Race Ug99 of the fungus Puccinia graminis tritici that causes stem or black rust disease on wheat was first detected in Uganda in 1998. Seven races belonging to the Ug99 lineage are now known and have spread to various wheat-growing countries in the eastern African highlands, as well as Zimbabwe, South Africa, Sudan, Yemen, and Iran. Because of the susceptibility of 90% of the wheat varieties grown worldwide, the Ug99 group of races was recognized as a major threat to wheat production and food security. Its spread, either wind-mediated or human-aided, to other countries in Africa, Asia, and beyond is evident. Screening in Kenya and Ethiopia has identified a low frequency of resistant wheat varieties and breeding materials. Identification and transfer of new sources of race-specific resistance from various wheat relatives is underway to enhance the diversity of resistance. Although new Ug99-resistant varieties that yield more than current popular varieties are being released and promoted, major efforts are required to displace current Ug99 susceptible varieties with varieties that have diverse race-specific or durable resistance and mitigate the Ug99 threat.

We report the cloning of a gene, S2P, that encodes a putative metalloprotease required for intramembrane proteolysis of sterol-regulatory element-binding proteins (SREBPs) at Site-2. SREBPs are membrane-bound transcription factors that activate genes regulating cholesterol metabolism. The active NH2-terminal domains of SREBPs are released from membranes by sequential cleavage at two sites: Site-1, within the lumen of the endoplasmic reticulum; and Site-2, within a transmembrane segment. The human S2P gene was cloned by complementation of mutant CHO cells that cannot cleave SREBPs at Site-2 and are cholesterol auxotrophs. S2P defines a new family of polytopic membrane proteins that contain an HEXXH sequence characteristic of zinc metalloproteases. Mutation of the putative zinc-binding residues abolishes S2P activity. S2P encodes an unusual metalloprotease that cleaves proteins within transmembrane segments.

To analyze the function of the chromosomal kinase JIL-1, we generated an allelic series of hypomorphic and null mutations. JIL-1 is an essential kinase for viability, and reduced levels of JIL-1 kinase activity lead to a global change in chromatin structure. In JIL-1 hypomorphs, euchromatic regions of polytene chromosomes are severely reduced and the chromosome arms condensed. This is correlated with decreased levels of histone H3 Ser10 phosphorylation. These levels can be restored by a JIL-1 transgene placing JIL-1 directly in the pathway mediating histone H3 phosphorylation. We propose a model where JIL-1 kinase activity is required for maintaining the structure of the more open chromatin regions that facilitate gene transcription.

Oridonin (Ori) is the major active ingredient of the traditional Chinese medicinal herb Rabdosia rubescens and has anti-inflammatory activity, but the target of Ori remains unknown. NLRP3 is a central component of NLRP3 inflammasome and has been involved in a wide variety of chronic inflammation-driven human diseases. Here, we show that Ori is a specific and covalent inhibitor for NLRP3 inflammasome. Ori forms a covalent bond with the cysteine 279 of NLRP3 in NACHT domain to block the interaction between NLRP3 and NEK7, thereby inhibiting NLRP3 inflammasome assembly and activation. Importantly, Ori has both preventive or therapeutic effects on mouse models of peritonitis, gouty arthritis and type 2 diabetes, via inhibition of NLRP3 activation. Our results thus identify NLRP3 as the direct target of Ori for mediating Ori’s anti-inflammatory activity. Ori could serve as a lead for developing new therapeutics against NLRP3-driven diseases.

No abstract

Stem or black rust, caused by Puccinia graminis tritici, has historically caused severe losses to wheat (Triticum aestivum) production worldwide. Successful control of the disease for over three decades through the use of genetic resistance has resulted in a sharp decline in research activity in recent years. Detection and spread in East Africa of race TTKS, commonly known as Ug99, is of high significance as most wheat cultivars currently grown in its likely migration path, i.e. to North Africa through Arabian Peninsula and then to Middle East and Asia, are highly susceptible to this race and the environment is conducive to disease epidemics. Identifying/developing adapted resistant cultivars in a relatively short time and replacing the susceptible cultivars before rust migrates out of East Africa is the strategy to mitigate potential losses. Although several alien genes will provide resistance to this race, the long-term strategy should focus on rebuilding the 'Sr2-complex' (combination of slow rusting gene Sr2 with other unknown additive genes of similar nature) to achieve long-term durability. A Global Rust Initiative has been launched to monitor the further migration of this race, facilitate field testing in Kenya or Ethiopia of wheat cultivars and germplasm developed by wheat breeding programmes worldwide, understand the genetic basis of resistanceespecially the durable type, carry out targeted breeding to incorporate diverse resistance genes into key cultivars and germplasm, and enhance the capacity of national programmes. A few wheat genotypes that combine stem rust resistance with high yield potential and other necessary traits have been identified but need rigorous field testing to determine their adaptation in target areas.

Lectins possess unique binding properties and are of particular value in molecular recognition. However, lectins suffer from several disadvantages, such as being hard to prepare and showing poor storage stability. Boronate-affinity glycan-oriented surface imprinting was developed as a new strategy for the preparation of lectin-like molecularly imprinted polymers (MIPs). The prepared MIPs could specifically recognize an intact glycoprotein and its characteristic fragments, even within a complex sample matrix. Glycan-imprinted MIPs could thus prove to be powerful tools for important applications such as proteomics, glycomics, and diagnostics.

Immunoassay has been an essential tool in many areas, including clinical diagnostics. However, it suffers from drawbacks, such as poor availability of high specificity antibodies, limited stability of biological reagents, as well as damage to health and susceptibility of chemical labels to the sample environment. Here we present a new approach, a boronate-affinity sandwich assay (BASA), for the specific and sensitive determination of trace glycoproteins in complex samples. BASA relies on the formation of sandwiches between boronate-affinity molecularly imprinted polymers (MIPs), target glycoproteins, and boronate-affinity surface-enhanced Raman scattering (SERS) probes. The MIP ensures the specificity, while the SERS detection provides the sensitivity. BASA overcomes the drawbacks of traditional immunoassays and offers a great prospect for application.