Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Probiotic lactobacilli inhibit early stages of Candida albicans biofilm development by reducing their growth, cell adhesion, and filamentation

We evaluated the inhibitory effects of the probiotic Lactobacillus species on different phases of Candida albicans biofilm development. Quantification of biofilm growth and ultrastructural analyses were performed on C. albicans biofilms treated with Lactobacillus rhamnosus, Lactobacillus casei, and Lactobacillus acidophilus planktonic cell suspensions as well as their supernatants. Planktonic lactobacilli induced a significant reduction (p\ua0\ua00.05), but significantly reduced the early stages of Candida biofilm formation (p\ua

Particle retention efficiency of a coastal ecosystem in the Northeastern Atlantic Ocean

Based on filtration rates obtained in situ at several habitats (mud flats, sand flats, and seagrass beds of Cymodocea nodosa), particle retention efficiency of benthic communities was estimated at Ria Formosa, a coastal lagoon in southern Portugal. The distinct physical characteristics of the water flow (water depth, current speed) at different tidal regimes (spring tide and neap tide) were also considered. Median filtration rates ranged 5.0−45.0 lm−2 h−1, despite the lack of dense bivalve beds or reefs. Based on median filtration rates of benthic communities on the studied substrate types, a model we developed showed that seagrass bed areas retained 15% of suspended particles during spring tide and 47% during neap tide. These retention efficiencies were much higher than those observed on mud flats (2.8% during spring tide, and 8% during neap tide), sand flats of finer grain size (8.8% during spring tide, and 50% during neap tide), and sand flats of coarser grain size (7% during spring tide, and 31% during neap tide). Removal of particles from water column was higher during the ebb tide than during flow tide, with particles of <5 μm diameter (especially diatoms, flagellates, and small-sized particulate matter) being the most commonly removed

Estudo fenotípico e genotípico da resistência aos macrolídeos de "Streptococcus pneumoniae" isolados em hospitais de Porto Alegre - RS

OBJETIVO: O objetivo deste estudo foi determinar a prevalência do S. pneumoniae resistente aos macrolídeos e identificar suas características fenotípicas e genotípicas. MÉTODOS: Amostras de S. pneumoniae isoladas entre maio de 2002 e agosto de 2004, em Porto Alegre (RS), a partir de materiais clínicos coletados de diferentes sítios anatômicos foram analisadas. Para o teste de difusão em ágar foram utilizados discos de eritromicina, claritromicina, azitromicina e clindamicina. As concentrações inibitórias mínimas de eritromicina foram determinadas nos isolados resistentes aos macrolídeos pelo método de diluição em ágar. Os fenótipos dos isolados resistentes aos macrolídeos foram investigados pelo teste de difusão em ágar e a genotipagem pela reação em cadeia da polimerase. RESULTADOS: Foram avaliados 229 isolados de pneumococos, e 12 mostraram-se resistentes aos macrolídeos (5,2%). Entre estes, 9 apresentaram o fenótipo MLSB (75%) e 3 o fenótipo M (25%). A reação em cadeia da polimerase indicou que 8 isolados com o fenótipo MLSB portavam apenas o gene ermB, enquanto que o gene mefE estava presente em todos os 3 isolados com o fenótipo M. Um isolado com o fenótipo MLSB apresentou ambos os genes. CONCLUSÃO: A resistência aos macrolídeos do S. pneumoniae em Porto Alegre permanece baixa, sendo devida principalmente à presença do gene ermB, com expressão do fenótipo MLSB.<br>OBJECTIVE: The aim of this study was to determine the prevalence of macrolide-resistant S. pneumoniae and to identify its phenotypic and genotypic characteristics. METHODS: Strains of S. pneumoniae isolated in the city of Porto Alegre between May 2002 and August 2004 from samples collected from different anatomical sites were analyzed. For the agar diffusion test, disks of erythromycin, clarithromycin, azithromycin and clindamycin were used. The minimum inhibitory concentrations of erythromycin were determined for macrolide-resistant isolates by the agar dilution method. Macrolide-resistant isolates were phenotyped by agar diffusion test and genotyped by polymerase chain reaction. RESULTS: A total of 229 pneumococcal strains were evaluated, 12 (5.2%) of which were macrolide-resistant. Among the 12 resistant strains, 9 (75%) presented the MLSB phenotype, and 3 (25%) presented the M phenotype. Polymerase chain reaction testing indicated that 8 MLSB phenotype isolates harbored the ermB gene only, whereas the mefE gene was present in all 3 M phenotype isolates. One MLSB phenotype isolate presented both genes. CONCLUSION: In Porto Alegre, the S. pneumoniae resistance to macrolides is still low since such resistance is due primarily to the presence of the ermB gene expressing the MLSB phenotype