscal degeneration is a very common condition in elderly individuals, but the underlying mechanisms of its occurrence are not completely clear. This study examines the molecular mechanisms of meniscal degeneration. The anterior cruciate ligament (ACL) and lateral collateral ligament (LCL) of the right rear limbs of seven Wuzhishan mini-pigs were resected (meniscal degeneration group), and the left rear legs were sham-operated (control group). After 6 months, samples were taken for gene chip analysis, including differentially expressed gene (DEG) analysis, gene ontology (GO) analysis, clustering analysis, and pathway analysis. The selected 12 DEGs were validated by real time reverse transcription-polymerase chain reaction (RT-PCR). The two groups showed specific and highly clustered DEGs. A total of 893 DEGs were found, in which 537 are upregulated, and 356 are downregulated. The GO analysis showed that the significantly affected biological processes include nitric oxide metabolic process, male sex differentiation, and mesenchymal morphogenesis, the significantly affected cellular components include the endoplasmic reticulum membrane, and the significantly affected molecular functions include transition metal ion binding and iron ion binding. The pathway analysis showed that the significantly affected pathways include type II diabetes mellitus, inflammatory mediator regulation of TRP channels, and AMPK signaling pathway. The results of RT-PCR indicate that the microarray data accurately reflects the gene expression patterns. These findings indicate that several molecular mechanisms are involved in the development of meniscal degeneration, thus improving our understanding of meniscal degeneration and provide molecular therapeutic targets in the future.

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Gene Expression Patterns Underlying the Reinstatement of Plasticity in the Adult Visual System

Neural Plasticity ◽

10.1155/2013/605079 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 11

Author(s):

Ettore Tiraboschi ◽

Ramon Guirado ◽

Dario Greco ◽

Petri Auvinen ◽

Jose Fernando Maya-Vetencourt ◽

...

Keyword(s):

Gene Expression ◽

Visual Cortex ◽

Large Scale ◽

Molecular Mechanisms ◽

Expression Patterns ◽

Monocular Deprivation ◽

Adult Brain ◽

Gene Expression Patterns ◽

Postnatal Life ◽

Critical Periods

The nervous system is highly sensitive to experience during early postnatal life, but this phase of heightened plasticity decreases with age. Recent studies have demonstrated that developmental-like plasticity can be reactivated in the visual cortex of adult animals through environmental or pharmacological manipulations. These findings provide a unique opportunity to study the cellular and molecular mechanisms of adult plasticity. Here we used the monocular deprivation paradigm to investigate large-scale gene expression patterns underlying the reinstatement of plasticity produced by fluoxetine in the adult rat visual cortex. We found changes, confirmed with RT-PCRs, in gene expression in different biological themes, such as chromatin structure remodelling, transcription factors, molecules involved in synaptic plasticity, extracellular matrix, and excitatory and inhibitory neurotransmission. Our findings reveal a key role for several molecules such as the metalloproteases Mmp2 and Mmp9 or the glycoprotein Reelin and open up new insights into the mechanisms underlying the reopening of the critical periods in the adult brain.

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Effects of Cutting, Pruning, and Grafting on the Expression of Age-Related Genes in Larix kaempferi

Forests ◽

10.3390/f11020218 ◽

2020 ◽

Vol 11 (2) ◽

pp. 218

Author(s):

Yao Zhang ◽

Qiao-Lu Zang ◽

Li-Wang Qi ◽

Su-Ying Han ◽

Wan-Feng Li

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Regular Expression ◽

Molecular Mechanisms ◽

Expression Patterns ◽

Reproductive Development ◽

Larix Kaempferi ◽

Clonal Forestry ◽

Cdna Sequences ◽

Age Related

Grafting, cutting, and pruning are important horticultural techniques widely used in the establishment of clonal forestry. After the application of these techniques, some properties of the plants change, however, the underlying molecular mechanisms are still unclear. In our previous study, 27 age-related transcripts were found to be expressed differentially between the juvenile vegetative (1- and 2-year-old) and adult reproductive (25- and 50-year-old) phases of Larix kaempferi. Here, we re-analyzed the 27 age-related transcripts, cloned their full-length cDNA sequences, and measured their responses to grafting, cutting, and pruning. After sequence analysis and cloning, 20 transcription factors were obtained and annotated, most of which were associated with reproductive development, and six (LaAGL2-1, LaAGL2-2, LaAGL2-3, LaSOC1-1, LaAGL11, and LaAP2-2) showed regular expression patterns with L. kaempferi aging. Based on the expression patterns of these transcription factors in L. kaempferi trees subjected to grafting, cutting, and pruning, we concluded that (1) cutting and pruning rejuvenate the plants and change their expression, and the effects of cutting on gene expression are detectable within 14 years, although the cutting seedlings are still maturing during these years; (2) within three months after grafting, the rootstock is more sensitive to grafting than the scion and readily becomes mature with the effect of the scion, while the scion is not readily rejuvenated by the effect of the rootstock; and (3) LaAGL2-2 and LaAGL2-3 are more sensitive to grafting, while LaAP2-2 is impervious to it. These findings not only provide potential molecular markers to assess the state of plants but also aid in studies of the molecular mechanisms of rejuvenation.

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Comparative Genomics and Transcriptomics To Analyze Fruiting Body Development in Filamentous Ascomycetes

Genetics ◽

10.1534/genetics.119.302749 ◽

2019 ◽

Vol 213 (4) ◽

pp. 1545-1563 ◽

Cited By ~ 2

Author(s):

Ramona Lütkenhaus ◽

Stefanie Traeger ◽

Jan Breuer ◽

Laia Carreté ◽

Alan Kuo ◽

...

Keyword(s):

Gene Expression ◽

Fruiting Body ◽

Molecular Mechanisms ◽

Expression Patterns ◽

Regulation Of Gene Expression ◽

Comparative Transcriptomics ◽

Fruiting Bodies ◽

Body Development ◽

Fruiting Body Development ◽

Genes Encoding

Many filamentous ascomycetes develop three-dimensional fruiting bodies for production and dispersal of sexual spores. Fruiting bodies are among the most complex structures differentiated by ascomycetes; however, the molecular mechanisms underlying this process are insufficiently understood. Previous comparative transcriptomics analyses of fruiting body development in different ascomycetes suggested that there might be a core set of genes that are transcriptionally regulated in a similar manner across species. Conserved patterns of gene expression can be indicative of functional relevance, and therefore such a set of genes might constitute promising candidates for functional analyses. In this study, we have sequenced the genome of the Pezizomycete Ascodesmis nigricans, and performed comparative transcriptomics of developing fruiting bodies of this fungus, the Pezizomycete Pyronema confluens, and the Sordariomycete Sordaria macrospora. With only 27 Mb, the A. nigricans genome is the smallest Pezizomycete genome sequenced to date. Comparative transcriptomics indicated that gene expression patterns in developing fruiting bodies of the three species are more similar to each other than to nonsexual hyphae of the same species. An analysis of 83 genes that are upregulated only during fruiting body development in all three species revealed 23 genes encoding proteins with predicted roles in vesicle transport, the endomembrane system, or transport across membranes, and 13 genes encoding proteins with predicted roles in chromatin organization or the regulation of gene expression. Among four genes chosen for functional analysis by deletion in S. macrospora, three were shown to be involved in fruiting body formation, including two predicted chromatin modifier genes.

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Circulating melanoma cells isolated from clinical blood samples and characterized by full-length mRNA sequencing at single-cell level.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.10539 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 10539-10539 ◽

Cited By ~ 1

Author(s):

Yu-Chieh Wang ◽

Daniel Ramskold ◽

Shujun Luo ◽

Robin Li ◽

Qiaolin Deng ◽

...

Keyword(s):

Gene Expression ◽

Single Cell ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Expression Patterns ◽

Melanoma Cells ◽

Clinical Samples ◽

Single Cell Level ◽

Cell Level ◽

Blood Samples

10539 Background: Melanoma is the most aggressive type of skin cancer. Late-stage melanoma is highly metastatic and currently lacks effective treatment. This discouraging clinical observation highlights the need for a better understanding of the molecular mechanisms underlying melanoma initiation and progression and for developing new therapeutic approaches based on novel targets. Although genome-wide transcriptome analyses have been frequently used to study molecular alterations in clinical samples, it has been technically challenging to obtain the transcriptomic profiles at single-cell level. Methods: Using antibody-mediated magnetic activated cell separation (MACS), we isolated and individualized putative circulating melanoma cells (CMCs) from the blood samples of the melanoma patients at advance stages. The transcriptomic analysis based on a novel and robust mRNA-Seq protocol (Smart-Seq) was established and applied to the putative CMCs for single-cell profiling. Results: We have discovered distinct gene expression patterns, including new putative markers for CMCs. Meanwhile, the gene expression profiles derived of the CMC candidates isolated from the patient’s blood samples are closely-related to the expression profiles of other cells originated from human melanocytes, including normal melanocytes in primary culture and melanoma cell lines. Compared with existing methods, Smart-Seq has improved read coverage across transcripts, which provides advantage for better analyzing transcript isoforms and SNPs. Conclusions: Our results suggest that the techniques developed in this research for cell isolation and transcriptomic analyses can potentially be used for addressing many biological and clinical questions requiring genomewide transcriptome profiling in rare cells.

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What can we learn from gene expression profiling of mouse oocytes?

Reproduction ◽

10.1530/rep-07-0430 ◽

2008 ◽

Vol 135 (5) ◽

pp. 581-592 ◽

Cited By ~ 22

Author(s):

Toshio Hamatani ◽

Mitsutoshi Yamada ◽

Hidenori Akutsu ◽

Naoaki Kuji ◽

Yoshiyuki Mochimaru ◽

...

Keyword(s):

Gene Expression ◽

Gene Expression Profiling ◽

Expression Profiling ◽

Molecular Mechanisms ◽

Expression Patterns ◽

Oocyte Quality ◽

Preimplantation Development ◽

Preimplantation Embryos ◽

Gene Expressions ◽

Oocyte Competence

Mammalian ooplasm supports the preimplantation development and reprograms the introduced nucleus transferred from a somatic cell to confer pluripotency in a cloning experiment. However, the underlying molecular mechanisms of oocyte competence remain unknown. Recent advances in microarray technologies have allowed gene expression profiling of such tiny specimens as oocytes and preimplantation embryos, generating a flood of information about gene expressions. So, what can we learn from it? Here, we review the initiative global gene expression studies of mouse and/or human oocytes, focusing on the lists of maternal transcripts and their expression patterns during oogenesis and preimplantation development. Especially, the genes expressed exclusively in oocytes should contribute to the uniqueness of oocyte competence, driving mammalian development systems of oocytes and preimplantation embryos. Furthermore, we discuss future directions for oocyte gene expression profiling, including discovering biomarkers of oocyte quality and exploiting the microarray data for ‘making oocytes’.

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