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Cross-modal Action Complexity: Action- and Rule-related Memory Retrieval in Dual-response Control
(2017)
Normally, we do not act within a single effector system only, but rather coordinate actions across several output modules (cross-modal action). Such cross-modal action demands can vary substantially with respect to their complexity in terms of the number of task-relevant response combinations and to-be-retrieved stimulus-response (S-R) mapping rules. In the present study, we study the impact of these two types of cross-modal action complexity on dual-response costs (i.e., performance differences between single- and dual-action demands). In Experiment 1, we combined a manual and an oculomotor task, each involving four response alternatives. Crucially, one (unconstrained) condition involved all 16 possible combinations of response alternatives, whereas a constrained condition involved only a subset of possible response combinations. The results revealed that preparing for a larger number of response combinations yielded a significant, but moderate increase in dual-response costs. In Experiment 2, we utilized one common lateralized auditory (e.g., left) stimulus to trigger incompatible response compounds (e.g., left saccade and right key press or vice versa). While one condition only involved one set of task-relevant S-R rules, another condition involved two sets of task-relevant rules (coded by stimulus type: noise/tone), while the number of task-relevant response combinations was the same in both conditions. Here, an increase in the number of to-be-retrieved S-R rules was associated with a substantial increase in dual-response costs that were also modulated on a trial-by-trial basis when switching between rules. Taken together, the results shed further light on the dependency of cross-modal action control on both action- and rule-related memory retrieval processes.
Background/Aims:
Acute kidney injury (AKI) is a postoperative complication after cardiac surgery with a high impact on mortality and morbidity. Nephrocheck® [TIMP-2*IGFBP7] determines markers of tubular stress, which occurs prior to tubular damage. It is unknown at which time-point [TIMP-2*IGFBP7] measurement should be performed to ideally predict AKI. We investigated the association of [TIMP-2*IGFBP7] at various time-points with the incidence of AKI in patients undergoing elective cardiac surgery including cardio-pulmonary bypass.
Methods: In a prospective cohort study, serial blood and urine samples were collected from 150 patients: pre-operative, at ICU-admission, 24h and 48h post-surgery. AKI was defined as Serum-Creatinine rise >0.3 mg/dl within 48hrs. Urinary [TIMP-2*IGFBP7] was measured at pre-operative, ICU-admission and 24h post-surgery; medical staff was kept blinded to these results.
Results: A total of 35 patients (23.5%) experienced AKI, with a higher incidence in those with high [TIMP-2*IGFBP7] values at ICU admission (57.1% vs. 10.1%, p<0.001). In logistic regression [TIMP-2*IGFBP7] at ICU admission was independently associated with the occurrence of AKI (Odds Ratio 11.83; p<0.001, C-statistic= 0.74) after adjustment for EuroSCORE II and CBP-time.
Conclusions: Early detection of elevated [TIMP-2*IGFBP7] at ICU admission was strongly predictive for postoperative AKI and appeared to be more precise as compared to subsequent measurements.
RNA-binding proteins (RBPs) have been established as core components of several post-transcriptional gene regulation mechanisms. Experimental techniques such as cross-linking and co-immunoprecipitation have enabled the identification of RBPs, RNA-binding domains (RBDs) and their regulatory roles in the eukaryotic species such as human and yeast in large-scale. In contrast, our knowledge of the number and potential diversity of RBPs in bacteria is poorer due to the technical challenges associated with the existing global screening approaches. We introduce APRICOT, a computational pipeline for the sequence-based identification and characterization of proteins using RBDs known from experimental studies. The pipeline identifies functional motifs in protein sequences using position-specific scoring matrices and Hidden Markov Models of the functional domains and statistically scores them based on a series of sequence-based features. Subsequently, APRICOT identifies putative RBPs and characterizes them by several biological properties. Here we demonstrate the application and adaptability of the pipeline on large-scale protein sets, including the bacterial proteome of Escherichia coli. APRICOT showed better performance on various datasets compared to other existing tools for the sequence-based prediction of RBPs by achieving an average sensitivity and specificity of 0.90 and 0.91 respectively. The command-line tool and its documentation are available at https://pypi.python.org/pypi/bio-apricot.
Somatic mutations in protein kinase A catalytic α subunit (PRKACA) were found to be causative for 30-40% of cortisol-producing adenomas (CPA) of the adrenal gland, rendering PKA signalling constitutively active. In its resting state, PKA is a stable and inactive heterotetramer, consisting of two catalytic and two regulatory subunits with the latter inhibiting PKA activity. The human genome encodes three different PKA catalytic subunits and four different regulatory subunits that are preferentially expressed in different organs. In normal adrenal glands all regulatory subunits are expressed, while CPA exhibit reduced protein levels of the regulatory subunit IIβ. In this study, we linked for the first time the loss of RIIβ protein levels to the PRKACA mutation status and found the down-regulation of RIIβ to arise post-transcriptionally. We further found the PKA subunit expression pattern of different tumours is also present in the zones of the normal adrenal cortex and demonstrate that the different PKA subunits have a differential expression pattern in each zone of the normal adrenal gland, indicating potential specific roles of these subunits in the regulation of different hormones secretion.
Predators of highly defensive prey likely develop cost-reducing adaptations. The ant Megaponera analis is a specialized termite predator, solely raiding termites of the subfamily Macrotermitinae (in this study, mostly colonies of Pseudocanthotermes sp.) at their foraging sites. The evolutionary arms race between termites and ants led to various defensive mechanisms in termites (for example, a caste specialized in fighting predators). Because M. analis incurs high injury/mortality risks when preying on termites, some risk-mitigating adaptations seem likely to have evolved. We show that a unique rescue behavior in M. analis, consisting of injured nestmates being carried back to the nest, reduces combat mortality. After a fight, injured ants are carried back by their nestmates; these ants have usually lost an extremity or have termites clinging to them and are able to recover within the nest. Injured ants that are forced experimentally to return without help, die in 32% of the cases. Behavioral experiments show that two compounds, dimethyl disulfide and dimethyl trisulfide, present in the mandibular gland reservoirs, trigger the rescue behavior. A model accounting for this rescue behavior identifies the drivers favoring its evolution and estimates that rescuing enables maintenance of a 28.7% larger colony size. Our results are the first to explore experimentally the adaptive value of this form of rescue behavior focused on injured nestmates in social insects and help us to identify evolutionary drivers responsible for this type of behavior to evolve in animals.
Current brain-computer interface (BCIs) software is often tailored to the needs of scientists and technicians and therefore complex to allow for versatile use. To facilitate home use of BCIs a multifunctional P300 BCI with a graphical user interface intended for non-expert set-up and control was designed and implemented. The system includes applications for spelling, web access, entertainment, artistic expression and environmental control. In addition to new software, it also includes new hardware for the recording of electroencephalogram (EEG) signals. The EEG system consists of a small and wireless amplifier attached to a cap that can be equipped with gel-based or dry contact electrodes. The system was systematically evaluated with a healthy sample, and targeted end users of BCI technology, i.e., people with a varying degree of motor impairment tested the BCI in a series of individual case studies. Usability was assessed in terms of effectiveness, efficiency and satisfaction. Feedback of users was gathered with structured questionnaires. Two groups of healthy participants completed an experimental protocol with the gel-based and the dry contact electrodes (N = 10 each). The results demonstrated that all healthy participants gained control over the system and achieved satisfactory to high accuracies with both gel-based and dry electrodes (average error rates of 6 and 13%). Average satisfaction ratings were high, but certain aspects of the system such as the wearing comfort of the dry electrodes and design of the cap, and speed (in both groups) were criticized by some participants. Six potential end users tested the system during supervised sessions. The achieved accuracies varied greatly from no control to high control with accuracies comparable to that of healthy volunteers. Satisfaction ratings of the two end-users that gained control of the system were lower as compared to healthy participants. The advantages and disadvantages of the BCI and its applications are discussed and suggestions are presented for improvements to pave the way for user friendly BCIs intended to be used as assistive technology by persons with severe paralysis.
Division of labor is a hallmark of social insects. In the honeybee (Apis mellifera) each sterile female worker performs a series of social tasks. The most drastic changes in behavior occur when a nurse bee, who takes care of the brood and the queen in the hive, transitions to foraging behavior. Foragers provision the colony with pollen, nectar or water. Nurse bees and foragers differ in numerous behaviors, including responsiveness to gustatory stimuli. Differences in gustatory responsiveness, in turn, might be involved in regulating division of labor through differential sensory response thresholds. Biogenic amines are important modulators of behavior. Tyramine and octopamine have been shown to increase gustatory responsiveness in honeybees when injected into the thorax, thereby possibly triggering social organization. So far, most of the experiments investigating the role of amines on gustatory responsiveness have focused on the brain. The potential role of the fat body in regulating sensory responsiveness and division of labor has large been neglected. We here investigated the role of the fat body in modulating gustatory responsiveness through tyramine signaling in different social roles of honeybees. We quantified levels of tyramine, tyramine receptor gene expression and the effect of elevating fat body tyramine titers on gustatory responsiveness in both nurse bees and foragers. Our data suggest that elevating the tyramine titer in the fat body pharmacologically increases gustatory responsiveness in foragers, but not in nurse bees. This differential effect of tyramine on gustatory responsiveness correlates with a higher natural gustatory responsiveness of foragers, with a higher tyramine receptor (Amtar1) mRNA expression in fat bodies of foragers and with lower baseline tyramine titers in fat bodies of foragers compared to those of nurse bees. We suggest that differential tyramine signaling in the fat body has an important role in the plasticity of division of labor through changing gustatory responsiveness.
Differential effects of FTY720 on the B cell compartment in a mouse model of multiple sclerosis.
(2017)
Background:
MP4-induced experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis (MS), which enables targeted research on B cells, currently much discussed protagonists in MS pathogenesis. Here, we used this model to study the impact of the S1P1 receptor modulator FTY720 (fingolimod) on the autoreactive B cell and antibody response both in the periphery and the central nervous system (CNS).
Methods:
MP4-immunized mice were treated orally with FTY720 for 30 days at the peak of disease or 50 days after EAE onset. The subsequent disease course was monitored and the MP4-specific B cell/antibody response was measured by ELISPOT and ELISA. RNA sequencing was performed to determine any effects on B cell-relevant gene expression. S1P\(_{1}\) receptor expression by peripheral T and B cells, B cell subset distribution in the spleen and B cell infiltration into the CNS were studied by flow cytometry. The formation of B cell aggregates and of tertiary lymphoid organs (TLOs) was evaluated by histology and immunohistochemistry. Potential direct effects of FTY720 on B cell aggregation were studied in vitro.
Results:
FTY720 significantly attenuated clinical EAE when treatment was initiated at the peak of EAE. While there was a significant reduction in the number of T cells in the blood after FTY720 treatment, B cells were only slightly diminished. Yet, there was evidence for the modulation of B cell receptor-mediated signaling upon FTY720 treatment. In addition, we detected a significant increase in the percentage of B220\(^{+}\) B cells in the spleen both in acute and chronic EAE. Whereas acute treatment completely abrogated B cell aggregate formation in the CNS, the numbers of infiltrating B cells and plasma cells were comparable between vehicle- and FTY720-treated mice. In addition, there was no effect on already developed aggregates in chronic EAE. In vitro B cell aggregation assays suggested the absence of a direct effect of FTY720 on B cell aggregation. However, FTY720 impacted the evolution of B cell aggregates into TLOs.
Conclusions:
The data suggest differential effects of FTY720 on the B cell compartment in MP4-induced EAE.
Background:
There is a paucity of studies examining the safety of venom immunotherapy (VIT) in children. We aimed to assess the incidence of anaphylactic side effects during rush VIT in a cohort of pediatric patients and adult controls.
Methods:
72 consecutive cycles of VIT-buildup in 71 children/adolescents aged 7–17 years were retrospectively evaluated and compared to an adult control group (n = 981) with regard to baseline parameters (sex, causative venom, severity of index sting reaction, results of allergy testing, comorbidities) and the incidence of anaphylactic adverse reactions.
Results:
Compared to adults, severe index sting-induced anaphylaxis was significantly less common in children (P = .001). Children were more likely to suffer from bee venom allergy (P < .001) and showed higher levels of bee venom-specific IgE (P = .013), but lower serum tryptase concentrations (P = .014). The overall rate of VIT-induced anaphylactic reactions was higher in children than in adults (6.9% vs 2.5%, P = .046 by univariate analysis). In the final binary logistic regression model, however, only bee VIT (P = .039; odds ratio 2.25; confidence interval 1.04–4.87) and 5-day compared to 3-day buildup protocols (P = .011; odds ratio 2.64; confidence interval 1.25–5.57) were associated with an increased risk of treatment-induced anaphylaxis. All pediatric patients finally reached and tolerated the target maintenance dose of 100 µg.
Conclusions:
The higher anaphylactic reaction rate observed in pediatric patients may be attributed to a greater prevalence of bee venom allergy. VIT-induced anaphylaxis in children is usually mild and does not affect further updosing and maintenance of VIT.
Background:
In 2004, routine varicella vaccination was introduced in Germany for children aged 11–14 months. Routine measles vaccination had already been introduced in 1973 for the same age group, but coverage is still too low (<95%) in some areas to eliminate measles. The present study assessed varicella and measles vaccination coverage and determinants of parental acceptance in two study regions, situated in Northern and Southern Bavaria (Germany).
Methods:
From 2009 to 2011, annual cross-sectional parent surveys were performed on random samples of 600 children aged 18–36 months in the Bavarian regions of both Munich and Würzburg. Logistic regression models were used to identify factors associated with varicella and measles vaccination.
Results:
In 2009, 2010 and 2011, vaccination coverage was lower in Munich than in Würzburg, for both varicella (Munich 53%, 67%, 69% vs. Würzburg 72%, 81%, 83%) and for measles (Munich 88%, 89%, 91% vs. Würzburg 92%, 93%, 95%). Recommendation by the physician was the main independent factor associated with varicella vaccination in both regions (adjusted odd ratios (OR) with 95% confidence interval (CI): Munich OR 19.7, CI 13.6–28.6; Würzburg OR 34.7, CI 22.6–53.2). Attendance at a childcare unit was positively associated with a higher acceptance of varicella vaccination in Munich (OR 1.5, CI 1.1–2.2). Regarding measles vaccination, attendance at a childcare unit was positively associated in both regions (Munich OR 2.0; CI 1.3–3.0; Würzburg OR 1.8; CI 1.1–3.1), and a higher level of parental school education was negatively associated in Würzburg (OR 0.5, CI 0.3–0.9).
Conclusions:
Vaccination rates differed between regions, with rates constantly higher in Würzburg. Within each region, vaccination rates were lower for varicella than for measles. Measles vaccination status was mainly dependent upon socio-demographic factors (attendance at a childcare unit, parental school education), whereas for the more recently introduced varicella vaccination recommendation by the physician had the strongest impact. Hence, different strategies are needed to further improve vaccination rates for both diseases.