Bone mineral as a drug-seeking moiety and a waste dump

Bone is a dynamic tissue with a quarter of the trabecular and a fifth of the cortical bone being replaced continuously each year in a complex process that continues throughout an individual’s lifetime. Bone has an important role in homeostasis of minerals with non-stoichiometric hydroxyapatite bone mineral forming the inorganic phase of bone. Due to its crystal structure and chemistry, hydroxyapatite (HA) and related apatites have a remarkable ability to bind molecules. This review article describes the accretion of trace elements in bone mineral giving a historical perspective. Implanted HA particles of synthetic origin have proved to be an efficient recruiting moiety for systemically circulating drugs which can locally biomodulate the material and lead to a therapeutic effect. Bone mineral and apatite however also act as a waste dump for trace elements and drugs, which significantly affects the environment and human health

A qualitative study of the understanding and use of ‘compassion focused coping strategies’ in people who suffer from serious weight difficulties.

Abstract Background The physical and psychological health problems associated with obesity are now well documented, as is the urgency for addressing them. In addition, associations between quality of life, depression, self-esteem, self-criticism, and obesity are now established indicating a need for a better understanding of the links between self-evaluation, affect-regulation and eating behaviours. Methods Compassion has now been identified as a major source of resilience, helpful self-relating and affect regulation. Thus this study used semi-structured interviews to explore the understanding and experiences of compassion in 2 overweight men and 10 women seeking help for weight problems. The interviews examined people's understandings of compassion, their recall of experiences of compassion in childhood, their current experiences of receiving compassion from others, being compassionate to others, being self-compassionate, and whether they would be compassionate or self-critical for relapses in overeating. Interviews were transcribed and analysed using thematic analysis (Qual Res Psychol, 3: 77-101, 2006). Results Participants saw compassion as related to ‘caring’ and being ‘listened to’. However, their recall of earlier experiences of compassion was of primarily practical help rather than emotional engagement. Typically their response to their own relapse and setbacks were self-criticism, self-disgust and even self-hatred rather than self-caring or understanding. Self-critical/hating responses tend to be associated with poor weight regulation. Conclusions When people with weight problems relapse, or struggle to control their eating, they can become quite self-critical, even self-hating, which may increase difficulties with emotionally coping and maintaining healthy lifestyles and eating habits. Although turning to others for support and compassion, and becoming self-compassionate are antidotes to self-criticism, and are associated with better coping and mental health, many participants did not utilise compassionate strategies – often the opposite. It is possible that interventions that include mindfulness and compassion training could be helpful for these difficulties.N/

Mathematically Gifted Adolescents Have Deficiencies in Social Valuation and Mentalization

Many mathematically gifted adolescents are characterized as being indolent, underachieving and unsuccessful despite their high cognitive ability. This is often due to difficulties with social and emotional development. However, research on social and emotional interactions in gifted adolescents has been limited. The purpose of this study was to observe differences in complex social strategic behaviors between gifted and average adolescents of the same age using the repeated Ultimatum Game. Twenty-two gifted adolescents and 24 average adolescents participated in the Ultimatum Game. Two adolescents participate in the game, one as a proposer and the other as a responder. Because of its simplicity, the Ultimatum Game is an apt tool for investigating complex human emotional and cognitive decision-making in an empirical setting. We observed strategic but socially impaired offers from gifted proposers and lower acceptance rates from gifted responders, resulting in lower total earnings in the Ultimatum Game. Thus, our results indicate that mathematically gifted adolescents have deficiencies in social valuation and mentalization

Axion Protection from Flavor

The QCD axion fails to solve the strong CP problem unless all explicit PQ violating, Planck-suppressed, dimension n<10 operators are forbidden or have exponentially small coefficients. We show that all theories with a QCD axion contain an irreducible source of explicit PQ violation which is proportional to the determinant of the Yukawa interaction matrix of colored fermions. Generically, this contribution is of low operator dimension and will drastically destabilize the axion potential, so its suppression is a necessary condition for solving the strong CP problem. We propose a mechanism whereby the PQ symmetry is kept exact up to n=12 with the help of the very same flavor symmetries which generate the hierarchical quark masses and mixings of the SM. This "axion flavor protection" is straightforwardly realized in theories which employ radiative fermion mass generation and grand unification. A universal feature of this construction is that the heavy quark Yukawa couplings are generated at the PQ breaking scale.Comment: 16 pages, 2 figure

Enteric dysbiosis and fecal calprotectin expression in premature infants.

BackgroundPremature infants often develop enteric dysbiosis with a preponderance of Gammaproteobacteria, which has been related to adverse clinical outcomes. We investigated the relationship between increasing fecal Gammaproteobacteria and mucosal inflammation, measured by fecal calprotectin (FC).MethodsStool samples were collected from very-low-birth weight (VLBW) infants at ≤2, 3, and 4 weeks' postnatal age. Fecal microbiome was surveyed using polymerase chain reaction amplification of the V4 region of 16S ribosomal RNA, and FC was measured by enzyme immunoassay.ResultsWe enrolled 45 VLBW infants (gestation 27.9 ± 2.2 weeks, birth weight 1126 ± 208 g) and obtained stool samples at 9.9 ± 3, 20.7 ± 4.1, and 29.4 ± 4.9 days. FC was positively correlated with the genus Klebsiella (r = 0.207, p = 0.034) and its dominant amplicon sequence variant (r = 0.290, p = 0.003), but not with the relative abundance of total Gammaproteobacteria. Klebsiella colonized the gut in two distinct patterns: some infants started with low Klebsiella abundance and gained these bacteria over time, whereas others began with very high Klebsiella abundance.ConclusionIn premature infants, FC correlated with relative abundance of a specific pathobiont, Klebsiella, and not with that of the class Gammaproteobacteria. These findings indicate a need to define dysbiosis at genera or higher levels of resolution

A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2.

There is great potential for host-based gene expression analysis to impact the early diagnosis of infectious diseases. In particular, the influenza pandemic of 2009 highlighted the challenges and limitations of traditional pathogen-based testing for suspected upper respiratory viral infection. We inoculated human volunteers with either influenza A (A/Brisbane/59/2007 (H1N1) or A/Wisconsin/67/2005 (H3N2)), and assayed the peripheral blood transcriptome every 8 hours for 7 days. Of 41 inoculated volunteers, 18 (44%) developed symptomatic infection. Using unbiased sparse latent factor regression analysis, we generated a gene signature (or factor) for symptomatic influenza capable of detecting 94% of infected cases. This gene signature is detectable as early as 29 hours post-exposure and achieves maximal accuracy on average 43 hours (p = 0.003, H1N1) and 38 hours (p-value = 0.005, H3N2) before peak clinical symptoms. In order to test the relevance of these findings in naturally acquired disease, a composite influenza A signature built from these challenge studies was applied to Emergency Department patients where it discriminates between swine-origin influenza A/H1N1 (2009) infected and non-infected individuals with 92% accuracy. The host genomic response to Influenza infection is robust and may provide the means for detection before typical clinical symptoms are apparent

Modes, mechanisms and evidence of bet hedging in rotifer diapause traits

In this contribution, we review our knowledge on bet-hedging strategies associated with rotifer diapause. First, we describe the ecological scenario under which bet hedging is likely to have evolved in three diapause-related traits in monogonont rotifer populations: (1) the timing of sex (because diapausing eggs are produced via sexual reproduction), (2) the sexual reproduction ratio (i.e. the fraction of sexually reproducing females) and (3) the timing of diapausing egg hatching. Then, we describe how to discriminate among bet-hedging modes and discuss which modes and mechanisms better fit the variability observed in these traits in rotifers. Finally, we evaluate the strength of the empirical evidence for bet hedging in the scarce studies available, and we call for the need of research at different levels of biological complexity to fully understand bet hedging in rotifer diapause

Phylogenetic Position of a Copper Age Sheep (Ovis aries) Mitochondrial DNA

BACKGROUND: Sheep (Ovis aries) were domesticated in the Fertile Crescent region about 9,000-8,000 years ago. Currently, few mitochondrial (mt) DNA studies are available on archaeological sheep. In particular, no data on archaeological European sheep are available. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe the first portion of mtDNA sequence of a Copper Age European sheep. DNA was extracted from hair shafts which were part of the clothes of the so-called Tyrolean Iceman or Ötzi (5,350-5,100 years before present). Mitochondrial DNA (a total of 2,429 base pairs, encompassing a portion of the control region, tRNA(Phe), a portion of the 12S rRNA gene, and the whole cytochrome B gene) was sequenced using a mixed sequencing procedure based on PCR amplification and 454 sequencing of pooled amplification products. We have compared the sequence with the corresponding sequence of 334 extant lineages. CONCLUSIONS/SIGNIFICANCE: A phylogenetic network based on a new cladistic notation for the mitochondrial diversity of domestic sheep shows that the Ötzi's sheep falls within haplogroup B, thus demonstrating that sheep belonging to this haplogroup were already present in the Alps more than 5,000 years ago. On the other hand, the lineage of the Ötzi's sheep is defined by two transitions (16147, and 16440) which, assembled together, define a motif that has not yet been identified in modern sheep populations

Truss geometry and topology optimization with global stability constraints

In this paper, we introduce geometry optimization into an existing topology optimization workflow for truss structures with global stability constraints, assuming a linear buckling analysis. The design variables are the cross-sectional areas of the bars and the coordinates of the joints. This makes the optimization problem formulations highly nonlinear and yields nonconvex semidefinite programming problems, for which there are limited available numerical solvers compared with other classes of optimization problems. We present problem instances of truss geometry and topology optimization with global stability constraints solved using a standard primal-dual interior point implementation. During the solution process, both the cross-sectional areas of the bars and the coordinates of the joints are concurrently optimized. Additionally, we apply adaptive optimization techniques to allow the joints to navigate larger move limits and to improve the quality of the optimal designs