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BackgroundLittle is known about the effects of social exclusion on youth with bipolar disorder (BD). Understanding these effects and the functional neural correlates of social exclusion in youth with BD may establish differences from healthy youth and help identify areas of intervention.MethodsWe investigated brain function in 19 youth with BD and 14 age and gender matched healthy control (HC) participants while performing Cyberball, an fMRI social exclusion task. Whole brain activation, region-of-interest, and functional connectivity were compared between groups and examined with behavioral measures.ResultsCompared with the HC group, youth with BD exhibited greater activation in the left fusiform gyrus (FFG) during social exclusion. Functional connectivity between the left FFG and the posterior cingulate/precuneus was significantly greater in the HC compared with the BD group. For the HC group only, age and subjective distress during Cyberball significantly predicted mean FFG activation. No significant differences in distress during social exclusion were found between groups.ConclusionAlthough preliminary due to small sample size, these data suggest that youth with BD process social exclusion in a manner that focuses on basic visual information while healthy youth make use of past experiences to interpret current social encounters. This difference may account for the social cognitive issues experienced by youth with BD, which can lead to more severe anxiety and mood symptoms.

Candida albicans is an opportunistic pathogen found throughout multiple body sites and is frequently co-isolated from infections of the respiratory tract and oral cavity with Staphylococcus aureus. Herein we present the first report of the effects that S. aureus elicits on the C. albicans transcriptome. Dual-species biofilms containing S. aureus and C. albicans mutants defective in ALS3 or ECE1 were optimised and characterised, followed by transcriptional profiling of C. albicans by RNA-sequencing (RNA-seq). Altered phenotypes in C. albicans mutants revealed specific interaction profiles between fungus and bacteria. The major adhesion and virulence proteins Als3 and Ece1, respectively, were found to have substantial effects on the Candida transcriptome in early and mature biofilms. Despite this, deletion of ECE1 did not adversely affect biofilm formation or the ability of S. aureus to interact with C. albicans hyphae. Upregulated genes in dual-species biofilms corresponded to multiple gene ontology terms, including those attributed to virulence, biofilm formation and protein binding such as ACE2 and multiple heat-shock protein genes. This shows that S. aureus pushes C. albicans towards a more virulent genotype, helping us to understand the driving forces behind the increased severity of C. albicans-S. aureus infections.

ObjectiveCT-guided, frameless robotic radiosurgery is a novel radiotherapy technique for the treatment of intracranial arteriovenous malformations (AVMs) that serves as an alternative to traditional catheter-angiography targeted, frame-based methods.MethodsPatients diagnosed with AVMs who completed single fraction frameless robotic radiosurgery at Medstar Georgetown University Hospital between July 20, 2006 – March 11, 2013 were included in the present study. All patients received pre-treatment planning with CT angiogram (CTA) and MRI, and were treated using the CyberKnife radiosurgery platform. Patients were followed for at least four years or until radiographic obliteration of the AVM was observed.ResultsTwenty patients were included in the present study. The majority of patients were diagnosed with Spetzler Martin Grade II (35%) or III (35%) AVMs. The AVM median nidus diameter and nidal volume was 1.8 cm and 4.38 cc, respectively. Median stereotactic radiosurgery dose was 1,800 cGy. After a median follow-up of 42 months, the majority of patients (81.3%) had complete obliteration of their AVM. All patients who were treated to a total dose of 1800 cGy demonstrated complete obliteration. One patient treated at a dose of 2,200 cGy developed temporary treatment-related toxicity, and one patient developed post-treatment hemorrhage.ConclusionsFrameless robotic radiosurgery with non-invasive CTA and MRI radiography appears to be a safe and effective radiation modality and serves as a novel alternative to traditional invasive catheter-angiography, frame-based methods for the treatment of intracranial AVMs. Adequate obliteration can be achieved utilizing 1,800 cGy in a single fraction, and minimizes treatment-related side effects.

Cell adhesion molecules (CAMs) mediate interactions of neurons with the extracellular environment by forming adhesive bonds with CAMs on adjacent membranes or via binding to proteins of the extracellular matrix. Binding of CAMs to their extracellular ligands results in the activation of intracellular signaling cascades, leading to changes in neuronal structure and the molecular composition and function of neuronal contacts. Ultimately, many of these changes depend on the synthesis of new proteins. In this review, we summarize the evidence showing that CAMs regulate protein synthesis by modulating the activity of transcription factors, gene expression, protein translation, and the structure and distribution of organelles involved in protein synthesis and transport.

The unique symbiosis between a vertebrate salamander, Ambystoma maculatum, and unicellular green alga, Oophila amblystomatis, involves multiple modes of interaction. These include an ectosymbiotic interaction where the alga colonizes the egg capsule, and an intracellular interaction where the alga enters tissues and cells of the salamander. One common interaction in mutualist photosymbioses is the transfer of photosynthate from the algal symbiont to the host animal. In the A. maculatum–O. amblystomatis interaction, there is conflicting evidence regarding whether the algae in the egg capsule transfer chemical energy captured during photosynthesis to the developing salamander embryo. In experiments where we took care to separate the carbon fixation contributions of the salamander embryo and algal symbionts, we show that inorganic carbon fixed by A. maculatum embryos reaches 2% of the inorganic carbon fixed by O. amblystomatis algae within an egg capsule after 2 h in the light. After 2 h in the dark, inorganic carbon fixed by A. maculatum embryos is 800% of the carbon fixed by O. amblystomatis algae within an egg capsule. Using photosynthesis inhibitors, we show that A. maculatum embryos and O. amblystomatis algae compete for available inorganic carbon within the egg capsule environment. Our results confirm earlier studies suggesting a role of heterotrophic carbon fixation during vertebrate embryonic development. Our results also show that the considerable capacity of developing A. maculatum embryos for inorganic carbon fixation precludes our ability to distinguish any minor role of photosynthetically transferred carbon from algal symbionts to host salamanders using bicarbonate introduced to the egg system as a marker.

CD28 plays a critical role in regulating immune responses both by enhancing effector T cell activation and differentiation and controlling the development and function of regulatory T cells. CD28 is expressed at the cell surface as a disulfide linked homodimer that is thought to bind ligand monovalently. How ligand binding triggers CD28 to induce intracellular signaling as well as the proximal signaling pathways that are induced are not well-understood. In addition, recent data suggest inside-out signaling initiated by the T cell antigen receptor can enhance CD28 ligand binding, possibly by inducing a rearrangement of the CD28 dimer interface to allow for bivalent binding. To understand how possible conformational changes during ligand-induced receptor triggering and inside-out signaling are mediated, we examined the CD28 transmembrane domain. We identified an evolutionarily conserved YxxxxT motif that is shared with CTLA-4 and resembles the transmembrane dimerization motif within CD3ζ. We show that the CD28 transmembrane domain can drive protein dimerization in a bacterial expression system at levels equivalent to the well-known glycophorin A transmembrane dimerization motif. In addition, ectopic expression of the CD28 transmembrane domain into monomeric human CD25 can drive dimerization in murine T cells as detected by an increase in FRET by flow cytometry. Mutation of the polar YxxxxT motif to hydrophobic leucine residues (Y145L/T150L) attenuated CD28 transmembrane mediated dimerization in both the bacterial and mammalian assays. Introduction of the Y145L/T150L mutation of the CD28 transmembrane dimerization motif into the endogenous CD28 locus by CRISPR resulted in a dramatic loss in CD28 cell surface expression. These data suggest that under physiological conditions the YxxxxT dimerization motif within the CD28 transmembrane domain plays a critical role in the assembly and/or expression of stable CD28 dimers at the cell surface.

In this paper, we study how stress affects risk taking in three tasks: individual lotteries, Stag Hunt (coordination) games, and Hawk-Dove (anti-coordination) games. Both control and stressed subjects take more risks in all three tasks when the value of the safe option is decreased and in lotteries when the expected gain is increased. Also, subjects take longer to take decisions when stakes are high, when the safe option is less attractive and in the conceptually more difficult Hawk-Dove game. Stress (weakly) increases reaction times in those cases. Finally, our main result is that the behavior of stressed subjects in lotteries, Stag Hunt and Hawk-Dove are all highly predictive of each other (p-value < 0.001 for all three pairwise correlations). Such strong relationship is not present in our control group. Our results illustrate a “contextual blindness” caused by stress. The mathematical and behavioral tensions of Stag Hunt and Hawk-Dove games are axiomatically different, and we should expect different behavior across these games, and also with respect to the individual task. A possible explanation for the highly significant connection across tasks in the stress condition is that stressed subjects habitually rely on one mechanism to make a decision in all contexts whereas unstressed subjects utilize a more cognitively flexible approach.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the degeneration of motor neurons. Though many molecular and genetic causes are thought to serve as predisposing or disease propagating factors, the underlying pathogenesis of the disease is not known. Recent discoveries have demonstrated the presence of inflammation propagating substrates in the central nervous system of patients afflicted with ALS. Over the past decade, this hypothesis has incited an effort to better understand the role of the immune system in ALS and has led to the trial of several potential immune-modulating therapies. Here, we briefly review advances in the role of such therapies. The clinical trials discussed here are currently ongoing or have been concluded at the time of writing.