An Integrated NMR, LC-DAD-MS, LC-QTOF Metabolomic Characterization of Sartoria hedysaroides: Correlation of Antioxidant and Enzyme Inhibitory Activity with Chemical Composition by Multivariate Data Analysis

Sartoria hedysaroides Boiss and Heldr. (Fabaceae) is an endemic plant of Turkey that has received little scientific consideration so far. In the present study, the chemical profiles of extracts from the aerial part and roots of S. hedysaroides obtained using solvents with different polarities were analyzed combining integrated NMR, LC-DAD-MSn, and LC-QTOF methods. In vitro antioxidant and enzyme inhibitory activities were evaluated, and the results were combined with chemical data using multivariate approaches. Phenolic acids, flavonoids, ellagitannins, and coumarins were identified and quantified in the extracts of aerial part and roots. Methanolic extract of S. hedysaroides aerial part showed the highest phenolic content and the highest antioxidant activity and cupric ion reducing antioxidant capacity. Dichloromethane extract of S. hedysaroides roots showed the highest inhibition of butyryl cholinesterase, while methanolic extract of S. hedysaroides aerial part was the most active tyrosinase inhibitor. Multivariate data analysis allowed us to observe a good correlation between phenolic compounds, especially caffeoylquinic derivatives and flavonoids and the antioxidant activity of extracts. Acetylcholinesterase inhibition was correlated with the presence of caffeoylquinic acids and coumarins. Overall, the present study appraised the biological potential of understudied S. hedysaroides, and provided a comprehensive approach combining metabolomic characterization of plant material and multivariate data analysis for the correlation of chemical data with results from multi-target biological assays

TEPEE/GReAT (General Relativity Accuracy Test in an Einstein Elevator): Ready to start

TEPEE/GReAT is an experiment aimed at testing the principle of equivalence at a level of accuracy equal to 5 parts in 1015 by means of a differential acceleration detector free falling inside a co-moving, cryogenic, evacuated capsule, released from a stratospheric balloon. The detector is spun about a horizontal axis during the fall in order to modulate the equivalence principle violation signal at the spin frequency. Thanks to the recent funding of the Italian side, the project is ready to enter its second phase. The main activities related to detector prototype (both non-cryogenic and cryogenic versions) development and testing, free-fall tests, signal extraction from noise (in particular related to the common-mode rejection factor) and flight model requirements are discussed

The relevance of mitochondrial DNA variants fluctuation during reprogramming and neuronal differentiation of human iPSCs

The generation of inducible pluripotent stem cells (iPSCs) is a revolutionary technique allowing production of pluripotent patient-specific cell lines used for disease modeling, drug screening, and cell therapy. Integrity of nuclear DNA (nDNA) is mandatory to allow iPSCs utilization, while quality control of mitochondrial DNA (mtDNA) is rarely included in the iPSCs validation process. In this study, we performed mtDNA deep sequencing during the transition from parental fibroblasts to reprogrammed iPSC and to differentiated neuronal precursor cells (NPCs) obtained from controls and patients affected by mitochondrial disorders. At each step, mtDNA variants, including those potentially pathogenic, fluctuate between emerging and disappearing, and some having functional implications. We strongly recommend including mtDNA analysis as an unavoidable assay to obtain fully certified usable iPSCs and NPCs

Spectral Theory of Sparse Non-Hermitian Random Matrices

Sparse non-Hermitian random matrices arise in the study of disordered physical systems with asymmetric local interactions, and have applications ranging from neural networks to ecosystem dynamics. The spectral characteristics of these matrices provide crucial information on system stability and susceptibility, however, their study is greatly complicated by the twin challenges of a lack of symmetry and a sparse interaction structure. In this review we provide a concise and systematic introduction to the main tools and results in this field. We show how the spectra of sparse non-Hermitian matrices can be computed via an analogy with infinite dimensional operators obeying certain recursion relations. With reference to three illustrative examples --- adjacency matrices of regular oriented graphs, adjacency matrices of oriented Erd\H{o}s-R\'{e}nyi graphs, and adjacency matrices of weighted oriented Erd\H{o}s-R\'{e}nyi graphs --- we demonstrate the use of these methods to obtain both analytic and numerical results for the spectrum, the spectral distribution, the location of outlier eigenvalues, and the statistical properties of eigenvectors.Comment: 60 pages, 10 figure

Desenvolvimento do Calopogonium muconoides em latossolo de cerrado sob diferentes correções de fertilidade.

Foram tomadas de um mesmo contínuo de latossolo vermelho-escuro amostras de três locais para pesquisa que resultaram em quatro tratamentos: a - Testemunha (LE original sob mata); b - LE original sob mata + 40t ha-1 de esterco bovino; c - LE cultivado em declive; e d - LE cultivado com controle de erosão. Cada solo recebeu três níveis de calagem de acordo com a recomendação oficial para o Estado de Goiás (0, 1 e 2t ha-1). A planta indicadora foi o Calopogonium muconoides. O delineamento experimental foi o de blocos ao acaso, em esquema fatorial 3x4, três níveis de calcário e quatro amostras, de solos, com quatro repetições. Foram observados o desenvolvimento de planta através da altura, os pesos verde e seco, e o comprimento da raiz. Foram também observados os efeitos dos tratamentos nos nutrientes residuais no solo e na concentração foliar de nutriente e no complexo sortivo do solo. A produção e o desenvolvimento do Calopogonium responderam aos níveis de fertilidade do solo, mas não responderam à calagem. Tanto a fertilidade quanto a calagem afetaram a absorção de nutrientes, a fertilidade residual após acolheita e o complexo sortivo do solo

SETBP1 variants outside the degron disrupt DNA-binding and transcription independent of protein abundance to cause a heterogeneous neurodevelopmental disorder

Germline de novo SETBP1 variants cause clinically distinct and heterogeneous neurodevelopmental disorders. Heterozygous missense variants at a hotspot encoding a canonical degron lead to SETBP1 accumulation and Schinzel-Giedion syndrome (SGS), a rare severe developmental disorder involving multisystem malformations. Heterozygous loss-of-function variants result in SETBP1 haploinsufficiency disorder which is phenotypically much milder than SGS. Following an initial description of four individuals with atypical SGS carrying heterozygous missense variants adjacent to the degron, a few individual cases of variants outside the degron were reported. Due to the lack of systematic investigation of genotype-phenotype associations of different types of SETBP1 variants, and limited understanding of the roles of the gene in brain development, the extent of clinical heterogeneity and how this relates to underlying pathophysiological mechanisms remain elusive, imposing challenges for diagnosis and patient care. Here, we present a comprehensive investigation of the largest cohort to-date of individuals carrying SETBP1 missense variants outside the degron (n=18, including one in-frame deletion). We performed thorough clinical and speech phenotyping with functional follow-up using cellular assays and transcriptomics. Our findings suggest that such variants cause a clinically and functionally variable developmental syndrome, showing only partial overlaps with classical SGS and SETBP1 haploinsufficiency disorder, and primarily characterised by intellectual disability, epilepsy, speech and motor impairment. We provide evidence of loss-of-function pathophysiological mechanisms impairing ubiquitination, DNA-binding and transcription. In contrast to SGS and SETBP1 haploinsufficiency, these effects are independent of protein abundance. Overall, our study provides important novel insights into diagnosis, patient care and aetiology of SETBP1-related disorders