Genome-wide analysis of N1-methyl-adenosine modification in human tRNAs

The N¹-methyl-Adenosine (m¹A58) modification at the conserved nucleotide 58 in the TΨC loop is present in most eukaryotic tRNAs. In yeast, m¹A58 modification is essential for viability because it is required for the stability of the initiator-tRNA^Met. However, m¹A58 modification is not required for the stability of several other tRNAs in yeast. This differential m¹A58 response for different tRNA species raises the question of whether some tRNAs are hypomodified at A58 in normal cells, and how hypomodification at A58 may affect the stability and function of tRNA. Here, we apply a genomic approach to determine the presence of m¹A58 hypomodified tRNAs in human cell lines and show how A58 hypomodification affects stability and involvement of tRNAs in translation. Our microarray-based method detects the presence of m¹A58 hypomodified tRNA species on the basis of their permissiveness in primer extension. Among five human cell lines examined, approximately one-quarter of all tRNA species are hypomodified in varying amounts, and the pattern of the hypomodified tRNAs is quite similar. In all cases, no hypomodified initiator-tRNA^Met is detected, consistent with the requirement of this modification in stabilizing this tRNA in human cells. siRNA knockdown of either subunit of the m¹A58-methyltransferase results in a slow-growth phenotype, and a marked increase in the amount of m¹A58 hypomodified tRNAs. Most m¹A58 hypomodified tRNAs can associate with polysomes in varying extents. Our results show a distinct pattern for m¹A58 hypomodification in human tRNAs, and are consistent with the notion that this modification fine tunes tRNA functions in different contexts.     

Pulsed Regime of the Diffusive Mode of a Barrier Discharge in Helium

Periodic pulsations of the active current component are revealed experimentally in transversely homogeneous barrier discharges in helium at small values of the parameter Pd (below 500 torr mm) and moderate frequencies of the applied voltage (f < 100 kHz). The frequency of the current pulsations is higher than the frequency of the well-studied pulsations in a transversely inhomogeneous streamer barrier discharge in air by a factor of approximately 100. Numerical calculations show that the physical nature of the observed pulsations can be explained in terms of the negative differential resistance of the cathode fall region, which occupies essentially the entire interelectrode gap in each half-period of the applied voltage.     

Multiple species of wild tree peonies gave rise to the ‘king of flowers’, Paeonia suffruticosa Andrews

The origin of cultivated tree peonies, known as the ‘king of flowers'' in China for more than 1000 years, has attracted considerable interest, but remained unsolved. Here, we conducted phylogenetic analyses of explicitly sampled traditional cultivars of tree peonies and all wild species from the shrubby section Moutan of the genus Paeonia based on sequences of 14 fast-evolved chloroplast regions and 25 presumably single-copy nuclear markers identified from RNA-seq data. The phylogeny of the wild species inferred from the nuclear markers was fully resolved and largely congruent with morphology and classification. The incongruence between the nuclear and chloroplast trees suggested that there had been gene flow between the wild species. The comparison of nuclear and chloroplast phylogenies including cultivars showed that the cultivated tree peonies originated from homoploid hybridization among five wild species. Since the origin, thousands of cultivated varieties have spread worldwide, whereas four parental species are currently endangered or on the verge of extinction. The documentation of extensive homoploid hybridization involved in tree peony domestication provides new insights into the mechanisms underlying the origins of garden ornamentals and the way of preserving natural genetic resources through domestication.     

Diverse phylogeny and morphology of magnetite biomineralized by magnetotactic cocci

Magnetotactic bacteria (MTB) are diverse prokaryotes that produce magnetic nanocrystals within intracellular membranes (magnetosomes). Here, we present a large-scale analysis of diversity and magnetosome biomineralization in modern magnetotactic cocci, which are the most abundant MTB morphotypes in nature. Nineteen novel magnetotactic cocci species are identified phylogenetically and structurally at the single-cell level. Phylogenetic analysis demonstrates that the cocci cluster into an independent branch from other Alphaproteobacteria MTB, that is, within the Etaproteobacteria class in the Proteobacteria phylum. Statistical analysis reveals species-specific biomineralization of magnetosomal magnetite morphologies. This further confirms that magnetosome biomineralization is controlled strictly by the MTB cell and differs among species or strains. The post-mortem remains of MTB are often preserved as magnetofossils within sediments or sedimentary rocks, yet paleobiological and geological interpretation of their fossil record remains challenging. Our results indicate that magnetofossil morphology could be a promising proxy for retrieving paleobiological information about ancient MTB.     

Studies on the trehalose-phosphate synthase of Mycobacterium smegmatis: binding of heparin to the enzyme

We have studied the binding of azide ion to ferrihemoglobin in various water/ethylene glycol mixtures. The results show that the thermodynamic parameters are strongly dependent on the mole fraction of ethylene glycol. This dependence has been explained in terms of solvent effects and the transition between two forms of ferrihemoglobin stabilized in water and ethylene glycol.     

Kruppel‐like factor 4 improves obesity‐related nephropathy through increasing mitochondrial biogenesis and activities

Obesity is positively linked to multiple metabolic complications including renal diseases. Several studies have demonstrated Kruppel‐like factor 4 (KLF4) participated in renal dysfunction and structural disorders in acute kidney injuries, but whether it affected the process of chronic kidney diseases was unknown. Therefore, present study was to disclose the role of renal KLF4 in dietary‐induced renal injuries and underlying mechanisms in obesity. Through utilizing high‐fat diet‐fed mice and human renal biopsies, we provided the physiological roles of KLF4 in protecting against obesity‐related nephropathy. Decreased levels of renal KLF4 were positively correlated with dietary‐induced renal dysfunction, including increased levels of creatinine and blood urea nitrogen. Overexpression of renal KLF4 suppressed inflammatory response in palmitic acid‐treated mouse endothelial cells. Furthermore, overexpressed KLF4 also attenuated dietary‐induced renal functional disorders, abnormal structural remodelling and inflammation. Mechanistically, KLF4 maintained renal mitochondrial biogenesis and activities to combat obesity‐induced mitochondrial dysfunction. In clinical renal biopsies and plasma, the renal Klf4 level was negatively associated with circulating levels of creatinine but positively associated with renal creatinine clearance. In conclusions, the present findings firstly supported that renal KLF4 played an important role in combating obesity‐related nephropathy, and KLF4/mitochondrial function partially determined the energy homeostasis in chronic kidney diseases.     

Identification of novel susceptibility loci for non‐syndromic cleft lip with or without cleft palate

Although several genome‐wide association studies (GWAS) of non‐syndromic cleft lip with or without cleft palate (NSCL/P) have been reported, more novel association signals are remained to be exploited. Here, we performed an in‐depth analysis of our previously published Chinese GWAS cohort study with replication in an extra dbGaP case‐parent trios and another in‐house Nanjing cohort, and finally identified five novel significant association signals (rs11119445: 3’ of SERTAD4, P = 6.44 × 10⁻¹⁴; rs227227 and rs12561877: intron of SYT14, P = 5.02 × 10⁻¹³ and 2.80 × 10⁻¹¹, respectively; rs643118: intron of TRAF3IP3, P = 4.45 × 10⁻⁶; rs2095293: intron of NR6A1, P = 2.98 × 10⁻⁵). The mean (standard deviation) of the weighted genetic risk score (wGRS) from these SNPs was 1.83 (0.65) for NSCL/P cases and 1.58 (0.68) for controls, respectively (P = 2.67 × 10⁻¹⁶). Rs643118 was identified as a shared susceptible factor of NSCL/P among Asians and Europeans, while rs227227 may contribute to the risk of NSCL/P as well as NSCPO. In addition, sertad4 knockdown zebrafish models resulted in down‐regulation of sox2 and caused oedema around the heart and mandibular deficiency, compared with control embryos. Taken together, this study has improved our understanding of the genetic susceptibility to NSCL/P and provided further clues to its aetiology in the Chinese population.