Infinite motion and 2-distinguishability of graphs and groups

A group A acting faithfully on a set X is 2-distinguishable if there is a 2-coloring of X that is not preserved by any nonidentity element of A, equivalently, if there is a proper subset of X with trivial setwise stabilizer. The motion of an element a in A is the number of points of X that are moved by a, and the motion of the group A is the minimal motion of its nonidentity elements. When A is finite, the Motion Lemma says that if the motion of A is large enough (specifically at least 2 log_2 |A|), then the action is 2-distinguishable. For many situations where X has a combinatorial or algebraic structure, the Motion Lemma implies that the action of Aut(X) on X is 2-distinguishable in all but finitely many instances. We prove an infinitary version of the Motion Lemma for countably infinite permutation groups, which states that infinite motion is large enough to guarantee 2-distinguishability. From this we deduce a number of results, including the fact that every locally finite, connected graph whose automorphism group is countably infinite is 2-distinguishable. One cannot extend the Motion Lemma to uncountable permutation groups, but nonetheless we prove that (under the permutation topology) every closed permutation group with infinite motion has a dense subgroup which is 2-distinguishable. We conjecture an extension of the Motion Lemma which we expect holds for a restricted class of uncountable permutation groups, and we conclude with a list of open questions. The consequences of our results are drawn for orbit equivalence of infinite permutation groups

Complex exon-intron marking by histone modifications is not determined solely by nucleosome distribution

It has recently been shown that nucleosome distribution, histone modifications and RNA polymerase II (Pol II) occupancy show preferential association with exons (“exon-intron marking”), linking chromatin structure and function to co-transcriptional splicing in a variety of eukaryotes. Previous ChIP-sequencing studies suggested that these marking patterns reflect the nucleosomal landscape. By analyzing ChIP-chip datasets across the human genome in three cell types, we have found that this marking system is far more complex than previously observed. We show here that a range of histone modifications and Pol II are preferentially associated with exons. However, there is noticeable cell-type specificity in the degree of exon marking by histone modifications and, surprisingly, this is also reflected in some histone modifications patterns showing biases towards introns. Exon-intron marking is laid down in the absence of transcription on silent genes, with some marking biases changing or becoming reversed for genes expressed at different levels. Furthermore, the relationship of this marking system with splicing is not simple, with only some histone modifications reflecting exon usage/inclusion, while others mirror patterns of exon exclusion. By examining nucleosomal distributions in all three cell types, we demonstrate that these histone modification patterns cannot solely be accounted for by differences in nucleosome levels between exons and introns. In addition, because of inherent differences between ChIP-chip array and ChIP-sequencing approaches, these platforms report different nucleosome distribution patterns across the human genome. Our findings confound existing views and point to active cellular mechanisms which dynamically regulate histone modification levels and account for exon-intron marking. We believe that these histone modification patterns provide links between chromatin accessibility, Pol II movement and co-transcriptional splicing

Appropriate disclosure of a diagnosis of dementia : identifying the key behaviours of 'best practice'

Background: Despite growing evidence that many people with dementia want to know their diagnosis, there is wide variation in attitudes of professionals towards disclosure. The disclosure of the diagnosis of dementia is increasingly recognised as being a process rather than a one-off behaviour. However, the different behaviours that contribute to this process have not been comprehensively defined. No intervention studies to improve diagnostic disclosure in dementia have been reported to date. As part of a larger study to develop an intervention to promote appropriate disclosure, we sought to identify important disclosure behaviours and explore whether supplementing a literature review with other methods would result in the identification of new behaviours. Methods: To identify a comprehensive list of behaviours in disclosure we conducted a literature review, interviewed people with dementia and informal carers, and used a consensus process involving health and social care professionals. Content analysis of the full list of behaviours was carried out. Results: Interviews were conducted with four people with dementia and six informal carers. Eight health and social care professionals took part in the consensus panel. From the interviews, consensus panel and literature review 220 behaviours were elicited, with 109 behaviours over-lapping. The interviews and consensus panel elicited 27 behaviours supplementary to the review. Those from the interviews appeared to be self-evident but highlighted deficiencies in current practice and from the panel focused largely on balancing the needs of people with dementia and family members. Behaviours were grouped into eight categories: preparing for disclosure; integrating family members; exploring the patient's perspective; disclosing the diagnosis; responding to patient reactions; focusing on quality of life and well-being; planning for the future; and communicating effectively. Conclusion: This exercise has highlighted the complexity of the process of disclosing a diagnosis of dementia in an appropriate manner. It confirms that many of the behaviours identified in the literature (often based on professional opinion rather than empirical evidence) also resonate with people with dementia and informal carers. The presence of contradictory behaviours emphasises the need to tailor the process of disclosure to individual patients and carers. Our combined methods may be relevant to other efforts to identify and define complex clinical practices for further study.This project is funded by UK Medical Research Council, Grant reference number G0300999

Projections from the paralemniscal nucleus to the spinal cord in the mouse

The present study investigated the projection from the paralemniscal nucleus (PL) to the spinal cord in the mouse by injecting the retrograde tracer fluoro-gold to different levels of the spinal cord and injecting the anterograde tracer biotinylated dextran amine into PL. We found that PL projects to the entire spinal cord with obvious contralateral predominance—420 neurons projected to the contralateral cervical cord and 270 to the contralateral lumbar cord. Fibers from PL descended in the dorsolateral funiculus on the contralateral side and terminated in laminae 5, 6, 7, and to a lesser extent in the dorsal and ventral horns. A smaller number of fibers also descended in the ventral funiculus on the ipsilateral side and terminated in laminae 7, 8 and, to a lesser extent in lamina 9. The present study is the first demonstration of the PL fiber termination in the spinal cord in mammals. The PL projection to the spinal cord may be involved in vocalization and locomotion

Rare and common genetic determinants of metabolic individuality and their effects on human health

Garrod’s concept of ‘chemical individuality’ has contributed to comprehension of the molecular origins of human diseases. Untargeted high-throughput metabolomic technologies provide an in-depth snapshot of human metabolism at scale. We studied the genetic architecture of the human plasma metabolome using 913 metabolites assayed in 19,994 individuals and identified 2,599 variant–metabolite associations (P < 1.25 × 10−11) within 330 genomic regions, with rare variants (minor allele frequency ≤ 1%) explaining 9.4% of associations. Jointly modeling metabolites in each region, we identified 423 regional, co-regulated, variant–metabolite clusters called genetically influenced metabotypes. We assigned causal genes for 62.4% of these genetically influenced metabotypes, providing new insights into fundamental metabolite physiology and clinical relevance, including metabolite-guided discovery of potential adverse drug effects (DPYD and SRD5A2). We show strong enrichment of inborn errors of metabolism-causing genes, with examples of metabolite associations and clinical phenotypes of non-pathogenic variant carriers matching characteristics of the inborn errors of metabolism. Systematic, phenotypic follow-up of metabolite-specific genetic scores revealed multiple potential etiological relationships

Gratefully received, gratefully repaid:The role of perceived fairness in cooperative interactions

It is well documented that people would remunerate fair behaviours and penalize unfair behaviours. It is argued that individuals' reactions following the receipt of a gift depend on the perceived intentions of the donors. Fair intentions should prompt positive affect, like gratitude, triggering cooperative behaviours; while intended unfairness should trigger negative affect, like anger, fostering anti-social actions. It is, however, contended that when people lack information to infer others' intention they may use 'normative' beliefs about fairness - what a typical fair individual 'should' do in these circumstances - to guide their behaviour. In this experiment we examined this assertion. We had 122 participants play a one-shot, double-anonymous game with half playing as potential helpers (P1s) and half as recipients (P2s). Whether a participant was a P1 or P2 was chance-determined and all participants knew this. P1s decided whether to help P2s and whether to make their help unconditional (no repayment needed) or conditional (full or 'taxed' repayment). P2s decided whether to accept the offer and whatever conditions attached but were blind to the list of helping options available to P1s. We anticipated that recipients would refer to the 'injunctive norm' that 'fair people should help "for free" when it is only by chance that they are in a position to help'. Therefore, without knowing P1s' different helping options, unconditional offers should be rated by recipients as fairer than conditional offers, and this should be linked to greater gratitude with greater gratitude linked to greater reciprocation. Path analyses confirmed this serial mediation. The results showed that recipients of unconditional offers, compared to conditional ones, interpreted the helpers' motives as more helpful, experienced greater gratitude and were more eager to reciprocate. The behavioural data further revealed that, when given a latter option to default, 38% of recipients of conditional offers did so

Is post-trabeculectomy hypotony a risk factor for subsequent failure? A case control study

BACKGROUND: Ocular hypotony results in an increased break down of the blood-aqueous barrier and an increase in inflammatory mediator release. We postulate that this release may lead to an increased risk of trabeculectomy failure through increased bleb scarring. This study was designed to try to address the question if hypotony within one month of trabeculectomy for Primary Open Angle Glaucoma (POAG), is a risk factor for future failure of the filter. METHODS: We performed a retrospective, case notes review, of patients who underwent trabeculectomy for POAG between Jan 1995 and Jan 1996 at our hospital. We identified those with postoperative hypotony within 1 month of surgery. Hypotony was defined as an intraocular pressure (IOP) < 8 mmHg or an IOP of less than 10 mmHg with choroidal detachment or a shallow anterior chamber. We compared the survival times of the surgery in this group with a control group (who did not suffer hypotony as described above), over a 5 year period. Failure of trabeculectomy was defined as IOP > 21 mmHg, or commencement of topical antihypertensives or repeat surgery. RESULTS: 97 cases matched our inclusion criteria, of these 38 (39%) experienced hypotony within 1 month of surgery. We compared the survival times in those patients who developed hypotony with those who did not using the log-rank test. This data provided evidence of a difference (P = 0.0492) with patients in the hypotony group failing more rapidly than the control group. CONCLUSION: Early post-trabeculectomy hypotony (within 1 month) is associated with reduced survival time of blebs

The complete sequences and gene organisation of the mitochondrial genomes of the heterodont bivalves Acanthocardia tuberculata and Hiatella arctica – and the first record for a putative Atpase subunit 8 gene in marine bivalves

BACKGROUND: Mitochondrial (mt) gene arrangement is highly variable among molluscs and especially among bivalves. Of the 30 complete molluscan mt-genomes published to date, only one is of a heterodont bivalve, although this is the most diverse taxon in terms of species numbers. We determined the complete sequence of the mitochondrial genomes of Acanthocardia tuberculata and Hiatella arctica, (Mollusca, Bivalvia, Heterodonta) and describe their gene contents and genome organisations to assess the variability of these features among the Bivalvia and their value for phylogenetic inference. RESULTS: The size of the mt-genome in Acanthocardia tuberculata is 16.104 basepairs (bp), and in Hiatella arctica 18.244 bp. The Acanthocardia mt-genome contains 12 of the typical protein coding genes, lacking the Atpase subunit 8 (atp8) gene, as all published marine bivalves. In contrast, a complete atp8 gene is present in Hiatella arctica. In addition, we found a putative truncated atp8 gene when re-annotating the mt-genome of Venerupis philippinarum. Both mt-genomes reported here encode all genes on the same strand and have an additional trnM. In Acanthocardia several large non-coding regions are present. One of these contains 3.5 nearly identical copies of a 167 bp motive. In Hiatella, the 3' end of the NADH dehydrogenase subunit (nad)6 gene is duplicated together with the adjacent non-coding region. The gene arrangement of Hiatella is markedly different from all other known molluscan mt-genomes, that of Acanthocardia shows few identities with the Venerupis philippinarum. Phylogenetic analyses on amino acid and nucleotide levels robustly support the Heterodonta and the sister group relationship of Acanthocardia and Venerupis. Monophyletic Bivalvia are resolved only by a Bayesian inference of the nucleotide data set. In all other analyses the two unionid species, being to only ones with genes located on both strands, do not group with the remaining bivalves. CONCLUSION: The two mt-genomes reported here add to and underline the high variability of gene order and presence of duplications in bivalve and molluscan taxa. Some genomic traits like the loss of the atp8 gene or the encoding of all genes on the same strand are homoplastic among the Bivalvia. These characters, gene order, and the nucleotide sequence data show considerable potential of resolving phylogenetic patterns at lower taxonomic levels

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT