Diagnosis and genetic analysis of a case of Waardenburg syndrome type 2 with hypogonadotropic hypogonadism caused by SOX10 gene deletion.

Hypogonadotropic hypogonadism (HH) is a disease defined by dysfunction of the hypothalamic- pituitary-gonadal hormone axis, leading to low sex hormone levels and impaired fertility. HH with anosmia or hyposmia is known as Kallmann syndrome (KS). Waardenburg syndrome (WS) is a rare autosomal dominant genetic disorder characterized by sensorineural hearing loss and abnormal pigmentation. In this report, we collected the clinical data of a patient with hypogonadotropic hypogonadism and congenital hearing loss of unknown cause. The patient had no obvious secondary sexual characteristics development after puberty, and had a heterozygous deletion (at least 419 kb) in 22q13.1 region (Chr.22:38106433-38525560), which covered the SOX10 gene. The abnormalities were not found in gene sequencing analysis of both the parents and sister of the proband. By summarizing and analyzing the characteristics of this case, we further discussed the molecular biological etiological association between HH and WS type 2. This case also enriches the clinical data of subsequent genetic studies, and provides a reference for the diagnosis and treatment of such diseases.

Characterization of ZmCOLD1, novel GPCR-Type G Protein genes involved in cold stress from Zea mays L. and the evolution analysis with those from other species.

Maize is one of the most vital staple crops worldwide. G proteins modulate plentiful signaling pathways, and G protein-coupled receptor-type G proteins (GPCRs) are highly conserved membrane proteins in plants. However, researches on maize G proteins and GPCRs are scarce. In this study, we identified three novel GPCR-Type G Protein (GTG) genes from chromosome 10 (Chr 10) in maize, designated as ZmCOLD1-10A, ZmCOLD1-10B and ZmCOLD1-10C. Their amino acid sequences had high similarity to TaCOLD1 from wheat and OsCOLD1 from rice. They contained the basic characteristics of GTG/COLD1 proteins, including GPCR-like topology, the conserved hydrophilic loop (HL) domain, DUF3735 (domain of unknown function 3735) domain, GTPase-activating domain, and ATP/GTP-binding domain. Subcellular localization analyses of ZmCOLD1 proteins suggested that ZmCOLD1 proteins localized on plasma membrane (PM) and endoplasmic reticulum (ER). Furthermore, amino acid sequence alignment verified the conservation of the key 187th amino acid T in maize and other wild maize-relative species. Evolutionary relationship among plants GTG/COLD1 proteins family displayed strong group-specificity. Expression analysis indicated that ZmCOLD1-10A was cold-induced and inhibited by light. Together, these results suggested that ZmCOLD1 genes had potential value to improve cold tolerance and to contribute crops growth and molecular breeding.

Association of Interleukin-6 -174G/C Polymorphism with the Risk of Diabetic Nephropathy in Type 2 Diabetes: A Meta-analysis.

Previous studies reported the association between interleukin-6 (IL-6) -174G/C gene polymorphism and the risk of diabetic nephropathy in type 2 diabetes mellitus (T2DN). However, the results remain controversial. In the present study, we conducted a meta-analysis to further examine this relationship between IL-6-174G/C gene polymorphism and T2DN. Three databases (PubMed, SinoMed and ISI Web of Science) were used to search clinical case-control studies about IL-6-174G/C polymorphism and T2DN published until Apr. 14, 2018. Fixed- or random-effects models were used to calculate the effect sizes of odds ratio (OR) and 95% confidence intervals (95% CI). Moreover, subgroup analysis was performed in terms of the excretion rate of albuminuria. All the statistical analyses were conducted using Stata 12.0. A total of 11 case-control studies were included in this study, involving 1203 cases of T2DN and 1571 cases of T2DM without DN. Meta-analysis showed that there was an association between IL-6-174G/C polymorphism and increased risk of T2DN under the allelic and recessive genetic models (G vs. C: OR=1.10, 95%CI 1.03-1.18, P=0.006; GG vs. CC+GC: OR=1.11, 95%CI 1.02-1.21 P=0.016). In the subgroup analysis by albuminuria, a significant association of IL-6-174G/C polymorphism with risk of T2DN was noted in the microalbuminuria group under the recessive model (OR=1.54, 95% CI 1.02-2.32, _P=0.038). In conclusion, this meta-analysis suggests that IL-6-174G/C gene polymorphism is associated with the risk of T2DN.

Liraglutide protects ß-cell function by reversing histone modification of Pdx-1 proximal promoter in catch-up growth male rats.

AIMS: Catch-up growth after a period of nutritional deprivation in adulthood is related to the onset of metabolic disorders. This process involves chromatin remodelling of the Pdx-1 gene in pancreas. The objective of this study was to determine the chromatin remodelling mechanism of GLP-1 analogue Liraglutide upon Pdx-1 in catch-up growth rats in vivo and in vitro. METHODS: Five-week-old male specific pathogen free (SPF) Wistar rats were randomly divided into normal group, catch-up growth group and Liraglutide group. Hyperglycemic clamp test and glucose-stimulated insulin secretion test were carried out to evaluate ß-cell function in vivo and in vitro. The histone H3 modification changes at the Pdx-1 proximal promoter were assessed by chromatin immunoprecipitation. RESULTS: The catch-up growth state was characterized by less recruitment of histone H3 lysine4 trimethylation and histone H3 acetylation and more recruitment of histone H3 lysine9 dimethylation at the Pdx-1 proximal promoter. Liraglutide treatment reversed these epigenetic changes and increased Pdx-1 expression, which could be abrogated by GLP-1 receptor antagonist Exendin 9-39. The ß-cell function of catch-up growth rats was improved after Liraglutide treatment. CONCLUSIONS: The protective effects of Liraglutide on pancreatic islet ß-cell function may be related to histone H3 modification at the Pdx-1 proximal promoter during catch-up growth and could be used to treat catch-up growth-related metabolic disorders.

ATX3, ATX4, and ATX5 Encode Putative H3K4 Methyltransferases and Are Critical for Plant Development.

Methylation of Lys residues in the tail of the H3 histone is a key regulator of chromatin state and gene expression, conferred by a large family of enzymes containing an evolutionarily conserved SET domain. One of the main types of SET domain proteins are those controlling H3K4 di- and trimethylation. The genome of Arabidopsis (Arabidopsis thaliana) encodes 12 such proteins, including five ARABIDOPSIS TRITHORAX (ATX) proteins and seven ATX-Related proteins. Here, we examined three until-now-unexplored ATX proteins, ATX3, ATX4, and ATX5. We found that they exhibit similar domain structures and expression patterns and are redundantly required for vegetative and reproductive development. Concurrent disruption of the ATX3, ATX4, and ATX5 genes caused marked reduction in H3K4me2 and H3K4me3 levels genome-wide and resulted in thousands of genes expressed ectopically. Furthermore, atx3/atx4/atx5 triple mutants resulted in exaggerated phenotypes when combined with the atx2 mutant but not with atx1 Together, we conclude that ATX3, ATX4, and ATX5 are redundantly required for H3K4 di- and trimethylation at thousands of sites located across the genome, and genomic features associated with targeted regions are different from the ATXR3/SDG2-controlled sites in Arabidopsis.

Dissipation of excess excitation energy of the needle leaves in Pinus trees during cold winters.

Photooxidative damage to the needle leaves of evergreen trees results from the absorption of excess excitation energy. Efficient dissipation of this energy is essential to prevent photodamage. In this study, we determined the fluorescence transients, absorption spectra, chlorophyll contents, chlorophyll a/b ratios, and relative membrane permeabilities of needle leaves of Pinus koraiensis, Pinus tabulaeformis, and Pinus armandi in both cold winter and summer. We observed a dramatic decrease in the maximum fluorescence (F m) and substantial absorption of light energy in winter leaves of all three species. The F m decline was not correlated with a decrease in light absorption or with changes in chlorophyll content and chlorophyll a/b ratio. The results suggested that the winter leaves dissipated a large amount of excess energy as heat. Because the cold winter leaves had lost normal physiological function, the heat dissipation depended solely on changes in the photosystem II supercomplex rather than the xanthophyll cycle. These findings imply that more attention should be paid to heat dissipation via changes in the photosystem complex structure during the growing season.