Tip off the HAT– Epigenetic control of learning and memory by Drosophila Tip60

Disruption of epigenetic gene control mechanisms involving histone acetylation in the brain causes cognitive impairment, a debilitating hallmark of most neurodegenerative disorders. Histone acetylation regulates cognitive gene expression via chromatin packaging control in neurons. Unfortunately, the histone acetyltransferases (HATs) that generate such neural epigenetic signatures and their mechanisms of action remain unclear. Our recent findings provide insight into this question by demonstrating that Tip60 HAT action is critical for morphology and function of the mushroom body (MB), the learning and memory center in the Drosophila brain. We show that Tip60 is robustly produced in MB Kenyon cells and extending axonal lobes and that targeted MB Tip60 HAT loss results in axonal outgrowth disruption. Functional consequences of loss and gain of Tip60 HAT levels in the MB are evidenced by defects in memory. Tip60 ChIP-Seq analysis reveals enrichment for genes that function in cognitive processes and accordingly, key genes representing these pathways are misregulated in the Tip60 HAT mutant fly brain. Remarkably, increasing levels of Tip60 in the MB rescues learning and memory deficits resulting from Alzheimer''s disease associated amyloid precursor protein (APP) induced neurodegeneration. Our studies highlight the potential of HAT activators as a therapeutic option for cognitive disorders.     

Structural modulation of gut microbiota during alleviation of type 2 diabetes with a Chinese herbal formula

The gut microbiota is hypothesized to have a critical role in metabolic diseases, including type 2 diabetes (T2D). A traditional Chinese herbal formula, Gegen Qinlian Decoction (GQD), can alleviate T2D. To find out whether GQD modulates the composition of the gut microbiota during T2D treatment, 187 T2D patients were randomly allocated to receive high (HD, n=44), moderate (MD, n=52), low dose GQD (LD, n=50) or the placebo (n=41) for 12 weeks in a double-blinded trial. Patients who received the HD or MD demonstrated significant reductions in adjusted mean changes from baseline of fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) compared with the placebo and LD groups. Pyrosequencing of the V3 regions of 16S rRNA genes revealed a dose-dependent deviation of gut microbiota in response to GQD treatment. This deviation occurred before significant improvement of T2D symptoms was observed. Redundancy analysis identified 47 GQD-enriched species level phylotypes, 17 of which were negatively correlated with FBG and 9 with HbA1c. Real-time quantitative PCR confirmed that GQD significantly enriched Faecalibacterium prausnitzii, which was negatively correlated with FBG, HbA1c and 2-h postprandial blood glucose levels and positively correlated with homeostasis model assessment of β-cell function. Therefore, these data indicate that structural changes of gut microbiota are induced by Chinese herbal formula GQD. Specifically, GQD treatment may enrich the amounts of beneficial bacteria, such as Faecalibacterium spp. In conclusion, changes in the gut microbiota are associated with the anti-diabetic effects of GQD.     

1H-NMR and MS Based Metabolomics Study of the Intervention Effect of Curcumin on Hyperlipidemia Mice Induced by High-Fat Diet

Curcumin, a principle bioactive component of Curcuma longa L, is well known for its anti-hyperlipidemia effect. However, no holistic metabolic information of curcumin on hyperlipidemia models has been revealed, which may provide us an insight into the underlying mechanism. In the present work, NMR and MS based metabolomics was conducted to investigate the intervention effect of curcumin on hyperlipidemia mice induced by high-fat diet (HFD) feeding for 12 weeks. The HFD induced animals were orally administered with curcumin (40, 80 mg/kg) or lovastatin (30 mg/kg, positive control) once a day during the inducing period. Serum biochemistry assay of TC, TG, LDL-c, and HDL-c was conducted and proved that treatment of curcumin or lovastatin can significantly improve the lipid profiles. Subsequently, metabolomics analysis was carried out for urine samples. Orthogonal Partial Least Squares-Discriminant analysis (OPLS-DA) was employed to investigate the anti-hyperlipidemia effect of curcumin and to detect related potential biomarkers. Totally, 35 biomarkers were identified, including 31 by NMR and nine by MS (five by both). It turned out that curcumin treatment can partially recover the metabolism disorders induced by HFD, with the following metabolic pathways involved: TCA cycle, glycolysis and gluconeogenesis, synthesis of ketone bodies and cholesterol, ketogenesis of branched chain amino acid, choline metabolism, and fatty acid metabolism. Besides, NMR and MS based metabolomics proved to be powerful tools in investigating pharmacodynamics effect of natural products and underlying mechanisms.     

Rice blast resistance gene Pikahei-1(t), a member of a resistance gene cluster on chromosome 4, encodes a nucleotide-binding site and leucine-rich repeat protein

Pikahei-1(t) is the strongest quantitative trait locus (QTL) for blast resistance in upland rice cv. Kahei, which has strong field resistance to the rice blast disease. A high-quality bacterial artificial chromosome library was used to fine-map Pikahei-1(t) within ~300 kb on the 31-Mb region on rice chromosome 4. Of the 42 predicted open reading frames, seven resistance gene analogs (RGAs) with the nucleotide-binding site and leucine-rich repeat (NBS-LRR) domain were identified. Among these, RGA1, 2, 3, 5, and 7, but not RGA4 and 6, were found to be expressed in Kahei and monogenic lines containing Pikahei-1(t). Blast inoculation of transgenic rice lines carrying the genomic fragment of each RGA revealed that only RGA3 was associated with blast resistance. On the basis of these results, we concluded that RGA3 is the Pikahei-1(t) and named it Pi63. Pi63 encoded a typical coiled-coil-NBS-LRR protein and showed isolate-specificity. These results suggest that Pi63 behaves like a typical Resistance (R) gene, and the strong and broad-spectrum resistance of Kahei is dependent on natural pyramiding of multiple QTLs. The blast resistance levels of Pi63 were closely correlated with its gene expression levels, indicating a dose-dependent response of Pi63 function in rice resistance. Pi63 is the first cloned R gene in the R gene cluster on rice chromosome 4, and its cloning might facilitate genomic dissection of this cluster region.     

Coexistence of nitrifiers, denitrifiers and Anammox bacteria in a sequencing batch biofilm reactor as revealed by PCR-DGGE

Aims:  The bacterial diversity in a sequencing batch biofilm reactor (SBBR) treating landfill leachate was studied to explain the mechanism of nitrogen removal.
Methods and Results:  The total microbial DNA was extracted from samples collected from landfill leachate and biofilm of the reactor with the removal efficiencies of NH₄⁺-N higher than 97% and that of chemical oxygen demand (determined by K₂Cr₂O₇, COD_Cr) higher than 86%. Denaturing gradient gel electrophoresis (DGGE) fingerprints based on total community 16S rRNA genes were analyzed with statistical methods, and excised DNA bands were sequenced. The results of phylogenetic analyses revealed high diversity within the SBBR biofilm community, and DGGE banding patterns showed that the community structure in the biofilm remained stable during the running period.
Conclusions:  A coexistence of nitrifiers, including ammonia-oxidizing bacteria and nitrite-oxidizing bacteria, denitrifiers, including aerobic or anaerobic denitrifying bacteria and Anammox bacteria were detected, which might be the real matter of high removal efficiencies of NH₄⁺-N and COD_Cr in the reactor.
Significance and Impact of the Study:  The findings in this study indicated that PCR-DGGE analysis could be used for microbial community detection as prior method, and the SBBR technique could provide preferable growing environment for bacteria with N removal function.     

Molecular mapping of stripe rust resistance gene YrCH42 in Chinese wheat cultivar Chuanmai 42 and its allelism with Yr24 and Yr26

Stripe rust, caused by Puccinia striiformis f. sp. tritici (PST), is one of the most devastating diseases in common wheat (Triticum aestivum L.) worldwide. The objectives of this study were to map a stripe rust resistance gene in Chinese wheat cultivar Chuanmai 42 using molecular markers and to investigate its allelism with Yr24 and Yr26. A total of 787 F₂ plants and 186 F₃ lines derived from a cross between resistant cultivar Chuanmai 42 and susceptible line Taichung 29 were used for resistance gene tagging. Also 197 F₂ plants from the cross Chuanmai 42×Yr24/3*Avocet S and 726 F₂ plants from Chuanmai 42×Yr26/3*Avocet S were employed for allelic test of the resistance genes. In all, 819 pairs of wheat SSR primers were used to test the two parents, as well as resistant and susceptible bulks. Subsequently, nine polymorphic markers were employed for genotyping the F₂ and F₃ populations. Results indicated that the stripe rust resistance in Chuanmai 42 was conferred by a single dominant gene, temporarily designated YrCH42, located close to the centromere of chromosome 1B and flanked by nine SSR markers Xwmc626, Xgwm273, Xgwm11, Xgwm18, Xbarc137, Xbarc187, Xgwm498, Xbarc240 and Xwmc216. The resistance gene was closely linked to Xgwm498 and Xbarc187 with genetic distances of 1.6 and 2.3 cM, respectively. The seedling tests with 26 PST isolates and allelic tests indicated that YrCH42, Yr24 and Yr26 are likely to be the same gene.G.Q. Li and Z.F. Li contributed equally to the work.     

AFLP-derived SCARs facilitate construction of a 1.1 Mb sequence-ready map of a region that spans the Vf locus in the apple genome

The availability of high-density anchored markers is a prerequisite for reliable construction of a deep coverage BAC contig, which leads to creation of a sequence-ready map in the target chromosomal region. Unfortunately, such markers are not available for most plant species, including woody perennial plants. Here, we report on an efficient approach to build a megabase-size sequence-ready map in the apple genome for the Vf region containing apple scab resistance gene(s) by targeting AFLP-derived SCAR markers to this specific genomic region. A total of 11 AFLP-derived SCAR markers, previously tagged to the Vf locus, along with three other Vf-linked SCAR markers have been used to screen two apple genome BAC libraries. A single BAC contig which spans the Vf region at a physical distance of approximately 1,100 kb has been constructed by assembling the recovered BAC clones, followed by closure of inter-contig gaps. The contig is 4 ×deep, and provides a minimal tiling path of 16 contiguous and overlapping BAC clones, thus generating a sequence-ready map. Within the Vf region, duplication events have occurred frequently, and the Vf locus is restricted to the ca. 290 kb region covered by a minimum of three overlapping BAC clones.