Apoptosis of Purified CD4+ T Cell Subsets Is Dominated by Cytokine Deprivation and Absence of Other Cells in New Onset Diabetic NOD Mice

BACKGROUND: Regulatory T cells (Treg) play a significant role in immune homeostasis and self-tolerance. Excessive sensitivity of isolated Treg to apoptosis has been demonstrated in NOD mice and humans suffering of type 1 diabetes, suggesting a possible role in the immune dysfunction that underlies autoimmune insulitis. In this study the sensitivity to apoptosis was measured in T cells from new onset diabetic NOD females, comparing purified subsets to mixed cultures. PRINCIPAL FINDINGS: Apoptotic cells are short lived in vivo and death occurs primarily during isolation, manipulation and culture. Excessive susceptibility of CD25(+) T cells to spontaneous apoptosis is characteristic of isolated subsets, however disappears when death is measured in mixed splenocyte cultures. In variance, CD25(-) T cells display balanced sensitivity to apoptosis under both conditions. The isolation procedure removes soluble factors, IL-2 playing a significant role in sustaining Treg viability. In addition, pro- and anti-apoptotic signals are transduced by cell-to-cell interactions: CD3 and CD28 protect CD25(+) T cells from apoptosis, and in parallel sensitize naïve effector cells to apoptosis. Treg viability is modulated both by other T cells and other subsets within mixed splenocyte cultures. Variations in sensitivity to apoptosis are often hindered by fast proliferation of viable cells, therefore cycling rates are mandatory to adequate interpretation of cell death assays. CONCLUSIONS: The sensitivity of purified Treg to apoptosis is dominated by cytokine deprivation and absence of cell-to-cell interactions, and deviate significantly from measurements in mixed populations. Balanced sensitivity of naïve/effector and regulatory T cells to apoptosis in NOD mice argues against the concept that differential susceptibility affects disease evolution and progression

The domain of organizational cognitive neuroscience:theoretical and empirical challenges

In this editorial, the authors respond to the 2011 article in the Journal of Management by Becker, Cropanzano, and Sanfey, titled “Organizational Neuroscience: Taking Organizational Theory Inside the Neural Black Box.” More specifically, the authors build on the ideas of Becker et al. first to clarify and extend their work and then to explore the critical philosophical issues involved in drawing inferences from neuroscientific research. They argue that these problems are yet to be solved and that organizational researchers who wish to incorporate neuroscientific advances into their work need to engage with them

Effector and Naturally Occurring Regulatory T Cells Display No Abnormalities in Activation Induced Cell Death in NOD Mice

BACKGROUND: Disturbed peripheral negative regulation might contribute to evolution of autoimmune insulitis in type 1 diabetes. This study evaluates the sensitivity of naïve/effector (Teff) and regulatory T cells (Treg) to activation-induced cell death mediated by Fas cross-linking in NOD and wild-type mice. PRINCIPAL FINDINGS: Both effector (CD25(-), FoxP3(-)) and suppressor (CD25(+), FoxP3(+)) CD4(+) T cells are negatively regulated by Fas cross-linking in mixed splenocyte populations of NOD, wild type mice and FoxP3-GFP trangeneess. Proliferation rates and sensitivity to Fas cross-linking are dissociated in Treg cells: fast cycling induced by IL-2 and CD3/CD28 stimulation improve Treg resistance to Fas-ligand (FasL) in both strains. The effector and suppressor CD4(+) subsets display balanced sensitivity to negative regulation under baseline conditions, IL-2 and CD3/CD28 stimulation, indicating that stimulation does not perturb immune homeostasis in NOD mice. Effective autocrine apoptosis of diabetogenic cells was evident from delayed onset and reduced incidence of adoptive disease transfer into NOD.SCID by CD4(+)CD25(-) T cells decorated with FasL protein. Treg resistant to Fas-mediated apoptosis retain suppressive activity in vitro. The only detectable differential response was reduced Teff proliferation and upregulation of CD25 following CD3-activation in NOD mice. CONCLUSION: These data document negative regulation of effector and suppressor cells by Fas cross-linking and dissociation between sensitivity to apoptosis and proliferation in stimulated Treg. There is no evidence that perturbed AICD in NOD mice initiates or promotes autoimmune insulitis

Importance of Polaronic Effects for Charge Transport in CdSe Quantum Dot Solids

We developed an accurate model accounting for electron-phonon interaction in colloidal quantum dot supercrystals that allowed us to identify the nature of charge carriers and the electrical transport regime. We find that in experimentally analyzed CdSe nanocrystal solids the electron-phonon interaction is sufficiently strong that small polarons localized to single dots are formed. Charge-carrier transport occurs by small polaron hopping between the dots, with mobility that decreases with increasing temperature. While such a temperature dependence of mobility is usually considered as a proof of band transport, we show that the same type of dependence occurs in the system where transport is dominated by small polaron hopping

Semantic transparency in free stems: the effect of orthography-semantics consistency in word recognition

A largely overlooked side effect in most studies of morphological priming is a consistent main effect of semantic transparency across priming conditions. That is, participants are faster at recognizing stems from transparent sets (e.g., farm) in comparison to stems from opaque sets (e.g., fruit), regardless of the preceding primes. This suggests that semantic transparency may also be consistently associated with some property of the stem word. We propose that this property might be traced back to the consistency, throughout the lexicon, between the orthographic form of a word and its meaning, here named Orthography-Semantics Consistency (OSC), and that an imbalance in OSC scores might explain the "stem transparency" effect. We exploited distributional semantic models to quantitatively characterize OSC, and tested its effect on visual word identification relying on large-scale data taken from the British Lexicon Project (BLP). Results indicated that (a) the "stem transparency" effect is solid and reliable, insofar as it holds in BLP lexical decision times (Experiment 1); (b) an imbalance in terms of OSC can account for it (Experiment 2); and (c) more generally, OSC explains variance in a large item sample from the BLP, proving to be an effective predictor in visual word access (Experiment 3)

Resting-State Connectivity of the Left Frontal Cortex to the Default Mode and Dorsal Attention Network Supports Reserve in Mild Cognitive Impairment

Reserve refers to the phenomenon of relatively preserved cognition in disproportion to the extent of neuropathology, e.g., in Alzheimer’s disease. A putative functional neural substrate underlying reserve is global functional connectivity of the left lateral frontal cortex (LFC, Brodmann Area 6/44). Resting-state fMRI-assessed global LFC-connectivity is associated with protective factors (education) and better maintenance of memory in mild cognitive impairment (MCI). Since the LFC is a hub of the fronto-parietal control network that regulates the activity of other networks, the question arises whether LFC-connectivity to specific networks rather than the whole-brain may underlie reserve. We assessed resting-state fMRI in 24 MCI and 16 healthy controls (HC) and in an independent validation sample (23 MCI/32 HC). Seed-based LFC-connectivity to seven major resting-state networks (i.e., fronto-parietal, limbic, dorsal-attention, somatomotor, default-mode, ventral-attention, visual) was computed, reserve was quantified as residualized memory performance after accounting for age and hippocampal atrophy. In both samples of MCI, LFC-activity was anti-correlated with the default-mode network (DMN), but positively correlated with the dorsal-attention network (DAN). Greater education predicted stronger LFC-DMN-connectivity (anti-correlation) and LFC-DAN-connectivity. Stronger LFC-DMN and LFC-DAN-connectivity each predicted higher reserve, consistently in both MCI samples. No associations were detected for LFC-connectivity to other networks. These novel results extend our previous findings on global functional connectivity of the LFC, showing that LFC-connectivity specifically to the DAN and DMN, two core memory networks, enhances reserve in the memory domain in MCI

GreekLex 2: a comprehensive lexical database with part-of-speech, syllabic, phonological, and stress information

Databases containing lexical properties on any given orthography are crucial for psycholinguistic research. In the last ten years, a number of lexical databases have been developed for Greek. However, these lack important part-of-speech information. Furthermore, the need for alternative procedures for calculating syllabic measurements and stress information, as well as combination of several metrics to investigate linguistic properties of the Greek language are highlighted. To address these issues, we present a new extensive lexical database of Modern Greek (GreekLex 2) with part-of-speech information for each word and accurate syllabification and orthographic information predictive of stress, as well as several measurements of word similarity and phonetic information. The addition of detailed statistical information about Greek part-of-speech, syllabification, and stress neighbourhood allowed novel analyses of stress distribution within different grammatical categories and syllabic lengths to be carried out. Results showed that the statistical preponderance of stress position on the pre-final syllable that is reported for Greek language is dependent upon grammatical category. Additionally, analyses showed that a proportion higher than 90% of the tokens in the database would be stressed correctly solely by relying on stress neighbourhood information. The database and the scripts for orthographic and phonological syllabification as well as phonetic transcription are available at http://www.psychology.nottingham.ac.uk/greeklex/

Friend versus foe: Neural correlates of prosocial decisions for liked and disliked peers

Although the majority of our social interactions are with people we know, few studies have investigated the neural correlates of sharing valuable resources with familiar others. Using an ecologically valid research paradigm, this functional magnetic resonance imaging study examined the neural correlates of prosocial and selfish behavior in interactions with real-life friends and disliked peers in young adults. Participants (N = 27) distributed coins between themselves and another person, where they could make selfish choices that maximized their own gains or prosocial choices that maximized outcomes of the other. Participants were more prosocial toward friends and more selfish toward disliked peers. Individual prosociality levels toward friends were associated negatively with supplementary motor area and anterior insula activity. Further preliminary analyses showed that prosocial decisions involving friends were associated with heightened activity in the bilateral posterior temporoparietal junction, and selfish decisions involving disliked peers were associated with heightened superior temporal sulcus activity, which are brain regions consistently shown to be involved in mentalizing and perspective taking in prior studies. Further, activation of the putamen was observed during prosocial choices involving friends and selfish choices involving disliked peers. These findings provide insights into the modulation of neural processes that underlie prosocial behavior as a function of a positive or negative relationship with the interaction partner

Left dorsolateral prefrontal cortex supports context-dependent prioritisation of off-task thought

When environments lack compelling goals, humans often let their minds wander to thoughts with greater personal relevance; however, we currently do not understand how this context-dependent prioritisation process operates. Dorsolateral prefrontal cortex (DLPFC) maintains goal representations in a context-dependent manner. Here, we show this region is involved in prioritising off-task thought in an analogous way. In a whole brain analysis we established that neural activity in DLPFC is high both when ‘on-task’ under demanding conditions and ‘off-task’ in a non-demanding task. Furthermore, individuals who increase off-task thought when external demands decrease, show lower correlation between neural signals linked to external tasks and lateral regions of the DMN within DLPFC, as well as less cortical grey matter in regions sensitive to these external task relevant signals. We conclude humans prioritise daydreaming when environmental demands decrease by aligning cognition with their personal goals using DLPFC