Understanding the benefits of extrinsic emotion regulation in depression

Depression is a serious psychiatric illness that negatively affects people’s feelings, thoughts, and actions. Providing emotion regulation support to others, also termed Extrinsic Emotion Regulation (EER), reduces depressive symptoms such as perseverative thinking and negative mood. In this conceptual review paper, we argue that EER may be especially beneficial for individuals with depression because it enhances the cognitive and affective processes known to be impaired in depression. Behavioral studies have shown that EER recruits processes related to cognitive empathy, intrinsic emotion regulation (IER), and reward, all impaired in depression. Neuroimaging data support these findings by showing that EER recruits brain regions related to these three processes, such as the ventrolateral prefrontal cortex which is associated with IER, the ventral striatum, which is associated with reward-related processes, and medial frontal regions related to cognitive empathy. This conceptual review paper sheds light on the mechanisms underlying the effectiveness of EER for individuals with depression and therefore offers novel avenues for treatment

Deterministic Combinatorial Replacement Paths and Distance Sensitivity Oracles

In this work we derandomize two central results in graph algorithms, replacement paths and distance sensitivity oracles (DSOs) matching in both cases the running time of the randomized algorithms. For the replacement paths problem, let G = (V,E) be a directed unweighted graph with n vertices and m edges and let P be a shortest path from s to t in G. The replacement paths problem is to find for every edge e in P the shortest path from s to t avoiding e. Roditty and Zwick [ICALP 2005] obtained a randomized algorithm with running time of O~(m sqrt{n}). Here we provide the first deterministic algorithm for this problem, with the same O~(m sqrt{n}) time. Due to matching conditional lower bounds of Williams et al. [FOCS 2010], our deterministic combinatorial algorithm for the replacement paths problem is optimal up to polylogarithmic factors (unless the long standing bound of O~(mn) for the combinatorial boolean matrix multiplication can be improved). This also implies a deterministic algorithm for the second simple shortest path problem in O~(m sqrt{n}) time, and a deterministic algorithm for the k-simple shortest paths problem in O~(k m sqrt{n}) time (for any integer constant k > 0). For the problem of distance sensitivity oracles, let G = (V,E) be a directed graph with real-edge weights. An f-Sensitivity Distance Oracle (f-DSO) gets as input the graph G=(V,E) and a parameter f, preprocesses it into a data-structure, such that given a query (s,t,F) with s,t in V and F subseteq E cup V, |F| <=f being a set of at most f edges or vertices (failures), the query algorithm efficiently computes the distance from s to t in the graph G F (i.e., the distance from s to t in the graph G after removing from it the failing edges and vertices F). For weighted graphs with real edge weights, Weimann and Yuster [FOCS 2010] presented several randomized f-DSOs. In particular, they presented a combinatorial f-DSO with O~(mn^{4-alpha}) preprocessing time and subquadratic O~(n^{2-2(1-alpha)/f}) query time, giving a tradeoff between preprocessing and query time for every value of 0 < alpha < 1. We derandomize this result and present a combinatorial deterministic f-DSO with the same asymptotic preprocessing and query time

Itsy bitsy spider? Valence and self-relevance predict size estimation

AbstractThe current study explored the role of valence and self-relevance in size estimation of neutral and aversive animals. In Experiment 1, participants who were highly fearful of spiders and participants with low fear of spiders rated the size and unpleasantness of spiders and other neutral animals (birds and butterflies). We found that although individuals with both high and low fear of spiders rated spiders as highly unpleasant, only the highly fearful participants rated spiders as larger than butterflies. Experiment 2 included additional pictures of wasps (not self-relevant, but unpleasant) and beetles. The results of this experiment replicated those of Experiment 1 and showed a similar bias in size estimation for beetles, but not for wasps. Mediation analysis revealed that in the high-fear group both relevance and valence influenced perceived size, whereas in the low-fear group only valence affected perceived size. These findings suggest that the effect of highly relevant stimuli on size perception is both direct and mediated by valence

Effect of hydrogen peroxide production and the Fenton reaction on membrane composition of Streptococcus pneumoniae

AbstractAs part of its aerobic metabolism, Streptococcus pneumoniae generates high levels of H2O2 by pyruvate oxidase (SpxB), which can be further reduced to yield the damaging hydroxyl radicals via the Fenton reaction. A universal conserved adaptation response observed among bacteria is the adjustment of the membrane fatty acids to various growth conditions. The aim of the present study was to reveal the effect of endogenous reactive oxygen species (ROS) formation on membrane composition of S. pneumoniae. Blocking carbon aerobic metabolism, by growing the bacteria at anaerobic conditions or by the truncation of the spxB gene, resulted in a significant enhancement in fatty acid unsaturation, mainly cis-vaccenic acid. Moreover, reducing the level of OH· by growing the bacteria at acidic pH, or in the presence of an OH· scavenger (salicylate), resulted in increased fatty acid unsaturation, similar to that obtained under anaerobic conditions. RT-PCR results demonstrated that this change does not originate from a change in mRNA expression level of the fatty acid synthase II genes. We suggest that endogenous ROS play an important regulatory role in membrane adaptation, allowing the survival of this anaerobic organism at aerobic environments of the host

What is the mechanism for persistent coexistence of drug-susceptible and drug-resistant strains of Streptococcus pneumoniae?

The rise of antimicrobial resistance in many pathogens presents a major challenge to the treatment and control of infectious diseases. Furthermore, the observation that drug-resistant strains have risen to substantial prevalence but have not replaced drug-susceptible strains despite continuing (and even growing) selective pressure by antimicrobial use presents an important problem for those who study the dynamics of infectious diseases. While simple competition models predict the exclusion of one strain in favour of whichever is ‘fitter’, or has a higher reproduction number, we argue that in the case of Streptococcus pneumoniae there has been persistent coexistence of drug-sensitive and drug-resistant strains, with neither approaching 100 per cent prevalence. We have previously proposed that models seeking to understand the origins of coexistence should not incorporate implicit mechanisms that build in stable coexistence ‘for free’. Here, we construct a series of such ‘structurally neutral’ models that incorporate various features of bacterial spread and host heterogeneity that have been proposed as mechanisms that may promote coexistence. We ask to what extent coexistence is a typical outcome in each. We find that while coexistence is possible in each of the models we consider, it is relatively rare, with two exceptions: (i) allowing simultaneous dual transmission of sensitive and resistant strains lets coexistence become a typical outcome, as does (ii) modelling each strain as competing more strongly with itself than with the other strain, i.e. self-immunity greater than cross-immunity. We conclude that while treatment and contact heterogeneity can promote coexistence to some extent, the in-host interactions between strains, particularly the interplay between coinfection, multiple infection and immunity, play a crucial role in the long-term population dynamics of pathogens with drug resistance

SIRT6 Promotes Hepatic Beta-Oxidation via Activation of PPARα

The pro-longevity enzyme SIRT6 regulates various metabolic pathways. Gene expression analyses in SIRT6 heterozygotic mice identify significant decreases in PPARα signaling, known to regulate multiple metabolic pathways. SIRT6 binds PPARα and its response element within promoter regions and activates gene transcription. Sirt6+/− results in significantly reduced PPARα-induced β-oxidation and its metabolites and reduced alanine and lactate levels, while inducing pyruvate oxidation. Reciprocally, starved SIRT6 transgenic mice show increased pyruvate, acetylcarnitine, and glycerol levels and significantly induce β-oxidation genes in a PPARα-dependent manner. Furthermore, SIRT6 mediates PPARα inhibition of SREBP-dependent cholesterol and triglyceride synthesis. Mechanistically, SIRT6 binds PPARα coactivator NCOA2 and decreases liver NCOA2 K780 acetylation, which stimulates its activation of PPARα in a SIRT6-dependent manner. These coordinated SIRT6 activities lead to regulation of whole-body respiratory exchange ratio and liver fat content, revealing the interactions whereby SIRT6 synchronizes various metabolic pathways, and suggest a mechanism by which SIRT6 maintains healthy liver

Strangeness nuclear physics: a critical review on selected topics

Selected topics in strangeness nuclear physics are critically reviewed. This includes production, structure and weak decay of $\Lambda$--Hypernuclei, the $\bar K$ nuclear interaction and the possible existence of $\bar K$ bound states in nuclei. Perspectives for future studies on these issues are also outlined.Comment: 63 pages, 51 figures, accepted for publication on European Physical Journal

Discovery of microRNAs and other small RNAs in solid tumors

MicroRNAs (miRNAs) are ∼22-nt long, non-coding RNAs that regulate gene silencing. It is known that many human miRNAs are deregulated in numerous types of tumors. Here we report the sequencing of small RNAs (17–25 nt) from 23 breast, bladder, colon and lung tumor samples using high throughput sequencing. We identified 49 novel miRNA and miR-sized small RNAs. We further validated the expression of 10 novel small RNAs in 31 different types of blood, normal and tumor tissue samples using two independent platforms, namely microarray and RT–PCR. Some of the novel sequences show a large difference in expression between tumor and tumor-adjacent tissues, between different tumor stages, or between different tumor types. We also report the identification of novel small RNA classes in human: highly expressed small RNA derived from Y-RNA and endogenous siRNA. Finally, we identified dozens of new miRNA sequence variants that demonstrate the existence of miRNA-related SNP or post-transcriptional modifications. Our work extends the current knowledge of the tumor small RNA transcriptome and provides novel candidates for molecular biomarkers and drug targets