Search

The aim of this article is to investigate the state of conservation of the Roman Theatre of Regina Turdulorum during its history. Therefore, a first part is presented, dedicated to understanding those documents referred to the preservation of this theatre. Then, the criteria for restoration of the different interventions in the theatre are analyzed. In the third and last part, the current situation of the theatre site is presented to examine its compatibility with the Roman ruins. [ABSTRACT FROM AUTHOR]

The concept of a pedal curve is used in geometry as a generation method for a multitude of curves. The definition of a pedal curve is linked to the concept of minimal distance. However, an interesting distinction can be made for ℝ². In this space, the pedal curve of another curve C is defined as the locus of the foot of the perpendicular from the pedal point P to the tangent to the curve. This allows the generalization of the definition of the pedal curve for any given angle that is not 90°. In this paper, we use the generalization of the pedal curve to describe a different method to generate a limaçon of Pascal, which can be seen as a singular case of the locus generation method and is not well described in the literature. Some additional properties that can be deduced from these definitions are also described. [ABSTRACT FROM AUTHOR]

Early interactions of influenza A virus (IAV) with respiratory epithelium might determine the outcome of infection. The study of global cellular innate immune responses often masks multiple aspects of the mechanisms by which populations of cells work as organized and heterogeneous systems to defeat virus infection, and how the virus counteracts these systems. In this study, we experimentally dissected the dynamics of IAV and human epithelial respiratory cell interaction during early infection at the single-cell level. We found that the number of viruses infecting a cell (multiplicity of infection [MOI]) influences the magnitude of virus antagonism of the host innate antiviral response. Infections performed at high MOIs resulted in increased viral gene expression per cell and stronger antagonist effect than infections at low MOIs. In addition, single-cell patterns of expression of interferons (IFN) and IFN-stimulated genes (ISGs) provided important insights into the contributions of the infected and bystander cells to the innate immune responses during infection. Specifically, the expression of multiple ISGs was lower in infected than in bystander cells. In contrast with other IFNs, IFN lambda 1 (IFNL1) showed a widespread pattern of expression, suggesting a different cell-to-cell propagation mechanism more reliant on paracrine signaling. Finally, we measured the dynamics of the antiviral response in primary human epithelial cells, which highlighted the importance of early innate immune responses at inhibiting virus spread. [ABSTRACT FROM AUTHOR]

The incoming influenza A virus (IAV) genome must pass through two distinct barriers in order to establish infection in the cell: the plasma membrane and the nuclear membrane. A precise understanding of the challenges imposed by the nuclear barrier remains outstanding. Passage across is mediated by host karyopherins (KPNAs), which bind to the viral nucleoprotein (NP) via its N-terminal nuclear localization sequence (NLS). The binding affinity between the two molecules is low, but NP is present in a high copy number, which suggests that binding avidity plays a compensatory role during import. Using nanobody-based technology, we demonstrate that a high binding avidity is required for infection, though the absolute value differs between cell types and correlates with their relative susceptibility to infection. In addition, we demonstrate that increasing the affinity level caused a decrease in avidity requirements for some cell types but blocked infection in others. Finally, we show that genomes that become frustrated by low avidity and remain cytoplasmic trigger the type I interferon response. Based on these results, we conclude that IAV balances affinity and avidity considerations in order to overcome the nuclear barrier across a broad range of cell types. Furthermore, these results provide evidence to support the long-standing hypothesis that IAV's strategy of import and replication in the nucleus facilitates immune evasion. IMPORTANCE We used intracellular nanobodies to block influenza virus infection at the step prior to nuclear import of its ribonucleoproteins. By doing so, we were able to answer an important but outstanding question that could not be addressed with conventional tools: how many of the ~500 available NLS motifs are needed to establish infection? Furthermore, by controlling the subcellular localization of the incoming viral ribonucleoproteins and measuring the cell's antiviral response, we were able to provide direct evidence for the long-standing hypothesis that influenza virus exploits nuclear localization to delay activation of the innate immune response. [ABSTRACT FROM AUTHOR]

Graphical abstract Our results suggest that alpha-cell dysfunction precedes the Type 2 diabetes mellitus (T2DM) development. T2DM Risk Assessment by COX analysis using glucagon/insulin (G/I) ratio at 30 min after an OGTT was able to assess the T2DM risk with an HR of 2.514. This process seems to be independent of diet consumed, whereas prediabetes (PreDM) regression might be differentially modulated by diets. Specifically, the consumption of Mediterranean diet was associated with a decrease in G/I ratio suggesting an improvement in alpha cell functionality. By contrast, the consumption of low-fat diet seems to induce PreDM regression by reducing insulin resistance as evidenced by the lower insulin levels in this group. Unlabelled Image [ABSTRACT FROM AUTHOR]

On 30 March 2018, protesters in the Gaza Strip engaged in a peaceful demonstration for “Land Day,” a Palestinian commemoration of the expropriation of lands for Israeli settlements in 1976. During the march, Palestinians approached the border with Israel where the Israeli army opened fire with live ammunition and tank shells, killing at least fifteen demonstrators. Dozens of others were wounded. In the weeks and months that followed, Palestinian protesters continued to protest at the Gaza border. As this issue goes to print, the International Committee of the Red Cross reports that at least 116 Palestinians have been killed in protests framed as the “Great March of Return” since 30 March 2018, and as many as thirteen thousand have been injured. This spring's events, coinciding with the seventieth anniversary of the founding of the state of Israel and the US decision to move its embassy to Jerusalem, offer yet another reminder of the violence and dispossession that for decades have characterized Palestinian life under Israeli occupation. [ABSTRACT FROM AUTHOR]

Influence of culinary treatments (boiling, microwaving, grilling, and deep frying) on proximate composition and antioxidant capacity of cultivated mushrooms (Agaricus bisporus, Lentinula edodes, Pleurotus ostreatus, and Pleurotus eryngii) was studied. Proximate composition was affected by the cooking method and the mushrooms species. Frying induced more severe losses in protein, ash, and carbohydrates content but increased the fat and energy. Boiling improved the total glucans content by enhancing the β-glucans fraction. A significant decrease was detected in the antioxidant activity especially after boiling and frying, while grilled and microwaved mushrooms reached higher values of antioxidant activity. Maillard reaction products could be partially responsible, as supported by the absorbance values measured at 420 nm. Since cooking techniques clearly influence the nutritional attributes of mushrooms, the proper selection of treatments is a key factor to prevent/reduce nutritional losses. Microwaving and grilling were established as the best processes to maintain the nutritional profile of mushrooms. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effects of the consumption of Maillard reaction products (MRPs) from bread crust (BC) on iron, copper and zinc body retention and tissue distribution, determining whether these effects are related to the molecular weight of browning products. Methods: During an 88-day study period, rats were fed a Control diet or diets containing BC as source of MRPs, its soluble high or low molecular weight fractions (BC, LMW or HMW diets). A mineral balance was conducted throughout the experiment to determine iron, copper and zinc retention. At day 88, animals were killed, blood was drawn for haemoglobin determination and some organs removed to analyse minerals. Results: Copper and zinc balances were unchanged, and scant modification detected in their body delivery. However, the Fe retention rate from the diet increased (13, 22 and 32 % for BC, LMW and HMW diets), and a parallel higher Fe body concentration was observed (13-18 % higher than the Control group). Incoming iron accumulated particularly in the liver, femur and small intestine, but functional iron tended to decrease, as reflected by haemoglobin levels. Conclusions: The long-term intake of BC or derivatives did not produce a notable effect on copper or zinc balances, although slightly increased iron retention rate and the body concentration of this mineral were observed. Iron accumulated in some organs, but the production of haemoglobin was not improved. In view of the differences observed between the effects of BC and its derivatives, our results underline the importance of working with real food matrices, where the joint presence of different components modulates the in vivo final effects. [ABSTRACT FROM AUTHOR]

Three cases of influenza A(H10N8) virus infection in humans have been reported; 2 of these infected persons died. Characterization of the receptor binding pattern of H10 hemagglutinin from avian and human isolates showed that both interact weakly with human-like receptors and maintain strong affinity for avian-like receptors. [ABSTRACT FROM AUTHOR]

The objective of the present study was to evaluate the in vivo uptake of antioxidant capacity (AC) in rats fed on diets containing commonly consumed MRPs obtained from bread crust (BC) at long-term. Additionally we focused on understanding the effects of those compounds on the oxidative status of these animals. The global antioxidant response of the diets was measured. During 88 days, rats were fed control diet or diets containing BC or its soluble high molecular weight, soluble low molecular weight or insoluble fractions (BC, HMW, LMW and insoluble diets, respectively). In the final week, faeces from different dietary treatments were collected to determine the AC still retained in it and then calculate the uptake efficiency of AC. Animals were sacrificed and the liver and biceps brachii muscle were removed to investigate catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and reduced glutathione (GSH) levels. The addition of BC or its derivatives in the diet led to a significantly higher AC excreted with the faeces and to a lower uptake rate (around 90% in these groups vs. 98% in the control group). The muscle and liver showed different oxidative status after consumption of experimental diets. The muscle evidenced certain oxidative damage due to the BC consumption, more pronounced when the isolated fractions were ingested. However, the BC diet, but not the rest, induced a positive effect on the antioxidant defence in the liver, the key organ for xenobiotic metabolism, with increases in the CAT and GPx activities as well as the GSH stock (56, 20 and 14% with respect to the control group, respectively). The discordance found between the antioxidant status of muscle and antioxidant status of liver highlights the importance of considering several tissues to establish the effect of glycated compounds on the redox balance in an organism. [ABSTRACT FROM AUTHOR]

We investigate the effects of consumption of MRPs from the glucose-lysine model system heated 15°C-90 min on protein digestibility and its utilisation in young (3-week) and adult (12-week) rats. Nitrogen faecal excretion significantly increased after MRP consumption, especially during the third week. Protein digestibility was lower in both age groups studied, but the utilisation was unaffected. Parallelly, the nitrogen retention and its net utilisation for the entire experimental period did not vary. In young rats the faecal nitrogen exceeded the amount of ingested nitrogen coming from MRPs, suggesting that digestibility of undamaged nitrogen was affected. The same action is suspected in adult animals, but the results were not quantitatively conclusive, and therefore the effect should be moderate in this period. [ABSTRACT FROM AUTHOR]

Background Physical and biomechanical properties of bone can be affected by non-enzymatic crosslinks, which are implicated in bone pathologies such as osteoporosis. The purpose of this study was to analyse the effects of the consumption of model Maillard reaction product ( MRP) from glucose-lysine heated for 90 min at 150 °C ( GL90) on bone composition and features. Rats were fed either a control diet or a diet containing 30 g kg−1 GL90 for 88 days. Food consumption and the animals' body weights were monitored. After sacrifice, the femur, pelvic bone and tibia were removed for analysis of their composition and physical and biomechanical properties. Results The organic matrix of the femur and the density of the pelvic bone decreased after MRP intake, whereas pentosidine content increased greatly with respect to the control group (41.7 ± 9.9 vs 171.4 ± 3.3 mmol mol−1 collagen). The rising level of C-telopeptide degradation products from type I collagen ( β- CTX) suggested a possible situation of increased bone resorption and/or higher turnover. Conclusion In conjunction, the detrimental effect on the organic matrix, the situation of higher resorption and/or bone turnover indicated by the β- CTX values and the high pentosidine content in bone provoked negative consequences on certain mechanical properties such as the ability to withstand force and absorb energy without failure. © 2013 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

BACKGROUND Consumption of Maillard reaction products ( MRPs) present in food has been related to deterioration of protein digestibility and changes in mineral bioavailability. We aimed to investigate the effects of MRP intake from bread crust on magnesium balance and tissue distribution, seeking causative factors among its different components. RESULTS During the final stage of the trial, magnesium digestibility improved by around 15% in rats fed diets containing bread crust or its derivatives compared with the control diet. Despite certain enhancements in magnesium bioavailability in this stage, for the experimental period as a whole, this parameter remained unchanged. However, specific changes in the content and/or concentration in some organs were observed, particularly in the femur, where magnesium levels were higher due to the smaller size of the bones. CONCLUSIONS Consumption of MRPs from bread crust or its different components did not modify the magnesium balance. Nevertheless, the bread crust fractions led to some changes in magnesium tissue distribution which did not match the effects induced by complete bread crust intake, suggesting the importance of designing studies with real-food systems, in order to reinforce the validity of the findings obtained. © 2012 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Maillard reaction products (MRP) consumption has been related with the development of bone degenerative disorders, probably linked to changes in calcium metabolism. We aimed to investigate the effects of MRP intake from bread crust on calcium balance and its distribution, and bone metabolism. During 88 days, rats were fed control diet or diets containing bread crust as source of MRP, or its soluble high molecular weight, soluble low molecular weight or insoluble fractions (bread crust, HMW, LMW and insoluble diets, respectively). In the final week, a calcium balance was performed, then animals were sacrified and some organs removed to analyse calcium levels. A second balance was carried out throughout the experimental period to calculate global calcium retention. Biochemical parameters and bone metabolism markers were measured in serum or urine. Global calcium bioavailability was unmodified by consumption of bread crust or its isolate fractions, corroborating the previously described low affinity of MRP to bind calcium. Despite this, a higher calcium concentration was found in femur due to smaller bones having a lower relative density. The isolate consumption of the fractions altered some bone markers, reflecting a situation of increased bone resorption or higher turnover; this did not take place in the animals fed the bread crust diet. Thus, the bread crust intake does not affect negatively calcium bioavailability and bone metabolism. [ABSTRACT FROM AUTHOR]

The influenza virus nonstructural protein 1 (NS1) inhibits innate immunity by multiple mechanisms. We previously reported that NS1 is able to inhibit the production of type I interferon (IFN) and proinflammatory cytokines in human primary dendritic cells (DCs). Here, we used recombinant viruses expressing mutant NS1 from the A/T exas/36/91 and A/Puerto Rico/08/34 strains in order to analyze the contribution of different NS1 domains to its antagonist functions. We show that the polyadenylation stimulating factor 30 (CPSF30) binding function of the NS1 protein from A/T exas/36/91 influenza virus, which is absent in the A/Puerto Rico/08/34 strain, is essential for counteracting these innate immune events in DCs. However, the double-stranded RNA (dsRNA) binding domain, present in both strains, specifically inhibits the induction of type I IFN genes in infected DCs, while it is essential only for inhibition of type I IFN proteins and proinflammatory cytokine production in cells infected with influenza viruses lacking a functional CPSF30 binding domain, such as A/Puerto Rico/08/34. [ABSTRACT FROM AUTHOR]

Herpes simplex virus 2 (HSV-2) may cause frequent recurrences, highlighting its ability to evade host defense. This study tested the hypothesis that HSV-2 interferes with dendritic cell (DC) function as an escape mechanism, which may contribute to enhanced HIV replication in coinfected populations. Immature monocyte-derived human DCs were exposed to live or UV-inactivated HSV-2 or lipopolysaccharide. Little or no increase in the maturation marker CD83 was observed in response to HSV-2 and HSV-2 exposed DCs were impaired in their ability to present antigen (influenza) to T cells. Exposure to UV-inactivated virus stimulated a modest, but significant increase in CD83, suggesting that viral gene expression contributes to the block in DC maturation. The functional impairment of HSV-2-exposed DCs could be partially attributed to the induction of apoptosis. Live and inactivated HSV-2 triggered an increase in the number of early and late apoptotic cells in both the infected and bystander cell populations; apoptosis was associated with a decrease in cellular FLICE-inhibitory protein (c-FLIP). Paradoxically, HSV-2 induced Akt phosphorylation, which typically promotes DC maturation and survival. Despite these aberrant responses, live and inactivated HSV-2 induced the release of cytokines into culture supernatants, which were sufficient to activate HIV-1 replication in latently infected U1 cells. Together, these findings suggest that in the presence of overt or subclinical HSV-2, the function of mucosal DCs would be impaired. These responses may allow HSV to escape immune surveillance but may also promote HIV infection and contribute to the epidemiological link between HIV and HSV. [ABSTRACT FROM AUTHOR]

Avian influenza virus infections in the human population are rare due to their inefficient direct human-to-human transmission. However, when humans are infected, a strong inflammatory response is usually induced, characterized by elevated levels of cytokines and chemokines in serum, believed to be important in the severe pathogenesis that develops in a high proportion of these patients. Extensive research has been performed to understand the molecular viral mechanisms involved in the H5N1 pathogenesis in humans, providing interesting insights about the virus-host interaction and the regulation of the innate immune response by these highly pathogenic viruses. In this review we summarize and discuss the most important findings in this field, focusing mainly on H5N1 virulence factors and their impact on the modulation of the innate immunity in humans. [ABSTRACT FROM AUTHOR]

Background: Maillard reaction products (MRP) improve food palatability and are linked to some positive biological actions. However, diverse negative consequences, some related to protein damage and mineral availability, have been established. Aim of study: We investigated the effects of MRP, from a bread crust diet, on phosphorus bioavailability and tissue distribution in rats to determine whether these effects are related to the molecular weight of browning products. Methods: During a study period of 88 days, rats were fed either a control diet or one of the following: with bread crust as a source of MRP, or one with its soluble high molecular weight, soluble low molecular weight or insoluble fraction (bread crust, HMW, LMW and insoluble diets, respectively). In the final week, a phosphorus balance was performed, after which the animals were sacrificed and some organs removed to analyse phosphorus content. A second balance was carried out throughout the experimental period to calculate phosphorus retention. Results: Phosphorus balance in the last week was unchanged. However, considering the whole experimental period, a trend towards improved bioavailability, significant in the HMW group, was observed. Higher phosphorus concentrations were measured in the small intestine and bone. Conclusions: The consumption of MRP derived from bread did not alter phosphorus retention, due to increased bioavailability, especially concerning HMW compounds. The overall phosphorus body content remained unchanged and there were no changes in the bone, its principal metabolic destination. However, MRP consumption markedly raised phosphorus levels at the digestive level, especially when consumed as isolate fractions. The slower rate of stomach emptying is assumed to be related to this effect. [ABSTRACT FROM AUTHOR]

PB1-F2 is a 90 amino acid protein that is expressed from the +1 open reading frame in the PB1 gene of some influenza A viruses and has been shown to contribute to viral pathogenicity. Notably, a serine at position 66 (66S) in PB1-F2 is known to increase virulence compared to an isogenic virus with an asparagine (66N) at this position. Recently, we found that an influenza virus expressing PB1-F2 N66S suppresses interferon (IFN)-stimulated genes in mice. To characterize this phenomenon, we employed several in vitro assays. Overexpression of the A/Puerto Rico/8/1934 (PR8) PB1-F2 protein in 293T cells decreased RIG-I mediated activation of an IFN-b reporter and secretion of IFN as determined by bioassay. Of note, the PB1-F2 N66S protein showed enhanced IFN antagonism activity compared to PB1-F2 wildtype. Similar observations were found in the context of viral infection with a PR8 PB1-F2 N66S virus. To understand the relationship between NS1, a previously described influenza virus protein involved in suppression of IFN synthesis, and PB1-F2, we investigated the induction of IFN when NS1 and PB1-F2 were co-expressed in an in vitro transfection system. In this assay we found that PB1-F2 N66S further reduced IFN induction in the presence of NS1. By inducing the IFN-β reporter at different levels in the signaling cascade, we found that PB1-F2 inhibited IFN production at the level of the mitochondrial antiviral signaling protein (MAVS). Furthermore, immunofluorescence studies revealed that PB1-F2 co-localizes with MAVS. In summary, we have characterized the anti-interferon function of PB1-F2 and we suggest that this activity contributes to the enhanced pathogenicity seen with PB1-F2 N66S- expressing influenza viruses. [ABSTRACT FROM AUTHOR]

The pollen content of twenty-four unifloral honey samples from twelve different apiaries in La Palma (Canary Islands) was subjected to qualitative and quantitative melissopalynological analysis. The quantitative analysis showed that 4% of the honey belonged to Maurizio's Class I, 8% to Class II, 58% to Class III, 17% to Class IV and 13% to Class V. According to the qualitative analysis, eight honeys were typified as unifloral of Castanea sativa, five of Carlina salicifolia, three of Echium brevirame, three of Reseda luteola, two of Erica arborea, two of Lotus hillebrandii and one of Lamiaceae Origanum vulgare ssp. virens-type. No honeydew elements were found. 62 pollen types were identified belonging to 42 different families. There is no pollen type common to all samples but Foeniculum vulgare-type is present in 22 of the samples (91.7%) and the combination Cistus sp., Erica arborea, Aspalthium bituminosum, Origanum vulgare ssp. virens-type and Rumex sp. in 21 (87.5%). The organoleptic analysis indicated that they are of good quality. [ABSTRACT FROM AUTHOR]

The pollen content of twenty-five honey samples from twelve different apiaries on La Palma (Canary Islands) was subjected to qualitative and quantitative melissopalynological analysis. The quantitative analysis showed that 4% of the honey belonged to Maurizio Class II, 88% to Class III, 4% to Class IV and 4% to Class V. In the qualitative analysis, 60 pollen types were identified from 40 different families. The number of pollen types per honey sample ranges between 16 and 37 (mean of 25.8). Foeniculum vulgare-type and Rumex sp. pollen were present in all the samples. Castanea sativa and Echium plantagineum pollen were found in 96% of them and the combination Aspalathium bituminosum, Bidens pilosa-type and Erica arborea in 92%. [ABSTRACT FROM AUTHOR]

Currently, Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry (MALDI-TOF MS) is being evaluated for its efficacy as a fast bacterial typing tool due to its great speed compared to other molecular methods. In this study, we evaluated MALDI-TOF as a tool for quick identification and typing of Francisella tularensis. This study encompassed 86 strains from two different geographical origins (Spain and the Czech Republic), which were previously characterised by Pulsed-Field Gel Electrophoresis (PFGE) and Multiple-Locus Variable Number Tandem Repeat Analysis (MLVA). The direct colony method was used for microbial identification. High-quality spectra of the 86 strains were obtained and their main spectra profiles (MSPs) were created for epidemiological typing using MALDI-TOF. Based on the MSPs, principal components were generated and a dendrogram was constructed. An in-house MALDI-TOF library entry was created for each group of PFGE and MLVA strains based on their high-quality spectra. Two dendrograms were obtained using these entries and the unique peaks in each entry were searched. All strains were correctly identified to the species level. No clear divisions were found in the 86-strain dendrogram; however, Spanish and Czech strains appeared separately in dendrograms created using MLVA and PFGE entries. Entries from our in-house MALDI-TOF library revealed 2–4 biomarker peaks for the detection of the five PFGE groups and 1–12 biomarker peaks for the detection of the seven MLVA groups. Finally, two and one specific biomarkers were found in the Czech and Spanish strains, respectively. MALDI-TOF can be used to accurately identify F. tularensis strains in less than 15 min. Moreover, data on geographical origin and PFGE and MLVA groups could be obtained in less than one hour after colony growing. • Mass Spectrometry correctly identifies Francisella tularensis strains in less than 15 min, even if protein extraction is not performed. • A reliable clustering could not be achieved by the dendrogram obtained of all strains. • Dendrograms generated from the entries of our in-house library could be useful for the determination of the geographical origin of F. tularensis strains. [ABSTRACT FROM AUTHOR]

Vimentin is an intermediate filament protein that plays key roles in integration of cytoskeletal functions, and therefore in basic cellular processes such as cell division and migration. Consequently, vimentin has complex implications in pathophysiology. Vimentin is required for a proper immune response, but it can also act as an autoantigen in autoimmune diseases or as a damage signal. Although vimentin is a predominantly cytoplasmic protein, it can also appear at extracellular locations, either in a secreted form or at the surface of numerous cell types, often in relation to cell activation, inflammation, injury or senescence. Cell surface targeting of vimentin appears to associate with the occurrence of certain posttranslational modifications, such as phosphorylation and/or oxidative damage. At the cell surface, vimentin can act as a receptor for bacterial and viral pathogens. Indeed, vimentin has been shown to play important roles in virus attachment and entry of severe acute respiratory syndrome-related coronavirus (SARS-CoV), dengue and encephalitis viruses, among others. Moreover, the presence of vimentin in specific virus-targeted cells and its induction by proinflammatory cytokines and tissue damage contribute to its implication in viral infection. Here, we recapitulate some of the pathophysiological implications of vimentin, including the involvement of cell surface vimentin in interaction with pathogens, with a special focus on its role as a cellular receptor or co-receptor for viruses. In addition, we provide a perspective on approaches to target vimentin, including antibodies or chemical agents that could modulate these interactions to potentially interfere with viral pathogenesis, which could be useful when multi-target antiviral strategies are needed. [ABSTRACT FROM AUTHOR]

Dear Editor, Type 2 diabetes is widely considered as a chronic, progressive disease that is a consequence of the seemingly inexorable decline in -cell function.1 However, recent studies have demonstrated that in the early stages of development, it may be reversible. We evaluated the probability of type 2 diabetes remission by COX regressions of the score generated by categorizing patients into (ascending) tertiles of the microbiome-based response prediction score value (Figure 3A). A microbiota-based predictive model for type 2 diabetes remission induced by dietary intervention: From the CORDIOPREV study In conclusion, our results suggest that there is a gut microbiota profile associated with type 2 diabetes remission and provide compelling evidence of a potential role of the microbiome as a predictive factor for responders to diet-induced type 2 diabetes remission in newly diagnosed patients with CHD. [Extracted from the article]

Infections caused by acute respiratory viruses induce a systemic innate immune response, which can be measured by the increased levels of expression of inflammatory genes in immune cells. There is growing evidence that these acute viral infections, alongside transient transcriptomic responses, induce epigenetic remodeling as part of the immune response, such as DNA methylation and histone modifications, which might persist after the infection is cleared. In this article, we first review the primary mechanisms of epigenetic remodeling in the context of innate immunity and inflammation, which are crucial for the regulation of the immune response to viral infections. Next, we delve into the existing knowledge concerning the impact of respiratory virus infections on the epigenome, focusing on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Influenza A Virus (IAV), and Respiratory Syncytial Virus (RSV). Finally, we offer perspectives on the potential consequences of virus-induced epigenetic remodeling and open questions in the field that are currently under investigation. [ABSTRACT FROM AUTHOR]

A detailed understanding of the innate immune mechanisms involved in restricting SARS-CoV-2 infection and how the virus disrupts these processes could reveal new strategies to boost antiviral mechanisms and develop therapeutics for COVID-19. Here, we identify cellular nucleic acid-binding protein (CNBP) as a key host factor controlling SARS-CoV-2 infection. In response to RNA-sensing pathways, CNBP is phosphorylated and translocates from the cytosol to the nucleus where it binds to the interferon-ß enhancer to initiate transcription. Because SARS-CoV-2 evades immune detection by the host's RNA-sensing pathways, CNBP is largely retained in the cytosol where it restricts SARS-CoV-2 directly, leading to a battle between the host and SARS-CoV-2 that extends beyond antiviral immune signaling pathways. We further demonstrated that CNBP binds SARS-CoV-2 viral RNA directly and competes with the viral nucleocapsid protein to prevent viral RNA and nucleocapsid protein from forming liquid-liquid phase separation (LLPS) condensates critical for viral replication. Consequently, cells and animals lacking CNBP have higher viral loads, and CNBP-deficient mice succumb rapidly to infection. Altogether, these findings identify CNBP as a key antiviral factor for SARS-CoV-2, functioning both as a regulator of antiviral IFN gene expression and a cell-intrinsic restriction factor that disrupts LLPS to limit viral replication and spread. In addition, our studies also highlight viral condensates as important targets and strategies for the development of drugs to combat COVID-19. [ABSTRACT FROM AUTHOR]

DNA methylation comprises a cumulative record of lifetime exposures superimposed on genetically determined markers. Little is known about methylation dynamics in humans following an acute perturbation, such as infection. We characterized the temporal trajectory of blood epigenetic remodeling in 133 participants in a prospective study of young adults before, during, and after asymptomatic and mildly symptomatic SARS‐CoV‐2 infection. The differential methylation caused by asymptomatic or mildly symptomatic infections was indistinguishable. While differential gene expression largely returned to baseline levels after the virus became undetectable, some differentially methylated sites persisted for months of follow‐up, with a pattern resembling autoimmune or inflammatory disease. We leveraged these responses to construct methylation‐based machine learning models that distinguished samples from pre‐, during‐, and postinfection time periods, and quantitatively predicted the time since infection. The clinical trajectory in the young adults and in a diverse cohort with more severe outcomes was predicted by the similarity of methylation before or early after SARS‐CoV‐2 infection to the model‐defined postinfection state. Unlike the phenomenon of trained immunity, the postacute SARS‐CoV‐2 epigenetic landscape we identify is antiprotective. Synopsis: Characterization of the temporal dynamics of blood methylation changes in young adults following asymptomatic and mild SARS‐CoV‐2 infection brings insights into the long‐term memory of environmental exposure and potential disease associations.Both symptomatic and asymptomatic infections induce methylation changes that are not always associated with gene expression changes.Methylation changes persist for longer than gene expression changes.The complex dynamics of methylation alterations can be used to predict the timing of infection.Contrary to the trained immunity phenomenon, the presence of a post‐infection‐like methylation state at baseline is anti‐protective for subsequent SARS‐CoV‐2 infection. [ABSTRACT FROM AUTHOR]

Background The development of memory B cells after asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is not well understood. Methods We compared spike antibody titers, pseudovirus neutralizing antibody titers, and memory B-cell responses among SARS-CoV-2 PCR-positive Marine recruits who either reported asymptomatic or symptomatic infection. Results Thirty-six asymptomatic participants exhibited similar spike IgG titers, spike IgA titers, and pseudovirus neutralization titers compared to 30 symptomatic participants. Pseudovirus neutralization and spike IgG titers showed significant positive correlations with frequency of memory B cells. Conclusions Among young adults, asymptomatic SARS-CoV-2 infection induced antibody and memory B-cell responses comparable to mild symptomatic infection. [ABSTRACT FROM AUTHOR]

Background: Protein degradation is essential for cell homeostasis. Targeting of proteins for degradation is often achieved by specific protein sequences or posttranslational modifications such as ubiquitination. Methodology/Principal Findings: By using biochemical and genetic tools we have monitored the localization and degradation of endogenous and chimeric proteins in live primary cells by confocal microscopy and ultra-structural analysis. Here we identify an eight amino acid sequence from the C-terminus of the short-lived GTPase RhoB that directs the rapid degradation of both RhoB and chimeric proteins bearing this sequence through a lysosomal pathway. Elucidation of the RhoB degradation pathway unveils a mechanism dependent on protein isoprenylation and palmitoylation that involves sorting of the protein into multivesicular bodies, mediated by the ESCRT machinery. Moreover, RhoB sorting is regulated by late endosome specific lipid dynamics and is altered in human genetic lipid traffic disease. Conclusions/Significance: Our findings characterize a short-lived cytosolic protein that is degraded through a lysosomal pathway. In addition, we define a novel motif for protein sorting and rapid degradation, which allows controlling protein levels by means of clinically used drugs. [ABSTRACT FROM AUTHOR]

Monoclonal antibodies (mAbs) have become one of the main therapeutic weapons in modern oncology, mainly as targeted therapies, and immune checkpoint inhibitors. The generation of anti-drug antibodies (ADAs) after their administration can alter their pharmacokinetic, pharmacodynamic, efficacy and safety profile causing infusion-related reactions. Several risk factors have been associated with ADAs development, notably host genetics and immune status, comorbidity, concomitant medications, mAbs molecular structure, dose and route of administration. ADAs are not usually tested on daily clinical practice, being their analysis generally placed in early stages of drug development. ELISA-type assay the most common method. ADAs detection can involve important implications for treatment strategies of cancer patients, guiding therapeutic adjustment. In oncology, some studies about ADAs synthesis related to targeted therapies and immune checkpoint inhibitors have been recently published. Several strategies are proposed to reduce mAbs immunogenicity, such as different schedules, routes of administration or even the use of immunosuppressants. Another question that arises in relation to ADAs generation is the need to measure the concentration levels of active drug to guide the administration schedule. In this review, we will discuss all the aspects that are currently under discussion in relation with ADAs in oncology. [ABSTRACT FROM AUTHOR]

[Display omitted] • Type 2 diabetes (T2DM) increases the risk of recurrence in myocardial infarction patients. • A gut microbiota profile is associated to the further T2DM development. • Microbiome data improved the prediction of T2DM development when added to clinical parameters. • A risk score including the most predictive genera was associated with the probability of T2DM. • A high risk score was associated with a higher hepatic insulin resistance and β-cell dysfunction. A distinctive gut microbiome have been linked to type 2 diabetes mellitus (T2DM). We aimed to evaluate whether gut microbiota composition, in addition to clinical biomarkers, could improve the prediction of new incident cases of diabetes in patients with coronary heart disease. All the patients from the CORDIOPREV (Clinical Trials.gov.Identifier: NCT00924937) study without T2DM at baseline were included (n = 462). Overall, 107 patients developed it after a median of 60 months. The gut microbiota composition was determined by 16S rRNA gene sequencing and predictive models were created using hold-out method. A gut microbiota profile associated with T2DM development was determined through a microbiome-based predictive model. The addition of microbiome data to clinical parameters (variables included in FINDRISC risk score and the diabetes risk score of the American Diabetes Association, HDL, triglycerides and HbA1c) improved the prediction increasing the area under the curve from 0.632 to 0.946. Furthermore, a microbiome-based risk score including the ten most discriminant genera, was associated with the probability of develop T2DM. These results suggest that a microbiota profile is associated to the T2DM development. An integrate predictive model of microbiome and clinical data that can improve the prediction of T2DM is also proposed, if is validated in independent populations to prevent this disease. [ABSTRACT FROM AUTHOR]

In a study of US Marine recruits, seroprevalence of severe acute respiratory syndrome coronavirus 2 IgG was 9.0%. Hispanic and non-Hispanic Black participants and participants from states affected earlier in the pandemic had higher seropositivity rates. These results suggest the need for targeted public health strategies among young adults at increased risk for infection. [ABSTRACT FROM AUTHOR]

The influenza A virus (IAV) nonstructural protein 1 (NS1) contributes to disease pathogenesis through the inhibition of host innate immune responses. Dendritic cells (DCs) release interferons (IFNs) and proinflammatory cytokines and promote adaptive immunity upon viral infection. In order to characterize the strainspecific effects of IAV NS1 on human DC activation, we infected human DCs with a panel of recombinant viruses with the same backbone (A/Puerto Rico/08/1934) expressing different NS1 proteins from human and avian origin. We found that these viruses induced a clearly distinct phenotype in DCs. Specifically, viruses expressing NS1 from human IAV (either H1N1 or H3N2) induced higher levels of expression of type I (IFN-α and IFN-β) and type III (IFN-γ1 to IFNγ3) IFNs than viruses expressing avian IAV NS1 proteins (H5N1, H7N9, and H7N2), but the differences observed in the expression levels of proinflammatory cytokines like tumor necrosis factor alpha (TNF-α) or interleukin-6 (IL-6) were not significant. In addition, using imaging flow cytometry, we found that human and avian NS1 proteins segregate based on their subcellular trafficking dynamics, which might be associated with the different innate immune profile induced in DCs by viruses expressing those NS1 proteins. Innate immune responses induced by our panel of IAV recombinant viruses were also characterized in normal human bronchial epithelial cells, and the results were consistent with those in DCs. Altogether, our results reveal an increased ability of NS1 from avian viruses to antagonize innate immune responses in human primary cells compared to the ability of NS1 from human viruses, which could contribute to the severe disease induced by avian IAV in humans. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that postprandial hypertriglyceridemia (PPT) is associated with the incidence of CVD. Several non-modifiable factors (genetics, age, gender) and lifestyle factors (physical activity, smoking, regular alcohol) have shown their ability to modulate PPT. We evaluate the influence of regular alcohol intake, physical activity and smoking habit modulating PPT in the CORDIOPREV study (NCT00924937). 1002 patients were subject to an oral fat load test meal and serial blood samples were drawn at 0, 1, 2, 3 and 4 h during postprandial state. A PPT concentration above 2.5 mmol/L (220 mg/dL) at any time point has been established as a detrimental response. Alcohol consumption was defined as non-drinkers, moderate and severe intake; regular physical activity exceeding than or lower than 1000 MET/week; smoking habit was classified in current, never, recent ex-smokers and long-term ex-smokers. The prevalence of undesirable PPT response was 68% in current, 58% in recent ex-smokers, 49% in long-term ex-smokers and 48% in never smokers (p < 0.001). Current and recent ex-smokers displayed higher PPT response as well as a greater area under the curve (AUC) and higher incremental (iAUC) of triglycerides (TG) compared with long-term ex-smokers and never smokers (p < 0.05), without differences among these subgroups. No differences were observed in the magnitude of PPT according to regular physical activity or alcohol intake habits. Smoking is an independent risk factor modulating the magnitude of PPT. However, after tobacco cessation, ex-smokers show a progressive decrease on their PPT to reach levels similar to those of never smokers. Image 1 • We studied the influence of regular alcohol intake, physical activity and smoking habit modulating PPT in the CORDIOPREV study. • PPT and the prevalence of undesirable response was evaluate in each subgroups. We assessed the main determinants risk factors in the presence of undesirable response. • Smoking is an independent risk factor modulating the magnitude of PPT. • After tobacco cessation, in long-term ex-smokers, PPT progressively decreases to similar magnitude to never smokers. • No differences observed in the magnitude of PPT according to regular physical activity or alcohol intake habits. [ABSTRACT FROM AUTHOR]

Granuloma annulare (GA) is an entity of unknown origin classified among granulomatous skin diseases. GA diagnosis was made and treatment with cyclosporine 200 mg per day was started with only partial improvement after 10 months. TNF is known to participate in the formation and maintenance of granulomas, especially in its transmembrane form.1 Therefore, it seems logical to speculate that drugs that inhibit TNF- could prevent GA progression. [Extracted from the article]

Background Aging is an important determinant of the rate of atherosclerosis development, mainly through low-grade inflammation. Diet, and particularly its fat content, modulates the inflammatory response in fasting and postprandial states. Objective We aimed to study the effects of dietary fat on endotoxemia in healthy older adults. Materials and methods Twenty healthy older adults were randomized to three diets, lasting three-weeks each, using a crossover design: 1. A Mediterranean diet enriched in MUFA with virgin olive oil. 2. An SFA-rich diet. 3. A low-fat high-carbohydrate diet enriched in n-3 PUFA (α-linolenic acid of plant origin) (CHO-PUFA diet). At the end of each period, after a 12-h fast, the subjects received a meal with a composition similar to the dietary period just completed. We determined the fasting and the postprandial plasma levels of lipopolysaccharide (LPS) and LPS-binding protein (LBP). Results In the fasting state, we observed lower LPS plasma levels after the consumption of the CHO-PUFA diet ( P = 0.046) in comparison with the consumption of the Med and SFA-rich diets. In the postprandial measurements, we observed a statistically significant increase in plasma levels of LPS ( P = 0.044) and a decrease in LBP ( P = 0.003) after the intake of the CHO-PUFA meal, whereas no postprandial changes were observed after the ingestion of the Med and SFA-rich meals. Conclusion Our results, together with those obtained in a previous study, support the concept that the consumption of the Med Diet, in contrast to a low-fat PUFA diet, constitutes a more suitable dietary lifestyle for preventing the development of atherosclerosis in a population at risk, such as older adults. [ABSTRACT FROM AUTHOR]

Two types of bentonites were modified using a cleaner method to prepare aluminum-pillared clays. This methodology involved a purifying stage, an intercalation process, and a microwave irradiation step at low energy power. Structural changes induced by pillaring process were demonstrated by thermal behavior, as well as morphological characterization. The effect of pillaring process on thermal stability of clays was studied, and the mass lost associated with the dehydroxylation of the octahedral clay sheets was not detected for modified bentonites. In addition, an analysis of their chemical composition and crystalline structure was also performed. Concerning industrial applications of these bentonites, two potential uses were proposed: (1) as reinforcement of different polymers matrices such as thermoplastic starch (TPS), high-density polyethylene (HDPE), and poly (styrene- b-butadiene- b-styrene), SBS; and (2) as removal agent for cadmium (Cd) species present in wastewaters. Bentonite particles reinforced thermoplastic starch matrix and increased ultraviolet barrier capacity of HDPE composites. Besides, bentonites improved the mechanical performance and modified barrier properties of SBS. Regarding effluents purification, an adequate Cd adsorption from aqueous solutions was observed (77%), proving their feasibility to be used as non-conventional removal agents. [ABSTRACT FROM AUTHOR]

The durability of computer–assisted cognitive remediation (CACR) therapy over time and the cost-effectiveness of treatment remains unclear. The aim of the current study is to investigate the effectiveness of CACR and to examine the use and cost of acute psychiatric admissions before and after of CACR. Sixty-seven participants were initially recruited. For the follow-up study a total of 33 participants were enrolled, 20 to the CACR condition group and 13 to the active control condition group. All participants were assessed at baseline, post-therapy and 12 months post-therapy on neuropsychology, QoL and self-esteem measurements. The use and cost of acute psychiatric admissions were collected retrospectively at four assessment points: baseline, 12 months post-therapy, 24 months post-therapy, and 36 months post-therapy. The results indicated that treatment effectiveness persisted in the CACR group one year post-therapy on neuropsychological and well-being outcomes. The CACR group showed a clear decrease in the use of acute psychiatric admissions at 12, 24 and 36 months post-therapy, which lowered the global costs the acute psychiatric admissions at 12, 24 and 36 months post-therapy. The CACR is durable over at least a 12-month period, and CACR may be helping to reduce health care costs for schizophrenia patients. [ABSTRACT FROM AUTHOR]

Current vaccines against influenza virus infection rely on the induction of neutralizing antibodies targeting the globular head of the viral hemagglutinin (HA). Protection against seasonal antigenic drift or sporadic pandemic outbreaks requires further vaccine development to induce cross-protective humoral responses, potentially to the more conserved HA stalk region. Here, we present a novel viral vaccine adjuvant comprised of two synthetic ligands for Toll-like receptor 4 (TLR4) and TLR7. 1Z105 is a substituted pyrimido[5,4-b]indole specific for the TLR4-MD2 complex, and 1V270 is a phospholipid-conjugated TLR7 agonist. Separately, 1Z105 induces rapid Th2-associated IgG1 responses, and 1V270 potently generates Th1 cellular immunity. 1Z105 and 1V270 in combination with recombinant HA from the A/Puerto Rico/8/1934 strain (rPR/8 HA) effectively induces rapid and sustained humoral immunity that is protective against lethal challenge with a homologous virus. More importantly, immunization with the combined adjuvant and rPR/8 HA, a commercially available split vaccine, or chimeric rHA antigens significantly improves protection against both heterologous and heterosubtypic challenge viruses. Heterosubtypic protection is associated with broadly reactive antibodies to HA stalk epitopes. Histological examination and cytokine profiling reveal that intramuscular (i.m.) administration of 1Z105 and 1V270 is less reactogenic than a squalene-based adjuvant, AddaVax. In summary, the combination of 1Z105 and 1V270 with a recombinant HA induces rapid, long-lasting, and balanced Th1- and Th2-type immunity; demonstrates efficacy in a variety of murine influenza virus vaccine models assaying homologous, heterologous, and heterosubtypic challenge viruses; and has an excellent safety profile. [ABSTRACT FROM AUTHOR]

We assessed the relative susceptibilities to disease of the DBA.2 and C57BL/6 mouse models upon infection with a range of influenza A and B viruses. DBA.2 mice were more susceptible to disease upon inoculation with human H1N1 influenza A virus strains, several swine influenza viruses, and influenza B viruses but were not overtly susceptible to infection with human seasonal H3N2 strains. Hemagglutination inhibition and immunoglobulin isotype profiling indicated that DBA.2 and C57BL/6 mice generate comparable humoral responses upon equivalent 50% mouse lethal dose (MLD50) challenges with influenza virus. Our data demonstrate the utility of DBA.2 mice for the elucidation of influenza virus pathogenicity determinants and the testing of influenza vaccines. [ABSTRACT FROM AUTHOR]

Objective Systemic lupus erythematosus (SLE) patients exhibit T cell dysfunction, which can be regulated through mitochondrial transmembrane potential (Δψm) and mammalian target of rapamycin (mTOR) by glutathione (GSH). This randomized, double-blind, placebo-controlled study was undertaken to examine the safety, tolerance, and efficacy of the GSH precursor N-acetylcysteine (NAC). Methods A total of 36 SLE patients received either daily placebo or 1.2 gm, 2.4 gm, or 4.8 gm of NAC. Disease activity was evaluated monthly by the British Isles Lupus Assessment Group (BILAG) index, the SLE Disease Activity Index (SLEDAI), and the Fatigue Assessment Scale (FAS) before, during, and after a 3-month treatment period. Mitochondrial transmembrane potential and mTOR were assessed by flow cytometry. Forty-two healthy subjects matched to patients for age, sex, and ethnicity were studied as controls. Results NAC up to 2.4 gm/day was tolerated by all patients, while 33% of those receiving 4.8 gm/day had reversible nausea. Placebo or NAC 1.2 gm/day did not influence disease activity. Considered together, 2.4 gm and 4.8 gm NAC reduced the SLEDAI score after 1 month ( P = 0.0007), 2 months ( P = 0.0009), 3 months ( P = 0.0030), and 4 months ( P = 0.0046); the BILAG score after 1 month ( P = 0.029) and 3 months ( P = 0.009); and the FAS score after 2 months ( P = 0.0006) and 3 months ( P = 0.005). NAC increased Δψm ( P = 0.0001) in all T cells, profoundly reduced mTOR activity ( P = 0.0009), enhanced apoptosis ( P = 0.0004), reversed expansion of CD4−CD8− T cells (mean ± SEM 1.35 ± 0.12-fold change; P = 0.008), stimulated FoxP3 expression in CD4+CD25+ T cells ( P = 0.045), and reduced anti-DNA production ( P = 0.049). Conclusion This pilot study suggests that NAC safely improves lupus disease activity by blocking mTOR in T lymphocytes. [ABSTRACT FROM AUTHOR]

Myeloid blood cells are largely resistant to infection with human immunodeficiency virus type 1 (HIV-1). Recently, it was reported that Vpx from HIV-2/SIVsm facilitates infection of these cells by counteracting the host restriction factor SAMHD1. Here, we independently confirmed that Vpx interacts with SAMHD1 and targets it for ubiquitin-mediated degradation. We found that Vpx-mediated SAMHD1 degradation rendered primary monocytes highly susceptible to HIV-1 infection; Vpx with a T17A mutation, defective for SAMHD1 binding and degradation, did not show this activity. Several single nucleotide polymorphisms in the SAMHD1 gene have been associated with Aicardi-Goutières syndrome (AGS), a very rare and severe autoimmune disease. Primary peripheral blood mononuclear cells (PBMC) from AGS patients homozygous for a nonsense mutation in SAMHD1 (R164X) lacked endogenous SAMHD1 expression and support HIV-1 replication in the absence of exogenous activation. Our results indicate that within PBMC from AGS patients, CD14+ cells were the subpopulation susceptible to HIV-1 infection, whereas cells from healthy donors did not support infection. The monocytic lineage of the infected SAMHD1 -/- cells, in conjunction with mostly undetectable levels of cytokines, chemokines and type I interferon measured prior to infection, indicate that aberrant cellular activation is not the cause for the observed phenotype. Taken together, we propose that SAMHD1 protects primary CD14+ monocytes from HIV-1 infection confirming SAMHD1 as a potent lentiviral restriction factor. [ABSTRACT FROM AUTHOR]

Rapid control of protein degradation is usually achieved through the ubiquitin-proteasome pathway. We recently found that the short-lived GTPase RhoB is degraded in lysosomes. Moreover, the fusion of the RhoB C-terminal sequence CINCCKVL, containing the isoprenylation and palmitoylation sites, to other proteins directs their sorting into multivesicular bodies (MVBs) and rapid lysosomal degradation. Here, we show that this process is highly specific for RhoB. Alteration of late endosome lipid dynamics produced the accumulation of RhoB, but not of other endosomal GTPases, including Rab5, Rab7, Rab9 or Rab11, into enlarged MVB. Other isoprenylated and bipalmitoylated GTPases, such as H-Ras, Rap2A, Rap2B and TC10, were not accumulated into MVB and were stable. Remarkably, although TC10, which is highly homologous to RhoB, was stable, a sequence derived from its C-terminus (CINCCLIT) elicited MVB sorting and degradation of a green fluorescent protein (GFP)-chimeric protein. This led us to identify a cluster of basic amino acids (KKH) in the TC10 hypervariable region, constituting a secondary signal potentially involved in electrostatic interactions with membrane lipids. Mutation of this cluster allowed TC10 MVB sorting and degradation, whereas inserting it into RhoB hypervariable region rescued this protein from its lysosomal degradation pathway. These findings define a highly specific structural module for entering the MVB pathway and rapid lysosomal degradation. [ABSTRACT FROM AUTHOR]

Abstract: Metacyclic promastigotes are transmitted during bloodmeals after development inside the gut of the sandfly vector. The isolation from axenic cultures of procyclic and metacyclic promastigotes by peanut lectin agglutination followed by differential centrifugation is controversial in Leishmania infantum. The purpose of this study has been to isolate both fractions simultaneously from the same population in stationary phase of axenic culture and compare their expression profiles by whole-genome shotgun DNA microarrays. The 317 genes found with meaningful values of stage-specific regulation demonstrate that negative selection of metacyclic promastigotes by PNA agglutination is feasible in L. infantum and both fractions can be isolated. This subpopulation up-regulates a cysteine peptidase A and several genes involved in lipophosphoglycan, proteophosphoglycan and glycoprotein biosynthesis, all related with infectivity. In fact, we have confirmed the increased infection rate of PNA− promastigotes by U937 human cell line infection experiments. These data support that metacyclic promastigotes are related with infectivity and the lack of agglutination with PNA is a phenotypic marker for this subpopulation. [Copyright &y& Elsevier]

Background: We try to explore whether long‐term consumption of two healthy dietary patterns (low‐fat [LF] diet or Mediterranean diet [MedDiet]) interacts with the apolipoprotein E (APOE) single‐nucleotide polymorphisms (SNPs: rs439401, rs440446 and rs7412) modulating postprandial hypertriglyceridemia (ppHTG) in coronary heart disease (CHD) patients. Methods and results: We selected patients from the CORDIOPREV study with genotyping and who underwent an oral fat load test (FLT) at baseline and after 3 years follow‐up (n = 506). After 3 years of follow‐up, we found a gene‐diet interaction between the APOE rs439401 SNP and MedDiet. Specifically, T‐allele carriers in the MedDiet group showed a more significant decrease in postprandial triglycerides (TG: P = 0.03) and large triacylglycerol‐rich lipoproteins (TRLs) TG (large TRLs TG; P = 0.01) compared with CC subjects. Consistently, the area under the curve of TG (AUC‐TG; P‐interaction = 0.03) and AUC‐large TRLs TG (P‐interaction = 0.02) were significantly lower in T‐allele carriers compared with CC subjects. Conclusions: The long‐term consumption of a MedDiet modulates ppHTG through APOE genetic variants in CHD patients. This gene‐diet interaction may contribute to a more precise dietary advice in CHD patients. [ABSTRACT FROM AUTHOR]

Comparative studies between systemic inducing bone neoformation medications showed favorable results for homeopathic medicines. (Almeida et al., 2000; Werkman et al., 2006, FARINA, 2010). The Calcareas, are described in the literature for their action in the mineralization processes and increase of the levels of Ca ++ tissue ((LATHOUD, 1998; ARGENTA, 2005; VIJNOVSKY, 1999; VOISIN, 1971). NARDY-MELO, 2013, found that Calcarea carbonica 6CH, Calcarea phosphorica 6CH and Calcarea fluorica 6CH, when given as a compound, are statistically significant for increasing tissue Ca ++ levels. Objective This randomized controlled multicentric study, approved by the UniFOA's Human beings Research Ethics Committee CAAE:39002914.0.0000.5237, has aspiration to quantify the level of Ca + + salivary in front of the administration of homeopathic medicines Calcarea Carbonica, Calcarea Phosphorica, Calcarea Fluorica, as supporting in the prevention of dental caries, Demineralization and Dental l, from the stimulus to increase of Ca + + salivary. Method (n=48) Children in the age range of 04 to 16 years, with high rate of dental caries, submitted to dental treatment, without the preventive application of fluoride topical and specific food guidelines were divided randomly, in 2 groups according to the medication experienced: GI - Calcarea Carbonica 6CH; Calcarea phosphorica 6 CH; Calcarea fluorica 6CH, in the dose of 3 daily drops for 15 days a month for three months. GII - Upward scales of Calcarea Carbonica 6CH; Calcarea phosphorica 6CH; Calcarea fluorica 6CH, in the dose of 3 daily drops, in the first month. Calcarea Carbonica 9CH; Calcarea phosphorica 9CH; Calcarea fluorica 9CH, in the dose of 3 daily drops, in the second month. Calcarea Carbonica 12CH; Calcarea phosphorica 12CH; Calcarea fluorica 12CH, in the dose of 3 daily drops, in the third month. The salivary Ca + + levels was measured before the administration of the first dose and monthly, for 03 consecutive months. The calcium (mg/dl) salivary indices were determined by optical emission spectrometry (ICP-OES). Results The results were submitted to statistical analysis with Student TTest (significance with P < 0.05) and analysis of variance Shapiro-Wilk normality test. Conclusion: The averages of calcium increase under the action of homeopathic medicinal products: Calcarea Carbonica, Calcarea Phosphorica and Calcarea Fluorica, in this study, do not differ in G I and G II and in both groups the increase in salivary calcium level was statistically significant to 0.5%. [ABSTRACT FROM AUTHOR]

Investigation of the human antibody response to the 1957 pandemic H2N2 influenza A virus has been largely limited to serologic studies. We generated five influenza virus hemagglutinin (HA)-reactive human monoclonal antibodies (MAbs) by hybridoma technology from the peripheral blood of healthy donors who were born between 1950 and 1968. Two MAbs reacted with the pandemic H2N2 virus, two recognized the pandemic H3N2 virus, and remarkably, one reacted with both the pandemic H2N2 and H3N2 viruses. Each of these five naturally occurring MAbs displayed hemagglutination inhibition activity, suggesting specificity for the globular head domain of influenza virus HA. When incubated with virus, MAbs 8F8, 8M2, and 2G1 each elicited H2N2 escape mutations immediately adjacent to the receptor-binding domain on the HA globular head in embryonated chicken eggs. All H2N2-specific MAbs were able to inhibit a 2006 swine H2N3 influenza virus. MAbs 8M2 and 2G1 shared the VH1-69 germ line gene, but these antibodies were otherwise not genetically related. Each antibody was able to protect mice in a lethal H2N2 virus challenge. Thus, even 43 years after circulation of H2N2 viruses, these subjects possessed peripheral blood B cells encoding potent inhibiting antibodies specific for a conserved region on the globular head of the pandemic H2 HA. [ABSTRACT FROM AUTHOR]