Genetic diversity of Phytophthora infestans in the Northern Andean region.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: Phytophthora infestans (Mont.) de Bary, the causal agent of potato late blight, is responsible for tremendous crop losses worldwide. Countries in the northern part of the Andes dedicate a large proportion of the highlands to the production of potato, and more recently, solanaceous fruits such as cape gooseberry (Physalis peruviana) and tree tomato (Solanum betaceum), all of which are hosts of this oomycete. In the Andean region, P. infestans populations have been well characterized in Ecuador and Peru, but are poorly understood in Colombia and Venezuela. To understand the P. infestans population structure in the Northern part of the Andes, four nuclear regions (ITS, Ras, β-tubulin and Avr3a) and one mitochondrial (Cox1) region were analyzed in isolates of P. infestans sampled from different hosts in Colombia and Venezuela. RESULTS: Low genetic diversity was found within this sample of P. infestans isolates from crops within several regions of Colombia and Venezuela, revealing the presence of clonal populations of the pathogen in this region. We detected low frequency heterozygotes, and their distribution patterns might be a consequence of a high migration rate among populations with poor effective gene flow. Consistent genetic differentiation exists among isolates from different regions. CONCLUSIONS: The results here suggest that in the Northern Andean region P. infestans is a clonal population with some within-clone variation. P. infestans populations in Venezuela reflect historic isolation that is being reinforced by a recent self-sufficiency of potato seeds. In summary, the P. infestans population is mainly shaped by migration and probably by the appearance of variants of key effectors such as Avr3a

Pathogenic variants in the human m(6)A reader YTHDC2 are associated with primary ovarian insufficiency

Primary ovarian insufficiency (POI) affects 1% of women and carries significant medical and psychosocial sequelae. Approximately 10% of POI has a defined genetic cause, with most implicated genes relating to biological processes involved in early fetal ovary development and function. Recently, Ythdc2, an RNA helicase and N6-methyladenosine reader, has emerged as a regulator of meiosis in mice. Here, we describe homozygous pathogenic variants in YTHDC2 in 3 women with early-onset POI from 2 families: C. 2567C>G, p.P856R in the helicase-associated (HA2) domain and c.1129G>T, p.E377*. We demonstrated that YTHDC2 is expressed in the developing human fetal ovary and is upregulated in meiotic germ cells, together with related meiosisassociated factors. The p.P856R variant resulted in a less flexible protein that likely disrupted downstream conformational kinetics of the HA2 domain, whereas the p.E377*variant truncated the helicase core. Taken together, our results reveal that YTHDC2 is a key regulator of meiosis in humans and pathogenic variants within this gene are associated with POI

Diversidad genética de Phytophthora infestans en la región andina norte

Background Phytophthora infestans (Mont.) de Bary, the causal agent of potato late blight, is responsible for tremendous crop losses worldwide. Countries in the northern part of the Andes dedicate a large proportion of the highlands to the production of potato, and more recently, solanaceous fruits such as cape gooseberry (Physalis peruviana) and tree tomato (Solanum betaceum), all of which are hosts of this oomycete. In the Andean region, P. infestans populations have been well characterized in Ecuador and Peru, but are poorly understood in Colombia and Venezuela. To understand the P. infestans population structure in the Northern part of the Andes, four nuclear regions (ITS, Ras, ?-tubulin and Avr3a) and one mitochondrial (Cox1) region were analyzed in isolates of P. infestans sampled from different hosts in Colombia and Venezuela. Results Low genetic diversity was found within this sample of P. infestans isolates from crops within several regions of Colombia and Venezuela, revealing the presence of clonal populations of the pathogen in this region. We detected low frequency heterozygotes, and their distribution patterns might be a consequence of a high migration rate among populations with poor effective gene flow. Consistent genetic differentiation exists among isolates from different regions. Conclusions The results here suggest that in the Northern Andean region P. infestans is a clonal population with some within-clone variation. P. infestans populations in Venezuela reflect historic isolation that is being reinforced by a recent self-sufficiency of potato seeds. In summary, the P. infestans population is mainly shaped by migration and probably by the appearance of variants of key effectors such as Avr3a

Diversidad genética de Phytophthora infestans en la región andina norte

Background Phytophthora infestans (Mont.) de Bary, the causal agent of potato late blight, is responsible for tremendous crop losses worldwide. Countries in the northern part of the Andes dedicate a large proportion of the highlands to the production of potato, and more recently, solanaceous fruits such as cape gooseberry (Physalis peruviana) and tree tomato (Solanum betaceum), all of which are hosts of this oomycete. In the Andean region, P. infestans populations have been well characterized in Ecuador and Peru, but are poorly understood in Colombia and Venezuela. To understand the P. infestans population structure in the Northern part of the Andes, four nuclear regions (ITS, Ras, ?-tubulin and Avr3a) and one mitochondrial (Cox1) region were analyzed in isolates of P. infestans sampled from different hosts in Colombia and Venezuela. Results Low genetic diversity was found within this sample of P. infestans isolates from crops within several regions of Colombia and Venezuela, revealing the presence of clonal populations of the pathogen in this region. We detected low frequency heterozygotes, and their distribution patterns might be a consequence of a high migration rate among populations with poor effective gene flow. Consistent genetic differentiation exists among isolates from different regions. Conclusions The results here suggest that in the Northern Andean region P. infestans is a clonal population with some within-clone variation. P. infestans populations in Venezuela reflect historic isolation that is being reinforced by a recent self-sufficiency of potato seeds. In summary, the P. infestans population is mainly shaped by migration and probably by the appearance of variants of key effectors such as Avr3a

Mitochondrial transfer from MSCs to T cells induces Treg differentiation and restricts inflammatory response

Mesenchymal stem cells (MSCs) have fueled ample translation for the treatment of immune-mediated diseases. They exert immunoregulatory and tissue-restoring effects. MSC-mediated transfer of mitochondria (MitoT) has been demonstrated to rescue target organs from tissue damage, yet the mechanism remains to be fully resolved. Therefore, we explored the effect of MitoT on lymphoid cells. Here, we describe dose-dependent MitoT from mitochondria-labeled MSCs mainly to CD4(+) T cells, rather than CD8(+) T cells or CD19(+) B cells. Artificial transfer of isolated MSC-derived mitochondria increases the expression of mRNA transcripts involved in T-cell activation and T regulatory cell differentiation including FOXP3, IL2RA, CTLA4, and TGF beta 1, leading to an increase in a highly suppressive CD25(+)FoxP3(+) population. In a GVHD mouse model, transplantation of MitoT-induced human T cells leads to significant improvement in survival and reduction in tissue damage and organ T CD4(+), CD8(+), and IFN-gamma(+) expressing cell infiltration. These findings point to a unique CD4(+) T-cell reprogramming mechanism with pre-clinical proof-of-concept data that pave the way for the exploration of organelle-based therapies in immune diseases.National Agency for Investigation and Development: ANID (Agencia Nacional de Investigacion y Desarrollo) 1170852 15130011 PAI7917002

Mitochondrial transfer from MSCs to T cells induces Treg differentiation and restricts inflammatory response

Mesenchymal stem cells (MSCs) have fueled ample translation for the treatment of immune-mediated diseases. They exert immunoregulatory and tissue-restoring effects. MSC-mediated transfer of mitochondria (MitoT) has been demonstrated to rescue target organs from tissue damage, yet the mechanism remains to be fully resolved. Therefore, we explored the effect of MitoT on lymphoid cells. Here, we describe dose-dependent MitoT from mitochondria-labeled MSCs mainly to CD4(+) T cells, rather than CD8(+) T cells or CD19(+) B cells. Artificial transfer of isolated MSC-derived mitochondria increases the expression of mRNA transcripts involved in T-cell activation and T regulatory cell differentiation including FOXP3, IL2RA, CTLA4, and TGF beta 1, leading to an increase in a highly suppressive CD25(+)FoxP3(+) population. In a GVHD mouse model, transplantation of MitoT-induced human T cells leads to significant improvement in survival and reduction in tissue damage and organ T CD4(+), CD8(+), and IFN-gamma(+) expressing cell infiltration. These findings point to a unique CD4(+) T-cell reprogramming mechanism with pre-clinical proof-of-concept data that pave the way for the exploration of organelle-based therapies in immune diseases.National Agency for Investigation and Development: ANID (Agencia Nacional de Investigacion y Desarrollo) 1170852 15130011 PAI7917002