Broad-spectrum cyclic boronate ß-lactamase inhibitors featuring an intramolecular prodrug for oral bioavailability.

Early efforts to broaden the spectrum and potency of cyclic boronic acid ß-lactamase inhibitor vaborbactam included a series of 7-membered ring boronates. Exploration of stereoisomers and incorporation of heteroatoms allowed identification of the all-carbon cyclic boronate with substituents trans as the preferred core structure, showing inhibition of Class A and C enzymes. Crystal structures of one analog bound to important ß-lactamase enzymes were obtained. When isolated under acidic conditions, these compounds spontaneously formed a neutral cyclic anhydride (intramolecular prodrug) which was shown to have much-improved oral bioavailability (52-69%) compared to the ring-opened carboxylate salt (9%).

Alterations in the leaf lipidome of Brassica carinata under high-temperature stress.

BACKGROUND: Brassica carinata (A) Braun has recently gained increased attention across the world as a sustainable biofuel crop. B. carinata is grown as a summer crop in many regions where high temperature is a significant stress during the growing season. However, little research has been conducted to understand the mechanisms through which this crop responds to high temperatures. Understanding traits that improve the high-temperature adaption of this crop is essential for developing heat-tolerant varieties. This study investigated lipid remodeling in B. carinata in response to high-temperature stress. A commercial cultivar, Avanza 641, was grown under sunlit-controlled environmental conditions in Soil-Plant-Atmosphere-Research (SPAR) chambers under optimal temperature (OT; 23/15°C) conditions. At eight days after sowing, plants were exposed to one of the three temperature treatments [OT, high-temperature treatment-1 (HT-1; 33/25°C), and high-temperature treatment-2 (HT-2; 38/30°C)]. The temperature treatment period lasted until the final harvest at 84 days after sowing. Leaf samples were collected at 74 days after sowing to profile lipids using electrospray-ionization triple quadrupole mass spectrometry. RESULTS: Temperature treatment significantly affected the growth and development of Avanza 641. Both high-temperature treatments caused alterations in the leaf lipidome. The alterations were primarily manifested in terms of decreases in unsaturation levels of membrane lipids, which was a cumulative effect of lipid remodeling. The decline in unsaturation index was driven by (a) decreases in lipids that contain the highly unsaturated linolenic (18:3) acid and (b) increases in lipids containing less unsaturated fatty acids such as oleic (18:1) and linoleic (18:2) acids and/or saturated fatty acids such as palmitic (16:0) acid. A third mechanism that likely contributed to lowering unsaturation levels, particularly for chloroplast membrane lipids, is a shift toward lipids made by the eukaryotic pathway and the channeling of eukaryotic pathway-derived glycerolipids that are composed of less unsaturated fatty acids into chloroplasts. CONCLUSIONS: The lipid alterations appear to be acclimation mechanisms to maintain optimal membrane fluidity under high-temperature conditions. The lipid-related mechanisms contributing to heat stress response as identified in this study could be utilized to develop biomarkers for heat tolerance and ultimately heat-tolerant varieties.

Elevated carbon dioxide and drought modulate physiology and storage-root development in sweet potato by regulating microRNAs.

Elevated CO2 along with drought is a serious global threat to crop productivity. Therefore, understanding the molecular mechanisms plants use to protect these stresses is the key for plant growth and development. In this study, we mimicked natural stress conditions under a controlled Soil-Plant-Atmosphere-Research (SPAR) system and provided the evidence for how miRNAs regulate target genes under elevated CO2 and drought conditions. Significant physiological and biomass data supported the effective utilization of source-sink (leaf to root) under elevated CO2. Additionally, elevated CO2 partially rescued the effect of drought on total biomass. We identified both known and novel miRNAs differentially expressed during drought, CO2, and combined stress, along with putative targets. A total of 32 conserved miRNAs belonged to 23 miRNA families, and 25 novel miRNAs were identified by deep sequencing. Using the existing sweet potato genome database and stringent analyses, a total of 42 and 22 potential target genes were predicted for the conserved and novel miRNAs, respectively. These target genes are involved in drought response, hormone signaling, photosynthesis, carbon fixation, sucrose and starch metabolism, etc. Gene ontology and KEGG ontology functional enrichment revealed that these miRNAs might target transcription factors (MYB, TCP, NAC), hormone signaling regulators (ARF, AP2/ERF), cold and drought factors (corA), carbon metabolism (ATP synthase, fructose-1,6-bisphosphate), and photosynthesis (photosystem I and II complex units). Our study is the first report identifying targets of miRNAs under elevated CO2 levels and could support the molecular mechanisms under elevated CO2 in sweet potato and other crops in the future.

First Report of Tobacco streak virus Infecting Kenaf (Hibiscus cannabinus) in India.

The natural occurrence of Tobacco streak virus (TSV) in Hibiscus cannabinus was detected by enzyme-linked immunosorbent assay using an antiserum raised against TSV and reverse transcription polymerase chain reaction (PCR) using primers specific for the coat protein gene of the virus. Sequence analysis of the PCR products showed 99.6 and 99.5% of maximum identity at nucleotide and amino acid levels, respectively with TSV onion isolate from Kurnool (HM131490).This is the first report of the natural occurrence of TSV on kenaf in India.

Regulation of photosynthesis, fluorescence, stomatal conductance and water-use efficiency of cowpea (Vigna unguiculata [L.] Walp.) under drought.

Drought is the major abiotic stress factor that causes extensive losses to agriculture production worldwide. The objective of this study was to evaluate the dynamics of photosynthesis and water-use efficiency parameters in 15 cowpea genotypes under well-watered and drought condition. Photosynthesis (A) and chlorophyll fluorescence (Fv'/Fm') declined linearly with decreasing soil water content whereas intrinsic water-use efficiency (WUE) increased under drought stress, suggesting stomatal regulation was a major limitation to photosynthesis. However, under increasing drought conditions, increase in ratio of intercellular CO(2) to ambient CO(2) concentrations along with reduced WUE showed the role of non-stomatal limitation of photosynthesis. The resistant nature of Fv'/Fm' and electron transport rate under drought appeared to be important mechanisms for photoinhibition protection under drought stress. Oxidative stress was apparent due to drought-induced reduction in total chlorophyll and carotenoid which was accompanied with increased leaf wax contents. The accumulation of proline appeared to be in response of drought injury rather than a drought tolerance mechanism. A clear separation based on the genotypes site of origin among the genotypes for drought tolerance could not be established when analyzed using principal component analysis. The identified genotypes and physiological traits from this study may be useful for genetic engineering and breeding programs integrating drought adaptation in cowpea.