Miracle-dz/UniFAR-FTUs huggingface dataset:
MCP-1 Stimulates MMP-9 Expression via ERK 1/2 and p38 MAPK Signaling Pathways in Human Aortic Smooth Muscle Cells

Objective: We investigated the molecular mechanism underlying the role of monocyte chemoattractant protein-1 (MCP-1) in the formation and development of human abdominal aortic aneurysm (AAA). Methods: We examined protein expression profiles using a protein array and found that MCP-1 was the most highly expressed protein in AAA tissues compared with normal aortas. To investigate the potential mechanism of MCP-1 involvement in the pathogenesis of AAA, we treated human aortic smooth muscle cells (HASMCs) with human recombinant MCP-1. Results: MCP-1 was the most highly expressed protein in AAA tissues compared with normal aorta; matrix metalloproteinase-9 (MMP-9) expression was also significantly increased. Treatment with MCP-1 significantly increased the expression and activation of MMP-9 and activated the three major mitogen activated protein kinases (MAPKs) extracellular signal regulated kinase (ERK), c-Jun amino terminal kinase (JNK1/2) and p38 MAPK. Furthermore, MCP-1-induced secretion of MMP-9 was inhibited by U0126 (inhibitor of the ERK 1/2 pathway) and SB203580 (inhibitor of the p38 MAPK pathway), but not SP600125 (inhibitor of the JNK1/2 pathway). Conclusion: These data demonstrate that MCP-1 stimulates secretion of MMP-9 directly through the ERK1/2 and p38 MAPK mediated pathways in HASMCs. Thus, inhibition of this molecular mechanism might be a potential therapeutic target in the non-surgical treatment of AAA.
U1 RNA induces innate immunity signaling.

OBJECTIVE The U1-70-kd RNP is a prominent target of autoimmunity in connective tissue diseases. In this study, we explored whether its endogenous ligand, U1 RNA, mediates a proimmune signal and may be immunogenic. METHODS We assayed the proliferation of control and MyD88-knockout splenocytes in response to in vitro-synthesized U1 RNA, and measured interleukin-6 (IL-6) and IL-8 secretion induced by U1 RNA in a human cell line competent for signaling through Toll-like receptor 3 (TLR-3) and TLR-5. RESULTS Treatment with U1 RNA or with poly(I-C), a known agonist of TLR-3, induced approximately twice as much control splenocyte proliferation as did treatment with RNase-digested U1 RNA. Proliferation in response to either poly(I-C) or U1 RNA by MyD88-knockout splenocytes was similarly attenuated. Similar to poly(I-C), U1 RNA induced significant secretion of both IL-6 and IL-8 from a TLR-3-expressing human cell line; in contrast, the TLR-5 agonist flagellin induced predominantly IL-8 secretion. Pretreatment of U1 RNA with RNase abolished IL-6 and IL-8 secretion. CONCLUSION U1 RNA is capable of inducing manifestations consistent with TLR-3 activation. The ability of U1 RNA (which has a substantial double-stranded secondary structure) to activate TLR-3 may contribute to the immunogenicity of the U1-70-kd autoantigen. Stimulation of innate immunity by native RNA molecules with a double-stranded secondary structure may help explain the high prevalence of autoimmunity to RNA binding proteins.
Differences in risk of Crohn's disease in offspring of mothers and fathers with inflammatory bowel disease.

OBJECTIVE To determine whether there are any unusual patterns of transmission of susceptibility to inflammatory bowel disease (IBD) within multiplex families. METHODS Individuals with IBD were recruited for genome-wide screening of susceptibility genes. The extent of familial aggregation and blood relationships in multiplex families were determined by questionnaires given to participants followed up by confirmation of disease diagnosis by participants' physicians. RESULTS Of 135 families identified in which both a parent and a child had IBD, 93 involved transmission of susceptibility to disease from mother to child versus 42 examples of transmission from father to child (p = 0.00001, exact two-tailed binomial test). This distortion in transmission on the basis of the sex of the parent was observed only among non-Jewish pairs with Crohn's disease (CD), in which, of 33 parent-child pairs with CD, disease susceptibility was transmitted from the mother 28 times (p = 0.00007). CONCLUSION Susceptibility to CD in a subset of patients may involve a gene that is imprinted.
Short-term projection of cancer incidence in Japan using an age-period interaction model with spline smoothing.

OBJECTIVE In Japan, population-based cancer incidence data are reported several years behind the latest year of cancer mortality data. To bridge this gap, we aimed to determine a short-term projection method for cancer incidence. METHODS Data between 1985 and 2007 were obtained from the population-based cancer registries in four prefectures (Miyagi, Yamagata, Fukui and Nagasaki). Three projection models were examined: generalized linear model with age and period (A + P linear); generalized linear model with age, period and their interactions (A*P linear); and generalized additive model with age, period and their interactions smoothed by spline (A*P spline). We performed a 5-year projection for the years 2000 and 2005, based on the data of 1985-95 and 1985-2000, respectively. Seven cancer sites (stomach, liver, colorectal, lung, female breast, cervix uteri and prostate) and all cancers combined were analyzed. The accuracy of projection was evaluated by whether each observed number fell within the 95% confidence interval of the projected number. RESULTS The A*P spline model accurately projected 8 of 13 cancer site-sex combinations, whereas the number of site-sex combinations of accurate projection was 2 and 6 for A + P linear and A*P linear models, respectively. For liver and colorectal cancers, the A*P spline model alone performed accurate projections; the relative differences between projected and observed numbers of cancer incidence ranged between -0.4 and +10.9% for the A*P spline, and between +7.4 and +37.6% for the other two models. All three models failed to project sudden increases in prostate cancer between 2000 and 2005. CONCLUSIONS The A*P spline model is a candidate method for the projection of cancer incidence in Japan. However, we need a continuous validation for prostate cancer.
[Food consumption, dietary habits and nutritional status of the population of Reus: follow-up from preconception throughout pregnancy and after birth].

BACKGROUND AND OBJECTIVE To describe the evolution of food, energy and nutritional consumption at preconception, weeks 6, 10, 26 and 38 of pregnancy, and 6 and 26 weeks after birth. SUBJECTS AND METHOD Longitudinal evaluation of the nutritional status in 80 healthy volunteers with the intention of immediate conception was performed. Food consumption was estimated using the 7 day register. Toxic habits and physical activity in each phase were also estimated. Education level, weight, height and parity were recorded at preconception. RESULTS Food and nutritional consumption varied slightly between preconception and pregnancy with the exception of increased consumption of milk, fruit and vegetables and reduced consumption of sugars, sugar-containing and alcoholic drinks. Energy intake did not vary significantly during pregnancy but increased 6 weeks after birth, coinciding with lactation. However recommended energy intakes were not met in any of the phases of the study. Six months after birth, women had lower food, energy and nutritional intakes than during the preconception period. The probability of inadequate intake of iron, calcium, vitamin B6 and folates was increased in the last weeks of pregnancy and this continued until up to 6 months after birth. CONCLUSIONS In this study, pregnant women did not increase energy and nutritional intake during pregnancy with respect to the preconception period. Energy intake was increased immediately after birth, coinciding with lactation. Throughout the study, however, the reported consumption was lower than recommended daily intakes.
A study of the translations of terms related to practical laws of religion (furū al-dīn): Raising students’ awareness of culture-bound items

Translation of culture-bound terms is of special importance in translation theory and practice. The present study is an attempt to examine the procedures used in translating these terms in the English translations of the Holy Qur’an. As such, English equivalents of terms related to Practical laws of religion (Furū al-Dīn) in five English versions of the Qur'an are identified and the translation procedures used in them in addition to the frequency of occurrence of each procedure have been examined. The study reveals that literal translation is not only the most frequently used procedure but also the most appropriate one in translating such terms.
Biology of Reproduction Highlights

Adolescent pregnancy and maternal overnourishment. In a paper on p. 231 of this issue, Wallace and colleagues provide important new results from a study of overnourished adolescent sheep in which maternal tissue synthesis has been shown to take priority and result in reduced placental growth and, consequently, a significant decrease in birth weight of the lamb. The authors provide results of a study to determine whether GH can influence fetal growth and body composition by increasing placental size or by altering maternal metabolism. The effects of exogenous GH were on maternal endocrinology, metabolism, and body composition; however, GH also increased fetal growth and fetal adiposity without affecting placental size. The results provide evidence that treatment of ewes with GH during late gestation can partially alleviate intrauterine growth retardation in overnourished primiparous ewes without affecting reduced placental growth that is characteristic of this sheep model for adolescent pregnancy in humans.
Results of laparoscopic adrenalectomy for suspected and unsuspected malignant adrenal neoplasms.

BACKGROUND Laparoscopic resection for malignant adrenal tumors is controversial, because they are rare and limited data exist in the literature. HYPOTHESIS Laparoscopic adrenalectomy for malignant adrenal tumors is safe and effective. PATIENTS AND METHODS Twenty-three patients who had a laparoscopic approach for suspected and unsuspected malignant adrenal tumors were studied retrospectively. The adrenal mass was suspected to be metastatic if the patient had a history of previous extra-adrenal primary malignancy and/or positive fine-needle aspiration cytologic findings. A primary adrenal cancer was suspected if there were positive fine-needle aspiration cytologic findings and/or a malignant adrenal imaging phenotype. MAIN OUTCOME MEASURES (1) Margins of tumor resection, (2) tumor recurrence (locoregional, port site, and distant), and (3) disease-free survival. RESULTS Twenty-three patients (15 men and 8 women) had 24 laparoscopic procedures (20 adrenalectomies, 3 biopsies, and 1 diagnostic laparoscopy). Permanent histologic specimens in the 23 patients showed 5 adrenocortical cancers, 1 undifferentiated adrenal cancer, 13 adrenal metastases, 2 lymphomas, and 2 cases with no evidence of tumor. Clinically suspected adrenal metastases were true positive in 19 patients (83%). The sensitivity of fine-needle aspiration cytology was 57% (n = 7). Only 1 of 6 patients with primary adrenal cancer was suspected to have a malignant tumor preoperatively. The tumor resection margin was negative in all adrenalectomies. There were 3 locoregional recurrences (2 local and 1 lymph node metastasis) in the 6 patients with primary adrenal cancer, no port site recurrences, and 4 distant recurrences in 13 patients with metastatic adrenal tumors. The disease-free survival was 65% at a mean follow-up time of 3.3 years (range, 1-7 years). CONCLUSIONS A laparoscopic approach in patients with suspected adrenal metastasis can be both diagnostic and therapeutic, and achieves complete tumor resection. In contrast, laparoscopic adrenalectomy for clinically unsuspected adrenocortical cancer is associated with a high recurrence rate. Furthermore, preoperative fine-needle aspiration cytology for the evaluation of suspected malignant adrenal tumors is unreliable.
Analysis of expressed sequence tags (ESTs) from the scaly green flagellate Scherffelia dubia Pascher emend. Melkonian et Preisig.

Partial sequencing of cDNA libraries to generate expressed sequence tags (ESTs) is an effective means of gene discovery, generation of molecular markers and characterization of transcription patterns. We have constructed an EST-database of the scaly green flagellate Scherffelia dubia (Chlorophyta) containing 361 sequences. cDNAs were obtained from interphase cells and from cells regenerating flagella. Analysis of the ESTs identified 138 EST-groups with significant similarity to known sequences. 134 EST-groups showed no significant similarity to any sequences in the databases. Most of the ESTs with similarity to known proteins are associated with typical interphase cell functions of a photosynthetic plant cell: assimilation of nutrients and biosynthesis of proteins. Others are related to the activation of the secretory pathway or the biogenesis of scales (e.g. kdo-synthase). Comparison of S. dubia ESTs with the genome of Arabidopsis thaliana and the EST database of Chlamydomonas reinhardtii revealed that S. dubia ESTs with similarity to known proteins were more similar to sequences in C. reinhardtii than to those of A. thaliana. Additionally, ESTs for guanylyl cyclase and cGMP phosphodiesterase are present in the two flagellates, but so far these gene products have not been found in embryophytes.
Fiduciary Law and Responsible Investing: In Nature's Trust

This book investigates fiduciary law’s influence on the financial economy’s environmental performance. It focuses on how the law affects responsible investing and considers possible legal reforms to shift financial markets towards sustainability. Fiduciary law governs how trustees, fund managers and other custodians administer the investment portfolios owned by beneficiaries. Written for a diverse audience, not just legal scholars, the book examines in a multi-jurisdictional context an array of philosophical, institutional and economic issues that have shaped the movement for responsible investing and its legal framework. Fiduciary law has acquired greater influence in the financial economy in tandem with the extraordinary recent growth of institutional funds such as pension plans and insurance company portfolios. While the fiduciary prejudice against responsible investing has somewhat waned in recent years, owing mainly to reinterpretations of fiduciary and trust law, significant barriers remain. This book advances the notion of ‘nature’s trust’ to metaphorically signal how fiduciary responsibility should accommodate society’s dependence on long-term environmental well-being. Financial institutions, managing vast investment portfolios on behalf of millions of beneficiaries, should manage those investments with regard to the broader social interest in sustaining ecological health. Even for their own financial self-interest, investors over the long term should benefit from maintaining nature’s capital. We should expect everyone to act in nature’s trust, from individual funds to market regulators. The ancient public trust doctrine could be refashioned for stimulating this change, and sovereign wealth funds should take the lead in pioneering best practices for environmentally responsible investing.
Suppression of Virus Load by Highly Active Antiretroviral Therapy in Rhesus Macaques Infected with a Recombinant Simian Immunodeficiency Virus Containing Reverse Transcriptase from Human Immunodeficiency Virus Type 1

ABSTRACT We have modeled highly active antiretroviral therapy (HAART) for AIDS in rhesus macaques infected with a chimera (RT-SHIV) of simian immunodeficiency virus containing reverse transcriptase from human immunodeficiency virus type-1 (HIV-1). Seven RT-SHIV-infected macaques were treated with a combination of efavirenz (200 mg orally once daily), lamivudine (8 mg/kg subcutaneously once daily), and tenofovir (30 mg/kg subcutaneously once daily). Plasma viral RNA levels in all animals were reduced by more than 1,000-fold after 4 weeks and, in six of the seven animals, were reduced to undetectable levels after 10 weeks. Virus loads increased slightly between 12 and 16 weeks of treatment, associated with problems with the administration of efavirenz. After a change in the method of efavirenz administration, virus loads declined again and remained undetectable in the majority of animals for the duration of therapy. Treatment was stopped for three animals after 36 weeks of therapy, and virus loads increased rapidly. Posttreatment RT-SHIV isolates had no mutations associated with resistance to any of the three drugs. Efavirenz treatment was stopped, but lamivudine and tenofovir treatment for two other macaques was continued. The virus load in one of these two animals rebounded; virus from this animal was initially free of drug-resistance mutations but acquired the K65R mutation in reverse transcriptase at 11 weeks after efavirenz treatment was withdrawn. These results mimic HAART of HIV-1-infected humans. The RT-SHIV/rhesus macaque model should be useful for studies of tissue reservoirs and sites of residual replication that are not possible or practical with humans.
Comparative genomic analysis of intracranial germ cell tumors – the preliminary study focused on Sonic Hedgehog signaling pathway

Aim of the study Examination of copy number changes in a group of intracranial germ cell tumors (GCTs) with particular focus on putative aberrations of the main genes coding SHh pathway proteins. Material and methods The study was performed on DNA isolated from fresh-frozen tumor tissue samples from eight GCTs, including six intracranial GCTs. The intracranial group consisted of three germinomas, two mature teratomas and one mixed germ cell tumor. Comparative genomic profiling analysis was carried out using microarray-CGH method (Cytosure ISCA UPD 4×180k, OGT). The results were analyzed with Feature Extraction (Agilent Technologies) and Nexus Copy Number (BioDiscovery) softwares. Results and conclusions Chromosomal aberrations were found in two intracranial germinomas. These tumors were characterized by complex genomic profiles encompassing chromosomes 7, 8, 9, 10, 11, 12, 16, 17 and 19. Common findings were gain at 12p13.33p11. 1 of 35 Mbp and gain at 17q11.1q25. 3 of 55 Mbp. In one tumor, also SHh (7q36.3), SMO (7q32.1) and GLI3 (7p14.1) copy gains occurred together with 9q21.11q34. 3 loss, including PTCH1, all being elements of SHh signaling pathway. Moreover, both tumors showed various copy gain of genes being ligands, regulators, receptors or target genes of SHh (MTSS1; PRKACA and FKBP8) as well as gain of genes of SHh coopting WNT pathway (WNT3, WNT5B, WNT9B in both tumors; WNT16, WNT2 in pineal lesion). Further studies on larger group are needed to characterize SHh-related gene alterations in intracranial GCTs and for searching genotype-phenotype relations.
On the Moment-Determinance and Random Mixture of Nakagami-m Variates

We study complex-valued Nakagami-m variates, establishing the moment determinance of the envelope, phase and joint envelope-phase Nakagami-m probability density functions (pdf's). Inspired by that result, we then show that Nakagami-m variates with arbitrary fading figure m can be accurately decomposed onto a mixture of Nakagami-m variates with integer or half-integer m, i.e, 2m ∈ ℕ+. The latter has the immediate theoretical implication that results currently known to hold for Nakagami-m channels under the constraint 2m ∈ ℕ+ can accurately be extended to arbitrary m via simple linear decomposition, with weights given by the random mixture probabilities, for which formulas are provided. The latter is illustrated with an example of the application of the random mixture decomposition to the simplification and generalization of bit error rate (BER) expressions for PSK modulation in the Nakagami-m relay channel. For completeness, implications on possible extensions and improvements of existing methods to generate Nakagami-m variates is also briefly discussed in the form of further examples.
UNILATERAL PERIPAPILLARY INTRACHOROIDAL CAVITATION AND OPTIC DISK ROTATION

Purpose: To examine the morphology of the optic nerve head in patients with unilateral peripapillary intrachoroidal cavitations (PICCs). Methods: The hospital-based observational study included patients with unilateral PICCs. Tomographic images of the parapapillary fundus were taken by enhanced depth imaging mode of optical coherent tomography. The ocular biometric parameters were compared between the affected eyes and the contralateral unaffected eyes. Results: The study population consisted of 30 patients with a mean age of 42.7 ± 13.8 years (range: 22–72 years), mean axial length of 26.7 ± 2.4 mm (range: 22.00–32.30 mm), and mean refractive error of −8.71 ± 5.21 diopters (range: −20.50 to +0.50 diopters). In the eyes affected by PICC as compared with the contralateral eyes, the vertical (P = 0.001) and the minimal optic disk diameters (P = 0.01) were significantly shorter, the ratio of minimal to maximal disk diameter was significantly lower (P = 0.03), and the angle of disk rotation was significantly higher (P < 0.001). Conclusion: In patients with unilateral PICCS, the eyes with PICCs had optic disks that were more spindlelike configured because of a disk rotation around the vertical axis and around the sagittal axis as compared with the contralateral eyes.
Early assessment of outcome in cardiogenic shock: Relevance of plasma N-terminal pro-B-type natriuretic peptide and interleukin-6 levels*

Objective:Plasma N-terminal pro-B-type natriuretic peptide (Nt-pro-BNP) levels are frequently elevated in critically ill patients and are associated with an increased mortality. In this study, we determined Nt-pro-BNP levels in patients with cardiogenic shock (CS) and evaluated its association with clinical and hemodynamic parameters and 30-day mortality. Design:Retrospective study. Setting:Two, eight-bed intensive care units at a university and a community hospital. Patients:Retrospective study on stored plasma samples of 58 patients with CS, obtained at admission to the intensive care unit. Interventions:None. Measurements and Main Results:Massively elevated Nt-pro-BNP concentrations showed no significant association with duration of shock, total Sequential Organ Failure Assessment score, or invasive hemodynamic parameters at the time of blood sampling but a significant association with estimated glomerular filtration rate (p < 0.001), C-reactive protein (p = 0.03), age (p = 0.005), and body weight (p = 0.03). Both in univariate and multivariate survival analyses, Nt-pro-BNP levels above the median (>12,782 pg/mL) were significant predictors of 30-day mortality (p < 0.001) and showed a complementary role with interleukin (IL)-6 in predicting outcome. Patients with IL-6 >195 pg/mL and Nt-pro-BNP above the median value had the highest 30-day mortality (93.7%), whereas patients with lower IL-6 levels together with lower Nt-pro-BNP levels had significantly better survival (mortality rate 26.3%). Among patients who had acute myocardial infarction, those with Nt-pro-BNP concentrations above the median level showed a highly impaired clinical course even if coronary revascularization was successful (30-day mortality 90.9% vs. 29.4%, p = 0.001), whereas survival of patients with unsuccessful revascularization did not differ significantly with respect to the median of Nt-pro-BNP (30-day survival rate 81.8% vs. 75.0%, p = 0.71). Conclusion:The massive elevations of Nt-pro-BNP observed in the early phase of CS seem to be independent of ventricular performance. Nt-pro-BNP levels are nevertheless predictive of 30-day survival in patients with CS especially in those with successful revascularization and might be used in combination with IL-6 for estimation of outcome early on.