Biology subjects

Franco, J.

Publications and source records attributed to Franco, J..

4 recordsLinked to original sources

bioRxiv2022

Multi-omics approach reveals dysregulation of protein phosphorylation correlated with lipid metabolism in mouse fatty liver

Obesity caused by overnutrition is a major risk factor for non-alcoholic fatty liver disease (NAFLD). Several lipid intermediates such as fatty acids, glycerophospholipids and sphingolipids are implicated in NAFLD, but detailed characterization of lipids and their functional links to proteome and phosphoproteome remain to be elucidated. To characterize this complex molecular relationship, we used multi-omics approach by conducting comparative proteomic, phoshoproteomic and lipidomic analyses of high fat (HFD) and low fat (LFD) diet fed mice livers. We quantified 2447 proteins and 1339 phosphoproteins containing 1650 class I phosphosites (with localization probability > 0.75), of which 669 phosphosites were significantly different between HFD and LFD mice livers. We detected alterations of proteins associated with cellular metabolic processes such as small molecule catabolic process, monocarboxylic acid, long- and medium-chain fatty acid, and ketone body metabolic processes, and peroxisome organization. We observed significant downregulation of protein phosphorylation in HFD fed mice liver in general. Untargeted lipidomics identified upregulation of triacylglycerols, glycerolipids and ether glycerophosphocholines and downregulation of glycerophospholipids such as lysoglycerophospholipids, as well as ceramides and acylcarnitines. Analysis of differentially regulated phosphosites revealed phosphorylation dependent deregulation of insulin signaling as well as lipogenic and lipolytic pathways during HFD induced obesity. Thus, this study reveals a molecular connection between decreased protein phosphorylation and lipolysis, as well as lipid-mediated signaling in diet-induced obesity.

systems biology↗

bioRxiv2020

Identification of new insect Host Defense Peptides (HDP) from Dung Beetles (Coleoptera: Scarabaeidae) transcriptomes

IntroductionThe Coleoptera Scarabaeidae family is one of the most diverse groups of insects on the planet, living in complex microbiological environments. Their immune systems have evolved with the generation of host defense peptides but only a small number of these peptides have been characterized. MethodsIn this work two sources of information were retrieved: 1) De novo transcriptomic data from two species of neotropical Scarabidae (Dichotomius satanas and Ontophagus curvicornis); 2) Sequence data deposited in available databases. A BLAST-based search against the transcriptomes with a subset of sequences representative of the Host Defense Peptides (HDP). The HDP were described with the cecropin, defensin, attacin, and coleoptericin families; their physical/chemical and structural properties were described. ResultsThis work reports 155 novel sequences of HDP identified in 9 transcriptomes from seven species from the Coleoptera order: D. satanas (n= 76; 49.03%), O. curvicornis (n= 23; 14.83%), T. dichotomus (n= 18; 11.61%), O. nigriventris (n= 10; 6.45%), Heterochelus sp (n= 6; 3.87%), O. conspicillatum (n= 18; 11.61%) and P. japonica (n= 4; 2.58%). These sequences were identified based on similarity to known HDP insect families. New members of defensins (n= 58; 37.42%), cecropins (n= 18; 11.61%), attancins (n= 41; 26.45%) and coleoptericins (n= 38; 24.52%), with their physicochemical, structural characteristics, and sequence relationship to other insect HDP were analyzed. Conclusions155 new HDP could be identified, based on similarity to known HDP insect families on nine transcriptome sequences of seven beetle species. HighlightsO_LIThis work identified 155 novel sequences of HDP found in nine transcriptomes from seven Coleoptera species. C_LIO_LIDe novo transcriptomic data from two species of neotropical Scarabaeidae (Dichotomius satanas and Ontophagus curvicornis). C_LIO_LIIn silico prediction of physicochemical properties, structural features, sequence similarity, and antimicrobial activity of Scarabaeidae HDP. C_LI

molecular biology↗

bioRxiv2020

Citrus vascular proteomics highlights the role of peroxidases and serine proteases during Huanglongbing disease progression

Huanglongbing (HLB) is the most devastating and widespread citrus disease. All commercial citrus varieties are susceptible to the HLB-associated bacterium, Candidatus Liberibacter asiaticus (CLas), which resides in the phloem. The phloem is part of the plant vascular system and is involved in sugar transport. To investigate the plant response to CLas, we enriched for proteins surrounding the phloem in an HLB susceptible sweet orange variety, Washington navel (Citrus sinensis (L) Osbeck). Quantitative proteomics revealed global changes in the citrus proteome after CLas inoculation. Plant metabolism and translation were suppressed, while defense-related proteins such as peroxidases, proteases and protease inhibitors were induced in the vasculature. Transcript accumulation and enzymatic activity of plant peroxidases in CLas infected sweet orange varieties under greenhouse and field conditions were assessed. While peroxidase transcript accumulation was induced in CLas infected sweet orange varieties, peroxidase enzymatic activity varied. Specific serine proteases were upregulated in Washington navel in the presence of CLas based on quantitative proteomics. Subsequent activity-based protein profiling revealed increased activity of two serine proteases, and reduced activity of one protease in two C. sinensis sweet orange varieties under greenhouse and field conditions. The observations in the current study highlight global reprogramming of the citrus vascular proteome and differential regulation of enzyme classes in response to CLas infection. These results open an avenue for further investigation of diverse responses to HLB across different environmental conditions and citrus genotypes.

plant biology↗

bioRxiv2019

Genetic risk for major depressive disorder and loneliness in gender-specific associations with coronary artery disease

ImportanceEpidemiological evidence indicates that major depressive disorder (MDD) and loneliness both reduce life expectancies, but mechanisms underlying the excess morbidity are unclear. Electronic health records (EHRs) linked to genetic data offer new opportunities to address this knowledge gap.\n\nObjectiveTo determine the medical morbidity pattern associated with genetic risk factors for MDD and loneliness, two common psychological traits with adverse health outcomes.\n\nDesignPhenome-wide association study using EHRs spanning 1990 to 2017 from the Vanderbilt University Medical Center biobank, BioVU. Top associations with coronary artery disease (CAD) were replicated in the Atherosclerosis Risk in Communities (ARIC) cohort.\n\nSettingHospital-based EHR study, with replication in a population-based cohort study.\n\nParticipants18,385 genotyped adult patients in BioVU. Replication in ARIC included 7,197 genotyped participants. All participants were of European ancestry.\n\nExposuresPolygenic scores for MDD and loneliness were developed for each individual using previously published meta-GWAS summary statistics.\n\nMain Outcomes and MeasuresThe phenome-wide association study included 882 clinical diagnoses ascertained via billing codes in the EHR. ARIC included 1598 incident CAD cases.\n\nResultsBioVU patients had a median EHR length of 9.91 years. In the phenome-wide association study, polygenic scores for MDD and loneliness were significantly associated with psychiatric and cardiac phenotypes. Targeted analyses of CAD in 3,893 cases and 4,197 controls in BioVU found odds ratios of 1.11 (95% CI, 1.04-1.18; P=8.43x10-4) and 1.13 (95% CI, 1.07-1.20; P=4.51x10-6) per 1-SD increase in the polygenic scores for MDD and loneliness, respectively. Comparable hazard ratios in ARIC were 1.07 (95% CI, 0.99-1.14; P=0.07) and 1.07 (1.01-1.15; P=0.03). Across both studies, the increased risk persisted in women after adjusting for multiple conventional risk factors, a polygenic score for CAD, and psychiatric symptoms (available in BioVU). Controlling for genetic risk factors shared between MDD and loneliness, the polygenic score for loneliness conditioned on MDD remained associated with CAD risk, but the polygenic score for MDD conditioned on loneliness did not.\n\nConclusions and RelevanceGenetic risk factors for MDD and loneliness act pleiotropically to increase CAD risk in women. Continued research into the biological and clinical connections between the heart and mind is warranted.

genetics↗