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Morpho-phonological patterns and semantic density influence the processing of spoken complex words and contribute to the dissociation between regularly and irregularly inflected forms. However, it is unclear whether all listeners rely on morpho-phonological and semantic cues to the same degree. The present paper examines whether a listener's cognitive profile, indicated by processing efficiency, affects the processing strategy employed when listening to morphologically complex words. Two auditory judgement experiments demonstrate that slower responders rely more strongly on semantic processing than faster responders, but all listeners show morpho-phonological effects regardless of processing speed and form effects. This demonstrates that morpho-phonological processing is automatic for all listeners, but processing efficiency determines whether additional semantic cues are engaged. The results highlight the importance of integrating cognitive variability into current models of complex word processing. [ABSTRACT FROM AUTHOR]

N1,N2-diphenylacenaphthylene-1,2-diimines (BIANs) have been used to reduce the undesired high viscosity of alkyl magnesium solutions, which are known to form polymeric structures. In order to understand the mechanisms, analyses of the BIAN alkyl magnesium solutions have been carried out under inert conditions with SEC-MS, NMR, and FTIR and were compared to the structures obtained from HPLC-MS, FTIR, and NMR after aqueous workup. While viscosity reduction was shown for all BIAN derivatives used, only the bis (diisopropyl)-substituted BIAN could be clearly assigned to a single reaction product, which also could be reused without loss of efficiency or decomposition. All other derivatives have been shown to behave differently, even under inert conditions, and decompose upon contact with acidic solvents. While the chemical reactions observed after the workup of the used BIANs are dominated by (multiple) alkylation, mainly on the C = N double bond, the observation of viscosity reduction cannot be assigned to this reaction alone, but to the interaction of the nitrogen atoms of BIANs with the Mg of the alkyl magnesium polymers, as could be shown by FTIR and NMR measurements under inert conditions. [ABSTRACT FROM AUTHOR]

The Earth is home to environments characterized by low pH, including the gastrointestinal tract of vertebrates and large areas of acidic soil. Most bacteria are neutralophiles, but can survive fluctuations in pH. Herein, we review how Escherichia, Salmonella, Helicobacter, Brucella , and other acid-resistant Gram-negative bacteria adapt to acidic environments. We discuss the constitutive and inducible defense mechanisms that promote survival, including proton-consuming or ammonia-producing processes, cellular remodeling affecting membranes and chaperones, and chemotaxis. We provide insights into how Gram-negative bacteria sense environmental acidity using membrane-integrated and cytosolic pH sensors. Finally, we address in more detail the powerful proton-consuming decarboxylase systems by examining the phylogeny of their regulatory components and their collective functionality in a population. [ABSTRACT FROM AUTHOR]

Magnesium alkyls such as butyl octyl magnesium and butyl ethyl magnesium are used as precursors for highly active and water-free magnesium chloride support materials for Ziegler–Natta catalysts. These alkyls show a high viscosity in hydrocarbon solvents which negatively affect their industrial application. Density functional theory (DFT) calculations supported the hypothesis that magnesium alkyls can form oligomeric chain structures responsible for the high viscosity. Heterocumulenes such as isocyanates, isothiocyanates and carbodiimides were studied as additives reducing the viscosity, supported by DFT calculations. The modified alkyls have further been tested in catalyst synthesis and in the polymerization of ethylene. The polymerization results showed high activities and similar polymer properties compared with a catalyst prepared without modified magnesium alkyl. [ABSTRACT FROM AUTHOR]

Rapid diagnostic tests (RDTs) have the potential to identify infectious diseases quickly, minimize disease transmission, and could complement and improve surveillance and control of infectious and vector-borne diseases during outbreaks. The U.S. Defense Threat Reduction Agency's Joint Science and Technology Office (DTRA-JSTO) program set out to develop novel point-of-need RDTs for infectious diseases and deploy them for home use with no training. The aim of this formative study was to address two questions: 1) could community members in Iquitos, Peru and Phnom Penh, Cambodia competently use RDTs of different levels of complexity at home with visually based instructions provided, and 2) if an RDT were provided at no cost, would it be used at home if family members displayed febrile symptoms? Test kits with written and video (Peru only) instructions were provided to community members (Peru [n = 202]; Cambodia [n = 50]) or community health workers (Cambodia [n = 45]), and trained observers evaluated the competency level for each of the several steps required to successfully operate one of two multiplex RDTs on themselves or other consenting participant (i.e., family member). In Iquitos, >80% of residents were able to perform 11/12 steps and 7/15 steps for the two- and five-pathogen test, respectively. Competency in Phnom Penh never reached 80% for any of the 12 or 15 steps for either test; the percentage of participants able to perform a step ranged from 26–76% and 23–72%, for the two- and five-pathogen tests, respectively. Commercially available NS1 dengue rapid tests were distributed, at no cost, to households with confirmed exposure to dengue or Zika virus; of 14 febrile cases reported, six used the provided RDT. Our findings support the need for further implementation research on the appropriate level of instructions or training needed for diverse devices in different settings, as well as how to best integrate RDTs into existing local public health and disease surveillance programs at a large scale. Author summary: Rapid diagnostic tests (RDTs) are becoming increasingly available and are useful during outbreaks of infectious and vector-borne diseases. This study set out to answer two questions regarding the use of RDTs in community settings. First, how well could community members at two diverse sites–Iquitos, Peru and Phnom Penh, Cambodia–perform an RDT on themselves and willing family members with only written and/or video instructions, and with two tests of different complexity? Second, and only in Iquitos, if RDTs were made widely available at no cost to households, would residents choose to use one for a family member showing febrile symptoms? In Peru, 202 community members were provided written and/or video instructions and a test kit, and then were observed operating the RDT on themselves or family members in their own homes. In Cambodia, 45 Community Health Workers and 50 community members were provided only written instructions at a local health center and asked to carry out the test. In both locations, trained observers scored each of the 12–15 steps necessary to conduct the test on a 3-point scale (1 being lowest proficiency level, 3 being highest), for one of the two RDTs in this study. In Iquitos, >80% of residents were able to perform 11/12 steps and 7/15 steps for the two- and five-pathogen test, respectively. Competency in Phnom Penh never reached 80% for any of the 12 or 15 steps for either test, with the percentage of participants demonstrating high competency ranging from 26–76% and 23–72%, for the two- and five-pathogen tests, respectively. Finally, in Iquitos, RDTs were distributed to households with earlier confirmed cases of dengue or Zika virus: about half of all household members that developed fevers were self-tested or tested by another family member. This study is consistent with our earlier findings from focus group discussions suggesting that implementation of simple home-based rapid diagnostic devices, could be used in different settings, but further research is needed to determine the best type and level of instructions to do this. [ABSTRACT FROM AUTHOR]

Climate change is expected to pose major direct and indirect threats to groundwater-dependent forest ecosystems. Forests that concurrently experience increased rates of water extraction may face unprecedented exposure to droughts. Here, we examined differences in stem growth and xylem hydraulic architecture of 216 oak trees from sites with contrasting groundwater availability, including sites where groundwater extraction has led to reduced water availability for trees over several decades. We expected reduced growth and xylem hydraulic capacity for trees at groundwater extraction sites both under normal and unfavourable growing conditions. Compared to sites without extraction, trees at sites with groundwater extraction showed reduced growth and hydraulic conductivity both during periods of moderate and extremely low soil water availability. Trees of low vigour, which were more frequent at sites with groundwater extraction, were not able to recover growth and hydraulic capacity following drought, pointing to prolonged drought effects. Long-term water deficit resulting in reduced CO2 assimilation and hydraulic capacity after drought are very likely responsible for observed reductions in tree vitality at extraction sites. Our results demonstrate that groundwater access maintains tree function and resilience to drought and is therefore important for tree health in the context of climate change. [ABSTRACT FROM AUTHOR]

Previously it was demonstrated that triptycene end‐capping can be used as a crystal engineering strategy to direct the packing of quinoxalinophenanthrophenazines (QPPs) towards cofacially stacked π dimers with large molecular overlap resulting in high charge transfer integrals. Remarkably, this packing motif was formed under different crystallization conditions and with a variety of derivatives bearing additional functional groups or aromatic substituents. Benzothienobenzothiophene (BTBT) and its derivatives are known as some of the best performing compounds for organic field‐effect transistors. Here, the triptycene end‐capping concept is introduced to this class of compounds and polymorphic crystal structures are investigated to evaluate the potential of triptycene end‐caps as synthons for crystal engineering. [ABSTRACT FROM AUTHOR]

Gold‐catalyzed cyclization of 1,5‐diynes with ketones as reagents and solvent provides diversely substituted vinyl ethers under mild conditions. The regioselectivity of such gold‐catalyzed cyclizations is usually controlled by the scaffold of the diyne. Herein, we report the first solvent‐controlled switching of regioselectivity from a 6‐endo‐dig‐ to 5‐endo‐dig‐cyclization in these transformations, providing fulvene derivatives. With respect to the functional‐group tolerance, aryl fluorides, chlorides, bromides, and ethers are tolerated. Furthermore, the mechanism and selectivity are put to scrutiny by experimental studies and a thermodynamic analysis of the product. Additionally, 6‐(vinyloxy)fulvenes are a hitherto unknown class of compounds. Their reactivity is briefly evaluated, to give insights into their potential applications. [ABSTRACT FROM AUTHOR]

There is increasing evidence that mixed‐species forests can provide multiple ecosystem services at a higher level than their monospecific counterparts. However, most studies concerning tree diversity and ecosystem functioning relationships use data from forest inventories (under noncontrolled conditions) or from very young plantation experiments. Here, we investigated temporal dynamics of diversity–productivity relationships and diversity–stability relationships in the oldest tropical tree diversity experiment. Sardinilla was established in Panama in 2001, with 22 plots that form a gradient in native tree species richness of one‐, two‐, three‐ and five‐species communities. Using annual data describing tree diameters and heights, we calculated basal area increment as the proxy of tree productivity. We combined tree neighbourhood‐ and community‐level analyses and tested the effects of both species diversity and structural diversity on productivity and its temporal stability. General patterns were consistent across both scales indicating that tree–tree interactions in neighbourhoods drive observed diversity effects. From 2006 to 2016, mean overyielding (higher productivity in mixtures than in monocultures) was 25%–30% in two‐ and three‐species mixtures and 50% in five‐species stands. Tree neighbourhood diversity enhanced community productivity but the effect of species diversity was stronger and increased over time, whereas the effect of structural diversity declined. Temporal stability of community productivity increased with species diversity via two principle mechanisms: asynchronous responses of species to environmental variability and overyielding. Overyielding in mixtures was highest during a strong El Niño‐related drought. Overall, positive diversity–productivity and diversity–stability relationships predominated, with the highest productivity and stability at the highest levels of diversity. These results provide new insights into mixing effects in diverse, tropical plantations and highlight the importance of analyses of temporal dynamics for our understanding of the complex relationships between diversity, productivity and stability. Under climate change, mixed‐species forests may provide both high levels and high stability of production. [ABSTRACT FROM AUTHOR]

As part of a study to investigate drivers of dengue virus (DENV) transmission dynamics, this qualitative study explored whether DENV-infected residents of Iquitos, Peru, considered it acceptable (1) to participate in direct mosquito feeding experiments (lab-reared Aedes aegypti mosquitoes fed directly on human volunteers) and (2) to provide blood meals indirectly (Ae. aegypti fed on blood drawn from participants by venipuncture). Twelve focus group discussions (FGDs; 94 participants: 82 females and 12 males) were conducted in January 2014 to explore six themes: (1) concerns and preferences regarding direct mosquito feeds and blood draws, (2) comprehension of and misconceptions about study procedures, (3) motivating factors for participation, (4) acceptability of children’s participation, (5) willingness to provide multiple samples over several days, and (6) preference for direct feedings in homes versus the study laboratory. Results of FGDs, including one with 5 of 53 past direct mosquito feed participants, indicated that mosquito feeding procedures are acceptable to Iquitos residents when they are provided with information and a few key messages are properly reinforced. FGD participants’ concerns focused primarily on safety issues rather than discomfort associated with mosquito bites. A video explaining the study dramatically increased comprehension of the study procedures. The majority of participants expressed a preference for mosquito feeding over venipuncture. Adults supported child participation if the children themselves assented. For most participants, home feedings were preferred over those in a laboratory. A major impetus for participation was the idea that results would contribute to an improved understanding of DENV transmission in Iquitos. Findings from our study will support future large-scale studies that employ direct mosquito feeding, a low-risk, non-invasive procedure that is experimentally superior to artificial mosquito feeding methods. [ABSTRACT FROM AUTHOR]

Bacteria have evolved different systems to sense and adapt to acid stress. For example, Vibrio campbellii, a marine pathogen for invertebrates, encounters acidic conditions in the digestive glands of shrimp. The main acid resistance system of V. campbellii is the Cad system, which is activated when cells are in a low-pH, amino acid-rich environment. The Cad system consists of the pH-responsive transcriptional activator CadC, the lysine decarboxylase CadA, and the lysine/cadaverine antiporter CadB. In many Vibrio species, the LysR-type transcriptional regulator AphB is involved in the regulation of the Cad system, but its precise role is unclear. Here, we examined AphB of V. campbellii in vivo and in vitro in the context of Cad activation. At low pH, an aphB deletion mutant was less able to grow and survive compared with the wild-type because it did not excrete sufficient alkaline cadaverine to increase the extracellular pH. AphB was found to upregulate the transcription of cadC, thereby increasing its protein copy number per cell. Moreover, AphB itself was shown to be a pH-sensor, and binding to the cadC promoter increased under low pH, as shown by surface plasmon resonance spectroscopy. By monitoring the activation of the Cad system over a wide range of pH values, we found that AphB-mediated upregulation of cadC not only adjusts CadC copy numbers depending on acid stress strength, but also affects the response of individual cells and thus the degree of heterogeneous Cad system activation in the V. campbellii population. [ABSTRACT FROM AUTHOR]

The bacteria Streptomyces davawensis and Streptomyces cinnabarinus produce roseoflavin, the only known natural riboflavin (vitamin B2) analogue with antibiotic activity. Roseoflavin can be considered a natural antimetabolite and has been postulated to be biosynthesized from riboflavin via the key intermediate 8-demethyl-8-aminoriboflavin (AF). The required site-specific substitution of one of the methyl groups on the dimethylbenzene ring of riboflavin by an amino group (to give AF) is challenging. The pathway from riboflavin to AF has remained elusive, and the corresponding enzyme/s was/were unknown. Herein, we show by systematic gene deletion, heterologous gene expression, and biochemical studies that the enzyme specified by the gene BN159_7989 from S. davawensis is able to carry out a whole set of chemical reactions starting from riboflavin-5′-phosphate to give the final product 8-demethyl-8-aminoriboflavin-5′-phosphate (AFP). [ABSTRACT FROM AUTHOR]

Die Bakterienarten Streptomyces davawensis und Streptomyces cinnabarinus produzieren Roseoflavin, das einzige bekannte natürliche Analogon von Riboflavin (Vitamin B2) mit antibiotischer Wirkung. Roseoflavin kann als natürlicher Antimetabolit bezeichnet werden und soll aus Riboflavin über das Schlüsselintermediat 8 ‐ Demethyl ‐ 8 ‐ aminoriboflavin (AF) synthetisiert werden. Der ortsspezifische Austausch einer Methylgruppe des Dimethylbenzolrings von Riboflavin gegen eine Aminogruppe (der zu AF führt) ist mechanistisch schwierig. Der Biosyntheseweg von Riboflavin zu AF war unklar, und das/die zugehörige/n Enzym/e war/en unbekannt. Systematische Gendeletions ‐ und ‐ expressionsexperimente sowie biochemische Analysen zeigten jetzt, dass das vom Gen BN159_7989 aus S. davawensis kodierte Enzym mehrere chemischer Reaktionen katalysieren kann: Ausgehend von Riboflavin ‐ 5′ ‐ phosphat bildet BN159_7989 8 ‐ Demethyl ‐ 8 ‐ aminoriboflavin ‐ 5′ ‐ phosphat. Wer braucht hier Hilfe? Anders als erwartet katalysiert ein einziges Enzym die wesentlichen Schritte der Biosynthese von Roseoflavin aus Riboflavin, dem Vitamin B2. Dieses Enzym wurde RosB genannt. Roseoflavin, ein Antibiotikum, wird vom Bakterium Streptomyces davawensis beim Wachstum auf einem flüssigen Nährboden gebildet, der lösliche Stärke und Hefeextrakt enthält (siehe Bild). [ABSTRACT FROM AUTHOR]

Abstract: In the present study, porcine buccal and vaginal mucosae were successfully characterised by ATR–FTIR for the first time and compared to porcine ear skin. By analysing typical bands of the spectra, the structure of proteins and the lipid matrix were elucidated. According to the body site, differences in membrane permeability were detected when analysing the CH2-stretching and -scissoring vibrations. The results indicated a higher permeability for porcine vaginal and buccal tissue compared to skin. Furthermore, the influence of a lecithin-based microemulsion on the barrier properties of the above mentioned tissues was investigated by ATR–FTIR; the results revealed structural changes in all tissues. In addition, the ATR–FTIR technique was employed to semi-quantitatively analyse compounds directly on skin. To this end, tape stripping experiments were performed with a deuterated liposomal drug delivery system containing the model drug flufenamic acid. While the amount of penetrated deuterated liposomes was determined directly on skin samples by ATR–FTIR, the drug amount was analysed by HPLC after extraction of the tape strips since higher sensitivity was achieved in this fashion. Thus, it was possible to monitor the skin penetration of drug and vehicle simultaneously. Interestingly, the results indicated an independent drug penetration after release from the liposomal carrier system. [Copyright &y& Elsevier]

The skin penetration of flufenamic acid (Fluf) and fluconazole (Fluc) from innovative natural microemulsions was investigated in tape-stripping experiments on pig ears. The formulations were based on the eudermic surfactants lecithin, sucrose laurate, alkylpolyglycoside or a mixture thereof. The quantification of the penetrated drug amounts was executed by 19F nuclear magnetic resonance (NMR) in comparison with high-performance liquid chromatography (HPLC). The data obtained by the 19F NMR method were confirmed by additional quantitative studies using HPLC. An excellent linear correlation was found for Fluf as well as for Fluc between 19F NMR and HPLC data. This work presents a strategy outlining the use of 19F NMR to selectively monitor the skin penetration routes of fluorinated compounds. Fluc penetrated generally well into the stratum corneum with the significantly highest amounts from the sucrose laurate microemulsion on the tape strips 1-5. Similarly, the highest amounts of penetrated Fluf could be observed from the formulation based on sucrose laurate. In addition, NMR self-diffusion studies were conducted and revealed a bicontinuous microstructure of the investigated microemulsions. The skin penetration results are in good agreement with the obtained 19F NMR self-diffusion coefficients of the active compounds in the microemulsion systems. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:2699-2706, 2013 [ABSTRACT FROM AUTHOR]

Abstract: Coenzyme Q10 (CoQ10) acts as an antioxidant in the skin and is frequently contained in anti-aging products. In previous studies, it could be shown that nano-structured lipid carriers (NLC) with a size of about 230nm are beneficial for the dermal delivery of CoQ10. They increased Q10 skin penetration when compared to equally sized nanoemulsion. In this study, ultra-small NLC were prepared with even smaller mean particles sizes of around 80nm. The influence of this decrease of particle size was investigated in terms of skin permeation and penetration as well as physicochemical stability of the NLC. Improved dermal delivery of CoQ10 by ultra-small NLC could be achieved. [Copyright &y& Elsevier]

Background Despite the frequent use of porcine ear skin for tape-stripping experiments, the peculiarities of this skin type have not been characterised in detail yet. Thus, different techniques were employed to investigate the skin surface structure of porcine ear skin and the changes in barrier function during in vitro tape stripping. To this end, the potential of capacitance-based skin hydration imaging as a means of skin quality control was investigated for the first time. Methods The porcine ear model was characterised before and during tape stripping using transepidermal water loss ( TEWL) measurements, capacitance-based sensor imaging, attenuated total reflection Fourier transform infrared spectroscopy ( ATR- FTIR) and optical light microscopy. Results The capacitance-based sensor was found to deliver precise information about the quality of the employed skin sites before and during tape stripping. The removal of stratum corneum proteins was highly reproducible even for different porcine ear types. The mean greyscale values showed an excellent linear correlation to the corresponding TEWL values and the respective penetration depth. Optical light microscopy confirmed the presence of canyons on the surface of porcine ear skin. Conclusion The results suggest that the capacitance-based sensor is a suitable tool for skin integrity testing of porcine ear skin in vitro and for monitoring changes in skin barrier function. [ABSTRACT FROM AUTHOR]

Streptomyces davawensis JCM 4913 synthesizes the antibiotic roseoflavin, a structural riboflavin (vitamin B2) analog. Here, we report the 9,466,619-bp linear chromosome of S. davawensis JCM 4913 and a 89,331-bp linear plasmid. The sequence has an average G+C content of 70.58% and contains six rRNA operons (16S-23S-5S) and 69 tRNA genes. The 8,616 predicted proteincoding sequences include 32 clusters coding for secondary metabolites, several of which are unique to S. davawensis. The chromosome contains long terminal inverted repeats of 33,255 bp each and atypical telomeres. Sequence analysis with regard to riboflavin biosynthesis revealed three different patterns of gene organization in Streptomyces species. Heterologous expression of a set of genes present on a subgenomic fragment of S. davawensis resulted in the production of roseoflavin by the host Streptomyces coelicolor M1152. Phylogenetic analysis revealed that S. davawensis is a close relative of Streptomyces cinnabarinus, and much to our surprise, we found that the latter bacterium is a roseoflavin producer as well. [ABSTRACT FROM AUTHOR]

Abstract: Nanocarriers are highly interesting delivery systems for the dermal application of drugs. Based on a eudermic alkylpolyglycosid nanoemulsions, solid lipid nanoparticles (SLN) and nano-structured lipid carriers (NLC) were prepared by ultrasonic dispersion. The ultrasound preparation technique turned out to be convenient and rapid. For reasons of comparison, nanoemulsions were also prepared by high-pressure homogenisation with highly similar physicochemical properties. Cryo electron microscopy was employed to elucidate the microstructure of the ultrasound-engineered nanocarriers. Furthermore, in vitro skin experiments showed excellent skin permeation and penetration properties for flufenamic acid from all formulations. Moreover, ATR-FTIR studies revealed barrier-restorative properties for NLC and SLN. Furthermore, the rheological characteristics of all nanocarriers were determined. In order to increase the viscosity, three different polymers were employed to also prepare semi-solid NLC drug delivery systems. All of them exhibited comparable skin diffusion properties, but may offer improved dermal applicability. [Copyright &y& Elsevier]

Abstract: In the present study multiple W/O/W nanoemulsions were optimised for the dermal application of the antiviral drug aciclovir. The phase inversion temperature method was employed to prepare the formulations without the input of high pressure. During formulation design the ethoxylated surfactants were varied and if possible partly replaced by natural sugar surfactants. Multiple nanoemulsions with mean droplet sizes around 100nm and polydispersity indices below 0.1 were prepared. At room temperature, they exhibited excellent physicochemical stability over an observation period of 6 months. Furthermore, cryo electron microscopy gave an insight into the microstructure of the multiple nanoemulsions. Moreover, the formulations’ interaction with skin was analysed by ATR-FTIR. In Franz-type diffusion cell and tape stripping experiments aciclovir showed satisfying skin permeation from the novel nanoemulsions. [Copyright &y& Elsevier]

Abstract: Microemulsions are thermodynamically stable, colloidal drug delivery systems. This study presents the first substantiated comparison of natural, skin-compatible and biodegradable surfactants in terms of their suitability to form isotropic microemulsions and their skin interaction. Pseudoternery phase diagrams were constructed for lecithin, sucrose laurate and alkylpolyglycoside as single surfactants. Moreover, also mixed surfactant films of lecithin and alkylpolyglycoside as well as lecithin and sucrose laurate were tested. Large isotropic areas could be identified for lecithin, sucrose laurate and lecithin–sucrose laurate. One defined composition was chosen from the pseudoternery phase diagram, prepared with all investigated surfactants and 1:1 surfactant mixtures, respectively, and analysed for their effect on the stratum corneum on a molecular level by ATR-FTIR. Significantly higher frequency values of the symmetric and asymmetric CH2-stretching bands compared to the control were recorded for all microemulsions, indicating a hexagonal arrangement of the lipid chains. A similar trend was observed for the lateral packing of the alkyl chains as suggested by the shift of the CH2-scissoring bands. Moreover, diffusion cell experiments using porcine skin were performed with the two model drugs flufenamic acid and fluconazole. In both cases, the lecithin-based microemulsions showed the highest permeation rates followed by the alkylpolyglycoside–lecithin microemulsions. [Copyright &y& Elsevier]

Abstract: Porcine ear skin is frequently used as a substitute for human skin in dermatological research and is especially useful for tape stripping experiments where the penetration of active substances into the uppermost skin layers is investigated. However, certain differences between the surface properties of these skin types exist, and reports on the comparability of tape stripping data obtained in vitro using porcine ear skin and data obtained in vivo on human forearm skin are scarce. Thus, we performed comparative tape stripping experiments in which the skin penetration of curcumin and fluorescein sodium from conventional microemulsions and hydrogels was investigated. In this context, the skin penetration potential of novel semi-solid macroemulsions and fluid nanoemulsions based on sucrose stearate was evaluated as well. The removed corneocytes were quantified by NIR-densitometry using recent correlation data for human and porcine proteins. The trends observed for the skin penetration into porcine ear skin were highly representative for the in vivo situation on human skin, confirming that the porcine ear is an excellent in vitro model for tape stripping experiments. Moreover, the validity of the NIR-densitometric approach for the quantification of both human and porcine stratum corneum proteins was confirmed in this study for the first time. [Copyright &y& Elsevier]

Liposomes are ideal dermal drug delivery systems because of their ability to alter the biodistribution profile of incorporated drugs. In a novel approach to optimize the liposomal microstructure, lysine derivatives were employed. The effect of the oligopeptides Lys-5 and Lys-7 on the structure as well as on the skin permeation of the antimycotic drug fluconazole in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine vesicles was studied using a variety of techniques. It was demonstrated by addition of the shift reagent praseodymium(III)chloride and subsequent P NMR measurements that the liposomes produced consisted mainly of unilamellar vesicles. This was confirmed by cryo-transmission electron microscopy. The addition of Lys-5 and Lys-7 induced a structural change resulting in a decrease in particle size between 10% and 40% and a retarding effect on fluconazole skin permeation. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:2911-2919, 2011 [ABSTRACT FROM AUTHOR]

Mild non-ionic sucrose ester surfactants can be employed to produce lipid-based drug delivery systems for dermal application. Moreover, sucrose esters of intermediate lipophilicity such as sucrose stearate S-970 possess a peculiar rheological behavior which can be employed to create highly viscous semi-solid formulations without any further additives. Interestingly, it was possible to develop both viscous macroemulsions and fluid nanoemulsions with the same chemical composition merely by slight alteration of the production process. Optical light microscopy and cryo transmission electron microscopy (TEM) revealed that the sucrose ester led to the formation of an astonishing hydrophilic network at a concentration of only 5% w/w in the macroemulsion system. A small number of more finely structured aggregates composed of surplus surfactant were likewise detected in the nanoemulsions. These discoveries offer interesting possibilities to adapt the low viscosity of fluid O/W nanoemulsions for a more convenient application. Moreover, a simple and rapid production method for skin-friendly creamy O/W emulsions with excellent visual long-term stability is presented. It could be shown by franz-cell diffusion studies and in vitro tape stripping that the microviscosity within the semi-solid formulations was apparently not influenced by their increased macroviscosity: the release of three model drugs was not impaired by the complex network-like internal structure of the macroemulsions. These results indicate that the developed semi-solid emulsions with advantageous application properties are highly suitable for the unhindered delivery of lipophilic drugs despite their comparatively large particle size and high viscosity. [ABSTRACT FROM AUTHOR]

The impacts of temperature on the activity and on the size as well as on the community composition of denitrifiers in an agricultural soil were studied in a controlled laboratory experiment. Soil slurries were incubated at different temperatures (4, 15, 20, 25, and 37 °C) under nonlimiting substrate conditions for 3 weeks. The abundance of the nitrate-reducer community in general was determined using the most probable number (MPN) technique; denitrifier activity and community composition were assessed by measuring potential denitrifier enzyme activity and by terminal restriction fragment length polymorphisms as well as by phylogenetic analysis of nitrite reductase gene amplicons ( nirK and nirS). Increasing incubation temperatures resulted in gradually enhanced denitrification activity, but also in higher abundance of nitrate reducers and in different denitrifier community compositions. Genetic and physiological characterization of isolates purified from the highest dilution of the MPN series emphasized community differences. Overall, temperature apparently not only affected process rates but also resulted in the enrichment of denitrifiers and shifts in the community composition. [ABSTRACT FROM AUTHOR]

Acetate is an important intermediate in the decomposition of organic matter in anoxic freshwater sediments. Here, we identified distinct microorganisms active in its oxidation and transformation to methane in the anoxic methanogenic layers of Lake Kinneret (Israel) profundal sediment by rRNA-based stable isotope probing (RNA-SIP). After 18 days of incubation with amended [U-13C]acetate we found that archaeal 16S rRNA was 13C-labelled to a far greater extent than bacterial rRNA. We identified acetoclastic methanogens related to Methanosaeta concilii as being most active in the degradation and assimilation of acetate. Oxidation of the acetate-methyl group played only a minor role, but nevertheless ‘heavy’13C-labelled bacterial rRNA templates were identified. ‘Heavy’ bacteria were mainly affiliated with the Betaproteobacteria (mostly Rhodocyclales and Nitrosomonadales), the Nitrospira phylum (related to ‘ Magnetobacterium bavaricum’ and Thermodesulfovibrio yellowstonii), and also with the candidate phylum ‘ Endomicrobia’. However, the mode of energy gain that allowed for the assimilation of 13C-acetate by these bacterial groups remains unknown. It may have involved syntrophic oxidation of acetate, reduction of chlorinated compounds, reduction of humic substances, fermentation of organic compounds, or even predation of 13C-labelled Methanosaeta spp. In summary, this SIP experiment shows that acetate carbon was predominantly consumed by acetoclastic methanogens in profundal Lake Kinneret sediment, while it was also utilized by a small and heterogeneous community of bacteria. [ABSTRACT FROM AUTHOR]

Ziegler‐Natta (ZN) based co‐polymerization processes for the production of linear low‐density polyethylene (LLDPE) generally give rise to a non‐uniform incorporation distribution of the comonomer. It has been shown that lowering the titanation temperature during catalyst synthesis can increase the evenness of this distribution. However, polymerization process parameters also affect the resulting incorporation distribution. To investigate these factors, a ZN system using a variety of comonomer‐types, at various ‐concentrations and polymerization temperatures is studied. The molecular properties of the polymer samples obtained are analyzed by high‐temperature size‐exclusion chromatography (HT‐SEC). It is shown that a more uniform incorporation distribution of the comonomer can be achieved by lowering either the polymerization temperature or the comonomer concentration, and that lowering both increases the effect. [ABSTRACT FROM AUTHOR]

An algal bloom of Peridinium gatunenese generally precedes the annual maximum of methane release from the profundal sediment of Lake Kinneret. Therefore, we investigated the response of the sediment methanogenic microbial community to simulated algal deposition. Addition of algal biomass on top of sediment cores resulted in increased CH4 production rates and concentrations of the fermentation products acetate and propionate in the upper 4-cm layers with maximum values at 1-cm depth. Addition of algae to sediment slurries also resulted in increased CH4 production rates and a transient increase of H2, propionate, and acetate concentrations within the first 10 d after addition. The composition of the active microbial community was determined by analysis of terminal restriction fragment polymorphism (T-RFLP) targeting ribosomal RNA and cloning and sequencing of reverse-transcribed 16S rRNA. Analysis of the sediment in the presence and absence of algae indicated that among the Bacteria, members of Deltaproteobacteria and Clostridiales responded by synthesis of ribosomes after 1 d of incubation and those of Bacteroidetes after 6 d. Among the Archaea, ribosomal RNA of the Methanosaetaceae (i.e., acetate-utilizing methanogens) slightly increased after 6 d. Algal deposition apparently stimulated ribosomal synthesis in these sediment microorganisms, thus resulting in increased activity. We conclude that these microorganisms were involved in degradation of the algal biomass resulting in transient release of acetate and other fermentation products and increased production of CH4. [ABSTRACT FROM AUTHOR]

Extreme droughts are expected to increase in frequency and severity in many regions of the world, threatening multiple ecosystem services provided by forests. Effective strategies to adapt forests to such droughts require comprehensive information on the effects and importance of the factors influencing forest resistance and resilience. We used a unique combination of inventory and dendrochronological data from a long‐term (>30 years) silvicultural experiment in mixed silver fir and Norway spruce mountain forests along a temperature and precipitation gradient in southwestern Germany. We aimed at examining the mechanisms and forest stand characteristics underpinning the resistance and resilience to past mild and severe droughts. We found that (i) fir benefited from mild droughts and showed higher resistance (i.e., lower growth loss during drought) and resilience (i.e., faster return to pre‐drought growth levels) than spruce to all droughts; (ii) species identity determined mild drought responses while species interactions and management‐related factors strongly influenced the responses to severe droughts; (iii) intraspecific and interspecific interactions had contrasting effects on the two species, with spruce being less resistant to severe droughts when exposed to interaction with fir and beech; (iv) higher values of residual stand basal area following thinning were associated with lower resistance and resilience to severe droughts; and (v) larger trees were resilient to mild drought events but highly vulnerable to severe droughts. Our study provides an analytical approach for examining the effects of different factors on individual tree‐ and stand‐level drought response. The forests investigated here were to a certain extent resilient to mild droughts, and even benefited from such conditions, but were strongly affected by severe droughts. Lastly, negative effects of severe droughts can be reduced through modifying species composition, tree size distribution and stand density in mixed silver fir‐Norway spruce forests. [ABSTRACT FROM AUTHOR]

In 2012, the U.S. Defense Threat Reduction Agency Joint Science and Technology Office initiated a program to develop novel point-of-need diagnostic devices for surveillance of emerging infectious diseases including dengue, malaria, plague, and melioidosis. Prior to distribution of devices to observe their correct use among community members in Iquitos, Peru, and Phnom Penh, Cambodia, research was conducted to: 1) assess acceptability of use, including the motivation to use a rapid diagnostic test (RDT) before or instead of seeking care at a health facility, 2) explore comprehension of RDT use instructions, and 3) examine possible strategies for large scale RDT distribution and use at each site. In February 2014, 9 focus group discussions (FGD) with community members and 5 FGD with health professionals were conducted in Iquitos, and 9 FGD with community members and 9 in-depth interviews with health professionals in Phnom Penh. In both places, participants agreed to use the device themselves (involving finger prick) or could identify someone who could do so in their home or neighborhood. The main incentive to RDT use in both sites was the ability for device results to be used for care facilitation (post confirmatory tests), specifically reduced wait times to be seen or obtain a diagnosis. Comprehension of RDT use instructions was assessed in Iquitos by asking some participants to apply the device to research team members; after watching a short video, most steps were done correctly. In Phnom Penh, participants were asked to describe each step after reading the instructions; they struggled with comprehension. Health professionals' main concerns in both sites were their community's ability to accurately use the test, handle complicated instructions, and safety (i.e., disposal of lancets). Health system structure and ability to use home diagnostic devices varied in the two disease endemic sites, with substantial challenges in each, suggesting the need for different strategies for RDT large scale community use, and illustrating the value of formative research before deployment of novel technologies. Development and use of devices to diagnose infectious diseases outside of health facilities (i.e., at home or in remote areas) continues to increase, providing new options for the follow up and treatment options of individuals, depending on the diseases. In this qualitative study, researchers in Iquitos, Peru, and Phnom Penh, Cambodia explored what local people thought about the possible availability of such a device to diagnose dengue and malaria in their own houses, and what would motivate them to use such a device instead of going directly to a health facility for the diagnosis. Participants reported being willing to use device on themselves and were motivated by the possibility that, by using this diagnostic device and taking the result to their health facility, they might be able to obtain quicker and more optimized attention at the health facility; for example, by obtaining a positive result to dengue or malaria on the rapid diagnostic device, they are aware they might still need confirmatory tests, but they would be able to reduce the wait time for obtaining a definitive diagnosis and starting treatment by a full day. Questions regarding accuracy of tests, complicated instructions and safety of using these devices in the community were brought up by participants—individuals living in the communities and local health professionals. Also, in this study, it was clear that if these devices were to be made available in Peru and Cambodia, different strategies for disseminating and using these in the communities would be needed to accommodate for different health infrastructure in both sites. [ABSTRACT FROM AUTHOR]

Background Histo-blood group antigens (HBGAs) such as fucosyltransferase (FUT)2 and 3 may act as innate host factors that differentially influence susceptibility of individuals and their offspring to pediatric enteric infections. Methods In 3 community-based birth cohorts, FUT2 and FUT3 statuses were ascertained for mother-child dyads. Quantitative polymerase chain reaction panels tested 3663 diarrheal and 18 148 asymptomatic stool samples for 29 enteropathogens. Cumulative diarrhea and infection incidence were compared by child (n = 520) and mothers' (n = 519) HBGA status and hazard ratios (HRs) derived for all-cause diarrhea and specific enteropathogens. Results Children of secretor (FUT2 positive) mothers had a 38% increased adjusted risk of all-cause diarrhea (HR = 1.38; 95% confidence interval (CI), 1.15–1.66) and significantly reduced time to first diarrheal episode. Child FUT2 and FUT3 positivity reduced the risk for all-cause diarrhea by 29% (HR = 0.81; 95% CI, 0.71–0.93) and 27% (HR = 0.83; 95% CI, 0.74–0.92), respectively. Strong associations between HBGAs and pathogen-specific infection and diarrhea were observed, particularly for noroviruses, rotaviruses, enterotoxigenic Escherichia coli , and Campylobacter jejuni / coli. Conclusions Histo-blood group antigens affect incidence of all-cause diarrhea and enteric infections at magnitudes comparable to many common disease control interventions. Studies measuring impacts of interventions on childhood enteric disease should account for both child and mothers' HBGA status. [ABSTRACT FROM AUTHOR]

Background: Transmission of dengue virus (DENV) from humans to mosquitoes represents a critical component of dengue epidemiology. Examinations of this process have generally been hampered by a lack of methods that adequately represent natural acquisition of DENV by mosquitoes from humans. In this study, we assessed artificial and natural blood feeding methods based on rates of DENV infection and dissemination within mosquitoes for use in a field-based epidemiological cohort study in Iquitos, Peru. Methodology/Principal findings: Our study was implemented, stepwise, between 2011 and 2015. Participants who were 5 years and older with 5 or fewer days of fever were enrolled from ongoing clinic- and neighborhood-based studies on dengue in Iquitos. Wild type, laboratory-reared Aedes aegypti were fed directly on febrile individuals or on blood collected from participants that was either untreated or treated with EDTA. Mosquitoes were tested after approximately 14 days of extrinsic incubation for DENV infection and dissemination. A total of 58 participants, with viremias ranging from 1.3 × 102 to 2.9 × 106 focus-forming units per mL of serum, participated in one or more feeding methods. DENV infection and dissemination rates were not significantly different following direct and indirect-EDTA feeding; however, they were significantly lower for mosquitoes that fed indirectly on blood with no additive. Relative to direct feeding, infection rates showed greater variation following indirect-EDTA than indirect-no additive feeding. Dissemination rates were correlated across all feeding methods. No differences were detected in DENV infection or dissemination rates in mosquitoes fed directly on participants with different dengue illness severity. Conclusions/Significance: Our study demonstrates the feasibility of using direct and indirect feeding methods for field-based studies on vector competence. Direct mosquito feeding is preferable in terms of logistical ease, biosecurity, and reliability. [ABSTRACT FROM AUTHOR]

FMN riboswitches are genetic elements that, in many bacteria, control genes responsible for biosynthesis and/or transport of riboflavin (vitamin B2). We report that the Escherichia coli ribB FMN riboswitch controls expression of the essential gene ribB coding for the riboflavin biosynthetic enzyme 3,4-dihydroxy-2-butanone-4-phosphate synthase (RibB; ). Our data show that the E. coli ribB FMN riboswitch is unusual because it operates at the transcriptional and also at the translational level. Expression of ribB is negatively affected by FMN and by the FMN analog roseoflavin mononucleotide, which is synthesized enzymatically from roseoflavin and ATP. Consequently, in addition to flavoenzymes, the E. coli ribB FMN riboswitch constitutes a target for the antibiotic roseoflavin produced by Streptomyces davawensis. [ABSTRACT FROM AUTHOR]

HbpS is an extracellular oligomeric protein, which has been shown to act in concert with the two-component system SenS-SenR during the sensing of redox stress. HbpS can bind and degrade heme under oxidative stress conditions, leading to a free iron ion. The liberated iron is subsequently coordinated on the protein surface. Furthermore, HbpS has been shown to modulate the phosphorylation state of the sensor kinase SenS as, in the absence of oxidative stress conditions, HbpS inhibits SenS autophosphorylation whereas the presence of heme or iron ions and redox-stressing agents enhances it. Using HbpS wild type and mutants as well as different biochemical and biophysical approaches, we show that iron-mediated oxidative stress induces both secondary structure and overall intrinsic conformational changes within HbpS. We demonstrate in addition that HbpS is oxidatively modified, leading to the generation of highly reactive carbonyl groups and tyrosine-tyrosine bonds. Further examination of the crystal structure and subsequent mutational analyses allowed the identification of the tyrosine residue participating in dityrosine formation, which occurs between two monomers within the octomeric assembly. Therefore, it is proposed that oxidative modifications causing structural and conformational changes are responsible for the control of SenS and hence of the HbpS-SenS-SenR signaling cascade. [ABSTRACT FROM AUTHOR]

Background: Histo-blood group antigens (HBGAs) such as fucosyltransferase (FUT)2 and 3 may act as innate host factors that differentially influence susceptibility of individuals and their offspring to pediatric enteric infections.Methods: In 3 community-based birth cohorts, FUT2 and FUT3 statuses were ascertained for mother-child dyads. Quantitative polymerase chain reaction panels tested 3663 diarrheal and 18 148 asymptomatic stool samples for 29 enteropathogens. Cumulative diarrhea and infection incidence were compared by child (n = 520) and mothers' (n = 519) HBGA status and hazard ratios (HRs) derived for all-cause diarrhea and specific enteropathogens.Results: Children of secretor (FUT2 positive) mothers had a 38% increased adjusted risk of all-cause diarrhea (HR = 1.38; 95% confidence interval (CI), 1.15-1.66) and significantly reduced time to first diarrheal episode. Child FUT2 and FUT3 positivity reduced the risk for all-cause diarrhea by 29% (HR = 0.81; 95% CI, 0.71-0.93) and 27% (HR = 0.83; 95% CI, 0.74-0.92), respectively. Strong associations between HBGAs and pathogen-specific infection and diarrhea were observed, particularly for noroviruses, rotaviruses, enterotoxigenic Escherichia coli, and Campylobacter jejuni/coli.Conclusions: Histo-blood group antigens affect incidence of all-cause diarrhea and enteric infections at magnitudes comparable to many common disease control interventions. Studies measuring impacts of interventions on childhood enteric disease should account for both child and mothers' HBGA status. [ABSTRACT FROM AUTHOR]

All living cells have a large number of proteins that are anchored with one transmembrane helix in the cytoplasmic membrane. Almost nothing is known about their spatiotemporal organization in whole cells. Here we report on the localization and dynamics of one representative, the pH sensor and transcriptional regulator CadC in Escherichia coli. Fluorophore-tagged CadC was detectable as distinct cluster only when the receptor was activated by external stress, which results in DNA-binding. Clusters immediately disappeared under non-stress conditions. CadC variants that mimic the active state of CadC independent of environmental stimuli corroborated the correlation between CadC clustering and binding to the DNA, as did altering the number or location of the DNA-binding site(s) in whole cells. These studies reveal a novel diffusion-and-capture mechanism to organize a membrane-integrated receptor dependent on the DNA in a rod-shaped bacterium. Brameyer et al. identify a diffusion-and-capture mechanism responsible for the localization of the membrane integrated receptor and transcriptional activator CadC in E. coli. They find that external stress activates CadC, resulting in DNA-binding and cluster formation in the cytoplasmic membrane. [ABSTRACT FROM AUTHOR]

All living cells have a large number of proteins that are anchored with one transmembrane helix in the cytoplasmic membrane. Almost nothing is known about their spatiotemporal organization in whole cells. Here we report on the localization and dynamics of one representative, the pH sensor and transcriptional regulator CadC in Escherichia coli. Fluorophore-tagged CadC was detectable as distinct cluster only when the receptor was activated by external stress, which results in DNA-binding. Clusters immediately disappeared under non-stress conditions. CadC variants that mimic the active state of CadC independent of environmental stimuli corroborated the correlation between CadC clustering and binding to the DNA, as did altering the number or location of the DNA-binding site(s) in whole cells. These studies reveal a novel diffusion-and-capture mechanism to organize a membrane-integrated receptor dependent on the DNA in a rod-shaped bacterium. Brameyer et al. identify a diffusion-and-capture mechanism responsible for the localization of the membrane integrated receptor and transcriptional activator CadC in E. coli. They find that external stress activates CadC, resulting in DNA-binding and cluster formation in the cytoplasmic membrane. [ABSTRACT FROM AUTHOR]