Host antimicrobial peptide S100A12 disrupts the fungal membrane by direct binding and inhibits growth and biofilm formation of Fusarium species.

Fungal keratitis is the foremost cause of corneal infections worldwide, of which Fusariumspp. is the common etiological agent that causes loss of vision and warrants surgical intervention. An increase in resistance to the available drugs along with severe side effects of the existing antifungals demands for new effective antimycotics. Here, we demonstrate that antimicrobial peptide S100A12 directly binds to the phospholipids of the fungal membrane, disrupts the structural integrity, and induces generation of reactive oxygen species in fungus. In addition, it inhibits biofilm formation by Fusariumspp. and exhibits antifungal property against Fusariumspp. both in vitro and in vivo. Taken together, our results delve into specific effect of S100A12 against Fusariumspp. with an aim to investigate new antifungal compounds to combat fungal keratitis.

Tremor signals during fluid injection are generated by fault slip.

Seismic tremor signals, also known as long-period, long-duration signals, have been reported in several locations where fluid injection for enhanced oil and gas exploration is taking place. However, the origin of these signals remains poorly constrained. We studied seismic tremor signals in Wellington Field, Kansas, using a seismic array during a carbon dioxide injection program. We show that these signals are generated below the surface during the time of carbon dioxide injection. They have a distinct spectral signature, similar to those observed in glacial and volcanic environments. The tremor sources are located near the injection site and aligned with preexisting faults. Modeling results imply that such tremors are generated by frictional slip on fault. These observations may reveal an important deformation mode, which is useful for studying associated stress, seismicity, and triggering, as well as for tracking fault activities during injection operations of all fluids, including supercritical carbon dioxide.

Understanding sanitation dynamics in Bihar, India: Evidence from the field survey.

Background: Although a good number of individual household latrines have been constructed in Bihar during the past few years, still, a huge task remains to be completed. The paper is based on the study of "concurrent monitoring of LSBA/SBM [G] in select districts of Bihar". Objectives: The aim is to understand different dimensions of the sanitation situation in Bihar. The objective is to suggest policy based on the findings. Materials and Methods: This study is based on primary data collected at the household level and public institutions in six districts of Bihar. Results: The analysis reveals that except a few categories, socioeconomic indicators such as religion, economic condition, or educational attainments have no significant impact on having a latrine at the household level. The variations in the construction of latrines among different districts emphasize that the public program needs to be implemented more effectively. It is also found that women are more vulnerable in a situation of open defecation. Conclusion: The challenge is to encourage people for the sustained use of the constructed latrines. This puts emphasis on changing the behavioral pattern of the people. This requires organizing a continuous awareness generation program with the aim to change the behavior.

CKD subpopulations defined by risk-factors: A longitudinal analysis of electronic health records.

Chronic kidney disease (CKD) is a progressive disease that evades early detection and is associated with various comorbidities. Although clinical comprehension and control of these comorbidities is crucial for CKD management, complex pathophysiological interactions and feedback loops make this a formidable task. We have developed a hybrid semimechanistic modeling methodology to investigate CKD progression. The model is represented as a system of ordinary differential equations with embedded neural networks and takes into account complex disease progression pathways, feedback loops, and effects of 53 medications to generate time trajectories of eight clinical biomarkers that capture CKD progression due to various risk factors. The model was applied to real world data of US patients with CKD to map the available longitudinal information onto a set of time-invariant patient-specific parameters with a clear biological interpretation. These parameters describing individual patients were used to segment the cohort using a clustering approach. Model-based simulations were conducted to investigate cluster-specific treatment strategies. The model was able to reliably reproduce the variability in biomarkers across the cohort. The clustering procedure segmented the cohort into five subpopulations - four with enhanced sensitivity to a specific risk factor (hypertension, hyperlipidemia, hyperglycemia, or impaired kidney) and one that is largely insensitive to any of the risk factors. Simulation studies were used to identify patient-specific strategies to restrain or prevent CKD progression through management of specific risk factors. The semimechanistic model enables identification of disease progression phenotypes using longitudinal data that aid in prioritizing treatment strategies at individual patient level.

Morus alba Prevented the Cyclophosphamide Induced Somatic and Germinal Cell Damage in Male Rats by Ameliorating the Antioxidant Enzyme Levels.

Cytogenetic analysis is essential to determine the effect of mutagens and antimutagens on genetic material. This study was done to evaluate the protective effect of root bark extract of Morus alba (M. alba) against cyclophosphamide induced somatic and germinal cell damage in male rats. The ethanolic extract of M. alba (0.25, 0.5 and 1 g/kg, 2 weeks) was evaluated against cyclophosphamide (75 mg/kg, single dose) induced nuclear damage. The sampling was done after 48 h of the clastogen treatment. The somatic and germinal nuclear damage was studied by bone marrow micronucleus and sperm analysis, respectively. Serum superoxide and catalase levels were estimated to determine the antioxidant status in each group. The results were analyzed statistically to find the significant variation. The administration of M. alba for 2 weeks suppressed dose-dependently the changes induced by cyclophosphamide. M. alba (0.5 g/kg) decreased the frequency of micronucleated erythrocyte, sperm shape abnormality and enhanced the sperm count, sperm motility and polychromatic-normochromatic erythrocytes ratio significantly (p < 0.05) in comparison with the cyclophosphamide treated group. The highest tested dose of M. alba (1 g/kg) produced more prominent suppression (p < 0.01) in the cyclophosphamide-induced somatic and germinal cell defects. The results also showed significant (p < 0.05) improvement in the serum antioxidant enzymes levels with M. alba when compared with the challenge group. The lower dose of M. alba extract (0.25 g/kg) prevented the CP-induced changes but was found to be statistically insignificant. Therefore, antimutagenic potential of the high dose of the extract of M. alba is possibly due to its antioxidant nature. The ability of the M. alba extract to prevent the nuclear damage could play an important role in overcoming several mutational defects that are associated with anticancer chemotherapy.

Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA): Zone I Balloon Occlusion Time Affects Spinal Cord Injury in the Nonhuman Primate Model.

OBJECTIVES: Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) has been used clinically to limit torso bleeding and restore central perfusion. The objective of this study was to determine the sequelae of prolonged REBOA in a nonhuman primate animal model. SUMMARY BACKGROUND DATA: Prolonged duration of REBOA is associated with adverse clinical outcomes. Threshold occlusion values tied to relative risk have yet to be determined. METHODS: Juvenile baboons were subjected to 40% to 55% total blood volume hemorrhage to achieve profound hypotension and shock. Zone I REBOA was performed for 60 minutes to assess acute injury and survival at 4 hours (group 1; n = 7). Post-REBOA 10-day survival and complications were then compared between 60 minutes (group 2; n = 8) and 30 minutes (group 3; n = 6) REBOA animals. RESULTS: Overall survival was 20/21 (95%). IL-6 and IL-8 were elevated at 1 and 4 hours in group 1 (P = 0.005; P = 0.001). Comparing 60-minute REBOA with 30-minute REBOA, there was (1) hypertension compared with normotension (P = 0.005), (2) increased base deficit (P = 0.003), (3) elevated Troponin I (P = 0.04), and histological evidence of kidney injury (P = 0.004). In addition, group 2 demonstrated paralysis with histopathologic changes of spinal cord ischemia (SCI) in 4/8 (50%), with no SCI in group 3 (P = 0.033). CONCLUSIONS: REBOA limits mortality in the primate model of severe hemorrhagic shock. However, unopposed balloon inflation in the distal thoracic aorta for 60 minutes results in high rates of spinal cord ischemia, an effect mitigated by limiting balloon inflation to 30 minutes.

Emergent Dynamics of Artificial Spin-Ice Lattice Based on an Ultrathin Ferromagnet.

We present high-frequency dynamics of magnetic nanostructure lattices, fabricated in the form of "artificial spin-ice", that possess magnetically frustrated states. Dynamics of such structures feature multiple resonance excitation that reveals rich and intriguing microwave characteristics, which are highly dependent on field-cycle history. Geometrical parameters such as dimensions and ferromagnetic layer thickness, which control the interplay of different demagnetizing factors, are found to play a pivotal role in governing the dynamics. Our findings are highlighted by the evolution of unique excitations pertaining to magnetic frustration, which are well supported by static magnetometry studies and micromagnetic simulations.

Correlation between MMP and TIMP levels and elastic moduli of ascending thoracic aortic aneurysms.

OBJECTIVE: The objective of this preliminary investigation is to determine if there is a relation between the biological levels of matrix metalloproteinases and tissue inhibitor of matrix metalloproteinase (TIMP) and the elastic moduli of the ascending aortic wall in patients with ascending thoracic aortic aneurysms (ATAA). METHODS: Circumferential specimens from twelve patients with ATAA were obtained from the greater curvature and their tensile properties (maximum elastic modulus) were tested uniaxially. The levels of MMP1, 2, 3, 8, and 9 as well as TIMP1 and 2 were determined in these aortic wall specimens using MMP/TIMP antibodies array. RESULTS: Direct relations were found between MMP2 and the elastic modulus of the ascending aorta wall (R2 = 0.52) and between MMP9 and TIMP1 (R2 = 0.63). However, weak positive relation was found between MMP2 and TIMP2 (R2 = 0.23). We found inverse relations between MMP3 and MMP8 levels and the elastic module. There were no relations between MMP1 and MMP9 levels and the elastic modulus of aortic wall. CONCLUSIONS: This preliminary study looks at the relationship between the elastic modulii and the MMPs/TIMPs levels found in aortic wall specimens. Given that the value of the elastic moduli can be obtained non-invasively, a close relation might permit to infer the value of MMPs and TIMPs levels from the non-invasive determination of the elasticity of the aortic wall. By allowing the non-invasive determination of the mechanical and biological properties of the aorta in in-vivo, the method proposed here might improve the prediction of outcomes of ascending aortic aneurysms. This is a very preliminary study (small sample size) and the outcomes of this study cannot be used as final conclusions and should be verified in further studies with larger sample of patients.

Stainless-Steel Column for Robust, High-Temperature Microchip Gas Chromatography.

This paper reports the first results of a robust, high-performance, stainless-steel microchip gas-chromatography (GC) column that is capable of analyzing complex real-world mixtures as well as operating at very high temperatures. Using a serpentine design, a 10 m column with an approximately semicircular cross-section with a 52 µm hydraulic diameter ( Dh) was produced in a 17 × 6.3 × 0.1 cm rectangular steel chip. The channels were produced using a multilayer-chemical-etch and diffusion-bonding process, and metal nuts were brazed onto the inlet and outlet ports allowing for column interfacing with ferrules and fused silica capillary tubing. After deactivating the metal surface, channels were statically coated with a ≈0.1 µm layer of 5% phenyl-1% vinyl-methylpolysiloxane (SE-54) stationary phase and cross-linked with dicumyl peroxide. By using n-tridecane ( n-C13) as a test analyte with a retention factor ( k) of 5, a total of 44 500 plates (≈4500 plates per meter) was obtained isothermally at 120 °C. The column was thermally stable to at least 350 °C, and rapid temperature programming (35 °C/min) was demonstrated for the boiling-point range from n-C5 to n-C44 (ASTM D2887 simulated-distillation standard). The column was also tested for separation of two complex mixtures: gasoline headspace and kerosene. These initial experiments demonstrate that the planar stainless-steel column with proper interfacing can be a viable alternative platform for portable, robust microchip GC that is capable of high-temperature operation for low-volatility-compound analysis.

Microchip gas chromatography columns, interfacing and performance.

Almost four decades of investigations have opened up many avenues to explore the production and utilization of planar (i.e., microchip) gas chromatographic columns. However, there remain many practical constraints that limit their widespread commercialization and use. The main challenges arise from non-ideal column geometries, dead volume issues and inadequate interfacing technologies, which all affect both column performance and range of applications. This review reflects back over the years on the extensive developments in the field, with the goal to stimulate future creative approaches and increased efforts to accelerate microchip gas chromatography development toward reaching its full potential.

Extending the upper temperature range of gas chromatography with all-silicon microchip columns using a heater/clamp assembly.

Miniaturization of gas chromatography (GC) instrumentation is of interest because it addresses current and future issues relating to compactness, portability and field application. While incremental advancements continue to be reported in GC with columns fabricated in microchips (referred to in this paper as "microchip columns"), the current performance is far from acceptable. This lower performance compared to conventional GC is due to factors such as pooling of the stationary phase in corners of non-cylindrical channels, adsorption of sensitive compounds on incompletely deactivated surfaces, shorter column lengths and less than optimum interfacing to injector and detector. In this work, a GC system utilizing microchip columns was developed that solves the latter challenge, i.e., microchip interfacing to injector and detector. A microchip compression clamp was constructed to heat the microchip (i.e., primary heater), and seal the injector and detector fused silica interface tubing to the inlet and outlet ports of the microchip channels with minimum extra-column dead volume. This clamp allowed occasional operation up to 375°C and routine operation up to 300°C. The compression clamp was constructed of a low expansion alloy, Kovar™, to minimize leaking due to thermal expansion mismatch at the interface during repeated thermal cycling, and it was tested over several months for more than one hundred injections without forming leaks. A 5.9m long microcolumn with rectangular cross section of 158µm×80µm, which approximately matches a 100µm i.d. cylindrical fused silica column, was fabricated in a silicon wafer using deep reactive ion etching (DRIE) and high temperature fusion bonding; finally, the channel was coated statically with a 1% vinyl, 5% phenyl, 94% methylpolysiloxane stationary phase. High temperature separations of C10-C40 n-alkanes and a commercial diesel sample were demonstrated using the system under both temperature programmed GC (TPGC) and thermal gradient GC (TGGC) conditions. TGGC analysis of a complex essential oil sample was also demonstrated. Addition of a secondary heater and polyimide insulation proved to be helpful in achieving the desired elution temperature without having to raise the primary heater temperature above 300°C for high boiling point compounds.

Comparing the Effects of Electronic Cigarette Vapor and Cigarette Smoke in a Novel In Vivo Exposure System.

Electronic cigarettes (E-cigarettes) are being widely used, and growing in popularity. It is estimated that more than 9 million adults use them regularly. The potential adverse health effects of electronic cigarette vapor (E-vapor) exposure are poorly defined. While several animal models of E-vapor exposure have been developed, few models expose rodents to clinically relevant quantities of nicotine and make direct comparisons to cigarette smoke within the same exposure system. Here, we present a method for constructing and operating an E-vapor chamber and cigarette smoke chamber. The chambers are constructed by outfitting anesthesia chambers with a computer controlled pumping system that delivers consistent amounts of E-vapor or cigarette smoke to rodents. Nicotine exposure is measured indirectly by quantifying pre and post-exposure serum cotinine levels. This exposure system can be modified to accommodate various types of E-cigarettes and tobacco cigarettes, and can be used to compare the effects of E-vapor and cigarette smoke in vivo.

Tuning of azine derivatives for selective recognition of Ag+ with the in vitro tracking of endophytic bacteria in rice root tissue.

Several azine derivatives have been prepared and structurally characterized by spectroscopic and single-crystal X-ray diffraction analysis. Two of them, viz. naphthalene based (A10) and anthracene based (A11) show fluorescence enhancement in the presence of Ag+ in aqueous-methanol. Moreover, A11 efficiently tracks Ag+in vitro endophytic bacteria infected rice root tissue. Experimental results have been substantiated by theoretical DFT calculations.

Faceted particles formed by the frustrated packing of anisotropic colloids on curved surfaces.

We use computer simulations and simple theoretical models to analyze the morphologies that result when rod-like particles end-attach onto a curved surface, creating a finite-thickness monolayer aligned with the surface normal. This geometry leads to two forms of frustration, one associated with the incompatibility of hexagonal order on surfaces with Gaussian curvature, and the second reflecting the deformation of a layer with finite thickness on a surface with non-zero mean curvature. We show that the latter effect leads to a faceting mechanism. Above threshold values of inter-particle attraction strength and surface mean curvature, the adsorbed layer undergoes a transition from orientational disorder to an ordered state that is demarcated by reproducible patterns of line defects. The number of facets is controlled by the competition between line defect energy and intra-facet strain. Tuning control parameters thus leads to a rich variety of morphologies, including icosahedral particles and irregular polyhedra. In addition to suggesting a new strategy for the synthesis of aspherical particles with tunable symmetries, our results may shed light on recent experiments in which rod-like HIV GAG proteins assemble around nanoscale particles.

Allosteric Inhibitory Molecular Recognition of a Photochromic Dye by a Digestive Enzyme: Dihydroindolizine makes α-chymotrypsin Photo-responsive.

The structural-functional regulation of enzymes by the administration of an external stimulus such as light could create photo-switches that exhibit unique biotechnological applications. However, molecular recognition of small ligands is a central phenomenon involved in all biological processes. We demonstrate herein that the molecular recognition of a photochromic ligand, dihydroindolizine (DHI), by serine protease α-chymotrypsin (CHT) leads to the photo-control of enzymatic activity. We synthesized and optically characterized the photochromic DHI. Light-induced reversible pyrroline ring opening and a consequent thermal back reaction via 1,5-electrocyclization are responsible for the photochromic behavior. Furthermore, DHI inhibits the enzymatic activity of CHT in a photo-controlled manner. Simultaneous binding of the well-known inhibitors 4-nitrophenyl anthranilate (NPA) or proflavin (PF) in the presence of DHI displays spectral overlap between the emission of CHT-NPA or CHT-PF with the respective absorption of cis or trans DHI. The results suggest an opportunity to explore the binding site of DHI using Förster resonance energy transfer (FRET). Moreover, to more specifically evaluate the DHI binding interactions, we employed molecular docking calculations, which suggested binding near the hydrophobic site of Cys-1-Cys-122 residues. Variations in the electrostatic interactions of the two conformers of DHI adopt unfavorable conformations, leading to the allosteric inhibition of enzymatic activity.

Dual mode ratiometric recognition of zinc acetate: nanomolar detection with in vitro tracking of endophytic bacteria in rice root tissue.

Several naphthalene-based aldazine derivatives were developed as efficient colorimetric and fluorescence probes for selective ratiometric recognition of traces of zinc acetate. The derivative structures were characterized by single-crystal X-ray diffraction. The probes were used for in vitro tracking of zinc acetate in endophytic bacteria within rice root tissue and to image zinc acetate in human breast cancer cells (MCF7) by normal and fluorescence microscopy. Density functional theoretical studies were in close agreement with the experimental findings.

Cross-talk between macrophages, smooth muscle cells, and endothelial cells in response to cigarette smoke: the effects on MMP2 and 9.

We hypothesized that matrix metalloproteinase secretion in response to cigarette smoke is modulated by cross-talk between resident cells within the aorta, namely, aortic smooth muscles, endothelial cells, and infiltrating macrophages, and this may be crucial for in vivo formation/progression of abdominal aortic aneurysm (AAA). Cigarette smoke extract (CSE) was applied to rat aortic smooth muscle (RASMC), endothelial (RAEC) or RAW cells, and conditioned media (CSE-CM) collected. Fresh cells were treated with CSE-CM for 24 h and then maintained in serum-free medium (SFM) for 72 h to analyze MMP2 and MMP9 in media by zymography and the ratio (pS/pJ) of phospho-Stat3 (pStat3) and phospho-Jak2 (pJak2) inside the cells by Western blot. We observed that CSE-CM from RAW and RAEC increased MMP9 by 200 and 17 %, respectively, in RASMC and also increased pS/pJ ratio (305 and 228 %, respectively) in RASMC. RAW cell-derived CSE-CM induced RAEC to produce moderate amounts of MMP2 (17 %), MMP9 (30 %), and a 137 % increase in pS/pJ. RAW cells receiving unstimulated CM from RASMC and RAEC produced significant amounts of MMP9 (128 and 155 %, respectively) and increased pS/pJ (45 and 1283 %, respectively). CSE-CM from RASMC and RAEC induced significant production of MMP9 from RAW cells (237 and 162 %, respectively) and increase in pS/pJ ratios (1348 and 1494 %, respectively). This is the first in vitro study demonstrating cigarette smoke extract-mediated differential interactions between resident cells in the aorta leads to altered modulation of signaling molecules that may be vital for AAA formation under in vivo conditions.

Ant groups optimally amplify the effect of transiently informed individuals.

To cooperatively transport a large load, it is important that carriers conform in their efforts and align their forces. A downside of behavioural conformism is that it may decrease the group's responsiveness to external information. Combining experiment and theory, we show how ants optimize collective transport. On the single-ant scale, optimization stems from decision rules that balance individuality and compliance. Macroscopically, these rules poise the system at the transition between random walk and ballistic motion where the collective response to the steering of a single informed ant is maximized. We relate this peak in response to the divergence of susceptibility at a phase transition. Our theoretical models predict that the ant-load system can be transitioned through the critical point of this mesoscopic system by varying its size; we present experiments supporting these predictions. Our findings show that efficient group-level processes can arise from transient amplification of individual-based knowledge.

Lysine triggered ratiometric conversion of dynamic to static excimer of a pyrene derivative: aggregation-induced emission, nanomolar detection and human breast cancer cell (MCF7) imaging.

A simple pyrene based probe (A3) derived from pyrene-1-carboxaldehyde and 2-amino-1-phenylpropan-1-ol shows unique optical response triggered by the concentration of lysine (Lys). This allows selective nanomolar detection of Lys via a cascade of processes, dynamic to static-excimer conversion in a ratiometric manner followed by aggregation-induced emission (AIE). Imaging of Lys in the human breast cancer cell (MCF7) has been achieved.

X-ray structurally characterized sensors for ratiometric detection of Zn(2+) and Al(3+) in human breast cancer cells (MCF7): development of a binary logic gate as a molecular switch.

A very simple molecule derived from salicylaldehyde and N-phenyl ethylenediamine (L1) functions as dual-mode ratiometric fluorescence "turn on" sensors for Zn(2+) and Al(3+) at two different wavelengths. The sensing is based on the combined effect of inhibition of excited-state intra-molecular proton transfer (ESIPT), CH=N isomerization and chelation-enhanced fluorescence (CHEF). Moreover, the [L1-Zn(2+)] system functions as a better Al(3+) sensor where Al(3+) ratiometrically displaces Zn(2+) from the [L1-Zn(2+)] complex. Emission wavelength dependent differentiation of Zn(2+) and Al(3+) using L1 allows us to develop a binary logic gate that functions as a molecular switch. L1 efficiently detects Zn(2+) and Al(3+) in human breast cancer cells (MCF7) while the [L1-Zn(2+)] complex specifically detects Al(3+) in the said cells.