Ornithine Transcarbamylase Deficiency: If at First You Do Not Diagnose, Try and Try Again

Ornithine transcarbamylase (OTC) deficiency is well known for its diagnosis in the neonatal period. Presentation often occurs after protein feeding and manifests as poor oral intake, vomiting, lethargy progressing to seizure, respiratory difficulty, and eventually coma. Presentation at adulthood is rare (and likely underdiagnosed); however, OTC deficiency can be life-threatening and requires prompt investigation and treatment. Reports and guidelines are scarce due to its rarity. Here, we present a 59-year-old woman with a past history of irritable bowel syndrome who underwent a reparative operation for rectal prolapse and enterocele. Her postoperative course was complicated by a bowel perforation (which was repaired), prolonged mechanical ventilation, tracheostomy, critical illness myopathy, protein-caloric malnutrition, and altered mental status. After standard therapy for delirium failed, further investigation showed hyperammonemia and increased urine orotic acid, ultimately leading to the diagnosis of OTC deficiency. This case highlights the importance of considering OTC deficiency in hospitalized adults, especially during the diagnostic evaluation for altered mental status

Critical temperature of non-interacting Bose gases on disordered lattices

For a non-interacting Bose gas on a lattice we compute the shift of the critical temperature for condensation when random-bond and onsite disorder are present. We evidence that the shift depends on the space dimensionality D and the filling fraction f. For D -> infinity (infinite-range model), using results from the theory of random matrices, we show that the shift of the critical temperature is negative, depends on f, and vanishes only for large f. The connections with analogous results obtained for the spherical model are discussed. For D=3 we find that, for large f, the critical temperature Tc is enhanced by disorder and that the relative shift does not sensibly depend on f; at variance, for small f, Tc decreases in agreement with the results obtained for a Bose gas in the continuum. We also provide numerical estimates for the shift of the critical temperature due to disorder induced on a non-interacting Bose gas by a bichromatic incommensurate potential.Comment: 18 pages, 8 figures; Fig. 8 improved adding results for another value of q (q=830/1076

Effect of light and sucrose on photoautotrophic and photomixotrophic micropropagation of Physalis angulata

The biotechnological interest in genus Physalis has increased in the last decades, however, there are still few micropropagation studies of this genus. The objective of this study was to evaluate P. angulata photoautotrophic and photomixotrophic micropropagation with gas exchange under seven light spectra and five concentrations of sucrose. Lighting were yellow, blue, white, red, green, red + blue LEDs and natural light filtered by mesh. Sucrose concentrations were 0, 7.5, 15, 22.5 and 30 g.L-1. Phytotechnical, anatomical features and photopigment contents were evaluated through stem and root segment length, leaf number, leaf area, chlorophyll a and b contents, carotenoids, adaxial epidermis, palisadic and spongy parenchyma and abaxial epidermis. The data were compared by Scott-Knott's mean test and principal components analysis using the R software. Comparing the variables within lighting types, it was observed that only the screen treatment, screen-filtered natural illumination, obtained assessment in all variables. Comparing the levels of sucrose, it was observed that the treatment 15 g.L-1 sucrose obtained the highest number of averages with maximum evaluation. It was concluded that the natural light filtered by screen with 50% of shading allowed the photoautotrophic micropropagation of P. angulata. Better development results were observed in photomixotrophic micropropagation with 15 g.L-1 of sucrose

An investigation into the stability of an oregano essential oil emulsion for the preparation of microparticles using spray drying.

The objective of this study was to evaluate the viscosity, zeta potential and soluble and total solids of the emulsion and microparticles of oregano essential oil (Origanum vulgare) using gum arabic as a coating agent and to analyze the morphology of the microparticles produced by the spray drying method. The rheological analysis showed a viscosity for emulsion of 36.23 ± 0.59 mPas and for microparticles of 20.13 ± 0.15 mPa.s. The zeta potential of the emulsion was - 6.67 ± 0.32 mV and of the oregano oil microparticles -16.47 ± 0.70 mV. Soluble solids showed Brix° of 8.44 ± 0.13 and 0.98 ± 0.36 and total solids 8.95 ± 0.42 and 1.03 ± 0.02 % for emulsion and microparticles, respectively. The morphology of the microparticles presented irregular spherical shapes and agglomeration

HPLC-MS identification and expression of Candida drug-resistance proteins from African HIV-infected patients

The objective of this study was to elucidate the proteomic mechanisms of drug resistance in HIV-infected African patients. Cell membrane fractions from forty oral Candida isolates isolated from African HIV-positive patients were analysed using HPLC-MS with the aim of identifying proteins associated with their pathogenicity and drug resistance. Heat shock proteins that mediate the fungicidal activity of salivary peptides were found in all tested Candida fractions, with pH-responsive proteins associated with increased pathogenicity only being present in the three most commonly isolated species. ABC multidrug transporter efflux pumps and estrogen binding proteins were only found in C. albicans fractions, while ergosterol biosynthesis proteins were identified in four species. The combination of various adherence, invasion, upregulation and efflux pump mechanisms appear to be instrumental for the Candida host colonization and drug resistance emergence in HIV-infected individuals.This material is based upon work partially supported financially by the National Research Foundation of South Africa [Grant number TTK2008052700013]

A functional genomics approach reveals suggestive quantitative trait loci associated with combined TLR4 and BCP crystal-induced inflammation and osteoarthritis

Objective: Basic calcium phosphate (BCP) crystals can activate the NLRP3 inflammasome and are potentially involved in the pathogenesis of osteoarthritis (OA). In order to elucidate relevant inflammatory mechanisms in OA, we used a functional genomics approach to assess genetic variation influencing BCP crystal-induced cytokine production. Method: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy volunteers who were previously genotyped and stimulated with BCP crystals and/or lipopolysaccharide (LPS) after which cytokines release was assessed. Cytokine quantitative trait locus (cQTL) mapping was performed. For in vitro validation of the cQTL located in anoctamin 3 (ANO3), PBMCs were incubated with Tamoxifen and Benzbromarone prior to stimulation. Additionally, we performed co-localisation analysis of our top cQTLs with the most recent OA meta-analysis of genome-wide association studies (GWAS). Results: We observed that BCP crystals and LPS synergistically induce IL-1β in human PBMCs. cQTL analysis revealed several suggestive loci influencing cytokine release upon stimulation, among which are quantitative trait locus annotated to ANO3 and GLIS3. As functional validation, anoctamin inhibitors reduced IL-1β release in PBMCs after stimulation. Co-localisation analysis showed that the GLIS3 locus was shared between LPS/BCP crystal-induced IL-1β and genetic association with Knee OA. Conclusions: We identified and functionally validated a new locus, ANO3, associated with LPS/BCP crystal-induced inflammation in PBMCs. Moreover, the cQTL in the GLIS3 locus co-localises with the previously found locus associated with Knee OA, suggesting that this Knee OA locus might be explained through an inflammatory mechanism. These results form a basis for further exploration of inflammatory mechanisms in OA.</p

Anandamide Effects in a Streptozotocin-Induced Alzheimer’s Disease-Like Sporadic Dementia in Rats

Alzheimer’s disease (AD) is characterized by multiple cognitive deficits including memory and sensorimotor gating impairments as a result of neuronal and synaptic loss. The endocannabinoid system plays an important role in these deficits but little is known about its influence on the molecular mechanism regarding phosphorylated tau (p-tau) protein accumulation – one of the hallmarks of AD –, and on the density of synaptic proteins. Thus, the aim of this study was to investigate the preventive effects of anandamide (N-arachidonoylethanolamine, AEA) on multiple cognitive deficits and on the levels of synaptic proteins (syntaxin 1, synaptophysin and synaptosomal-associated protein, SNAP-25), cannabinoid receptor type 1 (CB1) and molecules related to p-tau degradation machinery (heat shock protein 70, HSP70), and Bcl2-associated athanogene (BAG2) in an AD-like sporadic dementia model in rats using intracerebroventricular (icv) injection of streptozotocin (STZ). Our hypothesis is that AEA could interact with HSP70, modulating the level of p-tau and synaptic proteins, preventing STZ-induced cognitive impairments. Thirty days after receiving bilateral icv injections of AEA or STZ or both, the cognitive performance of adult male Wistar rats was evaluated in the object recognition test, by the escape latency in the elevated plus maze (EPM), by the tone and context fear conditioning as well as in prepulse inhibition tests. Subsequently, the animals were euthanized and their brains were removed for histological analysis or for protein quantification by Western Blotting. The behavioral results showed that STZ impaired recognition, plus maze and tone fear memories but did not affect contextual fear memory and prepulse inhibition. Moreover, AEA prevented recognition and non-associative emotional memory impairments induced by STZ, but did not influence tone fear conditioning. STZ increased the brain ventricular area and this enlargement was prevented by AEA. Additionally, STZ reduced the levels of p-tau (Ser199/202) and increased p-tau (Ser396), although AEA did not affect these alterations. HSP70 was found diminished only by STZ, while BAG2 levels were decreased by STZ and AEA. Synaptophysin, syntaxin and CB1 receptor levels were reduced by STZ, but only syntaxin was recovered by AEA. Altogether, albeit AEA failed to modify some AD-like neurochemical alterations, it partially prevented STZ-induced cognitive impairments, changes in synaptic markers and ventricle enlargement. This study showed, for the first time, that the administration of an endocannabinoid can prevent AD-like effects induced by STZ, boosting further investigations about the modulation of endocannabinoid levels as a therapeutic approach for AD

A model for transition of 5 '-nuclease domain of DNA polymerase I from inert to active modes

Bacteria contain DNA polymerase I (PolI), a single polypeptide chain consisting of similar to 930 residues, possessing DNA-dependent DNA polymerase, 3'-5' proofreading and 5'-3' exonuclease (also known as flap endonuclease) activities. PolI is particularly important in the processing of Okazaki fragments generated during lagging strand replication and must ultimately produce a double-stranded substrate with a nick suitable for DNA ligase to seal. PolI's activities must be highly coordinated both temporally and spatially otherwise uncontrolled 5'-nuclease activity could attack a nick and produce extended gaps leading to potentially lethal double-strand breaks. To investigate the mechanism of how PolI efficiently produces these nicks, we present theoretical studies on the dynamics of two possible scenarios or models. In one the flap DNA substrate can transit from the polymerase active site to the 5'-nuclease active site, with the relative position of the two active sites being kept fixed; while the other is that the 5'-nuclease domain can transit from the inactive mode, with the 5'-nuclease active site distant from the cleavage site on the DNA substrate, to the active mode, where the active site and substrate cleavage site are juxtaposed. The theoretical results based on the former scenario are inconsistent with the available experimental data that indicated that the majority of 5'-nucleolytic processing events are carried out by the same PolI molecule that has just extended the upstream primer terminus. By contrast, the theoretical results on the latter model, which is constructed based on available structural studies, are consistent with the experimental data. We thus conclude that the latter model rather than the former one is reasonable to describe the cooperation of the PolI's polymerase and 5'-3' exonuclease activities. Moreover, predicted results for the latter model are presented

PIT telemetry as a method to study the habitat requirements of fish populations: application to native and stocked trout movements

Passive integrated transponder (PIT) technology was used to study the behaviour of fishes during the summer season in two headwater streams of northeastern Portugal. A total of 71 PIT tags (12 mm long x 2.1 mm diameter) were surgically implanted in 1+ stocked (39) and native (32) brown trout of two size classes (< 20.0 and ≥ 20.0 cm). Eight independent antennae, connected to a multi-point decoder (MPD reader) unit, were placed in different microhabitats, selected randomly every three days during the observation period (29 August to 9 September in Baceiro stream and 19 September to 4 October in Sabor stream). The results confirmed this method as a suitable labour efficient tool to assess the movement and habitat use of sympatric stocked and native trout populations. About 76.9% of stocked and 59.4% of native PIT tagged trouts were detected. Multivariate techniques (CCA, DFA and classification tree) showed a separation in habitat use between the two sympatric populations. Stocked trout mainly used the microhabitats located in the middle of the channel with higher depths and without cover. Furthermore, these fishes displayed a greater mobility and a diel activity pattern different to native trout populations