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Type 1 diabetes (T1D) is an autoimmune disease characterized by a progressive destruction of β-cells and several candidate genes associated with T1D have been linked to innate immunity. Recently, N6-methyladenosine (m6A) has been shown to modulate human β-cell biology and to target type I interferons. Here, we focused on the contribution of m6A mRNA methylation in modulating innate immunity and β-cell destruction. Immune cells contribute to β-cell apoptosis by the release of pro-inflammatory cytokines during the onset of T1D. We assessed whether m6A abundance or expression of m6A modulators was altered in human islets and EndoC-βH1 cells treated with cytokines to mimick T1D onset. LC-MS/MS analyses of human islets showed that treatment with IL-1β plus IFN-α for 48h increased m6A levels. Consistently, IL-1β plus IFN-α treatment of human islets and EndoC-βH1 induced upregulation of the m6A writer METTL3. Next, we applied m6A-sequencing in cytokine-treated human islet preparations, and in parallel studies, treated EndoC-βH1 cells followed by RNA-sequencing. Intersection of m6A-decorated genes in cytokine-treated human islets with common differentially expressed genes in human islets and EndoC-βH1 cells revealed enrichment in pathways associated with the innate immune response, negative regulation of immune response, and extrinsic apoptotic signaling pathway. Differentially expressed and m6A decorated genes included genes associated with T1D that are involved in innate immunity. Re-analyses of RNA-seq. data in sorted-β-cells from T1D patients revealed downregulation of METTL3. These data suggest that while healthy β-cells are able to upregulate m6A levels and METTL3 early in T1D (e.g., when they are exposed to cytokines), this response is lost in established T1D that allows an exacerbated immune response and β-cell death. Together, these results point to a possible therapeutic approach in targeting METTL3 to modulate innate immunity and promote β-cell survival. Disclosure D. F. De jesus: None. C. He: None. R. Kulkarni: None. Z. Zhang: None. N. K. Brown: None. J. Hu: None. S. Kahraman: None. C. E. Mathews: None. A. C. Powers: None. M. A. Atkinson: None. D. L. Eizirik: None. Funding National Institutes of Health (1UC4DK116278)

Developing endothelial-protective, nonthrombogenic antirestenotic treatments has been a challenge. A major hurdle to this has been the identification of a common molecular target in both smooth muscle cells and endothelial cells, inhibition of which blocks dysfunction of both cell types. The authors' findings suggest that the PERK kinase could be such a target. Importantly, PERK inhibition mitigated both restenosis and thrombosis in preclinical models, implicating a low-thrombogenic antirestenotic paradigm.

Background and aims Allograft inflammatory factor-1 (AIF1) has been characterized as a pro-inflammatory molecule expressed primarily in the monocyte/macrophage (MP) lineage and positively associated with various forms of vascular disease, including atherosclerosis. Studies of AIF1 in atherosclerosis have relied on mouse models in which AIF1 was overexpressed in either myeloid or smooth muscle cells, resulting in increased atherosclerotic plaque burden. How physiologic expression of AIF1 contributes to MP biology in atherogenesis is not known. Methods Effects of global AIF1 deficiency on atherosclerosis were assessed by crossing Aif1−/− and ApoE−/− mice, and provoking hyperlipidemia with high fat diet feeding. Atherosclerotic plaques were studied en face and in cross section. Bone marrow-derived MPs (BMDMs) were isolated from Aif1−/− mice for study in culture. Results Atherosclerotic plaques in Aif1−/−;ApoE−/− mice showed larger necrotic cores compared to those in ApoE−/− animals, without change in overall lesion burden. In vitro, lack of AIF1 reduced BMDM survival, phagocytosis, and efferocytosis. Mechanistically, AIF1 supported activation of the NF-κB pathway and expression of related target genes involved in stress response, inflammation, and apoptosis. Consistent with this in vitro BMDM phenotype, AIF1 deficiency reduced NF-κB pathway activity in vivo and increased apoptotic cell number in atherosclerotic lesions from Aif1−/−;ApoE−/− mice. Conclusions These findings characterize AIF1 as a positive regulator of the NF-κB pathway that supports MP functions such as survival and efferocytosis. In inflammatory settings such as atherosclerosis, these AIF1-dependent activities serve to clear cellular and other debris and limit necrotic core expansion, and may oppose lesion destabilization.

Background: Pancreatic β-cells adapt to high metabolic demand by expanding their β-cell mass and/or enhancing insulin secretion to maintain glucose homeostasis. Type 2 diabetes (T2D) is typically characterized by β-cell decompensation. Scope of the review: The current review focuses on summarizing the “omics” and “epi-omics” approaches that particularly focus on addressing the β-cell adaptation to insulin resistance and T2D. Major conclusions: The molecular mechanisms underlying successful versus compromised β-cell adaptation to insulin resistance are not entirely understood. The last decade has seen an exponential increase in the use of “omics” and “epi-omics” approaches to dissect pathophysiology of metabolic diseases. One recent example is the emergence of m6A mRNA methylation as a new layer of regulation of gene expression with the potential to impact diverse physiological processes in metabolic cells. Keywords: β-cells, Insulin resistance, Genomics, Transcriptomics, Epigenomics, Epitranscriptomics

The regulation of islet cell biology is critical for glucose homeostasis1.N6 -methyladenosine (m6A) is the most abundant internal messenger RNA (mRNA) modification in mammals2. Here we report that the m6A landscape segregates human type 2 diabetes (T2D) islets from controls significantly better than the transcriptome and that m6A is vital for β-cell biology. m6A-sequencing in human T2D islets reveals several hypomethylated transcripts involved in cell-cycle progression, insulin secretion, and the Insulin/IGF1-AKT-PDX1 pathway. Depletion of m6A levels in EndoC-βH1 induces cell-cycle arrest and impairs insulin secretion by decreasing AKT phosphorylation and PDX1 protein levels. β-cell specific Mettl14 knock-out mice, which display reduced m6A levels, mimic the islet phenotype in human T2D with early diabetes onset and mortality due to decreased β-cell proliferation and insulin degranulation. Our data underscore the significance of RNA methylation in regulating human β-cell biology, and provide a rationale for potential therapeutic targeting of m6A modulators to preserve β-cell survival and function in diabetes.

Type 1 diabetes (T1D) is characterized by pancreatic islet infiltration by autoreactive immune cells and a nearly complete loss of β cells1. Restoration of insulin-producing β cells coupled with immunomodulation to suppress the autoimmune attack has emerged as a potential approach to counter T1D2–4. Here we report that enhancing β-cell mass early in life, in two models of female non-obese diabetic (NOD) mice, results in immunomodulation of T cells, reduced islet infiltration and lower β-cell apoptosis, which together protect them from developing T1D. The animals displayed altered β-cell antigens; islet transplantation studies showed prolonged graft survival in the NOD-liver-specific insulin receptor knockout (LIRKO) model. Adoptive transfer of splenocytes from NOD-LIRKO mice prevented development of diabetes in prediabetic NOD mice. A substantial increase in the splenic CD4+CD25+Foxp3+ regulatory T cell (Treg) population was observed to underlie the protected phenotype since Treg-cell depletion rendered NOD-LIRKO mice diabetic. An increase in Treg cells coupled with activation of transforming growth factor-β/SMAD family member 3 signalling pathway in pathogenic T cells favoured reduced ability to kill β cells. These data support a previously unidentified observation that initiating β-cell proliferation, alone, before islet infiltration by immune cells alters the identity of β cells, decreases pathological self-reactivity of effector T cells and increases Treg cells to prevent the progression of T1D. Type 1 diabetes (T1D) involves immune-mediated destruction of pancreatic β cells. Here, the authors show that inducing β-cell replication before immune cell infiltration of the pancreas alters β-cell antigen expression and prevents T1D disease progression in female NOD mice in a regulatory-T-cell-dependent manner.

Objectives Insulin receptor (IR)-mediated signaling is involved in the regulation of pluripotent stem cells; however, its direct effects on regulating the maintenance of pluripotency and lineage development are not fully understood. The main objective of this study is to understand the role of IR signaling in pluripotency and lineage development. Methods To explore the role of IR signaling, we generated IR knock-out (IRKO) mouse induced pluripotent stem cells (miPSCs) from E14.5 mouse embryonic fibroblasts (MEFs) of global IRKO mice using a cocktail of four reprogramming factors: Oct4, Sox2, Klf4, cMyc. We performed pluripotency characterization and directed the differentiation of control and IRKO iPSCs into neural progenitors (ectoderm), adipocyte progenitors (mesoderm), and pancreatic beta-like cells (endoderm). We mechanistically confirmed these findings via phosphoproteomics analyses of control and IRKO iPSCs. Results Interestingly, expression of pluripotency markers including Klf4, Lin28a, Tbx3, and cMyc were upregulated, while abundance of Oct4 and Nanog were enhanced by 4-fold and 3-fold, respectively, in IRKO iPSCs. Analyses of signaling pathways demonstrated downregulation of phospho-STAT3, p-mTor and p-Erk and an increase in the total mTor and Erk proteins in IRKO iPSCs in the basal unstimulated state. Stimulation with leukemia inhibitory factor (LIF) showed a ∼33% decrease of phospho-ERK in IRKO iPSCs. On the contrary, Erk phosphorylation was increased during in vitro spontaneous differentiation of iPSCs lacking IRs. Lineage-specific directed differentiation of the iPSCs revealed that cells lacking IR showed enhanced expression of neuronal lineage markers (Pax6, Tubb3, Ascl1 and Oligo2) while exhibiting a decrease in adipocyte (Fas, Acc, Pparγ, Fabp4, C/ebpα, and Fsp27) and pancreatic beta cell markers (Ngn3, Isl1, and Sox9). Further molecular characterization by phosphoproteomics confirmed the novel IR-mediated regulation of the global pluripotency network including several key proteins involved in diverse aspects of growth and embryonic development. Conclusion We report, for the first time to our knowledge, the phosphoproteome of insulin, IGF1, and LIF stimulation in mouse iPSCs to reveal the importance of insulin receptor signaling for the maintenance of pluripotency and lineage determination., Graphical abstract Image 1, Highlights • Insulin receptor signaling regulates expression of key pluripotency genes including Oct4 and Nanog. • IRKO iPSCs show upregulation of neuronal markers during differentiation. • Adipocyte and pancreatic beta cell differentiation are perturbed in IRKO iPSCs. • Phosphoproteomics analyses confirmed the role of IR in regulation of pluripotency and developmental proteins.

Aims Graft vascular disease (GVD), a clinically important and highly complex vascular occlusive disease, arises from the interplay of multiple cellular and molecular pathways. While occlusive intimal lesions are composed predominantly of smooth muscle-like cells (SMLCs), the origin of these cells and the stimuli leading to their accumulation in GVD are uncertain. Macrophages have recently been identified as both potential drivers of intimal hyperplasia and as precursors that undergo transdifferentiation to become SMLCs in non-transplant settings. Colony stimulating factor-1 (CSF1) is a well-known regulator of macrophage development and differentiation, and prior preclinical studies have shown that lack of CSF1 limits GVD. We sought to identify the origins of SMLCs and of cells expressing the CSF1 receptor (CSF1R) in GVD, and to test the hypothesis that pharmacologic inhibition of CSF1 signaling would curtail both macrophage and SMLC activities and decrease vascular occlusion. Methods and results We used genetically modified mice and a vascular transplant model with minor antigen mismatch to assess cell origins. We found that neointimal SMLCs derive from both donor and recipient, and that transdifferentiation of macrophages to SMLC phenotype is minimal in this model. Cells expressing CSF1R in grafts were identified as recipient-derived myeloid cells of Cx3cr1-lineage, and these cells rarely expressed smooth muscle marker proteins. Blockade of CSF1R activity using the tyrosine kinase inhibitor PLX3397 limited the expression of genes associated with innate immunity and decreased levels of circulating monocytes and intimal macrophages. Importantly, PLX3397 attenuated the development of GVD in arterial allografts. Conclusion These studies provide proof of concept for pharmacologic inhibition of the CSF1/CSF1R signaling pathway as a therapeutic strategy in GVD. Further preclinical testing of this pathway in GVD is warranted. Translational perspective Graft vascular disease is a major limitation to the long-term success of clinical solid organ transplantation. Currently, there are no effective treatment options to prevent the development of neointimal lesions that obstruct blood flow to the graft. In this study we found that PLX3397, a selective inhibitor of CSF1R signaling, reduced the accumulation of macrophages and ACTA2+ cells within neointimal lesions in a preclinical model of graft vascular disease. Our study highlights a promising role for the pharmacologic targeting of CSF1R signaling to further study the molecular mechanisms that regulate allotransplantation-induced vascular remodeling.

Three-dimensional (3D) structures of protein complexes provide fundamental information to decipher biological processes at the molecular scale. The vast amount of experimentally and computationally resolved protein-protein interfaces (PPIs) offers the possibility of training deep learning models to aid the predictions of their biological relevance.We present here DeepRank, a general, configurable deep learning framework for data mining PPIs using 3D convolutional neural networks (CNNs). DeepRank maps features of PPIs onto 3D grids and trains a user-specified CNN on these 3D grids. DeepRank allows for efficient training of 3D CNNs with data sets containing millions of PPIs and supports both classification and regression.We demonstrate the performance of DeepRank on two distinct challenges: The classification of biological versus crystallographic PPIs, and the ranking of docking models. For both problems DeepRank is competitive or outperforms state-of-the-art methods, demonstrating the versatility of the framework for research in structural biology.

Ti3C2TX nano-sheets (MXenes) with excellent light-conversion capacity have gained importance in treating infectious diseases due to their limited bacterial resistance. In this study, we exploit this property to design photothermal antibacterial therapy using few- (FX) and multi-layer (MX) Ti3C2Tx nano-sheets. We demonstrate that FX have a higher cytocompatibility and conversion of light to heat, but MX show a better efficacy in inhibiting growth of S. aureus and E. coli due to MXenes’ reversible bacteria trapping. For MX (25 µg/mL), □37% of E. coli and □23% of S. aureus cells survived, while the effect was less pronounced for FX with □72% of E. coli and □46% of S. aureus viable cells after treatment. After using 100 µg/mL of MX, □11% of E. coli and □4% of S. aureus survived, while FX had only a mild effect on both species. The NIR laser treatment increased the efficacy of both materials: 100 µg/mL of MX combined with 5 min laser treatment at 5.7 W cm − 2 completely killed both species. For FX, the treatment with 3 W cm − 2 and the highest concentration (100 µg/mL) induced an effect comparable to MX (87% on E. coli, 95% on S.aureus). The combined NIR-MXene treatment causes an irreversible cell death linked to the loss of cell integrity (DNA release quantification and bacteria debris observation).

This chapter briefly describes activities related to small modular nuclear reactor research and development and deployment in Argentina. Since the 1950s Argentina has developed and constructed research reactors. This activity was very successful and many research reactors were exported. Small and medium reactors based on heavy water reactors were installed, and many facilities were constructed. Since the 1980s Argentina is developing CAREM Project. This project consists on the development, design, and construction of small nuclear power plants based on integrated pressurized water reactors. CAREM prototype is under construction.

This coastal to mid-continental shelf, pelagic species is widely distributed from Brazil to Argentina. It is a short-lived species with an estimated generation length of 2-4 years. Biomass fluctuates naturally with environmental conditions. It is currently commercially exploited only in Argentina. The global population is comprised of three stocks (1. southeast Brazil north of 28°S, 2. Brazil south of 28°S, Uruguay and Argentina to 41°S and 3. Argentine Patagonia between 41°S and 48°S). Abundance of the species in Brazil is stable. According to fishery independent scientific surveys, the Buenos Aires stock has a high biomass close to historical levels and it is underexploited. The Argentine population is regularly monitored and there are stringent fishing regulations in place. Fishing activity is not expected to be driving global-level declines approaching a Near Threatened or threatened level at this time. It is listed as Least Concern with a recommendation to continue to conduct research cruises to improve stock assessments. Research is also needed to better understand the observed changes in body size structure of the southern stocks. Fil: Buratti, C.. Instituto Nacional de Investigaciones y Desarrollo Pesquero; Argentina Fil: Díaz de Astarloa, Juan Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; Argentina Fil: Hüne, M.. Universidad Austral de Chile; Chile Fil: Irigoyen, A.. No especifíca; Fil: Landaeta, M.. Universidad de Valparaíso; Chile Fil: Riestra, C.. Instituto Nacional de Investigaciones y Desarrollo Pesquero; Argentina Fil: Vieira, J.P.. Universidade Federal Do Rio Grande.; Brasil Fil: Di Dario F.. Universidade Federal do Rio de Janeiro; Brasil

This coastal, pelagic species is widely distributed in the southwestern Atlantic and southeastern Pacific. It is short-lived and has an estimated generation length of 3-4 years. It is targeted by commercial, artisanal fisheries in the northern part of its range in Chile. Total biomass has declined by about 40% over the past three generation lengths, or since 2006, in the Lakes Region of Chile, and that stock is considered overfished. However, it is not targeted elsewhere in its range at this time, including in the area that contains the largest proportion of its global population. Fishing activity is not expected to be driving global-level declines approaching a Near Threatened or threatened level at this time; therefore, it is listed as Least Concern. However, fishing effort may expand further south where it remains abundant, and this is a concern. Fil: Buratti, C.. Instituto Nacional de Investigaciones y Desarrollo Pesquero; Argentina Fil: Díaz de Astarloa, Juan Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; Argentina Fil: Hüne, M.. Universidad Austral de Chile; Chile Fil: Irigoyen, Alejo Joaquin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; Argentina Fil: Landaeta, M.. Universidad de Valparaíso; Chile Fil: Riestra, C.. Instituto Nacional de Investigaciones y Desarrollo Pesquero; Argentina Fil: Vieira, J. P.. Universidade Federal Do Rio Grande.; Brasil Fil: Di Dario, F.. Universidade Federal do Estado do Rio de Janeiro; Brasil

Microgrids have been introduced as powerful concepts to tackle the transition toward a decentralized power supplying. For this reason, complex methodologies for their planning have been proposed, and the selection of effective algorithms for its solution has become a transcendental task. In this work, the Multiobjective Evolutionary Algorithm Based On Decomposition (MOEA/D) is tested in the PG&E 69-bus. Optimization planning and results show the performance and advantages of their implementation for solving this practical problem.

While it is known that patients with nonalcoholic fatty liver disease exhibit enhanced insulin secretion, the factor(s) that contribute to this effect are not fully understood especially in nondiabetic subjects. Our aim was to examine crosstalk between a steatotic liver induced by a diet that is deficient in methionine choline (MCD) and pancreatic islets in the absence of diabetes/insulin resistance. Nine-week old male C57BL/6J mice were fed normal chow (CTL) or the MCD diet for 3 weeks followed by evaluation of glucose homeostasis, liver and pancreas pathology and hepatic gene expression by RNA-sequencing. Three weeks of MCD diet caused simple hepatic steatosis with hepatic triglyceride content 2-fold higher in MCD compared to CTL (n=5; p Disclosure T. Kimura: None. D.F. De Jesus: None. K. Fukuda: None. S. Kahraman: None. K. Shibue: None. K. Orime: None. R. Kulkarni: None. Funding National Institutes of Health (R01DK067536, R01DK103215)

Obesity and type 2 diabetes mellitus are global emergencies and long noncoding RNAs (lncRNAs) are regulatory transcripts with elusive functions in metabolism. Here we show that a high fraction of lncRNAs, but not protein-coding mRNAs, are repressed during diet-induced obesity (DIO) and refeeding, whilst nutrient deprivation induced lncRNAs in mouse liver. Similarly, lncRNAs are lost in diabetic humans. LncRNA promoter analyses, global cistrome and gain-of-function analyses confirm that increased MAFG signaling during DIO curbs lncRNA expression. Silencing Mafg in mouse hepatocytes and obese mice elicits a fasting-like gene expression profile, improves glucose metabolism, de-represses lncRNAs and impairs mammalian target of rapamycin (mTOR) activation. We find that obesity-repressed LincIRS2 is controlled by MAFG and observe that genetic and RNAi-mediated LincIRS2 loss causes elevated blood glucose, insulin resistance and aberrant glucose output in lean mice. Taken together, we identify a MAFG-lncRNA axis controlling hepatic glucose metabolism in health and metabolic disease., Despite widespread transcription of LncRNA in mammalian systems, their contribution to metabolic homeostasis at the cellular and tissue level remains elusive. Here Pradas-Juni et al. describe a transcription factor–LncRNA pathway that couples hepatocyte nutrient sensing to regulation of glucose metabolism in mice.

Family businesses are one of the main drivers of the economy, hence the relevance of studying them. There are several contributions from national specialists on the subject of family businesses, but the studies and tools developed with the purpose of to professionalize to this type of companies are insufficient. Therefore, the main objective of this research is to design a strategic teaching plan with interdisciplinary characteristics for the training of students towards the creation and management of family businesses in Barcelona, Spain, responding to the needs and demands of society. The methodology used is of a quantitative nature, with a scope according to the level of knowledge obtained with said research: exploratory-descriptive. It also required a non-experimental descriptive transactional type, all in order to investigate the incidence and provide a vision of the study community. The unit of analysis used was the teaching staff of the area of Organization of companies. Based on the proposed strategic teaching plan, it is intended that teachers first acquire the same skills that students are required to manage and lead family businesses. Key words: strategic plan, family businesses, teaching competencies JEL Classification: M13, M19, M53, M59

Abnormal endocardial cushion formation is a major cause of congenital heart valve disease, which is a common birth defect with significant morbidity and mortality. Although β-catenin and BMP2 are two well-known regulators of endocardial cushion formation, their interaction in this process is largely unknown. Here, we report that deletion of β-catenin in myocardium results in formation of hypoplastic endocardial cushions accompanying a decrease of mesenchymal cell proliferation. Loss of β-catenin reduced Bmp2 expression in myocardium and SMAD signaling in cushion mesenchyme. Exogenous BMP2 recombinant proteins fully rescued the proliferation defect of mesenchymal cells in cultured heart explants from myocardial β-catenin knockout embryos. Using a canonical WNT signaling reporter mouse line, we showed that cushion myocardium exhibited high WNT/β-catenin activities during endocardial cushion growth. Selective disruption of the signaling function of β-catenin resulted in a cushion growth defect similar to that caused by the complete loss of β-catenin. Together, these observations demonstrate that myocardial β-catenin signaling function promotes mesenchymal cell proliferation and endocardial cushion expansion through inducing BMP signaling.

The regulation of islet cell biology is critical for glucose homeostasis1.N6-methyladenosine (m6A) is the most abundant internal messenger RNA (mRNA) modification in mammals2. Here we report that the m6A landscape segregates human type 2 diabetes (T2D) islets from controls significantly better than the transcriptome and that m6A is vital for β-cell biology. m6A-sequencing in human T2D islets reveals several hypomethylated transcripts involved in cell-cycle progression, insulin secretion, and the Insulin/IGF1-AKT-PDX1 pathway. Depletion of m6A levels in EndoC-βH1 induces cell-cycle arrest and impairs insulin secretion by decreasing AKT phosphorylation and PDX1 protein levels. β-cell specific Mettl14 knock-out mice, which display reduced m6A levels, mimic the islet phenotype in human T2D with early diabetes onset and mortality due to decreased β-cell proliferation and insulin degranulation. Our data underscore the significance of RNA methylation in regulating human β-cell biology, and provide a rationale for potential therapeutic targeting of m6A modulators to preserve β-cell survival and function in diabetes.

Epitranscriptome profiling using MeRIP-seq is a powerful technique for in vivo functional studies of reversible RNA modifications. We develop RADAR, a comprehensive analytical tool for detecting differentially methylated loci in MeRIP-seq data. RADAR enables accurate identification of altered methylation sites by accommodating variability of pre-immunoprecipitation expression level and post-immunoprecipitation count using different strategies. In addition, it is compatible with complex study design when covariates need to be incorporated in the analysis. Through simulation and real datasets analyses, we show that RADAR leads to more accurate and reproducible differential methylation analysis results than alternatives, which is available at https://github.com/scottzijiezhang/RADAR.

Resumen Objetivo Realizar una evaluacion clinica y paraclinica y establecer la supervivencia del injerto y del paciente a 3 anos de seguimiento de pacientes trasplantados. Materiales y metodos Estudio descriptivo de corte transversal retrospectivo en pacientes trasplantados del Hospital Universitario de Neiva, desde febrero de 2007 hasta el cumplimiento de los 3 anos de seguimiento en diciembre de 2014. Se realizo caracterizacion sociodemografica, de variables clinicas y paraclinicas pretrasplante y postrasplante (al mes, a los 6 meses, al ano y a los 3 anos de seguimiento), comparaciones con los valores pretrasplante y analisis de sobrevida del injerto y del paciente a 3 anos de seguimiento por el metodo de Kaplan-Meier. Resultados Para el ano 2014, un total de 140 pacientes habian cumplido minimo 3 anos postrasplante. A los 3 anos de seguimiento hay diferencias estadisticamente significativas en los valores de porcentaje de neutrofilos, hemoglobina, creatinina y tasa de filtracion glomerular y las variables clinicas de presion arterial sistolica, presion arterial diastolica e indice de masa corporal. La sobrevida del injerto a 3 anos de seguimiento alcanzo el 84,5%, con 21 perdidas, y la sobrevida del paciente fue del 87,4%, con 16 defunciones. Conclusiones Se evidencian positivas diferencias estadisticamente significativas en las variables hemoglobina, creatinina y tasa de filtracion glomerular, y en los valores de presion arterial sistolica y diastolica e incremento del indice de masa corporal. La sobrevida del injerto y del paciente a 3 anos de seguimiento es similar a la reportada por la literatura mundial.