SUMMARY IDH1 and IDH2 mutations occur frequently in gliomas and acute myeloid leukemia, leading to simultaneous loss and gain of activities in the production of α-ketoglutarate (α-KG) and 2-hydroxyglutarate (2-HG), respectively. Here we demonstrate that 2-HG is a competitive inhibitor of multiple α-KG-dependent dioxygenases, including histone demethylases and the TET family of 5-methlycytosine (5mC) hydroxylases. 2-HG occupies the same space as α-KG does in the active site of histone demethylases. Ectopic expression of tumor-derived IDH1 and IDH2 mutants inhibits histone demethylation and 5mC hydroxylation. In glioma, IDH1 mutations are associated with increased histone methylation and decreased 5-hydroxylmethylcytosine (5hmC). Hence, tumor-derived IDH1 and IDH2 mutations reduce α-KG and accumulate an α-KG antagonist, 2-HG, leading to genome-wide histone and DNA methylation alterations.

CRISPR/Cas9 genome targeting systems have been applied to a variety of species. However, most CRISPR/Cas9 systems reported for plants can only modify one or a few target sites. Here, we report a robust CRISPR/Cas9 vector system, utilizing a plant codon optimized Cas9 gene, for convenient and high-efficiency multiplex genome editing in monocot and dicot plants. We designed PCR-based procedures to rapidly generate multiple sgRNA expression cassettes, which can be assembled into the binary CRISPR/Cas9 vectors in one round of cloning by Golden Gate ligation or Gibson Assembly. With this system, we edited 46 target sites in rice with an average 85.4% rate of mutation, mostly in biallelic and homozygous status. We reasoned that about 16% of the homozygous mutations in rice were generated through the non-homologous end-joining mechanism followed by homologous recombination-based repair. We also obtained uniform biallelic, heterozygous, homozygous, and chimeric mutations in Arabidopsis T1 plants. The targeted mutations in both rice and Arabidopsis were heritable. We provide examples of loss-of-function gene mutations in T0 rice and T1 Arabidopsis plants by simultaneous targeting of multiple (up to eight) members of a gene family, multiple genes in a biosynthetic pathway, or multiple sites in a single gene. This system has provided a versatile toolbox for studying functions of multiple genes and gene families in plants for basic research and genetic improvement.

To date, the monsoon-research community has not yet reached a consensus on a unified definition of monsoon rainy season or on the linkage between the onsets over the Asian continent and the adjacent oceans. A single rainfall parameter is proposed, and a suite of universal criteria for defining the domain, onset, peak, and withdrawal of the rainy season are developed. These results reveal a cohesive spatial-temporal structure of the Asian-Pacific monsoon rainy season characteristics, which will facilitate validation of monsoon hydrological cycles simulated by climate system models and improve our understanding of monsoon dynamics. The large-scale onset of the Asian monsoon rainy season consists of two phases. The first phase begins with the rainfall surges over the South China Sea (SCS) in mid-May, which establishes a planetary-scale monsoon rainband extending from the south Asian marginal seas (the Arabian Sea, the Bay of Bengal, and the SCS) to the subtropical western North Pacific (WNP). The rainband then advances northwestward, initiating the continental Indian rainy season, the Chinese mei-yu, and the Japanese baiu in early to mid-June (the second phase). The heights of the rainy seasons occur primarily in three stepwise phases: in late June over the mei-yu/baiu regions, the northern Bay of Bengal, and the vicinity of the Philippines, in late July over India and northern China; and in mid-August over the tropical WNP. The rainy season retreats northward over east Asia, yet it moves southward over India and the WNP. Clear distinctions in the characteristics of the rainy season exist among the Indian, east Asian, and WNP summer monsoon regions. Nevertheless, the rainy seasons of the three subsystems also show close linkage. The causes of the regional distinctions and linkages are discussed. Also discussed are the atypical monsoon rainy seasons, such as the skewed and bimodal seasonal distributions found in various places of Asian monsoon domain.

Analyses of 50-yr NCEP-NCAR reanalysis data reveal remarkably different interannual variability between the Indian summer monsoon (ISM) and western North Pacific summer monsoon (WNPSM) in their temporalspatial structures, relationships to El Niño, and teleconnections with midlatitude circulations. Thus, two circulation indices are necessary, which measure the variability of the ISM and WNPSM, respectively. A weak WNPSM features suppressed convection along 10Њ-20ЊN and enhanced rainfall along the mei-yu/baiu front. So the WNPSM index also provides a measure for the east Asian summer monsoon. An anomalous WNPSM exhibits a prominent meridional coupling among the Australian high, cross-equatorial flows, WNP monsoon trough, WNP subtropical high, east Asian subtropical front, and Okhotsk high. The WNP monsoon has leading spectral peaks at 50 and 16 months, whereas the Indian monsoon displays a primary peak around 30 months. The WNPSM is weak during the decay of an El Niño, whereas the ISM tends to abate when an El Niño develops. Since the late 1970s, the WNPSM has become more variable, but its relationship with El Niño remained steady; in contrast, the ISM has become less variable and its linkage with El Niño has dramatically declined. These contrasting features are in part attributed to the differing processes of monsoon-ocean interaction.Also found is a teleconnection between a suppressed WNPSM and deficient summer rainfall over the Great Plains of the United States. This boreal summer teleconnection is forced by the heat source fluctuation associated with the WNPSM and appears to be established through excitation of Rossby wave trains and perturbation of the jet stream that further excites downstream optimum unstable modes.