Lateralization of alpha oscillations in grapheme-color synaesthetes suggests altered color processing

In grapheme-color synaesthesia, the percept of a particular grapheme causes additional experiences of color. To investigate this interesting integration of modalities, brain activity was recorded of 7 synaesthetes and matched controls using magnetoencephalography. Subjects had to report the color change of one of two letters presented left and right of a fixation cross. One of the letters was neutral (eliciting no color percept), the other one could either be neutral, colored or elicit synaesthesia (in synaesthetes). Additionally, the side of color change was validly or invalidly cued. As expected, in both subject groups 10 Hz alpha oscillations decreased contralateral to the attended side leading to an alpha lateralization. Additionally, controls as well as synaesthetes showed a stronger alpha reduction if the attended letter was colored indicating that color increased the attentional allocation. Interestingly, synaesthetes show the same effect of alpha decrease for synaesthetic color. While color on the attended side reduced alpha power in controls and synaesthetes, color on the unattended side only reduced alpha power in synaesthetes. Indeed, also psychophysical measures indicated changed processing in synaesthetes of unattended color stimuli. Only controls profited from the cue when attending the noncolor stimulus. Synaesthetes, however, performed worse if the noncolor stimulus was validly compared to invalidly cued. This means that synaesthetes performed better on the colored stimulus despite an invalid attentional cue. Changed alpha power lateralization and psychophysics due to unattended colorful input indicate that synaesthetes are more affected by color than controls. This might be due to increased attentional demand

Augenveränderungen im All: Aktuelles zu Klinik, Pathogenese und Prävention [Eye changes in space : New insights into clinical aspects, pathogenesis and prevention]

Hintergrund Mehr denn je rückt die Erforschung der Veränderungen am Auge, die durch den Aufenthalt im All verursacht werden, ins Zentrum des Interesses der internationalen und nationalen Weltraumagenturen NASA (National Aeronautics and Space Administration), ESA (European Space Agency) und DLR (Deutsches Zentrum für Luft- und Raumfahrt). Neben weltraumstrahlungbedingten Katarakten können erhebliche Augenveränderungen, zusammengefasst unter dem „space flight-associated neuro-ocular syndrome“ (SANS) auftreten. Ziele der Arbeit Diese Übersicht soll den aktuellen Forschungsstand und künftige Bestrebungen auf dem Gebiet der Erforschung der Augenveränderungen bei SANS wiedergeben und die Relevanz für die terrestrische ophthalmologische Forschung aufzeigen. Material und Methoden Es erfolgt eine Analyse der bestehenden Publikationen zu dem Thema in PubMed sowie von Berichten bezüglich des Risikos von SANS, veröffentlicht von der NASA der USA. Ergebnisse Die Ursachen für die Entstehung der Augenveränderungen im All sind nicht geklärt. Faktoren wie die Erhöhung des intrakraniellen Drucks, Flüssigkeitsverschiebungen, Hyperkapnie und genetische Einflüsse sind Gegenstand intensiver Forschungsbemühungen. Ein terrestrisches Modell zur Induktion des Papillenödems konnte etabliert werden (Bettruhestudien mit −6° Kopftieflagerung als Weltraumanalogon). Gegenmaßnahmen zur Entwicklung der Augenveränderungen, wie beispielsweise intermittierend künstliche Schwerkraft, sind Gegenstand der aktuellen Studien. Schlussfolgerung Die Erforschung von SANS im Rahmen von Bettruhestudien wird in Zukunft sowohl für die Weltraumforschung als auch für die terrestrische Forschung weitere wichtige Erkenntnisse liefern. Klinische Forschungsprojekte können aus der Weltraumforschung abgeleitet werden

Experimental Simulation of the Effects of an Initial Antibiotic Treatment on a Subsequent Treatment after Initial Therapy Failure

General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Received: 24 October 2013; in revised form: 23 January 2014 / Accepted: 29 January 2014 / Published: 17 February 2014 Abstract: Therapy failure of empirical antibiotic treatments prescribed by primary care physicians occurs commonly. The effect of such a treatment on the susceptibility to second line antimicrobial drugs is unknown. Resistance to amoxicillin was rapidly induced or selected in E. coli at concentrations expected in the patient's body. Strains with reduced susceptibility outcompeted the wild-type whenever antibiotics were present, even in low concentrations that did not affect the growth rates of both strains. Exposure of E. coli to amoxicillin caused moderate resistance to cefotaxime. The combined evidence suggests that initial treatment by amoxicillin has a negative effect on subsequent therapy with beta-lactam antibiotics

Age-related changes in global motion coherence: conflicting haemodynamic and perceptual responses

Our aim was to use both behavioural and neuroimaging data to identify indicators of perceptual decline in motion processing. We employed a global motion coherence task and functional Near Infrared Spectroscopy (fNIRS). Healthy adults (n = 72, 18-85) were recruited into the following groups: young (n = 28, mean age = 28), middle-aged (n = 22, mean age = 50), and older adults (n = 23, mean age = 70). Participants were assessed on their motion coherence thresholds at 3 different speeds using a psychophysical design. As expected, we report age group differences in motion processing as demonstrated by higher motion coherence thresholds in older adults. Crucially, we add correlational data showing that global motion perception declines linearly as a function of age. The associated fNIRS recordings provide a clear physiological correlate of global motion perception. The crux of this study lies in the robust linear correlation between age and haemodynamic response for both measures of oxygenation. We hypothesise that there is an increase in neural recruitment, necessitating an increase in metabolic need and blood flow, which presents as a higher oxygenated haemoglobin response. We report age-related changes in motion perception with poorer behavioural performance (high motion coherence thresholds) associated with an increased haemodynamic response

Concerted nicking of donor and chromosomal acceptor DNA promotes homology-directed gene targeting in human cells

The exchange of genetic information between donor and acceptor DNA molecules by homologous recombination (HR) depends on the cleavage of phosphodiester bonds. Although double-stranded and single-stranded DNA breaks (SSBs) have both been invoked as triggers of HR, until very recently the focus has been primarily on the former type of DNA lesions mainly due to the paucity of SSB-based recombination models. Here, to investigate the role of nicked DNA molecules as HR-initiating substrates in human somatic cells, we devised a homology-directed gene targeting system based on exogenous donor and chromosomal target DNA containing recognition sequences for the adeno-associated virus sequence- and strand-specific endonucleases Rep78 and Rep68. We found that HR is greatly fostered if a SSB is not only introduced in the chromosomal acceptor but also in the donor DNA template. Our data are consistent with HR models postulating the occurrence of SSBs or single-stranded gaps in both donor and acceptor molecules during the genetic exchange process. These findings can guide the development of improved HR-based genome editing strategies in which sequence- and strand-specific endonucleolytic cleavage of the chromosomal target site is combined with that of the targeting vector

Selection-Independent Generation of Gene Knockout Mouse Embryonic Stem Cells Using Zinc-Finger Nucleases

Gene knockout in murine embryonic stem cells (ESCs) has been an invaluable tool to study gene function in vitro or to generate animal models with altered phenotypes. Gene targeting using standard techniques, however, is rather inefficient and typically does not exceed frequencies of 10−6. In consequence, the usage of complex positive/negative selection strategies to isolate targeted clones has been necessary. Here, we present a rapid single-step approach to generate a gene knockout in mouse ESCs using engineered zinc-finger nucleases (ZFNs). Upon transient expression of ZFNs, the target gene is cleaved by the designer nucleases and then repaired by non-homologous end-joining, an error-prone DNA repair process that introduces insertions/deletions at the break site and therefore leads to functional null mutations. To explore and quantify the potential of ZFNs to generate a gene knockout in pluripotent stem cells, we generated a mouse ESC line containing an X-chromosomally integrated EGFP marker gene. Applying optimized conditions, the EGFP locus was disrupted in up to 8% of ESCs after transfection of the ZFN expression vectors, thus obviating the need of selection markers to identify targeted cells, which may impede or complicate downstream applications. Both activity and ZFN-associated cytotoxicity was dependent on vector dose and the architecture of the nuclease domain. Importantly, teratoma formation assays of selected ESC clones confirmed that ZFN-treated ESCs maintained pluripotency. In conclusion, the described ZFN-based approach represents a fast strategy for generating gene knockouts in ESCs in a selection-independent fashion that should be easily transferrable to other pluripotent stem cells

Adult Type 3 Adenylyl Cyclase–Deficient Mice Are Obese

Background: A recent study of obesity in Swedish men found that polymorphisms in the type 3 adenylyl cyclase (AC3) are associated with obesity, suggesting the interesting possibility that AC3 may play a role in weight control. Therefore, we examined the weight of AC3 mice over an extended period of time. Methodology/Principal Findings: We discovered that AC3 2/2 mice become obese as they age. Adult male AC3 2/2 mice are about 40 % heavier than wild type male mice while female AC3 2/2 are 70 % heavier. The additional weight of AC3 2/2 mice is due to increased fat mass and larger adipocytes. Before the onset of obesity, young AC3 2/2 mice exhibit reduced physical activity, increased food consumption, and leptin insensitivity. Surprisingly, the obesity of AC3 2/2 mice is not due to a loss of AC3 from white adipose and a decrease in lipolysis. Conclusions/Significance: We conclude that mice lacking AC3 exhibit obesity that is apparently caused by low locomotor activity, hyperphagia, and leptin insensitivity. The presence of AC3 in primary cilia of neurons of the hypothalamus suggests that cAMP signals generated by AC3 in the hypothalamus may play a critical role in regulation of body weight

Predicting Transitions in Low and High Levels of Risk Behavior from Early to Middle Adolescence: The TRAILS Study

The present study examined the joint development of substance use and externalizing problems in early and middle adolescence. First, it was tested whether the relevant groups found in previous studies i.e., those with an early onset, a late onset, and no onset or low levels of risk behavior could be identified, while using a developmental model of a single, underlying construct of risk behavior. Second, departing from Moffitt’s taxonomy of antisocial behavior, it was tested if early, but not late, onset risk behavior is predicted by a problematic risk profile in childhood. Data were used from TRAILS, a population based cohort study, starting at age 11 with two follow-ups at mean ages of 13.6 and 16.3 years. Latent transition analyses demonstrated that, both in early and middle adolescence, a single underlying construct of risk behavior, consisting of two classes (labeled as low and high risk behavior), adequately represented the data. Respondents could be clearly classified into four possible transition patterns from early to middle adolescence, with a transition from high to low being almost non-existent (2.5 %), low to low (39.4 %) and low to high (41.8 %) being the most prevalent, and high to high (16.2 %) substantial. As hypothesized, only the high-high group was characterized by a clear adverse predictor profile in late childhood, while the low-high group was not. This study demonstrates that the development of substance use is correlated with externalizing problems and underscores the theory that etiologies of early and later onset risk behavior are different