Complete non-proline backbone resonance assignments of the S. aureus neutrophil serine protease inhibitor, EapH1.

The S. aureus extracellular adherence protein (Eap) and its homologs, EapH1 and EapH2, serve roles in evasion of the human innate immune system. EapH1 binds with high-affinity and inhibits the neutrophil azurophilic granule proteases neutrophil elastase, cathepsin-G and proteinase-3. Previous structural studies using X-ray crystallography have shown that EapH1 binds to neutrophil elastase and cathepsin-G using a globally similar binding mode. However, whether the same holds true in solution is unknown and whether the inhibitor experiences dynamic changes following binding remains uncertain. To facilitate solution-phase structural and biochemical studies of EapH1 and its complexes with neutrophil granule proteases, we have characterized EapH1 by multidimensional NMR spectroscopy. Here we report a total of 100% of the non-proline backbone resonance assignments of EapH1 with BMRB accession number 50,304.

Using delayed decoupling to attenuate residual signals in editing filters.

Isotope filtering methods are instrumental in biomolecular nuclear magnetic resonance (NMR) studies as they isolate signals of chemical moieties of interest within complex molecular assemblies. However, isotope filters suppress undesired signals of isotopically enriched molecules through scalar couplings, and variations in scalar couplings lead to imperfect suppressions, as occurs for aliphatic and aromatic moieties in proteins. Here, we show that signals that have escaped traditional filters can be attenuated with mitigated sensitivity losses for the desired signals of unlabeled moieties. The method uses a shared evolution between the detection and preceding preparation period to establish non-observable antiphase coherences and eliminates them through composite pulse decoupling. We demonstrate the method by isolating signals of an unlabeled post-translational modification tethered to an isotopically enriched protein.

Mutational signatures associated with exposure to carcinogenic microplastic compounds bisphenol A and styrene oxide.

Microplastic pollutants in oceans and food chains are concerning to public health. Common plasticizing compounds Bisphenol-A (BPA) and Styrene-7,8-Oxide (SO) are now labeled as carcinogens. We show that BPA and SO cause deoxyribonucleic acid damage and mutagenesis in human cells, and analyze the genome-wide point mutation and genomic rearrangement patterns associated with BPA and SO exposure. A subset of the single- and doublet base substitutions shows mutagenesis near or at guanine, consistent with these compounds' preferences to form guanosine adducts. Presence of other mutational signatures suggest additional mutagenesis probably due to complex effects of BPA and SO on diverse cellular processes. Analyzing data for 19 cancer cohorts, we find that tumors of digestive and urinary organs show relatively high similarity in mutational profiles, and the burden of such mutations increases with age. Even within the same cancer type, proportions of corresponding mutational patterns vary among the cohorts from different countries, as does the amount of microplastic waste in ocean waters. BPA and SO are relatively mild mutagens, and other environmental agents can also potentially generate similar, complex mutational patterns in cancer genomes. Nonetheless, our findings call for systematic evaluation of public health consequences of microplastic exposure worldwide.

1H, 15N, and 13C backbone resonance assignments of the C4b-binding region from the S. aureus extracellular adherence protein.

The Extracellular Adherence Protein (Eap) from Staphylococcus aureus is a potent inhibitor of the classical and lectin pathways of the complement system. Previous studies have shown that Eap binds with nanomolar affinity to complement component C4b and prevents C4b binding the pro-protease, C2, thereby inhibiting formation of the pro-C3 convertase shared by the classical and lectin pathways (Woehl et al. in J Immunol 193:6161-6171, 2014). The C4b-binding and complement-inhibitory properties of Eap from S. aureus strain Mu50 lie within the two C terminal-most Eap domains (i.e. Eap34) (Woehl et al. J Immunol 193:6161-6171, 2014). Interestingly, Eap34 binds C4b with an apparent KD that is nearly 100-fold tighter than that of either Eap3 or Eap4 alone (Woehl et al. in Protein Sci 26:1595-1608, 2017). This suggests that linking these two domains into a single molecule is a significant determinant of Eap function. To better understand this property at the structural level, we undertook a solution NMR study of the ~ 23 kDa Eap34 protein. In this communication, we report that greater than 98% of the total non-proline backbone residues have been assigned. These data have been deposited in the BMRB database under the accession number 50210.

Larger-scale ocean-atmospheric patterns drive synergistic variability and world-wide volatility of wheat yields.

Diagnosing potential predictability of global crop yields in the near term is of utmost importance for ensuring food supply and preventing socio-economic consequences. Previous studies suggest that a substantial proportion of global wheat yield variability depends on local climate and larger-scale ocean-atmospheric patterns. The science is however at its infancy to address whether synergistic variability and volatility (major departure from the normal) of multi-national crop yields can be potentially predicted by larger-scale climate drivers. Here, using observed data on wheat yields for 85 producing countries and climate variability from 1961-2013, we diagnose that wheat yields vary synergistically across key producing nations and can also be concurrently volatile, as a function of shared larger-scale climate drivers. We use a statistical approach called robust Principal Component Analysis (rPCA), to decouple and quantify the leading modes (PC) of global wheat yield variability where the top four PCs explain nearly 33% of the total variance. Diagnostics of PC1 indicate previous year's local Air Temperature variability being the primary influence and the tropical Pacific Ocean being the most dominating larger-scale climate stimulus. Results also demonstrate that world-wide yield volatility has become more common in the current most decades, associating with warmer northern Pacific and Atlantic oceans, leading mostly to global supply shortages. As the world warms and extreme weather events become more common, this diagnostic analysis provides convincing evidence that concurrent variability and world-wide volatility of wheat yields can potentially be predicted, which has major socio-economic and commercial importance at the global scale, underscoring the urgency of common options in managing climate risk.

Data of variability and joint variability of global crop yields and their association with climate.

We present the output data of Robust Principal Component Analysis (RPCA) applied to global crop yield variability of maize, rice, sorghum and soybean (MRSS) as presented in the publication "Climate drives variability and joint variability of global crop yields" (Najafi et al., 2019). Global maps of the correlation between all the principal components (PCs) acquired from the low rank matrix (L) of MRSS and Palmer Drought Severity Index (PDSI), air temperature anomalies (ATa) and sea surface temperature anomalies (SSTa) are provided in this article. We present co-varying countries, impacted cropland areas across global countries, and 10 global regions by climate and the association between PCs and multiple atmospheric and oceanic indices. Moreover, the joint dependency between PCs of MRSS yields are presented using two different approaches.

A Peptide-Nanoparticle System with Improved Efficacy against Multidrug Resistant Bacteria.

The recent rise of multidrug resistant microbial strains requires development of new and novel therapeutic alternatives. In this study, we present a novel antibacterial system that comprises of modified naturally abundant antimicrobial peptides in conjugation with silver nanoparticles. Further, we propose a simple route to incorporate a cysteine residue either at the N- or C-terminal of the parent peptide. Tagging a cysteine residue at the terminals not only enhances the binding propensity of the resultant peptide with the silver nanoparticle, but also increases its antimicrobial property against several pathogenic bacterial strains including K. pneumoniae. The minimum inhibitory concentration (MIC) values of the cysteine tagged nanoconjugates were obtained in the range of 5-15 µM compared to 50 µM for peptides devoid of the cysteines. The origin and mechanism of such improved activity of the conjugates were investigated using NMR spectroscopy and molecular dynamics (MD) simulations. The application of 13C-isotope labelled media to track the metabolic lifecycle of E. coli cells provided further insights into the system. MD simulations showed that pore formation in membrane bilayer is mediated through a hydrophobic collapse mechanism. The design strategy described herein opens up new-avenues for using biocompatible nanomedicines as a potential alternative to conventional antibiotics.

Climate drives variability and joint variability of global crop yields.

In this study, long-term national-based yields of maize, rice, sorghum and soybean (MRSS) from 1961 to 2013 are decomposed using Robust Principal Component Analysis (RPCA). After removing outliers, the first three principal components (PC) of the persistent yield anomalies are scrutinized to assess their association with climate and to identify co-varying countries and crops. Sea surface temperature anomalies (SSTa), atmospheric and oceanic indices, air temperature anomalies (ATa) and Palmer Drought Severity Index (PDSI) are used to study the association between the PCs and climate. Results show that large-scale climate, especially El Niño-Southern Oscillation (ENSO) and North Atlantic Oscillation (NAO) are strongly correlated with crop yield variability. Extensive maize harvesting regions in Europe and North America, rice in South America, Oceania and east of Asia, sorghum in west and southeast of Asia, North America and Caribbean and soybean in North and South America, Oceania and south of Asia experienced the influence of local climate variability in this period. Sorghum yield variability across the globe exhibits significant correlations with many atmospheric and oceanic indices. Results indicate that not only do the same crops in many countries co-vary significantly, but different crops, in particular maize, in different PCs also co-vary with other crops. Identifying the association between climate and crop yield variability and recognizing similar and dissimilar countries in terms of yield fluctuations can be informative for the identified nations with regard to the periodic and predictable nature of many large-scale climatic patterns.

Enhanced stability and activity of an antimicrobial peptide in conjugation with silver nanoparticle.

The conjugation of nanoparticles with antimicrobial peptides (AMP) is emerging as a promising route to achieve superior antimicrobial activity. However, the nature of peptide-nanoparticle interactions in these systems remains unclear. This study describes a system consisting of a cysteine containing antimicrobial peptide conjugated with silver nanoparticles, in which the two components exhibit a dynamic interaction resulting in a significantly enhanced stability and biological activity compared to that of the individual components. This was investigated using NMR spectroscopy in conjunction with other biophysical techniques. Using fluorescence assisted cell sorting and membrane mimics we carried out a quantitative comparison of the activity of the AMP-nanoparticle system and the free peptide. Taken together, the study provides new insights into nanoparticle-AMP interactions at a molecular level and brings out the factors that will be useful for consideration while designing new conjugates with enhanced functionality.

Chiral discrimination of secondary alcohols and carboxylic acids by NMR spectroscopy.

The manuscript reports two novel ternary ion-pair complexes, which serve as chiral solvating agents, for enantiodiscrimination of secondary alcohols and carboxylic acids. The protocol for discrimination of secondary alcohols is designed by using one equivalent mixture each of enantiopure mandelic acid, 4-dimethylaminopyridine (DMAP) and a chiral alcohol. For discrimination of carboxylic acids, the ternary complex is obtained by one equivalent mixture each of enantiopure chiral alcohol, DMAP and a carboxylic acid. The designed protocols also permit accurate measurement of enantiomeric composition.

Unprecedented chemical transformation of semicarbazones mediated by Wilkinson's catalyst.

para-Nitrobenzaldehyde semicarbazone undergoes an unusual chemical transformation upon reaction with [Rh(PPh(3))(3)Cl] in the presence of trialkyl and dialkylamines (NR(2)R'; R = Et,(i)Pr, (n)Bu; R' = H or R' = R) via dissociation of the C-NH(2) bond and formation of a new C-NR(2) bond (where the NR(2) fragment is provided by the amine). The transformed semicarbazone ligand binds to rhodium as a dianionic C,N,O-donor to afford complexes of type [Rh(PPh(3))(2)(CNO-NR(2))Cl] (CNO-NR(2) = the coordinated semicarbazone ligand). Another group of semicarbazones (viz. salicylaldehyde semicarbazone, 2-hydroxyacetophenone semicarbazone, and 2-hydroxynaphthaldehyde semicarbazone) has also been observed to undergo a similar chemical transformation upon reaction with [Rh(PPh(3))(3)Cl] under similar experimental conditions as before, and these transformed semicarbazones bind to rhodium as dianionic O,N,O-donors affording complexes of the type [Rh(PPh(3))(2)(ONO(n)-NR(2))Cl] (ONO(n)-NR(2) = the coordinated semicarbazone ligand; n = 1-3). The structure of the [Rh(PPh(3))(2)(CNO-NEt(2))Cl] and [Rh(PPh(3))(2)(ONO(2)-NR(2))Cl] complexes has been determined. All the complexes show characteristic (1)H NMR signals. They also show intense absorptions in the visible and ultraviolet region. Cyclic voltammetry on the complexes shows an oxidative response within 0.52-0.97 V versus SCE and a reductive response within -1.00 to -1.27 V versus SCE, where both the responses are believed to be centered on the semicarbazone ligand.

Synthesis, Structure, and Properties of a Novel Heterooctametallic Complex Containing a Cyclic Ru4 Ni4 Core.

From two to five: A mononuclear Ru complex of salicylaldehyde thiosemicarbazone (H3 saltsc, 1), in which only two of the coordination sites of 1 participate in bonding ([Ru(bpy)2 (H2 saltsc)]ClO4 ), could be used to synthesize the cyclic complex cation [{Ru(bpy)2 (saltsc)}4 Ni4 ]4+ (bpy=2,2'-bipyridine). Its formation demonstrates that the Ru complex can act as an N,N,O donor ligand for the construction of polynuclear complexes.