Polygenic inheritance plays a central role in Parkinson disease (PD). A priority in elucidating PD etiology lies in defining the biological basis of genetic risk. Unraveling how risk leads to ...disruption will yield disease-modifying therapeutic targets that may be effective. Here, we utilized a high-throughput and hypothesis-free approach to determine biological processes underlying PD using the largest currently available cohorts of genetic and gene expression data from International Parkinson’s Disease Genetics Consortium (IPDGC) and the Accelerating Medicines Partnership-Parkinson’s disease initiative (AMP-PD), among other sources. We applied large-scale gene-set specific polygenic risk score (PRS) analyses to assess the role of common variation on PD risk focusing on publicly annotated gene sets representative of curated pathways. We nominated specific molecular sub-processes underlying protein misfolding and aggregation, post-translational protein modification, immune response, membrane and intracellular trafficking, lipid and vitamin metabolism, synaptic transmission, endosomal–lysosomal dysfunction, chromatin remodeling and apoptosis mediated by caspases among the main contributors to PD etiology. We assessed the impact of rare variation on PD risk in an independent cohort of whole-genome sequencing data and found evidence for a burden of rare damaging alleles in a range of processes, including neuronal transmission-related pathways and immune response. We explored enrichment linked to expression cell specificity patterns using single-cell gene expression data and demonstrated a significant risk pattern for dopaminergic neurons, serotonergic neurons, hypothalamic GABAergic neurons, and neural progenitors. Subsequently, we created a novel way of building de novo pathways by constructing a network expression community map using transcriptomic data derived from the blood of PD patients, which revealed functional enrichment in inflammatory signaling pathways, cell death machinery related processes, and dysregulation of mitochondrial homeostasis. Our analyses highlight several specific promising pathways and genes for functional prioritization and provide a cellular context in which such work should be done.
Phytophthora citrophthora causes serious losses in Citrus fruits through brown rot lesion. The effect of infection with P. citrophthora on Citrus sinensis (cv. Valencia Late) fruits was studied, with ...particular reference to the levels of the flavanones hesperidin and isonaringin and the polymethoxyflavones sinensetin, nobiletin, tangeretin, and heptamethoxyflavone, because flavonoids are most probably involved as natural defense or resistance mechanisms in this genus. Changes in the levels of these flavonoids were detected after infection. The hesperidin and isonaringin contents fell by 13 and 67%, respectively, whereas the contents of their corresponding aglycons, hesperetin and naringenin, increased, suggesting the hydrolyzing effect of this fungus on the glycosylated flavanones. The heptamethoxyflavone, nobiletin, sinensetin, and tangeretin levels increased by 48, 28, 26, and 24%, respectively. The in vitro study revealed that these compounds acted as antifungal agents, the most active being the aglycons (naringenin and hesperetin), followed by the polymethoxyflavones and flavanone glycosides. The participation of these flavonoids in the defense mechanism of this Citrus species is discussed. Keywords: Phytophthora citrophthora; Citrus sinensis; polymethoxyflavones; flavanones
Abstract Weighted Gene Co-expression Network Analysis (WGCNA) is a widely used approach for the generation of gene co-expression networks. However, networks generated with this tool usually create ...large modules with a large set of functional annotations hard to decipher. We have developed TGCN, a new method to create Targeted Gene Co-expression Networks. This method identifies the transcripts that best predict the trait of interest based on gene expression using a refinement of the LASSO regression. Then, it builds the co-expression modules around those transcripts. Algorithm properties were characterized using the expression of 13 brain regions from the Genotype-Tissue Expression project. When comparing our method with WGCNA, TGCN networks lead to more precise modules that have more specific and yet rich biological meaning. Then, we illustrate its applicability by creating an APP -TGCN on The Religious Orders Study and Memory and Aging Project dataset, aiming to identify the molecular pathways specifically associated with APP role in Alzheimer’s disease. Main biological findings were further validated in two independent cohorts. In conclusion, we provide a new framework that serves to create targeted networks that are smaller, biologically relevant and useful in high throughput hypothesis driven research. The TGCN R package is available on Github: https://github.com/aliciagp/TGCN .
Labor market indicator for Colombia Cristiano-Botia, Deicy J; Hernandez-Bejarano, Manuel Dario; Ramos-Veloza, Mario A
Latin American economic review,
06/2021, Letnik:
30, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Although the unemployment rate is traditionally used to diagnose the current state of the labor market, this indicator does not reflect the existence of asymmetries, mobility costs, and rigidities ...which impede labor to freely flow over the business cycle. Thus, to get a better portrait of the momentum, we construct the Labor Market Indicator (LMI) focusing on the cyclical similarities of eighteen time series from the Colombian household, industrial, and opinion surveys between 2001 and 2019. Our indicator summarizes the growth cycle of the labor market and its evolution is closely related to the output and unemployment GAP. This indicator is useful for policy analysis as it is useful to forecast headline inflation, it also complements the diagnosis of the current momentum of the labor market, the general economic activity, and the characterization of economic phases and turning points.
The effect of UV irradiation on the levels of the flavanone, naringin, and the polymethoxyflavone, tangeretin, in the peel of Citrus aurantium fruits is described, as changes in the synthesis and/or ...accumulation of these compounds after infection with Penicillium digitatum. The growth of P. digitatum on previously irradiated fruit was reduced by up to 45%. Changes in flavonoid levels were detected, associated with inhibition of fungus growth, the naringin content falling by 69% and tangeretin levels increasing by 70%. The possible participation of naringin and tangeretin in the defence mechanism of this Citrus species is discussed.PUBLICATION ABSTRACT
The total phenol levels in different olive organs and tissues are studied. The HPLC-MS studies point to the presence of oleuropein, catechin and tyrosol as some of the main phenolic compounds in ...these extracts. The effect of Brotomax treatment on phenolic compound levels in this plant and the possible role of these compounds as antifungal agents against
Phytophthora sp. are also studied. An increase in the total phenol content of leaves and stems was observed 120 days after treatment with 0.3% Brotomax. The cortex was the stem tissue which showed the greatest accumulation of these secondary compounds. An in vitro study of the inhibitory effect of these compounds on fungal growth revealed that tyrosol was the most active agent, followed by catechin and oleuropein, their fungitoxic effect being greater when they acted synergically.
The production of the steroidal sapogenin, diosgenin, by callus cultures of
Trigonella foenum-graecum L. (fenugreek) is described. The levels of this secondary compound were examined by high ...performance liquid chromatography with a diode-array detector, and its identity was confirmed by mass spectrometry. The levels of diosgenin detected in leaf callus exceeded the levels detected in stem and root calli. The diosgenin levels accumulated in leaf, stem and root calli at 45 days (maximum production) represent 22, 10 and 27%, respectively, of the levels detected in the corresponding organs of the mother plant at 45 days.
The biosynthesis of scoparone (6,7-dimethoxycoumarin) was associated with resistance of mature fruits of tangelo Nova, Citrus aurantium, and Citrus paradisi to infection by Phytophthora parasitica. ...Levels of scoparone increased by treating fruit with Brotomax, which also enhanced the resistance of fruit to the fungus. Lesion development was reduced by as much as 40%. Scoparone is therefore proposed as a possible phytoalexin in fruits of these cultivars. Keywords: Citrus; coumarin; phytoalexin; scoparone
The effect of indole-3-acetic acid (10
−4 and 10
−5 M), gibberellic acid (10
−4 and 10
−5 M) and ethephon (50 ppm) as an ethylene releasing compound, on the diosgenin synthesis and/or accumulation ...process and their effects on the growth of
Trigonella foenum-graecum plants were investigated. Treatment with 10
−5 and 10
−4 M gibberellic acid led to 43 and 19% increases, respectively, of diosgenin in 30-day-old whole plants. These increases might be associated with the action that this growth regulator has in stimulating plant growth and the biosynthetic pathway of this sapogenin. A smaller increase was obtained with the 10
−5 M indole-3-acetic acid treatment (6%, in 30 day-old plants), probably due to a stimulation of the biosynthetic pathway, alone, since no effect on growth was observed. Treatment with 50 ppm ethephon increased the diosgenin levels observed in the leaves of 15- and 30-day-old plants, growth of the whole plant being substantially reduced at 30 days in comparison with the growth observed in control plants. These figures reflect a 77% increase in diosgenin levels in 15-day-old plants and a decrease of 68% in 30-day-old plants.
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