Mobilome and genetic modification of bifidobacteria

Until recently, proper development of molecular studies in Bifidobacterium species has been hampered by growth difficulties, because of their exigent nutritive requirements, oxygen sensitivity and lack of efficient genetic tools. These studies, however, are critical to uncover the cross-talk between bifidobacteria and their hosts' cells and to prove unequivocally the supposed beneficial effects provided through the endogenous bifidobacterial populations or after ingestion as probiotics. The genome sequencing projects of different bifidobacterial strains have provided a wealth of genetic data that will be of much help in deciphering the molecular basis of the physiological properties of bifidobacteria. To this end, the purposeful development of stable cloning and expression vectors based on robust replicons - either from temperate phages or resident plasmids - is still needed. This review addresses the current knowledge on the mobile genetic elements of bifidobacteria (prophages, plasmids and transposons) and summarises the different types of vectors already available, together with the transformation procedures for introducing DNA into the cells. It also covers recent molecular studies performed with such vectors and incipient results on the genetic modification of these organisms, establishing the basis that would allow the use of bifidobacteria for future biotechnological applications

Cost of chronic and episodic migraine patients in continuous treatment for two years in a tertiary level headache Centre

Background: Migraine is one of the most common neurological diseases and an estimated 1.04 billion people worldwide have been diagnosed with migraine. Available data suggest that migraine is world widely associated with a high economic burden, but there is great variability in estimated costs that depends on the geographical, methodological and temporal differences between the studies. The purpose of this study was to quantify the annual direct cost of episodic migraine (EM) and chronic migraine (CM), both for the patient and for the National Health System (NHS), using data from subjects who attended an Italian tertiary headache centre. Furthermore, we evaluated comparatively the impact of gender and age on the economic burden of migraine. Methods: We conducted a retrospective and non-interventional observational analysis of the electronic medical records of subjects with EM and CM who consecutively attended the Regional Referral Headache Centre of Rome and undergoing continuous treatment in the 2 years prior to 31 January 2019. This approach was intended to prevent distorsions due to natural fluctuations in migraine status over time. The collected data included demographic characteristics, number of specialist visits, consumption of medications, diagnostic tests, accesses in the emergency department (ED) and days of hospitalization due to the pathology. Results: Our sample consisted of 548 patients (85.4% women and 14.6% men): 65.5% had CM and 34.5% had EM. The average annual expenditure per patient was 1482. 82.8% of the total cost (1227) was covered by the NHS. The main item of expenditure were medications that represented 86.8% (1286), followed by specialist visits (10.2%), hospitalizations for (1.9%), diagnostic tests for (1%) and ED visits for (0.1%). Costs were significantly higher for women than men (1517 vs. 1274, p = 0.013) and increased with age (p = 0.002). The annual direct cost of CM was 4.8-fold higher than that of EM (2037 vs. 427, p = 0.001). Conclusion: Our results provide a valuable estimate of the annual direct cost of CM and EM patients in the specific setting of a tertiary headache centre and confirm the high economic impact of migraine on both the NHS and patients

Migraine and cluster headache show impaired neurosteroids patterns

Background: Perturbation of neuronal excitability contributes to migraine. Neurosteroids modulate the activity of γ-aminobutyric acid A and N-methyl-d-aspartate receptors, and might be involved in the pathogenesis of migraine. Here, we measured plasma levels of four neurosteroids, i.e., allopregnanolone, epiallopregnanolone, dehydroepiandrosterone and deydroepiandrosterone sulfate, in patients affected by episodic migraine, chronic migraine, or cluster headache. Methods: Nineteen female patients affected by episodic migraine, 51 female patients affected by chronic migraine, and 18 male patients affected by cluster headache were recruited to the study. Sex- and age-matched healthy control subjects (31 females and 16 males) were also recruited. Patients were clinically characterized by using validated questionnaires. Plasma neurosteroid levels were measured by liquid chromatography-tandem mass spectrometry. Results: We found disease-specific changes in neurosteroid levels in our study groups. For example, allopregnanolone levels were significantly increased in episodic migraine and chronic migraine patients than in control subjects, whereas they were reduced in patients affected by cluster headache. Dehydroepiandrosterone and dehydroepiandrosterone sulfate levels were reduced in patients affected by chronic migraine, but did not change in patients affected by cluster headache. Conclusion: We have shown for the first time that large and disease-specific changes in circulating neurosteroid levels are associated with chronic headache disorders, raising the interesting possibility that fluctuations of neurosteroids at their site of action might shape the natural course of migraine and cluster headache. Whether the observed changes in neurosteroids are genetically determined or rather result from exposure to environmental or intrinsic stressors is unknown. This might also be matter for further investigation because stress is a known triggering factor for headache attacks in both migraineurs and cluster headache patients

Synthesis and photochromic behaviour of new methyl induced linear and angular thieno-2H-chromenes

New methyl induced linear and angular thieno-2H-chromenes 4, 5 and 6 were prepared by reaction of new methylated 6-hydroxybenzo[b]thiophenes 2 (a, b and c) and propargylic alcohols 3a and 3b, using acidic Alumina Brockmann I as catalyst and drying agent. Compounds 2 were prepared in good to excellent yields in a “one pot” three step reaction from the corresponding bromo compounds 1. The photochromic behaviour of compounds 4, 5 and 6b was evaluated with the aid of a classical set of spectrokinetic parameters, and compared to reference compounds that are benzoannellated in the 5,6 and 6,7 positions of the chromene (naphthopyrans) and also to thieno-2H-chromenes 7 and 8, previously prepared, which are analogues of 5a. The resistance to fatigue (photodegradation) under continuous irradiation was also evaluated.Fundação para a Ciência e Tecnologia. Escola Superior de Tecnologia e Gestão do Instituto Politécnico de Bragança

Probiotics action on gliadin sequences relevant to gluten sensitivity

The Celiac disease in genetically predisposed individuals is mainly induced by specific repetitive sequences in gliadins (PQPYP). This autoimmune disease stems from the interaction between toxic sequences and lamina propria cells, that is relevant also to other forms of gluten sensitivity. Specific endo-esoprolinase were isolated from lactic acid bacteria, suggesting possible practical applications. The ability of some probiotics at removing "toxic" celiac sequences was investigated, at first by assessing the presence and level of endo- and eso-prolinase activity in some of the most popular probiotic bacteria. Significant activities were detected in Lactobacillus and Bifidum species, as well as in the probiotic Escherichia coli Niessle 1917. On the basis of prolinase data, we investigated by mass spectroscopy the removal of "toxic" sequences in gliadin. A complete disappearance of these sequences was observed only with Escherichia coli Niessle 1917. Among the Bifidus and Lactobacillus species, only B. bifidum MIMBb23SG and L. acidophilus LA5 showed a significant decrease in the "toxic" sequences. All together, this study suggests a potential use of lactic bacteria to lower gluten response in sensitive individuals, including celiacs and gluten-sensitive

Evidence of dysbiosis in the intestinal microbial ecosystem of children and adolescents with primary hyperlipidemia and the potential role of regular hazelnut intake

Hyperlipidemia starts at a pediatric age and represents an unquestionable risk factor for cardiovascular disease. Modulation of the intestinal microbial ecosystem (IME), in principle, can ameliorate lipid profiles. In this study, we characterized the IME of children and adolescents with primary hyperlipidemia by analyzing fecal samples through 16S rRNA gene profiling (n\ua0=\ua015) and short chain fatty acid (SCFA) quantification (n\ua0=\ua032). The same analyses were also carried out on age-matched normolipidemic controls (n\ua0=\ua015). Moreover, we evaluated the modulatory effect of regular hazelnut intake (approximately 0.43 g of hazelnuts with skin per kg of body weight) on the IME of 15 children and adolescents with hyperlipidemia for eight weeks. We found alterations of numerous operational taxonomic units potentially associated with SCFA-producing bacteria and reductions in the fecal levels of acetate, butyrate and propionate in hyperlipidemic subjects. Furthermore, we observed that an eight-week hazelnut intervention may induce limited changes in fecal microbiota composition but can significantly modulate the fecal levels of predominant intestinal SCFAs, such as acetate. Finally, correlation analyses indicated that changes in lipidemic parameters are linked to modifications of the abundance of specific bacterial taxa, such as the families Lachnospiraceae and Ruminococcaceae and the genera Akkermansia, Bacteroides, Roseburia, and Faecalibacterium. This study suggests that children and adolescents with primary hyperlipidemia possess an altered IME. The promising results presented here support the need for future dietary interventions aimed at positively modulating the IME of hyperlipidemic subjects

Biotransformation strategy to reduce allergens in propolis

Propolis (bee glue) is a resinous, sticky, dark-colored material produced by honeybees. Propolis today, due to its medicinal properties, is increasingly popular and is extensively used in food, beverages, and cosmetic products. Besides its numerous positive properties, propolis may also have adverse effects, such as, principally, allergic eczematous contact dermatitis in apiarists and in consumers with an allergic predisposition. In this study, we found appropriate conditions for removing caffeate esters, which are the main allergenic components, from raw propolis. The proposed method consists of the resuspension of propolis in a food grade solvent, followed by a biotransformation based on the cinnamoyl esterase activity of Lactobacillus helveticus. We showed that the reduction of caffeate esters by L. helveticus did not affect the content of flavonoids, which are the main bioactive molecules of propolis. Furthermore, we verified that the biotransformation of propolis did not cause a loss of antimicrobial activity. Finally, we demonstrated that the ability of L. helveticus to hydrolyze caffeate esters in propolis is strain specific. In conclusion, the proposed strategy is simple, employs food grade materials, and is effective in selectively removing allergenic molecules without affecting the bioactive fraction of propolis. This is the first study demonstrating that the allergenic caffeate esters of propolis can be eliminated by means of a bacterial biotransformation procedure

First Measurement of the He3+He3-->He4+2p Cross Section down to the Lower Edge of the Solar Gamow Peak

We give the LUNA results on the cross section measurement of a key reaction of the proton-proton chain strongly affecting the calculated neutrino luminosity from the Sun: He3+He3-->He4+2p. Due to the cosmic ray suppression provided by the Gran Sasso underground laboratory it has been possible to measure the cross section down to the lower edge of the solar Gamow peak, i.e. as low as 16.5 keV centre of mass energy. The data clearly show the cross section increase due to the electron screening effect but they do not exhibit any evidence for a narrow resonance suggested to explain the observed solar neutrino flux.Comment: 5 pages, RevTeX, and 2 figures in PostScript Submitted for publicatio

Impact of a revised 25^{25}Mg(p,γ\gamma)26^{26}Al reaction rate on the operation of the Mg-Al cycle

Proton captures on Mg isotopes play an important role in the Mg-Al cycle active in stellar H-burning regions. In particular, low-energy nuclear resonances in the $^{25}$Mg(p,$\gamma$)$^{26}$Al reaction affect the production of radioactive $^{26}$Al$^{gs}$ as well as the resulting Mg/Al abundance ratio. Reliable estimations of these quantities require precise measurements of the strengths of low-energy resonances. Based on a new experimental study performed at LUNA, we provide revised rates of the $^{25}$Mg(p,$\gamma$)$^{26}$Al$^{gs}$ and the $^{25}$Mg(p,$\gamma$)$^{26}$Al$^{m}$ reactions with corresponding uncertainties. In the temperature range 50 to 150 MK, the new recommended rate of the $^{26}$Al$^{m}$ production is up to 5 times higher than previously assumed. In addition, at T$=100$ MK, the revised total reaction rate is a factor of 2 higher. Note that this is the range of temperature at which the Mg-Al cycle operates in an H-burning zone. The effects of this revision are discussed. Due to the significantly larger $^{25}$Mg(p,$\gamma$)$^{26}$Al$^{m}$ rate, the estimated production of $^{26}$Al$^{gs}$ in H-burning regions is less efficient than previously obtained. As a result, the new rates should imply a smaller contribution from Wolf-Rayet stars to the galactic $^{26}$Al budget. Similarly, we show that the AGB extra-mixing scenario does not appear able to explain the most extreme values of $^{26}$Al/$^{27}$Al, i.e. $>10^{-2}$, found in some O-rich presolar grains. Finally, the substantial increase of the total reaction rate makes the hypothesis of a self-pollution by massive AGBs a more robust explanation for the Mg-Al anticorrelation observed in Globular-Cluster stars