Exclusion of repetitive DNA elements from gnathostome Hox clusters

Despite their homology and analogous function, the Hox gene clusters of vertebrates and invertebrates are subject to different constraints on their structural organization. This is demonstrated by a drastically different distribution of repetitive DNA elements in the Hox cluster regions. While gnathostomes have a strong tendency to exclude repetitive DNA elements from the inside of their Hox clusters, no such trend can be detected in the Hox gene clusters of protostomes. Repeats “invade” the gnathostome Hox clusters from the 5′ and 3′ ends while the core of the clusters remains virtually free of repetitive DNA. This invasion appears to be correlated with relaxed constraints associated with gene loss after cluster duplications

Independent Hox‐cluster duplications in lampreys

The analysis of the publicly available Hox gene sequences from the sea lamprey Petromyzon marinus provides evidence that the Hox clusters in lampreys and other vertebrate species arose from independent duplications. In particular, our analysis supports the hypothesis that the last common ancestor of agnathans and gnathostomes had only a single Hox cluster which was subsequently duplicated independently in the two lineages

Divergence of Conserved Non-Coding Sequences: Rate Estimate and Relative Rate Tests

In many eukaryotic genomes only a small fraction of the DNA codes for proteins, but the non-protein coding DNA harbors important genetic elements directing the development and the physiology of the organisms, like promoters, enhancers, insulators, and micro-RNA genes. The molecular evolution of these genetic elements is difficult to study because their functional significance is hard to deduce from sequence information alone. Here we propose an approach to the study of the rate of evolution of functional non-coding sequences at a macro-evolutionary scale. We identify functionally important non-coding sequences as Conserved Non-Coding Nucleotide (CNCN) sequences from the comparison of two outgroup species. The CNCN sequences so identified are then compared to their homologous sequences in a pair of ingroup species, and we monitor the degree of modification these sequences suffered in the two ingroup lineages. We propose a method to test for rate differences in the modification of CNCN sequences among the two ingroup lineages, as well as a method to estimate their rate of modification. We apply this method to the full sequences of the HoxA clusters from six gnathostome species: a shark, Heterodontus francisci; a basal ray finned fish, Polypterus senegalus; the amphibian, Xenopus tropicalis; as well as three mammalian species, human, rat and mouse. The results show that the evolutionary rate of CNCN sequences is not distinguishable among the three mammalian lineages, while the Xenopus lineage has a significantly increased rate of evolution. Furthermore the estimates of the rate parameters suggest that in the stem lineage of mammals the rate of CNCN sequence evolution was more than twice the rate observed within the placental amniotes clade, suggesting a high rate of evolution of cis-regulatory elements during the origin of amniotes and mammals. We conclude that the proposed methods can be used for testing hypotheses about the rate and pattern of evolution of putative cis-regulatory elements

Exchange-mediated, nonlinear, out-of-plane magnetic field dependence of the ferromagnetic vortex gyrotropic mode frequency driven by core deformation

We have performed micromagnetic simulations of low-amplitude gyrotropic dynamics of magnetic vortices in the presence of spatially uniform out-of-plane magnetic fields. For disks having small lateral dimensions, we observe a frequency drop-off when approaching the disk's out-of-plane saturation field. This nonlinear frequency response is shown to be associated with a vortex core deformation driven by nonuniform demagnetizing fields that act on the shifted core. The deformation results in an increase in the average out-of-plane magnetization of the displaced vortex state (contrasting the effect of gyrofield-driven deformation at low field), which causes the exchange contribution to the vortex stiffness to switch from positive to negative. This generates an enhanced reduction of the core stiffness at high field, leading to a nonlinear field dependence of the gyrotropic mode frequency

The Footprint Sorting Problem

Phylogenetic footprints are short pieces of noncoding DNA sequence in the vicinity of a gene that are conserved between evolutionary distant species. A seemingly simple problem is to sort footprints in their order along the genomes. It is complicated by the fact that not all footprints are collinear:  they may cross each other. The problem thus becomes the identification of the crossing footprints, the sorting of the remaining collinear cliques, and finally the insertion of the noncollinear ones at “reasonable” positions. We show that solving the footprint sorting problem requires the solution of the “Minimum Weight Vertex Feedback Set Problem”, which is known to be NP-complete and APX-hard. Nevertheless good approximations can be obtained for data sets of interest. The remaining steps of the sorting process are straightforward:  computation of the transitive closure of an acyclic graph, linear extension of the resulting partial order, and finally sorting w.r.t. the linear extension. Alternatively, the footprint sorting problem can be rephrased as a combinatorial optimization problem for which approximate solutions can be obtained by means of general purpose heuristics. Footprint sortings obtained with different methods can be compared using a version of multiple sequence alignment that allows the identification of unambiguously ordered sublists. As an application we show that the rat has a slighly increased insertion/deletion rate in comparison to the mouse genome

The effects of waveform and current direction on the efficacy and test–retest reliability of transcranial magnetic stimulation

[Abstract] The pulse waveform and current direction of transcranial magnetic stimulation (TMS) influence its interactions with the neural substrate; however, their role in the efficacy and reliability of single- and paired-pulse TMS measures is not fully understood. We investigated how pulse waveform and current direction affect the efficacy and test–retest reliability of navigated, single- and paired-pulse TMS measures. 23 healthy adults (aged 18–35 years) completed two identical TMS sessions, assessing resting motor threshold (RMT), motor-evoked potentials (MEPs), cortical silent period (cSP), short- and long-interval intra-cortical inhibition (SICI and LICI), and intracortical facilitation (ICF) using either monophasic posterior–anterior (monoPA; n = 9), monophasic anterior–posterior (monoAP; n = 7), or biphasic (biAP-PA; n = 7) pulses. Averages of each TMS measure were compared across the three groups and intraclass correlation coefficients were calculated to assess test–retest reliability. RMT was the lowest and cSP was the longest with biAP-PA pulses, whereas MEP latency was the shortest with monoPA pulses. SICI and LICI had the largest effect with monoPA pulses, whereas only monoAP and biAP-PA pulses resulted in significant ICF. MEP amplitude was more reliable with either monoPA or monoAP than with biAP-PA pulses. LICI was the most reliable with monoAP pulses, whereas ICF was the most reliable with biAP-PA pulses. Waveform/current direction influenced RMT, MEP latency, cSP, SICI, LICI, and ICF, as well as the reliability of MEP amplitude, LICI, and ICF. These results show the importance of considering TMS pulse parameters for optimizing the efficacy and reliability of TMS neurophysiologic measures

Evidence for independent Hox gene duplications in the hagfish lineage: a PCR-based gene inventory of Eptatretus stoutii

Hox genes code for transcription factors that play a major role in the development of all animal phyla. In invertebrates these genes usually occur as tightly linked cluster, with a few exceptions where the clusters have been dissolved. Only in vertebrates multiple clusters have been demonstrated which arose by duplication from a single ancestral cluster. This history of Hox cluster duplications, in particular during the early elaboration of the vertebrate body plan, is still poorly understood. In this paper we report the results of a PCR survey on genomic DNA of the pacific hagfish Eptatretus stoutii. Hagfishes are one of two clades of recent jawless fishes that are an offshoot of the early radiation of jawless vertebrates. Our data provide evidence for at least 33 distinct Hox genes in the hagfish genome, which is most compatible with the hypothesis of multiple Hox clusters. The largest number, seven, of distinct homeobox fragments could be assigned to paralog group 9, which could imply that the hagfish has more than four clusters. Quartet mapping reveals that within each paralog group the hagfish sequences are statistically more closely related to gnathostome Hox genes than with either amphioxus or lamprey genes. These results support two assumptions about the history of Hox genes: (1) The association of hagfish homeobox sequences with gnathostome sequences suggests that at least one Hox cluster duplication event happened in the stem of vertebrates, i.e., prior to the most recent common ancestor of jawed and jawless vertebrates. (2) The high number of paralog group 9 sequences in hagfish and the phylogenetic position of hagfish suggests that the hagfish lineage underwent additional independent Hox cluster/-gene duplication events

Sharing best practices through online communities of practice: a case study

<p>Abstract</p> <p>Introduction</p> <p>The USAID-funded Capacity Project established the Global Alliance for Pre-Service Education (GAPS) to provide an online forum to discuss issues related to teaching and acquiring competence in family planning, with a focus on developing countries' health related training institutions. The success of the Global Alliance for Nursing and Midwifery's ongoing web-based community of practice (CoP) provided a strong example of the successful use of this medium to reach many participants in a range of settings.</p> <p>Case description</p> <p>GAPS functioned as a moderated set of forums that were analyzed by a small group of experts in family planning and pre-service education from three organizations. The cost of the program included the effort provided by the moderators and the time to administer responses and conduct the analysis.</p> <p>Discussion and evaluation</p> <p>Family planning is still considered a minor topic in health related training institutions. Rather than focusing solely on family planning competencies, GAPS members suggested a focus on several professional competencies (e.g. communication, leadership, cultural sensitivity, teamwork and problem solving) that would enhance the resulting health care graduate's ability to operate in a complex health environment. Resources to support competency-based education in the academic setting must be sufficient and appropriately distributed. Where clinical competencies are incorporated into pre-service education, responsible faculty and preceptors must be clinically proficient. The interdisciplinary GAPS memberships allowed for a comparison and contrast of competencies, opportunities, promising practices, documents, lessons learned and key teaching strategies.</p> <p>Conclusions</p> <p>Online CoPs are a useful interface for connecting developing country experiences. From CoPs, we may uncover challenges and opportunities that are faced in the absorption of key public health competencies required for decreasing maternal mortality and morbidity. Use of the World Health Organization (WHO) Implementing Best Practices Knowledge Gateway, which requires only a low bandwidth connection, gave educators an opportunity to engage in the discussion even in the most Internet access-restricted places (e.g. Ethiopia). In order to sustain an online CoP, funds must come from an international organization (e.g. WHO regional office) or university that can program the costs long-term. Eventually, the long-term effectiveness and sustainability of GAPS rests on its transfer to the members themselves.</p

On Dimensionality, Measurement Invariance, and Suitability of Sum Scores for the PHQ-9 and the GAD-7.

In psychiatry, severity of mental health conditions and their change over time are usually measured via sum scores of items on psychometric scales. However, inferences from such scores can be biased if psychometric properties such as unidimensionality and temporal measurement invariance for instruments are not met. Here, we aimed to evaluate these properties for common measures of depression (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder Assessment-7) in a large clinical sample (N = 22,362) undergoing psychotherapy. In addition, we tested consistency in dimensionality results across different methods (parallel analysis, factor analysis, explained common variance, the partial credit model, and the Mokken model). Results showed that while both Patient Health Questionnaire-9 and Generalized Anxiety Disorder Assessment-7 are multidimensional instruments with highly correlated factors, there is justification for sum scores as measures of severity. Temporal measurement invariance across 10 therapy sessions was evaluated. Strict temporal measurement invariance was established in both scales, allowing researchers to compare sum scores as severity measures across time.NIH