Cage doping of Ti, Zr, and Hf-based 13-atom nanoclusters: two sides of the same coin.

Transition metal nanoclusters can exhibit unique and tunable properties which result not only from their chemical composition but also from their atomic packing and quantized electronic structures. Here, we introduce a promising family of bimetallic TM@Ti12, TM@Zr12, and TM@Hf12 nanoclusters with icosahedral geometry, where TM represents an atom from groups 3 to 12. Density functional theory calculations show that their stability can be explained with familiar concepts of metal cluster electronic and atomic shell structures. The magnetic properties of these quasispherical clusters are entirely consistent with superatom electronic shells and Hund's rules, and can be tuned by the choice of the TM dopant. The computed cluster atomization energies were analyzed in terms of the elements' cohesive energy, Ecoh, and contributions from geometric distortion, Edis, surface energy, Es, and ionic bonding, Ei. Some clusters have anomalous stability relative to Ecoh + Edis + Es + Ei. We attribute this to superatomic character associated with a favorable atomic and electronic shell structure. This raises the possibility of designing stable superatoms and materials with tailored electronic and magnetic properties.

Boosting life sciences research in Brazil: building a case for a local Drosophila stock center.

Drosophila melanogaster is undoubtedly one of the most useful model organisms in biology. Initially used in solidifying the principles of heredity, and establishing the basic concepts of population genetics and of the synthetic theory of evolution, it can currently offer scientists much more: the possibility of investigating a plethora of cellular and biological mechanisms, from development and function of the immune system to animal neurogenesis, tumorigenesis and beyond. Extensive resources are available for the community of Drosophila researchers worldwide, including an ever-growing number of mutant, transgenic and genomically-edited lines currently carried by stock centers in North America, Europe and Asia. Here, we provide evidence for the importance of stock centers in sustaining the substantial increase in the output of Drosophila research worldwide in recent decades. We also discuss the challenges that Brazilian Drosophila scientists face to keep their research projects internationally competitive, and argue that difficulties in importing fly lines from international stock centers have significantly stalled the progression of all Drosophila research areas in the country. Establishing a local stock center might be the first step towards building a strong local Drosophila community that will likely contribute to all areas of life sciences research.

Industrial egg residue as a calcium source in broiler feed: digestibility and growth performance.

Industrial egg residue (IER) possesses substantial concentrations of calcium and crude protein. The objective of this study was to measure the digestibility and performance of broilers when IER was added to the feed. Four treatments were tested, which caused increasing replacement of calcitic limestone by IER (0, 35, 70 and 100%) during a 42-day production cycle. First, total bird excreta were collected from broilers with and without IER, and we determined dry matter digestibility, apparent metabolizable energy (AME), calcium, and nitrogen retention. The IER presented 7.5% of crude protein, 31% of calcium, 209 kcal/kg of AME and the digestibility coefficients for dry matter, crude protein, and calcium were calculated at 83.95%, 86.20%, and 67%, respectively. After the digestibility test, the effects of IER on performance, carcass and meat yield were evaluated. No significant differences between the treatments were found in terms of performance (weight gain, feed conversion, consumption, and mortality), and no differences were found in terms of carcass or meat yield. A linear decrease in the percentage of abdominal fat was observed with increasing inclusion of IER in feed. These findings suggest that IER can totally replace limestone (calcium carbonate) in broiler diets.

Regulated hypothermia in response to endotoxin in birds.

KEY POINTS: The costs associated with immune and thermal responses may exceed the benefits to the host during severe inflammation. In this case, regulated hypothermia instead of fever can occur in rodents as a beneficial strategy to conserve energy for vital functions with consequent tissue protection and hypoxia prevention. We tested the hypothesis that this phenomenon is not exclusive to mammals, but extends to the other endothermic group, birds. A decrease in metabolic rate without any failure in mitochondrial respiration, nor oxygen delivery, is the main evidence supporting the regulated nature of endotoxin-induced hypothermia in chicks. Thermolytic mechanisms such as tachypnea and cutaneous vasodilatation can also be recruited to facilitate body temperature decrease under lipopolysaccharide treatment, especially in the cold. Our findings bring a new perspective for evolutionary medicine studies on energy trade-off in host defence because regulated hypothermia may be a phenomenon spread among vertebrates facing a severe immune challenge. ABSTRACT: A switch from fever to regulated hypothermia can occur in mammals under circumstances of reduced physiological fitness (e.g. sepsis) to direct energy to defend vital systems. Birds in which the cost to resist a pathogen is additive to the highest metabolic rate and body temperature (Tb ) among vertebrates may also benefit from regulated hypothermia during systemic inflammation. Here, we show that the decrease in Tb observed during an immune challenge in birds is a regulated hypothermia, and not a result of metabolic failure. We investigated O2 consumption (thermogenesis index), ventilation (respiratory heat loss), skin temperature (sensible heat loss) and muscle mitochondrial respiration (thermogenic tissue) during Tb fall in chicken chicks challenged with endotoxin [lipopolysaccharide (LPS)]. Chicks injected with LPS were also tested regarding the capacity to raise O2 consumption to meet an increased demand driven by 2,4-dinitrophenol. LPS decreased Tb and the metabolic rate of chicks without affecting muscle uncoupled, coupled and non-coupled mitochondrial respiration. LPS-challenged chicks were indeed capable of increasing metabolic rate in response to 2,4-dinitrophenol, indicating no O2 delivery limitation. Additionally, chicks did not attempt to prevent Tb from falling during hypothermia but, instead, activated cutaneous and respiratory thermolytic mechanisms, providing an additional cooling force. These data provide the first evidence of the regulated nature of the hypothermic response to endotoxin in birds. Therefore, it changes the current understanding of bird's thermoregulation during severe inflammation, indicating that regulated hypothermia is either a convergent trait for endotherms or a conserved response among vertebrates, which adds a new perspective for evolutionary medicine research.

Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice.

Zika virus (ZIKV) has the ability to cross placental and brain barriers, causing congenital malformations in neonates and neurological disorders in adults. However, the pathogenic mechanisms of ZIKV-induced neurological complications in adults and congenital malformations are still not fully understood. Gas6 is a soluble TAM receptor ligand able to promote flavivirus internalization and downregulation of immune responses. Here we demonstrate that there is a correlation between ZIKV neurological complications with higher Gas6 levels and the downregulation of genes associated with anti-viral response, as type I IFN due to Socs1 upregulation. Also, Gas6 gamma-carboxylation is essential for ZIKV invasion and replication in monocytes, the main source of this protein, which was inhibited by warfarin. Conversely, Gas6 facilitates ZIKV replication in adult immunocompetent mice and enabled susceptibility to transplacental infection. Our data indicate that ZIKV promotes the upregulation of its ligand Gas6, which contributes to viral infectivity and drives the development of severe adverse outcomes during ZIKV infection.

BKCa Channel Activation Attenuates the Pathophysiological Progression of Monocrotaline-Induced Pulmonary Arterial Hypertension in Wistar Rats.

PURPOSE: In the present study, the therapeutic efficacy of a selective BKCa channel opener (compound X) in the treatment of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) was investigated. METHODS: PAH was induced in male Wistar rats by a single injection of MCT. After two weeks, the MCT-treated group was divided into two groups that were either treated with compound X or vehicle. Compound X was administered daily at 28 mg/kg. Electrocardiographic, echocardiographic, and haemodynamic analyses were performed; ex vivo evaluations of pulmonary artery reactivity, right ventricle (RV) and lung histology as well as expression levels of α and ß myosin heavy chain, brain natriuretic peptide, and cytokines (TNFα and IL10) in heart tissue were performed. RESULTS: Pulmonary artery rings of the PAH group showed a lower vasodilatation response to acetylcholine, suggesting endothelial dysfunction. Compound X promoted strong vasodilation in pulmonary artery rings of both control and MCT-induced PAH rats. The untreated hypertensive rats presented remodelling of pulmonary arterioles associated with increased resistance to pulmonary flow; increased systolic pressure, hypertrophy and fibrosis of the RV; prolongation of the QT and Tpeak-Tend intervals (evaluated during electrocardiogram); increased lung and liver weights; and autonomic imbalance with predominance of sympathetic activity. On the other hand, treatment with compound X reduced pulmonary vascular remodelling, pulmonary flow resistance and RV hypertrophy and afterload. CONCLUSION: The use of a selective and potent opener to activate the BKCa channels promoted improvement of haemodynamic parameters and consequent prevention of RV maladaptive remodelling in rats with MCT-induced PAH.

Escherichia coli Capacity to Repopulate Microcosms Under Osmotic/U.V. Synergic Stress in Tropical Waters.

In both Brazilian and European regulations, the impact assessment of sewage discharges into coastal waters is based on microbiological analyses of fecal indicators such as Escherichia coli, frequently used in prevision hydrodynamic models. However, the decay rates of E. coli vary depending on environmental conditions, and analysis may lead to inaccurate conclusions. This study aimed to analyze the decay of culturable and viable (but not culturable) E. coli in outdoor conditions, by creating microcosms inoculated with pre-treated sewage. The microcosms were filled with 9.88 L of filtered water (0.22 µm membrane), 3.5% salt, 0.1-0.2% BHI, and 1% bacterial suspension obtained by reverse filtration. PMA-qPCR of E. coli uidA gene and Colilert measurements were applied to evaluate population counts after 2 h, 4 h, and 26 h. After nine hours of exposure to solar radiation, the viable cells decreased to 2.76% (interpolated value) of the initial population, and the cultivable fraction of the viable population accounted for 0.50%. In the dark period, the bacteria grew again, and viable cells reached 8.54%, while cultivable cells grew to 48.14% of initial population. This behavior is possibly due to the use of nutrients recycled from dead cells. Likewise, populations of E. coli in sewage outfalls remain viable in the sediments, where resuspension can renew blooming.

Comparing Data-Independent Acquisition and Parallel Reaction Monitoring in Their Abilities To Differentiate High-Density Lipoprotein Subclasses.

High-density lipoprotein (HDL) is a diverse group of particles with multiple cardioprotective functions. HDL proteome follows HDL particle complexity. Many proteins were described in HDL, but consistent quantification of HDL protein cargo is still a challenge. To address this issue, the aim of this work was to compare data-independent acquisition (DIA) and parallel reaction monitoring (PRM) methodologies in their abilities to differentiate HDL subclasses through their proteomes. To this end, we first evaluated the analytical performances of DIA and PRM using labeled peptides in pooled digested HDL as a biological matrix. Next, we compared the quantification capabilities of the two methodologies for 24 proteins found in HDL2 and HDL3 from 19 apparently healthy subjects. DIA and PRM exhibited comparable linearity, accuracy, and precision. Moreover, both methodologies worked equally well, differentiating HDL subclasses' proteomes with high precision. Our findings may help to understand HDL functional diversity.

Experimental infection with Escherichia coli in broilers: Impacts of the disease and benefits of preventive consumption of a stimulator of homeopathic immunity.

Colibacillosis is a disease caused by Escherichia coli that manifests itself when there are homeostatic imbalances or in the context of increased exposure, in which case the organism displays opportunistic behavior. To control this problem in poultry, antibiotics are used in the feed, because E. coli is component of the intestinal microbiota of birds. However, because of the changing dietary habits of the human population that seeks out healthier foods without antimicrobial residues, there have been many studies of alternatives to replace conventional antimicrobials as performance enhancers. Thus, the objective of the present study was to determine whether daily consumption of a homeopathic product (immune stimulator) by broilers stimulates immune responses and thereby minimizes the negative effects of experimental E. coli infection. We used 320 1-day-old Cobb 500 chicks, distributed in two groups with eight repetitions each, and 20 birds per repetition: control (CG) and homeopathy (HG). HG birds consumed doses of 0.02 mL/bird/day (1-7 d) via water, 0.01 ml/bird (8-21 d), 0.02 ml/bird (22-28 d), 0.01 mL/bird (29-35 d), and 0.02 mL/bird (35-45 d), as recommended by the manufacturer. At day 22 of the birds' life, the two groups were divided into four subgroups, with four repetitions per subgroup. On day 22, birds in CG1 and HG1 groups were infected intraperitoneally with 0.5 mL of inoculum containing 1.0 × 108 CFU of E. coli/mL. During the experimental period, data were collected for analysis of performance. On days 21 and 45 of age, we collected blood and feces. During the first 21 days of the experiment, we found that birds that consumed the immunostimulator had lower neutrophil counts and higher levels of globulins, however without significant difference between groups in terms of performance. Uninfected birds that consumed the homeopathic product in the water had less feed conversion (HG2) between days 1-35 and 1 to 45 compared to the other treatments. Mortality was higher in groups experimentally infected with E. coli (HG1 and CG1) from 22 to 35 days of life. There were greater numbers of lymphocytes in the HG2 group on day 45 than in CG1 and CG2; while numbers of neutrophils were lower at 42 days in birds of groups HG1 and HG2 than in CG1. Lower total bacterial counts, total coliforms and E. coli were observed in the feces of birds in the HG2 group compared to the other groups. Taken together, these findings suggest that inclusion of homeopathic product in the water of broilers had positive effects on the modulation of the immune response and on feed conversion in birds not challenged with E. coli. But the preventive protocol used in this study was not able to minimize the negative effects caused by the experimental E. coli intraperitoneal infection in broilers, featuring a substantial infectious challenge.

Impact of Escherichia coli infection in broiler breeder chicks: The effect of oxidative stress on weight gain.

The aim of this study was to determine whether oxidative stress occurs in Escherichia coli-infected broiler breeder chicks, as well as the impact of this infection on bird growth. Twenty birds, 25-day-old female birds were divided into two groups (n = 10 per group): an intraperitoneally-infected group (1 mL containing 1.5 × 108 CFU of E. coli) and a control group that received 1 mL of culture medium (uninfected birds). Birds were weighed individually at the beginning and at the end of the experiment, and samples were collected on days 0, 5 and 10 post-infection (PI). No clinical signs were observed throughout the experimental period; nevertheless, on day 10 PI, there was lower growth and weight gain in infected birds than in the control group. The infected birds showed pericarditis and liver congestion, as well as moderate periportal inflammatory infiltrates with predominance of neutrophils. Significantly higher numbers of total leukocytes, lymphocytes, heterophils and monocytes were observed in the infected group on days 5 and 10 PI, as well as significantly higher total protein and globulin levels; albumin values significantly decreased over the same period. Levels of serum oxidative biomarkers (lipid peroxidation (TBARS) and free radicals (ROS)) were significantly higher at 10 PI, as was glutathione S-transferase (GST) activity during the same period. Hepatic ROS and protein thiol levels were significantly higher in E. coli-infected birds, as well as activities of the antioxidant enzymes catalase, superoxide dismutase. In the spleen, only GST activity was significantly higher for the infected group, unlike the brain, where SOD activity, ROS and non-protein thiol levels were significantly higher in infected birds than in the control group. These data suggested that colibacillosis causes oxidative stress in broiler breeder chicks, negatively affecting their weight gain.

Impacts of Escherichia coli infection in young breeder chicks on the animal behavior and cerebral activity of purinergic and cholinergic enzymes involved in the regulation of molecules with neurotransmitter and neuromodulator function.

The objective of this study was to evaluate if infection by Escherichia coli in juvenile breeder chicks alters the activity of enzymes involved in neurotransmission and cerebral immunomodulation, including acetylcholinesterase (AChE), nucleoside triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase (5'NT) and adenosine deaminase (ADA), as well as their effects on the pathogenesis of the disease. We divided 20 growing breeder chicks into two groups (n = 10 per group). One group was experimentally infected with 1 mL of culture medium containing 1 × 108 CFU of E. coli intraperitoneally. The other was the negative control. On the tenth day after infection, the animals were euthanized and brain samples were collected. Macroscopically, pericarditis and hepatic congestion were observed in the birds, but without histopathological lesions in the encephalon although the bacterium was present in the cerebral cortex of all animals in the infected group (i.e., they were PCR-positive). The activity of AChE, NTPDase, 5'-NT and ADA were evaluated in the cerebral homogenates of the birds after 10 days of infection. AChE activity in the cerebral cortex was lower in the infected group than in the control; there was an increase in the activity of NTPDase, 5'-nucleotidase and ADA, possibly indicating greater hydrolysis of ATP (P < 0.001), ADP (P < 0.01) and AMP (P < 0.01), followed by increased adenosine deamination (P < 0.001). Despite these changes, no apparently diseased animals were observed throughout the experimental period. Therefore, such changes in enzymatic activity may affect the functioning of the central nervous system because these enzymes are responsible for extracellular regulation of molecules that act on neurotransmission and immunomodulation such as acetylcholine, ATP and adenosine.

Structural rearrangements in the mitochondrial genome of Drosophila melanogaster induced by elevated levels of the replicative DNA helicase.

Pathological conditions impairing functions of mitochondria often lead to compensatory upregulation of the mitochondrial DNA (mtDNA) replisome machinery, and the replicative DNA helicase appears to be a key factor in regulating mtDNA copy number. Moreover, mtDNA helicase mutations have been associated with structural rearrangements of the mitochondrial genome. To evaluate the effects of elevated levels of the mtDNA helicase on the integrity and replication of the mitochondrial genome, we overexpressed the helicase in Drosophila melanogaster Schneider cells and analyzed the mtDNA by two-dimensional neutral agarose gel electrophoresis and electron microscopy. We found that elevation of mtDNA helicase levels increases the quantity of replication intermediates and alleviates pausing at the replication slow zones. Though we did not observe a concomitant alteration in mtDNA copy number, we observed deletions specific to the segment of repeated elements in the immediate vicinity of the origin of replication, and an accumulation of species characteristic of replication fork stalling. We also found elevated levels of RNA that are retained in the replication intermediates. Together, our results suggest that upregulation of mtDNA helicase promotes the process of mtDNA replication but also results in genome destabilization.

Roles of the mitochondrial replisome in mitochondrial DNA deletion formation.

Mitochondrial DNA (mtDNA) deletions are a common cause of human mitochondrial diseases. Mutations in the genes encoding components of the mitochondrial replisome, such as DNA polymerase gamma (Pol γ) and the mtDNA helicase Twinkle, have been associated with the accumulation of such deletions and the development of pathological conditions in humans. Recently, we demonstrated that changes in the level of wild-type Twinkle promote mtDNA deletions, which implies that not only mutations in, but also dysregulation of the stoichiometry between the replisome components is potentially pathogenic. The mechanism(s) by which alterations to the replisome function generate mtDNA deletions is(are) currently under debate. It is commonly accepted that stalling of the replication fork at sites likely to form secondary structures precedes the deletion formation. The secondary structural elements can be bypassed by the replication-slippage mechanism. Otherwise, stalling of the replication fork can generate single- and double-strand breaks, which can be repaired through recombination leading to the elimination of segments between the recombination sites. Here, we discuss aberrances of the replisome in the context of the two debated outcomes, and suggest new mechanistic explanations based on replication restart and template switching that could account for all the deletion types reported for patients.

Structure, function and evolution of the animal mitochondrial replicative DNA helicase.

The mitochondrial replicative DNA helicase is essential for animal mitochondrial DNA (mtDNA) maintenance. Deleterious mutations in the gene that encodes it cause mitochondrial dysfunction manifested in developmental delays, defects and arrest, limited life span, and a number of human pathogenic phenotypes that are recapitulated in animals across taxa. In fact, the replicative mtDNA helicase was discovered with the identification of human disease mutations in its nuclear gene, and based upon its deduced amino acid sequence homology with bacteriophage T7 gene 4 protein (T7 gp4), a bi-functional primase-helicase. Since that time, numerous investigations of its structure, mechanism, and physiological relevance have been reported, and human disease alleles have been modeled in the human, mouse, and Drosophila systems. Here, we review this literature and draw evolutionary comparisons that serve to shed light on its divergent features.

Xenotopic expression of alternative electron transport enzymes in animal mitochondria and their impact in health and disease.

The mitochondrial respiratory chain in vertebrates and arthropods is different from that of most other eukaryotes because they lack alternative enzymes that provide electron transfer pathways additional to the oxidative phosphorylation (OXPHOS) system. However, the use of diverse experimental models, such as human cells in culture, Drosophila melanogaster and the mouse, has demonstrated that the transgenic expression of these alternative enzymes can impact positively many phenotypes associated with human mitochondrial and other cellular dysfunction, including those typically presented in complex IV deficiencies, Parkinson's, and Alzheimer's. In addition, these enzymes have recently provided extremely valuable data on how, when, and where reactive oxygen species, considered by many as "by-products" of OXPHOS, can contribute to animal longevity. It has also been shown that the expression of the alternative enzymes is thermogenic in cultured cells, causes reproductive defects in flies, and enhances the deleterious phenotype of some mitochondrial disease models. Therefore, all the reported beneficial effects must be considered with caution, as these enzymes have been proposed to be deployed in putative gene therapies to treat human diseases. Here, we present a brief review of the scientific data accumulated over the past decade that show the benefits and the risks of introducing alternative branches of the electron transport into mammalian and insect mitochondria, and we provide a perspective on the future of this research field.

Quantification through TLC-densitometric analysis, repellency and anticholinesterase activity of the homemade extract of Indian cloves.

The rise of the mosquitoes-transmitted diseases, like dengue, zika and chikungunya in Brazil in the last years has increased concerns on protection against mosquitoes bites. However, the prohibitive prices of the commercially available repellents for the majority of the Brazilian population has provoked a search for cheaper solutions, like the use of the homemade ethanolic extract of Indian clove (Syzygium aromaticum L.) as repellent, which has been reported as quite efficient by the local press. In order to verify this, we performed here the quantification of the main components of this extract through high-performance thin-layer chromatography (HPTLC)-densitometry and evaluated its efficiency as a repellent and its acetylcholinesterase (AChE) inhibition capacity. Our results have proved HPTLC-densitometry as an efficient and appropriate method for this quantification and confirmed the repellency activity, as well as its capacity of AChE inhibition.

Human Regulatory Protein Ki-1/57 Is a Target of SUMOylation and Affects PML Nuclear Body Formation.

Ki-1/57 is a nuclear and cytoplasmic regulatory protein first identified in malignant cells from Hodgkin's lymphoma. It is involved in gene expression regulation on both transcriptional and mRNA metabolism levels. Ki-1/57 belongs to the family of intrinsically unstructured proteins and undergoes phosphorylation by PKC and methylation by PRMT1. Previous characterization of its protein interaction profile by yeast two-hybrid screening showed that Ki-1/57 interacts with proteins of the SUMOylation machinery, the SUMO E2 conjugating enzyme UBC9 and the SUMO E3 ligase PIAS3, which suggested that Ki-1/57 could be involved with this process. Here we identified seven potential SUMO target sites (lysine residues) on Ki-1/57 sequence and observed that Ki-1/57 is modified by SUMO proteins in vitro and in vivo. We showed that SUMOylation of Ki-1/57 occurred on lysines 213, 276, and 336. In transfected cells expressing FLAG-Ki-1/57 wild-type, its paralog FLAG-CGI-55 wild-type, or their non-SUMOylated triple mutants, the number of PML-nuclear bodies (PML-NBs) is reduced compared with the control cells not expressing the constructs. More interestingly, after treating cells with arsenic trioxide (As2O3), the number of PML-NBs is no longer reduced when the non-SUMOylated triple mutant Ki-1/57 is expressed, suggesting that the SUMOylation of Ki-1/57 has a role in the control of As2O3-induced PML-NB formation. A proteome-wide analysis of Ki-1/57 partners in the presence of either SUMO-1 or SUMO-2 suggests that the involvement of Ki-1/57 with the regulation of gene expression is independent of the presence of either SUMO-1 or SUMO-2; however, the presence of SUMO-1 strongly influences the interaction of Ki-1/57 with proteins associated with cellular metabolism, maintenance, and cell cycle.

Expression of Ciona intestinalis AOX causes male reproductive defects in Drosophila melanogaster.

BACKGROUND: Mitochondrial alternative respiratory-chain enzymes are phylogenetically widespread, and buffer stresses affecting oxidative phosphorylation in species that possess them. However, they have been lost in the evolutionary lineages leading to vertebrates and arthropods, raising the question as to what survival or reproductive disadvantages they confer. Recent interest in using them in therapy lends a biomedical dimension to this question. METHODS: Here, we examined the impact of the expression of Ciona intestinalis alternative oxidase, AOX, on the reproductive success of Drosophila melanogaster males. Sperm-competition assays were performed between flies carrying three copies of a ubiquitously expressed AOX construct, driven by the α-tubulin promoter, and wild-type males of the same genetic background. RESULTS: In sperm-competition assays, AOX conferred a substantial disadvantage, associated with decreased production of mature sperm. Sperm differentiation appeared to proceed until the last stages, but was spatially deranged, with spermatozoids retained in the testis instead of being released to the seminal vesicle. High AOX expression was detected in the outermost cell-layer of the testis sheath, which we hypothesize may disrupt a signal required for sperm maturation. CONCLUSIONS: AOX expression in Drosophila thus has effects that are deleterious to male reproductive function. Our results imply that AOX therapy must be developed with caution.

Nanostructured SBA-15 silica: An effective protective vehicle to oral hepatitis B vaccine immunization.

Due to its physicochemical properties, nanostructured mesoporous SBA-15 silica shows great potential as a vaccine adjuvant. This study evaluated the capacity of SBA-15 to encapsulate/adsorb the recombinant purified HBsAg from the Hepatitis B virus and the immunoresponsiveness of mice orally immunized with HBsAg inside SBA-15. A simulation of small angle X-ray scattering experimental results, together with the nitrogen adsorption isotherms data, allowed to determine the appropriate mass ratio of HBsAg:SBA-15, indicating antigen encapsulation into SBA-15 macroporosity. This was also evaluated by bicinchoninic acid assay and gel electrophoresis. The recruitment of inflammatory cells, an increase in production of specific antibodies, and the non-influence of silica on TH1 or TH2 polarization were observed after oral immunization. Besides, SBA-15 enhanced the phagocytosis of ovalbumin by dendritic cells, an important key to prove how this adjuvant works. Thus, it seems clear that the nanostructured SBA-15 is an effective and safe adjuvant for oral immunizations.