👤 Daniela B Rivera

Neurodevelopmental disorders have been increasingly associated with maternal immune activation (MIA) during pregnancy, particularly in response to viral infections. However, the impact of human respiratory syncytial virus (hRSV) infection during gestation on offspring neurodevelopment remains poorly understood. This study aimed to characterize hRSV-induced MIA and evaluate its effects on fetal brain development and offspring behavior using a murine model. Pregnant mice were infected with hRSV at gestational day 14, and tissues were analyzed at day 19. Infection induced pulmonary inflammation, evidenced by increased neutrophil infiltration, and viral replication was detected in maternal lungs and placental tissue, but not in fetal organs. Placental infection was associated with increased decidual immune cells and a shift toward a pro-inflammatory cytokine profile, including elevated IL-6, TNF-α, IFN-γ, and IL-1β, along with decreased IL-10 and IFN-λ. Increased levels of IL-6, TNF-α, and IL-4 were also detected in maternal serum and fetal brains, suggesting vertical transfer of cytokines. Additionally, reduced brain-derived neurotrophic factor levels and altered expression of tight junction-related genes were observed in fetal brains. Behavioral analyses revealed that offspring of infected dams exhibited impaired short-term memory and altered anxiety-like and repetitive behaviors, which persisted or intensified with age. These findings demonstrate that maternal hRSV infection induces MIA, disrupts the fetal neuroimmune environment, and leads to long-term behavioral alterations in offspring, highlighting hRSV as a potential risk factor for neurodevelopmental disorders. Show less

Breast cancer is the leading cause of cancer-related mortality in African American (AA) women. In this study we evaluated the serum proteomic profile of AA women with breast cancer using an integrated proteomic framework with multivariate pattern analysis. Using 2D-DIGE, thousands of serum protein spots were detected across 33 gels; 46 spots met criteria for presence, statistical significance, and differential expression. Proteins from the spots were identified by MALDI-TOF/TOF and matched in curated databases, highlighting serum biomarkers including ceruloplasmin, alpha-2-macroglobulin, complement component C3 and C6, alpha-1-antitrypsin, alpha-1B-glycoprotein, alpha-2-HS-glycoprotein and haptoglobin-related protein. LC-MS/MS analysis revealed 163 differentiating peptides after imputing and filtering 286 peptides. These were evaluated using cumulative distribution function (CDF) analysis, a nonparametric method suited for limited sample sizes. Peptide patterns were explored with Random Forest, showing concordance with CDF. The model achieved an AUC of 0.85 at the peptide level. This workflow identified differentiating proteins (CERU, A2MG, CO3, VTDB, HEMO, APOB, APOA4, CFAH, CO4A, AACT, K1C10, ITIH2, ITIH4), highlighting CERU, A2MG, and CO3 with overexpression and reproducible identification across platforms. We present an integrated, non-invasive serum protein biomarker signature panel specific to AA women, through reproducible proteomic sensor framework to support early detection and breast cancer prevention. Show less

Fragile X-associated tremor/ataxia syndrome (FXTAS), caused by the FMR1 premutation allele, is associated with brain degeneration, yet the mechanisms behind this neurodegeneration still need to be elucidated. Apoε polymorphism has been widely implicated in brain aging in cognitively healthy individuals and brain deterioration in Alzheimer's disease. This study aimed to examine the interaction of Apoε genotypes, FXTAS clinical symptoms, FMR1 molecular measures, and age, towards brain pathophysiology and cognitive functions. This longitudinal study includes MRI data collected from 205 male premutation carriers with and without FXTAS clinical symptoms and compared to 86 healthy male controls aged 40-85 years. The investigation includes FXTAS-related brain volumes, IQ, self-control behaviors, FMR1 molecular measures, and Apoε genotypes. In carriers with FXTAS, the presence of the Apoε2 allele showed a possible association with more favorable neuroimaging markers, such as reduced white matter hyperintensities, and lower incidence of the middle cerebellar peduncle sign, patterns that were not observed in carriers without FXTAS. Specifically, the presence of Apoε2 allele exhibited a potential protective effect on brain degeneration, and cognitive functions among FXTAS patients; on the contrary, the Apoε4 allele was associated with a worsening of brain volume and brain degeneration in carriers with no FXTAS symptoms. The identification of Apoε genotypes in FMR1 premutation carriers before any clinical symptoms of FXTAS are observed may improve symptomatic management leading to better outcomes for these individuals. Show less

Circulating metabolites can identify biochemical risk factors related to Alzheimer's disease (AD). We measured plasma metabolites in 1,068 participants of Caribbean Hispanic ancestry (250 patients with AD and 818 healthy controls) across 2 cohorts and analyzed their relationship with clinical AD, biomarker-supported AD and plasma biomarkers (P-tau181, P-tau217, P-tau231 and Aβ42:Aβ40). Amino acid metabolism pathways were enriched among metabolites associated with P-tau biomarkers, whereas sialic acid and N-glycan pathways were associated with Aβ42:Aβ40. Through several dimensionality reduction approaches, we identified an APOE-ε4 dependent relationship between lysophosphatidylcholines (lysoPCs) carrying polyunsaturated fatty acids and biomarker-supported AD and P-tau biomarkers. In an independent dataset of 110 postmortem brain tissues from non-Hispanic white participants, lysoPCs in the brain were also associated with AD neuropathological features. Our results show that biomarker-based diagnostic criteria identified an APOE-ε4 dependent association with lysoPCs, which play a critical role in the transport of neuroprotective polyunsaturated fatty acids into the brain, and AD. Show less

Obesity increases the risk of respiratory diseases that reduce respiratory chemosensitivity, such as Obesity Hypoventilation Syndrome and sleep apnea. Recent evidence suggests that obesity-related changes in the brain, including alterations in melanocortin signaling via the melanocortin-4 receptor (MC4R), may underly altered chemosensitivity. Setmelanotide, an MC4R agonist, causes weight loss in both humans and animal models. However, it is unknown the extent to which setmelanotide affects respiratory chemosensitivity independent of body weight loss. The present study uses diet-induced obese, male C57bl/6 J mice to determine the extent to which acute setmelanotide treatment affects the hypercapnic ventilatory response (HCVR). We find that ten days of daily setmelanotide treatment at 1 mg/kg, but not 0.2 mg/kg, is sufficient to cause weight loss and increase HCVR. In a separate group of animals, we find that we can emulate setmelanotide's effect on weight loss by restricting daily calories to match the hypophagia triggered by setmelanotide. These pair-fed animals exhibit improvements in HCVR similar to those who receive setmelanotide. We conclude that acute treatment with setmelanotide is as effective as weight loss at improving respiratory hypercapnic chemosensitivity. Show less

Resistance and resilience are pathways through which modifiable behaviors may reduce Alzheimer's disease (AD) risk. Sleep - a known modifiable factor - is understudied in this context, especially among older women at elevated risk for AD. Forty-five functionally intact older women (≥65 years) at heightened risk for AD completed wrist actigraphy to capture average nocturnal sleep duration. Tau positron emission tomography imaging ( Shorter sleep duration amplified the association between APOE ε4 status and tau, while longer sleep mitigated it. Similarly, tau burden was related to worse memory performance only among those with short sleep duration. Longer sleep duration may promote resistance and resilience to AD in at-risk older women, highlighting sleep as a critical intervention target. Sleep was measured via wrist actigraphy, tau via PET imaging, and memory with a composite score. Longer sleep attenuated the link between APOE ε4 carriership and tau PET across Braak regions. Greater sleep duration weakened the negative impact of tau on memory performance. This is the first study to examine sleep in AD resistance and resilience among older women at heightened risk. Show less

Obicetrapib is a novel cholesteryl ester transfer protein (CETP) inhibitor with promising lipid-lowering effects. While earlier CETP inhibitors have shown inconsistent cardiovascular outcomes and safety concerns, the efficacy and safety of obicetrapib remain under active investigation. We systematically searched PubMed, Embase, and Cochrane Central databases for randomized controlled trials (RCTs) comparing obicetrapib versus placebo in adults with dyslipidemia or at high cardiovascular risk. We pooled mean differences (MDs) with 95 % confidence intervals (CI) with a random effects model. We used R software version 4.4.2 for statistical analysis. We included 7 RCTs comprising 3381 participants, of whom 2151 (63 %) received obicetrapib. The mean age was 64.3 years, and 36 % were women. Compared with placebo, obicetrapib significantly reduced mean LDL-C (MD: -37.21 %; 95 % CI: -41.53 to -32.90; Among patients with dyslipidemia and/or high cardiovascular risk, obicetrapib significantly reduces LDL-C, lipoprotein(a), apolipoprotein B, and non-HDL-C. No significant differences were observed in adverse events, supporting the favorable safety profile of obicetrapib. Show less

FGFR1 genetic alterations are associated with brain malignancies, including FGFR1 mutations in familial and sporadic cases of low-grade glioneuronal tumors, suggesting intrinsic mechanisms of selective pressure toward FGFR1 multiple events arising in the context of a quiet genome. To decipher the molecular mechanisms triggered by multiple concurrent FGFR1 mutations, we have mapped the proximal interactome of wild-type, single- and double-mutant FGFR1 proteins through a BioID-MS approach. Our data reveal novel oncogenic functionality for the two hotspot mutations N546K and K656E, linked to evasion of lysosomal degradation. Further, we identified a modulatory tumor-suppressive role for the susceptibility variant R661P, which hampers the oncogenic potential of both hotspot N546K and K656E mutations by rescuing receptor degradation and reducing N546K affinity for the downstream effector PLCγ. Introducing the R661P missense variant was sufficient to abolish self-renewal capacity of oligodendroglioma cells and downregulate genes involved in neurodevelopment and neuro-glial cell fate decisions, both aspects overcome in the double mutants. This study sheds light on contextual oncogenic effects associated with FGFR1 alterations and their recurrence in low-mutation burden and therapy naive tumors. Show less

B cells express many protein ligands, yet their regulatory functions are incompletely understood. We profiled ligand expression across murine B sublineage cells, including those activated by defined receptor signals, and assessed their regulatory capacities and specificities through in silico analysis of ligand-receptor interactions. Consequently, we identified a B cell subset that expressed cytokine interleukin-27 (IL-27) and chemokine CXCL10. Through the IL-27-IL-27 receptor interaction, these IL-27/CXCL10-producing B cells targeted CD40-activated B cells in vitro and, upon induction by immunization and viral infection, optimized antibody responses and antiviral immunity in vivo. Also present in breast cancer tumors and retained there through CXCL10-CXCR3 interaction-mediated self-targeting, these cells promoted B cell PD-L1 expression and immune evasion. Mechanistically, Show less

Intestinal immunity defends against enteric pathogens, mediates symbiotic relationships with the resident microbiota, and provides tolerance to food antigens, safeguarding critical nutrient absorption and barrier functions of this mucosal tissue. Despite the abundance of tissue resident activated T cells, their contributions to these various roles remains poorly understood. Here, we identify a dominant population of IL-10 producing, T-bet expressing CD4+ Tr1 T cells, residing in the small intestinal lamina propria at homeostasis. Remarkably, these intestinal Tr1 cells emerge at the time of weaning and accumulate independently of the microbiota displaying similar abundance, function and TCR repertoire under germ-free conditions. Instead, the small intestinal T-bet+ Tr1 program is driven and shaped by dietary antigens, and accumulates in a cDC1-IL-27 dependent manner. Upon activation, these cells robustly express IL-10 and multiple inhibitory receptors, establishing a distinct suppressive profile. Altogether, this work uncovers a previously unappreciated dominant player in homeostatic small intestinal immunity with the potential to play critical suppressive roles in this tissue, raising important implications for the understanding of immune regulation in the intestine. Establishing immunological tolerance to self and environmental antigens is critical to preserve tissue homeostasis and function. In the intestine, both dietary and microbiota derived antigens are routinely encountered by the immune system, which deploys a variety of mechanisms to maintain tolerance to these innocuous antigens. Understanding how immunological tolerance is established is critical, a when this process goes awry it can lead to severe inflammatory and autoimmune diseases such as food allergy and inflammatory bowel disease. However, how tolerance is established in the intestine is still poorly understood. In this study we describe a novel dominant T cell population in the small intestine shaped by dietary components with the potential to play important roles in immune tolerance at this site. back # IntroductionBarrier surfaces such as the gut and skin represent the first line of defense against the environment. These organs must strike a delicate balance between providing protection against environmental and infectious agents, maintaining tissue function, and establishing a homeostatic symbiotic relationship with resident microbes collectively known as the microbiota (1). The immune system plays a critical role in establishing these dynamic and carefully regulated relationships, as evidenced by the large number of immune cells present at these sites. Of particular note, activated T cells are very abundant at barrier tissues, where they orchestrate immune effector functions geared towards these varied tasks (1, 2). In the small intestine, the intraepithelial compartment harbors innate like natural CD8aa⁺ IELs, many of which are self reactive; as well as CD4⁺CD8aa⁺ and CD8ab⁺ IELs responding to dietary and microbial antigens (3). The underlying lamina propria (SILP) harbors predominantly CD4⁺ T cells, which participate in responses to commensal-derived and dietary antigens (2, 4). Despite the abundance of small intestinal CD4 T cells, only a handful of cognate immune interactions focusing on Type 17 and T regulatory helper subsets have been described. Thus, whether immune responses in this tissue are truly limited to a small number of antigenic triggers and effector functions remains to be fully elucidated. The small number of gut homeostatic CD4 T cell responses described thus far have been shown to primarily respond to specific commensal bacteria or dietary antigens (1, 2, 5-8): Among other examples, SFB induces cognate Th17 cells in the small intestine (9, 10), a consortium human commensal bacteria induces CD8b⁺ cells in the colon (11), and Show less

Genetic studies have largely focused on homogeneous populations, limiting our understanding of the genetic architecture of complex traits in admixed individuals. The advent of diverse biobanks like the Show less

Multifocal papillary thyroid carcinomas (PTCs) are common and the majority of the tumors harbor mutual BRAF p.V600E mutation. This study aimed to investigate a contemporary series of multifocal PTCs with discordant molecular drivers. Consecutive thyroidectomies diagnosed with multifocal PTCs ≥0.5 cm between 2019 and 2023 were reviewed. Immunohistochemistry (IHC) for BRAF VE1 was performed for all tumors. Cases with discordant BRAF IHC results or morphologic discrepancy were identified, and BRAF IHC-negative tumors were subjected to RAS Q61R IHC and/or targeted RNA next-generation sequencing. A total of 770 patients with a main PTC ≥0.5 cm were identified; 255 (33.1%) had multifocal disease, and 142 (18.4%) had at least another PTC ≥0.5 cm. Among them, 13 cases (9.2%, 13/142) had discordant molecular drivers. Twelve cases had one or more BRAF -positive PTCs accompanied by a BRAF -negative PTC (3 with CCDC6::RET fusion, 1 with NCOA4::RET fusion, 1 with ACBD5::RET fusion, 2 with ETV6::NTRK3 fusion, 1 with TG::FGFR1 fusion, 1 with LMTK2::BRAF fusion, 1 with AGK::BRAF fusion and RAS p.Q61R mutation, 1 with RAS p.Q61R mutation, and 1 without detectable molecular drivers). The last case had tumors with discordant fusion drivers ( VIM::NTRK3 and TNS1::BRAF ). Most cases showed tumors that were morphologically distinct (92.3%, 12/13) and occurred in the contralateral lobes (76.9%, 10/13). Notably, we identified 4 cases (30.8%) that presented as collision tumors and 6 cases (46.2%) that showed lymph node metastases, including 2 with simultaneous involvement by tumors with discordant molecular drivers, as novel findings. In summary, a subset (9.2%) of multifocal PTCs had discordant molecular drivers and 84.6% of them were a combination of BRAF -positive and kinase gene fusion-associated PTCs, most with distinct morphologies. Almost half of the cases had nodal metastasis and a third of them showed simultaneous involvement by tumors with discordant molecular drivers. The results highlight the clinical importance of identifying such cases, given the potentially different treatments. Show less

Clearance of residual Host Cell Proteins (HCPs) is critical for the manufacturing processes of biotherapeutics. HCPs have the potential to impact product efficacy and quality, posing a risk to patient safety. It is therefore essential to be able to both identify and quantitate HCPs throughout drug development, even if the proteins are present in low concentrations. Traditional Enzyme-Linked Immunosorbent Assays (ELISAs) have historically served as the gold standard for monitoring HCPs; however, ELISA methods are labor-intensive and costly. With an increase of HCPs being identified below detectable quantification levels, there is a need for simultaneous detection of selectively targeted HCPs. Here, we develop a Luminex multiplexing method that is able to accurately quantify two "high-risk" lipases Lipoprotein Lipase (LPL) and Phospholipase B-Like 2 (PLBL2) within the same assay. This study outlines the method development for optimizing parameters such as antibody constructs, conjugation ratios, signal enhancement, and more in order to create the most efficient multiplexing method. As a result, a Luminex multiplexing method can provide a similar result to a monoplexing ELISA method but in a faster and more cost-effective manner. This method can be expanded to include other "high-risk" HCPs and used for future HCP applications. Show less

Men taking antioxidant vitamin E supplements have increased prostate cancer (PC) risk. However, whether pro-oxidants protect from PC remained unclear. In this work, we show that a pro-oxidant vitamin K precursor [menadione sodium bisulfite (MSB)] suppresses PC progression in mice, killing cells through an oxidative cell death: MSB antagonizes the essential class III phosphatidylinositol (PI) 3-kinase VPS34-the regulator of endosome identity and sorting-through oxidation of key cysteines, pointing to a redox checkpoint in sorting. Testing MSB in a myotubular myopathy model that is driven by loss of Show less

Sarcomas are a rare and diverse group of cancers occurring mainly in young individuals for which an underlying germline genetic cause remains unclear in most cases. Germline DNA from 177 children, adolescents and young adults with soft tissue or bone sarcomas was tested using multigene panels with 113 or 126 cancer predisposing genes (CPGs) to describe the prevalence of germline pathogenic/likely pathogenic variants (GPVs). Subsequent testing of a subset of tumours for loss of heterozygosity (LOH) evaluation was performed to investigate the clinical and molecular significance of these variants. GPVs were detected in 21.5% (38/177) of the patients (15.8% in children and 21.6% in adolescents and young adults), with dominant CPGs being altered in 15.2% overall. These variants were found in genes previously associated with the risk of developing sarcomas ( Our findings reveal that a high proportion of young patients with sarcomas presented a GPV in a CPG, underscoring the urgency of establishing appropriate genetic screening strategies for these individuals and their families. Show less

Inflammation is critical for controlling pathogens, but also responsible for symptoms of infectious diseases. IL-27 is an important regulator of inflammation and can limit development of IFNγ-producing Tbet+ CD4+ T (Th1) cells. IL-27 is thought to do this by stimulating IL-10 production by CD4+ T cells, but the underlying mechanisms of these immunoregulatory pathways are not clear. Here we studied the role of IL-27 signalling in experimental visceral leishmaniasis (VL) caused by infection of C57BL/6 mice with the human pathogen Leishmania donovani. We found IL-27 signalling was critical for the development of IL-10-producing Th1 (Tr1) cells during infection. Furthermore, in the absence of IL-27 signalling, there was improved control of parasite growth, but accelerated splenic pathology characterised by the loss of marginal zone macrophages. Critically, we discovered that IL-27 signalling limited glycolysis in Th1 cells during infection that in turn attenuated inflammation. Furthermore, the modulation of glycolysis in the absence of IL-27 signalling restricted tissue pathology without compromising anti-parasitic immunity. Together, these findings identify a novel mechanism by which IL-27 mediates immune regulation during disease by regulating cellular metabolism. Show less

To evaluate whether the levels of some molecules implicated in nucleocytoplasmic transport in human cardiomyocytes are related to the severity of heart failure (HF) in patients on the heart transplantation (HT) waiting list, and to determine whether there is a differential pattern of molecular alteration between ischemic cardiomyopathy (ICM) and non-ischemic dilated cardiomyopathy (DCM). Sixty-three blood samples collected before HT were analyzed to identify the levels of IMPORTIN5 (IMP5); IMPORTINalpha2; ATPaseCaTransp (ATPCa); NUCLEOPORIN153kDa (Nup153); NUCLEOPORIN160kDa (Nup160); RANGTPaseAP1 (RanGAP1) and EXPORTIN4 (EXP4). These data were then compared between patients with advanced HF with or without the need for ventricular support with extracorporeal membrane oxygenation (ECMO) as a bridge for HT, as well as between patients with non-ischemic DCM and patients with ICM. Thirty-three patients had ICM, 26 had non-ischemic DCM, and 4 had heart disease. Seventeen patients required ventricular assistance as a bridge to HT. The levels of ATPCa, RanGAP1, and IMP5 were significantly higher in patients with ECMO, while EXP4 was significantly higher in patients without ECMO. Patients with DCM showed higher levels of IMP5, RanGAP1, and Nup153 than those with ICM. Patients with advanced HF in critical condition (with ECMO as a bridge for HT) presented with significantly higher levels of ATPCa, RanGAP1, and IMP5, while patients with DCM had significantly higher levels of RanGAP1, IMP5, and Nup153. It remains to be clarified whether the determination of these molecules would facilitate the early identification of this group or if their alteration occurs as consequence of circulatory support with ECMO. Show less

Sarcoidosis is a multisystem disease of unknown cause. Löfgren's syndrome (LS) is a characteristic subgroup of sarcoidosis that is associated with a good prognosis in sarcoidosis. However, little is known about its genetic architecture or its broader phenotype, non-LS sarcoidosis. To address the genetic architecture of sarcoidosis phenotypes, LS and non-LS. An association study in a white Swedish cohort of 384 LS, 664 non-LS, and 2,086 control subjects, totaling 3,134 subjects using a fine-mapping genotyping platform was conducted. Replication was performed in four independent cohorts, three of white European descent (Germany, n = 4,975; the Netherlands, n = 613; and Czech Republic, n = 521), and one of black African descent (United States, n = 1,657), totaling 7,766 subjects. A total of 727 LS-associated variants expanding throughout the extended major histocompatibility complex (MHC) region and 68 non-LS-associated variants located in the MHC class II region were identified and confirmed. A shared overlap between LS and non-LS defined by 17 variants located in the MHC class II region was found. Outside the MHC region, two LS-associated loci, in ADCY3 and between CSMD1 and MCPH1, were observed and replicated. Comprehensive and integrative analyses of genetics, transcription, and pathway modeling on LS and non-LS indicates that these sarcoidosis phenotypes have different genetic susceptibility, genomic distributions, and cellular activities, suggesting distinct molecular mechanisms in pathways related to immune response with a common region. Show less

Fibromyalgia (FM) is a highly disabling syndrome defined by a low pain threshold and a permanent state of pain. The mechanisms explaining this complex disorder remain unclear, and its genetic factors have not yet been identified. With the aim of elucidating FM genetic susceptibility factors, we selected 313 FM cases having low comorbidities, and we genotyped them on the Illumina 1 million duo array. Genotypic data from 220 control women (Illumina 610k array) was obtained for genome-wide association scan (GWAS) analysis. Copy number variants in FM susceptibility were analyzed by array comparative genomic hybridization (aCGH) experiments on pooled samples using the Agilent 2×400K platform. No single nucleotide polymorphism (SNP) reached GWAS association threshold, but 21 of the most associated SNPs were chosen for replication in 952 cases and 644 controls. Four of the SNPs selected for replication showed a nominal association in the joint analysis, and rs11127292 (MYT1L) was found to be associated to FM with low comorbidities (P=4.28×10(-5), odds ratio [95% confidence interval]=0.58 [0.44-0.75]). aCGH detected 5 differentially hybridized regions. They were followed up, and an intronic deletion in NRXN3 was demonstrated to be associated to female cases of FM with low levels of comorbidities (P=.021, odds ratio [95% confidence interval]=1.46 [1.05-2.04]). Both GWAS and aCGH results point to a role for the central nervous system in FM genetic susceptibility. If the proposed FM candidate genes were further validated in replication studies, this would highlight a neurocognitive involvement in agreement with latest reports. Show less

The objectives of this study were to analyse the effect of heart failure (HF) on several proteins of nuclear pore complex (NPC) and their relationship with the human ventricular function. A total of 88 human heart samples from ischemic (ICM, n = 52) and dilated (DCM, n = 36) patients undergoing heart transplant and control donors (CNT, n = 9) were analyzed by Western blot. Subcellular distribution of nucleoporins was analysed by fluorescence and immunocytochemistry. When we compared protein levels according to etiology, ICM showed significant higher levels of NDC1 (65%, p<0.0001), Nup160 (88%, p<0.0001) and Nup153 (137%, p = 0.004) than those of the CNT levels. Furthermore, DCM group showed significant differences for NDC1 (41%, p<0.0001), Nup160 (65%, p<0.0001), Nup153 (155%, p = 0.006) and Nup93 (88%, p<0.0001) compared with CNT. However, Nup155 and translocated promoter region (TPR) did not show significant differences in their levels in any etiology. Regarding the distribution of these proteins in cell nucleus, only NDC1 showed differences in HF. In addition, in the pathological group we obtained good relationship between the ventricular function parameters (LVEDD and LVESD) and Nup160 (r = -0382, p = 0.004; r = -0.290, p = 0.033; respectively). This study shows alterations in specific proteins (NDC1, Nup160, Nup153 and Nup93) that compose NPC in ischaemic and dilated human heart. These changes, related to ventricular function, could be accompanied by alterations in the nucleocytoplasmic transport. Therefore, our findings may be the basis for a new approach to HF management. Show less