Reciprocal Expression Research Articles

Needs of carers participating in support groups and caring for a person with dementia: A focused ethnographic study.

The aim is to explore and understand how support group participation meets carers' perceived needs for information and social and emotional support when caring for a person with dementia who lives at home. Focused ethnographic design. Participant observations and semi-structured interviews with 25 carers were conducted. An inductive content analysis of the data was performed. Two themes were identified: "Strengthening the sense of self" and "Managing uncertain benefits." Carers' level of information about dementia was partly met, thereby strengthening their sense of self and joy. Maintaining shared decision-making in financial matters was viewed as an expression of respect and reciprocity. Getting acquainted with peers and dementia coordinators was viewed as emotional and social support but was also used strategically to gain easier access to health care services. By fulfilling their needs, support group meetings became meaningful, which motivated carers to continue providing care.

Comparative Proteomic Profiling Identifies Reciprocal Expression of Mitochondrial Proteins Between White and Gray Matter Lesions From Multiple Sclerosis Brains.

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system, where ongoing demyelination and remyelination failure are the major factors for progressive neurological disability. In this report, we employed a comprehensive proteomic approach and immunohistochemical validation to gain insight into the pathobiological mechanisms that may be associated with the progressive phase of MS. Isolated proteins from myelinated regions, demyelinated white-matter lesions (WMLs), and gray-matter lesions (GMLs) from well-characterized progressive MS brain tissues were subjected to label-free quantitative mass spectrometry. Using a system-biology approach, we detected increased expression of proteins belonging to mitochondrial electron transport complexes and oxidative phosphorylation pathway in WMLs. Intriguingly, many of these proteins and pathways had opposite expression patterns and were downregulated in GMLs of progressive MS brains. A comparison to the human MitoCarta database mapped the mitochondrial proteins to mitochondrial subunits in both WMLs and GMLs. Taken together, we provide evidence of opposite expression of mitochondrial proteins in response to demyelination of white- and gray-matter regions in progressive MS brain.

Reciprocal Homer1a and Homer2 Isoform Expression Is a Key Mechanism for Muscle Soleus Atrophy in Spaceflown Mice

The molecular mechanisms of skeletal muscle atrophy under extended periods of either disuse or microgravity are not yet fully understood. The transition of Homer isoforms may play a key role during neuromuscular junction (NMJ) imbalance/plasticity in space. Here, we investigated the expression pattern of Homer short and long isoforms by gene array, qPCR, biochemistry, and laser confocal microscopy in skeletal muscles from male C57Bl/N6 mice (n = 5) housed for 30 days in space (Bion-flight = BF) compared to muscles from Bion biosatellite on the ground-housed animals (Bion ground = BG) and from standard cage housed animals (Flight control = FC). A comparison study was carried out with muscles of rats subjected to hindlimb unloading (HU). Gene array and qPCR results showed an increase in Homer1a transcripts, the short dominant negative isoform, in soleus (SOL) muscle after 30 days in microgravity, whereas it was only transiently increased after four days of HU. Conversely, Homer2 long-form was downregulated in SOL muscle in both models. Homer immunofluorescence intensity analysis at the NMJ of BF and HU animals showed comparable outcomes in SOL but not in the extensor digitorum longus (EDL) muscle. Reduced Homer crosslinking at the NMJ consequent to increased Homer1a and/or reduced Homer2 may contribute to muscle-type specific atrophy resulting from microgravity and HU disuse suggesting mutual mechanisms.

BRAFV600E induces reversible mitotic arrest in human melanocytes via microrna-mediated suppression of AURKB.

Benign melanocytic nevi frequently emerge when an acquired BRAFV600E mutation triggers unchecked proliferation and subsequent arrest in melanocytes. Recent observations have challenged the role of oncogene-induced senescence in melanocytic nevus formation, necessitating investigations into alternative mechanisms for the establishment and maintenance of proliferation arrest in nevi. We compared the transcriptomes of melanocytes from healthy human skin, nevi, and melanomas arising from nevi and identified a set of microRNAs as highly expressed nevus-enriched transcripts. Two of these microRNAs-MIR211-5p and MIR328-3p-induced mitotic failure, genome duplication, and proliferation arrest in human melanocytes through convergent targeting of AURKB. We demonstrate that BRAFV600E induces a similar proliferation arrest in primary human melanocytes that is both reversible and conditional. Specifically, BRAFV600E expression stimulates either arrest or proliferation depending on the differentiation state of the melanocyte. We report genome duplication in human melanocytic nevi, reciprocal expression of AURKB and microRNAs in nevi and melanomas, and rescue of arrested human nevus cells with AURKB expression. Taken together, our data describe an alternative molecular mechanism for melanocytic nevus formation that is congruent with both experimental and clinical observations.

Comprehensive analyses of microRNA and mRNA expression in colorectal serrated lesions and colorectal cancer with a microsatellite instability phenotype.

MicroRNA (miRNA) expression is dysregulated in human tumors, thereby contributing to tumorigenesis through altered expression of mRNA. Thus, identification of the relationships between miRNAs and mRNAs is important for evaluating the molecular mechanisms of tumors. In addition, elucidation of the molecular features of serrated lesions is essential in colorectal tumorigenesis. Here, we examined the relationships of miRNA and mRNA expressed in serrated lesions, including 26 sessile serrated lesions (SSLs), 12 traditional serrated adenomas (TSAs), and 11 colorectal cancers (CRCs) with a microsatellite instability (MSI) phenotype using crypt isolation. We divided the samples into the first and second cohorts for validation. Array-based expression analyses were used to evaluate miRNAs and mRNAs with opposite expression patterns in isolated tumor glands. In addition, we validated the relationships of miRNA/mRNA pairs in the second cohort using real-time polymerase chain reaction. We found that the expression of miRNA-5787 was correlated with reciprocal expression of two mRNAs, that is, SRRM2 and POLR2J3, in SSL samples. In TSA samples, two pairs of miRNAs/mRNAs showing opposite expression patterns, that is, miRNA-182-5p/ETF1 and miRNA-200b-3p/MYB, were identified. Ultimately, three pairs of miRNAs/mRNAs with opposite expression patterns, including miRNA-222-3p/SLC26A3, miRNA-6753-3p/FABP1, and miRNA-222-3p/OLFM4, were retained in CRC with an MSI phenotype. Finally, we performed transfection with an miR-222-3p mimic to confirm the expression of SLC26A3 and OLFM4; the results showed that ectopic expression of miR-222-3p moderately suppressed OLFM4 and downregulated SLC26A3 to some extent. Overall, our results provided basic insights into the evaluation of colorectal tumorigenesis of serrated lesions and CRC with an MSI phenotype.

Eph signaling is regulated by miRNA-210: Implications for corneal epithelial repair.

A distinct boundary exists between the progenitor cells in the basal limbal epithelium and the more differentiated corneal epithelial basal cells. We have shown that reciprocal expression patterns of EphA2 and Ephrin-A1 are likely to contribute to normal limbal-corneal epithelial compartmentalization as well as play a role in response to injury. How this signaling axis is regulated remains unclear. We have demonstrated that microRNAs (miRNAs) play critical roles in corneal epithelial wound healing and several miRNAs (e.g. miR-210) have been predicted to target ephrins. Previous expression profiling experiments demonstrated that miR-210 is prominently expressed in corneal epithelial cells. RNA-seq data acquired from miR-210-depleted HCECs showed up-regulation of genes involved in cellular migration. In addition, miR-210 is decreased after corneal injury while EphA2 is increased. Moreover, antago-210-treated HCECs markedly enhanced wound closure in a scratch wound assay. Antago-210 treatment resulted in increased EphA2 protein levels as well as pS897-EphA2, the pro-migratory form of EphA2. As expected, Ephrin-A1levels were reduced, while levels of a well-known target of miR-210, Ephrin-A3, were increased by antago-210 treatment. The increase in migration with antago-210 could be inhibited by Ephrin-A1 overexpression, Ephrin-A1-Fc treatment or siRNA depletion of EphA2. However, depletion of Ephrin-A3 did not have effects on the antago-210-induced increase in migration. In addition, Ephrin-A1 overexpression and siEphA2 dampened EGFR signaling, which is increased by antago-210. Our data clearly demonstrate a link between miR-210 and EphA2/Ephrin-A1signaling that regulates, in part, corneal epithelial migration. This interaction might potentially control the limbal-corneal epithelial boundary.

OncomiR miR-182-5p Enhances Radiosensitivity by Inhibiting the Radiation-Induced Antioxidant Effect through SESN2 in Head and Neck Cancer.

Radiotherapy is routinely used for the treatment of head and neck squamous cell carcinoma (HNSCC). However, the therapeutic efficacy is usually reduced by acquired radioresistance and locoregional recurrence. In this study, The Cancer Genome Atlas (TCGA) analysis showed that radiotherapy upregulated the miR-182/96/183 cluster and that miR-182 was the most significantly upregulated. Overexpression of miR-182-5p enhanced the radiosensitivity of HNSCC cells by increasing intracellular reactive oxygen species (ROS) levels, suggesting that expression of the miR-182 family is beneficial for radiotherapy. By intersecting the gene targeting results from three microRNA target prediction databases, we noticed that sestrin2 (SESN2), a molecule resistant to oxidative stress, was involved in 91 genes predicted in all three databases to be directly recognized by miR-182-5p. Knockdown of SESN2 enhanced radiation-induced ROS and cytotoxicity in HNSCC cells. In addition, the radiation-induced expression of SESN2 was repressed by overexpression of miR-182-5p. Reciprocal expression of the miR-182-5p and SESN2 genes was also analyzed in the TCGA database, and a high expression of miR-182-5p combined with a low expression of SESN2 was associated with a better survival rate in patients receiving radiotherapy. Taken together, the current data suggest that miR-182-5p may regulate radiation-induced antioxidant effects and mediate the efficacy of radiotherapy.

The Effect of Inhibin Immunization in Seminiferous Epithelium of Yangzhou Goose Ganders: A Histological Study.

Simple SummaryAchieving optimum fertility is the ultimate goal of keeping gander flock in commercial geese farming. Being seasonal breeders, geese exhibit poor reproductive efficiency. Inhibin (INH) immunization has improved reproductive parameters in some mammalian species but remained obscure in birds, especially geese. The present study aimed to check the effect of INH immunization on testicular histoarchitecture of Yangzhou ganders. Results illustrated that INH immunization disrupted seminiferous epithelium, germ cells development, lowered efficiency of spermatogenesis, and caused apoptosis in seminiferous tubules of Yangzhou ganders.The current study investigated the effect of inhibin immunization on germ cell numbers (spermatogonia, spermatocytes, round, and elongated spermatids), seminiferous tubules (ST) diameter, Johnsen’s score, epithelial height (μm), luminal tubular diameter (μm), and number of ST per field (ST/field) of Yangzhou goose ganders. Histological evaluation showed apoptosis and regression of testes after inhibin (INH) immunization, with a concomitantly marked reduction in the round and elongated spermatids in the experiment (INH) group compared to the control group. The diameter of seminiferous tubules (ST) and epithelial height (EH) were positively correlated at 181, 200, and 227 days of age. In comparison, luminal tubular diameter (LD) was negatively correlated on day 227 to ST diameter and epithelial height. On day 227, many seminiferous tubules per field (ST/field) were negatively correlated to ST diameter, EH, and LD. INH immunization elevated ST diameter, EH, and LD, while Johnsen’s score and number of ST/field had reciprocal expression. In conclusion, the concomitant effect of INH immunization and seasonality in breeding regressed germ cells and damaged spermatogenesis in seminiferous epithelium Yangzhou ganders.

Reciprocal YAP1 loss and INSM1 expression in neuroendocrine prostate cancer.

Neuroendocrine prostate cancer (NEPC) is a rare but aggressive histologic variant of prostate cancer that responds poorly to androgen deprivation therapy. Hybrid NEPC-adenocarcinoma (AdCa) tumors are common, often eluding accurate pathologic diagnosis and requiring ancillary markers for classification. We recently performed an outlier-based meta-analysis across a number of independent gene expression microarray datasets to identify novel markers that differentiate NEPC from AdCa, including up-regulation of insulinoma-associated protein 1 (INSM1) and loss of Yes-associated protein 1 (YAP1). Here, using diverse cancer gene expression datasets, we show that Hippo pathway-related genes, including YAP1, are among the top down-regulated gene sets with expression of the neuroendocrine transcription factors, including INSM1. In prostate cancer cell lines, transgenic mouse models, and human prostate tumor cohorts, we confirm that YAP1 RNA and YAP1 protein expression are silenced in NEPC and demonstrate that the inverse correlation of INSM1 and YAP1 expression helps to distinguish AdCa from NEPC. Mechanistically, we find that YAP1 loss in NEPC may help to maintain INSM1 expression in prostate cancer cell lines and we further demonstrate that YAP1 silencing likely occurs epigenetically, via CpG hypermethylation near its transcriptional start site. Taken together, these data nominate two additional markers to distinguish NEPC from AdCa and add to data from other tumor types suggesting that Hippo signaling is tightly reciprocally regulated with neuroendocrine transcription factor expression. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

RBP differentiation contributes to selective transmissibility of OPT3 mRNAs.

Long-distance mobile mRNAs play key roles in gene regulatory networks that control plant development and stress tolerance. However, the mechanisms underlying species-specific delivery of mRNA still need to be elucidated. Here, the use of grafts involving highly heterozygous apple (Malus) genotypes allowed us to demonstrate that apple (Malus domestica) oligopeptide transporter3 (MdOPT3) mRNA can be transported over a long distance, from the leaf to the root, to regulate iron uptake; however, the mRNA of Arabidopsis (Arabidopsis thaliana) oligopeptide transporter 3 (AtOPT3), the MdOPT3 homolog from A. thaliana, does not move from shoot to root. Reciprocal heterologous expression of the two types of mRNAs showed that the immobile AtOPT3 became mobile and moved from the shoot to the root in two woody species, Malus and Populus, while the mobile MdOPT3 became immobile in two herbaceous species, A. thaliana and tomato (Solanum lycopersicum). Furthermore, we demonstrated that the different transmissibility of OPT3 in A. thaliana and Malus might be caused by divergence in RNA-binding proteins between herbaceous and woody plants. This study provides insights into mechanisms underlying differences in mRNA mobility and validates the important physiological functions associated with this process.

Investigating the Lived Experiences of Working Couples about Marital Conflicts: A Phenomenological Study

Aim: The purpose of this study was to extract the lived experiences of working couples from marital conflicts. Methods: This study was conducted with a qualitative approach using interpretive phenomenology. In this study, researchers interviewed 12 working couples with marital conflicts using purposeful sampling. Interviews were analyzed using interpretive phenomenology. Findings: Analyzing the data from the interviews led to the identification of the 14 main themes: financial conflict, inappropriate interactions in social media, lack of participation in house chores, ineffective communication, inability in reciprocal empathy and expression, lack of time management, conflict of roles and responsibilities, cognition vulnerability, adherence to gender stereotypes, inability to manage tasks at job and work environment, work-family conflict, power struggles, ultra-personal destructive factors and belief and ethical problems, 55 primary and 12 secondary themes in the lived experiences of working couples from marital conflicts. Conclusion: A dual-career family is a place where couples are more likely to enter into marital conflicts if they do not realize fairness in various areas of family and work. The results of the present study showed that the families of career couples may be a high-risk group in terms of conflict, and this factor indicates the need for a negotiating role in the relationship between this type of couple. This highlights the need for special couple therapy for these couples. The results of the present study also showed that ineffective communication, cognitive vulnerability, work-family interaction, financial conflict and lack of participation in home affairs, were the most common causes of marital conflict; so it is recommended that preventive and educational programs for couples include the abovementioned factors.

MRNP granule proteins Fmrp and Dcp1a differentially regulate mRNP complexes to contribute to control of muscle stem cell quiescence and activation

BackgroundDuring skeletal muscle regeneration, satellite stem cells use distinct pathways to repair damaged myofibers or to self-renew by returning to quiescence. Cellular/mitotic quiescence employs mechanisms that promote a poised or primed state, including altered RNA turnover and translational repression. Here, we investigate the role of mRNP granule proteins Fragile X Mental Retardation Protein (Fmrp) and Decapping protein 1a (Dcp1a) in muscle stem cell quiescence and differentiation.MethodsUsing isolated single muscle fibers from adult mice, we established differential enrichment of mRNP granule proteins including Fmrp and Dcp1a in muscle stem cells vs. myofibers. We investigated muscle tissue homeostasis in adult Fmr1-/- mice, analyzing myofiber cross-sectional area in vivo and satellite cell proliferation ex vivo. We explored the molecular mechanisms of Dcp1a and Fmrp function in quiescence, proliferation and differentiation in a C2C12 culture model. Here, we used polysome profiling, imaging and RNA/protein expression analysis to establish the abundance and assembly status of mRNP granule proteins in different cellular states, and the phenotype of knockdown cells.ResultsQuiescent muscle satellite cells are enriched for puncta containing the translational repressor Fmrp, but not the mRNA decay factor Dcp1a. MuSC isolated from Fmr1-/- mice exhibit defective proliferation, and mature myofibers show reduced cross-sectional area, suggesting a role for Fmrp in muscle homeostasis. Expression and organization of Fmrp and Dcp1a varies during primary MuSC activation on myofibers, with Fmrp puncta prominent in quiescence, but Dcp1a puncta appearing during activation/proliferation. This reciprocal expression of Fmrp and Dcp1a puncta is recapitulated in a C2C12 culture model of quiescence and activation: consistent with its role as a translational repressor, Fmrp is enriched in non-translating mRNP complexes abundant in quiescent myoblasts; Dcp1a puncta are lost in quiescence, suggesting stabilized and repressed transcripts. The function of each protein differs during proliferation; whereas Fmrp knockdown led to decreased proliferation and lower cyclin expression, Dcp1a knockdown led to increased cell proliferation and higher cyclin expression. However, knockdown of either Fmrp or Dcp1a led to compromised differentiation. We also observed cross-regulation of decay versus storage mRNP granules; knockdown of Fmrp enhances accumulation of Dcp1a puncta, whereas knockdown of Dcp1a leads to increased Fmrp in puncta.ConclusionsTaken together, our results provide evidence that the balance of mRNA turnover versus utilization is specific for distinct cellular states.

Changes in cytoarchitecture and mobility in B16F1 melanoma cells induced by 5-Br-2'-dU coincide with Rock2, miRNAs 138-5p and 455-3p reciprocal expressions

ROCK2 is a protein involved in the restructuring of the cytoskeleton in cell adhesion and contractibility processes. miR-138-5p and miR-455-3p regulate Rock2 expression, cell proliferation, migration, and invasion in different experimental cell models. However, their participation in the cytoarchitecture and mobility of B16F1 melanoma cells exposed to 5-Br-2'-dU is partially known. This work aimed to analyze ROCK2 and miRs 138-5p and 455-3p expression associated with morphological and mobility changes of B16F1 mouse melanoma cells exposed to the thymidine analog 5-Bromo-2'-deoxyuridine (5-Br-2'-dU). We observed an increase (2.2X n = 3, p < 0.05) in the cell area, coinciding with an increase in cell diameter (1.27X n = 3, p < 0.05), as well as greater cell granularity, capacity for circularization, adhesion, which was associated with more significant polymerization of F-actin, collapsed in the intermediate filaments of vimentin (VIM), and coinciding with a decrease in migration (87%). Changes coincided with a decrease in Rock2 mRNA expression (2.88X n = 3, p < 0.05), increased vimentin and a reciprocal decrease in miR-138-5p (1.8X), and an increase in miR-455-3p (2.39X). The Rock2 kinase inhibitor Y27632 partially rescued these changes. These results suggest ROCK2 and VIM regulate the morphological and mobility changes of B16 melanoma cells after exposure to 5-Br-2'-dU, and its expression may be reciprocally regulated, at least in part, by miR-138-5p and miR-455-3p.

Reflexive and Reciprocal Encoding in the Australian Mixed Language, Light Warlpiri

Mixed languages combine significant amounts of grammatical and lexical material from more than one source language in systematic ways. The Australian mixed language, Light Warlpiri, combines nominal morphology from Warlpiri with verbal morphology from Kriol (an English-lexified Creole) and English, with innovations. The source languages of Light Warlpiri differ in how they encode reflexives and reciprocals—Warlpiri uses an auxiliary clitic for both reflexive and reciprocal expression, while English and Kriol both use pronominal forms, and largely have separate forms for reflexives and reciprocals. English distinguishes person and number in reflexives, but not in reciprocals; the other source languages do not distinguish person or number. This study draws on naturalistic and elicited production data to examine how reflexive and reciprocal events are encoded in Light Warlpiri. The study finds that Light Warlpiri combines near-maximal distinctions from the source languages, but in a way that is not a mirror of any. It retains the person and number distinctions of English reflexives and extends them to reciprocals, using the same forms for reflexives and reciprocals (like Warlpiri). Reflexives and reciprocals occur within a verbal structure (perhaps under influence from Warlpiri). The results show that a mixed language can have discrete contributions from three languages, that the source languages can influence different subsystems to different extents, and that near-maximal distinctions from the source languages can be maintained.

Hope, Solidarity, and Justice

This article defends an account of collective hope that arises through solidarity in the pursuit of justice. I begin by reviewing recent literature on the nature of hope. I then explore the relationship between hope and solidarity to demonstrate the ways in which solidarity can give rise to hope. I suggest that the hope born of solidarity is collective when it is shared by at least some others, when it is caused or strengthened by activity in a collective action setting, and when the reciprocal hopeful expressions of individual group members result in an emotional atmosphere of hope that extends across the group. In the context of social movements, collective hope emerges alongside the collective intentions and actions of the solidarity group; namely, in the pursuit of a form of social justice that inspires the movement. I then suggest that the object of collective hope born of solidarity is the guiding ideal of justice and reflect on what it might mean to hope well for justice.

Calcitriol and Retinoic acid antagonize each other to suppress the production of IL-9 by Th9 cells

Distinct T helper cells, including Th9 cells help maintain homeostasis in the immune system. Vitamins play pivotal role in the immune system through many mechanisms, including regulating the differentiation of T helper cells. Calcitriol (1,25-dihydroxyvitamin D3) and retinoic acid possess hormone-like properties and are the bioactive metabolites of vitamin D and A, respectively, that signal through heterodimers containing the common retinoid X receptor. In contrast to individual treatment with the vitamins that significantly attenuates IL-9 production from Th9 cells, Th9 cells treated with both vitamins demonstrated IL-9 production similar to untreated Th9 cells. This is associated with reciprocal expression of PU.1 and Foxp3. While the recruitment of PU.1 was significantly impaired to the Il9 gene in the presence of calcitriol or retinoic acid in Th9 cells, addition of both vitamins together increased the recruitment of PU.1 to the Il9 gene. Calcitriol and retinoic acid together impaired the recruitment of HDAC1 to the Il9 gene without impacting Gcn5 recruitment. Importantly, retinoic acid negated the effect of calcitriol and impaired the binding of VDR on the Il9 gene by dampened VDR-RXR formation. Collectively, our data show that calcitriol and retinoic acid antagonize each other to regulate the differentiation of Th9 cells.

The impact of gratitude letters and visits on relationships, happiness, well-being, and meaning of graduate students

In this mixed-methods research, we examined the practice of writing and delivering letters of gratitude (gratitude visits) and its impact on well-being, happiness, meaning and relationships for students in an online graduate program in psychology. Participants completed assessments and inventories relating to happiness, well-being and meaning in life, including the Satisfaction with Life Scale, Meaning in Life Questionnaire, Approaches to Happiness Questionnaire and open-ended qualitative questions before and after they wrote and delivered gratitude letters. Quantitative analyses found significant increases in meaning in life, satisfaction with life, and approaches to happiness after the gratitude visit intervention. Using a grounded theory qualitative analysis of the data, eight primary themes emerged related to the impact and meaning of gratitude letters on graduate students: (1) the impact on the relationship; (2) positive emotions experienced; (3) experiencing a reciprocal expression of gratitude from the receiver; (4) overcoming uncomfortable emotions; (5) relief, release or liberation after sharing; (6) impact on spiritual growth; (7) unexpected responses; and (8) greater reflection on the meaning of life and a changed perspective. Overall, providing graduate students with the opportunity to engage in gratitude visit interventions was related to greater meaning and well-being. This study suggests implications and recommendations related to the use of positive psychology interventions in educational settings.

Distinct miRNA Signatures and Networks Discern Fetal from Adult Erythroid Differentiation and Primary from Immortalized Erythroid Cells.

MicroRNAs (miRNAs) are small non-coding RNAs crucial for post-transcriptional and translational regulation of cellular and developmental pathways. The study of miRNAs in erythropoiesis elucidates underlying regulatory mechanisms and facilitates related diagnostic and therapy development. Here, we used DNA Nanoball (DNB) small RNA sequencing to comprehensively characterize miRNAs in human erythroid cell cultures. Based on primary human peripheral-blood-derived CD34+ (hCD34+) cells and two influential erythroid cell lines with adult and fetal hemoglobin expression patterns, HUDEP-2 and HUDEP-1, respectively, our study links differential miRNA expression to erythroid differentiation, cell type, and hemoglobin expression profile. Sequencing results validated by reverse-transcription quantitative PCR (RT-qPCR) of selected miRNAs indicate shared differentiation signatures in primary and immortalized cells, characterized by reduced overall miRNA expression and reciprocal expression increases for individual lineage-specific miRNAs in late-stage erythropoiesis. Despite the high similarity of same-stage hCD34+ and HUDEP-2 cells, differential expression of several miRNAs highlighted informative discrepancies between both cell types. Moreover, a comparison between HUDEP-2 and HUDEP-1 cells displayed changes in miRNAs, transcription factors (TFs), target genes, and pathways associated with globin switching. In resulting TF-miRNA co-regulatory networks, major therapeutically relevant regulators of globin expression were targeted by many co-expressed miRNAs, outlining intricate combinatorial miRNA regulation of globin expression in erythroid cells.

Selective time-dependent changes in activity and cell-specific gene expression in human postmortem brain

As a means to understand human neuropsychiatric disorders from human brain samples, we compared the transcription patterns and histological features of postmortem brain to fresh human neocortex isolated immediately following surgical removal. Compared to a number of neuropsychiatric disease-associated postmortem transcriptomes, the fresh human brain transcriptome had an entirely unique transcriptional pattern. To understand this difference, we measured genome-wide transcription as a function of time after fresh tissue removal to mimic the postmortem interval. Within a few hours, a selective reduction in the number of neuronal activity-dependent transcripts occurred with relative preservation of housekeeping genes commonly used as a reference for RNA normalization. Gene clustering indicated a rapid reduction in neuronal gene expression with a reciprocal time-dependent increase in astroglial and microglial gene expression that continued to increase for at least 24 h after tissue resection. Predicted transcriptional changes were confirmed histologically on the same tissue demonstrating that while neurons were degenerating, glial cells underwent an outgrowth of their processes. The rapid loss of neuronal genes and reciprocal expression of glial genes highlights highly dynamic transcriptional and cellular changes that occur during the postmortem interval. Understanding these time-dependent changes in gene expression in post mortem brain samples is critical for the interpretation of research studies on human brain disorders.

Reciprocal Expression of Differentiated Embryonic Chondrocyte Expressed Genes Result in Functional Antagonism in Gastric Cancer.

Differentiated embryonic chondrocyte expressed genes (DECs) are critical regulators of cellular proliferation and differentiation. However, DEC1 and DEC2 as family member have opposite or identical roles in tumor, acting as an "accelerator" or a "brake" in progression. The possible crosstalk between DEC1 and DEC2 in the gastric cancer (GC). The association of DEC1 and DEC2 expression with prognosis was investigated by immunohistochemistry. The expression pattern of DECs in GC cells was examined using the CCLE database. DECs knockdown or overexpression was conducted via lentiviral transfection. The proliferation of GC cells was evaluated by CCK8, EdU, and Colony forming. ChIP and luciferase reporter assays were used to verify interaction between DEC1 and the DEC2 promoter. The combination downstream with DEC1 and DEC2 was predicted by bioinformation, with Western blot providing further verification. We found that reciprocal expression of DEC1 and DEC2 works together to sustain the progression of GC by promoting cell growth. We confirmed this observation in vivo, showing that inhibition DEC1expression could increase DEC2 expression. DEC1 suppresses DEC2 expression by directly binding to the E-box of the DEC2 promoter in GC cells. Furthermore, this regulation of DEC1 on DEC2 enables the further indirect or cooperative activation of additional downstream target genes, MAPK, and STAT3. Our data demonstrate that DEC1 and DEC2 interact physically and functionally and identify a novel mode of cross-regulatory interaction between DECs that abrogates their functional activity.