BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions.

Thermogenesis in brown adipose tissue (BAT) is fundamental to energy balance and is also relevant for humans. Bone morphogenetic proteins (BMPs) regulate adipogenesis, and, here, we describe a role for BMP8B in the direct regulation of thermogenesis. BMP8B is induced by nutritional and thermogenic factors in mature BAT, increasing the response to noradrenaline through enhanced p38MAPK/CREB signaling and increased lipase activity. Bmp8b(-/-) mice exhibit impaired thermogenesis and reduced metabolic rate, causing weight gain despite hypophagia. BMP8B is also expressed in the hypothalamus, and Bmp8b(-/-) mice display altered neuropeptide levels and reduced phosphorylation of AMP-activated protein kinase (AMPK), indicating an anorexigenic state. Central BMP8B treatment increased sympathetic activation of BAT, dependent on the status of AMPK in key hypothalamic nuclei. Our results indicate that BMP8B is a thermogenic protein that regulates energy balance in partnership with hypothalamic AMPK. BMP8B may offer a mechanism to specifically increase energy dissipation by BAT.

An insight into differential protein abundance throughout Leishmania donovani promastigote growth and differentiation.

Leishmania donovani causes anthroponotic visceral leishmaniasis, responsible for about 50,000 annual deaths worldwide. Current therapies have considerable side effects. Drug resistance has been reported and no vaccine is available nowadays. The development of undifferentiated promastigotes in the sand fly vector's gut leads to the promastigote form that is highly infective to the mammalian host. Fully differentiated promastigotes play a crucial role in the initial stages of mammalian host infection before internalization in the host phagocytic cell. Therefore, the study of protein levels in the promastigote stage is relevant for disease control, and proteomics analysis is an ideal source of vaccine candidate discovery. This study aims to get insight into the protein levels during the differentiation process of promastigotes by 2DE-MALDI-TOF/TOF. This partial proteome analysis has led to the identification of 75 proteins increased in at least one of the L. donovani promastigote differentiation and growth phases. This study has revealed the differential abundance of said proteins during growth and differentiation. According to previous studies, some are directly involved in parasite survival or are immunostimulatory. The parasite survival-related proteins are ascorbate peroxidase; cystathionine ß synthase; an elongation factor 1ß paralog; elongation factor 2; endoribonuclease L-PSP; an iron superoxide dismutase paralog; GDP-mannose pyrophosphorylase; several heat shock proteins-HSP70, HSP83-17, mHSP70-rel, HSP110; methylthioadenosine phosphorylase; two thiol-dependent reductase 1 paralogs; transitional endoplasmic reticulum ATPase; and the AhpC thioredoxin paralog. The confirmed immunostimulatory proteins are the heat shock proteins, enolase, and protein kinase C receptor analog. The potential immunostimulatory molecules according to findings in patogenic bacteria are fructose-1,6-diphophate aldolase, dihydrolipoamide acetyltransferase, isocitrate dehydrogenase, pyruvate dehydrogenase E1α and E1ß subunits, and triosephosphate isomerase. These proteins may become disease control candidates through future intra-vector control methods or vaccines.

Distribution and Clinical Significance of HPV16 Variants in Head and Neck Squamous Cell Carcinomas: Data from a Portuguese Cohort and Systematic Review.

INTRODUCTION: Genomic variants of the human papillomavirus type 16 (HPV16) are thought to play differential roles in the susceptibility to head and neck squamous cell carcinomas (HNSCC) and its biological behaviour. This study aimed to establish the prevalence of HPV16 variants in an HNSCC cohort and associate them with clinical pathological characteristics and patient survival. METHODS: We retrieved samples and clinical data from 68 HNSCC patients. DNA samples were available from tumour biopsy at the time of the primary diagnosis. Targeted next-generation sequencing was used to obtain whole-genome sequences, and variants were established based on phylogenetic classification. RESULTS: 74% of samples clustered in lineage A, 5.7% in lineage B, 2.9% in lineage C, and 17.1% in lineage D. Comparative genome analysis revealed 243 single nucleotide variations. Of these, one hundred were previously reported, according to our systematic review. No significant associations with clinical pathological variables or patient survival were observed. The E6 amino acid variations E31G, L83V, and D25E and E7 N29S, associated with cervical cancer, were not observed, except for N29S in a single patient. CONCLUSION: These results provide a comprehensive genomic map of HPV16 in HSNCC, highlighting tissue-specific characteristics which will help design tailored therapies for cancer patients.

Isolated massive histiocytes renal interstitial infiltration: a case report of an unexpected cause of acute kidney injury in a kidney transplant recipient.

BACKGROUND: Acute kidney injury is a frequent cause of hospital readmission in kidney transplant recipients (KTR), usually associated with infections and graft rejection. Herein, we report a case of an unusual cause of acute kidney injury in a KTR (massive histiocytes renal interstitial infiltration). CASE PRESENTATION: A 40-year-old woman was submitted to a second kidney transplant. One year after surgery, she presented asthenia, myalgia, and fever, haemoglobin 6.1 g/dL; neutrophils: 1.3 × 109/µL; platelets: 143 × 109/µL; blood creatinine 11.8 mg/dL, requiring dialysis. A kidney biopsy revealed diffuse histiocytic infiltration, which was assumed due to dysregulated immunological activation triggered by infections. The patient had multiple infections, including cytomegalovirus infection (CMV), aspergillosis, bacteraemia, and urinary tract infections, which could trigger the immune response. Haemophagocytic lymphohistiocytosis (HLH) was ruled out. The present case highlights the occurrence of isolated massive renal interstitial infiltration of histiocytes that does not meet the criteria for HLH or other related pathologies. CONCLUSIONS: Renal histiocyte activation and infiltration may have been initiated by an immunological mechanism similar to what occurs in HLH and infectious processes. The present case highlights the occurrence of isolated massive renal interstitial infiltration of histiocytes that does not meet the criteria for HLH or other related pathologies.

Towards valorization of pectin-rich agro-industrial residues: Engineering of Saccharomyces cerevisiae for co-fermentation of d-galacturonic acid and glycerol.

Pectin-rich plant biomass residues represent underutilized feedstocks for industrial biotechnology. The conversion of the oxidized monomer d-galacturonic acid (d-GalUA) to highly reduced fermentation products such as alcohols is impossible due to the lack of electrons. The reduced compound glycerol has therefore been considered an optimal co-substrate, and a cell factory able to efficiently co-ferment these two carbon sources is in demand. Here, we inserted the fungal d-GalUA pathway in a strain of the yeast S. cerevisiae previously equipped with an NAD-dependent glycerol catabolic pathway. The constructed strain was able to consume d-GalUA with the highest reported maximum specific rate of 0.23 g gCDW-1 h-1 in synthetic minimal medium when glycerol was added. By means of a 13C isotope-labelling analysis, carbon from both substrates was shown to end up in pyruvate. The study delivers the proof of concept for a co-fermentation of the two 'respiratory' carbon sources to ethanol and demonstrates a fast and complete consumption of d-GalUA in crude sugar beet pulp hydrolysate under aerobic conditions. The future challenge will be to achieve co-fermentation under industrial, quasi-anaerobic conditions.

Cross-validation of four different survey methods used to estimate illicit cigarette consumption in Brazil.

OBJECTIVE: To cross-validate estimates of the size of the illicit cigarette trade based on the results of four different survey methods. METHODS: In 2018/2019, four non-industry-funded, large-scale studies were conducted in selected Brazilian cities: packs discarded in household garbage/PDG (1 city), packs littered in the streets/PLS (5 cities), a phone survey of tobacco users' purchase behaviors/VIGITEL (5 cities), and a face-to-face household survey of tobacco users' purchase behaviors/FTF-household (2 cities). The proportions of illicit cigarettes consumed were based on the price paid by smokers in their last purchase (VIGITEL or FTF-household) and/or direct observation of brand names and health warnings (PDG, PLS or FTF-household). RESULTS: Based on PLS, the share of packs that avoided taxation ranged from 30.4% (95% CI 25.6% to 35.7%) in Rio de Janeiro to 70.1% (95% CI 64.6% to 75.0%) in Campo Grande; and PDG conducted in Rio de Janeiro found an even lower proportion point estimate of illicit cigarette use (26.8%, 95% CI 25.1% to 28.6%). In FTF-household, the share of illicit cigarette consumption based on the self-reported price ranged from 29.1% (95% CI 22.4% to 35.7%) in Rio de Janeiro to 37.5% (95% CI 31.2% to 43.7%) in São Paulo, while estimates based on pack observation ranged from 29.9% (95% CI 23.3% to 36.5%) in Rio de Janeiro to 40.7% (95% CI 34.3% to 47.0%) in São Paulo. For all cities, VIGITEL presented the lowest levels of illicit consumption, and most illicit brands were produced in Paraguay. CONCLUSIONS: Small differences in the estimated levels of illicit trade across methods were found, except for the phone survey. The cross-validation of estimates from independent studies is important to help effectively implement tobacco excise tax policy in Brazil and other low-income and middle-income countries.

YEASTRACT+: a portal for cross-species comparative genomics of transcription regulation in yeasts.

The YEASTRACT+ information system (http://YEASTRACT-PLUS.org/) is a wide-scope tool for the analysis and prediction of transcription regulatory associations at the gene and genomic levels in yeasts of biotechnological or human health relevance. YEASTRACT+ is a new portal that integrates the previously existing YEASTRACT (http://www.yeastract.com/) and PathoYeastract (http://pathoyeastract.org/) databases and introduces the NCYeastract (Non-Conventional Yeastract) database (http://ncyeastract.org/), focused on the so-called non-conventional yeasts. The information in the YEASTRACT database, focused on Saccharomyces cerevisiae, was updated. PathoYeastract was extended to include two additional pathogenic yeast species: Candida parapsilosis and Candida tropicalis. Furthermore, the NCYeastract database was created, including five biotechnologically relevant yeast species: Zygosaccharomyces baillii, Kluyveromyces lactis, Kluyveromyces marxianus, Yarrowia lipolytica and Komagataella phaffii. The YEASTRACT+ portal gathers 289 706 unique documented regulatory associations between transcription factors (TF) and target genes and 420 DNA binding sites, considering 247 TFs from 10 yeast species. YEASTRACT+ continues to make available tools for the prediction of the TFs involved in the regulation of gene/genomic expression. In this release, these tools were upgraded to enable predictions based on orthologous regulatory associations described for other yeast species, including two new tools for cross-species transcription regulation comparison, based on multi-species promoter and TF regulatory network analyses.

The mediating role of tolerance for psychological pain in the relationship of childhood trauma to suicidal ideation in individuals with a substance use disorder.

OBJECTIVES: The association between childhood trauma and suicidal ideation has been well documented in several populations, including individuals with a substance use disorder (SUD). However, a gap still exists in the literature regarding the mechanisms by which childhood trauma later impacts suicide risk. This cross-sectional study tested the effect of childhood trauma on suicidal ideation, as well as the mediating effect of tolerance for psychological pain (managing the pain and enduring the pain) in that relationship, controlling for the effect of depressive symptoms, in individuals with a SUD. METHODS: A sample of 102 adults with a SUD participated in the study. Path analysis by structural equation modelling tested a mediation model. RESULTS: Depressive symptoms and lower levels of managing the pain were found to fully mediate the association between childhood trauma and suicidal ideation. CONCLUSIONS: Our results suggest that depressive symptoms and a lack of ability to manage psychological pain contribute towards explaining why traumatic childhood experiences may result in suicidal cognitions in individuals with SUDs. Moreover, they have relevant implications for prevention and clinical interventions regarding suicidal ideation in this population. PRACTITIONER POINTS: Childhood trauma relates to suicidal ideation in individuals with a substance use disorder. Depressive symptoms contribute towards explaining why traumatic childhood experiences may result in suicidal cognitions. A lack of ability to manage psychological pain also contributes towards explaining this relationship. The obtained results have relevant implications for the prevention of and clinical intervention for suicidal ideation in SUD individuals.

Inertial Data-Based AI Approaches for ADL and Fall Recognition.

The recognition of Activities of Daily Living (ADL) has been a widely debated topic, with applications in a vast range of fields. ADL recognition can be accomplished by processing data from wearable sensors, specially located at the lower trunk, which appears to be a suitable option in uncontrolled environments. Several authors have addressed ADL recognition using Artificial Intelligence (AI)-based algorithms, obtaining encouraging results. However, the number of ADL recognized by these algorithms is still limited, rarely focusing on transitional activities, and without addressing falls. Furthermore, the small amount of data used and the lack of information regarding validation processes are other drawbacks found in the literature. To overcome these drawbacks, a total of nine public and private datasets were merged in order to gather a large amount of data to improve the robustness of several ADL recognition algorithms. Furthermore, an AI-based framework was developed in this manuscript to perform a comparative analysis of several ADL Machine Learning (ML)-based classifiers. Feature selection algorithms were used to extract only the relevant features from the dataset's lower trunk inertial data. For the recognition of 20 different ADL and falls, results have shown that the best performance was obtained with the K-NN classifier with the first 85 features ranked by Relief-F (98.22% accuracy). However, Ensemble Learning classifier with the first 65 features ranked by Principal Component Analysis (PCA) presented 96.53% overall accuracy while maintaining a lower classification time per window (0.039 ms), showing a higher potential for its usage in real-time scenarios in the future. Deep Learning algorithms were also tested. Despite its outcomes not being as good as in the prior procedure, their potential was also demonstrated (overall accuracy of 92.55% for Bidirectional Long Short-Term Memory (LSTM) Neural Network), indicating that they could be a valid option in the future.

Evaluation of pretreatments on intra-radicular dentin bond strength of self-adhesive resin cements.

OBJECTIVES: To evaluate the influence of dentin pretreatments on the push-out bond strength (POBS) of self-adhesive resin cements (SARCs) to radicular dentin. MATERIALS AND METHODS: Two experimental pretreatments (2.5% titanium tetrafluoride (TiF4 ) and 26% polyacrylic acid (PA)) and two SARCs: Maxcem Elite (MAX) and Calibra Universal (CAL) were used. For each cement, a control group was applied as indicated by the manufacturer. Sixty bovine incisors were restored (n = 10) and subjected to POBS evaluation. Failure mode, adhesive interface and surface morphology were analyzed by a Scanning Electron Microscopy (SEM) and resin infiltration was performed by confocal laser scanning microscopy (CLSM). Data for POBS and CLSM were analyzed by three-way ANOVA and Bonferroni post-hoc (α = 0.05). RESULTS: For MAX, both experimental pretreatments resulted in increased POBS in the cervical third, and for CAL, only the PA resulted in higher POBS in the cervical third. The most failures occurred between the dentin and the resin cement, except when TiF4 was applied. For PA, analysis of surface morphology showed open dentinal tubules, while TiF4 presented particle agglomerates. SEM and CLSM images confirmed presence of resin tags for both pretreatments. CONCLUSION: Pretreating radicular dentin with PA and TiF4 solutions improves the bond strength of SARCs.

Characterization of the Human Papillomavirus 16 Oncogenes in K14HPV16 Mice: Sublineage A1 Drives Multi-Organ Carcinogenesis.

The study of human papillomavirus (HPV)-induced carcinogenesis uses multiple in vivo mouse models, one of which relies on the cytokeratin 14 gene promoter to drive the expression of all HPV early oncogenes. This study aimed to determine the HPV16 variant and sublineage present in the K14HPV16 mouse model. This information can be considered of great importance to further enhance this K14HPV16 model as an essential research tool and optimize its use for basic and translational studies. Our study evaluated HPV DNA from 17 samples isolated from 4 animals, both wild-type (n = 2) and HPV16-transgenic mice (n = 2). Total DNA was extracted from tissues and the detection of HPV16 was performed using a qPCR multiplex. HPV16-positive samples were subsequently whole-genome sequenced by next-generation sequencing techniques. The phylogenetic positioning clearly shows K14HPV16 samples clustering together in the sub-lineage A1 (NC001526.4). A comparative genome analysis of K14HPV16 samples revealed three mutations to the human papillomaviruses type 16 sublineage A1 representative strain. Knowledge of the HPV 16 variant is fundamental, and these findings will allow the rational use of this animal model to explore the role of the A1 sublineage in HPV-driven cancer.

CD274 (PD-L1), CDKN2A (p16), TP53, and EGFR immunohistochemical profile in primary, recurrent and metastatic vulvar cancer.

Vulvar squamous cell carcinoma can be divided by human papillomaviruses (HPV) status into two distinct clinicopathological and molecular entities. New agents targeting the tumor surface expression of programmed cell death-1/programmed cell death-ligand-1 are becoming a therapeutic option in an increasing number of carcinomas. We evaluate CD274 (PD-L1), CDKN2A (p16), tumor protein p53 (TP53), and epidermal growth factor receptor (EGFR) immunoexpression in primary tumors, recurrences and lymph node metastases and its correlations with prognosis and HPV status. We report 93 cases of vulvar squamous cell carcinoma diagnosed between 2002 and 2016 with the description of their clinicopathological features and prognosis data. Immunohistochemistry for CD274, CDKN2A, TP53, and EGFR was performed on tissue microarrays collecting from primary tumor, recurrences and lymph node metastasis. Kaplan-Meier estimator and multivariable Cox regression analysis controlling for FIGO stage and age were used. Patients who underwent surgery had a superior overall survival (HR = 0.51, 95% CI = 0.26-0.99 p = 0.04). Lymph node metastasis size ≥5 mm was associated with an inferior overall survival (HR = 1.88, 95% CI = 1.22-2.92 p = 0.004). CDKN2A expression was correlated with an inferior rate of recurrent disease (p = 0.02). In high-risk HPV DNA+ vulvar squamous cell carcinomas patients with CDKN2A- carcinomas showed a significantly worse overall survival than women with CDKN2A+ tumors (56% vs.100%, p = 0.003). TP53 expression was associated with an increased rate of recurrent disease (p = 0.0005). CD274 expression was associated with lymph node metastasis (p = 0.04). In 16 patients the CD274, CDKN2A, TP53, and EGFR expression changed between primary tumors, recurrences and lymph node metastases during tumor progression. In conclusion, a significant percentage of vulvar squamous cell carcinoma has a heterogeneous biomarker expression during tumor progression. We highlight the importance of some of these markers to be used as prognostic biomarkers. This data brings new light to future treatment using targeted therapy to EGFR or CD274 to include retesting such biomarkers in recurrence and lymph nodes metastases.

The papillomavirus E5 gene does not affect EGFR transcription and overall survival in cervical cancer.

INTRODUCTION: The human papillomavirus (HPV) E5 gene encodes a small and highly hydrophobic oncoprotein that affects immune evasion, cell proliferation, loss of apoptotic capacity and angiogenesis in tumors. E5 shows an affinity for biological membranes and was associated with an increase of epidermal growth factor/epidermal growth factor receptor (EGF/EGFR) signaling through the accumulation of EGFR in cellular membranes. Due to the frequent integration of the HPV genome into the host cell genome, E5 is frequently not transcribed in cervical tumors. AIM: In this study we looked forward to verifying whether the potential expression of E5 protein in human papillomavirus 16 positive (HPV16+ ) and human papillomavirus 18 positive (HPV18+ ) cervical tumors was associated with levels of EGFR and vascular endothelial growth factor A (VEGFA) transcription and with patients overall survival. RESULTS: Association between the presence of E5 transcripts and viral genome disruption was observed for HPV16+ and HPV18+ tumors. Association was not observed between tumors potentially capable of translating E5 and EGFR or VEGFA transcriptional levels. Similarly, the capability of translating E5 and overall survival in patients with HPV16+ squamous cell carcinoma tumors stage ≥ IB2 were not associated. CONCLUSION: The likely presence of E5 transcripts was neither associated to a higher activity of the EGFR-VEGFA pathway nor to the overall survival of patients with HPV16+ squamous cell carcinoma in stages ≥ IB2.

Valorisation of pectin-rich agro-industrial residues by yeasts: potential and challenges.

Pectin-rich agro-industrial residues are feedstocks with potential for sustainable biorefineries. They are generated in high amounts worldwide from the industrial processing of fruits and vegetables. The challenges posed to the industrial implementation of efficient bioprocesses are however manyfold and thoroughly discussed in this review paper, mainly at the biological level. The most important yeast cell factory platform for advanced biorefineries is currently Saccharomyces cerevisiae, but this yeast species cannot naturally catabolise the main sugars present in pectin-rich agro-industrial residues hydrolysates, in particular D-galacturonic acid and L-arabinose. However, there are non-Saccharomyces species (non-conventional yeasts) considered advantageous alternatives whenever they can express highly interesting metabolic pathways, natively assimilate a wider range of carbon sources or exhibit higher tolerance to relevant bioprocess-related stresses. For this reason, the interest in non-conventional yeasts for biomass-based biorefineries is gaining momentum. This review paper focuses on the valorisation of pectin-rich residues by exploring the potential of yeasts that exhibit vast metabolic versatility for the efficient use of the carbon substrates present in their hydrolysates and high robustness to cope with the multiple stresses encountered. The major challenges and the progresses made related with the isolation, selection, sugar catabolism, metabolic engineering and use of non-conventional yeasts and S. cerevisiae-derived strains for the bioconversion of pectin-rich residue hydrolysates are discussed. The reported examples of value-added products synthesised by different yeasts using pectin-rich residues are reviewed. Key Points • Review of the challenges and progresses made on the bioconversion of pectin-rich residues by yeasts. • Catabolic pathways for the main carbon sources present in pectin-rich residues hydrolysates. • Multiple stresses with potential to affect bioconversion productivity. • Yeast metabolic engineering to improve pectin-rich residues bioconversion. Graphical abstract.

An investigation of cross-reactivity between the poultry red mite and house dust and storage mites in dogs with contact with chickens infested with red mites.

BACKGROUND: The European poultry red mite (PRM) Dermanyssus gallinae, a common ectoparasite of laying chickens and pigeons; it also can feed on other birds, humans and domestic animals, causing clinical signs ranging from mild discomfort to severe dermatitis. Little is known about possible hypersensitivity to PRM or cross-sensitization with house dust or storage mites. HYPOTHESIS/OBJECTIVES: Knowledge on possible PRM immunoglobulin E (IgE)-mediated allergy and possible cross-sensitization with house dust and storage mites may facilitate the clinical approach. The aim herein was to clarify possible evidence of type I hypersensitivity to PRM in dogs and possible occurrence of cross-sensitization with house dust and storage mites. ANIMALS: Sixteen dogs with chronic contact with PRM-infested chickens from traditional bird houses and 10 control dogs with no contact with birds. METHODS AND MATERIALS: Dogs were subjected to intradermal testing (IDT) and serum specific IgE (sIgE) determination for house dust and storage mites and D. gallinae. RESULTS: The highest wheal score was obtained with 0.1 mg/mL D. gallinae extract. Positive IDT reactions to PRM were found in four of 10 control dogs and in 10 of 16 from the chicken-exposed group. SIgE to PRM was detected in one control and in seven dogs exposed to chickens. No significant correlation was found between IDT or sIgE scores to PRM and house dust and storage mites. CONCLUSIONS AND CLINICAL SIGNIFICANCE: Contact with PRM-infested chickens may lead to sensitization without allergy, independently from sensitization to house dust and storage mites.

Implementation and certification of ISO 9001:2015 seal in human tissue bank HCFMRP-USP.

The Quality Management System has been a management technology applied to guarantee the quality of processes and products of a given organization. Thus, ISO 9001:2015 certification assists organizations that want to develop, implement, maintain, and improve a quality management system to enable process improvements and assessments to meet the needs of its customers. This experience report addresses the implementation and certification of the ISO 9001:2015 quality management seal at the Human Tissue Bank of the Ribeirão Preto Clinical Hospital (HCRP) at the University of São Paulo (USP) at Ribeirão Preto Medical School (FMRP)-Brazil. In 2018, the Human Tissue Bank, in partnership with HCRP, received consultancies from PRIMEMODE. The consulting consisted of visits that elucidated the processes to the employees of the Tissue Bank, enabling them to clarify the applicability of all items of the standard. In March 2019, the Tissue Bank received the audit visit and was certified with the ISO 9001:2015 Seal by the Carlos Alberto Vanzolini Foundation. The Tissue Bank aims to provide human tissues for transplantation and research from organ donors. It has a complex physical structure within the required health and legal standards. Also, now it has a quality management seal. The certification guarantees the process organization and the high quality standard of the supplied tissues.

From nano-emulsions to phase separation: evidence of nano-segregation in (alkane + perfluoroalkane) mixtures using 129Xe NMR Spectroscopy.

In this work we demonstrate that mixtures of (hexane + perfluorohexane) above the upper critical solution temperature segregate by forming domains at the nanometric scale. 129Xe NMR spectra obtained for solutions of xenon in liquid mixtures of (hexane + perfluorohexane) as a function of temperature suggest the existence of domains richer in the hydrogenated component, in which xenon "prefers" to be solvated. The average local concentration within the xenon coordination sphere is at least 0.05 higher in hexane mole fraction than the nominal concentration of the mixture. Atomistic molecular dynamics simulations support this analysis in excellent agreement with the experimental data. Additionally, 129Xe NMR spectra in pure perfluoroalkanes allow a detailed analysis of the liquid structure, continuing that previously reported for the liquid alkanes. It should be emphasised that nano-segregation is here observed in fluids governed exclusively by dispersion interactions, in contrast to other examples in which hydrogen bonding and polarity play important roles. Given its simplicity, this case study is thus prone to have a general impact in understanding the early mechanisms of segregation, phase separation and self-assembly.

Influence of silica nanocoating on stain susceptibility and superficial integrity of dimethacrylate-based composites.

The aim of this study was to investigate the ability of a novel silica (SiO2 )-based nanocoating approach to extend the superficial integrity of current composites. Cylindrical discs (7 × 2 mm) were produced from nanohybrid and nanofilled composites. Specimens in control groups were not coated, but SiO2 nanocoating was performed on specimens in experimental groups (n = 8). Specimens were stored for 24 h in distilled water at 37°C (baseline) and then artificially aged for 15, 90, or 180 d in a low-pH staining solution. Surface roughness (Ra) was measured using a profilometer, and a goniometer was used to determine surface free energy (SFE). Color change was evaluated by a reflectance spectrophotometer, applying the color distance metric, ΔE00 , according to the Commission Internationale de l'Eclairage (CIE) L*a*b* coordinates. Data were subjected to repeated-measures anova and the Tukey post-hoc test. Composites presented visually perceptible color changes (ΔE00  > 0.81) as early as 15 d of aging, with significantly higher ΔE00 values recorded over time. Nanocoating with SiO2 significantly reduced the SFE of composites at all storage times, and significantly lower Ra values were identified after aging. Nanohybrid and nanofilled composites were susceptible to substantial hydrolytic superficial degradation and staining, which was dramatically attenuated by the proposed SiO2 nanocoating approach. Nanocoating effectively lowered the SFE of composites, thus minimizing water-composite interactions, which contributed to reduced superficial deterioration and lower stain susceptibility over time.

Understanding the interactions of imidazolium-based ionic liquids with cell membrane models.

Cell membrane models have been used to evaluate the interactions of various imidazolium-based ionic liquids (ILs) with Langmuir monolayers of two types of phospholipids and cholesterol. Data from surface pressure isotherms, Brewster angle microscopy (BAM) and polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS) pointed to significant effects on the monolayers of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol, used to mimic the membranes of eukaryotic cells, for ILs containing more than 6 carbon atoms in the alkyl chain (i.e. n > 6). For ILs with less hydrophobic tails (n ≤ 6) and low concentrations, the effects were almost negligible, therefore, such ILs should not be toxic to eukaryotic cells. The hydrophobicity of the anion was also proved to be relevant, with larger impact from ILs containing tetrafluoroborate ([BF4]-) than chloride (Cl-). Molecular dynamics simulations for DPPC monolayers at the surface of aqueous solutions of alkylimidazolium chloride ([Cnmim]Cl) confirm the penetration of the IL cations with longer alkyl chains into the phospholid monolayer and provide information on their location and orientation within the monolayer. For monolayers of dipalmitoylphosphatidyl glycerol (DPPG), which is negatively charged like bacteria cell membranes, the ILs induced much larger effects. Similarly to the results for DPPC and cholesterol, effects increased with the number of carbon atoms in the alkyl chain and with a more hydrophobic anion [BF4]-. Overall, the approach used can provide relevant information of molecular-level interactions behind the toxicity mechanisms and support the design of (quantitative) structure-activity relationship models, which may help design more efficient and environmentally friendly ILs.

Lack of Ovarian Secretions Reverts the Anabolic Action of Olanzapine in Female Rats.

Background: Olanzapine is an orexigenic antipsychotic drug associated with serious metabolic adverse effects in humans. Development of valid rodent models for antipsychotic-induced metabolic adverse effects is hampered by the fact that such effects occur in females only. Estradiol is a predominant female hormone that regulates energy balance. We hypothesized that the female-specific hyperphagia and weight gain induced by olanzapine in the rat are dependent on the presence of estrogens. Methods: Female sham-operated or ovariectomized rats were treated with a single injection of olanzapine depot formulation. Food intake, body weight, plasma lipids, lipogenic gene expression, energy expenditure, and thermogenic markers including brown adipose tissue uncoupling protein 1 protein levels were measured. Olanzapine was also administered to ovariectomized rats receiving estradiol replacement via the subcutaneous (peripheral) or intracerebroventricular route. Results: Orexigenic effects of olanzapine were lost in ovariectomized female rats. Ovariectomized rats treated with olanzapine had less pronounced weight gain than expected from their food intake. Accordingly, brown adipose tissue temperature and protein levels of uncoupling protein 1 were elevated. Replacement in ovariectomized rats with either peripherally or centrally administered estradiol reduced food intake and body weight. Cotreatment with olanzapine blocked the anorexigenic effect of peripheral, but not central estradiol. Conclusions: Our results indicate that the ovarian hormone estradiol plays an important role in olanzapine-induced hyperphagia in female rats and pinpoint the complex effects of olanzapine on the balance between energy intake and thermogenesis.