Nanoadsorbents in focus for the remediation of environmentally-related contaminants with rising toxicity concerns.

Modern lifestyle demands high-end commodities, for instance, cosmetics, detergents, shampoos, household cleaning, sanitary items, medicines, and so forth. In recent years, these products' consumption has increased considerably, being antibiotics and some other pharmaceutical and personal care products (PPCPs). Several antibiotics and PPCPs represent a wide range of emerging contaminants with a straight ingress into aquatic systems, given their high persistence in seawater, effluent treatment plants, and even drinking water. Under these considerations, the necessity of developing new and affordable technologies for the treatment and sustainable mitigation of pollutants is highly requisite for a safer and cleaner environment. One possible mitigation solution is an effective deployment of nanotechnological cues as promising matrices that can contribute by attending issues and improving the current strategies to detect, prevent, and mitigate hazardous pollutants in water. Focused on nanoparticles' distinctive physical and chemical properties, such as high surface area, small size, and shape, metallic nanoparticles (MNPs) have been investigated for water remediation. MNPs gained increasing interest among research groups due to their superior efficiency, stability, and high catalyst activity compared with conventional systems. This review summarizes the occurrence of antibiotics and PPCPs and the application of MNPs as pollutant mitigators in the aquatic environment. The work also focuses on transportation fate, toxicity, and current regulations for environmental safety.

Insight Into Nanoliposomes as Smart Nanocarriers for Greening the Twenty-First Century Biomedical Settings.

The necessity to develop more efficient, biocompatible, patient compliance, and safer treatments in biomedical settings is receiving special attention using nanotechnology as a potential platform to design new drug delivery systems (DDS). Despite the broad range of nanocarrier systems in drug delivery, lack of biocompatibility, poor penetration, low entrapment efficiency, and toxicity are significant challenges that remain to address. Such practices are even more demanding when bioactive agents are intended to be loaded on a nanocarrier system, especially for topical treatment purposes. For the aforesaid reasons, the search for more efficient nano-vesicular systems, such as nanoliposomes, with a high biocompatibility index and controlled releases has increased considerably in the past few decades. Owing to the stratum corneum layer barrier of the skin, the in-practice conventional/conformist drug delivery methods are inefficient, and the effect of the administered therapeutic cues is limited. The current advancement at the nanoscale has transformed the drug delivery sector. Nanoliposomes, as robust nanocarriers, are becoming popular for biomedical applications because of safety, patient compliance, and quick action. Herein, we reviewed state-of-the-art nanoliposomes as a smart and sophisticated drug delivery approach. Following a brief introduction, the drug delivery mechanism of nanoliposomes is discussed with suitable examples for the treatment of numerous diseases with a brief emphasis on fungal infections. The latter half of the work is focused on the applied perspective and clinical translation of nanoliposomes. Furthermore, a detailed overview of clinical applications and future perspectives has been included in this review.

PRECISION MEDICINE - The Golden Gate for Detection, Treatment and Prevention of Alzheimer's Disease.

During this decade, breakthrough conceptual shifts have commenced to emerge in the field of Alzheimer's disease (AD) recognizing risk factors and the non-linear dynamic continuum of complex pathophysiologies amongst a wide dimensional spectrum of multi-factorial brain proteinopathies/neurodegenerative diseases. As is the case in most fields of medicine, substantial advancements in detecting, treating and preventing AD will likely evolve from the generation and implementation of a systematic precision medicine strategy. This approach will likely be based on the success found from more advanced research fields, such as oncology. Precision medicine will require integration and transfertilization across fragmented specialities of medicine and direct reintegration of Neuroscience, Neurology and Psychiatry into a continuum of medical sciences away from the silo approach. Precision medicine is biomarker-guided medicine on systems-levels that takes into account methodological advancements and discoveries of the comprehensive pathophysiological profiles of complex multi-factorial neurodegenerative diseases, such as late-onset sporadic AD. This will allow identifying and characterizing the disease processes at the asymptomatic preclinical stage, where pathophysiological and topographical abnormalities precede overt clinical symptoms by many years to decades. In this respect, the uncharted territory of the AD preclinical stage has become a major research challenge as the field postulates that early biomarker guided customized interventions may offer the best chance of therapeutic success. Clarification and practical operationalization is needed for comprehensive dissection and classification of interacting and converging disease mechanisms, description of genomic and epigenetic drivers, natural history trajectories through space and time, surrogate biomarkers and indicators of risk and progression, as well as considerations about the regulatory, ethical, political and societal consequences of early detection at asymptomatic stages. In this scenario, the integrated roles of genome sequencing, investigations of comprehensive fluid-based biomarkers and multimodal neuroimaging will be of key importance for the identification of distinct molecular mechanisms and signaling pathways in subsets of asymptomatic people at greatest risk for progression to clinical milestones due to those specific pathways. The precision medicine strategy facilitates a paradigm shift in Neuroscience and AD research and development away from the classical "one-size-fits-all" approach in drug discovery towards biomarker guided "molecularly" tailored therapy for truly effective treatment and prevention options. After the long and winding decade of failed therapy trials progress towards the holistic systems-based strategy of precision medicine may finally turn into the new age of scientific and medical success curbing the global AD epidemic.

Highly efficient assimilation of lactose by a metabolically engineered strain of Saccharomyces cerevisiae.

A diploid strain of Saccharomyces cerevisiae able to metabolize lactose with high efficiency has been obtained. Haploid strains of Saccharomyces able to grow on lactose were constructed by cotransformation with two genes of Kluyveromyces lactis required for the utilization of the sugar, LAC4 and LAC12, encoding beta-galactosidase and lactose permease respectively. Both genes were placed under the control of a galactose-inducible promoter and targeted to the rDNA encoding region (RDN1 locus) of the Saccharomyces genome. Lac+ transformants were selected on medium with lactose as the only carbon source. These transformants were mitotically stable, they maintained the Lac+ phenotype after growing in non-selective medium for more than 60 generations, but their growth was slow. We found that this lack of vigour was caused by their genetic background and not by a deficient expression of the heterologous genes. Therefore, their performance could be improved by crossing with a wild-type strain. Among the offspring of the crosses, two strains of opposite mating type were selected and mated to obtain a fast-growing Lac+ diploid. This diploid strain showed the typical fermentative behaviour of S. cerevisiae when it was grown in aerated liquid medium with glucose. In lactose medium, it exhibited a respiro-fermentative metabolism similar to that of K. lactis, with low ethanol production and high biomass yield.

Regulation of alcoholic fermentation in batch and chemostat cultures of Kluyveromyces lactis CBS 2359.

Kluyveromyces lactis is an important industrial yeast, as well as a popular laboratory model. There is currently no consensus in the literature on the physiology of this yeast, in particular with respect to aerobic alcoholic fermentation ('Crabtree effect'). This study deals with regulation of alcoholic fermentation in K. lactis CBS 2359, a proposed reference strain for molecular studies. In aerobic, glucose-limited chemostate cultures (D = 0.05-0.40 h-1) growth was entirely respiratory, without significant accumulation of ethanol or other metabolities. Alcoholic fermentation occurred in glucose-grown shake-flask cultures, but was absent during batch cultivation on glucose in fermenters under strictly aerobic conditions. This indicated that ethanol formation in the shake-flask cultures resulted from oxygen limitation. Indeed, when the oxygen feed to steady-state chemostat cultures (D = 0.10 h-1) was lowered, a mixed respirofermentative metabolism only occurred at very low dissolved oxygen concentrations (less than 1% of air saturation). The onset of respirofermentative metabolism as a result of oxygen limitation was accompanied by an increase of the levels of pyruvate decarboxylase and alcohol dehydrogenase. When aerobic, glucose-limited chemostat cultures (D = 0.10 h-1) were pulsed with excess glucose, ethanol production did not occur during the first 40 min after the pulse. However, a slow aerobic ethanol formation was invariably observed after this period. Since alcoholic fermentation did not occur in aerobic batch cultures this is probably a transient response, caused by an imbalanced adjustment of enzyme levels during the transition from steady-state growth at mu = 0.10 h to growth at mu max. It is concluded that in K. lactis, as in other Crabtree-negative yeasts, the primary environmental trigger for occurrence of alcoholic fermentation is oxygen limitation.

On-line estimation of biomass through pH control analysis in aerobic yeast fermentation systems.

The amount of acid or base consumed in yeast cultures has been recently assigned to the pathway of nitrogen assimilation under respiratory conditions with no contribution by carbon metabolism (Castrillo et al., 1995). In this investigation, experiments under respirofermentative conditions have shown that production or consumption of ethanol does not contribute significantly to the specific rate of proton production (qH+), thus extending the previously obtained relationships for all aerobic conditions in which other major acid/base contributions are not involved. Tests in batch and chemostat culture confirm the validity of qH+ as a formal control parameter in aerobic fermentations.

High-cell-density cultivation of yeasts on disaccharides in oxygen-limited batch cultures.

Many facultatively fermentative yeast species exhibit a "Kluyver effect": even under oxygen-limited growth conditions, certain disaccharides that support aerobic, respiratory growth are not fermented, even though the component monosaccharides are good fermentation substrates. This article investigates the applicability of this phenomenon for high-cell-density cultivation of yeasts. In glucose-grown batch cultures of Candida utilis CBS 621, the onset of oxygen limitation led to alcoholic fermentation and, consequently, a decrease of the biomass yield on sugar. In maltose-grown cultures, alcoholic fermentation did not occur and oxygen-limited growth resulted in high biomass concentrations (90 g dry weight L(-1) from 200 g L(-1) maltose monohydrate in a simple batch fermentation). It was subsequently investigated whether this principle could also be applied to Kluyveromyces species exhibiting a Kluyver effect for lactose. In oxygen-limited, glucose-grown chemostat cultures of K. wickerhamii CBS 2745, high ethanol concentrations and low biomass yields were observed. Conversely, ethanol was absent and biomass yields on sugar were high in oxygen-limited chemostat cultures grown on lactose. Batch cultures of K. wickerhamii grown on lactose exhibited the same growth characteristics as the maltose-grown C. utilis cultures: absence of ethanol formation and high biomass yields. Within the species K. marxianus, the occurrence of a Kluyver effect for lactose is known to be strain dependent. Thus, K. marxianus CBS 7894 could be grown to high biomass densities in lactose-grown batch cultures, whereas strain CBS 5795 produced ethanol after the onset of oxygen limitation and, consequently, yielded low amounts of biomass. Because the use of yeast strains exhibiting a Kluyver effect obviates the need for controlled substrate-feeding strategies to avoid oxygen limitation, such strains should be excellently suited for the production of biomass and growth-related products from low-cost disaccharide-containing feedstocks. (c) 1996 John Wiley & Sons, Inc.

Proton production and consumption pathways in yeast metabolism. A chemostat culture analysis.

In this investigation, a method for the accurate quantitative determination of net proton production or consumption in biological cultures has been devised. Cells are cultured under constant pH conditions. The specific rate of proton production or consumption by the culture (qH+, mmol h-1 per g biomass) is proportional to the mmol of base or acid required to maintain constant pH per unit time, and this equivalence is independent of the buffering capacity of the culture medium. The above method has been applied to chemostat cultures of Candida utilis growing on glucose or glycerol as carbon source, and different nitrogen sources. The results indicate that the nitrogen assimilation pathway alone determines the value of qH+, and a fixed stoichiometric relationship between nitrogen uptake rate qN (meq h-1 per g biomass) and qH+ has been found for each nitrogen source employed. Thus, qH+/qN values of +1, 0 and -1 were found for ammonium ions, urea and nitrate respectively. Under oxidative metabolism, the contribution of carbon catabolism to the value of qH+ was undetectable. Sine qN may be related to growth and production of type 1 compounds in fermentation processes, the parameter qH+ was incorporated into a model of growth and energy metabolism in chemostat culture (Castrillo and Ugalde, Yeast 10, 185 - 197, 1994), resulting in adequate simulations of experimentally observed culture performance. Thus, it is suggested that qH+ may be employed as a simple and effective control parameter for biotechnological processes involving biomass-related products.

Coordination of sucrose uptake and respiration in the yeast Debaryomyces yamadae.

Screening in batch cultures identified Debaryomyces yamadae as a yeast that exhibits the Kluyver effect for sucrose: this disaccharide can be respired but, even under oxygen-limited conditions, alcoholic fermentation of sucrose does not occur. Ethanol, glycerol and arabitol were the main fermentation products during oxygen-limited growth on glucose in chemostat cultures. None of these fermentation products were produced in oxygen-limited chemostat cultures grown on sucrose and the fraction of the sucrose that could not be respired remained unused in the culture medium. This absence of alcoholic fermentation was not due to repression of the key fermentative enzymes pyruvate decarboxylase and alcohol dehydrogenase. In contrast to some other yeasts that exhibit a Kluyver effect, D. yamadae did not exhibit a preference for ethanol in batch cultures grown on mixtures of ethanol and sucrose. Sucrose metabolism in D. yamadae involves intracellular hydrolysis by an alpha-glucosidase. Incubation of weakly buffered cell suspensions with sucrose led to a rapid transient alkalinization, indicating the presence of a sucrose-proton symport system. The apparent substrate saturation constant of the sucrose-uptake system was 0.2 mmol l-1. Sucrose-dependent alkalinization rates were much lower in samples from oxygen-limited cultures than in samples from aerobic cultures. Transient responses of D. yamadae to oxygen limitation were investigated by applying a sudden decrease in the oxygen feed to aerobic sugar-limited chemostat cultures. In glucose-grown cultures, this led to alcoholic fermentation and no significant accumulation of sugar occurred after the switch. In sucrose-limited cultures, sugar accumulation occurred instantaneously after the switch, and ethanol formation was virtually absent.(ABSTRACT TRUNCATED AT 250 WORDS)

Transient responses of Candida utilis to oxygen limitation: regulation of the Kluyver effect for maltose.

The facultatively fermentative yeast Candida utilis exhibits the Kluyver effect for maltose: this disaccharide is respired and assimilated but, in contrast to glucose, it cannot be fermented. To study the mechanism of the Kluyver effect, metabolic responses of C. utilis to a transition from aerobic, sugar-limited growth to oxygen-limited conditions were studied in chemostat cultures. Unexpectedly, the initial response of maltose-grown cultures to oxygen limitation was very similar to that of glucose-grown cultures. In both cases, alcoholic fermentation occurred after a lag phase of 1 h, during which glycerol, pyruvate and D-lactate were the main fermentation products. After ca. 10 h the behaviour of the maltose- and glucose-grown cultures diverged: ethanol disappeared from the maltose-grown cultures, whereas fermentation continued in steady-state, oxygen-limited cultures grown on glucose. The disappearance of alcoholic fermentation in oxygen-limited chemostat cultures growing on maltose was not due to a repression of the synthesis of pyruvate decarboxylase and alcohol dehydrogenase. The results demonstrate that the Kluyver effect for maltose in C. utilis does not reflect an intrinsic inability of this yeast to ferment maltose, but is caused by a regulatory phenomenon that affects a key enzyme in maltose metabolism, probably the maltose carrier. The observed kinetics indicate that this regulation occurs at the level of enzyme synthesis rather than via modification of existing enzyme activity.

A general model of yeast energy metabolism in aerobic chemostat culture.

The pattern of energy metabolism of different types of yeasts (obligate aerobes and facultative anaerobes) in aerobic chemostat cultures has been evaluated and interpreted on the basis of a coupling of metabolic fluxes between glycolytic and oxidative components. A model has been formulated which defines glycolytic and oxidative subunits through which the substrate C-flux (gram-atom g-1 h-1) is calculated, stating that a relative imbalance between glycolytic flux and subsequent oxidative steps alone is sufficient to account for the onset of oxidoreductive metabolism in any type of yeast, irrespective of the maximum respiratory capacity. The model is able to reproduce the patterns of behaviour reported for the different types of yeasts, and the individual features of each strain are explained on the basis of metabolic differences which are defined by a set of normalized parameters. The model can be applied to different substrates and conditions, providing a methodological basis for more detailed studies of the steps controlling yeast energy metabolism.