Pharmacologic blockade of monoamine oxidase A (MAOA) or serotonin transporter (5-HTT) has antidepressant and anxiolytic efficacy in adulthood. Yet, genetically conferred MAOA or 5-HTT hypoactivity is ...associated with altered aggression and increased anxiety/depression. Here we test the hypothesis that increased monoamine signaling during development causes these paradoxical aggressive and affective phenotypes. We find that pharmacologic MAOA blockade during early postnatal development (P2-P21) but not during peri-adolescence (P22-41) increases anxiety- and depression-like behavior in adult (>P90) mice, mimicking the effect of P2-21 5-HTT inhibition. Moreover, MAOA blockade during peri-adolescence, but not P2-21 or P182-201, increases adult aggressive behavior, and 5-HTT blockade from P22-P41 reduced adult aggression. Blockade of the dopamine transporter, but not the norepinephrine transporter, during P22-41 also increases adult aggressive behavior. Thus, P2-21 is a sensitive period during which 5-HT modulates adult anxiety/depression-like behavior, and P22-41 is a sensitive period during which DA and 5-HT bi-directionally modulate adult aggression. Permanently altered DAergic function as a consequence of increased P22-P41 monoamine signaling might underlie altered aggression. In support of this hypothesis, we find altered aggression correlating positively with locomotor response to amphetamine challenge in adulthood. Proving that altered DA function and aggression are causally linked, we demonstrate that optogenetic activation of VTA DAergic neurons increases aggression. It therefore appears that genetic and pharmacologic factors impacting dopamine and serotonin signaling during sensitive developmental periods can modulate adult monoaminergic function and thereby alter risk for aggressive and emotional dysfunction.
The aim of this study was to determine the antimicrobial and antiadhesive properties of a biosurfactant isolated from Lactobacillus paracasei ssp. paracasei A20 against several micro-organisms, ...including Gram-positive and Gram-negative bacteria, yeasts and filamentous fungi. Antimicrobial and antiadhesive activities were determined using the microdilution method in 96-well culture plates. The biosurfactant showed antimicrobial activity against all the micro-organisms assayed, and for twelve of the eighteen micro-organisms (including the pathogenic Candida albicans, Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus agalactiae), the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were achieved for biosurfactant concentrations between 25 and 50 mg ml⁻¹. Furthermore, the biosurfactant showed antiadhesive activity against most of the micro-organisms evaluated. As far as we know, this is the first compilation of data on antimicrobial and antiadhesive activities of biosurfactants obtained from lactobacilli against such a broad group of micro-organisms. Although the antiadhesive activity of biosurfactants isolated from lactic acid bacteria has been widely reported, their antimicrobial activity is quite unusual and has been described only in a few strains. The results obtained in this study regarding the antimicrobial and antiadhesive properties of this biosurfactant opens future prospects for its use against micro-organisms responsible for diseases and infections in the urinary, vaginal and gastrointestinal tracts, as well as in the skin, making it a suitable alternative to conventional antibiotics.
Recent advances have improved our understanding of the renin‐angiotensin system (RAS). These have included the recognition that angiotensin (Ang)‐(1‐7) is a biologically active product of the RAS ...cascade. The identification of the ACE homologue ACE2, which forms Ang‐(1‐7) from Ang II, and the GPCR Mas as an Ang‐(1‐7) receptor have provided the necessary biochemical and molecular background and tools to study the biological significance of Ang‐(1‐7). Most available evidence supports a counter‐regulatory role for Ang‐(1‐7) by opposing many actions of Ang II on AT1 receptors, especially vasoconstriction and proliferation. Many studies have now shown that Ang‐(1‐7) by acting via Mas receptor exerts inhibitory effects on inflammation and on vascular and cellular growth mechanisms. Ang‐(1‐7) has also been shown to reduce key signalling pathways and molecules thought to be relevant for fibrogenesis. Here, we review recent findings related to the function of the ACE2/Ang‐(1‐7)/Mas axis and focus on the role of this axis in modifying processes associated with acute and chronic inflammation, including leukocyte influx, fibrogenesis and proliferation of certain cell types. More attention will be given to the involvement of the ACE2/Ang‐(1‐7)/Mas axis in the context of renal disease because of the known relevance of the RAS for the function of this organ and for the regulation of kidney inflammation and fibrosis. Taken together, this knowledge may help in paving the way for the development of novel treatments for chronic inflammatory and renal diseases.
A rich body of literature exists that has demonstrated adverse human health effects following exposure to ambient air particulate matter (PM), and there is strong support for an important role of ...ultrafine (nanosized) particles. At present, relatively few human health or epidemiology data exist for engineered nanomaterials (NMs) despite clear parallels in their physicochemical properties and biological actions in
models.
NMs are available with a range of physicochemical characteristics, which allows a more systematic toxicological analysis. Therefore, the study of ultrafine particles (UFP, <100 nm in diameter) provides an opportunity to identify plausible health effects for NMs, and the study of NMs provides an opportunity to facilitate the understanding of the mechanism of toxicity of UFP.
A workshop of experts systematically analyzed the available information and identified 19 key lessons that can facilitate knowledge exchange between these discipline areas.
Key lessons range from the availability of specific techniques and standard protocols for physicochemical characterization and toxicology assessment to understanding and defining dose and the molecular mechanisms of toxicity. This review identifies a number of key areas in which additional research prioritization would facilitate both research fields simultaneously.
There is now an opportunity to apply knowledge from NM toxicology and use it to better inform PM health risk research and vice versa. https://doi.org/10.1289/EHP424.
The root system is a major determinant of a plant's access to water and nutrients. The architecture of the root system to a large extent depends on the repeated formation of new lateral roots. In ...this review, we discuss lateral root development from a systems biology perspective. We focus on studies combining experiments with computational modeling that have advanced our understanding of how the auxin-centered regulatory modules involved in different stages of lateral root development exert their specific functions. Moreover, we discuss how these regulatory networks may enable robust transitions from one developmental stage to the next, a subject that thus far has received limited attention. In addition, we analyze how environmental factors impinge on these modules, and the different manners in which these environmental signals are being integrated to enable coordinated developmental decision making. Finally, we provide some suggestions for extending current models of lateral root development to incorporate multiple processes and stages. Only through more comprehensive models we can fully elucidate the cooperative effects of multiple processes on later root formation, and how one stage drives the transition to the next.
The branched architecture of the plant root system depends on the repeated formation of lateral roots. This review discusses current knowledge on the development of lateral roots from a systems biology perspective, focusing on the insights gained from combining experiments with computational models. It also highlights the need for future models that should integrate the multiple processes and developmental stages during lateral root development.
Summary Background The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine was immunogenic, generally well tolerated, and effective against HPV-16 or HPV-18 infections, and associated ...precancerous lesions in an event-triggered interim analysis of the phase III randomised, double-blind, controlled PApilloma TRIal against Cancer In young Adults (PATRICIA). We now assess the vaccine efficacy in the final event-driven analysis. Methods Women (15–25 years) were vaccinated at months 0, 1, and 6. Analyses were done in the according-to-protocol cohort for efficacy (ATP-E; vaccine, n=8093; control, n=8069), total vaccinated cohort (TVC, included all women receiving at least one vaccine dose, regardless of their baseline HPV status; represents the general population, including those who are sexually active; vaccine, n=9319; control, n=9325), and TVC-naive (no evidence of oncogenic HPV infection at baseline; represents women before sexual debut; vaccine, n=5822; control, n=5819). The primary endpoint was to assess vaccine efficacy against cervical intraepithelial neoplasia 2+ (CIN2+) that was associated with HPV-16 or HPV-18 in women who were seronegative at baseline, and DNA negative at baseline and month 6 for the corresponding type (ATP-E). This trial is registered with ClinicalTrials.gov , number NCT00122681. Findings Mean follow-up was 34·9 months (SD 6·4) after the third dose. Vaccine efficacy against CIN2+ associated with HPV-16/18 was 92·9% (96·1% CI 79·9–98·3) in the primary analysis and 98·1% (88·4–100) in an analysis in which probable causality to HPV type was assigned in lesions infected with multiple oncogenic types (ATP-E cohort). Vaccine efficacy against CIN2+ irrespective of HPV DNA in lesions was 30·4% (16·4–42·1) in the TVC and 70·2% (54·7–80·9) in the TVC-naive. Corresponding values against CIN3+ were 33·4% (9·1–51·5) in the TVC and 87·0% (54·9–97·7) in the TVC-naive. Vaccine efficacy against CIN2+ associated with 12 non-vaccine oncogenic types was 54·0% (34·0–68·4; ATP-E). Individual cross-protection against CIN2+ associated with HPV-31, HPV-33, and HPV-45 was seen in the TVC. Interpretation The HPV-16/18 AS04-adjuvanted vaccine showed high efficacy against CIN2+ associated with HPV-16/18 and non-vaccine oncogenic HPV types and substantial overall effect in cohorts that are relevant to universal mass vaccination and catch-up programmes. Funding GlaxoSmithKline Biologicals.
Blends of chitosan (from Cuban lobster) and clay micro/nanoparticles were prepared by dispersion of the clay particles in the film matrix and the films obtained were characterized in terms of water ...solubility, water vapor, oxygen and carbon dioxide permeability, optical, mechanical and thermal properties using an Instron universal testing machine, differential scanning calorimetry, thermogravimetric analyses and scanning electron microscopy (
SEM). The water vapor barrier properties of the films were significantly improved by incorporation of clay in their composition, while the water solubility decreased as the clay concentration increased (for a constant chitosan concentration). The tensile strength of chitosan/clay films increased significantly with increasing chitosan and clay concentrations, while the values of elongation decreased slightly for high values of chitosan concentration.
T
m
increased with the increase of chitosan concentration, but the changes in
T
m
with the addition of clay were not significant.
Polynomial models were fitted to the experimental data in order to facilitate future design of chitosan/clay film systems.
The precipitate strengthening increment arising from a reasonably monotonic distribution of plate-shaped shear-resistant precipitates in an Al matrix is considered theoretically in terms of the ...average stress required to push dislocations between the particles. The radius of the solute diffusion field surrounding the tips of the plates is shown to be a key microstructural parameter in controlling the distance of closest approach between precipitates and therefore the maximum strengthening increment. Three new strategies for enhancing the strengthening increment are proposed based on minimizing the size of the solute diffusion fields surrounding plates. These approaches are contrasted with those previously advocated. A model Al–Cu alloy containing plate-shaped, shear-resistant
θ′ (Al
2Cu) precipitates is used to experimentally test the predictions of the proposed strengthening description. Quantitative agreement between experiment and theory is observed under isothermal annealing conditions at 473
K. Furthermore, one of the strategies advocated for increasing the strengthening response is the use of a decreasing transformation temperature. This is tested experimentally at three temperatures and the peak strengthening increment is shown to be in excellent agreement with the theoretical predictions. This work suggests a reinterpretation of the origins of the strengthening observed in current high-strength Al alloys containing plate-shaped precipitates is required.
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•Vibrational properties of the Bi2(MoO4)3 at room temperature.•Lattice dynamic calculations based on the rigid ion model.•Effect of the pressure on the vibrational properties of the ...Bi2(MoO4)3.•Pressure-induced phase transformation in the Bi2(MoO4)3.
This work reports a pressure-dependent Raman spectroscopic study and the theoretical lattice dynamics calculations of a Bi2(MoO4)3 crystal. The lattice dynamics calculations were performed, based on a rigid ion model, to understand the vibrational properties of the Bi2(MoO4)3 system and to assign the experimental Raman modes under ambient conditions. The calculated vibrational properties were helpful to support pressure-dependent Raman results, including eventual structural changes induced by pressure changes. Raman spectra were measured in the spectral region between 20 and 1000 cm−1 and the evolution of the pressures values was recorded in the range of 0.1–14.7 GPa. Pressure-dependent Raman spectra showed changes observed at 2.6, 4.9 and 9.2 GPa, these changes being associated with structural phase transformations. Finally, principal component analysis (PCA) and hierarchical cluster analysis (HCA) were performed to infer the critical pressure of phase transformations undergone by the Bi2(MoO4)3 crystal.
Innovations constantly appear in food packaging, always aiming at creating a more efficient quality preservation system while improving foods’ attractiveness and marketability.
The utilization of ...renewable sources for packaging materials, such as hydrocolloids from biological origin, is one the main trends of the industry. Edible films/coatings have been considered as one of the potential technologies that can be used to increase the storability of foods and to improve the existent packaging technology, helping to ensure the microbial safety and the preservation of food from the influence of external factors.
In view of these recent developments, the main objective of this review is to provide information concerning the utilization of galactomannans in the production of edible films/coatings. The most important features of these polysaccharides are discussed, namely: their structure and applications; physical, chemical, thermal and mechanical properties of galactomannan-based films/coatings; transport properties (in particular those related to moisture, oxygen, carbon dioxide exchange through the films/coatings); incorporation of active compounds (e.g. natural antimicrobials and/or antioxidants) and applications in food products.
It is viewed that in a near future tailored edible packaging based on polysaccharides can be applied to selected foods, partially replacing non-biodegradable/non-edible plastics.
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