The SRCAP chromatin remodeling complex promotes oxidative metabolism during prenatal heart development.

Mammalian heart development relies on cardiomyocyte mitochondrial maturation and metabolism. Embryonic cardiomyocytes make a metabolic shift from anaerobic glycolysis to oxidative metabolism by mid-gestation. VHL-HIF signaling favors anaerobic glycolysis but this process subsides by E14.5. Meanwhile, oxidative metabolism becomes activated but its regulation is largely elusive. Here, we first pinpointed a crucial temporal window for mitochondrial maturation and metabolic shift, and uncovered the pivotal role of the SRCAP chromatin remodeling complex in these processes in mouse. Disruption of this complex massively suppressed the transcription of key genes required for the tricarboxylic acid cycle, fatty acid ß-oxidation and ubiquinone biosynthesis, and destroyed respirasome stability. Furthermore, we found that the SRCAP complex functioned through H2A.Z deposition to activate transcription of metabolic genes. These findings have unveiled the important physiological functions of the SRCAP complex in regulating mitochondrial maturation and promoting oxidative metabolism during heart development, and shed new light on the transcriptional regulation of ubiquinone biosynthesis.

Natural variation in the promoter of rice calcineurin B-like protein10 (OsCBL10) affects flooding tolerance during seed germination among rice subspecies.

Rice (Oryza sativa L.) has two ecotypes, upland and lowland rice, that have been observed to show different tolerance levels under flooding stress. In this study, two rice cultivars, upland (Up221, flooding-intolerant) and lowland (Low88, flooding-tolerant), were initially used to study their molecular mechanisms in response to flooding germination. We observed that variations in the OsCBL10 promoter sequences in these two cultivars might contribute to this divergence in flooding tolerance. Further analysis using another eight rice cultivars revealed that the OsCBL10 promoter could be classified as either a flooding-tolerant type (T-type) or a flooding-intolerant type (I-type). The OsCBL10 T-type promoter only existed in japonica lowland cultivars, whereas the OsCBL10 I-type promoter existed in japonica upland, indica upland and indica lowland cultivars. Flooding-tolerant rice cultivars containing the OsCBL10 T-type promoter have shown lower Ca2+ flow and higher α-amylase activities in comparison to those in flooding-intolerant cultivars. Furthermore, the OsCBL10 overexpression lines were sensitive to both flooding and hypoxic treatments during rice germination with enhanced Ca2+ flow in comparison to wild-type. Subsequent findings also indicate that OsCBL10 may affect OsCIPK15 protein abundance and its downstream pathways. In summary, our results suggest that the adaptation to flooding stress during rice germination is associated with two different OsCBL10 promoters, which in turn affect OsCBL10 expression in different cultivars and negatively affect OsCIPK15 protein accumulation and its downstream cascade.

To unwind the biological knots: The DNA/RNA G-quadruplex resolvase RHAU (DHX36) in development and disease.

The G-quadruplex (G4) sequences are short fragments of 4-interval triple guanine (G) with frequent and ubiquitous distribution in the genome and RNA transcripts. The G4 sequences are usually folded into secondary "knot" structure via Hoogsteen hydrogen bond to exert negative regulation on a variety of biological processes, including DNA replication and transcription, mRNA translation, and telomere maintenance. Recent structural biological and mouse genetics studies have demonstrated that RHAU (DHX36) can bind and unwind the G4 "knots" to modulate embryonic development and postnatal organ function. Deficiency of RHAU gives rise to embryonic lethality, impaired organogenesis, and organ dysfunction. These studies uncovered the pivotal G4 resolvase function of RHAU to release the G4 barrier, which plays fundamental roles in development and physiological homeostasis. This review discusses the latest advancements and findings in deciphering RHAU functions using animal models.

[Effect of electroacupuncture combined with cutaneous "tongluo" stimulation on gastric electrical rhythms and gastromucosal prostaglandin content in rats with chronic atrophic gastritis ].

OBJECTIVE: To observe the effect of electroacupuncture (EA) combined with cutaneous "Tongluo" (meridian- dredging) stimulation on gastric electrical activities and gastromucosal prostaglandin (PG) level in rats with chronic atrophic gastritis (CAG), so as to investigate its mechanism underlying improvement of gastric function. METHODS: A total of 40 SD rats were randomly divided into blank control, CAG model, medication and combined therapy groups, with 10 rats being in each group. CAG model was established by. intragastric administration of deionized water with N-methyl-N '-nitro-N-nitrosoguanidine (MNNG) solution (5 mL/kg), once a day, in combination with alternate fasting and full-eating and lavage of 2% sodium salicylate and warm saline (15%) for 12 weeks. For rats of the combined therapy group, EA was applied to "Zusanli" (ST 36), "Zhong- wan" (CV 12), "Tianshu" (ST 25) and "Pishu" (BL 20), two acupoints for one session, followed by cutaneous "Tongluo" stimulation of ST 25 and BL 20 by using an intelligent Tongluo therapeutic instrument for 20 min, once daily for 2 months. Electrogas- trography (EGG) was recorded using an intelligent gastrointestinal electrographic instrument. Gastromucosal PGE2 and PGF2, contents were assayed by radioimmunoassay. RESULTS: compared to the control group, the mean frequency and amplitude of EGG, and gastromucosal PGE2 and PGF2a contents were obviously decreased while the abnormal rhythm index and frequency-variation- coefficiency levels were markedly increased in the model group (P<0. 01). Following treatment, the above-mentioned changes of the 6 indexes were significantly reversed by both medication and combined therapy (P<0. 01). No significant differences were found between the medication and combined therapy groups (P>0.05). CONCLUSION: Combined use of EA and intelligent Tongluo stimulation can significantly improve the gastroelectric dysrhythmia in CAG rats, which may be closely associated with its effect in up-regulating gastric mucosal PGE2 and PGF2, levels.