Two-component systems mediate bacterial signal transduction, employing a membrane sensor kinase and a cytoplasmic response regulator (RR). Environmental sensing is typically coupled to gene regulation. Understanding how input stimuli activate kinase autophosphorylation remains obscure. The EnvZ/OmpR system regulates expression of outer membrane proteins in response to osmotic stress. To identify EnvZ conformational changes associated with osmosensing, we used HDXMS to probe the effects of osmolytes (NaCl, sucrose) on the cytoplasmic domain of EnvZ (EnvZ c ). Increasing osmolality decreased deuterium exchange localized to the four-helix bundle containing the autophosphorylation site (His 243 ). EnvZ c exists as an ensemble of multiple conformations and osmolytes favoured increased helicity. High osmolality increased autophosphorylation of His 243 , suggesting that these two events are linked. In-vivo analysis showed that the cytoplasmic domain of EnvZ was sufficient for osmosensing, transmembrane domains were not required. Our results challenge existing claims of robustness in EnvZ/ OmpR and support a model where osmolytes promote intrahelical H-bonding enhancing helix stabilization, increasing autophosphorylation and downstream signalling. The model provides a conserved mechanism for signalling proteins that respond to diverse physical and mechanical stimuli.

In the Supplementary Information section of the above paper, the mass/charge (m/z) values of peptides in Supplementary Tables S1 and S2 (for a subset of peptides with z > 1) were erroneously reported.An equationwas incorrectly used for computing the m/z (Eqn. 1).The correct equation is:where M is the mass of the peptide, m H þ is the mass of a proton (~1), and z is the charge state of the peptide.Use of equation 1 or 2 does not alter the m/z values of the singly charged species (z = 1) reported. However for peptides with z > 1, the correct mass/charge would be marginally greater. For instance, a peptide with a mass (M) of 1515.7212 Da and z = 2 will show a m/z value of 758.86 for the 2+ charged ion based on Eqn. 2, instead of 758.36 reported in Supplementary Table S1. This subtle shift in value of the mass/charge for a subset of the peptides due to the error is regretted.In the Supplementary Information to this Corrigendum, we provide the corrected tables. These errors in computed m/z values do not alter any of the results, conclusions, or findings originally presented in the main paper or Supplementary Information. The subtle shift in m/z values does not change the peptide identification or alter the deuterium exchange values calculated for all the peptides across all m/z listed in the tables.

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Although the antidiabetic efficacy of Nyctanthes arbor-tristis flowers has been reported, antiproliferative and anti-obesity activities are yet to be explored. We examined the anti-obesity and antiproliferative potentials of different fractions (hexane, chloroform, ethyl acetate, methanol) of N. abor-tristis flower extract for the first time using 3T3-L1 cells, primary peripheral blood mononuclear cells (PBMC) isolated from healthy and adult acute myeloid (AML) and chronic lymphocytic leukemia (CLL) patients, recombinant Jurkat T cells, and MCF7 cell lines. The in vitro hypoglycemic activity was evaluated using the inhibition of α-amylase enzyme and glucose uptake by yeast cells. The percentage glucose uptake and α-amylase inhibitory activity increased in a dose-dependent manner in the crude and the tested fractions (hexane and ethyl acetate). Inhibition of the 3T3-L1 cells’ differentiation was observed in the ethyl acetate and chloroform fractions, followed by the hexane fraction. Antiproliferative analyses revealed that Nyctanthes exerted a high specific activity against anti-AML and anti-CLL PBMC cells, especially by the hexane and ethyl acetate fractions. The gas chromatography/mass spectrometry analysis indicated the presence of 1-heptacosanol (hexane fraction), 1-octadecene (hexane and chloroform fractions), and other organic compounds. Molecular docking demonstrated that phenol,2,5-bis(1,1-dimethylethyl) and 4-hydroxypyridine 1-oxide compounds showed specificity toward survivin protein, indicating the feasibility of N. abor-tristis in developing new drug leads against leukemia.

Protein cofactors represent a unique class of redox active posttranslational protein modifications formed in or by metalloproteins. Once formed, protein cofactors provide a one-electron oxidant, which is tethered to the protein backbone. Twenty-five proteins are known to contain protein cofactors, but this number is likely limited by the use of crystallography as the identification technique. In order to address this limitation, a search of all reported protein structures for chemical environments conducive to forming a protein cofactor through tyrosine and cysteine side chain crosslinking yielded three hundred candidate proteins. Using hydrogen bonding and metal center proximity, the three hundred proteins were narrowed to four highly viable candidates. An orphan metalloprotein (BF4112) was examined to validate this methodology, which identifies proteins capable of crosslinking tyrosine and cysteine sidechains. A tyrosine-cysteine crosslink was formed in BF4112 using copper-dioxygen chemistry, as in galactose oxidase. Liquid chromatography-MALDI mass spectrometry and optical spectroscopy confirmed tyrosine-cysteine crosslink formation in BF4112. This finding demonstrates the efficacy of these predictive methods and the minimal constraints, provided by the BF4112 protein structure, in tyrosine-cysteine crosslink formation. This search method, when coupled with physiological evidence for crosslink formation and function as a cofactor, could identify additional protein-derived cofactors.

Syzygium caryophyllatum L. Alston (Family: Myrtaceae, Sinhala: Heendan) is a red-listed plant that has been used in traditional medicine in Sri Lanka for the treatment of diabetes, but it is yet to be exploited for its potential uses as a functional food or a source of supplements. The present study focused on the evaluation of antidiabetic property of S. caryophyllatum fruits and leaves assessing antioxidant, antiglycation, and antiamylase activities and functional mineral element composition. The crude extracts (CR) of leaves and fruits were fractionated into hexane (Hex) ethyl acetate (EA) and aqueous (AQ) and evaluated for bioactivities along with the crude extracts. The isolated fraction (C3) of Hex fraction of fruit showed significantly high (p<0.05) antiamylase activity with IC50 value 2.27 ± 1.81 μg/mL where the Hex fraction of fruits exhibited the IC50 value as 47.20 ± 0.3 μg/mL which was higher than acarbose (IC50: 87.96 ± 1.43 μg/mL). The EA fraction of leaves showed highest values for DPPH radical scavenging activity, ferric reducing antioxidant power, and oxygen radical absorbance capacity. Significantly high (p<0.05) ABTS radical scavenging activity and iron chelating activity were observed in Hex fraction of fruit. The composition of volatiles in leaf oil was studied with GC-MS, and 58 compounds were identified. Inductively coupled plasma-mass spectrometry data revealed the presence of biologically significant trace elements such as Fe, Zn, Mg, Cu, Se, and Sr in leaves and fruits. It is concluded that the Hex fraction of S. caryophyllatum fruits will be a good source for the formulation of supplements for diabetic management with further evaluation of potency and efficacy.

Recent scientific breakthroughs in the field of agriculture have led to the abundant usage of nanoparticles in agrochemicals to maintain proper nutrient uptake in plants. Since less attention has been given to the supply of vital micronutrients to crop plants, the objective of this study was to develop a nanofertilizer capable of releasing micronutrients while nourishing its surrounding soil. As the initial nanonutrients, Zn and Cu were used in their metal oxide forms, which promote seed germination. Alginic acid was used as the agent responsible for soil conditioning. To form the fertilizing complex, nanoparticles were reacted with sodium alginate, which resulted in a hydrogel where alginate chains were cross-linked with Zn(II) and Cu(II) and excess metal oxide nanoparticles were distributed on the hydrogel. Spectroscopic characterization of the nanofertilizer confirmed that alginate chains were cross-linked by Zn(II) and Cu(II), while morphological analysis by scanning electron microscopy (SEM) showed that ZnO and CuO nanoparticles were embedded on the alginate matrix. The release behavior of cations in soil and water environments, experimented using the tea bag method, revealed that the cationic release was slowly increasing with time. Micronutrient uptake by plants was studied by conducting leaf analyses in tomato plants for 30 consecutive days. To experiment the release behavior of micronutrients in the presence of compost, the nanofertilizer was added with predetermined amounts of compost to tomato plants. Flame atomic absorption spectroscopy (FAAS) results indicated that in the fertilizer-applied plants, Cu concentrations showed a steady increase with time while Zn concentrations remained undetected.

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