Myotonic dystrophy is a complex neuromuscular disorder associated with DNA expansion mutations in two different genes. In DM1 a CTG repeat in the 3'-untranslated region of DMPK is expanded, whereas in DM2 an intronic CCTG expansion occurs in the gene ZNF9. Transcripts containing expanded repeats form foci in the nuclei of DM1 and DM2 cells. Recent work using antibodies has shown that proteins related to Drosophila muscleblind co-localize with repeat foci in DM1 and DM2 cells. We show that rather than there being a single human muscleblind gene producing multiple proteins through alternative splicing, there are in fact three different muscleblind genes, MBNL, MBLL and MBXL, which map to chromosomes 3, 13 and X, respectively, and which show extensive alternative splicing. Two of the genes, MBNL and MBLL, are expressed in many adult tissues whereas MBXL is expressed predominantly in the placenta. Green fluorescent protein-tagged versions of MBNL, MBLL and MBXL co-localize with nuclear foci in DM1 and DM2 cells, suggesting that all three proteins may play a role in DM pathophysiology.

Myotonic dystrophy (DM1) is the most common form of adult muscular dystrophy and is inherited as an autosomal dominant trait. The genetic basis of DM1 is the expansion of a CTG repeat in the 3' untranslated region of a protein kinase gene (DMPK). The molecular mechanism by which this expanded repeat produces the pathophysiology of DM1 remains unknown. Transcripts from the expanded allele accumulate as foci in the nucleus of DM1 cells and it has been suggested that these transcript foci sequester cellular proteins that are required for normal nuclear function. We have investigated the role of three RNA-binding proteins, CUG-BP, hnRNP C and MBNL, as possible sequestered factors. Using a combination of indirect immunofluorescence to detect endogenous proteins and overexpression of proteins with green fluorescent protein (GFP) tags we have shown that CUG-BP and hnRNP C do not co-localise with expanded repeat foci in DM1 cell lines. However, GFP-tagged MBNL does itself form foci in DM1 cell lines and co-localises with the foci of expanded repeat transcripts. GFP-tagged MBNL does not appear as foci in non-DM1 cell lines. This work provides further support for the involvement of MBNL in DM1.

Background Human leptin is a peptide hormone that is released from white adipocytes. The absence of leptin or its receptor leads to uncontrolled food intake, leading to obesity. In the present work, the effects of auricular acupressure combined with low-calorie diet on the leptin hormone level were investigated. Methods Volunteers (n=86) with body mass indices (BMI) between 25 and 45 kg/m 2 were randomised into a case (n=43) or a control (n=43) group. Participants in each group received a low-calorie diet for 6 weeks. The case group was treated with auricular acupressure and the control group received a sham procedure. Plasma leptin levels, body fat mass, body weight and BMI were measured before and after treatment. Results Participants who received auricular acupressure showed signifi cant reductions in their plasma leptin levels (18.57%, p<0.01) as well as in their body fat mass (4%, p<0.05). These changes were not observed in the control group. The reduction in leptin was signifi cantly greater in the acupressure group than the controls. Conclusions Auricular acupressure combined with a low-calorie diet signifi cantly reduced plasma levels of leptin. However, the mechanism of this reduction is not clear.

BackgroundThe prevalence of abdominal obesity is on the rise worldwide. Previous studies have indicated the higher diagnostic value of body fat distribution pattern compared with general body in abdominal obesity assessments. Several non-pharmacological methods have been suggested for obesity management, of which acupuncture has gained a great deal of research interest with promising results.This study aimed to comparatively evaluate the effects of conventional auricular and body electroacupuncture on abdominal fat mass in obese men.MethodsThe volunteers were randomly divided into four groups, including 2 interventions and 2 controls. This study was conducted on 80 obese volunteer men with Body Mass Index (BMI) range of 30–40 kg/m2.The intervention groups including real body electroacupuncture (A), real auricular acupuncture (C) and the control groups containing sham body electroacupuncture (B), and sham auricular acupuncture (D). All groups were in combination with a low-calorie diet for 6 weeks. BMI, Trunk Fat Mass (TFM), Waist Circumference (WC), and Hip Circumference (HC) were measured pre- and post-intervention.ResultsIn group A, respectively a significant reduction was shown in BMI (P < 0.005), TFM (P < 0.005), WC (P < 0.05, P < 0.005) and HC (P < 0.005) when compared with controls (Groups B and D). Interestingly, group C had significant decreases in BMI (P < 0.005), TFM (P < 0.01, P < 0.005), WC (P < 0.005) and HC (P < 0.001) after comparison with the sham. Likewise, WC (P < 0.05) and HC (P < 0.05) were significantly reduced post- intervention when compared with two treatment groups.ConclusionsIn our study, acupuncture treatment (body or auricular) seemed to have an effect on reducing BMI, TFM, WC and HC. Comparison of the two types of treatment (body and auricular acupuncture) suggests that the two types of acupuncture had similar effects on reducing BMI and TFM, but body electroacupuncture is more effective in reducing WC and auricular in HC. It seems that both auricular and body electro-acupuncture combined with a low-calorie diet are efficient, simple and painless methods to reduce respectively the HC and WC fat in obese men, compared with conventional techniques.Trial registrationIRCT201201127117N2

In myotonic dystrophy, muscleblind-like protein 1 (MBNL1) protein binds specifically to expanded CUG or CCUG repeats, which accumulate as discrete nuclear foci, and this is thought to prevent its function in the regulation of alternative splicing of pre-mRNAs. There is strong evidence for the role of the MBNL1 gene in disease pathology, but the roles of two related genes, MBNL2 and MBNL3, are less clear. Using new monoclonal antibodies specific for each of the three gene products , we found that MBNL2 decreased during human fetal development and myoblast culture , while MBNL1 was unchanged. In Duchenne muscular dystrophy muscle , MBNL2 was elevated in immature , regenerating fibres compared with mature fibres , supporting some developmental role for MBNL2. MBNL3 was found only in C2C12 mouse myoblasts. Both MBNL1 and MBNL2 were partially sequestered by nuclear foci of expanded repeats in adult muscle and cultured cells from myotonic dystrophy patients. In adult muscle nucleoplasm , both proteins were reduced in myotonic dystrophy type 1 compared with an age-matched control. In normal human myoblast cultures , MBNL1 and MBNL2 always co-distributed but their distribution could change rapidly from nucleoplasmic to cytoplasmic. Myotonic dystrophy type 1 (DM1) is a progressive multisystemic disorder showing considerable clinical variation between individuals. DM1 is characterized by skeletal muscle weakness, wasting and pain, as well as myotonia.1 Other symptoms may include cardiac arrhythmias, cataracts, insulin resistance, hypogonadism, neurological problems and premature male balding.1-4 The genetic mutation responsible for DM1 has been identified as the expansion of a CTG repeat in exon 15 in the 3Ј-untranslated region of the DM protein kinase (DMPK) gene on chromosome 19q13.3. [5][6][7] The largest germline expansions occur during maternal transmission but the length of repeats may also increase somatically in affected individuals. 8 The size of the CTG expansion is related to the disease severity. More than 50 CTG repeats cause mild to classical adult-onset DM and 700 to greater than 3000 repeats often result in the severe congenital form of the disease. However, repeat size in muscle and other tissues can be much higher than in lymphocytes.9 A second form of DM (DM2) is due to a CCTG repeat in intron 1 of the ZNF9 gene on chromosome 3q21.3. 10Clinical features of DM1 and DM2 are similar but not identical. DM2 patients may show proximal rather than distal muscle involvement, and the severe congenital form occurs in DM1 only. The number of repeats in DM2 may be 10-fold greater than in DM1.

FTO gene polymorphisms are associated with obesity and food intake. This study aimed to investigate the association of FTO rs9939609 polymorphism genotypes with serum glucose, lipid profile and serum hormones level. This cross-sectional study was carried out on 196 randomly selected overweight adults. Anthropometric measurements including weight, height, body mass index (BMI), fat mass, and fat-free mass were assessed. Serum TGs, total cholesterol, HDL cholesterol, LDL cholesterol, glucose and insulin levels were measured. The FTO gene was Genotyped for rs9939609 polymorphism. Dietary intake was assessed by avalid 168-item semiquantitative food frequency questionnaire (FFQ). The homozygotes for the FTO rs9939609 risk allele (A) had higher serum leptin (p = 0.005, F: 5.131) and lower HDL (p = 0.001, F: 7.687) level than TT genotype. The differences between TT and AT genotypes were not significant. The association remained significant for HDL level after adjustments for age and sex, calorie intake, physical activity, and BMI. The association between rs9939609 polymorphism genotypes and leptin was disappeared after adjustments for calorie intake and physical activity. In conclusion, rs9939609 risk allele was associated with higher serum leptin and lower HDL levels in overweight people. Further studies are warranted. ARTICLE HISTORY

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Hydatidiform mole is an aberrant human pregnancy characterized by early embryonic arrest and excessive trophoblastic proliferation. Recurrent hydatidiform moles are defined by the occurrence of at least two hydatidiform moles in the same patient. Fifty to eighty percent of patients with recurrent hydatidiform moles have biallelic pathogenic variants in NLRP7 or KHDC3L. However, in the remaining patients, the genotypic types of the moles are unknown. We characterized 80 new hydatidiform mole tissues, 57 of which were from patients with no mutations in the known genes, and we reviewed the genotypes of a total of 123 molar tissues. We also reviewed mutation analysis in 113 patients with recurrent hydatidiform moles. While all hydatidiform moles from patients with biallelic NLRP7 or KHDC3L mutations are diploid biparental, we demonstrate that those from patients without mutations are highly heterogeneous and only a small minority of them are diploid biparental (8%). The other mechanisms that were found to recur in patients without mutations are diploid androgenetic monospermic (24%) and triploid dispermic (32%); the remaining hydatidiform moles were misdiagnosed as moles due to errors in the analyses and/or their unusual mechanisms. We compared three parameters of genetic susceptibility in patients with and without mutations and show that patients without mutations are mostly from non-familial cases, have fewer reproductive losses, and more live births. Our data demonstrate that patients with recurrent hydatidiform moles and no mutations in the known genes are, in general, different from those with mutations; they have a milder genetic susceptibility and/or a multifactorial etiology underlying their recurrent hydatidiform moles. Categorizing these patients according to the genotypic types of their recurrent hydatidiform moles may facilitate the identification of novel genes for this entity.