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-i nterval triple guanine(G)with frequent and ubiquitous distribution in the genome and RNA transcripts.The G4sequences 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.

Broad H3K4me3 as A Novel Epigenetic Signature for Normal Development and Disease

The breadth of the enrichment site for post-translational trimethylation of histone H3 at lysine 4 （H3K4me3） on chromatin has attracted great attention recently. H3K4me3, an extensively-studied histone modification, is reported to promote gene transcription by directing preinitiation complex assembly through interaction with effector proteins, e.g.,

Myelin in development and disease

Myelin is an evolutionarUy novel and important structure for the proper functioning of the vertebrate nervous system. In the central nervous system （CNS）, the myelin sheath is elaborated by oligodendrocytes, and is composed of multiple layers of specialized cell membrane wrapping around axons with periodic interruptions at the nodes of Ranvier. The major function of the myelin sheath is to provide ionic insulation to ensure rapid and saltatory conduction of electrical pulses along axons. In addition, myelin provides neurotrophic support for axons, as they become increasingly dependent on myelin-derived signals for survival. Despite the importance of myelin in the functioning of the CNS, oligodendrocytes are particularly susceptible to genetic and environmental perturbations, and demyelination can be triggered by many pathological conditions including traumatic injury, autoimmune disease （multiple sclerosis, MS）, heavy metal toxicity, and hypoxia. Loss of myelin sheaths in the CNS not only results in the compromised conduction of electrical signals, but also causes progressive degeneration of axons and ultimately neuronal loss. Spontaneous myelin repair from immature oligodendrocyte progenitor cells （OPCs） is not effective in demyelinating lesions, due either to the absence of stimulatory developmental signals that are no longer produced in the adult environment, or to the presence of inhibitory factors peculiar to this environment.

TGF-β and BMP signaling in osteoblast,skeletal development,and bone formation,homeostasis and disease

INTRODUCTIONThe transforming growth factor-β （TGF-β） superfamily com- prises TGF-βs, Activin, bone morphogenetic proteins （BMPs） and other related proteins. TGF-β superfamily members act through a heteromeric receptor complex,, comprised of type I and type II receptors at the cell surface that transduce intracellular signals via Smad complex or mitogen-activated protein kinase （MAPK） cascade.

Maternal low protein diet and fetal programming of lean type 2 diabetes

Maternal nutrition is found to be the key factor that determines fetal health in utero and metabolic health during adulthood.Metabolic diseases have been primarily attributed to impaired maternal nutrition during pregnancy,and impaired nutrition has been an immense issue across the globe.In recent years,type 2 diabetes(T2D)has reached epidemic proportion and is a severe public health problem in many countries.Although plenty of research has already been conducted to tackle T2D which is associated with obesity,little is known regarding the etiology and pathophysiology of lean T2D,a variant of T2D.Recent studies have focused on the effects of epigenetic variation on the contribution of in utero origins of lean T2D,although other mechanisms might also contribute to the pathology.Observational studies in humans and experiments in animals strongly suggest an association between maternal low protein diet and lean T2D phenotype.In addition,clear sex-specific disease prevalence was observed in different studies.Consequently,more research is essential for the understanding of the etiology and pathophysiology of lean T2D,which might help to develop better disease prevention and treatment strategies.This review examines the role of protein insufficiency in the maternal diet as the central driver of the developmental programming of lean T2D.

Comprehensive understanding of developmental origins of health and disease concepts: Early intervention to non-communicable diseases in China

Introduction Mortality due to various kinds of noncommunicable diseases (NCDs) has become an increasing focus of attention in recent years.1 With rapidly increasing globalization, lifestyles in low-and middle-income countries increasingly include high-fat diets and inadequate physical exercises are resulting in an increased worldwide burden of NCDs.2,3 A study by the International Diabetes Federation (IDF) showed that about 382 million people had diabetes in 2013, and this will rise to 592 million by 2035.The number of people with type 2 diabetes is increasing in every country, and 80％ of people with diabetes live in low-and middle-income countries.The burden of NCDs and the prevalence of related risk factors such asoverweight and diabetes have also increased in China over the past decades.In 2005, NCDs accounted for an estimated 80％ of deaths and 70％ of disability-adjusted life-years lost in China.