Tasa estimada de disposición de glucosa en pacientes menores de 18 años con diabetes mellitus tipo 1 y sobrepeso-obesidad

ObjectiveTo assess the estimated glucose disposal rate (eGDR), insulin dose, and lipoprotein profile in children with type 1 diabetes mellitus (T1DM) and overweight or obesity as compared to children with T1DM and normal weight.MethodsA total of 115 patients (aged 5-16 years) with T1DM on intensive insulin therapy were recruited. The following parameters were measured: weight, height, body mass index, waist and hip circumference, insulin dose, eGDR, glycosylated hemoglobin, blood pressure, and lipoprotein profile. Results were stratified by sex and age.ResultsNo significant differences were found in eGDR between children with normal weight, overweight, and obesity. However, obese children older than 11 years had lower eGDR values (9.3 ± 1.3 vs 10.1 ± 0.8 mg kg^-1min^-1; p < 0.01). Insulin dose was higher in overweight and obese children, especially in IU/m²/day (37.7 vs 36.1 vs 29.4 respectively; p < 0.01). Obese children had higher low-density lipoprotein cholesterol levels than children with overweight and normal weight (106.5 vs 91.7 vs 91.5 mg/dL respectively; p < 0.01). No correlation was found between waist circumference and the different markers of insulin resistance.ConclusionsValues of eGDR values were lower in obese children with T1DM older than 11 years, and this may therefore be considered a marker of insulin resistance. Insulin dose was higher in diabetic patients with overweight or obesity, specially in IU/m²/day. Obese children with T1DM had a lipoprotein profile of cardiovascular risk.     

SPLUNC1 Regulates Cell Progression and Apoptosis through the miR-141-PTEN/p27 Pathway,but Is Hindered by LMP1

Little is known about the role of the host defensive protein short palate, lung and nasal epithelium clone 1 (SPLUNC1) in the carcinogenesis of nasopharyngeal carcinoma (NPC). Here we report that SPLUNC1 plays a role at a very early stage of NPC carcinogenesis. SPLUNC1 regulates NPC cell proliferation, differentiation and apoptosis through miR-141, which in turn regulates PTEN and p27 expression. This signaling axis is negatively regulated by the EBV-coded gene LMP1. Therefore we propose that SPLUNC1 suppresses NPC tumor formation and its inhibition by LMP1 provides a route for NPC tumorigenesis.     

QTL‐seq: rapid mapping of quantitative trait loci in rice by whole genome resequencing of DNA from two bulked populations

The majority of agronomically important crop traits are quantitative, meaning that they are controlled by multiple genes each with a small effect (quantitative trait loci, QTLs). Mapping and isolation of QTLs is important for efficient crop breeding by marker‐assisted selection (MAS) and for a better understanding of the molecular mechanisms underlying the traits. However, since it requires the development and selection of DNA markers for linkage analysis, QTL analysis has been time‐consuming and labor‐intensive. Here we report the rapid identification of plant QTLs by whole‐genome resequencing of DNAs from two populations each composed of 20–50 individuals showing extreme opposite trait values for a given phenotype in a segregating progeny. We propose to name this approach QTL‐seq as applied to plant species. We applied QTL‐seq to rice recombinant inbred lines and F₂ populations and successfully identified QTLs for important agronomic traits, such as partial resistance to the fungal rice blast disease and seedling vigor. Simulation study showed that QTL‐seq is able to detect QTLs over wide ranges of experimental variables, and the method can be generally applied in population genomics studies to rapidly identify genomic regions that underwent artificial or natural selective sweeps.     

Engineering,Structure and Immunogenicity of the Human Metapneumovirus F Protein in the Postfusion Conformation

Human metapneumovirus (hMPV) is a paramyxovirus that is a common cause of bronchiolitis and pneumonia in children less than five years of age. The hMPV fusion (F) glycoprotein is the primary target of neutralizing antibodies and is thus a critical vaccine antigen. To facilitate structure-based vaccine design, we stabilized the ectodomain of the hMPV F protein in the postfusion conformation and determined its structure to a resolution of 3.3 Å by X-ray crystallography. The structure resembles an elongated cone and is very similar to the postfusion F protein from the related human respiratory syncytial virus (hRSV). In contrast, significant differences were apparent with the postfusion F proteins from other paramyxoviruses, such as human parainfluenza type 3 (hPIV3) and Newcastle disease virus (NDV). The high similarity of hMPV and hRSV postfusion F in two antigenic sites targeted by neutralizing antibodies prompted us to test for antibody cross-reactivity. The widely used monoclonal antibody 101F, which binds to antigenic site IV of hRSV F, was found to cross-react with hMPV postfusion F and neutralize both hRSV and hMPV. Despite the cross-reactivity of 101F and the reported cross-reactivity of two other antibodies, 54G10 and MPE8, we found no detectable cross-reactivity in the polyclonal antibody responses raised in mice against the postfusion forms of either hMPV or hRSV F. The postfusion-stabilized hMPV F protein did, however, elicit high titers of hMPV-neutralizing activity, suggesting that it could serve as an effective subunit vaccine. Structural insights from these studies should be useful for designing novel immunogens able to induce wider cross-reactive antibody responses.     

E‐cadherin expression is associated with somatostatin analogue response in acromegaly

Acromegaly is a rare disease resulting from hypersecretion of growth hormone (GH) and insulin‐like growth factor 1 (IGF1) typically caused by pituitary adenomas, which is associated with increased mortality and morbidity. Somatostatin analogues (SSAs) represent the primary medical therapy for acromegaly and are currently used as first‐line treatment or as second‐line therapy after unsuccessful pituitary surgery. However, a considerable proportion of patients do not adequately respond to SSAs treatment, and therefore, there is an urgent need to identify biomarkers predictors of response to SSAs. The aim of this study was to examine E‐cadherin expression by immunohistochemistry in fifty‐five GH‐producing pituitary tumours and determine the potential association with response to SSAs as well as other clinical and histopathological features. Acromegaly patients with tumours expressing low E‐cadherin levels exhibit a worse response to SSAs. E‐cadherin levels are associated with GH‐producing tumour histological subtypes. Our results indicate that the immunohistochemical detection of E‐cadherin might be useful in categorizing acromegaly patients based on the response to SSAs.     

Multiparametric magnetic resonance imaging-guided salvage radiotherapy in prostate cancer

AimTo analyse the efficacy and toxicity of postprostatectomy SRT in patients with a BCR evaluated with mpMRI.BackgroundMultiparametric magnetic resonance imaging (mpMRI) has the ability to detect the site of pelvic recurrence in patients with biochemical recurrence (BCR) after radical prostatectomy (RP). However, we do not know the oncological outcomes of mpMRI-guided savage radiotherapy (SRT).ResultsLocal, lymph node, and pelvic bone recurrence was observed in 13, 4 and 2 patients, respectively. PSA levels were significantly lower in patients with negative mpMRI (0.4 ng/mL [0.4]) vs. positive mpMRI (2.2 ng/mL [4.1], p = 0.003). Median planning target volume doses in patients with visible vs. non-visible recurrences were 76 Gy vs. 70 Gy. Overall, mean follow-up was 41 months (6–81). Biochemical relapse-free survival (bRFS) at 3 years was 82.3% and 82.5%, respectively, for the negative and positive mpMRI groups (p = 0.800). Three-year rates of late grade ≥2 urinary and rectal toxicity were 14.8% and 1.9%, respectively; all but one patient recovered without sequelae.ConclusionSRT to the macroscopic recurrence identified by mpMRI is a feasible and well-tolerated option. In this study, there were no differences in bRFS between MRI-positive and MRI-negative patients, indicating effective targeting of MRI-positive lesions.     

Identifying molecularly defined antigens for a Histoplasma capsulatum-specific interferon gamma release assay

BackgroundIn a previous work we showed the feasibility of an interferon gamma release assay (IGRA) for detecting latent infection by Histoplasma capsulatum. While in that proof-of-concept study we used crude fungal extracts as antigens, the newest IGRAs developed for other infections are based on molecularly defined antigens, mostly on mixtures of immunogenic peptides.AimsTo identify proteins in H. capsulatum that might serve as molecularly defined antigens for an IGRA test.MethodsWe surveyed the literature looking for known H. capsulatum-immunogenic proteins and assayed two of them as antigens in an IGRA test, in a study that involved 80 volunteers. Furthermore, we used several bioinformatics tools to identify specific H. capsulatum proteins and to analyze possible strategies for the design of H. capsulatum-specific immunogenic peptides.ResultsSeven H. capsulatum-immunogenic proteins were retrieved from the literature. IGRA tests using either the heat shock protein 60 or the M antigen showed high sensitivities but low specificities, most likely due to the high sequence similarity with the corresponding orthologs in other pathogenic microorganisms. We identified around 2000 H. capsulatum-specific proteins, most of which remain unannotated. Class II T-cell epitope predictions for a small number of these proteins showed a great variability among different alleles, prompting for a “brute force” approach for peptide design.ConclusionsThe H. capsulatum genome encodes a large number of distinctive proteins, which represent a valuable source of potential specific antigens for an IGRA test. Among them, the Cfp4 protein stands out as a very attractive candidate.     

基于MaxEnt模型预测气候变化下杉木在中国的潜在地理分布

为研究杉木在中国的分布特征及其对气候变化的响应模式,本研究基于现有分布记录,应用最大熵(MaxEnt)模型和地理信息系统方法,结合气候、地形等环境要素,预测杉木在当前和未来气候变化下的潜在适生区。结果表明: 影响杉木分布的最主要因素是年平均降水量,在当前气候下,杉木适生区合计面积328万km²,占全国陆地总面积的34.5%,低、中和高适生区分别占18.3%、29.7%与52.0%。在未来气候情景下,杉木生长的适宜性在我国总体上呈上升趋势,适生区面积随气候变化增大,且明显向北扩张,南方湿润亚热带地区形成集中连片高适生区。模型经受试者工作特征曲线检验,训练集平均受试者工作特征曲线下面积为0.91,可信度高。