Evaluation of CXCL9 and CXCL10 as circulating biomarkers of human cardiac allograft rejection

BACKGROUND: Cardiac allograft rejection remains a significant clinical problem in the early phase after heart transplantation and requires frequent surveillance with endomyocardial biopsy. However, this is an invasive procedure, which is unpleasant for the patient and carries a certain risk. Therefore, a sensitive non-invasive biomarker of acute rejection would be desirable. METHODS: Endomyocardial tissue samples and serum were obtained in connection with clinical biopsies from twenty consecutive heart transplant patients followed for six months. A rejection episode was observed in 14 patients (11 men and 3 women) and biopsies obtained before, during and after the episode were identified. Endomyocardial RNA, from three patients, matching these three points in time were analysed with DNA microarray. Genes showing up-regulation during rejection followed by normalization after the rejection episode were evaluated further with real-time RT-PCR. Finally, ELISA was performed to investigate whether change in gene-regulation during graft rejection was reflected in altered concentrations of the encoded protein in serum. RESULTS: Three potential cardiac allograft rejection biomarker genes, chemokine (C-X-C motif) ligand 9 (CXCL9), chemokine (C-X-C motif) ligand 10 (CXCL10) and Natriuretic peptide precursor A (NPPA), from the DNA microarray analysis were selected for further evaluation. CXCL9 was significantly upregulated during rejection (p < 0.05) and CXCL10 displayed a similar pattern without reaching statistical significance. Serum levels of CXCL9 and CXCL10 were measured by ELISA in samples from 10 patients before, during and after cardiac rejection. There were no changes in CXCL9 and CXCL10 serum concentrations during cardiac rejection. Both chemokines displayed large individual variations in the selected samples, but the serum levels between the two chemokines correlated (p < 0.001). CONCLUSION: We conclude, that despite a distinct up-regulation of CXCL9 mRNA in human hearts during cardiac allograft rejection, this was not reflected in the serum levels of the encoded protein. Thus, in contrast to previous suggestions, serum CXCL9 does not appear to be a promising serum biomarker for cardiac allograft rejection

Chronic psychosocial and financial burden accelerates 5-year telomere shortening: findings from the Coronary Artery Risk Development in Young Adults Study.

Leukocyte telomere length, a marker of immune system function, is sensitive to exposures such as psychosocial stressors and health-maintaining behaviors. Past research has determined that stress experienced in adulthood is associated with shorter telomere length, but is limited to mostly cross-sectional reports. We test whether repeated reports of chronic psychosocial and financial burden is associated with telomere length change over a 5-year period (years 15 and 20) from 969 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a longitudinal, population-based cohort, ages 18-30 at time of recruitment in 1985. We further examine whether multisystem resiliency, comprised of social connections, health-maintaining behaviors, and psychological resources, mitigates the effects of repeated&nbsp;burden on telomere attrition over 5 years. Our results indicate that adults with high chronic burden do not show decreased telomere length over the 5-year period. However, these effects do vary by level of resiliency, as regression results revealed a significant interaction between chronic burden and multisystem resiliency. For individuals with high repeated&nbsp;chronic burden and low multisystem resiliency (1 SD below the mean), there was a significant 5-year shortening in telomere length, whereas no significant relationships between chronic burden and attrition were evident for those at moderate and higher levels of resiliency. These effects apply similarly across the three components of resiliency. Results imply that interventions should focus on establishing strong social connections, psychological resources, and health-maintaining behaviors when attempting to ameliorate stress-related decline in telomere length among at-risk individuals

Aortic root surgery in septuagenarians: impact of different surgical techniques

<p>Abstract</p> <p>Background</p> <p>To evaluate the impact and safety of different surgical techniques for aortic root replacement (ARR) on early and late morbidity and mortality in septuagenarians undergoing ARR.</p> <p>Methods</p> <p>Ninety-five patients (73.8 ± 3.2 years) were operated and divided into three groups according to the aortic root procedure; MECH-group (n = 51) patients with a mechanical composite graft, BIO-group (n = 22) patients with a customized biological composite graft, and REIMPL-group (n = 22) patients with a valve sparing aortic root reimplantation (David I). In 42.1% (40/95) of these patients the aortic arch was replaced. Follow-up was completed in 95.2% (79/83) of in-hospital survivors.</p> <p>Results</p> <p>Hospital mortality was 12.6% (12/95) in the entire population (MECH. 15.7% (8/51), BIO 19.7% (4/22), REIMPL 0% (0/22); p = 0.004). Two patients died intraoperatively. The most frequent postoperative complications were prolonged mechanical ventilation ((>48 h) in 16.8% (16/93) (MECH. 7% (7/51), BIO 36.4% (8/22), REIMPL 4.5% (1/22); p = 0.013) and rethoracotomy for postoperative bleeding in 12.6% (12/95) (MECH. 12% (6/51), BIO 22.7% (5/22), REIMPL 4.5% (1/22); p = 0.19). Nineteen late deaths (22.9%) (19/83) (MECH 34.8% (15/43), BIO 16.7% (3/18), REIMPL 4.5% (1/22); p = 0.012) occurred during a mean follow-up of 41 ± 42 months (MECH 48 ± 48 months, BIO 25 ± 37 months, REIMPL 40 ± 28 months, p = 0.028). Postoperative NYHA class decreased significantly (p = 0.017) and performance status (p = 0.027) increased for the entire group compared to preoperative values.</p> <p>Conclusion</p> <p>Our data indicate that valve sparing aortic root reimplantation is safe and effective in septuagenarians, and is associated with low early and late morbidity and mortality.</p

Patient Acceptance of Noninvasive and Invasive Coronary Angiography

BACKGROUND: Noninvasive angiography using multislice computed tomography (MSCT) is superior to magnetic resonance imaging (MRI) for detection of coronary stenoses. We compared patient acceptance of these two noninvasive diagnostic tests and invasive conventional coronary angiography (Angio). METHODS AND FINDINGS: A total of 111 consecutive patients with suspected coronary artery disease underwent MSCT, MRI, and Angio. Subsequently, patient acceptance of the three tests was evaluated with questionnaires in all patients. The main acceptance variables were preparation and information prior to the test, degree of concern, comfort, degree of helplessness, pain (on visual analog scales), willingness to undergo the test again, and overall satisfaction. Preparation for each test was not rated significantly differently, whereas patients were significantly more concerned about Angio than the two noninvasive tests (p<0.001). No pain during MSCT, MRI, and Angio as assessed on visual analog scales (0 to 100) was reported by 99, 93, and 31 patients, respectively. Among the 82 patients who felt pain during at least one procedure, both CT (0.9±4.5) and MRI (5.2±16.6) were significantly less painful than Angio (24.6±23.4, both p<0.001). MSCT was considered significantly more comfortable (1.49±0.64) than MRI (1.75±0.81, p<0.001). In both the no-revascularization (55 patients) and the revascularization group (56 patients), the majority of the patients (73 and 71%) would prefer MSCT to MRI and Angio for future imaging of the coronary arteries. None of the patients indicated to be unwilling to undergo MSCT again. The major advantages patients attributed to MSCT were its fast, uncomplicated, noninvasive, and painless nature. CONCLUSIONS: Noninvasive coronary angiography with MSCT is considered more comfortable than MRI and both MSCT and MRI are less painful than Angio. Patient preference for MSCT might tip the scales in favor of this test provided that the diagnostic accuracy of MSCT can be shown to be high enough for clinical application

Energy Restriction during Childhood and Early Adulthood and Ovarian Cancer Risk

Dietary energy restriction may protect against cancer. In parts of the Netherlands, mostly in larger cities, periods of chronically impaired nutrition and even severe famine (Hunger Winter 1944–1945) existed during the 1930s and World War II (1940–1945). We studied the association between energy restriction during childhood and early adulthood on the risk of ovarian cancer later in life. In 1986, the Netherlands Cohort Study was initiated. A self-administered questionnaire on dietary habits and other cancer risk factors was completed by 62,573 women aged 55–69 years at baseline. Follow-up for cancer was established by record linkage to the Netherlands Cancer Registry. After 16.3 years of follow-up, 364 invasive epithelial ovarian cancer cases and 2220 subcohort members (sampled from the total cohort directly after baseline) with complete information confounders were available for case-cohort analyses. In multivariable analysis, ovarian cancer risk was lower for participants with an unemployed father during the 1930s (Hazard Ratio (HR), 0.70; 95% Confidence Interval (CI), 0.47–1.06) compared to participants with an employed father as well as for participants living in a city during World War II (HR, 0.69; 95% CI, 0.54–0.90) compared to participants living in the country-side. Residence in a Western City during the famine (Hunger Winter) was not associated with a decreased risk. Our results show a relation between proxy variables for modest energy restriction over a longer period of time during childhood or early adulthood and a reduced ovarian cancer risk

Asteroseismology and Interferometry

Asteroseismology provides us with a unique opportunity to improve our understanding of stellar structure and evolution. Recent developments, including the first systematic studies of solar-like pulsators, have boosted the impact of this field of research within Astrophysics and have led to a significant increase in the size of the research community. In the present paper we start by reviewing the basic observational and theoretical properties of classical and solar-like pulsators and present results from some of the most recent and outstanding studies of these stars. We centre our review on those classes of pulsators for which interferometric studies are expected to provide a significant input. We discuss current limitations to asteroseismic studies, including difficulties in mode identification and in the accurate determination of global parameters of pulsating stars, and, after a brief review of those aspects of interferometry that are most relevant in this context, anticipate how interferometric observations may contribute to overcome these limitations. Moreover, we present results of recent pilot studies of pulsating stars involving both asteroseismic and interferometric constraints and look into the future, summarizing ongoing efforts concerning the development of future instruments and satellite missions which are expected to have an impact in this field of research.Comment: Version as published in The Astronomy and Astrophysics Review, Volume 14, Issue 3-4, pp. 217-36

Growth temperature and genotype both play important roles in sorghum grain phenolic composition.

Polyphenols in sorghum grains are a source of dietary antioxidants. Polyphenols in six diverse sorghum genotypes grown under two day/night temperature regimes of optimal temperature (OT, 32/21 °C and high temperature (HT, 38/21 °C) were investigated. A total of 23 phenolic compounds were positively or tentatively identified by HPLC-DAD-ESIMS. Compared with other pigmented types, the phenolic profile of white sorghum PI563516 was simpler, since fewer polyphenols were detected. Brown sorghum IS 8525 had the highest levels of caffeic and ferulic acid, but apigenin and luteolin were not detected. Free luteolinidin and apigeninidin levels were lower under HT than OT across all genotypes (p ≤ 0.05), suggesting HT could have inhibited 3-deoxyanthocyanidins formation. These results provide new information on the effects of HT on specific polyphenols in various Australian sorghum genotypes, which might be used as a guide to grow high antioxidant sorghum grains under projected high temperature in the future

Selective Breeding for a Behavioral Trait Changes Digit Ratio

The ratio of the length of the second digit (index finger) divided by the fourth digit (ring finger) tends to be lower in men than in women. This 2D∶4D digit ratio is often used as a proxy for prenatal androgen exposure in studies of human health and behavior. For example, 2D∶4D ratio is lower (i.e. more “masculinized”) in both men and women of greater physical fitness and/or sporting ability. Lab mice have also shown variation in 2D∶4D as a function of uterine environment, and mouse digit ratios seem also to correlate with behavioral traits, including daily activity levels. Selective breeding for increased rates of voluntary exercise (wheel running) in four lines of mice has caused correlated increases in aerobic exercise capacity, circulating corticosterone level, and predatory aggression. Here, we show that this selection regime has also increased 2D∶4D. This apparent “feminization” in mice is opposite to the relationship seen between 2D∶4D and physical fitness in human beings. The present results are difficult to reconcile with the notion that 2D∶4D is an effective proxy for prenatal androgen exposure; instead, it may more accurately reflect effects of glucocorticoids, or other factors that regulate any of many genes

A GIS Model Predicting Potential Distributions of a Lineage: A Test Case on Hermit Spiders (Nephilidae: Nephilengys)

BACKGROUND: Although numerous studies model species distributions, these models are almost exclusively on single species, while studies of evolutionary lineages are preferred as they by definition study closely related species with shared history and ecology. Hermit spiders, genus Nephilengys, represent an ecologically important but relatively species-poor lineage with a globally allopatric distribution. Here, we model Nephilengys global habitat suitability based on known localities and four ecological parameters. METHODOLOGY/PRINCIPAL FINDINGS: We geo-referenced 751 localities for the four most studied Nephilengys species: N. cruentata (Africa, New World), N. livida (Madagascar), N. malabarensis (S-SE Asia), and N. papuana (Australasia). For each locality we overlaid four ecological parameters: elevation, annual mean temperature, annual mean precipitation, and land cover. We used linear backward regression within ArcGIS to select two best fit parameters per species model, and ModelBuilder to map areas of high, moderate and low habitat suitability for each species within its directional distribution. For Nephilengys cruentata suitable habitats are mid elevation tropics within Africa (natural range), a large part of Brazil and the Guianas (area of synanthropic spread), and even North Africa, Mediterranean, and Arabia. Nephilengys livida is confined to its known range with suitable habitats being mid-elevation natural and cultivated lands. Nephilengys malabarensis, however, ranges across the Equator throughout Asia where the model predicts many areas of high ecological suitability in the wet tropics. Its directional distribution suggests the species may potentially spread eastwards to New Guinea where the suitable areas of N. malabarensis largely surpass those of the native N. papuana, a species that prefers dry forests of Australian (sub)tropics. CONCLUSIONS: Our model is a customizable GIS tool intended to predict current and future potential distributions of globally distributed terrestrial lineages. Its predictive potential may be tested in foreseeing species distribution shifts due to habitat destruction and global climate change

Phosphorylated Nucleolin Interacts with Translationally Controlled Tumor Protein during Mitosis and with Oct4 during Interphase in ES Cells

BACKGROUND: Reprogramming of somatic cells for derivation of either embryonic stem (ES) cells, by somatic cell nuclear transfer (SCNT), or ES-like cells, by induced pluripotent stem (iPS) cell procedure, provides potential routes toward non-immunogenic cell replacement therapies. Nucleolar proteins serve as markers for activation of embryonic genes, whose expression is crucial for successful reprogramming. Although Nucleolin (Ncl) is one of the most abundant nucleolar proteins, its interaction partners in ES cells have remained unidentified. METHODOLOGY: Here we explored novel Ncl-interacting proteins using in situ proximity ligation assay (PLA), colocalization and immunoprecipitation (IP) in ES cells. PRINCIPAL FINDINGS: We found that phosphorylated Ncl (Ncl-P) interacted with translationally controlled tumor protein (Tpt1) in murine ES cells. The Ncl-P/Tpt1 complex peaked during mitosis and was reduced upon retinoic acid induced differentiation, signifying a role in cell proliferation. In addition, we showed that Ncl-P interacted with the transcription factor Oct4 during interphase in human as well as murine ES cells, indicating of a role in transcription. The Ncl-P/Oct4 complex peaked during early stages of spontaneous human ES cell differentiation and may thus be involved in the initial differentiation event(s) of mammalian development. CONCLUSIONS: Here we described two novel protein-protein interactions in ES cells, which give us further insight into the complex network of interacting proteins in pluripotent cells