Protein fucosylation is required for Notch dependent vascular integrity in zebrafish.

The onset of circulation in a developing embryo requires intact blood vessels to prevent hemorrhage. The development of endothelial cells, and their subsequent recruitment of perivascular mural cells are important processes to establish and maintain vascular integrity. These processes are genetically controlled during development, and mutations that affect endothelial cell specification, pattern formation, or maturation through the addition of mural cells can result in early developmental hemorrhage. We created a strong loss of function allele of the zebrafish GDP-mannose 4,6 dehydratase (gmds) gene that is required for the de novo synthesis of GDP-fucose, and homozygous embryos display cerebral hemorrhages. Our data demonstrate that gmds mutants have early defects in vascular patterning with ectopic branches observed at time of hemorrhage. Subsequently, defects in the number of mural cells that line the vasculature are observed. Moreover, activation of Notch signaling rescued hemorrhage phenotypes in gmds mutants, highlighting a potential downstream pathway that requires protein fucosylation for vascular integrity. Finally, supplementation with fucose can rescue hemorrhage frequency in gmds mutants, demonstrating that synthesis of GDP-fucose via an alternative (salvage) pathway may provide an avenue toward therapeutic correction of phenotypes observed due to defects in de novo GDP-fucose synthesis. Together, these data are consistent with a novel role for the de novo and salvage protein fucosylation pathways in regulating vascular integrity through a Notch dependent mechanism.

GMDS knockdown impairs cell proliferation and survival in human lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma is the most common type of lung cancer and one of the most lethal and prevalent cancers. Aberrant glycosylation was common and essential in tumorigenesis, with fucosylation as one of the most common types disrupted in cancers. However, it is still unknown whether genes involved in fucosylation are important for lung adenocarcinoma development and process. METHODS: GMDS is involved in cellular fucosylation. Here we examined GMDS expression level at both mRNA and protein level in lung adenocarcinoma. The impact of GMDS knockdown on lung adenocarcinoma in vitro and in vivo was investigated. Transcriptome changes with GMDS knockdown in lung adenocarcinoma cells were also examined to provide insights into related molecular mechanisms. RESULTS: GMDS expression is significantly upregulated in lung adenocarcinoma at both mRNA and protein levels. Lentivirus-mediated shRNA strategy inhibited GMDS expression efficiently in human lung adenocarcinoma cells A549 and H1299, and GMDS knockdown impaired cell proliferation, colony formation ability, induced cell cycle arrest, and apoptosis in both cell lines. Furthermore, GMDS knockdown inhibited tumorigenesis in a xenograft mice model of lung adenocarcinoma. Microarray analysis explored the GMDS-mediated molecular network and revealed that the CASP8-CDKN1A axis might be critical for lung adenocarcinoma development. CONCLUSIONS: These findings suggest that GMDS upregulation is critical for cell proliferation and survival in human lung adenocarcinoma and might serve as a potential biomarker for lung adenocarcinoma diagnosis and treatment.

Correlations of AFAP1, GMDS and PTGFR gene polymorphisms with intra-ocular pressure response to latanoprost in patients with primary open-angle glaucoma.

WHAT IS KNOWN AND OBJECTIVE: Genomewide association studies have identified a number of genetic variants that are associated with the development of primary open-angle glaucoma (POAG). This study aimed to explore possible correlations of common single nucleotide polymorphisms (SNPs) in AFAP1, GMDS and PTGFR genes with intra-ocular pressure (IOP) response to latanoprost in POAG patients. METHODS: From January 2012 to December 2014, 135 patients with POAG were enrolled into our study. Direct sequencing of polymerase chain reaction (PCR) products was used to analyse the distribution of allelic and genotypic frequencies of AFAP1 rs11723068 G>A and rs757253 T>C, GMDS rs9503012 C>T and rs17134549 T>A, and PTGFR rs3753380 C>T and rs3766355 A>C. RESULTS AND DISCUSSION: After 1, 2 and 4 weeks of latanoprost treatment, the IOP of POAG patients decreased significantly (all P < 0·05). The genotype frequencies of six SNPs in AFAP1, GMDS and PTGFR genes were conformed to Hardy-Weinberg equilibrium (HWE). Before latanoprost treatment, the baseline IOP levels of POAG patients carrying CC+AC genotypes of PTGFR rs3766355 A>C were higher than those carrying AA genotype (P < 0·05). After 1, 2 and 4 weeks of latanoprost treatment, POAG patients carrying TT genotype of GMDS rs9503012 C>T showed better response to latanoprost than those carrying CC+CT genotype (P < 0·05). Similarly, POAG patients carrying AA genotype of PTGFR rs3766355 A>C showed better response to latanoprost than those carrying CC+AC genotypes (P < 0·05). Logistic regression analysis showed that age, CC+CT genotypes of GMDS rs9503012 C>T and CC+AC genotypes of PTGFR rs3766355 A>C were independent risk factors for poor response to latanoprost in POAG patients. WHAT IS NEW AND CONCLUSIONS: GMDS rs9503012 C>T and PTGFR rs3766355 A>C may be associated with IOP response to latanoprost in POAG patients.

The Indispensable Roles of GMDS and GMDS-AS1 in the Advancement of Cancer: Fucosylation, Signal Pathway and Molecular Pathogenesis.

Fucosylation is facilitated by converting GDP-mannose to GDP-4-keto-6-deoxymannose, which GDP-mannose 4,6-dehydratase, a crucial enzyme in the route, carries out. One of the most prevalent glycosylation alterations linked to cancer has reportedly been identified as fucosylation. There is mounting evidence that GMDS is intimately linked to the onset and spread of cancer. Furthermore, the significance of long-chain non-coding RNAs in the development and metastasis of cancer is becoming more well-recognized, and the regulatory mechanism of lncRNAs has emerged as a prominent area of study in the biological sciences. GMDS-AS1, an antisense RNA of GMDS, was discovered to have the potential to be an oncogene. We have acquired and analyzed relevant data to understand better how GMDS-AS1 and its lncRNA work physiologically and in tumorigenesis and progression. Additionally, we have looked into the possible effects of these molecules on cancer treatment approaches and patient outcomes. The physiological roles and putative processes of GMDS and lncRNA GMDS-AS1 throughout the development and progression of tumors have been assembled and examined. We also examined how these chemicals might affect patient prognosis and cancer therapy approaches. GMDS and GMDS-AS1 were determined to be research subjects by searching and gathering pertinent studies using the PubMed system. The analysis of these research articles demonstrated the close relationship between GMDS and GMDS-AS1 and tumorigenesis and the factors that influence them. GMDS plays a vital role in regulating fucosylation. The related antisense gene GMDS-AS1 affects the biological behaviors of cancer cells through multiple pathways, including the key processes of proliferation, migration, invasion, and apoptosis, providing potential biomarkers and therapeutic targets for cancer treatment and prognosis assessment.

lncRNA GMDS-AS1 restrains lung adenocarcinoma progression via recruiting TAF15 protein to stabilize SIRT1 mRNA.

Aim: To explore the roles of GMDS-AS1 in the epithelial-mesenchymal transition (EMT) of lung adenocarcinoma (LUAD). Materials & methods: Cell functions were detected by flow cytometry, cell counting kit-8, wound healing assays and transwell assays. RNA immunoprecipitation and pull-down assays were applied for determining the interaction among GMDA-AS1, TAF15 and SIRT1. A subcutaneous xenograft model was established. Results: GMDS-AS1 downregulation was associated with poor survival of LUAD patients. GMDS-AS1 repressed malignant phenotypes, tumor growth and EMT in vitro and in vivo. Mechanically, GMDS-AS1 recruited TAF15 protein to stabilize SIRT1 mRNA and thereby deacetylated p65 and reduced the recruitment of p65 to MMP-9 promoter, thus inhibiting MMP-9 expression. Conclusion: GMDS-AS1 represses EMT by recruiting TAF15 protein to stabilize SIRT1 mRNA and deacetylate p65, thus restraining LUAD progression.

GMDS-AS1, a novel lncRNA, is involved in the progression of lung adenocarcinoma (LUAD), but the mechanism by which GMDS-AS1 regulates LUAD progression remains largely unknown. This study found that GMDS-AS1 was downregulated in LUAD patients, and its low expression was associated with advanced metastasis and poor survival. Overexpression of GMDS-AS1 significantly impaired tumor cell viability, proliferation, migration, invasion and epithelial­mesenchymal transition but enhanced apoptosis. In addition, GMDS-AS1 repressed tumor growth in mice. GMDS-AS1 functioned as a tumor suppressor in LUAD by recruiting TAF15 protein to stabilize SIRT1 mRNA and deacetylate p65, thus decreasing the recruitment of p65 to MMP-9 promoter. These findings have uncovered a novel mechanism underlying LUAD progression and suggested potential prognostic biomarkers and therapeutic targets.

Epigenetic inhibition of lncRNA GMDS-AS1 by methyltransferase ESET promoted cell viability and metastasis of hepatocellular carcinoma.

BACKGROUND: Long noncoding RNA (lncRNAs) GMDS-AS1 has been reported as a tumor regulator in tumor growth and metastasis, but its effect in hepatocellular carcinoma (HCC) remains unclear. ESET, a histone H3K9 methyl-transferase, is involved in epigenomic regulation of tumor progression in multiple cancers. However, the correlation between ESET and lncRNA in HCC is less reported. METHODS: Quantitative real-time PCR (qRT-PCR) was taken to determine the expression of ESET and GMDS-AS1. Western blot was taken to determine the target protein levels of ESET and GMDS-AS1. Online database and bioinformatics analysis were used to screen abnormally expressed genes. Luciferase assay was performed to confirm the binding of GMDS-AS1 and PSMB1. Ki67 and Edu were used for evaluated the proliferation of tumor cells. ChIP assay was performed to verify the relationship between H3K9me1 and lncRNA GMDS-AS1 promoter. Transwell was taken to determine the migration and invasion ability of tumor cells. CCK-8 was used for determining the viability of tumor cells. Flow cytometry was performed to detect the cell cycle of tumor cells. RESULTS: The expression of GMDS-AS1 was decreased and the expression of ESET was increased in HCC. GMDS-AS1 inhibition contributed to tumor development, and this effect was closely related to epigenetic inhibition of GMDS-AS1 by ESET. PSMB1, a downstream target of GMDS-AS1, promoted the tumor proliferation and was negatively regulated by GMDS-AS1. CONCLUSION: Our result demonstrates anti-tumorigenic traits of lncRNA GMDS-AS1 in HCC and explains its pattern of regulation mediated by ESET. Our work unmasked an essential role of GMDS-AS1 in HCC progression and detected a novel pathway for ESET to promote HCC.

Establishment of a novel 70K Mac-2 binding protein antibody through screening of fucosylation-related antibodies.

Mac-2 binding protein (Mac-2bp) is a serum glycoprotein that contains seven N-glycans, and Mac-2bp serum levels are increased in patients with several types of cancer and liver disease. Mac-2bp glycosylation isomer has been applied as a clinical biomarker of several diseases, including liver fibrosis. In the present study, we identified fucosylated Mac-2bp in the conditioned medium of cancer cells resistant to anticancer therapies using glycoproteomic analyses. Fucosylation is one of the most important types of glycosylation involved in carcinogenesis and cancer stemness. To establish a next-generation glycan antibody for fucosylated Mac-2bp, we used fucosylation-deficient HEK293T cells to prepare reference Mac-2bp antigens and performed antibody screening. Unexpectedly, the 19-8H mAb obtained with our screen recognized 70K Mac-2bp, which is C-terminus-truncated product, rather than specifically recognizing fucosylated Mac-2bp. We performed immunocytochemistry using our novel 19-8H mAb, which resulted in strong cell surface staining of anticancer drug-resistant cancer cells. Therefore, our novel 19-8H mAb represents a valuable tool for cancer biology research that can help elucidate the biological function of 70K Mac-2bp.

Epilepsy and Molecular Phenotype Affect the Neurodevelopment of Pediatric Angelman Syndrome Patients in China.

Objective: This study investigated the mental development of children with Angelman syndrome (AS) in China and evaluated the relationship between neurodevelopment and molecular subtype, age, epilepsy, and sex using the Chinese version of the Griffith Mental Development Scale (GMDS-C) to provide detailed baseline data regarding neurodevelopment with AS in China. Methods: Participants were recruited from the AS Natural History Study. The GMDS-C was used to evaluate all participants' mental age and developmental quotients. The general quotient (GQ) and quotients of five subscales (sports, personal-social, auditory language, eye-hand coordination, and comprehensive performance) were calculated. Results: A total of 119 children (average age: 42.12 months; range, 7.5-95.5 months) with a genetic diagnosis of AS were enrolled. The median GQ score of the GMDS was 29.6 points (95% confidence interval, 28.6-33.25). The children had relatively good locomotor and personal-social skills but poor language skills. Overall, 89% (106/119) had mental ages younger than 24 months for all five subscales. The non-deletion group (i.e., without deletion in chromosome 15q11-13) had higher GQs and locomotor, personal-social, and performance subscale quotients. The GQ was significantly different among the three age subgroups and significantly correlated with age. Compared with the non-epilepsy group, the epilepsy group had lower GQs and lower quotients for the locomotor, personal-social, speech, language, and eye-hand coordination subscales. Conclusion: Children with AS in China experience severe neurodevelopmental deterioration. In addition to age, molecular subtypes and the onset of seizures may also correlate with these patients' intellectual development. The GMDS-C is an accurate tool that can assess the clinical characteristics of AS. The data of this study can be used as baseline data for clinical trials performed to evaluate drug development or other AS treatment development.

Monitoring of Communication Precursors in Extremely Low Birth Weight (ELBW) Newborns by Video Analysis Method: Preliminary Results.

Background: The survival of extremely low birth weight infants (ELBW) has increased worldwide. Even in the absence of major disabilities, ELBW infants show difficulty in simple language functions. It is relevant to assess early abilities, which are the base of early linguistic skills, in order to implement customized intervention programs in ELBW infants. Aims: To evaluate communication precursors of language development in ELBW infants at 12 and 24 months of correct age (C.A). To investigate the correlation of linguistic and communicative prerequisites with mental development outcome at 24 months CA. Method: 52 ELBW neonates (mean gestational age 26.6 weeks, mean birth weight was 775 g) who were admitted to the neonatal intensive care unit of the University Hospital of Modena, were enrolled. Data were collected from archived audio-video recordings of neurodevelopmental follow-up visits. Video analysis of communicative and linguistic developmental was performed at 12 and 24 months CA. Neurodevelopmental outcome was evaluated with Mental Developmental Scales (GMDS-R). Results: The video-analysis showed that infants at 12 months CA used predominantly eye contacts and gestural turns, while vocal turns were scant. At 24 months CA, a significant change in eye contacts, vocal turns, gestural turns, and utterances (p < 0.001) occurred. The total number of utterances (p = 0.036) and eye contacts (p = 0.045) were significantly correlated to the Development Quotient (DQ) of Hearing and Language scale. Moreover, a significant correlation was found with the Personal-Social scale vocal turns (p = 0.009) and the total number of utterances (p = 0,02). Finally, the Global Quotient of the GMDS-R was related to the Vocal Turns (p = 0.034) and the total number of Utterances (p = 0.013). Conclusions: ELBW infants at 12 months CA use predominantly eye contacts and gestural turns to communicate with adults. At 24 months CA, the child's communicative intention evolves from gestural to verbal communication. The latter is characterized by an increase in both vocal turns and the number of utterances produced during interaction. The video analysis we implement appears to be a sensitive tool for early assessment of communication and language development and to refine early intervention

lncRNA GMDS­AS1 upregulates IL­6, TNF­α and IL­1ß, and induces apoptosis in human monocytic THP­1 cells via miR­96­5p/caspase 2 signaling.

Long non­coding RNA (lncRNA) is considered a crucial modulator of the initiation and progression of several diseases. However, the roles of lncRNA in sepsis have yet to be fully elucidated. Thus, the aim of the present study was to investigate the effects of the lncRNA GDP­mannose 4,6­dehydratase antisense 1 (GMDS­AS1) and its target in order to understand its role in the pathogenesis of sepsis. An in vitro sepsis model was established by lipopolysaccharide (LPS) induction. Reverse transcription­quantitative PCR analysis was applied to detect the expression of inflammatory cytokines and the levels of GMDS­AS1, microRNA (miR)­96­5p and caspase­2 (CASP2). Flow cytometry was used to quantify the rate of apoptosis. In addition, the interaction between miR­96­5p and CASP2 was verified using a luciferase reporter assay. Western blot analysis was performed to assess the protein levels of CASP2 following alterations in GMDS­AS1 and miR­96­5p expression using transfection. The levels of interleukin (IL)­6, tumor necrosis factor­α and IL­1ß were increased by LPS treatment in THP­1 cells, whereas miR­96­5p expression was downregulated. miR­96­5p overexpression inhibited LPS­induced inflammatory responses and apoptosis. In addition, GMDS­AS1 expression increased, and upregulation of GMDS­AS1 inhibited, the expression of miR­96­5p in the in vitro sepsis model. Moreover, CASP2 was confirmed to be a direct target of miR­96­5p. Therefore, the lncRNA GMDS­AS1 regulated inflammatory responses and apoptosis by modulating CASP2 and sponging miR­96­5p in LPS­induced THP­1 cells. In summary, the findings of the present study demonstrated that lncRNA GMDS­AS1 could promote the development of sepsis by targeting miR­96­5p/CASP2, indicating that the GMDS­AS1/miR­96­5p/CASP2 axis may be a new therapeutic target and potential research direction for sepsis therapy.

One Conference, Three Proceedings - Which Papers Should I Submit and How? A Publication Strategy for Young Scientists Regarding the GMDS Annual Conference and Beyond (Editorial).

The primary intention of any scientific work is to share the gained knowledge and to contribute to the knowledge and progress in the scientific domain. The wide range of journals and conferences, each with specific submission requirements, can be difficult to navigate, especially for young scientists without extensive experience. But a suitable publication strategy can be helpful, especially at the beginning of a scientific career. Using the annual conference of the German Association for Medical Informatics, Biometry and Epidemiology (GMDS) e.V. as an example, this editorial highlights fundamental differences, advantages and disadvantages, as well as assistance in selecting the right form of submission.

Epigallocatechin-3-Gallate Plus Omega-3 Restores the Mitochondrial Complex I and F0F1-ATP Synthase Activities in PBMCs of Young Children with Down Syndrome: A Pilot Study of Safety and Efficacy.

Down syndrome (DS) is a major genetic cause of intellectual disability. DS pathogenesis has not been fully elucidated, and no specific pharmacological therapy is available. DYRK1A overexpression, oxidative stress and mitochondrial dysfunction were described in trisomy 21. Epigallocatechin-3-gallate (EGCG) is a multimodal nutraceutical with antioxidant properties. EGCG inhibits DYRK1A overexpression and corrects DS mitochondrial dysfunction in vitro. The present study explores safety profiles in DS children aged 1-8 years treated with EGCG (10 mg/kg/die, suspended in omega-3, per os, in fasting conditions, for 6 months) and EGCG efficacy in restoring mitochondrial complex I and F0F1-ATP synthase (complex V) deficiency, assessed on PBMCs. The Griffiths Mental Developmental Scales-Extended Revised (GMDS-ER) was used for developmental profiling. Results show that decaffeinated EGCG (>90%) plus omega-3 is safe in DS children and effective in reverting the deficit of mitochondrial complex I and V activities. Decline of plasma folates was observed in 21% of EGCG-treated patients and should be carefully monitored. GMDS-ER scores did not show differences between the treated group compared to the DS control group. In conclusion, EGCG plus omega-3 can be safely administered under medical supervision in DS children aged 1-8 years to normalize mitochondria respiratory chain complex activities, while results on the improvement of developmental performance are still inconclusive.

LncRNA GMDS-AS1 inhibits lung adenocarcinoma development by regulating miR-96-5p/CYLD signaling.

According to the global cancer statistic, lung cancer is one of the most dangerous tumors, which poses a serious threat to human health. Exploration the mechanism of lung cancer and new targeted therapeutic measures is always the hot topic. Long noncoding RNA (lncRNA) is an important factor affecting the development of tumors. However, the research on the mechanism of lncRNA in the progress of lung cancer needs to be further expanded. In this study, we found that the expression of lncRNA GMDS-AS1 was significantly reduced in lung adenocarcinoma (LUAD) tissues and cells. Upregulated GMDS-AS1 can significantly inhibit the proliferation of LUAD cells and promote cell apoptosis in vitro and in vivo. The results indicate that GMDS-AS1 acts as a tumor suppressor gene to affect the development of LUAD. Further studies revealed that GMDS-AS1 is a target gene of miR-96-5p, and GMDS-AS1 regulates proliferation and apoptosis of LUAD cells in association with miR-96-5p. In addition, we also confirmed that CYLD lysine 63 deubiquitinase (CYLD) is also a target gene of miR-96-5p. Through various validations, we confirmed that GMDS-AS1 can act as a ceRNA to upregulate the expression of CYLD by sponging miR-96-5p. Moreover, the intervention of GMDS-AS1/miR-96-5p/CYLD network can regulate the proliferation and apoptosis of LUAD cells. In this study, we revealed that the GMDS-AS1/miR-96-5p/CYLD network based on ceRNA mechanism plays an important role in the development of LUAD and provides a new direction and theoretical basis for targeted therapy of LUAD.

Impact of age at surgery on neurodevelopmental outcomes in sagittal synostosis.

OBJECTIVE: The aim of this study was to ascertain whether age at surgery has an impact on later neurodevelopmental outcomes for children with sagittal synostosis (SS). METHODS: The developmental outcome data from patients who had surgery for SS and who attended their routine preoperative, 6-7 months postoperative, and 5-year-old developmental assessments (yielding general quotients [GQs]) (n = 50), 10-year-old IQ assessment (n = 54), and 15-year-old IQ assessment (n = 23) were examined, comparing whether they had surgery at < 7 months, 7 to < 12 months, or ≥ 12 months). RESULTS: There was no significant effect for age at surgery for GQ at 5 years of age, but there was a significant effect (p = 0.0001) for those undergoing surgery at < 7 months in terms of preoperative gross locomotor deficit that resolved by 6-7 months postoperatively (increase of 22.1 points), and had further improved by 5 years of age (total increase of 29.4 points). This effect was lessened when surgery was performed later (total increase of 7.3 points when surgery was performed at ≥ 12 months). At 10 years of age, 1-way ANOVA showed a significant difference in Full Scale IQ (FSIQ) score (p = 0.013), with the highest mean FSIQ being obtained when surgery was performed at < 7 months of age (score 107.0), followed by surgery at 7 to < 12 months (score 94.4), and the lowest when surgery was performed at ≥ 12 months (score 93.6). One-way ANOVA for the Performance IQ (PIQ) was very similar (p = 0.012), with PIQ scores of 101.4, 91.4, and 87.3, respectively. One-way ANOVA for Verbal IQ (VIQ) was again significant (p = 0.05), with VIQ scores of 111.3, 98.9, and 100.4, respectively. At 15 years, 1-way ANOVA showed a significant difference in PIQ (p = 0.006), with the highest mean PIQ being obtained when surgery was performed at < 7 months (score 104.8), followed by surgery at 7 to < 12 months (score 90.0), and the lowest when surgery was at performed at ≥ 12 months of age (score 85.3). There were no significant results for FSIQ and VIQ, although there was a similar trend for better outcomes with early surgery. CONCLUSIONS: The findings of this study add to the literature that suggests that early surgery for SS may result in improved neurodevelopmental outcomes, with surgery optimally undertaken when patients are < 7 months of age, and with those undergoing surgery at ≥ 12 months performing the least well. These results also have potential implications for ensuring early diagnosis and referral and for the type of surgery offered. Further research is needed to control for confounding factors and to identify the mechanism by which late surgery may be associated with poorer neurodevelopmental outcomes.

Paternal Perinatal Depression Assessed by the Edinburgh Postnatal Depression Scale and the Gotland Male Depression Scale: Prevalence and Possible Risk Factors.

Several studies have used the Edinburgh Postnatal Depression Scale (EPDS), developed to screen new mothers, also for new fathers. This study aimed to further contribute to this knowledge by comparing assessment of possible depression in fathers and associated demographic factors by the EPDS and the Gotland Male Depression Scale (GMDS), developed for "male" depression screening. The study compared EPDS score ≥10 and ≥12, corresponding to minor and major depression, respectively, in relation to GMDS score ≥13. At 3-6 months after child birth, a questionnaire was sent to 8,011 fathers of whom 3,656 (46%) responded. The detection of possibly depressed fathers by EPDS was 8.1% at score ≥12, comparable to the 8.6% detected by the GMDS. At score ≥10, the proportion detected by EPDS increased to 13.3%. Associations with possible risk factors were analyzed for fathers detected by one or both scales. A low income was associated with depression in all groups. Fathers detected by EPDS alone were at higher risk if they had three or more children, or lower education. Fathers detected by EPDS alone at score ≥10, or by both scales at EPDS score ≥12, more often were born in a foreign country. Seemingly, the EPDS and the GMDS are associated with different demographic risk factors. The EPDS score appears critical since 5% of possibly depressed fathers are excluded at EPDS cutoff 12. These results suggest that neither scale alone is sufficient for depression screening in new fathers, and that the decision of EPDS cutoff is crucial.

Validity of Gotland Male Depression Scale for male depression in a community study: the Sudurnesjamenn study.

BACKGROUND: Several studies suggest a "male depressive syndrome", where not only the standard symptoms of major depressive disorder (MDD) but also symptoms of anxiety, anger, irritability and antisocial behaviour are prominent. METHOD: In a community study, 534 males were screened for possible depression by the Gotland Male Depression Scale (GMDS) and Beck's Depression Inventory (BDI). For comparison psychiatrists examined a sub-sample of healthy and depressive males (n=137). The validity of the GMDS was compared both with the BDI and MDD diagnosis according to DSM-IV. RESULTS: GMDS was as good as BDI for screening males. ROC-curve analysis gave AUC 0.945 (95% CI 0.923-0.968) for GMDS when tested against BDI. Second, when both scales were tested by ROC-curves against DSM-IV, the GMDS had AUC=0.861 (95% CI 0.800-0.921) and BDI had AUC=0.822 (95% CI 0.751-0.893). The estimated prevalence was 14-15%. LIMITATIONS: Low participation rate (25%) in the screening phase. CONCLUSION: GMDS is a valid screening tool for detecting male depression (MDD). Furthermore it is a short self-rating scale, easy to use in daily practice to screen for depression. Our results support recent reports of high prevalence of depressions in the community which supports active screening of males in clinical practice.

Human GMDS gene fragment hypermethylation in chronic high level of arsenic exposure with and without arsenic induced cancer.

Arsenic, though a poor mutagen, is an accepted environmental carcinogen. Perturbation of DNA methylation pattern leading to aberrant gene expression has been hypothesized as the mechanism for arsenic induced carcinogenesis. We had earlier demonstrated the hypermethylation of promoter region of p53 and p16 genes in persons exposed to different doses of arsenic. Till now no genomic hot spot has been identified which is frequently hypermethylated or hypomethylated in persons chronically exposed to environmental arsenic. In the present work, we have identified one hypermethylated sequence by methyl-sensitive arbitrarily primed polymerase chain reaction in the peripheral blood leukocyte DNA of chronically arsenic exposed persons with and without arsenic induced skin cancer. The sequence is from GMDS gene responsible for fucose metabolism. Southern hybridization of the sequence to the amplification products of methyl sensitive restriction enzyme digested genome of persons exposed to different doses of arsenic indicated that methylation increased in a dose dependent manner.

Epigenetic inhibition of lncRNA GMDS-AS1 by methyltransferase ESET promoted cell viability and metastasis of hepatocellular carcinoma

Background Long noncoding RNA (lncRNAs) GMDS-AS1 has been reported as a tumor regulator in tumor growth and metastasis, but its effect in hepatocellular carcinoma (HCC) remains unclear. ESET, a histone H3K9 methyl-transferase, is involved in epigenomic regulation of tumor progression in multiple cancers. However, the correlation between ESET and lncRNA in HCC is less reported. Methods Quantitative real-time PCR (qRT-PCR) was taken to determine the expression of ESET and GMDS-AS1. Western blot was taken to determine the target protein levels of ESET and GMDS-AS1. Online database and bioinformatics analysis were used to screen abnormally expressed genes. Luciferase assay was performed to confirm the binding of GMDS-AS1 and PSMB1. Ki67 and Edu were used for evaluated the proliferation of tumor cells. ChIP assay was performed to verify the relationship between H3K9me1 and lncRNA GMDS-AS1 promoter. Transwell was taken to determine the migration and invasion ability of tumor cells. CCK-8 was used for determining the viability of tumor cells. Flow cytometry was performed to detect the cell cycle of tumor cells. Results The expression of GMDS-AS1 was decreased and the expression of ESET was increased in HCC. GMDS-AS1 inhibition contributed to tumor development, and this effect was closely related to epigenetic inhibition of GMDS-AS1 by ESET. PSMB1, a downstream target of GMDS-AS1, promoted the tumor proliferation and was negatively regulated by GMDS-AS1. Conclusion Our result demonstrates anti-tumorigenic traits of lncRNA GMDS-AS1 in HCC and explains its pattern of regulation mediated by ESET. Our work unmasked an essential role of GMDS-AS1 in HCC progression and detected a novel pathway for ESET to promote HCC (AU)

The role of gangliosides in brain development and the potential benefits of perinatal supplementation.

The maternal diet provides critical nutrients that can influence fetal and infant brain development and function. This review highlights the potential benefits of maternal dietary ganglioside supplementation on fetal and infant brain development. English-language systematic reviews, preclinical studies, and clinical studies were obtained through searches on PubMed. Reports were selected if they included benefits and harms of maternal ganglioside supplementation during pregnancy or ganglioside-supplemented formula after pregnancy. The potential benefits of ganglioside supplementation were explored by investigating the following: (1) their role in neural development, (2) their therapeutic use in neural injury and disease, (3) their presence in human breast milk, and (4) their use as a dietary supplement during or after pregnancy. Preclinical studies indicate that ganglioside supplementation at high doses (1% of total dietary intake) can significantly increase cognitive development and body weight when given prenatally. However, lower ganglioside supplementation doses have no beneficial cognitive effects, even when given throughout pregnancy and lactation. In human clinical trials, infants given formula supplemented with gangliosides showed increased cognitive development and an increase in ganglioside content. Ganglioside supplementation may promote brain development and function in offspring when administered at the optimum dosage. We propose that prenatal maternal dietary supplementation with gangliosides throughout pregnancy may promote greater long-term effects on brain development and function. Before this concept can be encouraged in preconception clinics, future research and clinical trials are needed to confirm the ability of dietary gangliosides to improve cognitive development, but available results already encourage this area of research.