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Discharge of wastewater containing traces of cow dung from a dairy farm poses significant threat to the environment, which necessitates the effluent treatment. Microbes present in organic rich dairy effluent containing traces of cow dung produced electricity. The performance of Microbial Fuel Cell(MFC) was analyzed by drawing I-V curves and performing electrochemical impedance spectroscopy (EIS). The MFC produced maximum power density of 203 mWm-2 at a current density of 1191 mAm-2. The Chemical Oxygen Demand (COD) removal efficiency was found to be 81% after 10 days of MFC operation. Decrease in anode polarization resistance confirmed the formation of biofilm at anode surface.

In the present study KrF Excimer laser has been employed to irradiate the Cadmium (Cd) targets for various number of laser pulses of 500, 1000, 1500 and 2000, at constant fluence of 3.6 J cm−2. Scanning Electron Microscopy (SEM) analysis was utilized to reveal the formation of laser induced nano/micro structures on the irradiated target (Cd) surfaces. SEM results show the generation of cavities, cracks, micro/nano wires/rods, wrinkles along with re-deposited particles during irradiation in air, whereas subsurface boiling, pores, cavities and Laser Induced Periodic Surface Structures (LIPSS) on the inner walls of cavities are revealed at the central ablated area after irradiation in propanol. The ablated volume and depth of ablated region on irradiated Cd targets are evaluated for various number of pulses and is higher in air as compared to propanol ambient. Fast Fourier Transform Infrared spectroscopy (FTIR), Energy Dispersive X-ray Spectroscopy (EDS) and X-ray Diffraction (XRD) analyses show the presence of oxides and hydro-oxides of Cd after irradiation in propanol, whereas the existence of oxides is observed after irradiation in air ambient. Nano-hardness tester was used to investigate mechanical modifications of ablated Cd. It reveals an increase in hardness after irradiation which is more pronounced in propanol as compared to air.

This paper presents the production of mesoporous metals with periodic 3D nanostructures, showing control over the lattice parameter and therefore pore and wire dimensions. The materials have "single diamond"(Fd3m) symmetry and are produced by deposition within a "cubic phase"template of the lipid phytantriol, in a process previously published. The current work shows a mechanism for tuning the nanoscale dimensions of the metal by the addition of a cosurfactant that progressively reduces the lipid bilayer curvature in the template. This swells its lattice parameter and therefore that of the deposited metal. Mesoporous platinum samples were characterized using X-ray scattering, electron microscopy, and electrochemical analysis. The structures exhibit unit cell sizes ranging from 13 to 20 nm, with wire thicknesses from 3.0 to 5.3 nm and estimated pore dimensions from 6.2 to 8.8 nm. The size control in these materials provides a mechanism for control of electrochemical behavior in electrocatalysis and sensors. Furthermore, the use of the templates in other metal and semiconductor materials suggests that size control offers possibilities for metamaterials with designed optoelectronic properties.

Improper storage conditions or processing of milk leads to potential spoilage and illness, due in part to temperature abuse, allowing bacteria present to grow and spoil the product. However, certain proteins naturally found in raw milk, such as lactoferrin, have reported antibacterial properties. The levels of lactoferrin required to effectively inhibit growth of pathogens have not been investigated thoroughly. This study aimed to examine various concentrations of lactoferrin as a potential biopreservative and as an antimicrobial against the common dairy pathogens Salmonella enterica and Escherichia coli O157:H7. Minimum inhibitory concentration assays were conducted on raw bovine milk in which the bacteria were exposed to varying concentrations of lactoferrin. In the raw milk system, the growth of E. coli O157:H7 was significantly decreased at levels greater than 14.05 mg/mL lactoferrin based on the reduction of tetrazolium salts. For S. enterica, only lactoferrin concentrations at or above 112.5 mg/mL in the milk resulted in reduced growth. Taken together, these results indicate that lactoferrin may have biopreservative potential. To fully examine the practicality and effectiveness of lactoferrin as an antimicrobial additive, a similar study should be conducted using additional (gram-positive) pathogens, such as Bacillus cereus and Listeria monocytogenes. If effective, lactoferrin could prolong the shelf life of dairy products and help reduce the incidence of foodborne illnesses in developing countries with limited refrigeration capability.

Advancement of the effective, stable, earth-rich, low-cost, and highly efficient electro-catalysts commonly demanded large-scale commercial applications toward the low-carbon economy. Here our group demonstrated the synthesis, characterization and electrochemical performance of highly effective and versatile cobalt oxide nanoparticles (Co3O4 NP’s) layered on fluorinated tin oxide (FTO) for efficient water splitting strategy. The synthesized Co3O4 NP’s were analyzed by Scanning Electron Microscopy, Particle Size Analyzer, Zeta Potential, X-ray Diffraction, Ultraviolet–Visible Absorption Spectroscopy, Fourier Transform Infrared Spectroscopy (FTIR) and Raman spectroscopy. The Co3O4 NP’s were deposited on FTO using inexpensive as well as leading electro-deposition method and by simple spray method. Hence, prepared Co3O4 electrocatalysts is found to be highly efficient for water oxidation without any pre-conditioning. This Co3O4 electrocatalyst, layered at FTO through electro-deposition method, is first used in Oxygen evolution reactions (OER). Electrochemically deposited Co3O4 NP’s at FTO proved itself a better electrode than simple spray-coated Co3O4 NP’s at FTO electrode and initiated the oxygen onset potential around 1.49 V versus reversible hydrogen electrode (RHE) (ŋ = 260 mV). The observed Tafel slope was 53 mV dec−1 during the oxygen evolution reaction and the peak of the current density J/ 68 mA cm−2 was observed at 1.78 V versus RHE, which is novel for cobalt-based electrocatalyst system. The conclusions drawn were comparable with both the pricey state of the art IrO2 and RuO2 electrocatalyst systems. In the long term water electrolysis experiment, the electrocatalyst also offered durability and enduring stability. This innovative approach offers a simplest technique to prepare cost-effective and super effectual nanoscale electrocatalyst for water electrolysis.

Pakistan is amongst the developing countries, which have been strongly affected by several emerging and re-emerging disease outbreaks as a consequence of climate change. Various studies have clearly demonstrated the impact of climate change on human health in Pakistan. This has increased the rate of morbidity and mortality, related not only to vector-borne, water-borne and food-borne diseases but has also contributed to the prevalence of neurological, cardiovascular and respiratory disorders. It is therefore important to take adequate measurements for water management and improve sanitary conditions especially in case of natural disasters. In order to effectively control the emerging and re-emerging infections in the country, an early, more Rigorous response is required, by the national health department, to monitor and evaluate the spread of infections in future. Therefore, precise planning and management strategies should be defined in order to circumvent the damage caused by the natural disasters associated with climate changes. This mini-review gives an overview about the public health issues associated with environmental change with special reference to Pakistan. This will provide a baseline for policymakers to develop public health surveillance programs in Pakistan.

The goal of this research was to determine the effects of the growth of invasive plant Amur Honeysuckle (Lonicera maackii) on the rhizosphere bacterial community composition, and diversity in an urban wetland forest ecosystem. Bacterial communities from the rhizosphere of 5 L. maackii plants and control bulk soils that did not have any L. maackii were investigated at Nina Mason Pulliam EcoLab (NMPE) using a culture-independent pipeline. Bacterial communities were characterized by PCR amplification and cloning 16S rRNA gene fragments following total DNA isolation from the soil samples. Microbial communities associated with both L. maackii rhizosphere and control sites showed high bacterial diversity within each site and taxa unique to individual sites were observed. Phylogenetic analyses revealed 80% of 400 16S rDNA clones were classified as α-, β- and γ-Proteobacteria, Acidobacteria, Actinobacteria, Cytophaga-Flexibacter-Bacteroides (CFB) group, and Verrucomicrobia. Members of the Proteobacteria and Acidobacterium represented 66.5% and 14.5% of the clone library, respectively, whereas the remaining bacterial divisions each comprised less than 7% of the clone library. Twenty-five 16S rDNA clones could not be classified into any known bacterial divisions. Statistical analyses showed significant differences in the presence of L. maackii on the proportions of 16S rDNA clones affiliated with Proteobacteria and Acidobacterium, suggesting bacterial community composition and structure does significantly change in the presence of L. maackii. However, sequence-based community analysis and the corresponding lack of intact microbial cultures limit understanding of the potential influences of enriched microbial taxa on plant hosts and their roles in ecosystem functioning.

It is important to reinforce physiology and pathophysiology concepts during clinical rotations, which traditionally occur after the foundational sciences in the US medical school system. We took an opportunistic approach when the COVID-19 pandemic forced our content into virtual delivery mode, as clinical medical education required a shift to nonpatient contact. We describe our experience in building a 2-wk course that consisted of online small groups during week 1 and panels and cases during week 2. The physiology content involved faculty-vetted resources, along with both discrete and open-ended focus questions for each learning objective. The course also included mechanical ventilation, and the physiologist utilized discussion points and developed a formative quiz to emphasize the physiology correlates, in addition to the very clinical aspects of mechanical ventilation. There were pathophysiology opportunities with pneumonia, acute respiratory distress syndrome, systemic inflammatory response syndrome, and multiple-organ system dysfunction among the clinical correlates. Review and recall of the foundational sciences occurred, allowing links between the pre-clerkship and clerkship years that were previously undiscovered in our institution. This virtually delivered medical curriculum related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 is timely, carries high student interest, and can benefit medical students and the communities they serve.

In this work, we developed a lipid mixture based on phytantriol / polyoxyethylene surfactant (Brij-56) that forms a

In the present investigation, a novel strategy of continuous microwave assisted flow synthesis (CMFS) has been adopted in comparison to traditional synthesis procedures (sol-gel and chemical precipitation method) for the quick production of TiO2 nanoparticles with very fine particle properties. The X-ray powder diffraction analysis (XRPD) and transmission electron microscopy (TEM) were two techniques used for analysing the properties related to structure and particle morphology of the resultant samples. It was observed that the particles formed by using continuous flow route were less agglomerated, and particle size (~ 6 nm) was smaller in comparison with others obtained using sol-gel (~ 9 nm) and chemical precipitation method (~ 15 nm). X-ray diffraction impressions established the generation of Anatase phase with preferential [101] dimension. Zeta potential computations were taken to inspect the colloidal stability of nanoparticles. Antimicrobial nature of TiO2 nano-samples was analyzed by using various bacterial and fungal strains. The nanostructured TiO2 particles confirmed outstanding uniformity with respect to chemical and structure. This new ceramic substance with strong antimicrobial activity promised magnificent potential in bone tissue engineering.

Microbial fuel cells (MFCs) are devices that exploit the electrochemically active microorganisms for the oxidative conversion of organic compounds into electricity. MFC technology is therefore expected to be a viable solution for domestic and industrial wastewater treatment as an alternative to the currently applied activated-sludge process. Despite its potential, the technology is facing application challenges because of high cost, low stability, and limited understanding of cell design and operation. In this experimental study, a double-chambered MFC with graphite electrodes and a proton-conducting membrane is used in a batch mode to study the potential of resource recovery from dairy effluent and identify the process limitations. Results showed a promising cell performance as the chemical oxygen demand of the wastewater reduced from 4520 mg/l to 850 mg/l in 10 days including the time required for biofilm development. The highest open-circuit voltage of 396 mV was recorded on the third day along with the highest power density of 36.39 mW/m 2 corresponding to a current density of 0.30 A/m 2 . Further, the electrochemical impedance spectroscopy revealed that the activation polarization of aerated cathode is the main contributor to cell internal resistance followed by the ohmic resistance.

In this work, we developed a lipid mixture based on phytantriol / polyoxyethylene surfactant (Brij-56) that forms a Im3m symmetry bicontinuous cubic phase based on the Schwartz primitive surface (Q II P ), from which we templated highly ordered 3D nanoporous platinum with a novel ‘single primitive’ morphology (Pm3m symmetry). The Q II P template phase is obtained by incorporation of 17.5% w/w Brij-56 (C16EO10) (a type-I surfactant) into phytantriol under excess hydration conditions. Phytantriol alone forms the double diamond Q II D (Pn3m) phase, and in previous studies incorporating Brij-56 at different compositions the cubic phase maintained this morphology, but increased its lattice parameter; mesoporous metals templated from these Q II D lipid templates all exhibited the ‘single diamond’ (Fd3m) morphology. In contrast, the current paper presents the availability of our Q II P cubic phases to template nanoporous materials of single primitive Pm3m morphology via chemical and electrochemical methods. To explore the structure porosity and morphological features of the templated Pt material, x-ray scattering and transmission electron microscopy are used. The resulting 3D nanoporous Pt materials are found to exhibit a regular network of Pt nanowires of ∼4 nm in diameter with a unit cell dimension of 14.8 ± 0.8 nm, reflecting the aqueous network within the Q II P template.

Improper storage conditions or processing of milk leads to potential spoilage and illness, due in part to temperature abuse, allowing bacteria present to grow and spoil the product. However, certain proteins naturally found in raw milk, such as lactoferrin, have reported antibacterial properties. The levels of lactoferrin required to effectively inhibit growth of pathogens have not been investigated thoroughly. This study aimed to examine various concentrations of lactoferrin as a potential biopreservative and as an antimicrobial against the common dairy pathogens

Here, we report a systematic investigation of the effect of experimental parameters on the structure, morphology and electrochemically active surface area of 3-D mesoporous platinum (Pt) framework. Template-assisted deposition of the mesoporous Pt framework is achieved using phytantriol-based inverse bicontinuous cubic phase of double diamond morphology (QIID) with Pn3m symmetry. Platinum is deposited electrochemically using hexachloroplatinic acid solution present within the aqueous domains of the cubic phase template. Deposition conditions, particularly the deposition potentials, are shown to significantly affect the surface morphology, porosity and electrochemically active surface area of the deposited Pt framework. Furthermore, the effect of underlying substrate on the structure and morphology of the mesoporous Pt framework is also investigated.

Cancer proteomics is a diverse and challenging field. It provides the promising tool that aids in the understanding of the disease, yet early-stage diagnosis is still a question and crucial for successful treatment of cancer. Genomics aided with proteomics has emerged as a larger platform for understanding the disease spread, proliferation, metastasis, genomic aberrations, mutational changes, therapeutics, design drug delivery system, proteomic anomalies, structural changes, and signaling pathways and moving toward personalized approach. Biomarker identification and development of the panel are very precious in cancer treatment. Generally, biomarker identification, validation, and clinical examination are specific tools for accurate diagnostic, prognostic, and therapeutics. Present-day advances in proteomics and computational sciences have opened a gateway for the identification and quantitative analysis of protein variations associated with the complexities and heterogeneity of tumor development. Concept of personalized medicine is an emerging approach for cancer patient treatment, yet it has many challenges to overcome before its clinical application. Translational research in oncology still needs lots of quality research to overcome many challenges and for improvement in biomedical application and cancer patient care.

Platinum and platinum-based materials with high catalytic performance, and chemical and mechanical stability are vital to electronic devices, biomedical science, optics, petroleum, and automotive industries. Because of the limited supply and high cost of platinum, it is highly desirable to develop new effective methodologies which can decrease the platinum loading by increasing its electrocatalytic properties. Depending upon their size, shape, and morphology, platinum materials have shown significant improvement in the surface catalysed chemical transformation pathways in fuel cell technology. Much research is now focused on the manufacturing and engineering of platinum and platinum-based materials which proffer enhanced catalytic efficiency, and offer chemical and mechanical robustness.

In this paper, we reported a novel continuous microwave assisted flow synthesis (CMFS) of nanosized manganese substituted hydroxyapatite particles by using calcium nitrate and diammonium hydrogen phosphate precursor solutions in only 7 min retention time at pH 9. The identification of nanoproduct was made by using X-ray diffraction (XRD), Transmission electron microscopy (TEM), Scanning electron microscopy (SEM), Dynamic light scattering (DLS), Fourier Transform Infrared Spectroscopy (FTIR) and Raman spectroscopy. The results indicated that nanosized manganese substituted hydroxyapatite particles were synthesized successfully in a shorter time period. The degree of crystallinity of the nanoproduct decreased with increasing manganese contents from 0% to 4%. At such conditions, variations in particles’ size and morphology from larger rod shaped particles (~110 nm) to smaller semispherical form (~75 nm) was observed. Thus the use of continuous microwave assisted flow synthesis procedure facilitated faster production of manganese substituted hydroxyapatite nanoparticles suitable for bone replacement applications.

International audience; The lipolysis stimulated lipoprotein receptor (LSR) is an apolipoprotein (Apo) B and ApoE receptor that participates in the removal of triglyceride-rich lipoproteins during the postprandial phase. LSR gene is located upstream of APOE, an important risk factor for cardiovascular disease (CVD). Since the APOE common polymorphism significantly affects the variability of lipid metabolism, this study aimed to determine the potential impact of a functional SNP rs916147 in LSR gene on lipid traits in healthy subjects and to investigate potential epistatic interaction between LSR and APOE. Unrelated healthy adults (N = 432) and children (N = 328

Oxya velox (Grasshopper ) is considered to be one of the damaging pests. The Mangifera indica ( M. indica ) crude enzyme extracts (5 g powder/20 mL of water, ethyl acetate, butanol and chloroform separately) were evaluated for their cellulose ingestion inhibition activity in O. velox . The extracts activities were studied as a function of substrate concentration, pH and temperature. Dinitrosalisalic acid (DNSA) method was adopted to study the kinetic of both endoglucanase and exoglucanase enzymes. The K m values of both enzymes were recorded to be 2 mg/mL and 0.92 mg/mL, respectively, which revealed greater affinity of enzymes for the substrate. All solvents showed considerable enzymes inhibition activity and variation among solvents was insignificant. Results revealed that the cellulose digestion by O. velox enzymes could possibly be inhibited using M. indica extracts.

Synthetic nanosized hydroxyapatite (HA) particles (

Calcium phosphates predominantly hydroxyapatite (HA) has extensively been used as bone substitute material and as coatings on metallic implants because of its high biocompatibility and bioactivity in bone mineralization. In order to enhance bioactivity of HA, hydroxyapatite has been substituted with divalent cations and anions. In this research, zinc substituted hydroxyapatite powder ( The present study showed that all nanoscale particulates had rod like morphology (at low Zn concentration), which changed to semispherical morphology with increasing Zn contents. It was also investigated that zinc substituted hydroxyapatite gave better antibacterial protection than pure HA. Thus, the CPFS system facilitated rapid production of high surface area nanoscale crystals of hydroxyapatite modified by Zn ions with controlled particle properties (crystallinity, size, shape) at (near) ambient conditions.

Over the last decades, the polyunsaturated fatty acids (PUFAs) have been largely explored not only for their nutritional value but also for the numerous biological functions and therapeutic effects. The serum and erythrocyte levels of PUFAs depend on the genetic control of metabolism as well as the dietary intake and are considered to reflect the health and disease status of an individual. Two families of PUFAs, omega-3 (n-3) and omega-6 (n-6), have gained much attention because of their involvement in the production of bioactive lipid mediators and therefore, a balanced omega-6/omega-3 ratio is crucial in maintaining the overall health of an individual. Omega-3 PUFAs, notably eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) have been shown to exert beneficial effects, possibly due to their lipid-lowering, anti-inflammatory, anti-hypertensive and cardioprotective effects, whereas omega-6 fatty acids such as arachidonic acid (ARA, 20:4n-6) exhibit the opposite properties. Even though, numerous epidemiological studies and clinical interventions have clearly established the effectiveness of omega-3 PUFAs in various pathological conditions including dyslipidemia, obesity, diabetes, cancer, cardiovascular and neurodegenerative diseases, some controversies do exist about the beneficial effects of omega-3 PUFAs and need to be clarified. Larger clinical trials with extended follow-up periods are required along with a careful dose selection, in order to confirm the clinical significance and efficacy of omega-3 PUFAs as therapeutic agents.

Folic acid (FA) is an electroactive compound of biological origin. It helps our body to produce and maintain healthy cells. It can significantly reduce the occurrence of neural tube defects and also prevents change in DNA structure. FA deficiency can lead to various health risks. Therefore, a sensitive, specific, and reproducible way of FA detection is essential. A number of analytical methods are in practice for the quantification of FA. However, electroanalytical methods are attracting much attention because of their advantage over conventional methods, as they are fast, simple, sensitive, and cost effective. Moreover, modification of electrodes offers control over size and morphology which allows miniaturization for applicability in portable electrochemical devices.

Multiple drug resistance (MDR) in bacteria represents a notable problem but if carried on plasmid their spread could become a significant threat to public health. Plasmids in members of the Enterobacteriaceae family and in particular Salmonella and Escherichia coli strains have been implicated in the spread of antibiotic resistance genes. However, the mechanisms involved in the transfer of plasmid-borne resistance genes are not fully understood. Here, we analyzed the ability of Salmonella enterica clinical isolates to transfer plasmid-borne MDR to E. coli. We also determined whether possession of an Inc A/C plasmid by a S. enterica isolate would confer increased fitness compared to an isolate not carrying the plasmid. Sixteen human and animal isolates of S. enterica were screened using a three-panel multiplex PCR assay, and simplex PCR for the blaCMY-2 gene. Using these data we selected a suitable strain as a plasmid donor for the construction of a new Salmonella strain with an Inc A/C plasmid. This allowed us to compare isogenic strains with and without the Inc A/C plasmid in multiple growth, fitness, and invasion assays. The results showed that possession of Inc A/C plasmid confers significant fitness advantage when tested in J774 macrophages as opposed to HEp-2 cells where no significant difference was found. In addition, stress assays performed in vitro showed that the possession of this large plasmid by Salmonella strains tested here does not appear to incur a significant fitness cost. Gaining a better understanding of molecular mechanisms of plasmid transfer between pathogenic bacteria will allow us to characterize the role of MDR in pathogenicity of bacteria and to identify methods to reduce the frequency of dissemination of multiple antibiotic resistance genes.

International audience; The ε4 allele of the apolipoprotein E (APOE) gene common polymorphism is the strongest genetic risk factor for Alzheimer's disease (AD). Human APOE gene is located on chromosome 19q13.1, a region linked to AD that also includes the LSR gene, which encodes the lipolysis-stimulated lipoprotein receptor (LSR). As an APOE receptor, LSR is involved in the regulation of lipid homeostasis in both periphery and brain. This study aimed to determine the potential interactions between 2 LSR genetic variants, rs34259399 and rs916147, and the APOE common polymorphism in 142 AD subjects (mean age: 73.16 ± 8.50 years) and 63 controls (mean age: 70.41 ± 8.49 years). A significant epistatic interaction was observed between APOE and both LSR variants, rs34259399 (beta = -0.95; p = 2 × 10-5) and rs916147 (beta = -0.83; p = 6.8 × 10-3). Interestingly, the interaction of LSR polymorphisms with APOE non-ε4 alleles increased AD risk. This indicates the existence of complex molecular interactions between these 2 neighboring genes involved in the pathogenesis of AD, which merits further investigation.Copyright © 2018 Elsevier Inc. All rights reserved.

We present an attractive method for the fabrication of long, straight, highly crystalline, ultrathin platinum nanowires. The fabrication is simply achieved using an inverse hexagonal (HII) lyotropic liquid crystal phase of the commercial surfactant phytantriol as a template. A platinum precursor dissolved within the cylindrical aqueous channels of the liquid crystal phase is chemically reduced by galvanic displacement using stainless steel. We demonstrate the production of nanowires using the HII phase in the phytantriol/water system which we obtain either by heating to 55 °C or at room temperature by the addition of a hydrophobic liquid, 9-cis-tricosene, to relieve packing frustration. The two sets of conditions produced high aspect nanowires with diameters of 2.5 and 1.7 nm, respectively, at least hundreds of nanometers in length, matching the size of the aqueous channels in which they grow. This versatile approach can be extended to produce highly uniform nanowires from a range of metals.

International audience; Telomere length has been subject of studies for many decades, aiming to elucidate its role in physiological processes, in process of aging and in diverse pathologies. Yet today, there is still no "big title" discovery that would lead to a practical use of telomeres as a reliable biomarker or target for a new drug. However, therapies for chronic disease patients are being tested and companies are already offering commercial tests for telomere length measurement. The strong genetic heritability of telomeres is opening the place for pharmacogenomics researches that could promote the personalized treatment of diverse diseases. In this article, we present the recent knowledge of telomeres genetic determination obtained by genome-wide association studies (GWAS), important biomarkers related to telomere length and review the possibilities of telomere's practical implementation in the medical treatment of diverse diseases and as a potential biomarker in personalized medicine. Furthermore, we summarise commercial offers of telomere length measurements available and we discuss the actions that should be taken to make steps forward into final application of the accumulated knowledge into practical use.

Salmonellosis is one of the most common causes of food-borne disease in the United States. Increasing antimicrobial resistance and corresponding increases in virulence present serious challenges. Currently, empirical therapy for invasive Salmonella enterica infection includes either ceftriaxone or ciprofloxacin (E. L. Hohmann, Clin. Infect. Dis. 32:263–269, 2001). The bla CMY-2 gene confers resistance to ceftriaxone, the antimicrobial of choice for pediatric patients with invasive Salmonella enterica infections, making these infections especially dangerous (J. M. Whichard et al., Emerg. Infect. Dis. 11:1464–1466, 2005). We hypothesized that bla CMY-2 -positive Salmonella enterica would exhibit increased MICs to multiple antimicrobial agents and increased resistance gene expression following exposure to ceftriaxone using a protocol that simulated a patient treatment in vitro . Seven Salmonella enterica strains survived a simulated patient treatment in vitro and, following treatment, exhibited a significantly increased ceftriaxone MIC. Not only would these isolates be less responsive to further ceftriaxone treatment, but because the bla CMY-2 genes are commonly located on large, multidrug-resistant plasmids, increased expression of the bla CMY-2 gene may be associated with increased expression of other drug resistance genes located on the plasmid (N. D. Hanson and C. C. Sanders, Curr. Pharm. Des. 5:881–894, 1999). The results of this study demonstrate that a simulated patient treatment with ceftriaxone can alter the expression of antimicrobial resistance genes, including bla CMY-2 and floR in S. enterica serovar Typhimurium and S. enterica serovar Newport. Additionally, we have shown increased MICs following a simulated patient treatment with ceftriaxone for tetracycline, amikacin, ceftriaxone, and cefepime, all of which have resistance genes commonly located on CMY-2 plasmids. The increases in resistance observed are significant and may have a negative impact on both public health and antimicrobial resistance of Salmonella enterica .

The hepatic removal of triglyceride-rich chylomicrons during the postprandial phase represents an important step towards determining the bioavailability of dietary lipids amongst the peripheral tissues. Indeed, elevated postprandial lipemia is often associated with obesity and increased risk of coronary heart disease. The milk protein, lactoferrin, has been shown to inhibit hepatic chylomicron remnant removal by the liver, resulting in increased postprandial lipemia. Despite numerous studies on potential targets for lactoferrin, the molecular mechanisms underlying the effect of lactoferrin remain unclear. We recently demonstrated that the lipolysis stimulated lipoprotein receptor (LSR) contributes to the removal of triglyceride-rich lipoproteins during the postprandial phase. Here, we report that while lactoferrin does not have any significant effect on LSR protein levels in mouse Hepa1–6 cells, this protein colocalizes with LSR in cells but only in the presence of oleate, which is needed to obtain LSR in its active form as lipoprotein receptor. Ligand blotting using purified LSR revealed that lactoferrin binds directly to the receptor in the presence of oleate and prevents the binding of triglyceride-rich lipoproteins. Both C- and N-lobes of lactoferrin as well as a mixture of peptides derived from its hydrolysis retained the ability to bind LSR in its active form. We propose then that the elevated postprandial lipemia observed upon lactoferrin treatment in vivo is mediated in part by its direct interaction with free fatty acid activated LSR, thus preventing clearance of chylomicrons and their remnants through the LSR pathway. Structured digital abstract • Lsr and Lsr bind by comigration in gel electrophoresis (View interaction) • Lsr binds to Lf by filter binding (View interaction) • Lf and Lsr colocalize by fluorescence microscopy (View interaction) • Lsr physically interacts with VLDL by filter binding (View interaction)

From the last couple of decades, lyotropic liquid crystals have garnered enormous attentions in medical and pharmaceutical sciences. Non-toxic, chemically stable, and biocompatible properties of these liquid crystal systems are contributing to their applications for drug delivery. Among a large variety of liquid crystal phases, inverse bicontinuous cubic and inverse hexagonal mesophases have been extensively investigated for their ability to encapsulate and controlled release of bioactive molecules of various sizes and polarity. The concept of changing the drug release rate in situ by simply changing the mesophase structure is much more fascinating. The encapsulation of bioactive compounds in mesophase systems of desirable features in sub-micron sized particles such as hexosomes and cubosomes, at ambient and high temperature is bringing innovation in the development of new drug applications. This review article outlines unique structural features of cubosomes and hexosomes, their methods of productions, factors affecting their formations and their potential utilization as smart nano-carriers for biopharmaceuticals in drug delivery applications.

As a hepatic receptor for triglyceride-rich lipoproteins, the lipolysis-stimulated lipoprotein receptor (LSR) may be involved in the dynamics of lipid distribution between the liver and peripheral tissues. Here, we explore the potential role of leptin in regulating LSR. At physiological concentrations (1-10 ng/ml), leptin increased LSR protein and mRNA levels in Hepa1-6 cells through an ERK1/2-dependent and α-amanitin-sensitive pathway. In vivo, leptin treatment of C57BL6/Rj mice (1 μg 2×/d, 8 d) led to a significant increase in hepatic LSR mRNA and protein, decreased liver triglycerides and increased VLDL secretion as compared to controls. LSR(+/-) mice with elevated postprandial lipemia placed on a high-fat (60% kcal) diet exhibited accelerated weight gain and increased fat mass as compared to controls. While plasma leptin levels were increased 3-fold, hepatic leptin receptor protein levels and phosphorylation of ERK1/2 were significantly reduced. Therefore, leptin is an important regulator of LSR protein levels providing the means for the control of hepatic uptake of lipids during the postprandial phase. However, this may no longer be functional in LSR(+/-) mice placed under a chronic dietary fat load, suggesting that this animal model could be useful for the study of molecular mechanisms involved in peripheral leptin resistance.

A macroscopically oriented inverse hexagonal phase (HII) of the lipid phytantriol in water is converted to an oriented inverse double diamond bicontinuous cubic phase (QII(D)). The initial HII phase is uniaxially oriented about the long axis of a capillary with the cylinders parallel to the capillary axis. The HII phase is converted by cooling to a QII(D) phase which is also highly oriented, where the cylindrical axis of the former phase has been converted to a ⟨110⟩ axis in the latter, as demonstrated by small-angle X-ray scattering. This epitaxial relationship allows us to discriminate between two competing proposed geometric pathways to convert HII to QII(D). Our findings also suggest a new route to highly oriented cubic phase coatings, with applications as nanomaterial templates.

Elevated postprandial lipemia (PPL) as an important risk factor for cardiovascular disease has been attributed to the accumulation of atherogenic remnant lipoproteins in the circulation. The hepati...

Summary Salmonella typhimurium is a Gram-negative enteric pathogen that can infect intestinal epithelial cells and induce inflammation of the intestinal mucosa. These processes are mediated by a type III secretion system (TTSS), which is encoded on Salmonella pathogenicity island 1 (SPI1). Previous studies showed that four SPI1-encoded transcriptional regulators, HilD, HilC, HilA and InvF, act in an ordered fashion to co-ordinately activate expression of the SPI1 TTSS. HilD and HilC derepress hilA transcription. HilA activates invF as well as SPI1 genes that encode components of the TTS apparatus. InvF then activates genes that encode proteins secreted by the SPI1 TTS apparatus. In this scheme, HilD and HilC indirectly activate expression of the SPI1 TTS apparatus and its secreted substrates by affecting hilA expression. Here, we report that HilD and HilC can also activate expression of a subset of SPI1 genes independently of HilA. Our studies show that HilD and HilC activate transcription of invF from a promoter that is far upstream of its HilA-dependent promoter. This activation is most probably through direct binding of HilD and HilC to sequences upstream and downstream of this alternative HilA-independent promoter. We conclude that HilD and HilC have a second role in SPI1 gene regulation that is separate from their role in co-ordinating expression of the SPI1 TTSS through hilA .

Bacillus subtilis responds to signals of environmental and metabolic stress by inducing over 40 general stress genes under the control of the sigma B transcription factor. sigma B activity is regulated post-translationally by a multi-component network composed of two coupled partner-switching modules, RsbX-RsbS-RsbT and RsbU-RsbV-RsbW, each containing a serine phosphatase (X or U), an antagonist protein (S or V), and a switch protein/serine kinase (T or W). The upstream module (X-S-T) is required to transmit signals of environmental stress. In contrast, the downstream module (U-V-W) is required to transmit signals of energy stress as well as the environmental signals conveyed to it from the upstream module. Until now the function of the rsbR gene product was unknown. RsbR shares significant sequence similarity with the RsbS and RsbV antagonist proteins whose phosphorylation states control key protein-protein interactions within their respective modules. Here we present evidence that RsbR is associated with RsbS in the upstream, environmental-sensing module. To investigate RsbR function, we constructed deletion and point mutations within rsbR and tested their effects on expression of sigma B-dependent reporter fusions, both singly and in combination with other rsb mutations. To determine the possible interaction of RsbR with other Rsb proteins, we tested the ability of wild-type or mutant RsbR to activate transcription in the yeast two-hybrid system in conjunction with other Rsb regulators. On the basis of this genetic analysis, we conclude that RsbR is a positive regulator which modulates sigma B activity in response to salt and heat stress. Our data further suggest that: (i) RsbR influences the antagonist function of RsbS by direct protein-protein interaction; and (ii) this interaction with RsbS is likely controlled by the phosphorylation state of RsbR.

International audience; Although recent studies have demonstrated a link between environmental contaminants exposure and obesity, the molecular mechanisms remain to be determined. Reduced expression of the hepatic lipolysis stimulated lipoprotein receptor (LSR), which is important for chylomicron clearance, is associated with increased body fat mass in mice. Since the polycylic aromatic hydrocarbon benzo[a]pyrene (B[a]P) is associated with weight gain in mice, the objective of this study was to determine if B[a]P modified hepatic LSR and lipid status. In 11-wk old male C57BL/6RJ mice treated with B[a]P (0.5 mg/kg, i.p. every 48h, 15 days), the increased weight gain was associated with increased plasma triglycerides and cholesterol, and increased liver cholesterol content as compared to control mice. LDL-receptor protein was decreased, and the positive correlation between hepatic LSR and LDL-receptor protein in control animals was absent in the B[a]P-treated mice, pointing towards a dysregulation of hepatic lipid homeostasis in the mice exposed to this pollutant. Hepa1-6 cells treated with 0.001 mM B[a]P also led to decreased LSR and LDL-receptor protein, as well as modified LSR activity as lipoprotein receptor. We propose that dysregulation of lipid homeostasis in the liver may contribute towards B[a]P-induced weight gain in mice.

Direct electrochemical templating is carried out using a thin layer of a self-assembled diamond phase (QIID) of phytantriol to create a platinum film with a novel nanostructure. Small-angle X-ray scattering shows that the nanostructured platinum films are asymmetrically templated and exhibit “single diamond” morphology with Fd3m symmetry.

The lipolysis stimulated lipoprotein receptor (LSR) plays an important role in hepatic uptake of triglyceride (TG)-rich lipoproteins during the postprandial (PPL) phase. We recently reported the regulation of LSR by leptin, accompanied by changes in hepatic lipid metabolism. In this study, we sought to determine if a direct link exists between LSR and lipogenesis in the liver, focusing on ATP citrate lyase (ACL) and fatty acid synthase (FAS), two key enzymes for de novo fatty acid synthesis. Garcinia cambogia extract (GCE) contains hydroxycitric acid, an ACL potent inhibitor found to lower plasma TG and body weight in rodent and human studies. In female 10 wk-old C57BL/6Rj mice treated 30 days with corn oil emulsion containing 20 mg GCE (n=8), we observed reduced fasting (21%, p1.5 fold (p+/- (n=11) mice and LSR +/+ littermates (n=7) were placed on a high fat (60% kcal) diet for 6 wks; LSR +/- exhibited higher weight gain, fat mass and PPL plasma TG vs LSR +/+ as previously reported. A >2-fold (p+/- was observed as compared to controls. Interestingly, strong correlations were found between LSR and FAS (r = 0.8, p+/- mice. We therefore propose that there exists a close link between the regulation of the uptake of lipoproteins via the LSR and LDL-R pathways and de novo lipogenesis in the liver. Further studies will provide insight in the mechanisms involved in maintaining lipid homeostasis, leading towards potential treatments for hyperlipidemia associated with obesity, 2 high risk factors for atherosclerosis.

hilA encodes an activator of Salmonella enterica serovar Typhimurium virulence genes and is transcriptionally modulated by environmental conditions. We show that H-NS represses hilA under low-osmolarity conditions. H-NS, HU, and Fis also appear to affect the derepression of hilA by HilD. Modulation of hilA by counteracting repressing and derepressing mechanisms may allow Salmonella serovar Typhimurium to regulate its virulence genes in response to different situations in vivo.

Salmonella typhimurium is a Gram-negative enteric pathogen that can infect intestinal epithelial cells and induce inflammation of the intestinal mucosa. These processes are mediated by a type III secretion system (TTSS), which is encoded on Salmonella pathogenicity island 1 (SPI1). Previous studies showed that four SPI1-encoded transcriptional regulators, HilD, HilC, HilA and InvF, act in an ordered fashion to co-ordinately activate expression of the SPI1 TTSS. HilD and HilC derepress hilA transcription. HilA activates invF as well as SPI1 genes that encode components of the TTS apparatus. InvF then activates genes that encode proteins secreted by the SPI1 TTS apparatus. In this scheme, HilD and HilC indirectly activate expression of the SPI1 TTS apparatus and its secreted substrates by affecting hilA expression. Here, we report that HilD and HilC can also activate expression of a subset of SPI1 genes independently of HilA. Our studies show that HilD and HilC activate transcription of invF from a promoter that is far upstream of its HilA-dependent promoter. This activation is most probably through direct binding of HilD and HilC to sequences upstream and downstream of this alternative HilA-independent promoter. We conclude that HilD and HilC have a second role in SPI1 gene regulation that is separate from their role in co-ordinating expression of the SPI1 TTSS through hilA.