Dark matter within high surface brightness spiral galaxies

We present results from a detailed dynamical analysis of five high surface brightness, late type spirals, studied with the aim to quantify the luminous-to-dark matter ratio inside their optical radii. The galaxies' stellar light distribution and gas kinematics have been observed and compared to hydrodynamic gas simulations, which predict the 2D gas dynamics arising in response to empirical gravitational potentials, which are combinations of differing stellar disk and dark halo contributions. The gravitational potential of the stellar disk was derived from near-infrared photometry, color-corrected to constant (M/L); the dark halo was modelled by an isothermal sphere with a core. Hydrodynamic gas simulations were performed for each galaxy for a sequence of five different mass fractions of the stellar disk and for a wide range of spiral pattern speeds. These two parameters mainly determine the modelled gas distribution and kinematics. The agreement between the non-axisymmetric part of the simulated and observed gas kinematics permitted us to conclude that the galaxies with the highest rotation velocities tend to possess near-maximal stellar disks. In less massive galaxies, with v_max<200 km/s, the mass of the dark halo at least equals the stellar mass within 2-3 R_disk. The simulated gas morphology provides a powerful tool to determine the dominant spiral pattern speed. The corotation radius for all galaxies was found to be constant at R_corotation ~ 3 R_disk and encloses the strong part of the stellar spiral in all cases.Comment: 28 pages, 7 figures; to appear in the Astrophysical Journal, Vol. 586, March 200

Neuroimaging in the evaluation of patients with non-acute headache

Available studies offer only limited guidance on neuroimaging of non-acute headache patients. The aim of this study was to estimate the frequency of significant intracranial lesions in patients with headache and to determine the clinical variables helpful in identifying patients with intracranial lesions. All patients aged ≥l 15 years attending the Neurology Clinic with non-acute headache were included in the study and followed prospectively. Every patient was investigated by neuroimaging studies, either computed tomography or magnetic resonance imaging. Neuroimaging results were classified as ‘significant abnormalities’, ‘nonsignificant abnormalities’ or ‘normal’. Significant abnormalities included neoplastic disease, hydrocephalus, vascular malformations, Chiari malformation, large arachnoid cysts, intracranial haemorrhage, and acute cerebral infarcts. Consecutive patients (n = 1876; 1243 women and 633 men) were included. Their mean age was 38 years (range 15-95 years). Neuroimaging studies detected significant lesions in 22 patients [1.2%, 95% confidence interval (CI) 0.7, 1.8]. The rate of significant intracranial abnormalities in patients with headache and normal neurological examination was 0.9% (95% CI 0.5, 1.4). The only clinical variable associated with a higher probability of intracranial abnormalities was neurological examination. The proportion of patients with headache and intracranial lesions is relatively small, but neither neurological examination nor the features in the clinical history permit us to rule out such abnormalitie

Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK

Copyright © 2014 Elsevier Inc. All rights reserved.Peer reviewedPublisher PD

ID1 and ID4 Are Biomarkers of Tumor Aggressiveness and Poor Outcome in Immunophenotypes of Breast Cancer

Inhibitor of differentiation (ID) proteins are a family of transcription factors that contribute to maintaining proliferation during embryogenesis as they avoid cell differentiation. Afterward, their expression is mainly silenced, but their reactivation and contribution to tumor development have been suggested. In breast cancer (BC), the overexpression of ID1 has been previously described. However, whether the remaining ID genes have a specific role in this neoplasia is still unclear. We studied the mRNA expression of all ID genes by q RT-PCR in BC cell lines and 307 breast carcinomas, including all BC subtypes. Our results showed that ID genes are highly expressed in all cell lines tested. However, ID4 presented higher expression in BC cell lines compared to a healthy breast epithelium cell line. In accordance, ID1 and ID4 were predominantly overexpressed in Triple-Negative and HER2-enriched samples. Moreover, high levels of both genes were associated with larger tumor size, histological grade 3, necrosis and vascular invasion, and poorer patients’ outcomes. In conclusion, ID1 and ID4 may act as biomarkers of tumor aggressiveness and worse prognosis in breast cancer, and they could be used as potential targets for new treatments discover.This research was funded by the Alicante Institute for Health and Biomedical Research (ISABIAL) (UGP 16-149 and UGP 180184) and Navarro-Tripodi Foundation (BOLA00150). M.G.E. was supported by fellowships issued by the Valencian Government of Spain (GVA) and the European Social Fund (ACIF/2016/004)

The 3rd World Conference on Kisspeptin, â Kisspeptin 2017: Brain and Beyondâ : Unresolved questions, challenges and future directions for the field

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144298/1/jne12600-sup-0001-FigS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144298/2/jne12600-sup-0002-FigS2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144298/3/jne12600_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144298/4/jne12600.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144298/5/jne12600-sup-0003-FigS3.pd

Applying diagnosis and pharmacy-based risk models to predict pharmacy use in Aragon, Spain: The impact of a local calibration

<p>Abstract</p> <p>Background</p> <p>In the financing of a national health system, where pharmaceutical spending is one of the main cost containment targets, predicting pharmacy costs for individuals and populations is essential for budget planning and care management. Although most efforts have focused on risk adjustment applying diagnostic data, the reliability of this information source has been questioned in the primary care setting. We sought to assess the usefulness of incorporating pharmacy data into claims-based predictive models (PMs). Developed primarily for the U.S. health care setting, a secondary objective was to evaluate the benefit of a local calibration in order to adapt the PMs to the Spanish health care system.</p> <p>Methods</p> <p>The population was drawn from patients within the primary care setting of Aragon, Spain (n = 84,152). Diagnostic, medication and prior cost data were used to develop PMs based on the Johns Hopkins ACG methodology. Model performance was assessed through r-squared statistics and predictive ratios. The capacity to identify future high-cost patients was examined through c-statistic, sensitivity and specificity parameters.</p> <p>Results</p> <p>The PMs based on pharmacy data had a higher capacity to predict future pharmacy expenses and to identify potential high-cost patients than the models based on diagnostic data alone and a capacity almost as high as that of the combined diagnosis-pharmacy-based PM. PMs provided considerably better predictions when calibrated to Spanish data.</p> <p>Conclusion</p> <p>Understandably, pharmacy spending is more predictable using pharmacy-based risk markers compared with diagnosis-based risk markers. Pharmacy-based PMs can assist plan administrators and medical directors in planning the health budget and identifying high-cost-risk patients amenable to care management programs.</p

A novel microarray approach reveals new tissue-specific signatures of known and predicted mammalian microRNAs

Microarrays to examine the global expression levels of microRNAs (miRNAs) in a systematic in-parallel manner have become important tools to help unravel the functions of miRNAs and to understand their roles in RNA-based regulation and their implications in human diseases. We have established a novel miRNA-specific microarray platform that enables the simultaneous expression analysis of both known and predicted miRNAs obtained from human or mouse origin. Chemically modified 2′-O-(2-methoxyethyl)-(MOE) oligoribonucleotide probes were arrayed onto Evanescent Resonance (ER) microchips by robotic spotting. Supplementing the complementary probes against miRNAs with carefully designed mismatch controls allowed for accurate sequence-specific determination of miRNA expression profiles obtained from a panel of mouse tissues. This revealed new expression signatures of known miRNAs as well as of novel miRNAs previously predicted using bioinformatic methods. Systematic confirmation of the array data with northern blotting and, in particular, real-time PCR suggests that the described microarray platform is a powerful tool to analyze miRNA expression patterns with rapid throughput and high fidelity

Improving interMediAte Risk management. MARK study

<p>Abstract</p> <p>Background</p> <p>Cardiovascular risk functions fail to identify more than 50% of patients who develop cardiovascular disease. This is especially evident in the intermediate-risk patients in which clinical management becomes difficult. Our purpose is to analyze if ankle-brachial index (ABI), measures of arterial stiffness, postprandial glucose, glycosylated hemoglobin, self-measured blood pressure and presence of comorbidity are independently associated to incidence of vascular events and whether they can improve the predictive capacity of current risk equations in the intermediate-risk population.</p> <p>Methods/Design</p> <p>This project involves 3 groups belonging to REDIAPP (RETICS RD06/0018) from 3 Spanish regions. We will recruit a multicenter cohort of 2688 patients at intermediate risk (coronary risk between 5 and 15% or vascular death risk between 3-5% over 10 years) and no history of atherosclerotic disease, selected at random. We will record socio-demographic data, information on diet, physical activity, comorbidity and intermittent claudication. We will measure ABI, pulse wave velocity and cardio ankle vascular index at rest and after a light intensity exercise. Blood pressure and anthropometric data will be also recorded. We will also quantify lipids, glucose and glycosylated hemoglobin in a fasting blood sample and postprandial capillary glucose. Eighteen months after the recruitment, patients will be followed up to determine the incidence of vascular events (later follow-ups are planned at 5 and 10 years). We will analyze whether the new proposed risk factors contribute to improve the risk functions based on classic risk factors.</p> <p>Discussion</p> <p>Primary prevention of cardiovascular diseases is a priority in public health policy of developed and developing countries. The fundamental strategy consists in identifying people in a high risk situation in which preventive measures are effective and efficient. Improvement of these predictions in our country will have an immediate, clinical and welfare impact and a short term public health effect.</p> <p>Trial Registration</p> <p>Clinical Trials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01428934">NCT01428934</a></p

Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance

Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum(ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPK alpha 1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism.Peer reviewe

Generation of Immortal Cell Lines from the Adult Pituitary: Role of cAMP on Differentiation of SOX2-Expressing Progenitor Cells to Mature Gonadotropes

The pituitary is a complex endocrine tissue composed of a number of unique cell types distinguished by the expression and secretion of specific hormones, which in turn control critical components of overall physiology. The basic function of these cells is understood; however, the molecular events involved in their hormonal regulation are not yet fully defined. While previously established cell lines have provided much insight into these regulatory mechanisms, the availability of representative cell lines from each cell lineage is limited, and currently none are derived from adult pituitary. We have therefore used retroviral transfer of SV40 T-antigen to mass immortalize primary pituitary cell culture from an adult mouse. We have generated 19 mixed cell cultures that contain cells from pituitary cell lineages, as determined by RT-PCR analysis and immunocytochemistry for specific hormones. Some lines expressed markers associated with multipotent adult progenitor cells or transit-amplifying cells, including SOX2, nestin, S100, and SOX9. The progenitor lines were exposed to an adenylate cyclase activator, forskolin, over 7 days and were induced to differentiate to a more mature gonadotrope cell, expressing significant levels of α-subunit, LHβ, and FSHβ mRNAs. Additionally, clonal populations of differentiated gonadotropes were exposed to 30 nM gonadotropin-releasing hormone and responded appropriately with a significant increase in α-subunit and LHβ transcription. Further, exposure of the lines to a pulse paradigm of GnRH, in combination with 17β-estradiol and dexamethasone, significantly increased GnRH receptor mRNA levels. This array of adult-derived pituitary cell models will be valuable for both studies of progenitor cell characteristics and modulation, and the molecular analysis of individual pituitary cell lineages