592 research outputs found
High-field fMRI reveals brain activation patterns underlying saccade execution in the human superior colliculus
Background
The superior colliculus (SC) has been shown to play a crucial role in the initiation and coordination of eye- and head-movements. The knowledge about the function of this structure is mainly based on single-unit recordings in animals with relatively few neuroimaging studies investigating eye-movement related brain activity in humans.
Methodology/Principal Findings
The present study employed high-field (7 Tesla) functional magnetic resonance imaging (fMRI) to investigate SC responses during endogenously cued saccades in humans. In response to centrally presented instructional cues, subjects either performed saccades away from (centrifugal) or towards (centripetal) the center of straight gaze or maintained fixation at the center position. Compared to central fixation, the execution of saccades elicited hemodynamic activity within a network of cortical and subcortical areas that included the SC, lateral geniculate nucleus (LGN), occipital cortex, striatum, and the pulvinar.
Conclusions/Significance
Activity in the SC was enhanced contralateral to the direction of the saccade (i.e., greater activity in the right as compared to left SC during leftward saccades and vice versa) during both centrifugal and centripetal saccades, thereby demonstrating that the contralateral predominance for saccade execution that has been shown to exist in animals is also present in the human SC. In addition, centrifugal saccades elicited greater activity in the SC than did centripetal saccades, while also being accompanied by an enhanced deactivation within the prefrontal default-mode network. This pattern of brain activity might reflect the reduced processing effort required to move the eyes toward as compared to away from the center of straight gaze, a position that might serve as a spatial baseline in which the retinotopic and craniotopic reference frames are aligned
Vulnerability of drugâresistant EML4âALK rearranged lung cancer to transcriptional inhibition
A subset of lung adenocarcinomas is driven by the EML4âALK translocation. Even though ALK inhibitors in the clinic lead to excellent initial responses, acquired resistance to these inhibitors due to onâtarget mutations or parallel pathway alterations is a major clinical challenge. Exploring these mechanisms of resistance, we found that EML4âALK cells parental or resistant to crizotinib, ceritinib or alectinib are remarkably sensitive to inhibition of CDK7/12 with THZ1 and CDK9 with alvocidib or dinaciclib. These compounds robustly induce apoptosis through transcriptional inhibition and downregulation of antiâapoptotic genes. Importantly, alvocidib reduced tumour progression in xenograft mouse models. In summary, our study takes advantage of the transcriptional addiction hypothesis to propose a new treatment strategy for a subset of patients with acquired resistance to firstâ, secondâ and thirdâgeneration ALK inhibitors
miRNA in situ hybridization in circulating tumor cells - MishCTC
irculating tumor cells (CTCs) must be phenotypically and genetically characterized before they can be utilized in clinical applications. Here, we present the first protocol for the detection of miRNAs in CTCs using in situ hybridization (ISH) combined with immunomagnetic selection based on cytokeratin (CK) expression and immunocytochemistry. Locked-Nucleic Acid (LNA) probes associated with an enzyme-labeled fluorescence (ELF) signal amplification approach were used to detect miRNA-21 in CTCs. This protocol was optimized using both epithelial tumor (MDA-MB468) and epithelial non-tumor (MCF-10A) cell lines, and miRNA-21 was selected as the target miRNA because of its known role as an onco-miRNA. Hematopoietic cells do not express miRNA-21; thus, miRNA-21 is an ideal marker for detecting CTCs. Peripheral blood samples were taken from 25 cancer patients and these samples were analyzed using our developed protocol. Of the 25 samples, 11 contained CTCs. For all 11 CTC-positive samples, the isolated CTCs expressed both CK and miRNA-21. Finally, the protocol was applied to monitor miRNA-21 expression in epithelial to mesenchymal transition (EMT)-induced MCF-7 cells, an epithelial tumor cell line. CK expression was lost in these cells, whereas miRNA-21 was still expressed, suggesting that miRNA-21 might be a good marker for detecting CTCs with an EMT phenotype.JJDM thanks the Spanish Ministerio de EconomĂa y Competitividad for a RamĂłn y Cajal
Fellowship (Grant CTQ2012-34778). This research was partially supported by Marie Curie Career Integration Grants within the 7th European Community Framework Program
(FP7-PEOPLE-2011-CIG-Project Number 294142 to RMSM and FP7-PEOPLE-2012-CIG-Project Number 322276 toJJDM). Thisresearch wasalso partially
supported by Consejeria de Salud de la Junta de AndalucÄą
Ě
a (PI0294-2012)
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How predation and landscape fragmentation affect vole population dynamics
Background: Microtine species in Fennoscandia display a distinct north-south gradient from regular cycles to stable
populations. The gradient has often been attributed to changes in the interactions between microtines and their predators.
Although the spatial structure of the environment is known to influence predator-prey dynamics of a wide range of species,
it has scarcely been considered in relation to the Fennoscandian gradient. Furthermore, the length of microtine breeding
season also displays a north-south gradient. However, little consideration has been given to its role in shaping or generating
population cycles. Because these factors covary along the gradient it is difficult to distinguish their effects experimentally in
the field. The distinction is here attempted using realistic agent-based modelling.
Methodology/Principal Findings: By using a spatially explicit computer simulation model based on behavioural and
ecological data from the field vole (Microtus agrestis), we generated a number of repeated time series of vole densities
whose mean population size and amplitude were measured. Subsequently, these time series were subjected to statistical
autoregressive modelling, to investigate the effects on vole population dynamics of making predators more specialised, of
altering the breeding season, and increasing the level of habitat fragmentation. We found that fragmentation as well as the
presence of specialist predators are necessary for the occurrence of population cycles. Habitat fragmentation and predator
assembly jointly determined cycle length and amplitude. Length of vole breeding season had little impact on the
oscillations.
Significance: There is good agreement between our results and the experimental work from Fennoscandia, but our results
allow distinction of causation that is hard to unravel in field experiments. We hope our results will help understand the
reasons for cycle gradients observed in other areas. Our results clearly demonstrate the importance of landscape
fragmentation for population cycling and we recommend that the degree of fragmentation be more fully considered in
future analyses of vole dynamics
Liquid Biopsy in Non-Small Cell Lung Cancer (NSCLC)
Lung cancer is the leading cause of cancer deaths worldwide. To date, the gold standard for the molecular analysis of a patient affected by NSCLC is the tissue biopsy. The discovery of activating mutations and rearrangements in specific genes has revolutionized the therapeutic approaches of lung cancer over the last years. For this reason, a strict \u201cmolecular follow-up\u201d is mandatory to evaluate patient\u2019s disease evolution. Indeed, liquid biopsy has raised as the \u201cnew ambrosia of researchers\u201d as it could help clinicians to identify both prognostic and predictive biomarkers in a more accessible way. Liquid biopsy analysis can be used in different moments starting from diagnosis to relapse, earning multiple clinical meanings, offering thus a noninvasive but valid method to detect actionable mutations. Although the implementation of both exosomes and CTCs in clinical practice is several steps back, new advances and discoveries make them, together with the ctDNA, a very promising tool. In the following chapter we will discuss the recent advances of liquid biopsy in NSCLC highlighting the possible clinical utility of CTCs, ctDNA and exosomes
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Person-centred care in interventions to limit weight gain in pregnant women with obesity - a systematic review
Background
Person-centred care, asserting that individuals are partners in their care, has been associated with care satisfaction but the value of using it to support women with obesity during pregnancy is unknown. Excessive gestational weight gain is associated with increased risks for both mother and baby and weight gain therefore is an important intervention target. The aims of this review was to 1) explore to what extent and in what manner interventions assessing weight in pregnant women with obesity use person-centred care and 2) assess if interventions including aspects of person-centred care are more effective at limiting weight gain than interventions not employing person-centred care.
Methods
Ten databases were systematically searched in January 2014. Studies had to report an intervention offered to pregnant women with obesity and measure gestational weight gain to be included. All included studies were independently double coded to identify to what extent they included three defined aspects of person-centred care: 1) âinitiate a partnershipâ including identifying the personâs circumstances and motivation; 2) âworking the partnershipâ through sharing the decision-making regarding the planned action and 3) âsafeguarding the partnership through documentationâ of care preferences. Information on gestational weight gain, study quality and characteristics were also extracted.
Results
Ten studies were included in the review, of which five were randomised controlled trials (RCT), and the remaining observational studies. Four interventions included aspects of person-centred care; two observational studies included both âinitiating the partnershipâ, and âworking the partnershipâ. One observational study included âinitiating the partnershipâ and one RCT included âworking the partnershipâ. No interventions included âsafeguarding the partnership through documentationâ. Whilst all studies with person-centred care aspects showed promising findings regarding limiting gestational weight gain, so did the interventions not including person-centred care aspects.
Conclusions
The use of an identified person-centred care approach is presently limited in interventions targeting gestational weight gain in pregnant women with obesity. Hence to what extent person-centred care may improve health outcomes and care satisfaction in this population is currently unknown and more research is needed. That said, our findings suggest that use of routines incorporating person-centredness are feasible to include within these interventions
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