Galactosaminogalactan (GAG) is a prominent cell wall component of the opportunistic fungal pathogen Aspergillus fumigatus. GAG is a heteropolysaccharide composed of α‐1,4‐linked galactose, ...galactosamine and N‐acetylgalactosamine residues. To enable biochemical studies, a library of GAG‐fragments was constructed featuring specimens containing α‐galactose‐, α‐galactosamine and α‐N‐acetyl galactosamine linkages. Key features of the synthetic strategy include the use of di‐tert‐butylsilylidene directed α‐galactosylation methodology and regioselective benzoylation reactions using benzoyl‐hydroxybenzotriazole (Bz‐OBt). Structural analysis of the Gal, GalN and GalNAc oligomers by a combination of NMR and MD approaches revealed that the oligomers adopt an elongated, almost straight, structure, stabilized by inter‐residue H‐bonds, one of which is a non‐conventional C−H⋅⋅⋅O hydrogen bond between H5 of the residue (i+1) and O3 of the residue (i). The structures position the C‐2 substituents almost perpendicular to the oligosaccharide main chain axis, pointing to the bulk solvent and available for interactions with antibodies or other binding partners.
The completely stereoselective assembly of fungal Aspergillus fumigatus galactosaminogalactans, incorporating α‐Gal, α‐GalN and α‐GalNac residues up to dodecasaccharides, is reported. Structural studies reveal a non‐canonical C−H⋅⋅⋅O hydrogen bond to stabilize the elongated, linear structure that displays the Gal‐functional groups to the outside of the polymer, available for interactions with binding partners.
Animal models of alcohol (ethanol) self‐administration are crucial to dissect the neurobiological mechanisms underlying alcohol dependence, yet only a few of these induce pharmacologically relevant ...levels of alcohol consumption and rarely the alcohol self‐administration co‐occurs with other addictive behaviours. The present study aims to validate a novel model of voluntary ethanol consumption in male Wistar rats, in which ethanol access follows a binge eating experience. Over 10 sessions, Wistar rats were exposed to binge or control eating (i.e., the ingestion of 11.66 and 0.97 kcal/3 min, respectively, derived from a highly palatable food), immediately followed by two‐bottle choice intake tests (2%, 6%, 10% or 14% w/w ethanol vs. water). Rats exposed to binge eating drank significantly more 6% or 10% (w/w) ethanol than control peers, reaching up to 6.3 gEtOH/kg. Rats stimulated with 2%, 6%, 10% or 14% ethanol after binge eating, but not those given those ethanol concentrations after control eating, exhibited significant within‐group increases in ethanol drinking. This ethanol consumption was not altered by quinine adulteration (up to 0.1 g/L), and it was blocked by naltrexone (10 mg/kg), administered immediately before binge eating. Blood ethanol levels significantly correlated with ethanol consumption; and the more ethanol consumed, the greater the distance travelled in an open field test conducted after the two‐bottle choice test. Altogether, this self‐administration model seems a valid and robust alternative with remarkable potential for research on different stages of the alcohol addiction and, particularly, to assess interactions between alcohol consumption and others addictive‐like behaviours.
This study validated a novel model of voluntary ethanol consumption in male Wistar rats, in which ethanol access follows a binge eating experience. Rats stimulated with 2%, 6%, 10% or 14% ethanol immediately after binge eating, but not those given those ethanol concentrations after control eating, exhibited significant within‐group increases in ethanol drinking. This ethanol consumption was not altered by quinine adulteration (up to 0.1 g/L), and it was blocked by naltrexone (10 mg/kg), administered immediately before binge eating.
Scope
Dysbiosis of gut microbiota is involved in metabolic syndrome (MetS) development, which has a different incidence between men (M) and women (W). The differences in gut microbiota in MetS ...patients are explored according to gender, and whether consuming two healthy diets, Mediterranean (MED) and low‐fat (LF), may, over time, differentially shape the gut microbiota dysbiosis according to gender is evaluated.
Materials and Methods
All the women from the CORDIOPREV study whose feces samples were available and a similar number of men, matched by the main metabolic variables (N = 246, 123 women and 123 men), and categorized according to the presence or not of MetS are included. Gut microbiota is analyzed at baseline and after 3 years of dietary intervention.
Results
Higher abundance of Collinsella, Alistipes, Anaerotruncus, and Phascolarctobacterium genera is observed in MetS‐W than in MetS‐M, whereas the abundance of Faecalibacterium and Prevotella genera is higher in MetS‐M than in MetS‐W. Moreover, higher levels of Desulfovibrio, Roseburia, and Holdemania are observed in men than in women after the consumption of the LF diet.
Conclusion
The results suggest the potential involvement of differences in gut microbiota in the unequal incidence of metabolic diseases between genders, and a sex‐dependent effect on shaping the gut microbiota according to diet.
Dysbiosis of gut microbiota is involved in the development of metabolic syndrome, whose incidence is different between men and women. This work provides evidence of a different gut microbiota composition in metabolic syndrome, according to gender. Moreover, the study shows a differential shaping of the gut microbiota according to the gender in metabolic syndrome patients after the consumption of a Mediterranean or a low‐fat diet for three years.
The objective of this work was on the one hand to assess the antibacterial activity of amines anchored to the external surface of mesoporous silica particles against Listeria monocytogenes in ...comparison with the same dose of free amines as well. It was also our aim to elucidate the mechanism of action of the new antimicrobial device. The suitability of silica nanoparticles to anchor, concentrate and improve the antimicrobial power of polyamines against L. monocytogenes has been demonstrated in a saline solution and in a food matrix. Moreover, through microscope observations it has been possible to determine that the attractive binding forces between the positive amine corona on the surface of nanoparticles and the negatively charged bacteria membrane provoke a disruption of the cell membrane. The surface concentration of amines on the surface of the nanoparticles is so effective that immobilized‐amines were 100 times more effective in killing L. monocytogenes bacteria than the same amount of free polyamines. This novel approach for the creation of antimicrobial nanodevices opens the possibility to put in value the antimicrobial power of natural molecules that have been discarded because of its low antimicrobial power.
Practical Application
Consumers demand for high‐quality products, free from chemical preservatives, with an extended shelf‐life. In this study, a really powerful antimicrobial agent based on a nanomaterial functionalized with a non‐antimicrobial organic molecule was developed as a proof of concept. Following this approach it could be possible to develop a new generation of natural and removable antimicrobials based on their anchoring to functional surfaces for food, agricultural or medical purposes.
Up to 22 June 2022, 508 confirmed cases of monkeypox (MPX) have been reported in the Madrid region of Spain, 99% are men (n = 503) with a median age of 35 years (range: 18-67). In this ongoing ...outbreak, 427 cases (84.1%) reported condomless sex or sex with multiple partners within the 21 days before onset of symptoms, who were predominantly men who have sex with men (MSM) (n = 397; 93%). Both the location of the rash, mainly in the anogenital and perineal area, as well as the presence of inguinal lymphadenopathy suggest that close physical contact during sexual activity played a key role in transmission. Several cases reported being at a sauna in the city of Madrid (n = 34) or a mass event held on the Spanish island of Gran Canaria (n = 27), activities which may represent a conducive environment for MPX virus spread, with many private parties also playing an important role. Because of the rapid implementation of MPX surveillance in Madrid, one of the largest outbreaks reported outside Africa was identified. To minimise transmission, we continue to actively work with LGBTIQ+ groups and associations, with the aim of raising awareness among people at risk and encouraging them to adopt preventive measures.
Pseudomonas aeruginosa is an opportunistic pathogen able to infect any human tissue. One of the reasons for its high adaptability and colonization of host tissues is its capacity of maintaining iron ...homeostasis through a wide array of iron acquisition and removal mechanisms. Due to their ability to cause life‐threatening acute and chronic infections, especially among cystic fibrosis and immunocompromised patients, and their propensity to acquire resistance to many antibiotics, the World Health Organization (WHO) has encouraged the scientific community to find new strategies to eradicate this pathogen. Several recent strategies to battle P. aeruginosa focus on targeting iron homeostasis mechanisms, turning its greatest advantage into an exploitable weak point. In this review, we discuss the different mechanisms used by P. aeruginosa to maintain iron homeostasis and the strategies being developed to fight this pathogen by blocking these mechanisms. Among others, the use of iron chelators and mimics, as well as disruption of siderophore production and uptake, have shown promising results in reducing viability and/or virulence of this pathogen. The so‐called ‘Trojan‐horse’ strategy taking advantage of the siderophore uptake systems is emerging as an efficient method to improve delivery of antibiotics into the bacterial cells. Moreover, siderophore transporters are considered promising targets for the developing of P. aeruginosa vaccines.
Therapeutics directed to disrupt iron homeostasis in the human pathogen Pseudomonas aeruginosa.
Experimental evidence indicates that exercise performed at different times of the day may affect circadian rhythms and circadian disruption has been linked to breast and prostate cancer. We examined ...in a population‐based case‐control study (MCC‐Spain) if the time‐of‐day when physical activity is done affects prostate and breast cancer risk. Lifetime recreational and household physical activity was assessed by in‐person interviews. Information on time‐of‐day of activity (assessed approximately 3 years after the assessment of lifetime physical activity and confounders) was available for 781 breast cancer cases, 865 population female controls, 504 prostate cases and 645 population male controls from 10 Spanish regions, 2008‐2013. We estimated odds ratios (ORs) and 95% confidence intervals (95% CI) for different activity timings compared to inactive subjects using unconditional logistic regression adjusting for confounders. Early morning (8‐10 am) activity was associated with a protective effect compared to no physical activity for both breast (OR = 0.74, 95% CI = 0.48‐1.15) and prostate cancer (OR = 0.73, 95% CI = 0.44‐1.20); meta‐OR for the two cancers combined 0.74 (95%CI = 0.53‐1.02). There was no effect observed for breast or prostate cancer for late morning to afternoon activity while a protective effect was also observed for evening activity only for prostate cancer (OR = 0.75, 95% CI = 0.45‐1.24). Protective effects of early morning activity were more pronounced for intermediate/evening chronotypes for both cancers. This is the first population‐based investigation identifying a differential effect of timing of physical activity on cancer risk with more pronounced effects for morning hour activity. Our results, if confirmed, may improve current physical activity recommendations for cancer prevention.
What's new?
Exercise protects against a variety of cancers, but does time of day matter? Disrupting the body's circadian rhythm can boost cancer risk. Here, the authors compared breast and prostate cancer risk among people who exercised in the early morning, late morning, afternoon, and evening. They conducted a population‐based case‐control study, in which participants filled out a questionnaire about their patterns of sleeping, eating, and exercising. Exercising in the early morning appeared to be more strongly protective against breast and prostate cancer than exercising later in the day. Evening exercise appeared to have a moderate protective effect on prostate cancer.