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1.
Plant Cell Rep ; 43(5): 117, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38622429

RESUMEN

KEY MESSAGE: We constructed a gene expression atlas and co-expression network for potatoes and identified several novel genes associated with various agronomic traits. This resource will accelerate potato genetics and genomics research. Potato (Solanum tuberosum L.) is the world's most crucial non-cereal food crop and ranks third in food production after wheat and rice. Despite the availability of several potato transcriptome datasets at public databases like NCBI SRA, an effort has yet to be put into developing a global transcriptome atlas and a co-expression network for potatoes. The objectives of our study were to construct a global expression atlas for potatoes using publicly available transcriptome datasets, identify housekeeping and tissue-specific genes, construct a global co-expression network and identify co-expression clusters, investigate the transcriptional complexity of genes involved in various essential biological processes related to agronomic traits, and provide a web server (StCoExpNet) to easily access the newly constructed expression atlas and co-expression network to investigate the expression and co-expression of genes of interest. In this study, we used data from 2299 publicly available potato transcriptome samples obtained from 15 different tissues to construct a global transcriptome atlas. We found that roughly 87% of the annotated genes exhibited detectable expression in at least one sample. Among these, we identified 281 genes with consistent and stable expression levels, indicating their role as housekeeping genes. Conversely, 308 genes exhibited marked tissue-specific expression patterns. We exemplarily linked some co-expression clusters to important agronomic traits of potatoes, such as self-incompatibility, anthocyanin biosynthesis, tuberization, and defense responses against multiple pathogens. The dataset compiled here constitutes a new resource (StCoExpNet), which can be accessed at https://stcoexpnet.julius-kuehn.de . This transcriptome atlas and the co-expression network will accelerate potato genetics and genomics research.


Asunto(s)
Solanum tuberosum , Solanum tuberosum/genética , Solanum tuberosum/metabolismo , Fenotipo , Transcriptoma/genética , Genómica
2.
Am J Med Genet A ; 194(8): e63601, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38562122

RESUMEN

Biallelic variants in RSPRY1 have been found to result in spondyloepimetaphyseal dysplasia. Two siblings presenting with short stature, facial dysmorphism, progressive vertebral defects, small epiphysis, cupping and fraying of metaphyses, brachydactyly, and short metatarsals harbored a homozygous missense variant c.1652G>A;p.(Cys551Tyr) in the RSPRY1 gene. The phenotype in our patients resembles spondyloepimetaphyseal dysplasia, Faden-Alkuraya type. Thus, our study provides further evidence to support the association of RSPRY1 variants with spondyloepimetaphyseal dysplasia. We observed joint dislocation as a novel clinical feature of this condition.


Asunto(s)
Osteocondrodisplasias , Fenotipo , Hermanos , Humanos , Osteocondrodisplasias/genética , Osteocondrodisplasias/patología , Osteocondrodisplasias/diagnóstico , Femenino , Mutación Missense/genética , Niño , Linaje , Homocigoto , Mutación/genética
3.
Appl Environ Microbiol ; 90(5): e0026824, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38619268

RESUMEN

A new variant of Methanothermobacter wolfeii was isolated from an anaerobic digester using enrichment cultivation in anaerobic conditions. The new isolate was taxonomically identified via 16S rRNA gene sequencing and tagged as M. wolfeii BSEL. The whole genome of the new variant was sequenced and de novo assembled. Genomic variations between the BSEL strain and the type strain were discovered, suggesting evolutionary adaptations of the BSEL strain that conferred advantages while growing under a low concentration of nutrients. M. wolfeii BSEL displayed the highest specific growth rate ever reported for the wolfeii species (0.27 ± 0.03 h-1) using carbon dioxide (CO2) as unique carbon source and hydrogen (H2) as electron donor. M. wolfeii BSEL grew at this rate in an environment with ammonium (NH4+) as sole nitrogen source. The minerals content required to cultivate the BSEL strain was relatively low and resembled the ionic background of tap water without mineral supplements. Optimum growth rate for the new isolate was observed at 64°C and pH 8.3. In this work, it was shown that wastewater from a wastewater treatment facility can be used as a low-cost alternative medium to cultivate M. wolfeii BSEL. Continuous gas fermentation fed with a synthetic biogas mimic along with H2 in a bubble column bioreactor using M. wolfeii BSEL as biocatalyst resulted in a CO2 conversion efficiency of 97% and a final methane (CH4) titer of 98.5%v, demonstrating the ability of the new strain for upgrading biogas to renewable natural gas.IMPORTANCEAs a methanogenic archaeon, Methanothermobacter wolfeii uses CO2 as electron acceptor, producing CH4 as final product. The metabolism of M. wolfeii can be harnessed to capture CO2 from industrial emissions, besides producing a drop-in renewable biofuel to substitute fossil natural gas. If used as biocatalyst in new-generation CO2 sequestration processes, M. wolfeii has the potential to accelerate the decarbonization of the energy generation sector, which is the biggest contributor of CO2 emissions worldwide. Nonetheless, the development of CO2 sequestration archaeal-based biotechnology is still limited by an uncertainty in the requirements to cultivate methanogenic archaea and the unknown longevity of archaeal cultures. In this study, we report the adaptation, isolation, and phenotypic characterization of a novel variant of M. wolfeii, which is capable of maximum growth with minimal nutrients input. Our findings demonstrate the potential of this variant for the production of renewable natural gas, paving the way for the development of more efficient and sustainable CO2 sequestration processes.


Asunto(s)
Dióxido de Carbono , Methanobacteriaceae , Methanobacteriaceae/genética , Methanobacteriaceae/metabolismo , Methanobacteriaceae/crecimiento & desarrollo , Dióxido de Carbono/metabolismo , ARN Ribosómico 16S/genética , Genoma Arqueal , Filogenia , Fenotipo , Aguas Residuales/microbiología , Metano/metabolismo , Nutrientes/metabolismo
4.
Acta Derm Venereol ; 104: adv24360, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38655655

RESUMEN

The World Allergy Organization recommends probiotics in the prevention of atopic dermatitis in high-risk populations. Mutations in the filaggrin gene (FLG) result in an increased risk of atopic dermatitis through disruption of the skin keratin layer. This exploratory study investigated whether the preventive effect of maternal probiotics was evident in children with and without FLG mutations. DNA was collected from children (n = 228) from the Probiotic in the Prevention of Allergy among Children in Trondheim (ProPACT) study. Samples were analysed for 3 common FLG mutations (R501X, R2447X, and 2282del4). Overall, 7% of children had heterozygous FLG mutations; each child had only one of the 3 mutations. Mutation status had no association with atopic dermatitis (RR = 1.1; 95% CI 0.5 to 2.3). The risk ratio (RR) for having atopic dermatitis following maternal probiotics was 0.6 (95% CI 0.4 to 0.9) and RR was similar if the child expressed an FLG mutation (RR = 0.6; 95% CI 0.1 to 4.1) or wildtype FLG (RR = 0.6; 95% CI 0.4 to 0.9). The preventive  effect of probiotics for atopic dermatitis was also evident in children without FLG mutation. Larger confirmatory studies are needed.


Asunto(s)
Dermatitis Atópica , Proteínas Filagrina , Proteínas de Filamentos Intermediarios , Mutación , Probióticos , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Dermatitis Atópica/genética , Dermatitis Atópica/prevención & control , Dermatitis Atópica/diagnóstico , Suplementos Dietéticos , Análisis Mutacional de ADN , Predisposición Genética a la Enfermedad , Heterocigoto , Proteínas de Filamentos Intermediarios/genética , Fenómenos Fisiologicos Nutricionales Maternos , Fenotipo , Probióticos/uso terapéutico , Probióticos/administración & dosificación , Factores de Riesgo , Resultado del Tratamiento
5.
Integr Cancer Ther ; 23: 15347354241247061, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38641964

RESUMEN

To investigate the effect of Jiedu Xiaozheng Yin (JXY) on the polarization of macrophages in colitis-associated colon cancer (CAC). An orthotopic model of CAC was established to monitor changes in the pathological state of mice. Colon length, number of colon tumors were recorded, and indices for liver, spleen, and thymus were calculated. Hematoxylin and eosin (H&E) staining was employed to observe intestinal mucosal injury and tumor formation. Immunohistochemistry (IHC) staining was utilized to investigate the effect of JXY on M1 and M2 polarization of macrophages in the colonic mucosa of CAC mice. For in vitro experiments, RT-qPCR (Reverse Transcription-quantitative PCR) and flow cytometry were used to observe the effect of JXY on various M1-related molecules such as IL-1ß, TNF-α, iNOS, CD80, CD86, and its phagocytic function as well as M2-related molecules including Arg-1, CD206, and IL-10. Subsequently, after antagonizing the TLR4 pathway with antagonists (TAK242, PDTC, KG501, SR11302, LY294002), the expression of IL-6, TNF-α, iNOS, and IL-1ß mRNA were detected by RT-qPCR. In vivo experiments, the results showed that JXY improved the pathological condition of mice in general. And JXY treatment decreased the shortening of colon length and number of tumors as compared to non-treated CAC mice. Additionally, JXY treatment improved the lesions in the colonic tissue and induced a polarization of intestinal mucosal macrophages towards the M1 phenotype, while inhibiting polarization towards the M2 phenotype. In vitro experiments further confirmed that JXY treatment promoted the activation of macrophages towards the M1 phenotype, leading to increased expression of IL-1ß, TNF-α, iNOS, CD80, CD86, as well as enhanced phagocytic function. JXY treatment concomitantly inhibited the expression of M2-phenotype related molecules Arginase-1 (Arg-1), CD206, and IL-10. Furthermore, JXY inhibited M1-related molecules such as IL-6, TNF-α, iNOS, and IL-1ß after antagonizing the TLR4 pathway. Obviously, JXY could exhibit inhibitory effects on the development of colon tumors in mice with CAC by promoting M1 polarization through TLR4-mediated signaling and impeding M2 polarization of macrophages.


Asunto(s)
Neoplasias Asociadas a Colitis , Medicamentos Herbarios Chinos , Macrófagos , Animales , Ratones , Neoplasias Asociadas a Colitis/tratamiento farmacológico , Neoplasias Asociadas a Colitis/metabolismo , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Fenotipo , Receptor Toll-Like 4/efectos de los fármacos , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
6.
Brain Behav Immun ; 119: 120-128, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38555990

RESUMEN

BACKGROUND: Social psychoneuroimmunology suggests an interplay between social deficits (loneliness and isolation) and chronic inflammation, but the direction of these relationships remains unclear. We estimated the reciprocal associations of social deficits and social engagement with levels of C-reactive protein (CRP), compared the consistency of the findings depending on the biological sampling method used, and examined the modifying role of phenotypic and genotypic depression. METHODS: We used longitudinal nationally representative data from the US (Health and Retirement Study, 3 waves, 2006-16) and England (English Longitudinal Study of Ageing, 4 waves, 2004-18). Loneliness, social isolation, and social engagement were self-reported. CRP was measured using dried blood spots (US) and venous blood samples (England). Cross-lagged panel models were fitted and tested interactions with phenotypic depression (above-threshold depressive symptom scores) and genotypic depression (polygenic score for major depressive disorder). RESULTS: We included 15,066 participants (mean age = 66.1 years, SD = 9.8) in the US and 10,290 (66.9 years, SD = 10.5) in England. We found reciprocal associations between loneliness and CRP using dried blood spots and venous blood samples. Higher CRP predicted higher subsequent loneliness and higher loneliness predicted elevated CRP. Both phenotypic and genotypic depression modified this reciprocal association. There were also reciprocal associations for social engagement in venous blood samples: higher CRP predicted lower social engagement and greater social engagement predicted lower subsequent CRP. Associations between social isolation and CRP were inconsistent and unidirectional. CONCLUSIONS: Loneliness may increase chronic inflammation, whereas social engagement may reduce inflammation. As these relationships were reciprocal, there may be a loop between inflammation, loneliness, and social engagement. This loop was stronger in those with depression or at high genetic risk for major depressive disorder. This relationship for loneliness was present in both blood sampling methods despite contrasting methods of CRP measurement, indicating that the finding is not attributable to measurement bias in biomarkers.


Asunto(s)
Proteína C-Reactiva , Depresión , Pruebas con Sangre Seca , Inflamación , Soledad , Fenotipo , Aislamiento Social , Humanos , Masculino , Femenino , Anciano , Estudios Longitudinales , Inflamación/sangre , Soledad/psicología , Persona de Mediana Edad , Aislamiento Social/psicología , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Pruebas con Sangre Seca/métodos , Depresión/sangre , Depresión/psicología , Depresión/genética , Genotipo , Inglaterra , Trastorno Depresivo Mayor/sangre , Trastorno Depresivo Mayor/genética , Estados Unidos
7.
J Insect Sci ; 24(2)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38442352

RESUMEN

The shift to a pollen diet and the evolution of more highly organized societies, i.e., eusocial, were key milestones in bee diversification over their evolutionary history, culminating in a high dependence on feeding broods with a large variety of floral resources. Here, we hypothesized that obligatory eusocial bees have a wider diet diversity than their relatives with solitary lifestyles, and this would be related to colony size. To test both hypotheses, we surveyed diet breadth data (palynological analysis) based on the Shannon-Wiener index (H') for 85 bee taxa. We also obtained colony size for 47 eusocial bee species. These data were examined using phylogenetic comparative methods. The results support the generalist strategy as a derived trait for the bee taxa evaluated here. The dietary diversity of eusocial bees (H': 2.1, on average) was 67.5% higher than that of noneusocial bees (H': 1.21, on average). There was, however, no relationship between diet breadth and colony size, indicating that smaller colonies can harvest a pollen variety as diverse as larger colonies. Taken together, these results provide new insights into the impact of lifestyle on the diversity of collected pollen. Furthermore, this work sheds light on an advantage of living in more highly structured societies irrespective of the size of the colony.


Asunto(s)
Dieta , Polen , Abejas , Animales , Filogenia , Fenotipo
8.
Physiol Plant ; 176(2): e14247, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38499953

RESUMEN

Oilseed rape (Brassica napus) is one of the most important oil crops in the world and shows sensitivity to low phosphorus (P) availability. In many soils, organic P (Po) is the main component of the soil P pool. Po must be mineralised to Pi through phosphatases, and then taken up by plants. However, the relationship between root-secreted acid phosphatases (APase) and root morphology traits, two important P-acquisition strategies in response to P deficiency, is unclear among B. napus genotypes. This study aimed to understand their relationship and how they affect P acquisition, which is crucial for the sustainable utilisation of agricultural P resources. This study showed significant genotypic variations in root-secreted APase activity per unit root fresh weight (SAP) and total root-secreted APase activity per plant (total SAP) among 350 B. napus genotypes. Seed yield was positively correlated with total SAP but not significantly correlated with SAP. Six root traits of 18 B. napus genotypes with contrasting root biomass were compared under normal Pi, low Pi and Po. Genotypes with longer total root length (TRL) reduced SAP, but those with shorter TRL increased SAP under P deficiency. Additionally, TRL was important in P-acquisition under three P treatments, and total SAP was also important in P-acquisition under Po treatment. In conclusion, trade-offs existed between the two P-acquisition strategies among B. napus genotypes under P-deficient conditions. Total SAP was an important root trait under Po conditions. These results might help to breed B. napus with greater P-acquisition ability under low P availability conditions.


Asunto(s)
Brassica napus , Fósforo , Brassica napus/genética , Fosfatasa Ácida/genética , Fenotipo , Genotipo , Suelo
9.
Lab Invest ; 104(5): 102047, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38452902

RESUMEN

Sex differences in kidney stone formation are well known. Females generally have slightly acidic blood and higher urine pH when compared with males, which makes them more vulnerable to calcium stone formation, yet the mechanism is still unclear. We aimed to examine the role of sex in stone formation during hypercalciuria and urine alkalinization through acetazolamide and calcium gluconate supplementation, respectively, for 4 weeks in wild-type (WT) and moderately hypercalciuric [TRPC3 knockout [KO](-/-)] male and female mice. Our goal was to develop calcium phosphate (CaP) and CaP+ calcium oxalate mixed stones in our animal model to understand the underlying sex-based mechanism of calcium nephrolithiasis. Our results from the analyses of mice urine, serum, and kidney tissues show that female mice (WT and KO) produce more urinary CaP crystals, higher [Ca2+], and pH in urine compared to their male counterparts. We identified a sex-based relationship of stone-forming phenotypes (types of stones) in our mice model following urine alkalization/calcium supplementation, and our findings suggest that female mice are more susceptible to CaP stones under those conditions. Calcification and fibrotic and inflammatory markers were elevated in treated female mice compared with their male counterparts, and more so in TRPC3 KO mice compared with their WT counterparts. Together these findings contribute to a mechanistic understanding of sex-influenced CaP and mixed stone formation that can be used as a basis for determining the factors in sex-related clinical studies.


Asunto(s)
Hipercalciuria , Cálculos Renales , Ratones Noqueados , Fenotipo , Animales , Femenino , Masculino , Hipercalciuria/metabolismo , Hipercalciuria/orina , Ratones , Cálculos Renales/metabolismo , Cálculos Renales/orina , Cálculos Renales/etiología , Fosfatos de Calcio/metabolismo , Fosfatos de Calcio/orina , Concentración de Iones de Hidrógeno , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Riñón/metabolismo , Factores Sexuales , Caracteres Sexuales , Oxalato de Calcio/metabolismo , Oxalato de Calcio/orina , Canales Catiónicos TRPC/metabolismo , Canales Catiónicos TRPC/genética
10.
J Microbiol Immunol Infect ; 57(3): 385-395, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38453541

RESUMEN

BACKGROUND: Copper plays a role in urinary tract infection (UTI) and urinary copper content is increased during Proteus mirabilis UTI. We therefore investigated the effect of copper on uropathogenic P. mirabilis and the underlying mechanisms, focusing on the virulence associated aspects. METHODS: Mouse colonization, swarming/swimming assays, measurement of cell length, flagellin level and urease activity, adhesion/invasion assay, biofilm formation, killing by macrophages, oxidative stress susceptibility, OMPs analysis, determination of MICs and persister cell formation, RT-PCR and transcriptional reporter assay were performed. RESULTS: We found that copper-supplemented mice were more resistant to be colonized in the urinary tract, together with decreased swarming/swimming, ureases activity, expression of type VI secretion system and adhesion/invasion to urothelial cells and increased killing by macrophages of P. mirabilis at a sublethal copper level. However, bacterial biofilm formation and resistance to oxidative stress were enhanced under the same copper level. Of note, the presence of copper led to increased ciprofloxacin MIC and more persister cell formation against ampicillin. In addition, the presence of copper altered the outer membrane protein profile and triggered expression of RcsB response regulator. For the first time, we unveiled the pleiotropic effects of copper on uropathogenic P. mirabilis, especially for induction of bacterial two-component signaling system regulating fitness and virulence. CONCLUSION: The finding of copper-mediated virulence and fitness reinforced the importance of copper for prevention and therapeutic interventions against P. mirabilis infections. As such, this study could facilitate the copper-based strategies against UTI by P. mirabilis.


Asunto(s)
Biopelículas , Cobre , Pruebas de Sensibilidad Microbiana , Infecciones por Proteus , Proteus mirabilis , Infecciones Urinarias , Proteus mirabilis/efectos de los fármacos , Proteus mirabilis/patogenicidad , Proteus mirabilis/fisiología , Proteus mirabilis/genética , Animales , Infecciones Urinarias/microbiología , Cobre/farmacología , Ratones , Virulencia , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Infecciones por Proteus/microbiología , Femenino , Fenotipo , Antibacterianos/farmacología , Estrés Oxidativo/efectos de los fármacos , Macrófagos/microbiología , Adhesión Bacteriana/efectos de los fármacos , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo
11.
Theor Appl Genet ; 137(3): 70, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38446220

RESUMEN

Predictive breeding approaches, like phenomic or genomic selection, have the potential to increase the selection gain for potato breeding programs which are characterized by very large numbers of entries in early stages and the availability of very few tubers per entry in these stages. The objectives of this study were to (i) explore the capabilities of phenomic prediction based on drone-derived multispectral reflectance data in potato breeding by testing different prediction scenarios on a diverse panel of tetraploid potato material from all market segments and considering a broad range of traits, (ii) compare the performance of phenomic and genomic predictions, and (iii) assess the predictive power of mixed relationship matrices utilizing weighted SNP array and multispectral reflectance data. Predictive abilities of phenomic prediction scenarios varied greatly within a range of - 0.15 and 0.88 and were strongly dependent on the environment, predicted trait, and considered prediction scenario. We observed high predictive abilities with phenomic prediction for yield (0.45), maturity (0.88), foliage development (0.73), and emergence (0.73), while all other traits achieved higher predictive ability with genomic compared to phenomic prediction. When a mixed relationship matrix was used for prediction, higher predictive abilities were observed for 20 out of 22 traits, showcasing that phenomic and genomic data contained complementary information. We see the main application of phenomic selection in potato breeding programs to allow for the use of the principle of predictive breeding in the pot seedling or single hill stage where genotyping is not recommended due to high costs.


Asunto(s)
Fenómica , Solanum tuberosum , Solanum tuberosum/genética , Dispositivos Aéreos No Tripulados , Fitomejoramiento , Fenotipo
12.
Nutrients ; 16(5)2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38474824

RESUMEN

The environment of the test laboratory affects the reproducibility of treatment effects on physiological phenotypes of rodents and may be attributed to the plasticity of the epigenome due to nutrient-gene-environment interactions. Here, we explored the reproducibility of adding a multi-vitamin-mineral (MVM) mix to a nutrient-balanced high-fat (HF) diet on obesity, insulin resistance (IR), and gene expression in the tissues of adult male mice. Experiments of the same design were conducted in three independent animal facilities. Adult C57BL/6J male mice were fed an HF diet for 6 weeks (diet induced-obesity model) and then continued for 9-12 weeks on the HF diet with or without 5-fold additions of vitamins A, B1, B6, B12, Zn, and 2-fold Se. The addition of the MVM affected body weight, fat mass, gene expression, and markers of IR in all three locations (p < 0.05). However, the direction of the main effects was influenced by the interaction with the experimental location and its associated environmental conditions known to affect the epigenome. In conclusion, MVM supplementation influenced phenotypes and expression of genes related to adipose function in obese adult male mice, but the experimental location and its associated conditions were significant interacting factors. Preclinical studies investigating the relationship between diet and metabolic outcomes should acknowledge the plasticity of the epigenome and implement measures to reproduce studies in different locations.


Asunto(s)
Resistencia a la Insulina , Micronutrientes , Masculino , Animales , Ratones , Micronutrientes/uso terapéutico , Reproducibilidad de los Resultados , Ratones Endogámicos C57BL , Obesidad/metabolismo , Dieta Alta en Grasa , Fenotipo , Ratones Obesos
13.
BMC Genomics ; 25(1): 274, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38475714

RESUMEN

BACKGROUND: Tuber starch and steroidal glycoalkaloid (SGA)-related traits have been consistently prioritized in potato breeding, while allelic variation pattern of genes that underlie these traits is less explored. RESULTS: Here, we focused on the genes involved in two important metabolic pathways in the potato: starch metabolism and SGA biosynthesis. We identified 119 genes consisting of 81 involved in starch metabolism and 38 in the biosynthesis of steroidal glycoalkaloids, and discovered 96,166 allelic variants among 2,169 gene haplotypes in six autotetraploid potato genomes. Comparative analyses revealed an uneven distribution of allelic variants among gene haplotypes and that the vast majority of deleterious mutations in these genes are retained in heterozygous state in the autotetraploid potato genomes. Leveraging full-length cDNA sequencing data, we find that approximately 70% of haplotypes of the 119 genes are transcribable. Population genetic analyses identify starch and SGA biosynthetic genes that are potentially conserved or diverged between potato varieties with varying starch or SGA content. CONCLUSIONS: These results deepen the understanding of haplotypic diversity within functionally important genes in autotetraploid genomes and may facilitate functional characterization of genes or haplotypes contributing to traits related to starch and SGA in potato.


Asunto(s)
Solanum tuberosum , Solanum tuberosum/genética , Almidón/metabolismo , Fitomejoramiento , Alelos , Fenotipo , Esteroides
14.
ACS Chem Neurosci ; 15(5): 1010-1025, 2024 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-38382546

RESUMEN

Alteration of gut microbiota and microbial metabolites such as short-chain fatty acids (SCFAs) coexisted with stress-generated brain disorders, including depression. Herein, we investigated the effect of SCFAs in a treatment-resistant depression (TRD) model of rat. Rats were exposed to chronic-unpredictable mild stress (CUMS) and repeated adrenocorticotropic hormone (ACTH) injections to generate a TRD-like phenotype. The cecal contents of these animals were engrafted into healthy-recipient rats and allowed to colonize for 4 weeks (TRD-FMT group). Blood, brain, colon, fecal, and cecal samples were collected for molecular studies. Rats exposed to CUMS + ACTH showed TRD-like phenotypes in sucrose-preference (SPT), forced swim (FST), and elevated plus maze (EPM) tests. The TRD-FMT group also exhibited anxiety- and depression-like behaviors. Administration of SCFAs (acetate, propionate, and butyrate at 67.5, 25, and 40 mM, respectively) for 7 days exerted robust antidepressant and antianxiety effects by restoring the levels of SCFAs in plasma and fecal samples, and proinflammatory cytokines (TNF-α and IL-6), serotonin, GABA, norepinephrine, and dopamine in the hippocampus and/or frontal cortex of TRD and TRD-FMT animals. SCFAs treatment elevated the expression of free-fatty acid receptors 2/3, BDNF, doublecortin, and zonula-occludens, and reduced the elevated plasma levels of kynurenine and quinolinic acid and increased mucus-producing goblet cells in TRD and TRD-FMT animals. In 16S sequencing results, decreased microbial diversity in TRD rats corresponds with differences in the genus of Faecalibacterium, Anaerostipes, Allobaculum, Blautia, Peptococcus, Rombustia, Ruminococcaceae_UCG-014, Ruminococcaceae_UCG-002, Solobacterium, Subdolibacterium, and Eubacterium ventriosum. SCFAs may impart beneficial effects via modulation of tryptophan metabolism, inflammation, neurotransmitters, and microbiota-gut-brain axis in TRD rats.


Asunto(s)
Ansiedad , Depresión , Ratas , Animales , Depresión/tratamiento farmacológico , Depresión/metabolismo , Ansiedad/tratamiento farmacológico , Ansiedad/metabolismo , Ácidos Grasos Volátiles , Fenotipo , Hormona Adrenocorticotrópica , Suplementos Dietéticos , Estrés Psicológico/metabolismo
15.
Allergy ; 79(4): 908-923, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38311961

RESUMEN

BACKGROUND: Pollen allergy poses a significant health and economic burden in Europe. Disease patterns are relatively homogeneous within Central and Northern European countries. However, no study broadly assessed the features of seasonal allergic rhinitis (SAR) across different Southern European countries with a standardized approach. OBJECTIVE: To describe sensitization profiles and clinical phenotypes of pollen allergic patients in nine Southern European cities with a uniform methodological approach. METHODS: Within the @IT.2020 multicenter observational study, pediatric and adult patients suffering from SAR were recruited in nine urban study centers located in seven countries. Clinical questionnaires, skin prick tests (SPT) and specific IgE (sIgE) tests with a customized multiplex assay (Euroimmun Labordiagnostika, Lübeck, Germany) were performed. RESULTS: Three hundred forty-eight children (mean age 13.1 years, SD: 2.4 years) and 467 adults (mean age 35.7 years SD: 10.0 years) with a predominantly moderate to severe, persistent phenotype of SAR were recruited. Grass pollen major allergenic molecules (Phl p 1 and/or Phl p 5) ranged among the top three sensitizers in all study centers. Sensitization profiles were very heterogeneous, considering that patients in Rome were highly poly-sensitized (sIgE to 3.8 major allergenic molecules per patient), while mono-sensitization was prominent and heterogeneous in other cities, such as Marseille (sIgE to Cup a 1: n = 55/80, 68.8%) and Messina (sIgE to Par j 2: n = 47/82, 57.3%). Co-sensitization to perennial allergens, as well as allergic comorbidities also broadly varied between study centers. CONCLUSIONS: In Southern European countries, pollen allergy is heterogeneous in terms of sensitization profiles and clinical manifestations. Despite the complexity, a unique molecular, multiplex, and customized in-vitro IgE test detected relevant sensitization in all study centers. Nevertheless, this geographical diversity in pollen allergic patients imposes localized clinical guidelines and study protocols for clinical trials of SAR in this climatically complex region.


Asunto(s)
Hipersensibilidad , Rinitis Alérgica Estacional , Adulto , Humanos , Niño , Adolescente , Rinitis Alérgica Estacional/diagnóstico , Rinitis Alérgica Estacional/epidemiología , Inmunoglobulina E , Alérgenos , Polen , Pruebas Cutáneas , Fenotipo
16.
Neuropediatrics ; 55(2): 129-134, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38365198

RESUMEN

PGAP2 gene has been known to be the cause of "hyperphosphatasia, mental retardation syndrome-3" (HPMRS3). To date, 14 pathogenic variants in PGAP2 have been identified as the cause of this syndrome in 24 patients described in single-case reports or small clinical series with pan-ethnic distribution. We aim to present a pediatric PGAP2-mutated case, intending to further expand the clinical phenotype of the syndrome and to report our experience on a therapeutic approach to drug-resistant epilepsy.We present the clinical, neuroradiological, and genetic characterization of a Caucasian pediatric subject with biallelic pathogenic variants in the PGAP2 gene revealed by next generation sequencing analysis.We identified a subject who presented with global developmental delay and visual impairment. Brain magnetic resonance imaging showed mild hypoplasia of the inferior cerebellar vermis and corpus callosum and mild white matter reduction. Laboratory investigations detected an increase in alkaline phosphatase. At the age of 13 months, he began to present epileptic focal seizures with impaired awareness, which did not respond to various antiseizure medications. Electroencephalogram (EEG) showed progressive background activity disorganization and multifocal epileptic abnormalities. Treatment with high-dose pyridoxine showed partial benefit, but the persistence of seizures and the lack of EEG amelioration prompted us to introduce ketogenic diet treatment.Our case provides a further phenotypical expansion of HPMRS3 to include developmental and epileptic encephalopathy. Due to the limited number of patients reported so far, the full delineation of the clinical spectrum of HPMRS3 and indications for precision medicine would benefit from the description of new cases and their follow-up evaluations.


Asunto(s)
Anomalías Múltiples , Epilepsia , Discapacidad Intelectual , Humanos , Lactante , Masculino , Anomalías Múltiples/patología , Encéfalo/patología , Epilepsia/diagnóstico por imagen , Epilepsia/tratamiento farmacológico , Epilepsia/genética , Discapacidad Intelectual/genética , Discapacidad Intelectual/patología , Fenotipo , Convulsiones , Síndrome
17.
BMJ Case Rep ; 17(2)2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38350705

RESUMEN

Bartter syndrome (BS) is a rare genetic tubulopathy affecting the loop of Henle leading to salt wasting. It is commonly seen in utero or in the early neonatal period. Rare cases of acquired BS are reported in association with infections like tuberculosis, granulomatous conditions like sarcoidosis, autoimmune diseases and drugs. The mainstay of management includes potassium, calcium and magnesium supplementation. We report the case of a woman in her 50s with a history of type 2 diabetes mellitus for the last 10 years, who presented with diabetic foot ulcers and generalised weakness with ECG changes suggestive of hypokalaemia. She had severe hypokalaemia with high urine potassium excretion and hypochloraemic metabolic alkalosis. She poorly responded to intravenously administered potassium supplements and had persistent hypokalaemia. On further evaluation of the persistent hypokalaemia, a diagnosis of idiopathic Bartter-like phenotype was made. She responded well to tablet indomethacin and is presently asymptomatic and is being maintained on tablet indomethacin after 6 months of follow-up.


Asunto(s)
Síndrome de Bartter , Diabetes Mellitus Tipo 2 , Hipopotasemia , Recién Nacido , Femenino , Humanos , Síndrome de Bartter/complicaciones , Síndrome de Bartter/diagnóstico , Síndrome de Bartter/tratamiento farmacológico , Hipopotasemia/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Fenotipo , Potasio/metabolismo , Indometacina/uso terapéutico , Comprimidos
18.
Expert Opin Pharmacother ; 25(3): 301-313, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38393835

RESUMEN

INTRODUCTION: Fragile X syndrome (FXS) is the most common inherited cause of Intellectual Disability. There is a broad phenotype that includes deficits in cognition and behavioral changes, alongside physical characteristics. Phenotype depends upon the level of mutation in the FMR1 (fragile X messenger ribonucleoprotein 1) gene. The molecular understanding of the impact of the FMR1 gene mutation provides an opportunity to target treatment not only at symptoms but also on a molecular level. METHODS: We conducted a systematic review to provide an up-to-date narrative summary of the current evidence for pharmacological treatment in FXS. The review was restricted to randomized, blinded, placebo-controlled trials. RESULTS: The outcomes from these studies are discussed and the level of evidence assessed against validated criteria. The initial search identified 2377 articles, of which 16 were included in the final analysis. CONCLUSION: Based on this review to date there is limited data to support any specific pharmacological treatments, although the data for cannabinoids are encouraging in those with FXS and in future developments in gene therapy may provide the answer to the search for precision medicine. Treatment must be person-centered and consider the combination of medical, genetic, cognitive, and emotional challenges.


Asunto(s)
Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil , Síndrome del Cromosoma X Frágil , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Cannabinoides/uso terapéutico , Cannabinoides/farmacología , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/tratamiento farmacológico , Síndrome del Cromosoma X Frágil/genética , Terapia Genética/métodos , Mutación , Fenotipo , Medicina de Precisión/métodos
19.
J Autoimmun ; 144: 103174, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38377868

RESUMEN

In many autoimmune diseases, autoantigen-specific Th17 cells play a pivotal role in disease pathogenesis. Th17 cells can transdifferentiate into other T cell subsets in inflammatory conditions, however, there have been no attempts to target Th17 cell plasticity using vaccines. We investigated if autoantigen-specific Th17 cells could be specifically targeted using a therapeutic vaccine approach, where antigen was formulated in all-trans retinoic acid (ATRA)-containing liposomes, permitting co-delivery of antigen and ATRA to the same target cell. Whilst ATRA was previously found to broadly reduce Th17 responses, we found that antigen formulated in ATRA-containing cationic liposomes only inhibited Th17 cells in an antigen-specific manner and not when combined with an irrelevant antigen. Furthermore, this approach shifted existing Th17 cells away from IL-17A expression and transcriptomic analysis of sorted Th17 lineage cells from IL-17 fate reporter mice revealed a shift of antigen-specific Th17 cells to exTh17 cells, expressing functional markers associated with T cell regulation and tolerance. In the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, vaccination with myelin-specific (MOG) antigen in ATRA-containing liposomes reduced Th17 responses and alleviated disease. This highlights the potential of therapeutic vaccination for changing the phenotype of existing Th17 cells in the context of immune mediated diseases.


Asunto(s)
Encefalomielitis Autoinmune Experimental , Células Th17 , Ratones , Animales , Liposomas/metabolismo , Tretinoina/farmacología , Tretinoina/metabolismo , Autoantígenos/metabolismo , Adyuvantes Inmunológicos , Inmunización , Vacunación , Fenotipo , Ratones Endogámicos C57BL , Células TH1
20.
J Clin Invest ; 134(4)2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38357931

RESUMEN

Nicotinamide adenine dinucleotide (NAD) is essential for embryonic development. To date, biallelic loss-of-function variants in 3 genes encoding nonredundant enzymes of the NAD de novo synthesis pathway - KYNU, HAAO, and NADSYN1 - have been identified in humans with congenital malformations defined as congenital NAD deficiency disorder (CNDD). Here, we identified 13 further individuals with biallelic NADSYN1 variants predicted to be damaging, and phenotypes ranging from multiple severe malformations to the complete absence of malformation. Enzymatic assessment of variant deleteriousness in vitro revealed protein domain-specific perturbation, complemented by protein structure modeling in silico. We reproduced NADSYN1-dependent CNDD in mice and assessed various maternal NAD precursor supplementation strategies to prevent adverse pregnancy outcomes. While for Nadsyn1+/- mothers, any B3 vitamer was suitable to raise NAD, preventing embryo loss and malformation, Nadsyn1-/- mothers required supplementation with amidated NAD precursors (nicotinamide or nicotinamide mononucleotide) bypassing their metabolic block. The circulatory NAD metabolome in mice and humans before and after NAD precursor supplementation revealed a consistent metabolic signature with utility for patient identification. Our data collectively improve clinical diagnostics of NADSYN1-dependent CNDD, provide guidance for the therapeutic prevention of CNDD, and suggest an ongoing need to maintain NAD levels via amidated NAD precursor supplementation after birth.


Asunto(s)
Ligasas de Carbono-Nitrógeno con Glutamina como Donante de Amida-N , NAD , Femenino , Embarazo , Humanos , Ratones , Animales , NAD/metabolismo , Niacinamida , Fenotipo , Metaboloma , Ligasas de Carbono-Nitrógeno con Glutamina como Donante de Amida-N/metabolismo
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