Parkinson’s disease: A prionopathy?

The principal pathogenic event in Parkinson’s disease is characterized by the conforma-tional change of α‐synuclein, which form pathological aggregates of misfolded proteins, and then accumulate in intraneuronal inclusions causing dopaminergic neuronal loss in specific brain re-gions. Over the last few years, a revolutionary theory has correlated Parkinson’s disease and other neurological disorders with a shared mechanism, which determines α‐synuclein aggregates and progresses in the host in a prion‐like manner. In this review, the main characteristics shared between α‐synuclein and prion protein are compared and the cofactors that influence the remodeling of native protein structures and pathogenetic mechanisms underlying neuro-degeneration are discussed

Prophage association of mef(A) elements encoding efflux-mediated erythromycin resistance in Streptococcus pyogenes.

OBJECTIVES: To compare different mef(A) elements of Streptococcus pyogenes for a possible chimeric genetic nature, i.e. a transposon inserted into a prophage. METHODS: Eleven S. pyogenes isolates with efflux-mediated erythromycin resistance were used. The isolates were typed using several genotypic approaches. Gene detection was performed by PCR using specific primer pairs. The mef(A) elements of the test strains were induced with mitomycin C and phage DNA was extracted. Induction was monitored by PCR using primers targeting mef(A). RESULTS: Six tetracycline-susceptible isolates had PCR evidence of all of the eight open reading frames (ORFs) of the Tn1207.1 element; their mef(A) element was consistent with the Tn1207.3 element in four isolates and with the 58.8 kb chimeric element in two. Five tetracycline-resistant isolates had no PCR evidence of orf1 and orf2 and showed variable patterns as to orf3, orf7, and orf8. Three ORFs placed along the conserved region downstream of Tn1207.1 in the 58.8 kb mef(A) chimeric element were detected in the six tetracycline-susceptible, but not in the five tetracycline-resistant isolates. Induction assays with mitomycin C demonstrated that the mef(A) elements of all strains tested were present in culture supernatants in a DNAse-resistant form, such as a phage capsid. CONCLUSIONS: All recognized mef(A) elements of S. pyogenes appear to be prophage-associated. Whereas the two elements detected in tetracycline-susceptible isolates (Tn1207.3 and the 58.8 kb one) were apparently inserted into the same prophage, the tet(O)-mef(A) element was inserted into a different prophage. Phage transfer is likely to play a critical role in the dissemination of erythromycin resistance in S. pyogenes populations

Electromagnetic phenomena in heterogeneous media: Effective properties and local behavior

The purpose of this paper is the use of a mathematical homogenization approach based on the multiple scale expansion theory for modeling the electromagnetic phenomena arising in heterogeneous media under an imposed magnetic flux. The attention is focused on the analysis and discussion of the merits and limits of this theoretical approach in reproducing not only the effective macroscopic properties but also the local behavior, under a wide frequency range and considering different constitutive and geometrical parameters. The results show that the proposed method is able to predict local and integral physical quantities, ranging from a substantially global behavior in the whole media to significantly localized effects determined by the microscopic structure

Bichromonol, a dimeric coumarin with anti-HIV activity from the stem bark of Hypericum roeperianum

Infectious diseases caused by viruses like HIV and SARS-COV-2 (COVID-19) pose serious public health threats. In search for new antiviral small molecules from chemically underexplored Hypericum species, a previously undescribed atropisomeric C8-C8’ linked dimeric coumarin named bichromonol (1) was isolated from the stem bark of Hypericum roeperianum. The structure was elucidated by MS data and NMR spectroscopy. The absolute configuration at the biaryl axis was determined by comparing the experimental ECD spectrum with those calculated for the respective atropisomers. Bichromonol was tested in cell-based assays for cytotoxicity against MT-4 (CC50 = 54 µM) cells and anti-HIV activity in infected MT-4 cells. It exhibits significant activity at EC50 = 6.6–12.0 µM against HIV-1 wild type and its clinically relevant mutant strains. Especially, against the resistant variants A17 and EFVR, bichromonol is more effective than the commercial drug nevirapine and might thus have potential to serve as a new anti-HIV lead

Genetic diversity of Streptococcus suis clinical isolates from pigs and humans in Italy (2003-2007)

n/

Dynamics of Gut Microbiota and Clinical Variables after Ketogenic and Mediterranean Diets in Drug-Naïve Patients with Type 2 Diabetes Mellitus and Obesity

Type 2 diabetes mellitus (T2DM), the most common form of diabetes, is a progressive chronic metabolic disease that has increasingly spread worldwide, enhancing the mortality rate, particularly from cardiovascular diseases (CVD). Lifestyle improvement through diet and physical activity is, together with drug treatment, the cornerstone of T2DM management. The Mediterranean diet (MD), which favors a prevalence of unprocessed vegetable foods and a reduction in red meats and industrial foods, without excluding any food category, is usually recommended. Recently, scientific societies have promoted a very low-calorie ketogenic diet (VLCKD), a multiphasic protocol that limits carbohydrates and then gradually re-introduces them, with a favorable outcome on body weight and metabolic parameters. Indeed, gut microbiota (GM) modifications have been linked to overweight/obesity and metabolic alterations typical of T2DM. Diet is known to affect GM largely, but only a few studies have investigated the effects of VLCKD on GM, especially in T2DM. In this study, we have compared anthropometric, biochemical, lifestyle parameters, the quality of life, and the GM of eleven patients with recently diagnosed T2DM and overweight or obesity, randomly assigned to two groups of six and five patients who followed the VLCKD (KETO) or hypocaloric MD (MEDI) respectively; parameters were recorded at baseline (T0) and after two (T2) and three months (T3). The results showed that VLCKD had more significant beneficial effects than MD on anthropometric parameters, while biochemical improvements did not statistically differ. As for the GM, despite the lack of significant results regarding the alpha and beta diversity, and the Firmicutes/Bacteroidota ratio between the two groups, in the KETO group, a significant increase in beneficial microbial taxa such as Verrucomicrobiota phylum with its members Verrucomicrobiae, Verrucomicrobiales, Akkermansiaceae, and Akkermansia, Christensenellaceae family, Eubacterium spp., and a reduction in microbial taxa previously associated with obesity (Firmicutes and Actinobacteriota) or other diseases (Alistipes) was observed both at T2 and T3. With regards to the MEDI group, variations were limited to a significant increase in Actinobacteroidota phylum at T2 and T3 and Firmicutes phylum at T3. Moreover, a metagenomic alteration linked to some metabolic pathways was found exclusively in the KETO group. In conclusion, both dietary approaches allowed patients to improve their state of health, but VLCKD has shown better results on body composition as well as on GM profile

New observations with the gas electron multiplier (GEM)

We describe recent measurements realized with the Gas Electron Multiplier (GEM) mesh added as pre-amplification element to a multiwire and a micro-strip chamber. Large, stable combined gains are obtained, with good uniformity and energy resolution, in a wide range of filling gases including non-flammable mixtures; coupled to a micro-strip plate, the pre-amplification element allows to maintain the high rate capability and resolution at considerably lower operating voltages, completely eliminating discharge problems. Charge gains are large enough to allow detection of signals in the ionization mode on the last element, permitting the use of a simple printed circuit as read-out electrode; two-dimensional read-out can then be easily implemented. The absence of charge multiplication in the last stage avoids charge build-up on the substrate and prevents ageing phenomena. A new generation of simple, reliable and cheap fast position sensitive detectors seems at hand