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Population growth, economic growth, and changes in societal habits have led to significant changes in resource consumption. Therefore, it's crucial to accelerate the "reduce, reuse, recycle, and recover" of resources to ensure the balance of ecosystems, and water is surely one of the most fundamental resources. The acceleration of this approach in the water cycle makes sense only if we combine a circular economy (CE) transition with a sustainable perspective. In this context, more rational usage of water resources (which are under pressure) and more sustainable wastewater practices are expected to be a way towards the CE in the water and wastewater sector. This study provides a description and evaluation of existing frameworks that can be used to measure and assess the level of circularity of the wastewater treatment plant (WWTP). The treatment of urban wastewater requires new concepts of management and operation for the adaptation of existing plants, which lack robustness and flexibility, to face these new challenges and requirements because we can no longer continue to look at the WWTP only as treatment units, but as wastewater resource recovery facilities. This transformation must be transposed according to a matrix that allows the assessment to describe the current situation, analyse the problem, identify vulnerabilities and opportunities, identify, and evaluate measures, and identify and evaluate strategies. Considering that decision-makers face profound uncertainties such as climate change, population growth, population needs, innovative technologies, economic developments, ecosystem preservation and the impacts of human and natural activities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

In an increasing water scarcity and climate-vulnerable global context, treated wastewater represents a vital alternative water source, thereby enhancing resource sustainability. Despite its potential, only roughly 2.5 % of the treated wastewater is reused in the European Union, with Portugal's reuse rate being only 1.2 % in 2022. Considering this framework, this study evaluates the feasibility of increasing wastewater reuse in Portugal by focusing on the Tagus River and Ribeiras do Oeste Basins. The regional assessment identified eight key wastewater treatment plants (WWTP) with significant potential for irrigation reuse in the agriculture and tourism sectors. Analysing costs, quality requirements, and technological options, this study considered five treatment lines, incorporating filtration and disinfection methods. The findings indicate that reclaimed water costs may range from 0.02€/m 3 to 0.83€/m 3 , being competitive with other water sources and significantly lower than desalination processes (up to 1.66€/m 3 ). Distribution investments and energy consumption are primary cost drivers, suggesting a relocation of WWTP closer to end-users as a cost-saving strategy. The proposed reuse projects could quadruple regional reuse rates and double the national rate, mitigating water needs for over 2000 ha of agricultural land and golf courses. This study underscores the importance of treated wastewater reuse in addressing water scarcity, advocating for WWTP decentralisation, strategic investments and policy interventions to achieve cost-effective goals. The methodologies and insights presented offer valuable guidance for other regions facing similar challenges, promoting a paradigm shift towards circular water resource management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The development of innovative non-invasive neuroimaging methods and biomarkers is critical for studying brain disease. Imaging of cerebrospinal fluid (CSF) pulsatility may inform the brain fluid dynamics involved in clearance of cerebral metabolic waste. In this work, we developed a methodology to characterize the frequency and spatial localization of whole brain CSF pulsations in humans. Using 7 Tesla (T) human magnetic resonance imaging (MRI) and ultrafast echo-planar imaging (EPI), in-vivo images were obtained to capture pulsations of the CSF signal. Physiological data were simultaneously collected and compared with the 7 T MR data. The primary components of signal pulsations were identified using spectral analysis, with the most evident frequency bands identified around 0.3, 1.2, and 2.4 Hz. These pulsations were mapped spatially and temporally onto the MR image domain and temporally onto the physiological measures of electrocardiogram and respiration. We identified peaks in CSF pulsations that were distinct from peaks in grey matter and white matter regions. This methodology may provide novel in vivo biomarkers of disrupted brain fluid dynamics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Martins, de Almeida, Wu, Wilckens, Minhas, Ibinson, Aizenstein, Santini and Ibrahim.)

Aspergilli comprise a diversity of species that have been extensively studied due to their catabolic diversity, biotechnological and ecological value, and pathogenicity. An impressive level of structural and functional conservation has been shown for aspergilli, regardless of many (yet) cryptic genomic elements. We have hypothesized the existence of conserved genes responsive to stress in aspergilli. To test the hypothesis of such conserved stress regulators in aspergilli, a straightforward computational strategy integrating well-established bioinformatic tools was used as the starting point. Specifically, five transcriptome-based datasets on exposure to organic compounds were used, covering three distinct Aspergillus species. Among the identified up-regulated genes, only one gene showed the same response in all conditions, AN9181 . This gene encodes a protein containing a phenylcoumaran benzylic ether reductase- like domain and a Nitrogen metabolite repressor regulator domain (NmrA). Deletion of this gene caused significant phenotypic alterations compared to that of the parental strain across diverse conditions. Specifically, the deletion of AN9181 raised the mutant's metabolic activity in different nitrogen sources. The acquired data supports that AN9181 acts by repressing (slowing down) A. nidulans growth when exposed to aromatic compounds in a concentration dependent manner. The same phenotype was observed for amphotericin B. Finally, AN9181 underwent differential upregulation under oxidative stress conditions. Collectively, the data suggest that AN9181 , herein assigned as NmrB (Nitrogen Metabolite Repression Regulator B), builds up the genetic machinery of perception of oxidative stress by negatively regulating growth under such conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Jorge, Martins, Domingos, Martins, Hartmann, Goldman and Silva Pereira.)

Saprophytic fungi are able to catabolize many plant-derived aromatics, including, for example, gallate. The catabolism of gallate in fungi is assumed to depend on the five main central pathways, i.e., of the central intermediates' catechol, protocatechuate, hydroxyquinol, homogentisate and gentisate, but a definitive demonstration is lacking. To shed light on this process, we analysed the transcriptional reprogramming of the growth of Aspergillus terreus on gallate compared with acetate as the control condition. Surprisingly, the results revealed that the five main central pathways did not exhibit significant positive regulation. Instead, an in-depth analysis identified four highly expressed and upregulated genes that are part of a conserved gene cluster found in numerous species of fungi, though not in Aspergilli. The cluster comprises a monooxygenase gene and a fumarylacetoacetate hydrolase-like gene, which are recognized as key components of catabolic pathways responsible for aromatic compound degradation. The other two genes encode proteins with no reported enzymatic activities. Through functional analyses of gene deletion mutants in Aspergillus nidulans, the conserved short protein with no known domains could be linked to the conversion of the novel metabolite 5-hydroxydienelatone, whereas the DUF3500 gene likely encodes a ring-cleavage enzyme for 1,2,3,5-tetrahydroxybenzene. These significant findings establish the existence of a new 1,2,3,5-tetrahydroxybenzene central pathway for the catabolism of gallate and related compounds (e.g. 2,4,6-trihydroxybenzoate) in numerous fungi where this catabolic gene cluster was observed., (© 2023 The Authors. Microbial Biotechnology published by Applied Microbiology International and John Wiley & Sons Ltd.)

Biological complexity is achieved through elaborate interactions between relatively few individual components. Affinity purification (AP) has allowed these networks of protein-protein interactions that regulate key biological processes to be interrogated systematically. In order to perform these studies at the required scale, easily transfectable immortalized cell lines have typically been used. Gene-editing now affords the systematic creation of isogenic mouse models carrying endogenous tags for affinity proteomics. This may allow protein-protein interactions to be characterized in the appropriate tissue for a particular biological process or disease phenotype under physiological conditions, and for interaction landscapes to be compared across tissues. Here we demonstrate application to intraflagellar transport (IFT) proteins, which are WD40-domain-containing proteins that are essential for the formation and function of all types of cilia. We describe a method to generate mice with an endogenous C-terminal streptavidin/FLAG tag, using Ift80 as an example, and demonstrate the successful implementation of AP in this model. This method can easily be adapted for N- and C-terminal tagging of many other proteins in vivo., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Bardet-Biedl syndrome (BBS) is an archetypal ciliopathy caused by dysfunction of primary cilia. BBS affects multiple tissues, including the kidney, eye and hypothalamic satiety response. Understanding pan-tissue mechanisms of pathogenesis versus those which are tissue-specific, as well as gauging their associated inter-individual variation owing to genetic background and stochastic processes, is of paramount importance in syndromology. The BBSome is a membrane-trafficking and intraflagellar transport (IFT) adaptor protein complex formed by eight BBS proteins, including BBS1, which is the most commonly mutated gene in BBS. To investigate disease pathogenesis, we generated a series of clonal renal collecting duct IMCD3 cell lines carrying defined biallelic nonsense or frameshift mutations in Bbs1 , as well as a panel of matching wild-type CRISPR control clones. Using a phenotypic screen and an unbiased multi-omics approach, we note significant clonal variability for all assays, emphasising the importance of analysing panels of genetically defined clones. Our results suggest that BBS1 is required for the suppression of mesenchymal cell identities as the IMCD3 cell passage number increases. This was associated with a failure to express epithelial cell markers and tight junction formation, which was variable amongst clones. Transcriptomic analysis of hypothalamic preparations from BBS mutant mice, as well as BBS patient fibroblasts, suggested that dysregulation of epithelial-to-mesenchymal transition (EMT) genes is a general predisposing feature of BBS across tissues. Collectively, this work suggests that the dynamic stability of the BBSome is essential for the suppression of mesenchymal cell identities as epithelial cells differentiate.

Traditionally, studies that associate air pollution with health effects relate individual pollutants to outcomes such as mortality or hospital admissions. However, models capable of analyzing the effects resulting from the atmosphere mixture are demanded. In this study, multilayer perceptron neural networks were evaluated to associate PM 10 , NO 2 , and SO 2 concentrations, temperature, wind speed, and relative air humidity with cardiorespiratory mortality among the elderly in São Paulo, Brazil. Daily data from 2007 to 2019 were considered and different numbers of neurons on the hidden layer, algorithms, and a combination of activation functions were tested. The best-fitted artificial neural network (ANN) resulted in a MAPE equal to 13.46%. When individual season data were analyzed, the MAPE decreased to 11%. The most influential variables in cardiorespiratory mortality among the elderly were PM 10 and NO 2 concentrations. The relative humidity variable is more important during the dry season, and temperature is more important during the rainy season. The models were not subjected to the multicollinearity issue as with classical regression models. The use of ANNs to relate air quality to health outcomes is still very incipient, and this work highlights that it is a powerful tool that should be further explored.

Introduction: Pneumopericardium is a dreaded complication in esophageal carcinoma., Case Description: We report a case of a 62 year old patient with past history of esophageal cancer with pneumopericardium, without hemodynamic compromise. Admission echocardiogram that revealed a pneumopericadium with the presence of the "swirling bubbles" and the "air gap" sign. A small esophagopericardial fistula was postulated as the cause of the pneumopericardium. He underwent esophageal stent placement with almost complete resolution of the pneumopericardium., Discussion: Pneumopericardium is usually a sign of marked clinical deterioration in neoplasia and leads to patients' death few weeks. Here we presented a case, in which a more fortunate and unusual outcome happened., Case Description: We present a case of a 62 year old patient, with a past history of esophageal cancer with pulmonary metastases undergoing palliative chemotherapy treatment and with two palliative esophageal stents. Other past medical history included active hepatitis B, arterial hypertension and dyslipidaemia. He was an ex smoker of 80 pack-year units., (© 2022 Wiley Periodicals LLC.)

Competing Interests: Declaration of interests No interests are declared.

The Zero Trust concept is being adopted in information technology (IT) deployments, while human users remain to be the main risk for operational technology (OT) deployments. This article proposes to enhance the new Modbus/TCP Security protocol with authentication and authorization functions that guarantee security against intentional unauthorized access. It aims to comply with the principle of never trusting the person who is accessing the network before carrying out a security check. Two functions are tested and used in order to build an access control method that is based on a username and a password for human users with knowledge of industrial automation control systems (IACS), using simple means, low motivation, and few resources. A man-in-the-middle (MITM) component was added in order to intermediate the client and the server communication and to validate these functions. The proposed scenario was implemented using the Node-RED programming platform. The tests implementing the functions and the access control method through the Node-RED software have proven their potential and their applicability.

Background: American Academy of Sleep Medicine guidelines suggest that clinical prediction algorithms can be used to screen patients with obstructive sleep apnea (OSA) without replacing polysomnography, the gold standard., Objective: We aimed to identify, gather, and analyze existing machine learning approaches that are being used for disease screening in adult patients with suspected OSA., Methods: We searched the MEDLINE, Scopus, and ISI Web of Knowledge databases to evaluate the validity of different machine learning techniques, with polysomnography as the gold standard outcome measure and used the Prediction Model Risk of Bias Assessment Tool (Kleijnen Systematic Reviews Ltd) to assess risk of bias and applicability of each included study., Results: Our search retrieved 5479 articles, of which 63 (1.15%) articles were included. We found 23 studies performing diagnostic model development alone, 26 with added internal validation, and 14 applying the clinical prediction algorithm to an independent sample (although not all reporting the most common discrimination metrics, sensitivity or specificity). Logistic regression was applied in 35 studies, linear regression in 16, support vector machine in 9, neural networks in 8, decision trees in 6, and Bayesian networks in 4. Random forest, discriminant analysis, classification and regression tree, and nomogram were each performed in 2 studies, whereas Pearson correlation, adaptive neuro-fuzzy inference system, artificial immune recognition system, genetic algorithm, supersparse linear integer models, and k-nearest neighbors algorithm were each performed in 1 study. The best area under the receiver operating curve was 0.98 (0.96-0.99) for age, waist circumference, Epworth Somnolence Scale score, and oxygen saturation as predictors in a logistic regression., Conclusions: Although high values were obtained, they still lacked external validation results in large cohorts and a standard OSA criteria definition., Trial Registration: PROSPERO CRD42021221339; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=221339., (©Daniela Ferreira-Santos, Pedro Amorim, Tiago Silva Martins, Matilde Monteiro-Soares, Pedro Pereira Rodrigues. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 30.09.2022.)

Advances in research have boosted therapy development for congenital disorders of glycosylation (CDG), a group of rare genetic disorders affecting protein and lipid glycosylation and glycosylphosphatidylinositol anchor biosynthesis. The (re)use of known drugs for novel medical purposes, known as drug repositioning, is growing for both common and rare disorders. The latest innovation concerns the rational search for repositioned molecules which also benefits from artificial intelligence (AI). Compared to traditional methods, drug repositioning accelerates the overall drug discovery process while saving costs. This is particularly valuable for rare diseases. AI tools have proven their worth in diagnosis, in disease classification and characterization, and ultimately in therapy discovery in rare diseases. The availability of biomarkers and reliable disease models is critical for research and development of new drugs, especially for rare and heterogeneous diseases such as CDG. This work reviews the literature related to repositioned drugs for CDG, discovered by serendipity or through a systemic approach. Recent advances in biomarkers and disease models are also outlined as well as stakeholders' views on AI for therapy discovery in CDG.

The need for new therapeutic approaches for triple-negative breast cancer is a clinically relevant problem that needs to be solved. Using a multi-targeting approach to enhance cancer cell uptake, we synthesized a new family of ruthenium(II) organometallic complexes envisaging simultaneous active and passive targeting, using biotin and polylactide (PLA), respectively. All compounds with the general formula, [Ru(η 5 -CpR)(P)(2,2'-bipy-4,4'-PLA-biotin)][CF 3 SO 3 ], where R is -H or -CH 3 and P is P(C 6 H 5 ) 3 , P(C 6 H 4 F) 3 or P(C 6 H 4 OCH 3 ) 3 , were tested against triple-negative breast cancer cells MDA-MB-231 showing IC 50 values between 2.3-14.6 µM, much better than cisplatin, a classical chemotherapeutic drug, in the same experimental conditions. We selected compound 1 (where R is H and P is P(C 6 H 5 ) 3 ), for further studies as it was the one showing the best biological effect. In a competitive assay with biotin, we showed that cell uptake via SMVT receptors seems to be the main transport route into the cells for this compound, validating the strategy of including biotin in the design of the compound. The effects of the compound on the hallmarks of cancer show that the compound leads to apoptosis, interferes with proliferation by affecting the formation of cell colonies in a dose-dependent manner and disrupts the cell cytoskeleton. Preliminary in vivo assays in N: NIH(S)II-nu/nu mice show that the concentrations of compound 1 used in this experiment (maximum 4 mg/kg) are safe to use in vivo, although some signs of liver toxicity are already found. In addition, the new compound shows a tendency to control tumor growth, although not significantly. In sum, we showed that compound 1 shows promising anti-cancer effects, bringing a new avenue for triple-negative breast cancer therapy.

As machine learning is used to make strides in medical diagnostics, few methods provide heuristics from which human doctors can learn directly. This work introduces a method for leveraging human observable structures, such as macroscale vascular formations, for producing assessments of medical conditions with relatively few training cases, and uncovering patterns that are potential diagnostic aids. The approach draws on shape grammars, a rule-based technique, pioneered in design and architecture, and accelerated through a recursive subgraph mining algorithm. The distribution of rule instances in the data from which they are induced is then used as an intermediary representation enabling common classification and anomaly detection approaches to identify indicative rules with relatively small data sets. The method is applied to seven-tesla time-of-flight angiography MRI (n = 54) of human brain vasculature. The data were segmented and induced to generate representative grammar rules. Ensembles of rules were isolated to implicate vascular conditions reliably. This application demonstrates the power of automated structured intermediary representations for assessing nuanced biological form relationships, and the strength of shape grammars, in particular for identifying indicative patterns in complex vascular networks., (Copyright © 2022 by ASME.)

Fabric dyeing produces high amounts of wastewater containing organic and inorganic pollutants such as reactive dyes that are the most common textile dyes employed by the industry. Three vinylsulfonic reactive dyes, blue 19 (B-19), red 198 (R-198), and yellow 15 (Y-15), were removed from effluents of industrial-like dyeing processes employing three adsorbents: (1) magnetite nanoparticles (MNP), (2) yeast waste obtained after β-glucan removal from yeast biomass (YW), and (3) nanomagnetic composite produced from YW and MNP (YW-MNP). The non-linear kinetic pseudo-second-order and two-stage models best explained the experimental phenomena for the majority of adsorbate:adsorbent systems. The theoretical isotherm models were fitted to experimental isotherms obtained from experiments conducted with appropriated dilutions of effluents, which have a specific condition, limited by the maximum dye concentration established by the dye recipe. Thus, the saturation of adsorbents was not reached for all adsorbate:adsorbent systems. In this way, the best conditional sorption capacities (SC cond ) were obtained by YW (1.7, 2.3, and 2.5 g/kg for B-19, R-198, and Y-15, respectively). The SIPS model best described all dyes adsorbed by YW, while the D-R model best described the phenomena for MNP and YW-MNP.

Combining organic and inorganic components at a nanoscale is an effective way to obtain high performance coating materials with excellent chemical and physical properties. This review focuses on recent approaches to prepare hybrid nanostructured waterborne coating materials combining the mechanical properties and versatility of silica as the inorganic filler, with the flexural properties and ease of processing of the polymer matrix. We cover silica-polymer coupling agents used to link the organic and inorganic components, the formation of hybrid films from these silica-polymer nanostructures, and their different applications. These hybrid nanostructures can be used to prepare high performance functional coatings with different properties from optical transparency, to resistance to temperature, hydrophobicity, anti-corrosion, resistance to scratch, and antimicrobial activity.

Electromagnetic simulations are an important tool for the safety assessment of RF coils. They are a useful resource for MRI RF coil designers, especially when complemented with experimental measurements and testing using physical phantoms. Regular-shaped (spherical/cylindrical) homogeneous phantoms are the MRI standard for RF testing but are somewhat inaccurate when compared with anthropomorphic anatomies, especially at high frequencies. In this work, using a recently developed anthropomorphic heterogeneous human head phantom, studies were performed to analyze the scattering parameters (S-parameters) and the electric and magnetic field distributions using (1) the B 1 + field mapping method on a 7 T human MRI scanner and (2) numerical full-wave electromagnetic simulations. All studies used the following: a recently developed six-compartment refillable 3D-printed anthropomorphic head phantom (developed from MRI scans obtained in vivo), where the phantom itself is filled in its entirety with either heterogeneous loading, or homogeneous brain or water loading, in vivo imaging, and a commercial homogeneous spherical water phantom. Our results determined that the calculated S-parameters for all the anthropomorphic head phantom models were comparable to the model that is based on the volunteer (within 17% difference of the reflection coefficient value) but differed for the commercial homogeneous spherical water phantom (within 45% difference). The experimentally measured B 1 + field maps of the anthropomorphic heterogeneous and homogeneous brain head phantoms were most comparable to the in vivo measured values. The numerical simulations also show that both the anthropomorphic homogeneous water and brain phantom models were less accurate in terms of electric field intensities/distributions when compared with the segmented in-vivo-based head model and the anthropomorphic heterogeneous head phantom model. The presented data highlights the differences between the physical phantoms/phantom models, and the in vivo measurements/segmented in-vivo-based head model. The results demonstrate the usefulness of 3D-printed anthropomorphic phantoms for RF coil evaluation and testing., (© 2020 John Wiley & Sons, Ltd.)

Recently cleared by the FDA, 7 Tesla (7 T) MRI is a rapidly growing technology that can provide higher resolution and enhanced contrast in human MRI images. However, the increased operational frequency (~ 297 MHz) hinders its full potential since it causes inhomogeneities in the images and increases the power deposition in the tissues. This work describes the optimization of an innovative radiofrequency (RF) head coil coupled design, named Tic Tac Toe, currently used in large scale human MRI scanning at 7 T; to date, this device was used in more than 1,300 neuro 7 T MRI scans. Electromagnetic simulations of the coil were performed using the finite-difference time-domain method. Numerical optimizations were used to combine the calculated electromagnetic fields produced by these antennas, based on the superposition principle, resulting in homogeneous magnetic field distributions at low levels of power deposition in the tissues. The simulations were validated in-vivo using the Tic Tac Toe RF head coil system on a 7 T MRI scanner.

Background: Classic homocystinuria (HCU), or cystathionine beta-synthase (CBS) deficiency, is a rare inborn error of methionine metabolism. Main clinical features may include skeletal and vascular manifestations, developmental delay, intellectual disability and eye disorders., Material and Methods: This is an observational and retrospective study aiming at describing eye abnormalities presented by a cohort of late-diagnosed HCU patients. Data regarding ophthalmological evaluation included visual acuity, refraction, biomicroscopy, Perkins tonometry, fundus examination, retinography, biometry, ocular ultrasound, optical coherence tomography, anterior segment photography and topography., Results: Ten patients with HCU (20 eyes) were included. The most frequent findings were ectopia lentis (n = 20) and myopia (n = 9). Biometry, ultrasound, OCT and topography findings were available for four patients. One patient had keratoconus; one had abnormal retinal pigmentation; and two had lens surgery scars with irregular astigmatism., Conclusions: Eye abnormalities are very frequent in late-diagnosed HCU patients. The presence of ectopia lentis should always raise the diagnostic hypothesis of HCU.

In fungi, salicylate catabolism was believed to proceed only through the catechol branch of the 3-oxoadipate pathway, as shown, e.g., in Aspergillus nidulans However, the observation of a transient accumulation of gentisate upon the cultivation of Aspergillus terreus in salicylate medium questions this concept. To address this, we have run a comparative analysis of the transcriptome of these two species after growth in salicylate using acetate as a control condition. The results revealed the high complexity of the salicylate metabolism in A. terreus with the concomitant positive regulation of several pathways for the catabolism of aromatic compounds. This included the unexpected joint action of two pathways-3-hydroxyanthranilate and nicotinate-possibly crucial for the catabolism of aromatics in this fungus. Importantly, the 3-hydroxyanthranilate catabolic pathway in fungi is described here for the first time, whereas new genes participating in the nicotinate metabolism are also proposed. The transcriptome analysis showed also for the two species an intimate relationship between salicylate catabolism and secondary metabolism. This study emphasizes that the central pathways for the catabolism of aromatic hydrocarbons in fungi hold many mysteries yet to be discovered. IMPORTANCE Aspergilli are versatile cell factories used in industry for the production of organic acids, enzymes, and pharmaceutical drugs. To date, bio-based production of organic acids relies on food substrates. These processes are currently being challenged to switch to renewable nonfood raw materials-a reality that should inspire the use of lignin-derived aromatic monomers. In this context, aspergilli emerge at the forefront of future bio-based approaches due to their industrial relevance and recognized prolific catabolism of aromatic compounds. Notwithstanding considerable advances in the field, there are still important knowledge gaps in the central catabolism of aromatic hydrocarbons in fungi. Here, we disclose a novel central pathway, 3-hydroxyanthranilate, defying previously established ideas on the central metabolism of the aromatic amino acid tryptophan in Ascomycota We also observe that the catabolism of the aromatic salicylate greatly activated the secondary metabolism, furthering the significance of using lignin-derived aromatic hydrocarbons as a distinctive biomass source., (Copyright © 2021 Martins et al.)

Introduction and Objectives: Weekend admissions has previously been associated with worse outcomes in conditions requiring specialists. Our study aimed to determine in-hospital outcomes in patients with ascites admitted over the weekends versus weekdays. Time to paracentesis from admission was studied as current guidelines recommend paracentesis within 24h for all patients admitted with worsening ascites or signs and symptoms of sepsis/hepatic encephalopathy (HE)., Patients: We analyzed 70 million discharges from the 2005-2014 National Inpatient Sample to include all adult patients admitted non-electively for ascites, spontaneous bacterial peritonitis (SBP), and HE with ascites with cirrhosis as a secondary diagnosis. The outcomes were in-hospital mortality, complication rates, and resource utilization. Odds ratios (OR) and means were adjusted for confounders using multivariate regression analysis models., Results: Out of the total 195,083 ascites/SBP/HE-related hospitalizations, 47,383 (24.2%) occurred on weekends. Weekend group had a higher number of patients on Medicare and had higher comorbidity burden. There was no difference in mortality rate, total complication rates, length of stay or total hospitalization charges between the patients admitted on the weekend or weekdays. However, patients admitted over the weekends were less likely to undergo paracentesis (OR 0.89) and paracentesis within 24h of admission (OR 0.71). The mean time to paracentesis was 2.96 days for weekend admissions vs. 2.73 days for weekday admissions., Conclusions: We observed a statistically significant "weekend effect" in the duration to undergo paracentesis in patients with ascites/SBP/HE-related hospitalizations. However, it did not affect the patient's length of stay, hospitalization charges, and in-hospital mortality., (Copyright © 2020 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Black NiO powders were prepared by a hydrothermal method. Moreover, the visible light-driven Ag 3 PO 4 /NiO photocatalyst composites were successfully synthesized by in situ precipitation method. These samples were structurally characterized by X-ray diffraction and Rietveld refinement. The strong interaction between the phases and the defects in the samples was affected by the formation of the composites, as identified by Fourier transform infrared spectroscopy and Raman spectroscopy. UV-vis diffuse reflectance spectroscopy exhibited enhanced light absorption for all Ag 3 PO 4 /NiO composites, suggesting the effective interaction between the phases. Moreover, field-emission scanning electron microscopy images revealed the presence of NiO microflowers composed of nanoflakes in contact with Ag 3 PO 4 microparticles. The composite with 5% NiO presented enhanced photocatalytic efficiency in comparison with pure Ag 3 PO 4 , degrading 96% of rhodamine B (RhB) dye in just 15 min under visible light; however, the recycling experiments confirmed that the composite with 75% NiO showed superior stability. The recombination of the electron-hole pairs was considered for the measurement of the photoluminescence of the samples. These measurements were performed to evaluate the possible causes for the difference in the photocatalytic responses of the composites. From these experimental results, possible photocatalytic mechanisms for RhB degradation over Ag 3 PO 4 /NiO composites under visible-light irradiation were proposed., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Photodynamic therapy is a medical modality developed for the treatment of several diseases of oncological and non-oncological etiology that requires the presence of a photosensitizer, light and molecular oxygen, which combined will trigger physicochemical reactions responsible for reactive oxygen species production. Given the scarcity of photosensitizers that exhibit desirable characteristics for its potential application in this therapeutic strategy, the main aims of this work were the study of the photophysical and photochemical properties and the photobiological activity of several dicyanomethylene squaraine cyanine dyes. Thus, herein, the study of their aggregation character, photobleaching and singlet oxygen production ability, and the further application of the previously synthesized dyes in Caco-2 and HepG2 cancer cell lines, to evaluate their phototherapeutic effects, are described. Dicyanomethylene squaraine dyes exhibited moderate light-stability and, despite the low singlet oxygen quantum yields, were a core of dyes that exhibited relevant in vitro photodynamic activity, as there was an evident increase in the toxicity of some of the tested dyes exclusive to radiation treatments.

Background: Optimal nutrition for children with cystic fibrosis (CF) improves prognosis and survival, but an increased caloric intake recommendation for this population raises concerns about the nutrient profile of their diets., Objective: Our aim was to assess the relative contribution of food groups to the total macronutrient intake of European pediatric patients with CF., Design: We conducted a cross-sectional study in which the participants recorded dietary intake from 2016 to 2017. Specifically developed nutritional composition databases were used to obtain nutritional data, including macronutrients and food groups, according to previously standardized criteria., Participants/setting: Two hundred and seven pediatric patients with CF from six European centers were involved in the My App for Cystic Fibrosis self-management project., Main Outcome Measures: Participants reported dietary intake with a detailed 4-day food record., Statistical Analysis Performed: Descriptive analyses of nutrient intake, food group consumption, and dietary origin of macronutrients were conducted with R software., Results: Similar patterns were found in nutrient and food group intake; both sugar and saturated fatty acids contributed >10% each to the total daily energy intake in all the centers. Large mean and median percent differences were observed in the intake of other nutrient and food groups, because sweets and snacks were consumed once or twice a day, and fruit and vegetables were consumed two or three times a day. Milk, meat, sweets and snacks, and oils were the main sources of fat in all centers., Conclusions: Study findings indicated less than optimal nutrient profiles, especially for sugars and saturated fatty acids, resulting from the high consumption of meat, dairy, and processed products and low consumption of fish, nuts, and legumes. These results can serve as a basis for future tailored interventions that target improved adherence to nutritional recommendations for patients with CF., (Copyright © 2019 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

In this paper, we will provide a methodology for head phantom development based on in vivo imaging data attained utilizing MRI. The anthropomorphic phantom can be designed to mimic human anatomy., Competing Interests: Financial & competing interests disclosure This work was partially funded by the National Institutes of Health (NIH) R01MH111265, and R01AG063525; and by the CAPES Foundation, Ministry of Education of Brazil, 88881.128222/2016–01. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Defect-related luminescent materials have attracted interest because of their excellent optical properties and are considered as a less expensive and nontoxic alternative to commonly used lanthanide-based optical systems. These materials are fundamentally and technologically important for the next generation of full-color tunable light-emitting diodes as well as in the biomedical field. In this study, we report the preparation of α-silver vanadate (α-AgVO 3 , AV) decorated by hydroxyapatite (Ca 10 (PO 4 ) 6 (OH) 2 , HA) with intense photoluminescence (PL) emissions at various HA/AV molar ratios (1:1-1:1/32) by a simple route based on chemical precipitation. The well-defined diffraction peaks observed by X-ray diffraction were all indexed to the monoclinic AV and hexagonal HA phases. Analysis of the results obtained by Fourier transform infrared spectroscopy reveals the presence of short-range structural order as deduced by the characteristic vibrational modes assigned to AV and HA systems. Characterization by scanning and transmission electron microscopies confirms the presence of AV and HA micro- and nanorods, respectively. UV-vis spectroscopy renders band gap energies of 5.80 eV for HA and in the range 2.59-2.65 eV for pure AV and HA/AV samples. The PL data reveal the presence of broad-band emission profiles, typical of defect-related optical centers in materials. Depending on the molar ratio, the emission can be completely tunable from the blue to red spectral regions; in addition, pure white color emission was obtained. On the basis of these results, we propose an order-disorder model induced by structural and interface defects to explain the PL emissions in the HA/AV system. Moreover, our results show that HA/AV composites have superior bactericidal activity against Staphylococcus aureus (methicillin-resistant and methicillin-susceptible) and can be used as a novel multifunctional material.

The diversity and abundance of aromatic compounds in nature is crucial for proper metabolism in all biological systems, and also impacts greatly the development of many industrial processes. Naturally, understanding their catabolism becomes fundamental for many scientific fields of research, from clinical and environmental to technological. The genetic basis of the central pathways for the catabolism of aromatic compounds in fungi, particularly of benzene derivatives, remains however poorly understood largely overlooking their significance. In some Dikarya species the genes of the central pathways are clustered in the genome, often in an array with peripheral pathway genes, even if the existence of a specific pathway does not necessarily mean that the composing genes are clustered. The current availability of many annotated fungal genomes in the postgenomic era creates conditions to reach a more holistic view of these processes through target analysis of the central pathways gene clusters. Inspired by this, we have critically analyzed the established biochemical and genetic data on the catabolism of aromatic compounds in Dikarya after dissecting the presence and distribution of central catabolic gene clusters (at times including also details on gene diversity, order and orientation) and of peripheral genes. Our methodological approach illustrates the multiple degrees of separation in these central pathways gene clusters across Dikarya. Surprisingly, they show a great degree of similarity irrespectively of the Dikarya division, emphasizing that knowledge established on either phyla can guide the identification of clusters of comparable composition (in-cluster plus peripheral genes) in uncharacterized species., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The rates of recurrent venous thromboembolism (RVTE) vary widely, and its causes still need to be elucidated. Statistical multivariate methods can be used to determine disease predictors and improve current methods for risk calculation. The objective of this study was to apply principal component analysis to a set of data containing clinical records of patients with previous venous thromboembolism and extract the main factors that predict recurrent thrombosis. Records of 39 factors including blood and lipid parameters, hereditary thrombophilia, antiphospholipid syndrome, clinical data regarding previous thrombosis and treatment, and Doppler ultrasound results were collected from 235 patients. The results showed that 13 principal components were associated with RVTE and that 18 of 39 factors are the important for the analysis. These factors include red blood cell, white blood cell, hematocrit, red cell distribution width, glucose, lipids, natural anticoagulant, creatinine, age, as well as first deep vein thrombosis data (distal/proximal, d-dimer, and time of anticoagulation). The results demonstrated that simple clinical parameters easy to be collected can be used to predict rates of recurrence and to develop new clinical decision support systems to predict the rates of RVTE.

Radio-frequency (RF) field inhomogeneities and higher levels of specific absorption rate (SAR) still present great challenges in ultrahigh-field (UHF) MRI. In this study, an in-depth analysis of the eigenmodes of a 20-channel transmit Tic-Tac-Toe (TTT) RF array for 7T neuro MRI is presented. The eigenmodes were calculated for five different Z levels (along the static magnetic field direction) of the coil. Four eigenmodes were obtained for each Z level (composed of 4 excitation ports), and they were named based on the characteristics of their field distributions: quadrature, opposite-phase, anti-quadrature, and zero-phase. Corresponding finite-difference time-domain (FDTD) simulations were performed and experimental B1+ field maps were acquired using a homogeneous spherical phantom and human head (in-vivo). The quadrature mode is the most efficient and it excites the central brain regions; the opposite-phase mode excites the brain peripheral regions; anti-quadrature mode excites the head periphery; and the zero-phase mode excites cerebellum and temporal lobes. Using this RF array, up to five eigenmodes (from five different Z levels) can be simultaneously excited. The superposition of these modes has the potential to produce homogeneous excitation with full brain coverage and low levels of SAR at 7T MRI., Competing Interests: Tiejun Zhao is employed by Siemens Medical Solutions. There are no patents or products in development to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The present study evaluated the efficiency of a structured-bed reactor subjected to recirculation and intermittent aeration (SBRRIA) to promote nitrogen and carbon removal from domestic sewage. The intermittent aeration and the recycling rate of 3 keeps the desired mixing degree inside the SBRRIA. Four different operational conditions were tested by varying the hydraulic retention time (HRT) from 12 to 8 h and aerated and non-aerated periods (A/NA) from 2 h/1 h and 3 h/1 h. At the THD of 8 h and A/NA of 2 h/1 h there was a decrease in the nitrification process (77.5%) due to the increase of organic matter availability, affecting the total-N removal performance. However, by increasing the aerated period from 2 h to 3 h, the nitrification efficiency rose to 91.1%, reaching a total-N removal efficiency of 79%. The system reached a maximum total-N loading removed of 0.117 kgN.m -3 .d -1 by applying an HRT of 8 h and an intermittent aeration cycle of 3 h, aerated and 1 h non-aerated. The simultaneous nitrification and denitrification (SND) process was related to a complex interplay among microorganisms affiliated mostly to Acidovorax sp., Comamonas sp., Dechloromonas sp., Hydrogenophaga sp., Mycobacterium sp., Rhodobacter sp., and Steroidobacter sp., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The present work assesses in vitro the role of human Stanniocalcin 1 (hSTC-1) in 14 C-glucose metabolism in brown adipose tissue (BAT) from fed rat. In the fed state, hSTC-1 decreases the incorporation of 14 C from glucose into lipids in the rat BAT. The data support the hypothesis that the capacity of the glycerol-3-phosphate (G3P)-generating pathway (glycolysis) from glucose is regulated by hSTC-1, decreasing the adequate supply of G3P needed for fatty acid esterification and triacylglycerol (TG) storage in BAT. The results also suggest the effect of hSTC-1 on de novo fatty acid synthesis from pyruvate generated by 14 C-glucose in the glycolysis pathway. In addition, by decreasing lipogenesis, hSTC-1 increased ATP levels and these two factors may decrease BAT thermogenic function. The presence of hSTC-1 in the incubation medium did not alter 14 C-glucose and 14 C-1-palmitic acid oxidation. The uncoupling protein 1 (UCP-1) expression was not altered by hSTC-1 either. In conclusion, hSTC-1 is one of the hormonal factors that control glucose metabolism in BAT in the fed state. The decrease of TG capacity synthesis from 14 C-glucose by hSTC-1 compromises the BAT thermogenic capacity. Furthermore, the increase in ATP levels would inhibit a futile cycle via UCP-1, which dissipates oxidative energy as heat., (Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Background: The New European guidelines have established the most updated recommendations on nutrition and pancreatic enzyme replacement therapy (PERT) in CF. In the context of MyCyFAPP project - a European study in children with CF aimed at developing specific tools for improvement of self-management - the objective of the current study was to assess nutritional status, daily energy and macronutrient intake, and PERT dosing with reference to these new guidelines., Methods: Cross sectional study in paediatric patients with CF from 6 European centres. SD-scores for weight-for-age (WFA), height-for-age (HFA) and body mass index-for-age (BMI) were obtained. Through a specific 4-day food and enzyme-dose record, energy and macronutrients intake and PERT-use (LU/g lipids) were automatically calculated by the MyCyFAPP system. Comparisons were made using linear regression models., Results: The lowest quartiles for BMI and HFA were between 0 and -1SD in all the centres with no significant differences, and 33.5% of the patients had a SD-score <0 for all three parameters. The minimum energy intake recommendation was not reached by 40% of the children and mean nutrients intake values were 14%, 51% and 34% of the total energy for protein, carbohydrates and lipids respectively. When assessed per centre, reported PERT doses were in the recommended range in only 13.8% to 46.6% of the patients; from 5.6% up to 82.7% of children were above the recommended doses and 3.3% to 75% were below., Conclusion: Among the 6 centres, a large variability and inconsistency with new guidelines on nutrition and PERT-use was found. Our findings document the lack of a general criterion to adjust PERT and suggest the potential benefit of educational and self-managerial tools to ensure adherence to therapies, both for clinical staff and families. They will be taken into account when developing these new tools during the next stages of MyCyFAPP Project., (Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Introduction: The state of Minas Gerais, Brazil has no data on the prevalence of dizziness in the population and this information can be fundamental as the basis of public health policies, promotion, prevention and rehabilitation campaigns., Objective: Investigate the prevalence of the symptom of dizziness in the population of Minas Gerais according to Sample Survey of Households, as well as describe the profile of interviewed individuals and the association between dizziness and socioeconomic, demographic features and health status., Methods: This was a cross-sectional observational study that analyzed individuals with dizziness symptom reported in the previous month. The data entered in the Sample Survey of Households of 2011 were analyzed. An independent statistical association was determined between the selected variables and dizziness through multivariate analysis., Results: Dizziness was the third major complaint among individuals who mentioned any health problems in the previous month, with an estimated population of 209,025 individuals and reported by 6.7% of symptomatic ones, with higher prevalence values only reported for the symptoms of fever and headache. Among individuals who reported dizziness, 94% were adults or elderly (p≤0.001) and 63% were females (p=0.003). A statistically significant association (p<0.001) was observed between the response variable and the variables: self-perceived health, hypertension, heart disease, diabetes, depression, seeking or requiring medical or health care in the previous month and private health care plan or insurance. Among individuals with dizziness, 84.2% sought or required medical or health care and 80.1% did not have a private health plan or insurance in the assessed period., Conclusion: The dizziness symptom was highly prevalent in the population of Minas Gerais during the assessed month of the investigation. Dizziness was prevalent in adults and the elderly and showed a statistical association with socioeconomic and demographic characteristics, as well as the assessed health status., (Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

The present work assesses in vitro the role of human Stanniocalcin 1 (hSTC-1) in glucose metabolism in white retroperitoneal adipose tissue (WRAT) from fed rat. In the fed state, hSTC1 increases the incorporation of 14 C from glucose into lipids in the rat WRAT. The increase in lipogenesis capacity supports the hypothesis that the activity of the glycerol-3-phosphate-generating pathway (glycolysis) from glucose is regulated by hSTC-1. The effect of hSTC-1 on de novo fatty acid synthesis and on glucose oxidation in WRAT is supported by an 85 % increase in 14 CO 2 production from 14 C-glucose. The incubation of WRAT in the presence of hSTC-1 maintained the ADP/ATP ratio close to the control group. The presence of hSTC-1 in the incubation medium did not inhibit the lipolytic effect of epinephrine. In conclusion, hSTC-1 is one of the hormonal factors that control glucose metabolism in WRAT in the fed state.

Glaucoma is a leading cause of vision loss and blindness worldwide, characterized by chronic and progressive neuronal loss. Reactive microglial cells have been recognized as a neuropathologic feature, contributing to local inflammation and retinal neurodegeneration. In a recent in vitro work (organotypic cultures), we demonstrated that blockade of adenosine A2A receptor (A2AR) prevents the neuroinflammatory response and affords protection to retinal ganglion cells (RGCs) against exposure to elevated hydrostatic pressure (EHP), to mimic elevated intraocular pressure (IOP), the main risk factor for glaucoma development. Herein, we investigated whether a selective A2AR antagonist (SCH 58261) could modulate retinal microglia reactivity and their inflammatory response. Furthermore, we took advantage of the high IOP-induced transient ischemia (ischemia-reperfusion, I-R) animal model to evaluate the protective role of A2AR blockade in the control of retinal neuroinflammation and neurodegeneration. Primary microglial cell cultures were challenged either with lipopolysaccharide or with EHP, in the presence or absence of A2AR antagonist SCH 58261 (50 nM). In addition, I-R injury was induced in adult Wistar rats after intravitreal administration of SCH 58261 (100 nM, 5 μL). Our results showed that SCH 58261 attenuated microglia reactivity and the increased expression and release of proinflammatory cytokines. Moreover, intravitreal administration of SCH 58261 prevented I-R-induced cell death and RGC loss, by controlling microglial-mediated neuroinflammatory response. These results prompt the proposal that A2AR blockade may have great potential in the management of retinal neurodegenerative diseases characterized by microglia reactivity and RGC death, such as glaucoma and ischemic diseases., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The effect of the fungicide pyrimethanil (0.7 mg L(−1)) on biofilm development and alder leaf litter decomposition in aquatic ecosystems was assessed in outdoor lentic mesocosms immediately and 274 days after pyrimethanil application. Pyrimethanil decreased ergosterol concentrations (an indicator of fungal biomass) and the abundance and richness of the macroinvertebrate community associated with decomposing leaves. However, because neither fungi nor macroinvertebrates were main factors contributing to decomposition in this particular system, organic matter processing rates were not affected. After 274 days, pyrimethanil concentration in the water column was ≤0.004 mg L(−1) but richness, biomass and composition of the invertebrate community associated with decomposing leaf-litter still showed the effect. The comparison of ergosterol (a molecule existing on both algae and fungal cell membranes), with chlorophyll (an indicator of algal biomass) associated with biofilm suggests that pyrimethanil may decrease fungal biomass and alter the relative abundance of algae and fungi on biofilm developing in control- and treated-mesocosms.

Death of retinal neural cells, namely retinal ganglion cells (RGCs), is a characteristic of several retinal neurodegenerative diseases. Although the role of adenosine A3 receptor (A3R) in neuroprotection is controversial, A3R activation has been reported to afford protection against several brain insults, with few studies in the retina. In vitro models (retinal neural and organotypic cultures) and animal models [ischemia-reperfusion (I-R) and partial optic nerve transection (pONT)] were used to study the neuroprotective properties of A3R activation against retinal neurodegeneration. The A3R selective agonist (2-Cl-IB-MECA, 1 μM) prevented apoptosis (TUNEL(+)-cells) induced by kainate and cyclothiazide (KA + CTZ) in retinal neural cultures (86.5 ± 7.4 and 37.2 ± 6.1 TUNEL(+)-cells/field, in KA + CTZ and KA + CTZ + 2-Cl-IB-MECA, respectively). In retinal organotypic cultures, 2-Cl-IB-MECA attenuated NMDA-induced cell death, assessed by TUNEL (17.3 ± 2.3 and 8.3 ± 1.2 TUNEL(+)-cells/mm(2) in NMDA and NMDA+2-Cl-IB-MECA, respectively) and PI incorporation (ratio DIV4/DIV2 3.3 ± 0.3 and 1.3 ± 0.1 in NMDA and NMDA+2-Cl-IB-MECA, respectively) assays. Intravitreal 2-Cl-IB-MECA administration afforded protection against I-R injury decreasing the number of TUNEL(+) cells by 72%, and increased RGC survival by 57%. Also, intravitreal administration of 2-Cl-IB-MECA inhibited apoptosis (from 449.4 ± 37.8 to 207.6 ± 48.9 annexin-V(+)-cells) and RGC loss (from 1.2 ± 0.6 to 8.1 ± 1.7 cells/mm) induced by pONT. This study demonstrates that 2-Cl-IB-MECA is neuroprotective to the retina, both in vitro and in vivo. Activation of A3R may have great potential in the management of retinal neurodegenerative diseases characterized by RGC death, as glaucoma and diabetic retinopathy, and ischemic diseases., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The mammalian kidney contributes significantly to glucose homeostasis through gluconeogenesis. Considering that stanniocalcin 1 (STC1) regulates ATP production, is synthesized and acts in different cell types of the nephron, the present study hypothesized that STC1 may be implicated in the regulation of gluconeogenesis in the vertebrate kidney. Human STC1 strongly reduced gluconeogenesis from (14)C-glutamine in rat renal medulla (MD) slices but not in renal cortex (CX), nor from (14)C-lactic acid. Total PEPCK activity was markedly reduced by hSTC1 in MD but not in CX. Pck2 (mitochondrial PEPCK isoform) was down-regulated by hSTC1 in MD but not in CX. In fish (Dicentrarchus labrax) kidney slices, both STC1-A and -B isoforms decreased gluconeogenesis from (14)C-acid lactic, while STC1-A increased gluconeogenesis from (14)C-glutamine. Overall, our results demonstrate a role for STC1 in the control of glucose synthesis via renal gluconeogenesis in mammals and suggest that it may have a similar role in teleost fishes., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Pentachlorophenol (PCP) is globally dispersed and contamination of soil with this biocide adversely affects its functional biodiversity, particularly of fungi - key colonizers. Their functional role as a community is poorly understood, although a few pathways have been already elucidated in pure cultures. This constitutes here our main challenge - elucidate how fungi influence the pollutant mitigation processes in forest soils. Circumstantial evidence exists that cork oak forests in N. W. Tunisia - economically critical managed forests are likely to be contaminated with PCP, but the scientific evidence has previously been lacking. Our data illustrate significant forest contamination through the detection of undefined active sources of PCP. By solving the taxonomic diversity and the PCP-derived metabolomes of both the cultivable fungi and the fungal community, we demonstrate here that most strains (predominantly penicillia) participate in the pollutant biotic degradation. They form an array of degradation intermediates and by-products, including several hydroquinone, resorcinol and catechol derivatives, either chlorinated or not. The degradation pathway of the fungal community includes uncharacterized derivatives, e.g. tetrachloroguaiacol isomers. Our study highlights fungi key role in the mineralization and short lifetime of PCP in forest soils and provide novel tools to monitor its degradation in other fungi dominated food webs., (© 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.)

Aspergilli play major roles in the natural turnover of elements, especially through the decomposition of plant litter, but the end catabolism of lignin aromatic hydrocarbons remains largely unresolved. The 3-oxoadipate pathway of their degradation combines the catechol and the protocatechuate branches, each using a set of specific genes. However, annotation for most of these genes is lacking or attributed to poorly- or un-characterised families. Aspergillus nidulans can utilise as sole carbon/energy source either benzoate or salicylate (upstream aromatic metabolites of the protocatechuate and the catechol branches, respectively). Using this cultivation strategy and combined analyses of comparative proteomics, gene mining, gene expression and characterisation of particular gene-replacement mutants, we precisely assigned most of the steps of the 3-oxoadipate pathway to specific genes in this fungus. Our findings disclose the genetically encoded potential of saprophytic Ascomycota fungi to utilise this pathway and provide means to untie associated regulatory networks, which are vital to heightening their ecological significance., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Diabetic retinopathy is a leading cause of vision loss and blindness. Disruption of axonal transport is associated with many neurodegenerative diseases and might also play a role in diabetes-associated disorders affecting nervous system. We investigated the impact of type 1 diabetes (2 and 8 weeks duration) on KIF1A, KIF5B and dynein motor proteins in the retina. Additionally, since hyperglycemia is considered the main trigger of diabetic complications, we investigated whether prolonged exposure to elevated glucose could affect the content and distribution of motor proteins in retinal cultures. The immunoreactivity of motor proteins was evaluated by immunohistochemistry in retinal sections and by immunoblotting in total retinal extracts from streptozotocin-induced diabetic and age-matched control animals. Primary retinal cultures were exposed to high glucose (30 mM) or mannitol (osmotic control; 24.5 mM plus 5.5 mM glucose), for seven days. Diabetes decreased the content of KIF1A at 8 weeks of diabetes as well as KIF1A immunoreactivity in the majority of retinal layers, except for the photoreceptor and outer nuclear layer. Changes in KIF5B immunoreactivity were also detected by immunohistochemistry in the retina at 8 weeks of diabetes, being increased at the photoreceptor and outer nuclear layer, and decreased in the ganglion cell layer. Regarding dynein immunoreactivity there was an increase in the ganglion cell layer after 8 weeks of diabetes. No changes were detected in retinal cultures. These alterations suggest that axonal transport may be impaired under diabetes, which might contribute to early signs of neural dysfunction in the retina of diabetic patients and animal models., (Copyright © 2014 Elsevier Ltd. All rights reserved.)