A common founder for amyotrophic lateral sclerosis type 8 (ALS8) in the Brazilian population

The P56S mutation in the VAPB gene causes ALS8. Eight families, comprising more than 1,500 individuals of whom about 200 are affected, are now known to carry this mutation. Seven are of Portuguese–Brazilian ancestry and one of African–Brazilian ancestry. Haplotype analysis shows a common founder for all families regardless of ancestry, with a founding event 23 generations ago (95% CI 13–39), consistent with the Portuguese colonization of Brazil.Agnes L. Nishimura, Ammar Al-Chalabi contributed equally to this work     

Adsorption of sterigmatocystin by montmorillonite and inhibition of its genotoxicity in the Nile tilapia fish (Oreachromis nilaticus)

Sterigmatocystin (Stg) is closely related to the mycotoxin aflatoxin as a precursor in aflatoxin biosynthesis and classified as an IARC Group-2B carcinogen. The aim of this study was to investigate the efficacy of Egyptian montmorillonite (EM), a clay mineral, to adsorb Stg, to test the stability of the resulting complex under different conditions in vitro, and to utilize the Nile tilapia fish as an in vivo model to evaluate the protective effect of EM against Stg-induced toxicity and clastogenicity. In the in vitro study, four concentrations of EM (0.5, 1, 2 and 4 mg/L aqueous solution) and three concentrations of Stg (5, 10 and 50 microg/ml) were tested. The results show that EM had a high capacity of adsorbing Stg at different concentrations tested. The adsorption ranged from 93.1 to 97.8% of the available Stg in aqueous solutions. The complex was stable at different pHs at 37 degrees C in different organic solvents. An in vivo experiment was conducted to evaluate the ability of EM to prevent the toxicity and chromosomal aberrations induced by Stg in the Nile tilapia fish. Fish received an intragastric dose of EM in corn oil (0.5 mg/kg bw) with or without Stg (1.6 microg/kg bw) twice a week for 4 weeks. Body weight was recorded during dosing, and blood and tissue samples were collected at the end of treatment. Stg residues were determined in fish tissue. The results show that Stg was toxic and clastogenic to fish as indicated by the significant decrease of body weight and the increase in frequencies of micronucleated red blood cells (MN RBC) and chromosomal aberrations in the kidney. The intragastric administration of EM combined with Stg to fish resulted in a reduction of the number of MN RBC and the frequency of chromosomal aberrations in the kidney compared with the group treated with Stg alone. It could be concluded that EM itself was safe and successful in the prevention of Stg toxicity and clastogenicity.     

Fatty acids from seeds of Pinus pinea L.: composition and population profiling

Pinus pinea L. is widely disseminated all over the Mediterranean Basin. Qualitatively, P. pinea fatty acid seed composition is identical and typical of the genus Pinus. This composition is made of unsaturated oil with several unusual polymethylene-interrupted unsaturated fatty acids. Linoleic acid is the major fatty acid followed by oleic, palmitic and stearic acids. Quantitatively, for all Mediterranean populations, total amounts of fatty acids seem to be fairly constant and independent from their origin. When applying principal component analysis, it seems that there is not a distinct geographical variability. Tunisian populations appear to be integral part of the Mediterranean populations without any particular structuring. Taking into account this research and the data reported in the literature, we can confirm that P. pinea expresses no significant variability. This low genetic diversity revealed by fatty acid composition can be explained by anthropogenetic diffusion of genetically homogeneous reproductive material as early as the first explorations.     

Pyrrolizidine alkaloids from Anchusa strigosa and their antifeedant activity

The pyrrolizidine alkaloid (PA) content of flowers, leaves, and roots of Anchusa strigosa (Boraginaceae) was analysed by ESI-LC-MS. Six PAs, including two new natural compounds, were detected, characterized by NMR spectroscopy, and quantified in each plant organ. The results indicated that the highest total concentration of PAs was in the leaves (23.63 mg/g of dried part), followed by the flowers (19.77 mg/g), and finally by the roots (1.80 mg/g). All PAs isolated were subjected to Spodoptera exigua and Pieris brassicae larvae. Feeding activity by both herbivore species using a bioassay was inhibited up to circa 75% depending on PA and applied concentration.     

High androgen receptor immunoexpression in human "Sertoli cell only" testis

Our purpose was to evaluate cellular androgen receptor (AR) distribution and intensity of immunostaining in the human azoospermic testis. Thirty six biopsy specimens from azoospermic men were immunostained, using a monoclonal antibody of human AR. The localization and the intensity of AR immunostaining was evaluated in Sertoli Cell Only (SCO) testis (G1, n = 21), in spermatogenesis arrest testis (G2, n = 11) and in histologically normal testis (G3, n = 4). We found an AR immunostaining in Sertoli, peritubular myoid and Leydig cells, but not in germ cells. The intensity of the immunostaining varied substantially between biopsy specimens of different patients. Sertoli and Leydig cells AR immunostaining (score and intensity) in SCO group was higher than in the other groups. For Sertoli cells, the score means of AR immunoreactivity were 20 +/- 2.36, 10.18 +/- 1.0 and 1 +/- 1, for G1, G2 and G3 groups, respectively. For Leydig cells, the score means were 10.24 +/- 1.37, 6 +/- 0.71 and 0, for G1, G2 and G3 groups, respectively. We found significant differences between G1 and G2 (p = 0.0008), between G1 and G3 (p = 1.54 10-7) and G2 and G3 (p = 0.00032). These results suggest that in the testis AR is located exclusively in somatic cells and its expression is higher in SCO syndrome than in normal and in arrest spermatogenesis testes.     

Anopheles mosquito bites activate cutaneous mast cells leading to a local inflammatory response and lymph node hyperplasia

When Anopheles mosquitoes probe the skin for blood feeding, they inject saliva in dermal tissue. Mosquito saliva is known to exert various biological activities, but its perception by the immune system and its role in parasite transmission remain poorly understood. In the present study, we report on the cellular changes occurring in the mouse skin and draining lymph nodes after a Anopheles stephensi mosquito bite. We show that mosquito bites induce dermal mast cell degranulation, leading to fluid extravasation and neutrophil influx. This inflammatory response does not occur in mast cell-deficient W/W(v) mice, unless these are reconstituted specifically with mast cells. Mast cell activation caused by A. stephensi mosquito bites is followed by hyperplasia of the draining lymph node due to the accumulation of CD3(+), B220(+), CD11b(+), and CD11c(+) leukocytes. The T cell enrichment of the draining lymph nodes results from their sequestration from the circulation rather than local proliferation. These data demonstrate that mosquito bites and very likely saliva rapidly trigger the immune system, emphasizing the critical contribution of peripheral mast cells in inducing T cell and dendritic cell recruitment within draining lymph nodes, a prerequisite for the elicitation of T and B lymphocyte priming.     

Resistance to volatile anesthetics by mutations enhancing excitatory neurotransmitter release in Caenorhabditis elegans

The molecular mechanisms whereby volatile general anesthetics (VAs) disrupt behavior remain undefined. In Caenorhabditis elegans mutations in the gene unc-64, which encodes the presynaptic protein syntaxin 1A, produce large allele-specific differences in VA sensitivity. UNC-64 syntaxin normally functions to mediate fusion of neurotransmitter vesicles with the presynaptic membrane. The precise role of syntaxin in the VA mechanism is as yet unclear, but a variety of results suggests that a protein interacting with syntaxin to regulate neurotransmitter release is essential for VA action in C. elegans. To identify additional proteins that function with syntaxin to control neurotransmitter release and VA action, we screened for suppressors of the phenotypes produced by unc-64 reduction of function. Loss-of-function mutations in slo-1, which encodes a Ca(2+)-activated K+ channel, and in unc-43, which encodes CaM-kinase II, and a gain-of-function mutation in egl-30, which encodes Gqalpha, were isolated as syntaxin suppressors. The slo-1 and egl-30 mutations conferred resistance to VAs, but unc-43 mutations did not. The effects of slo-1 and egl-30 on VA sensitivity can be explained by their actions upstream or parallel to syntaxin to increase the level of excitatory neurotransmitter release. These results strengthen the link between transmitter release and VA action.     

Anti-genotoxic and free-radical scavenging activities of extracts from (Tunisian) Myrtus communis

The effect of extracts from leaves of Myrtus communis on the SOS reponse induced by Aflatoxin B1 (AFB1) and Nifuroxazide was investigated in a bacterial assay system, i.e. the SOS chromotest with Escherichia coli PQ37. Aqueous extract, the total flavonoids oligomer fraction (TOF), hexane, chloroform, ethyl acetate and methanol extracts and essential oil obtained from M. communis significantly decreased the SOS response induced by AFB1 (10 microg/assay) and Nifuroxazide (20 microg/assay). Ethyl acetate and methanol extracts showed the strongest inhibition of the induction of the SOS response by the indirectly genotoxic AFB1. The methanol and aqueous extracts exhibited the highest level of protection towards the SOS-induced response by the directly genotoxic Nifuroxazide. In addition to anti-genotoxic activity, the aqueous extract, the TOF, and the ethyl acetate and methanol extracts showed an important free-radical scavenging activity towards the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. These results suggest the future utilization of these extracts as additives in chemoprevention studies.     

A comparison of disease burden and symptoms with age among CoVid-19 patients from data in a Florida clinic

Our knowledge of the disease burden and symptoms with age in COVID-19 patients is limited. Therefore, it is of interest to document the clinical aspect of this association with respect to the disease. We used the data of 3363 patients enrolled with an urgent care clinic in Volusia county, Florida for this study. Data shows difference in age among COVID-19 antibody (Ab) - positive patients (48.3 years, 95% CI = 46.9,49.7 years) and Ab-negative patients (46.1 years, 95% CI = 45.4, 46.8 years). However, disease burden by age is not significant on average. Nonetheless, COVID-19 positive patients between 40-69-years of age experienced the highest burden of disease and highest average number of symptoms. Thus, COVID-19 disease burden and number of symptoms experienced were highest among the 40-69-year-old patients. Those above the populations mean age of 46.4 years old were more likely to test positive for COVID-19.     

Isolation and Characterization of Moderately Halophilic Bacteria from Tunisian Solar Saltern

Bacterial screenings from solar saltern in Sfax (Tunisia) lead to the isolation of 40 moderately halophilic bacteria which were able to grow optimally in media with 5–15% of salt. These isolates were phylogenetically characterized using 16S rRNA gene sequencing. Two groups were identified including 36 strains of Gamma-Proteobacteria (90%) and 4 strains of Firmicutes (10%). The Gamma-Proteobacteria group consisted of several subgroups of the Halomonadaceae (52.5%), the Vibrionaceae (15%), the Alteromonadaceae (10%), the Idiomarinaceae (7.5%), and the Alcanivoracaceae (5%). Moreover, three novel species: 183ZD08, 191ZA02, and 191ZA09 were found, show <97% sequence similarity of the 16S rRNA sequences while compared to previously published cultivated species. Most of these strains (70%) were able to produce hydrolases: amylases, proteases, phosphatases, and DNAases. Over the isolates, 60% produced phosphatases, 15.0% proteases, 12.5% amylases and DNAases equally. This study showed that the solar saltern of Sfax is an optimal environment for halophilic bacterial growth, where diverse viable bacterial communities are available and may have many industrial applications.