Virtual distillation for quantum error mitigation

Theoretical Physic

CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice

Neuroinflammation and microglial activation are significant processes in Alzheimer's disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer's disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer's disease and other tau-mediated neurodegenerative diseases

Inflammatory biomarkers in Alzheimer's disease plasma

Introduction: Plasma biomarkers for Alzheimer's disease (AD) diagnosis/stratification are a \u201cHoly Grail\u201d of AD research and intensively sought; however, there are no well-established plasma markers. Methods: A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL; 259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed. Results: Ten analytes showed significant intergroup differences. Logistic regression identified five (FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APO\u3b54 adjusted, optimally differentiated AD and CTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI (AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Two analytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71). Discussion: Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation

Error mitigation via verified phase estimation

Theoretical Physic

Genitores potenciais para hibridações identificados por divergência genética em feijão carioca Bean parents for hybridization identified by genetic divergence in "carioca" bean

Noventa genótipos de feijão carioca (Phaseolus vulgaris L.) foram avaliados, em dois anos agrícolas, em Santa Maria, RS, a fim de definir quais características agromorfológicas constituem-se como melhores descritores, realizar agrupamento em função de dissimilaridade genética e de definir quais combinações híbridas mais promissoras serão obtidas para o desenvolvimento de populações segregantes. Dos 20 caracteres agromorfológicos avaliados, apenas nove (ferrugem nos legumes, acamamento, nota geral, cor do tegumento, rendimento de grãos, massa de 100 sementes, altura de inserção do primeiro legume, altura de inserção do último legume e número de sementes por legume) apresentaram maior contribuição para a divergência genética. Os genótipos de feijão carioca foram agrupados pelo método hierárquico de ligação completa. Populações segregantes, com variabilidade genética superior, podem ser obtidas com hibridações entre o genótipo ESAL 550 com genótipos do grupo 2 (LH-6, 17-4-32, R-78, H-4-5 e R-102) e/ou com genótipos do grupo 3 (FT 97-188, Cati-Taquari, CII-328, Carioca Precoce, FT 97-41, LH-11, FT 91-4067, Iapar 31, CI 102, Carioca MG, CII-54 e R-102).<br>Carioca bean genotypes (Phaseolus vulgaris L.) were evaluated in two growing seasons in Santa Maria, RS, Brazil. The objectives of this work were to evaluate which morpho-agronomic characteristics were the best descriptors, to group the genotypes in relation to genetic diversity and to determine which hybrid combinations are promissing to obtain higher segregation populations in carioca bean. From the 20 morpho-agronomic characteristics evaluated, only seven (pod rust, lodging, general note, colour of seed tegument, grain yield, 100 seed weight, height of first and final pod insertion and number of seeds per pod) showed higher contribution to genetic diversity. The evaluated carioca bean genotypes were clustered by the complete linkage method. The following hybrid combinations were promissing for obtaining segregant population with higher genetic variability: the genotype ESAL 550 with the genotype of the group 2 (LH-6, 17-4-32, R-78, H-4-5 e R-102) and genotype of the group 3 (FT 97-188, Cati-Taquari, CII-328, Carioca Precoce, FT 97-41, LH-11, FT 91-4067, Iapar 31, CI 102, Carioca MG, CII-54 and R-102)

Sequence‐Based Introgression Mapping Identifies Candidate White Mold Tolerance Genes in Common Bean

Core Ideas Sequenced‐based introgression mapping rapidly maps QTL to a physical location A highly polymorphic candidate gene associated with apoptosis maps in the WM7.1 QTL A highly polymorphic gene associated with effector recognition maps in the WM8.3 QTL White mold, caused by the necrotrophic fungus Sclerotinia sclerotiorum (Lib.) de Bary, is a major disease of common bean (Phaseolus vulgaris L.). WM7.1 and WM8.3 are two quantitative trait loci (QTL) with major effects on tolerance to the pathogen. Advanced backcross populations segregating individually for either of the two QTL, and a recombinant inbred (RI) population segregating for both QTL were used to fine map and confirm the genetic location of the QTL. The QTL intervals were physically mapped using the reference common bean genome sequence, and the physical intervals for each QTL were further confirmed by sequence‐based introgression mapping. Using whole‐genome sequence data from susceptible and tolerant DNA pools, introgressed regions were identified as those with significantly higher numbers of single‐nucleotide polymorphisms (SNPs) relative to the whole genome. By combining the QTL and SNP data, WM7.1 was located to a 660‐kb region that contained 41 gene models on the proximal end of chromosome Pv07, while the WM8.3 introgression was narrowed to a 1.36‐Mb region containing 70 gene models. The most polymorphic candidate gene in the WM7.1 region encodes a BEACH‐domain protein associated with apoptosis. Within the WM8.3 interval, a receptor‐like protein with the potential to recognize pathogen effectors was the most polymorphic gene. The use of gene and sequence‐based mapping identified two candidate genes whose putative functions are consistent with the current model of Sclerotinia pathogenicity