Interictal Neurocognitive Processing of Visual Stimuli in Migraine: Evidence from Event-Related Potentials

Research has established decreased sensory habituation as a defining feature in migraine, while decreased cognitive habituation has only been found with regard to cognitive assessment of the relative probability of the occurrence of a stimulus event. Our study extended the investigation of interictal habituation in migraine to include cognitive processing when viewing of a series of visually-complex images, similar to those we encounter on the internet everyday. We examined interictal neurocognitive function in migraine from a habituation perspective, using a novel paradigm designed to assess how the response to a series of images changes over time. Two groups of participants--migraineurs (N = 25) and non-migraine controls (N = 25)--were asked to view a set of 232 unfamiliar logos in the context of a target identification task as their brain electrical responses were recorded via event-related potentials (ERPs). The set of logos was viewed serially in each of 10 separate trial blocks, with data analysis focusing on how the ERP responses to the logos in frontal electrodes from 200-600 ms changed across time within each group. For the controls, we found that the amplitude of the late positive potential (LPP) ERP component elicited by the logos had no significant change across trial blocks. In contrast, in migraineurs we found that the LPP significantly increased in amplitude across trial blocks, an effect consistent with a lack of habituation to visual stimuli seen in previous research. Our findings provide empirical support abnormal cognitive processing of complex visual images across time in migraineurs that goes beyond the sensory-level habituation found in previous research.     

Left atrium remodeling predicts late recurrence of paroxysmal atrial fibrillation after second generation cryoballoon ablation

Background

Atrial fibrillation (AF) is the most common arrhythmia worldwide. Nowadays, AF ablation is a valuable treatment option. It has been shown that the left atrium (LA) diameter is a predictor of AF recurrence after cryoballoon ablation (CBA). Since it does not reflect the true LA size, we compared the role of different LA anatomical parameters using echocardiography for the prediction of AF recurrence after CBA.

Methods

We retrospectively included 209 patients (mean age 56.1?±?13.6 years, male 62%) with paroxysmal AF undergoing CBA. A transthoracic echocardiography was performed in all patients.

Results

At a mean follow-up of 16.9?±?6.3 months, AF recurred in 25.4% of the patients. LA anterior - posterior diameter (LAD), LA minimum volume (LAmin) and early AF recurrence were independent predictors of recurrence. Based on receiver operating characteristics, cut – off values for LAD and, LAmin were 41 mm, 23.69 mL, respectively. The negative predictive values for recurrence were 73% and 87.3% respectively. In patients with AF recurrence, a significant proportion (30.2%) showed LA longitudinal remodeling (LA superior – inferior diameter) even though classically measured LAD was normal.

Conclusions

Longitudinal LA remodeling plays an additional role for predicting AF recurrence after CBA, in patients without LAD dilation. Moreover, LAmin had a high negative predictive value and was an independent predictor of AF recurrence. Therefore, a more complete LA anatomical assessment allows a better prediction of AF recurrences after CBA.

     

Dissecting the Signaling Events That Impact Classical Nuclear Import and Target Nuclear Transport Factors

Background

Signaling through MEK→ERK1/2 and PI3 kinases is implicated in many aspects of cell physiology, including the survival of oxidant exposure. Oxidants play a role in numerous physiological and pathophysiological processes, many of which rely on transport in and out of the nucleus. However, how oxidative stress impacts nuclear trafficking is not well defined.

Methodology/Principal Findings

To better understand the effect of stress on nucleocytoplasmic trafficking, we exposed cells to the oxidant diethyl maleate. This treatment activated MEK→ERK1/2 as well as PI3 kinase→Akt cascades and triggered the inhibition of classical nuclear import. To define the molecular mechanisms that regulate nuclear transport, we examined whether MEK and PI3 kinase signaling affected the localization of key transport factors. Using recently developed tools for image acquisition and analysis, the subcellular distributions of importin-α, CAS, and nucleoporins Nup153 and Nup88 were quantified in different cellular compartments. These studies identified specific profiles for the localization of transport factors in the nucleus and cytoplasm, and at the nuclear envelope. Our results demonstrate that MEK and PI3 kinase signaling as well as oxidative stress control nuclear trafficking and the localization of transport components. Furthermore, stress not only induced changes in transport factor distribution, but also upregulated post-translational modification of transport factors. Our results are consistent with the idea that the phosphorylation of importin-α, CAS, Nup153, and Nup88, and the O-GlcNAc modification of Nup153 increase when cells are exposed to oxidant.

Conclusions/Significance

Our studies defined the complex regulation of classical nuclear import and identified key transport factors that are targeted by stress, MEK, and PI3 kinase signaling.     

Phenotypic diversity and chaos in a minimal cell model

Gánti's chemoton model (Gánti, T., 2002. On the early evolution of biological periodicity. Cell. Biol. Int. 26, 729) is considered as an iconic example of a minimal protocell including three key subsystems: membrane, metabolism and information. The three subsystems are connected through stoichiometrical coupling which ensures the existence of a replication cycle for the chemoton. Our detailed exploration of a version of this model indicates that it displays a wide range of complex dynamics, from regularity to chaos. Here, we report the presence of a very rich set of dynamical patterns potentially displayed by a protocell as described by this implementation of a chemoton-like model. The implications for early cellular evolution and synthesis of artificial cells are discussed.     

UniEuk: Time to Speak a Common Language in Protistology!

Universal taxonomic frameworks have been critical tools to structure the fields of botany, zoology, mycology, and bacteriology as well as their large research communities. Animals, plants, and fungi have relatively solid, stable morpho‐taxonomies built over the last three centuries, while bacteria have been classified for the last three decades under a coherent molecular taxonomic framework. By contrast, no such common language exists for microbial eukaryotes, even though environmental ‘‐omics’ surveys suggest that protists make up most of the organismal and genetic complexity of our planet's ecosystems! With the current deluge of eukaryotic meta‐omics data, we urgently need to build up a universal eukaryotic taxonomy bridging the protist ‐omics age to the fragile, centuries‐old body of classical knowledge that has effectively linked protist taxa to morphological, physiological, and ecological information. UniEuk is an open, inclusive, community‐based and expert‐driven international initiative to build a flexible, adaptive universal taxonomic framework for eukaryotes. It unites three complementary modules, EukRef, EukBank, and EukMap, which use phylogenetic markers, environmental metabarcoding surveys, and expert knowledge to inform the taxonomic framework. The UniEuk taxonomy is directly implemented in the European Nucleotide Archive at EMBL‐EBI, ensuring its broad use and long‐term preservation as a reference taxonomy for eukaryotes.     

As,Pb, Sb,and Zn transfer from soil to root of wild rosemary: do native symbionts matter?

Background and aims

This is an in natura study aimed to determine the potential of Rosmarinus officinalis for phytostabilization of trace metal and metalloid (TMM)-contaminated soils in the Calanques National Park (Marseille, southeast of France). The link between rosemary tolerance/accumulation of As, Pb, Sb, and Zn and root symbioses with arbuscular mycorrhizal (AM) fungi and/or dark septate endophytes (DSE) was examined.

Methods

Eight sites along a gradient of contamination were selected for soil and root collections. TMM concentrations were analyzed in all the samples and root symbioses were observed. Moreover, in the roots of various diameters collected in the most contaminated site, X-ray microfluorescence methods were used to determine TMM localization in tissues.

Results

Rosemary accumulated, in its roots, the most labile TMM fraction in the soil. The positive linear correlation between TMM concentrations in soil and endophyte root colonization rates suggests the involvement of AM fungi and DSE in rosemary tolerance to TMM. Moreover, a typical TMM localization in root peripheral tissues of thin roots containing endophytes forming AM and DSE development was observed using X-ray microfluorescence.

Conclusions

Rosemary and its root symbioses appeared as a potential candidate for a phytostabilization process of metal-contaminated soils in Mediterranean area.     

Def1 Promotes the Degradation of Pol3 for Polymerase Exchange to Occur During DNA-Damage–Induced Mutagenesis in Saccharomyces cerevisiae

DNA damages hinder the advance of replication forks because of the inability of the replicative polymerases to synthesize across most DNA lesions. Because stalled replication forks are prone to undergo DNA breakage and recombination that can lead to chromosomal rearrangements and cell death, cells possess different mechanisms to ensure the continuity of replication on damaged templates. Specialized, translesion synthesis (TLS) polymerases can take over synthesis at DNA damage sites. TLS polymerases synthesize DNA with a high error rate and are responsible for damage-induced mutagenesis, so their activity must be strictly regulated. However, the mechanism that allows their replacement of the replicative polymerase is unknown. Here, using protein complex purification and yeast genetic tools, we identify Def1 as a key factor for damage-induced mutagenesis in yeast. In in vivo experiments we demonstrate that upon DNA damage, Def1 promotes the ubiquitylation and subsequent proteasomal degradation of Pol3, the catalytic subunit of the replicative polymerase δ, whereas Pol31 and Pol32, the other two subunits of polymerase δ, are not affected. We also show that purified Pol31 and Pol32 can form a complex with the TLS polymerase Rev1. Our results imply that TLS polymerases carry out DNA lesion bypass only after the Def1-assisted removal of Pol3 from the stalled replication fork.