D1 Gene Research Articles

Alpha-2-Macroglobulin (A2M) and Dopamine Receptor D2 (DRD2) expression analysis and Influence of Separation from Parents in Childhood on the Suicide and Self-injury Behavior and Psychological Adjustment in Adolescence.

To explore the influence of separation from parents in childhood on suicide and self-injury behavior and psychological adjustment in adolescence. A total of 880 subjects were selected, including 197 students who were separated from their parents in childhood and 683 students who were not separated from their parents in childhood. The scores of psychological resilience, self-compassion, forgiveness and suicide and self-injury were investigated and analyzed. Logistic regression analysis was made on the relationship between suicide and self-injury behavior and psychological adjustment in adolescence. The scores of psychological resilience, self-compassion, forgiveness and suicide and self-injury were statistically significant between children who were separated from their parents and those who were not separated. The students who were not separated had better psychological adjustment abilities and a lower rate of suicide and self-injury (P<0.05). There was a positive correlation between separation from parents in childhood and suicide and self-injury behavior and psychological adjustment in adolescence (P<0.05). The separation from parents in childhood is closely related to psychological resilience, forgiveness, self-compassion, and suicide-related psychological behavior and self-injury behavior in adolescence. Suicide and self-injury behavior can be reduced by reducing separation from parents in childhood and improving self-psychological adjustment ability in adolescence. During the past years, genetics, heritability, and genes' contribution to depression disorders have been well established. Alpha-2-Macroglobulin (A2M) and Dopamine Receptor D2 (DRD2) genes are very effective in behavioral and mood disorders. The results of this study showed the expression of these genes in different organs, especially in connection with the cerebrospinal system, so investigating the mechanism of their effect is very effective and promising, and it is hoped that they will be used in other research.

A dopamine receptor D2 genetic polymorphism associated with transition to mental disorders in a cohort of individuals with at-risk mental state for psychosis.

To test the association of 45 single nucleotide polymorphisms (SNPs) with transition to psychiatric disorders in a cohort of individuals at ultrahigh risk (UHR) mental state for psychosis. Through general population screening, 88 non-help-seeking UHR subjects and 130 healthy control individuals were genotyped for 45 SNPs related to psychosis. They were followed for a mean of 2.5 years, and conversion to psychotic and to general psychiatric disorders was assessed. Genotype frequencies between controls, converters, and non-converters were analyzed. There were no differences in sociodemographics between controls and UHR. Also, UHR converters and non-converters had no differences in their baseline symptoms scores. The dopamine receptor D2 gene (DRD2) SNP rs6277 was significantly more common among UHR who transitioned to psychosis (p < 0.001) and to UHR who transitioned to any psychiatric disorders (p = 0.001) when compared to UHR who did not transition. The rs6277 T allele was related to psychiatric morbidity in a dose-response fashion, being significantly more frequent in UHR converters than UHR non-converters and control subjects (p = 0.003). Our findings suggest that rs6277 could potentially constitute a genetic marker of transition to psychiatric disorders in subjects with at-risk mental states, warranting further investigation in larger samples.

Molecular Identification of Yeast Strains with High Fermentation Capacity Isolated from Kırkağaç Melon Varieties

The yield of fermentation process, bioethanol, is one of the important product obtained from renewable energy sources. Yeasts are commonly used in ethanol production due to their high ethanol tolerance, high ethanol productivity, and their ability to ferment different kinds of simple sugars. Saccharomyces cerevisiae yeast species is the most commonly used in industrial ethanol production. Therefore, isolation and identification of new yeast strains with high fermentation capacity is very important for the bioethanol industry. The aim of this study was isolation of novel and industrially applicable yeast species that can be used in bioethanol production. Yeast strains were isolated from the Dalaman, Altınbaş and Kıvırcık sarı dilim melon varieties that are unique to Kırkağaç district of Manisa province. The fermentation ability of yeast strains was evaluated and the selected yeast strains were identified by PCR-RFLP analysis of 26S and ITS1-5.8S-ITS2 rDNA gene regions. Sequence analysis of the 26S rDNA-D1/D2 gene region was used for molecular identification of yeast strains. The phylogenetic analysis of identified yeast strains was carried out using the MEGA XI phylogenetic analysis tool. It was determined that 14 of the 53 yeast strains isolated were able to ferment glucose and sucrose, and four of them were able to ferment lactose. The yeast strains having the fermentation capacity were identified as Pichia kluyverii, Lachancea thermotolerans, Pichia kudriavzevii, Saccharomyces cf. cerevisiae/paradoxus and Saccharomyces cerevisiae. These yeast strains have the potential to be used in the bioethanol industry after other physiological and biochemical tests are complete

Type 2 Deiodinase A/G (Thr92Ala) Polymorphism and Circulating Thyroid Hormone Level of Childbearing Age Women in Area Replete with Iodine Deficiency Disorders

BACKGROUND: Iodothyronine deiodinase (DIO) is an enzyme that regulates thyroid hormone activity. DIO consists of three types: deiodinase 1 (D1), 2 (D2), and 3 (D3). D2 is a gene that plays an important role in regulation of the biochemistry of the thyroid hormone in several tissues. D2 also plays a role in the production of triiodothyronine and controlling thyroid hormone signals. This study measured the observation that about 15% of the normal population show that D2 gene polymorphism (Thr92Ala) potentially affects the activity of D2. AIM: This study aimed to determine D2 polymorphisms and their association with thyroid hormone levels in women of childbearing age in replete iodine deficiency disorder areas. METHODS: Total number of subjects was 131. Analysis of serum TSH, T3, fT3, T4, and fT4 levels was done using ELISA. Polymorphism of Thr92Ala was analyzed by PCR-RFLP method. RESULTS: The results showed that the frequencies of the genotypes Thr92Ala were AA 16.79%, AG 41.22%, and GG 41.99%, whereas the allele frequency A 37.5% and G 62.5% (p HWE = 0.171). In this study, we found no differences of TSH and thyroid hormone level between group of each allel. Mean of TSH and thyroid hormone level was on normal range. CONCLUSION: This D2 polymorphism is associated with fT4 levels rather than fT3 but not statistically significant. Heterozygous alleles at D2 AG have higher TSH levels compared with homozygous alleles.

Identification of visual cortex cell types and species differences using single-cell RNA sequencing

The primate neocortex exerts high cognitive ability and strong information processing capacity. Here, we establish a single-cell RNA sequencing dataset of 133,454 macaque visual cortical cells. It covers major cortical cell classes including 25 excitatory neuron types, 37 inhibitory neuron types and all glial cell types. We identified layer-specific markers including HPCAL1 and NXPH4, and also identified two cell types, an NPY-expressing excitatory neuron type that expresses the dopamine receptor D3 gene; and a primate specific activity-dependent OSTN + sensory neuron type. Comparisons of our dataset with humans and mice show that the gene expression profiles differ between species in relation to genes that are implicated in the synaptic plasticity and neuromodulation of excitatory neurons. The comparisons also revealed that glutamatergic neurons may be more diverse across species than GABAergic neurons and non-neuronal cells. These findings pave the way for understanding how the primary cortex fulfills the high-cognitive functions.

Economizing marker assisted selection through cost-effective assay of sd1 gene in rice (Oryza sativa)

PCR amplification and detection of GC rich sequences in DNA is a challenge due to formation of secondary structures which resist denaturation, thereby stalling Taq DNA polymerases as well as affecting primer annealing. Presently, high fidelity Taq DNA polymerase is used for amplifying long and GC-rich fragments, while dimethyl sulfoxide (DMSO) has also been suggested as an additive in Polymerase Chain Reaction (PCR) mix to avoid formation of secondary structures in templates containing high GC content. In the present study, the amplification efficiency of normal Taq DNA polymerase with 5% DMSO as compared to high fidelity Taq DNA polymerase has been applied for better amplification of fragments with high GC content of sd1 gene in rice. Normal Taq DNA polymerase with 5% DMSO displayed better and reproducible results as compared to platinum DNA polymerase for the amplification of gene sd1, thereby successfully detecting the dominant wild type allele governing tall plant height from the recessive semi-dwarf allele. There were no adverse effects of 5% DMSO in PCR amplification and the amplified fragments improved significantly indicating the improvement in amplification efficiency. The modified PCR protocol including DMSO provides a cost effective and cheaper alternative for reliable assessment of the genomic differences in GCrich regions of the gene. This will help in eliminating the need for costly high fidelity Taq DNA polymerase, thereby helping in economizing marker assisted selection.

Large-Grain and Semidwarf Isogenic Rice Koshihikari Integrated with GW2 and sd1

Intending to contribute to sustainable agriculture by “New Green Revolution,” we developed a large-grain/semidwarf isogenic line “Koshihikari sd1GW2” that incorporates both the large-grain gene GW2 and semidwarf gene sd1. GW2 homozygous B3F2 plant with the genomic background of Koshihikari was backcrossed twice with “Koshihikari sd1.” Koshihikari sd1GW2 fixed in BC5F3 was found to be 12.6 cm shorter than Koshihikari. Whole-genome sequencing proved one deletion in GW2 at 8,147,416 bp on chromosome 2 and the SNPs in sd1 at 38,267,510 bp on chromosome 1. The size of the DNA fragments integrated with each gene was determined as the distance between both ends of SNP clusters. Through the backcrossing from BC4 to BC5, the DNA fragment integrated with GW2 decreased by 148,139 bp. The thousand-grain weight of Koshihikari sd1GW2 (27.8 g) was 18% greater than that of Koshihikari (23.6 g), and the grain yield of Koshihikari sd1GW2 (42.6 kg/a) was 0.5% higher than that of Koshihikari (42.4 kg/a). Our results suggested that Koshihikari sd1GW2 will be less susceptible to lodging by typhoons, cyclones, and heavy rainfall, ordinarily a concern in heavier panicle weight cultivars. We successfully integrated GW2 with sd1 for the first time, specifically in the genome of the leading, globally produced Japonica cultivar Koshihikari.

Isogenic Japonica Rice Koshihikari Integrated with Late Flowering Gene Hd16 and Semidwarfing Gene sd1 to Prevent High Temperature Maturation and Lodging by Typhoon.

We developed semidwarf and late-maturing isogenics of Koshihikari to stabilize high yield and avoid high temperature maturation. Whole-genome analysis (WGS) was conducted to examine the transitional changes in the entire genome, the size of DNA fragments integrated with the target gene, and genes accompanying the target gene owing to the progress of backcrossing. In both Koshihikari Hd16 (BC7F4) and Koshihikari sd1Hd16 (BC8F2), an SNP from adenine to guanine was detected in Hd16 at 32,996,608 bp on chromosome 3, which is known to be a causative mutation of Hd16 in Nipponbare. In Koshihikari sd1Hd16 (BC8F2), an SNP from thymine to guanine was detected in sd1 at 38,267,510 bp on chromosome 1. From BC7 to BC8, the size of the DNA fragment integrated with Hd16 decreased by 5871 bp. Koshihikari sd1Hd16 flowered 12.1 days later than Koshishikari or Koshihikari sd1 did and was 14.2 cm (15%) shorter than Koshihikari. The yield in Koshishikari sd1Hd16 (63.2 kg/a) was 7.0% higher than that of Koshihikari. This is a new germplasm designed to avoid heat damage at ripening during high-temperature summer periods by late maturation owing to Hd16 as well as to avoid lodging by autumn typhoons by semidwarfness owing to sd1.

Novel Biological Insights Into the Common Heritable Liability to Substance Involvement: A Multivariate Genome-wide Association Study

BackgroundConsumption of nicotine, alcohol, and cannabis commonly co-occurs, which is thought to partly stem from a common heritable liability to substance involvement. MethodsTo elucidate its genetic architecture, we modeled a common liability inferred from genetic correlations among 6 measures of dependence and frequency of use of nicotine, alcohol, and cannabis. ResultsForty-two genetic variants were identified in the multivariate genome-wide association study on the common liability to substance involvement, of which 67% were novel and not associated with the 6 phenotypes. Mapped genes highlighted the role of dopamine (e.g., dopamine receptor D2 gene) and showed enrichment for several components of the central nervous system (e.g., mesocorticolimbic brain regions) and molecular pathways (dopaminergic, glutamatergic, GABAergic [gamma-aminobutyric acidergic]) that are thought to modulate drug reinforcement. Genetic correlations with other traits were most prominent for reward-related behaviors (e.g., risk taking, cocaine use, and opioid use) and mood (e.g., depression, insomnia). ConclusionsThese genome-wide results triangulate and expand previous preclinical and human studies focusing on the neurobiological substrates of substance involvement and help to elucidate the genetic architecture underlying the use of common psychoactive substances.

DNA Methylation Profiles of the DRD2 and NR3C1 Genes in Patients with Recent-Onset Psychosis.

Objectives Dopamine receptor D2 gene (DRD2) and glucocorticoid receptor gene (NR3C1) are implicated in the development of psychosis. We investigated methylation levels of DRD2 and NR3C1 in peripheral blood of patients with recent-onset (RO) psychosis using bisulfite pyrosequencing as well as its association with childhood trauma and rumination. Methods In all, 51 individuals with RO psychosis and 47 healthy controls were recruited. DNA methylation levels in the targeted regions of two genes were analyzed and compared. Childhood trauma and rumination were evaluated using the Early Trauma Inventory Self-Report Short Form (ETI-SF) and Brooding Scale (BS), respectively. Correlations between the scores of the ETI-SF and BS and methylation levels were explored. Results For DRD2, we found no significant differences between groups in terms of methylation level or association with childhood trauma or rumination. For NR3C1, we found a trend level significance for average value of all CpG sites and significant hypermethylation or hypomethylation at specific sites. There was also a significant positive correlation between the methylation level at the CpG8 site of NR3C1 exon 1F and negative symptom subscale score of the PANSS (PANSS-N). Conclusion Epigenetic alterations of NR3C1 are associated with the pathophysiology of psychosis. Further epigenetic studies will elucidate the molecular mechanisms underpinning the pathophysiology of psychosis.

High Fat Diet Increases [3H] Flunitrazepam Binding in the Mouse Brain that is Dependent on the Expression of the Dopamine D2 Gene.

Dopamine is an important neuromodulator in the brain that binds to dopamine D1-like receptors (D1, D5) as well as dopamine D2-like receptors (D2, D3, D4). The D2 receptor is known to play an integral role in a variety of physiological processes including addictive behaviors, locomotion, motivation, feeding behavior, and more. It was recently reported that dopamine is a direct-acting modulator of mammalian GABA(A) receptors. To this end, we wanted to examine how the expression of the dopamine D2 gene impacts the expression of GABA(A) receptors in the brain under different dietary conditions. Adult female Drd2 wild-type (WT), heterozygous (HT), and knockout (KO) mice were given either normal or high-fat diet for a period of 30weeks. Following this, their brains were collected for [3H] Flunitrazepam binding in order to assess GABA(A) receptor expression. A high fat diet significantly increased [3H] Flunitrazepam binding in the regions of the somatosensory cortex, striatum, and various other cortical areas within WT mice. In contrast, no effect of diet was observed in HT or KO mice. As such, HT and KO mice displayed reduced [3H] Flunitrazepam binding in these areas relative to WT mice under high-fat dietary conditions. The effect of a high-fat diet on [3H] Flunitrazepam binding is consistent with recent evidence showing increases in GABA neurotransmitter levels following a high-fat diet. We demonstrate for the first time that the expression of the D2 gene plays a prominent role in the ability of a high-fat diet to impact GABA(A) receptors in the mouse brain.

The Personality Traits and P300 of Offspring of Parents With Alcohol Dependence Differ Depending on Current Risky Drinking: A Preliminary Case-Control Study.

AimsThe aim of this study was to investigate the personality traits, and P300 component in the offspring of parents with alcohol dependence (OPAD) currently engaged in risky drinking and those not engaged in risky drinking, and to further explore the correlates of problematic alcohol use.MethodsA case-control study was conducted according to the cutoff of the Alcohol Use Disorder Identification Test (AUDIT). The frequency of the TaqIA polymorphism of the dopamine receptor D2 gene associated with alcohol dependence was compared between the two OPAD groups. Tridimensional Personality Questionnaire (TPQ), The Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST), and the MINI-International Neuropsychiatric Interview (M.I.N.I.) were measured or interviewed in OPAD not engaged in risky drinking (resilient; n = 35) and those currently engaged in risky drinking (vulnerable; n = 20). P300 was measured to test the possible electrophysiological differences. The correlates of alcohol use were analyzed.ResultsVulnerable OPAD showed higher novelty seeking subscale scores (NS4; 4.45 ± 2.012 vs. 3.31 ± 1.728, P < 0.05) and harm avoidance subscale scores (HA4; 5.3 ± 2.319 vs. 3.66 ± 2.461, P < 0.05) than resilient OPAD, while the total scores of each dimension showed no significant difference. OPAD engaged in risky drinking showed more tobacco use than OPAD resistant to risky drinking. OPAD with risky drinking showed a shorter P300 latency than resilient OPAD on Fz electrodes. AUDIT scores of OPAD were correlated with P300 latency.ConclusionsP300 differed between OPAD with and without risky drinking and alcohol use was associated with P300 latency, indicating that P300 may be used in the early detection of vulnerable OPAD and early intervention in the future.

Impact of the DRD2 Polymorphisms on the Effectiveness of the Training Program.

Dopamine receptor D2 gene (DRD2) polymorphisms have been associated with cognitive abilities, obesity, addictions, and physical-activity-related behaviors, which may underlie differences in the effectiveness of training programs. What is not yet clear is the impact of DRD2 polymorphisms on the effectiveness of exercise programs. Thus, the aim of this study was to investigate the association between the DRD2 polymorphic sites (rs1076560, rs12364283, rs1799732, rs1800497, and rs1800498) and the body’s response to regular physical activity. We studied genotypes and haplotypes distribution in a group of 165 females measured for body mass and body composition measurements, lipid profile, and glucose levels before and after realization of a 12-week training program. When tested individually, statistical analyses revealed one significant genotype by training interaction under the general model (for the basal metabolic rate, BMR, p = 0.033). Carriers of the rs1076560 CC genotype exhibited a decrease in BMR in response to training (p = 0.006). Haplotype analyses also showed that (i) the CACCC and CACTT haplotypes were associated with a post-training decrease in glucose level (β = −4.11, p = 0.032; β = −6.86, p = 0.020, respectively); (ii) the CGCCT with an increase in BMR (β = 0.65, p = 0.003) and fat free mass (FFM, β = 1.20, p = 0.009); (iii) the CA-CT with a decrease in low-density lipoprotein cholesterol (LDL, β = −17.26, p = 0.046). These results provide some evidence that the DRD2 polymorphisms may play a role in post-training changes in lipid and carbohydrate metabolism, and, as a consequence, in the effectiveness of training programs.

Influence of COMT (rs4680) and DRD2 (rs1076560, rs1800497) Gene Polymorphisms on Safety and Efficacy of Methylphenidate Treatment in Children with Fetal Alcohol Spectrum Disorders

Fetal alcohol spectrum disorders (FASD) in a course of high prenatal alcohol exposure (hPAE) are among the most common causes of developmental disorders. The main reason for pharmacological treatment of FASD children is attention deficit hyperactivity disorder (ADHD), and methylphenidate (MPH) is the drug of choice. The aim of the study was to assess whether children born of hPAE with ADHD, with or without morphological FASD, differ in terms of catechol-O-methyltransferase (COMT) and dopamine receptor D2 (DRD2) gene polymorphisms, and if genetic predisposition affects response and safety of MPH treatment. The polymorphisms of COMT (rs4680) and DRD2 (rs1076560, rs1800497) were analyzed in DNA samples. A borderline significance was found for the correlation between MPH side effects and the G allele of COMT (rs4680) (p = 0.04994) in all ADHD children. No effect of COMT (rs4680) and DRD2 (rs1076560, rs1800497) polymorphisms and the treatment efficacy was observed. The analyzed DRD2 and COMT gene polymorphisms seem to play no role in MPH efficacy in ADHD children with hPAE, while low-activity COMT (Met158) variant carriers may be more intolerant to MPH. The MPH treatment is effective in ADHD independent of FASD, although the ADHD-FASD variant requires higher doses to be successful. These results may help in optimization and individualization in child psychiatry.

Chimpanzee Extraversion scores vary with epigenetic modification of dopamine receptor gene D2 (DRD2) and early rearing conditions

ABSTRACT Chimpanzees have consistent individual differences in behaviour, also referred to as personality. Similar to human personality structure, five dimensions are commonly found in chimpanzee studies that show evidence for convergent and predictive validity (Dominance, Openness, Extraversion, Agreeableness, and Reactivity/Undependability). These dimensions are to some extent heritable, indicating a genetic component that explains part of the variation in personality scores, but are also influenced by environmental factors, such as the early social rearing background of the individuals. In this study, we investigated the role of epigenetic modification of the dopamine receptor D2 gene (DRD2) as a potential mechanism underlying personality variation in 51 captive chimpanzees. We used previously collected personality trait rating data and determined levels of DRD2 CpG methylation in peripheral blood samples for these same individuals. Results showed that DRD2 methylation is most strongly associated with Extraversion, and that varying methylation levels at specific DRD2 sites are associated with changes in Extraversion in nursery-reared, but not mother-reared, individuals. These results highlight the role of dopaminergic signalling in chimpanzee personality, and indicate that environmental factors, such as social experiences early in life, can have long-lasting behavioural effects, potentially through modification of the epigenome. These findings add to the growing evidence demonstrating the importance of the experience-dependent methylome for the development of complex social traits like personality.

Differential effects of chronic adolescent glucocorticoid or methamphetamine on drug-induced locomotor hyperactivity and disruption of prepulse inhibition in adulthood in mice

Sensitization of dopaminergic activity has been suggested as an underlying mechanism in the psychotic symptoms of schizophrenia. Adolescent stress and chronic abuse of methamphetamine (Meth) are well-known risk factors for psychosis and schizophrenia; however it remains unknown how these factors compare in terms of dopaminergic behavioural sensitization in adulthood. In addition, while Brain-Derived Neurotrophic Factor (BDNF) has been implicated in dopaminergic activity and schizophrenia, its role in behavioural sensitization remains unclear. In this study we therefore compared the effect of chronic adolescent treatment with the stress hormone, corticosterone (Cort), or with Meth, on drug-induced locomotor hyperactivity and disruption of prepulse inhibition in adulthood in BDNF heterozygous mice and their wild-type controls, as well as on dopamine receptor gene expression. Between 6 and 9 weeks of age, the animals either received Cort in the drinking water or were treated with an escalating Meth dose protocol. In adulthood, Cort-pretreated mice showed significantly reduced Meth-induced locomotor hyperactivity compared to vehicle-pretreated mice. In contrast, Meth hyperlocomotion was significantly enhanced in animals pretreated with the drug in adolescence. There were no effects of either pretreatment on prepulse inhibition. BDNF Het mice showed greater Meth-induced hyperlocomotion and lower prepulse inhibition than WT mice. There were no effects of either pretreatment on D1 or D2 gene expression in either the dorsal or ventral striatum, while D3 mRNA was shown to be reduced in male mice only irrespective of genotype. These results suggest that in adolescence, chronically elevated glucocorticoid levels, a component of chronic stress, do not cause dopaminergic sensitization adulthood, in contrast to the effect of chronic Meth treatment in the same age period. BDNF does not appear to be involved in the effects of chronic Cort or chronic Meth.

Year-round flowering gene e1, a mutation at the E1 locus on rice chromosome 7 and its combination with green revolution gene sd1 in an isogenic cell line.

Genetic analysis on the year-round flowering gene e1, which was derived from Kanto No. 79, an induced mutant by Koshihikari gamma-ray irradiated, was conducted through the backcross process to combine e1 and sd1 in the genetic background of Koshihikari. e1 strongly forwarded flowering 14 days earlier than the original variety Koshihikairi. Isogenic Koshihiakri combining e1 and sd1 was developed by four times of backcross with either Koshihikari or Koshihikari sd1 as recurrent parents by using the e1sd1 homozygous F3 plant in Koshihikari sd1 × Kanto No. 79 as a non-recurrent parent. As a result, "Koshihikari e1sd1" maturing 14 days earlier was approximately 30 cm shorter than Koshihikari. e1 was linked with DNA markers, which were near to Ghd7 on the short arm of chromosome 7. The whole genome sequencing revealed a single candidate SNP, which is specific to Koshihikari e1sd1, in the Xa21-like sequence, at 35213 bp downstream from Ghd7 on chromosome 7. Koshihikari e1sd1-specific SNP beside Ghd7 is expected to downregulate with Ghd7.

Abstract P3-10-03: Enrichment of pro-oncogenic immune miRNAs in exosomes by cyclin D1, promote cancer stem cell expansion

Abstract The cyclin D1 (CCND1) gene, encodes the regulatory subunit of a holoenzyme that phosphorylates and inactivates the Rb protein. Cyclin D1 overexpression occurs in up to 50% of human breast cancers. Cyclin D1, governs the expression (1,3), processing (2), the secretion and the relative proportion of secreted non-coding RNA subtypes (miRNA, rRNA, tRNA, CDBox, scRNA, HAcaBox. scaRNA, piRNA) in human breast cancer and the secretion of piRNA (4). Through base-pairing to the complementary sequence in 3’ untranslated region (3’ UTR) of mRNA, miRNAs participate in diverse biological processes. A subset of miRNA regulate the ageing of innate and adaptive immune cells, which has been associated with breast cancer initiation, progression and therapy resistance. Immuno-miRs, ( miR-21 and miR-93), bind to the 3′-UTR region of mRNAs, and binding to- and or activate Toll-Like Receptor 8 (TLR8) in surrounding cells of the immune system. Exosomes which contain constituents of their cell of origin, including mRNA and miRNA are found in the tumor microenvironment and participate in therapy resistance, cancer metastasis and the metastatic niche. Herein, tet-inducible cyclin D1 shRNA knock down in MCF-7 breast cancer cells reduced MCF-7 cell proliferation and mammosphere formation. Exosomes isolated from wildtype and cyclin D1 knock-down MCF-7 cell culture media, showed that exosomes from cyclin D1 knock down cells decreased proliferation of both wildtype and cyclin D1 knock-down cells. Furthermore, wildtype exosomes partially reversed the cyclin D1 knock-down effects. Cyclin D1 knock-down exosomes decreased mammosphere formation of wildtype MCF-7 cells and wildtype exosomes increased mammosphere formation of cyclin D1 knock-down cells. miRNA profiles within the exosomes, showed that cyclin D1 regulated the abundance of miRNA within exosomes. &amp;gt;85% of the cyclin D1-induced exosome miRNA transcripts were the immune-mIR, miR21. hsa-mir-21 which has documented tumor promoting function, was the most enriched miRNAs in cyclin D1 knock-down exosomes. In contrast, exosome abundance of the transcripts for hsa-mir-16 and hsa-mir-92a, both of which were showed as tumor suppressor in breast cancer cells, were reduced by cyclin D1 shRNA. The cyclin D1-mediated miRNA exosome content may contribute to tumor initiation and progression through heterotypic expansion of cancer stem cells. 1.Yu, Z., etal ., A cyclin D1/microRNA 17/20 regulatory feedback loop in control of breast cancer cell proliferation. J Cell Biol. 2008 Aug 11; 182(3): p. 509-17. 2.Yu., Z,., et. al. Cyclin D1 induction of Dicer governs microRNA processing and expression in breast cancer. Nat Commun 2013;4:2812.doi: 10.1038/ncomms3812. 3.Yu Z, et al. Cyclin D1- Mediated MicroRNA Expression Signature in Breast Cancer Subtype and Outcome. Theranostics, 2018 Mar 11,8:8, 2251-2263. 4.Lü J, et al. Cyclin D1 promotes secretion of pro-oncogenic immuno-miRNAs and piRNAs. Clin Sci (Lond). 2020 Mar 27. pii: CS20191318. doi: 10.1042/CS20191318. [Epub ahead of print]PMID:32219337 Citation Format: Xuanmao Jiao, Chongwen Xu, Lifeng Tian, Zhao Zhang, Anthony W Ashton, Zhiping Li, Richard G Pestell. Enrichment of pro-oncogenic immune miRNAs in exosomes by cyclin D1, promote cancer stem cell expansion [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-10-03.

A synergistic, global approach to revising the trypanorhynch tapeworm family Rhinoptericolidae (Trypanobatoida).

Since 2010, the trypanorhynch tapeworm family Rhinoptericolidae Carvajal & Campbell, 1975 has housed just two distinctive, monotypic genera (Rhinoptericola Carvajal & Campbell, 1975 and Nataliella Palm, 2010). However, global collections of tapeworms from sharks and rays over the last more than three decades brought to light the need for major revision of the family by suggesting a much greater species-level diversity for the nominal genus Rhinoptericola. Through synonymy and the description of new species, the number of species in the genus is increased from one to eight. A phylogenetic analysis of the D1–D3 gene region of 28S rRNA (28S), including seven of the now nine species of rhinoptericolids, and a broad sampling of the other Trypanobatoida is the first to recover a monophyletic Rhinoptericolidae. In addition to systematic revision, this study allowed for the first evaluation of the degree of intraspecific vs interspecific variation in 28S for adult trypanorhynchs across the various hosts and geographic localities from which they have been reported, suggesting a relatively consistent boundary for Rhinoptericola. It is further suggested that detailed scanning electron microscopy (SEM) images of both the basal and metabasal armatures greatly aid in the interpretation of hook arrangement and shape. A schematic to streamline determination of the tentacular surface presented in scanning electron micrographs and line drawings of trypanorhynchs is presented for species with both two and four bothria. In combination, these methodological refinements can now be used as a model to resolve issues of classification and non-monophyly within both major lineages of the Trypanorhyncha. As a result of the taxonomic work, Rhinoptericola megacantha Carvajal & Campbell, 1975 (previously only known from the American cownose ray from the Chesapeake Bay and the Ticon cownose ray from the Gulf of Mexico, Venezuela, and Brazil) is now known from an additional species of cownose ray and a species of stingray, and is revealed to have a transatlantic distribution. Data from SEM suggest a simpler interpretation of hook arrangement in the metabasal armature for Rhinoptercola and—in combination with 28S sequence data—support Shirleyrhynchus Beveridge & Campbell, 1988 (a former rhinoptericolid) as its junior synonym. The three species formerly assigned to Shirleyrhynchus are thus transferred to Rhinoptericola. Data from light microscopy on whole-mounted specimens and histological sections, SEM, and 28S showed the eutetrarhynchid Prochristianella jensenae Schaeffner & Beveridge, 2012b to be morphologically consistent with species of Rhinoptericola and it is thus transferred to the genus. The type series of P. jensenae was determined to be mixed, representing two distinct species which are here redescribed and described as new, respectively. Two additional novel species of Rhinoptericola are described from cownose rays from off Mozambique and the Gulf of California.

Identification of Two Novel Mutations of ABCD1 Gene in Pedigrees with X-Linked Adrenoleukodystrophy and Review of the Literature.

Background X-linked adrenoleukodystrophy (ALD) is an inherited peroxisomal metabolism disorder, resulting from the loss-of-function mutation of ATP-binding cassette protein subfamily D1 (ABCD1) gene. The dysfunction of ALD protein, a peroxisomal ATP-binding cassette transporter, results in the excessive saturated very long-chain fatty acids (VLCFAs) accumulation in organs including the brain, spine, and adrenal cortex. X-ALD is characterized as the childhood, adolescent, adult cerebral ALD, adrenomyeloneuropathy (AMN), adrenal insufficiency, and asymptomatic phenotypes, exhibiting a high variety of clinical neurological manifestations with or without adrenocortical insufficiency. Results In this study, we reported two cases of X-ALD, which were first diagnosed as adrenal insufficiency (Addison's disease) and treated with adrenocortical supplement. However, both of the cases progressed as neurological symptoms and signs after decades. Elevated VLCFAs level, brain MRI scan, and genetic analysis confirmed final diagnosis. In addition, we identified two novel mutations of ABCD1 gene, NM_000033.3 (ABCD1): c.874_876delGAG (p.Glu292del) and NM_000033.3 (ABCD1): c.96_97delCT (p.Tyr33Profs∗161), in exon 1 of ABCD1 gene. Sanger sequencing confirmed that the proband's mother of the first case was heterozygous carrying the same variant. Adrenal insufficiency-only type is very rare; however, it may be the starting performance of X-ALD. In addition, we summarized reported mutation sites and clinical manifestations to investigate the correlationship of phenotype-genotype of X-ALD. Conclusions The early warning manifestations should be noticed, and the probability of X-ALD should be considered. This report could be beneficial for the early diagnosis and genetic counseling for patients with X-ALD.