A comprehensive quantification of global nitrous oxide sources and sinks.

Nitrous oxide (N2O), like carbon dioxide, is a long-lived greenhouse gas that accumulates in the atmosphere. Over the past 150 years, increasing atmospheric N2O concentrations have contributed to stratospheric ozone depletion1 and climate change2, with the current rate of increase estimated at 2 per cent per decade. Existing national inventories do not provide a full picture of N2O emissions, owing to their omission of natural sources and limitations in methodology for attributing anthropogenic sources. Here we present a global N2O inventory that incorporates both natural and anthropogenic sources and accounts for the interaction between nitrogen additions and the biochemical processes that control N2O emissions. We use bottom-up (inventory, statistical extrapolation of flux measurements, process-based land and ocean modelling) and top-down (atmospheric inversion) approaches to provide a comprehensive quantification of global N2O sources and sinks resulting from 21 natural and human sectors between 1980 and 2016. Global N2O emissions were 17.0 (minimum-maximum estimates: 12.2-23.5) teragrams of nitrogen per year (bottom-up) and 16.9 (15.9-17.7) teragrams of nitrogen per year (top-down) between 2007 and 2016. Global human-induced emissions, which are dominated by nitrogen additions to croplands, increased by 30% over the past four decades to 7.3 (4.2-11.4) teragrams of nitrogen per year. This increase was mainly responsible for the growth in the atmospheric burden. Our findings point to growing N2O emissions in emerging economies-particularly Brazil, China and India. Analysis of process-based model estimates reveals an emerging N2O-climate feedback resulting from interactions between nitrogen additions and climate change. The recent growth in N2O emissions exceeds some of the highest projected emission scenarios3,4, underscoring the urgency to mitigate N2O emissions.

Dynamic control of cascaded four-wave mixing via re-configurable dispersion.

We integrate a spatial light modulator-based dispersion controller into a cascaded four-wave mixing (CFWM) system. By tuning the group delay dispersion (GDD) and fourth-order dispersion (FOD) terms, we control the CFWM phase matching and demonstrate an output bandwidth tuning of over 3.3×. At the maximum bandwidth, our system covers the telecommunications S-, C-, and L-bands (1466-1641 nm) with an average output power of 300 mW, which is contained in 52 individual lines spaced 374 GHz apart. This method represents a reconfigurable alternative to photonic crystal fibers for dispersion engineering and allows for the use of step-index fiber and customizable power spectral density (PSD) profiles.

A 130-year global inventory of methane emissions from livestock: Trends, patterns, and drivers.

Livestock contributes approximately one-third of global anthropogenic methane (CH4 ) emissions. Quantifying the spatial and temporal variations of these emissions is crucial for climate change mitigation. Although country-level information is reported regularly through national inventories and global databases, spatially explicit quantification of century-long dynamics of CH4 emissions from livestock has been poorly investigated. Using the Tier 2 method adopted from the 2019 Refinement to 2006 IPCC guidelines, we estimated CH4 emissions from global livestock at a spatial resolution of 0.083° (~9 km at the equator) during the period 1890-2019. We find that global CH4 emissions from livestock increased from 31.8 [26.5-37.1] (mean [minimum-maximum of 95% confidence interval) Tg CH4 yr-1 in 1890 to 131.7 [109.6-153.7] Tg CH4 yr-1 in 2019, a fourfold increase in the past 130 years. The growth in global CH4 emissions mostly occurred after 1950 and was mainly attributed to the cattle sector. Our estimate shows faster growth in livestock CH4 emissions as compared to the previous Tier 1 estimates and is ~20% higher than the estimate from FAOSTAT for the year 2019. Regionally, South Asia, Brazil, North Africa, China, the United States, Western Europe, and Equatorial Africa shared the majority of the global emissions in the 2010s. South Asia, tropical Africa, and Brazil have dominated the growth in global CH4 emissions from livestock in the recent three decades. Changes in livestock CH4 emissions were primarily associated with changes in population and national income and were also affected by the policy, diet shifts, livestock productivity improvement, and international trade. The new geospatial information on the magnitude and trends of livestock CH4 emissions identifies emission hotspots and spatial-temporal patterns, which will help to guide meaningful CH4 mitigation practices in the livestock sector at both local and global scales.

Atomic-Scale Structure and Catalysis on Positively Charged Bimetallic Sites for Generation of H2.

Here, we report that a cationic bimetallic site consisting of one Pd and three Zn atoms (Pd1Zn3) supported on ZnO (Pd1Zn3/ZnO) exhibits an extraordinarily high catalytic activity for the generation of H2 through methanol partial oxidation (MPO) that is 2-3 orders of magnitude higher than that of a metallic Pd-Zn site on Pd-Zn nanoalloy (Pd-Zn/ZnO). Computational studies uncovered that the positively charged Pd atom of the subnanometer Pd1Zn3 bimetallic site largely decreases the activation barrier for dehydrogenation of methanol as compared to a metallic Pd atom of Pd-Zn alloy, thus switching the rate-determining step of MPO from methanol dehydrogenation over a Pd-Zn alloy with high barrier to the O2 dissociation step on a cationic Pd1Zn3 site with a low barrier, which is supported by our kinetics studies. The significantly higher catalytic activity and selectivity for H2 production over a cationic bimetallic site suggest a new approach to design bimetallic catalysts.

Suppressors of Cytokine Signaling (SOCS)1 and SOCS3 Proteins Are Mediators of Interleukin-10 Modulation of Inflammatory Responses Induced by Chlamydia muridarum and Its Major Outer Membrane Protein (MOMP) in Mouse J774 Macrophages.

The immunopathology of chlamydial diseases is exacerbated by a broad-spectrum of inflammatory mediators, which we reported are inhibited by IL-10 in macrophages. However, the chlamydial protein moiety that induces the inflammatory mediators and the mechanisms by which IL-10 inhibits them are unknown. We hypothesized that Chlamydia major outer membrane protein (MOMP) mediates its disease pathogenesis, and the suppressor of cytokine signaling (SOCS)1 and SOCS3 proteins are mediators of the IL-10 inhibitory actions. Our hypothesis was tested by exposing mouse J774 macrophages to chlamydial stimulants (live Chlamydia muridarum and MOMP) with and without IL-10. MOMP significantly induced several inflammatory mediators (IL-6, IL-12p40, CCL5, CXCL10), which were dose-dependently inhibited by IL-10. Chlamydial stimulants induced the mRNA gene transcripts and protein expression of SOCS1 and SOCS3, with more SOCS3 expression. Notably, IL-10 reciprocally regulated their expression by reducing SOCS1 and increasing SOCS3. Specific inhibitions of MAPK pathways revealed that p38, JNK, and MEK1/2 are required for inducing inflammatory mediators as well as SOCS1 and SOCS3. Chlamydial stimulants triggered an M1 pro-inflammatory phenotype evidently by an enhanced nos2 (M1 marker) expression, which was skewed by IL-10 towards a more M2 anti-inflammatory phenotype by the increased expression of mrc1 and arg1 (M2 markers) and the reduced SOCS1/SOCS3 ratios. Neutralization of endogenously produced IL-10 augmented the secretion of inflammatory mediators, reduced SOCS3 expression, and skewed the chlamydial M1 to an M2 phenotype. Inhibition of proteasome degradation increased TNF but decreased IL-10, CCL5, and CXCL10 secretion by suppressing SOCS1 and SOCS3 expressions and dysregulating their STAT1 and STAT3 transcription factors. Our data show that SOCS1 and SOCS3 are regulators of IL-10 inhibitory actions, and underscore SOCS proteins as therapeutic targets for IL-10 control of inflammation for Chlamydia and other bacterial inflammatory diseases.

A nanovaccine formulation of Chlamydia recombinant MOMP encapsulated in PLGA 85:15 nanoparticles augments CD4+ effector (CD44high CD62Llow) and memory (CD44high CD62Lhigh) T-cells in immunized mice.

Vaccine developmental strategies are utilizing antigens encapsulated in biodegradable polymeric nanoparticles. Here, we developed a Chlamydia nanovaccine (PLGA-rMOMP) by encapsulating its recombinant major outer membrane protein (rMOMP) in the extended-releasing and self-adjuvanting PLGA [poly (D, L-lactide-co-glycolide) (85:15)] nanoparticles. PLGA-rMOMP was small (nanometer size), round and smooth, thermally stable, and exhibited a sustained release of rMOMP. Stimulation of mouse primary dendritic cells (DCs) with PLGA-rMOMP augmented endosome processing, induced Th1 cytokines (IL-6 and IL-12p40), and expression of MHC-II and co-stimulatory (CD40, CD80, and CD86) molecules. BALB/c mice immunized with PLGA-rMOMP produced enhanced CD4+ T-cells-derived memory (CD44high CD62Lhigh), and effector (CD44high CD62Llow) phenotypes and functional antigen-specific serum IgG antibodies. In vivo biodistribution of PLGA-rMOMP revealed its localization within lymph nodes, suggesting migration from the injection site via DCs. Our data provide evidence that the PLGA (85:15) nanovaccine activates DCs and augments Chlamydia-specific rMOMP adaptive immune responses that are worthy of efficacy testing.

Is Standardization Necessary for Sharing of a Large Mid-Infrared Soil Spectral Library?

Recent developments in diffuse reflectance soil spectroscopy have increasingly focused on building and using large soil spectral libraries with the purpose of supporting many activities relevant to monitoring, mapping and managing soil resources. A potential limitation of using a mid-infrared (MIR) spectral library developed by another laboratory is the need to account for inherent differences in the signal strength at each wavelength associated with different instrumental and environmental conditions. Here we apply predictive models built using the USDA National Soil Survey Center-Kellogg Soil Survey Laboratory (NSSC-KSSL) MIR spectral library (n = 56,155) to samples sets of European and US origin scanned on a secondary spectrometer to assess the need for calibration transfer using a piecewise direct standardization (PDS) approach in transforming spectra before predicting carbon cycle relevant soil properties (bulk density, CaCO3, organic carbon, clay and pH). The European soil samples were from the land use/cover area frame statistical survey (LUCAS) database available through the European Soil Data Center (ESDAC), while the US soil samples were from the National Ecological Observatory Network (NEON). Additionally, the performance of the predictive models on PDS transfer spectra was tested against the direct calibration models built using samples scanned on the secondary spectrometer. On independent test sets of European and US origin, PDS improved predictions for most but not all soil properties with memory based learning (MBL) models generally outperforming partial least squares regression and Cubist models. Our study suggests that while good-to-excellent results can be obtained without calibration transfer, for most of the cases presented in this study, PDS was necessary for unbiased predictions. The MBL models also outperformed the direct calibration models for most of the soil properties. For laboratories building new spectroscopy capacity utilizing existing spectral libraries, it appears necessary to develop calibration transfer using PDS or other calibration transfer techniques to obtain the least biased and most precise predictions of different soil properties.

Fetal microchimerism by mode of delivery: a prospective cohort study.

OBJECTIVE: To compare fetal microchimerism (FMc) in pregnancies with uncomplicated vaginal delivery (VD) versus caesarean delivery (CD). DESIGN: Prospective cohort study. SETTING: University of Washington and Fred Hutchinson Cancer Research Center, USA. POPULATION: Women delivering singleton pregnancies without pertinent antenatal complications with uncomplicated deliveries (n = 36). METHODS: We collected maternal predelivery, postdelivery and umbilical cord blood for each mother-baby pair. Following maternal and fetal genotyping, FMc was measured with quantitative polymerase chain reaction assays targeting fetus-specific polymorphisms. Quantification of FMc is expressed as genome equivalents (gEq) of fetal DNA/100 000 total gEq tested. FMc detection was evaluated by logistic regression while controlling for total number of cell equivalents tested and clinically relevant covariates. FMc concentrations were compared using negative binomial regression while controlling for the same covariates and predelivery FMc positivity. MAIN OUTCOME MEASURE: Detection and concentration of FMc by mode of delivery. RESULTS: Twenty-four mother-baby pairs had a VD and 12 had a CD. Postdelivery FMc detection was higher following CD than after VD (58.3% versus 16.7%, P = 0.02). After controlling for covariates, the likelihood of postdelivery FMc detection was almost nine-fold higher after CD than VD (odds ratio 8.8, 95% CI 1.6-47.6; P = 0.01). With respect to postdelivery FMc concentration, the detection rate ratio for CD versus VD in the adjusted negative binomial regression model was 14.7 (95% CI 3.2-66.8; P = 0.001). CONCLUSION: Postdelivery peripheral FMc detection and concentration are significantly higher after CD than after VD. As FMc is associated with long-term maternal health, our findings suggest that the mode of delivery may impact this risk. TWEETABLE ABSTRACT: Greater fetal microchimerism found in maternal blood following caesarean delivery compared with vaginal delivery.

Colorectal Liver Metastasis: Overview of Treatment Paradigm Highlighting the Role of Ablation.

OBJECTIVE: The objective of this article is to discuss the current treatment options for colorectal cancer (CRC) liver metastases and the role of ablation. CONCLUSION: A randomized control trial of ablation combined with chemotherapy showed improved overall survival compared with chemotherapy alone. Local recurrence rates are comparable to those associated with resection when ablative margins of more than 5 mm are achieved and target lesions are smaller than 3 cm. In patients with unresectable disease, ablation for curative intent should be considered.

Proteomic analysis of antimicrobial effects of pegylated silver coated carbon nanotubes in Salmonella enterica serovar Typhimurium.

BACKGROUND: Synthesis of silver nano-compounds with enhanced antimicrobial effects is of great interest for the development of new antibacterial agents. Previous studies have reported the antibacterial properties of pegylated silver-coated carbon nanotubes (pSWCNT-Ag) showing less toxicity in human cell lines. However, the mechanism underlining the pSWCNT-Ag as a bactericidal agent remained unfolded. Here we assessed the pSWCNT-Ag effects against foodborne pathogenic bacteria growth and proteome profile changes. RESULTS: Measurements of bioluminescent imaging, optical density, and bacteria colony forming units revealed dose-dependent and stronger bactericidal activity of pSWCNT-Ag than their non-pegylated counterparts (SWCNT-Ag). In ovo administration of pSWCNT-Ag or phosphate-buffered saline resulted in comparable chicken embryo development and growth. The proteomic analysis, using two-dimensional electrophoresis combined with matrix assisted laser desorption/ionization time of flight/time of flight mass spectrometry, was performed on control and surviving Salmonella enterica serovar Typhimurium to pSWCNT-Ag. A total of 15 proteins (ten up-regulated and five down-regulated) differentially expressed proteins were identified. Functional analyses showed significant reduction of proteins associated with biofilm formation, nutrient and energy metabolism, quorum sensing and maintenance of cell structure and cell motility in surviving S. Typhimurium. In contrast, proteins associated with oxygen stress, DNA protection, starvation, membrane rebuilding, and alternative nutrient formation were induced as the compensatory reaction. CONCLUSIONS: This study provides further evidence of the antibacterial effects of pSWCNT-Ag nanocomposites and knowledge of their mechanism of action through various protein changes. The findings may lead to the development of more effective and safe antimicrobial agents.

Identification of Novel Quantitative Trait Loci Linked to Crown Rot Resistance in Spring Wheat.

Crown rot (CR), caused by various Fusarium species, is a major disease in many cereal-growing regions worldwide. Fusarium culmorum is one of the most important species, which can cause significant yield losses in wheat. A set of 126 advanced International Maize and Wheat Improvement Center (CIMMYT) spring bread wheat lines were phenotyped against CR for field crown, greenhouse crown and stem, and growth room crown resistance scores. Of these, 107 lines were genotyped using Diversity Array Technology (DArT) markers to identify quantitative trait loci linked to CR resistance by genome-wide association study. Results of the population structure analysis grouped the accessions into three sub-groups. Genome wide linkage disequilibrium was large and declined on average within 20 cM (centi-Morgan) in the panel. General linear model (GLM), mixed linear model (MLM), and naïve models were tested for each CR score and the best model was selected based on quarantine-quarantine plots. Three marker-trait associations (MTAs) were identified linked to CR resistance; two of these on chromosome 3B were associated with field crown scores, each explaining 11.4% of the phenotypic variation and the third MTA on chromosome 2D was associated with greenhouse stem score and explained 11.6% of the phenotypic variation. Together, these newly identified loci provide opportunity for wheat breeders to exploit in enhancing CR resistance via marker-assisted selection or deployment in genomic selection in wheat breeding programs.

Methane emission from global livestock sector during 1890-2014: Magnitude, trends and spatiotemporal patterns.

Human demand for livestock products has increased rapidly during the past few decades largely due to dietary transition and population growth, with significant impact on climate and the environment. The contribution of ruminant livestock to greenhouse gas (GHG) emissions has been investigated extensively at various scales from regional to global, but the long-term trend, regional variation and drivers of methane (CH4 ) emission remain unclear. In this study, we use Intergovernmental Panel on Climate Change (IPCC) Tier II guidelines to quantify the evolution of CH4 emissions from ruminant livestock during 1890-2014. We estimate that total CH4 emissions in 2014 was 97.1 million tonnes (MT) CH4 or 2.72 Gigatonnes (Gt) CO2 -eq (1 MT = 1012 g, 1 Gt = 1015 g) from ruminant livestock, which accounted for 47%-54% of all non-CO2 GHG emissions from the agricultural sector. Our estimate shows that CH4 emissions from the ruminant livestock had increased by 332% (73.6 MT CH4 or 2.06 Gt CO2 -eq) since the 1890s. Our results further indicate that livestock sector in drylands had 36% higher emission intensity (CH4 emissions/km2 ) compared to that in nondrylands in 2014, due to the combined effect of higher rate of increase in livestock population and low feed quality. We also find that the contribution of developing regions (Africa, Asia and Latin America) to the total CH4 emissions had increased from 51.7% in the 1890s to 72.5% in the 2010s. These changes were driven by increases in livestock numbers (LU units) by up to 121% in developing regions, but decreases in livestock numbers and emission intensity (emission/km2 ) by up to 47% and 32%, respectively, in developed regions. Our results indicate that future increases in livestock production would likely contribute to higher CH4 emissions, unless effective strategies to mitigate GHG emissions in livestock system are implemented.

Percutaneous Image-Guided Irreversible Electroporation for the Treatment of Unresectable, Locally Advanced Pancreatic Adenocarcinoma.

PURPOSE: To describe safety and effectiveness of percutaneous irreversible electroporation (IRE) for treatment of unresectable, locally advanced pancreatic adenocarcinoma (LAPC). MATERIALS AND METHODS: This retrospective study included 50 patients (23 women, 27 men; age range, 46-91 y; median age, 62.5 y) with biopsy-proven, unresectable LAPC who received percutaneous computed tomography (CT)-guided IRE. The primary objective was to assess the safety profile of the procedure; the secondary objective was to determine overall survival (OS). All patients had prior chemotherapy (1-5 lines, median 2), and 30 (60%) of 50 patients had prior radiation therapy. Follow-up included CT at 1 month and at 3-month intervals thereafter. RESULTS: There were no treatment-related deaths and no 30-day mortality. Serious adverse events occurred in 10 (20%) of 50 patients (abdominal pain [n = 7], pancreatitis [n = 1], sepsis [n = 1], gastric leak [n = 1]). Median OS was 27.0 months (95% confidence interval [CI], 22.7-32.5 months) from time of diagnosis and 14.2 months (95% CI, 9.7-16.2 months) from time of IRE. Patients with tumors ≤ 3 cm (n = 24) had significantly longer median OS than patients with tumors > 3 cm (n = 26): 33.8 vs 22.7 months from time of diagnosis (P = .002) and 16.2 vs 9.9 months from time of IRE (P = .031). Tumor size was confirmed as the only independent predictor of OS at multivariate analysis. CONCLUSIONS: Percutaneous image-guided IRE of unresectable LAPC is associated with an acceptable safety profile.

Advances in Skin Regeneration Using Tissue Engineering.

Tissue engineered skin substitutes for wound healing have evolved tremendously over the last couple of years. New advances have been made toward developing skin substitutes made up of artificial and natural materials. Engineered skin substitutes are developed from acellular materials or can be synthesized from autologous, allograft, xenogenic, or synthetic sources. Each of these engineered skin substitutes has their advantages and disadvantages. However, to this date, a complete functional skin substitute is not available, and research is continuing to develop a competent full thickness skin substitute product that can vascularize rapidly. There is also a need to redesign the currently available substitutes to make them user friendly, commercially affordable, and viable with longer shelf life. The present review focuses on providing an overview of advances in the field of tissue engineered skin substitute development, the availability of various types, and their application.

Novel cationic peptide TP359 down-regulates the expression of outer membrane biogenesis genes in Pseudomonas aeruginosa: a potential TP359 anti-microbial mechanism.

BACKGROUND: Antimicrobial peptides (AMPs) are a class of antimicrobial agents with broad-spectrum activities. Several reports indicate that cationic AMPs bind to the negatively charged bacterial membrane causing membrane depolarization and damage. However, membrane depolarization and damage may be insufficient to elicit cell death, thereby suggesting that other mechanism(s) of action could be involved in this phenomenon. In this study, we investigated the antimicrobial activity of a novel antimicrobial peptide, TP359, against two strains of Pseudomonas aeruginosa, as well as its possible mechanisms of action. RESULTS: TP359 proved to be bactericidal against P. aeruginosa as confirmed by the reduced bacteria counts, membrane damage and cytoplasmic membrane depolarization. In addition, it was non-toxic to mouse J774 macrophages and human lung A549 epithelial cells. Electron microscopy analysis showed TP359 bactericidal effects by structural changes of the bacteria from viable rod-shaped cells to those with cell membrane damages, proceeding into the efflux of cytoplasmic contents and emergence of ghost cells. Gene expression analysis on the effects of TP359 on outer membrane biogenesis genes underscored marked down-regulation, particularly of oprF, which encodes a major structural and outer membrane porin (OprF) in both strains studied, indicating that the peptide may cause deregulation of outer membrane genes and reduced structural stability which could lead to cell death. CONCLUSION: Our data shows that TP359 has potent antimicrobial activity against P aeruginosa. The correlation between membrane damage, depolarization and reduced expression of outer membrane biogenesis genes, particularly oprF may suggest the bactericidal mechanism of action of the TP359 peptide.

Genome-Wide Association Study in Wheat Identifies Resistance to the Cereal Cyst Nematode Heterodera filipjevi.

The cyst nematode Heterodera filipjevi is a plant parasite causing substantial yield loss in wheat. Resistant cultivars are the preferred method of controlling cyst nematodes. Association mapping is a powerful approach to detect associations between phenotypic variation and genetic polymorphisms; in this way favorable traits such as resistance to pathogens can be located. Therefore, a genome-wide association study of 161 winter wheat accessions was performed with a 90K iSelect single nucleotide polymorphism (SNP) chip. Population structure analysis grouped into two major subgroups and first principal component accounted 6.16% for phenotypic diversity. The genome-wide linkage disequilibrium across wheat was 3 cM. Eleven quantitative trait loci (QTLs) on chromosomes 1AL, 2AS, 2BL, 3AL, 3BL, 4AS, 4AL, 5BL, and 7BL were identified using a mixed linear model false discovery rate of P < 0.01 that explained 43% of total genetic variation. This is the first report of QTLs conferring resistance to H. filipjevi in wheat. Eight QTLs on chromosomes 1AL, 2AS, 2BL, 3AL, 4AL, and 5BL were linked to putative genes known to be involved in plant-pathogen interactions. Two other QTLs on 3BL and one QTL on 7BL linked to putative genes known to be involved in abiotic stress.

A novel covalent approach to bio-conjugate silver coated single walled carbon nanotubes with antimicrobial peptide.

BACKGROUND: Due to increasing antibiotic resistance, the use of silver coated single walled carbon nanotubes (SWCNTs-Ag) and antimicrobial peptides (APs) is becoming popular due to their antimicrobial properties against a wide range of pathogens. However, stability against various conditions and toxicity in human cells are some of the major drawbacks of APs and SWCNTs-Ag, respectively. Therefore, we hypothesized that APs-functionalized SWCNTs-Ag could act synergistically. Various covalent functionalization protocols described previously involve harsh treatment of carbon nanotubes for carboxylation (first step in covalent functionalization) and the non-covalently functionalized SWCNTs are not satisfactory. METHODS: The present study is the first report wherein SWCNTs-Ag were first carboxylated using Tri sodium citrate (TSC) at 37 °C and then subsequently functionalized covalently with an effective antimicrobial peptide from Therapeutic Inc., TP359 (FSWCNTs-Ag). SWCNTs-Ag were also non covalently functionalized with TP359 by simple mixing (SWCNTs-Ag-M) and both, the FSWCNTs-Ag (covalent) and SWCNTs-Ag-M (non-covalent), were characterized by Fourier transform infrared spectroscopy (FT-IR), Ultraviolet visualization (UV-VIS) and transmission electron microscopy (TEM). Further the antibacterial activity of both and TP359 were investigated against two gram positive (Staphylococcus aureus and Streptococcus pyogenes) and two gram negative (Salmonella enterica serovar Typhimurium and Escherichia coli) pathogens and the cellular toxicity of TP359 and FSWCNTs-Ag was compared with plain SWCNTs-Ag using murine macrophages and lung carcinoma cells. RESULTS: FT-IR analysis revealed that treatment with TSC successfully resulted in carboxylation of SWCNTs-Ag and the peptide was indeed attached to the SWCNTs-Ag evidenced by TEM images. More importantly, the present study results further showed that the minimum inhibitory concentration (MIC) of FSWCNTs-Ag were much lower (~7.8-3.9 µg/ml with IC50: ~4-5 µg/ml) compared to SWCNTs-Ag-M and plain SWCNTs-Ag (both 62.6 µg/ml, IC50: ~31-35 µg/ml), suggesting that the covalent conjugation of TP359 with SWCNTs-Ag was very effective on their counterparts. Additionally, FSWCNTs-Ag are non-toxic to the eukaryotic cells at their MIC concentrations (5-2.5 µg/ml) compared to SWCNTs-Ag (62.5 µg/ml). CONCLUSION: In conclusion, we demonstrated that covalent functionalization of SWCNTs-Ag and TP359 exhibited an additive antibacterial activity. This study described a novel approach to prepare SWCNT-Ag bio-conjugates without loss of antimicrobial activity and reduced toxicity, and this strategy will aid in the development of novel and biologically important nanomaterials.

Gold nanorods inhibit respiratory syncytial virus by stimulating the innate immune response.

Respiratory syncytial virus (RSV) causes severe pneumonia and bronchiolitis in infants, children and older adults. The use of metallic nanoparticles as potential therapeutics is being explored against respiratory viruses like Influenza, Parainfluenza and Adenovirus. In this study, we showed that gold nanorods (GNRs) inhibit RSV in HEp-2 cells and BALB/c mice by 82% and 56%, respectively. The RSV inhibition correlated with marked upregulated antiviral genes due to GNR mediated TLR, NOD-like receptor and RIG-I-like receptor signaling pathways. Transmission electron microscopy of lungs showed GNRs in the endocytotic vesicles and histological analyses indicated infiltration by neutrophils, eosinophils and monocytes correlating with clearance of RSV. In addition, production of cytokines and chemokines in the lungs indicates recruitment of immune cells to counter RSV replication. To our knowledge, this is the first in vitro and in vivo report that provides possible antiviral mechanisms of GNRs against RSV.

Structural and Magnetic Phase Transitions near Optimal Superconductivity in BaFe2(As(1-x)Px)2.

We use nuclear magnetic resonance (NMR), high-resolution x-ray, and neutron scattering studies to study structural and magnetic phase transitions in phosphorus-doped BaFe2(As(1-x)P(x)2. Previous transport, NMR, specific heat, and magnetic penetration depth measurements have provided compelling evidence for the presence of a quantum critical point (QCP) near optimal superconductivity at x=0.3. However, we show that the tetragonal-to-orthorhombic structural (T{s}) and paramagnetic to antiferromagnetic (AF, TN) transitions in BaFe2(As(1-x)Px)2 are always coupled and approach T{N}≈T{s}≥T{c} (≈29 K) for x=0.29 before vanishing abruptly for x≥0.3. These results suggest that AF order in BaFe_{2}(As(1-x)Px)2 disappears in a weakly first-order fashion near optimal superconductivity, much like the electron-doped iron pnictides with an avoided QCP.

Novel pegylated silver coated carbon nanotubes kill Salmonella but they are non-toxic to eukaryotic cells.

BACKGROUND: Resistance of food borne pathogens such as Salmonella to existing antibiotics is of grave concern. Silver coated single walled carbon nanotubes (SWCNTs-Ag) have broad-spectrum antibacterial activity and may be a good treatment alternative. However, toxicity to human cells due to their physico-chemical properties is a serious public health concern. Although pegylation is commonly used to reduce metal nanoparticle toxicity, SWCNTs-Ag have not been pegylated as yet, and the effect of pegylation of SWCNTs-Ag on their anti-bacterial activity and cell cytotoxicity remains to be studied. Further, there are no molecular studies on the anti-bacterial mechanism of SWCNTs-Ag or their functionalized nanocomposites. MATERIALS AND METHODS: In this study we created novel pegylated SWCNTS-Ag (pSWCNTs-Ag), and employed 3 eukaryotic cell lines to evaluate their cytotoxicity as compared to plain SWCNTS-Ag. Simultaneously, we evaluated their antibacterial activity on Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) by the MIC and growth curve assays. In order to understand the possible mechanisms of action of both SWCNTs-Ag and pSWCNTs-Ag, we used electron microscopy (EM) and molecular studies (qRT-PCR). RESULTS: pSWCNTs-Ag inhibited Salmonella Typhimurium at 62.5 µg/mL, while remaining non-toxic to human cells. By comparison, plain SWCNTs-Ag were toxic to human cells at 62.5 µg/mL. EM analysis revealed that bacteria internalized either of these nanocomposites after the outer cell membranes were damaged, resulting in cell lysis or expulsion of cytoplasmic contents, leaving empty ghosts. The expression of genes regulating the membrane associated metabolic transporter system (artP, dppA, and livJ), amino acid biosynthesis (trp and argC) and outer membrane integrity (ompF) protiens, was significantly down regulated in Salmonella treated with both pSWCNTs-Ag and SWCNTs-Ag. Although EM analysis of bacteria treated with either SWCNTs-Ag or pSWCNTs-Ag revealed relatively similar morphological changes, the expression of genes regulating the normal physiological processes of bacteria (ybeF), quorum sensing (sdiA), outer membrane structure (safC), invasion (ychP) and virulence (safC, ychP, sseA and sseG) were exclusively down regulated several fold in pSWCNTs-Ag treated bacteria. CONCLUSIONS: Altogether, the present data shows that our novel pSWCNTs-Ag are non-toxic to human cells at their bactericidal concentration, as compared to plain SWCNTS-Ag. Therefore, pSWCNTs-Ag may be safe alternative antimicrobials to treat foodborne pathogens.