The centrosomal kinase NEK2 is a novel splicing factor kinase involved in cell survival

NEK2 is a serine/threonine kinase that promotes centrosome splitting and ensures correct chromosome segregation during the G2/M phase of the cell cycle, through phosphorylation of specific substrates. Aberrant expression and activity of NEK2 in cancer cells lead to dysregulation of the centrosome cycle and aneuploidy. Thus, a tight regulation of NEK2 function is needed during cell cycle progression. In this study, we found that NEK2 localizes in the nucleus of cancer cells derived from several tissues. In particular, NEK2 co-localizes in splicing speckles with SRSF1 and SRSF2. Moreover, NEK2 interacts with several splicing factors and phosphorylates some of them, including the oncogenic SRSF1 protein. Overexpression of NEK2 induces phosphorylation of endogenous SR proteins and affects the splicing activity of SRSF1 toward reporter minigenes and endogenous targets, independently of SRPK1. Conversely, knockdown of NEK2, like that of SRSF1, induces expression of pro-apoptotic variants from SRSF1-target genes and sensitizes cells to apoptosis. Our results identify NEK2 as a novel splicing factor kinase and suggest that part of its oncogenic activity may be ascribed to its ability to modulate alternative splicing, a key step in gene expression regulation that is frequently altered in cancer cells

Pulse processing routines for neutron time-of-flight data

A pulse shape analysis framework is described, which was developed for n_TOF-Phase3, the third phase in the operation of the n_TOF facility at CERN. The most notable feature of this new framework is the adoption of generic pulse shape analysis routines, characterized by a minimal number of explicit assumptions about the nature of pulses. The aim of these routines is to be applicable to a wide variety of detectors, thus facilitating the introduction of the new detectors or types of detectors into the analysis framework. The operational details of the routines are suited to the specific requirements of particular detectors by adjusting the set of external input parameters. Pulse recognition, baseline calculation and the pulse shape fitting procedure are described. Special emphasis is put on their computational efficiency, since the most basic implementations of these conceptually simple methods are often computationally inefficient.Comment: 13 pages, 10 figures, 5 table

miRNAs in the vitreous humor of patients affected by idiopathic epiretinal membrane and macular hole

The aim of the present study was to assess the expression of miRNAs in the Vitreous Humor (VH) of patients with Macular Hole (MH) and Epiretinal Membrane (ERM) compared to a control group. assays. Finally, we created a biological network of differentially expressed miRNA targets and their nearest neighbors. assays of the VH of patients affected by MH and ERM, with respect to controls, showed that the most differentially expressed were miR-19b (FC -9.13, p:<0.00004), mir-24 (FC -7.52, p:<0.004) and miR-142-3p (FC -5.32, p:<0.011). Our network data showed that deregulation of differentially expressed miRNAs induces an alteration of several pathways associated with genes involved in both MH and ERM.The present study suggests that disregulation of miR-19b, miR-24 and miR-142-3p, might be related to the alterations that characterize patients affected by MH and ERM

Regional Development of Glioblastoma: The Anatomical Conundrum of Cancer Biology and Its SurgicalImplication

Glioblastoma (GBM) are among the most common malignant central nervous system (CNS) cancers, they are relatively rare. This evidence suggests that the CNS microenvironment is naturally equipped to control proliferative cells, although, rarely, failure of this system can lead to cancer development. Moreover, the adult CNS is innately non-permissive to glioma cell invasion. Thus, glioma etiology remains largely unknown. In this review, we analyze the anatomical and biological basis of gliomagenesis considering neural stem cells, the spatiotemporal diversity of astrocytes, microglia, neurons and glutamate transporters, extracellular matrix and the peritumoral environment. The precise understanding of subpopulations constituting GBM, particularly astrocytes, is not limited to glioma stem cells (GSC) and could help in the understanding of tumor pathophysiology. The anatomical fingerprint is essential for non-invasive assessment of patients' prognosis and correct surgical/radiotherapy planning

Performance evaluation of SiPMʼs for low threshold gamma detection

In the context of the on-line monitoring of short and medium term for radioactive waste repository, a new system has been planned. Such system makes use a new kind of detector, named Silicon Photomultiplier, coupled to scintillating fibres to be positioned around each waste drum in shape of fine grid. The purpose of this design is evaluate the variations of the radioactivity distribution by counting the gamma radiation

Non-invasive evaluation of tacalcitol plus puva versus tacalcitol plus UVB-NB in the treatment of psoriasis: "right-left intra-individual pre/post comparison design".

Photochemotherapy with psoralen plus ultraviolet A (PUVA) and phototherapy with UVB narrow band (UVB-NB) are used in the treatment of psoriasis. Numerous studies have shown that the additional administration of either topical or systemic antipsoriatic agents may effectively increase the efficacy of these therapies. This study aimed to compare through objective data the efficacy of topical tacalcitol in combination with PUVA or UVB-NB versus PUVA and UVB-NB monotherapy in the treatment of mild to moderate chronic plaque psoriasis. Modified Psoriasis Area and Severity Index (PASI) score, transepidermal water loss (TEWL) and stratum corneum hydration were used to monitor the restoration of skin barrier in the psoriatic plaques of 40 patients during photochemotherapy. The study was a right-left, intra-individual, pre/post comparison trial. PUVA and UVB-NB treatments were given three times a week. On those plaques localized on the right side of the body tacalcitol ointment was applied once a day, in the evening. Corneometry, TEWL and modified PASI score were used to evaluate the response to the treatment at baseline, one month and two months. Thirty-six of the forty enrolled subjects completed the study. The comparison between combination treatments and the PUVA/UVB-NB monotherapy showed no significant differences with regard to modified PASI index. However, significant differences were recorded with regard to TEWL and corneometry. The combination of tacalcitol plus PUVA or tacalcitol plus UVB-NB restored epidermal barrier functions as well as skin hydration faster than PUVA or UVB-NB monotherapy (TEWL: p=0.0050 and corneometry: p=0.003). The combination of tacalcitol plus UVB-NB allowed a better restoration of skin barrier functions than tacalcitol plus PUVA (p=0.013). In conclusion, the combination of tacalcitol plus PUVA or plus UVB-NB improves the therapeutic result. In addition, the data from TEWL and skin hydration suggest a means in which tacalcitol plus UVB-NB induces a better normalization of skin biophysical parameters

Increased adiposity appraised with cun-bae is highly predictive of incident hypertension. The sun project

Overweight and obesity are growing worldwide and strongly associated with hypertension. The Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) index is proposed as an optimal indicator of body fatness. We aimed to investigate the association of body fat as captured by the CUN-BAE index with incident hypertension in a Mediterranean population. We assessed 15,950 participants of the SUN (Seguimiento Universidad de Navarra) prospective cohort (63.7% women) initially free of hypertension. Participants completed follow-up questionnaires biennially. A validated 136-item food-frequency questionnaire was administered at baseline. We used Cox models adjusted for multiple confounders. Among 12.3 years of median follow-up (interquartile range: 8.3, 15.0 years), 2160 participants reported having received a diagnosis of hypertension. We observed a strong direct association between progressively higher the CUN-BAE index at baseline and incident hypertension during follow-up in multivariable-adjusted models for men and women, even after further adjustment for BMI ≥ 30 kg/m2, showing a significant association also in non-obese participants. For each 2-unit increase in the CUN-BAE index, hypertension risk increased by 27% and 29% in men and women, respectively. The results remained significant when considering longitudinal repeated measures of changes in body fat assessed with the CUN-BAE index among the different biennial follow-up questionnaires. Our results emphasize the importance of reducing and maintaining a low body fat to prevent hypertension