Meningococcal genetic variation mechanisms viewed through comparative analysis of Serogroup C strain FAM18

Copyright @ 2007 Public Library of ScienceThe bacterium Neisseria meningitidis is commonly found harmlessly colonising the mucosal surfaces of the human nasopharynx. Occasionally strains can invade host tissues causing septicaemia and meningitis, making the bacterium a major cause of morbidity and mortality in both the developed and developing world. The species is known to be diverse in many ways, as a product of its natural transformability and of a range of recombination and mutation-based systems. Previous work on pathogenic Neisseria has identified several mechanisms for the generation of diversity of surface structures, including phase variation based on slippage-like mechanisms and sequence conversion of expressed genes using information from silent loci. Comparison of the genome sequences of two N. meningitidis strains, serogroup B MC58 and serogroup A Z2491, suggested further mechanisms of variation, including C-terminal exchange in specific genes and enhanced localised recombination and variation related to repeat arrays. We have sequenced the genome of N. meningitidis strain FAM18, a representative of the ST-11/ET-37 complex, providing the first genome sequence for the disease-causing serogroup C meningococci; it has 1,976 predicted genes, of which 60 do not have orthologues in the previously sequenced serogroup A or B strains. Through genome comparison with Z2491 and MC58 we have further characterised specific mechanisms of genetic variation in N. meningitidis, describing specialised loci for generation of cell surface protein variants and measuring the association between noncoding repeat arrays and sequence variation in flanking genes. Here we provide a detailed view of novel genetic diversification mechanisms in N. meningitidis. Our analysis provides evidence for the hypothesis that the noncoding repeat arrays in neisserial genomes (neisserial intergenic mosaic elements) provide a crucial mechanism for the generation of surface antigen variants. Such variation will have an impact on the interaction with the host tissues, and understanding these mechanisms is important to aid our understanding of the intimate and complex relationship between the human nasopharynx and the meningococcus.This work was supported by the Wellcome Trust through the Beowulf Genomics Initiative

Frequency locking of modulated waves

We consider the behavior of a modulated wave solution to an $\mathbb{S}^1$-equivariant autonomous system of differential equations under an external forcing of modulated wave type. The modulation frequency of the forcing is assumed to be close to the modulation frequency of the modulated wave solution, while the wave frequency of the forcing is supposed to be far from that of the modulated wave solution. We describe the domain in the three-dimensional control parameter space (of frequencies and amplitude of the forcing) where stable locking of the modulation frequencies of the forcing and the modulated wave solution occurs. Our system is a simplest case scenario for the behavior of self-pulsating lasers under the influence of external periodically modulated optical signals

Prevalence of under and over weight in children with neurodisability, using body composition measures

We aimed to compare rates of under and overweight in children with different neurodevelopmental disorders (NDD) by measuring weight, height/length, arm-to-leg bioelectrical impedance (BIA) and subscapular and triceps skinfolds in 146 children aged 4-16 years attending special schools. Z scores were calculated and skinfolds and lean mass Z scores were further adjusted for height. Underweight was found in 9% (14) children (body mass index (BMI) < 2nd) but only 3% (4) had skinfolds <5th centile. Overweight was much commoner, with 41% (58) children having BMI > 95th and 20% (14) had skinfolds >95th centile. Children with cerebral palsy were very short with low BMI and lean mass, but only 8% (3) had skinfolds <5th centile. The children with Down syndrome were also very short and once adjusted for height, half had skinfolds >95th centile. We conclude that overweight and raised body fat is now common in children with NDD, even when the BMI is low

Connected components of spaces of Morse functions with fixed critical points

Let $M$ be a smooth closed orientable surface and $F=F_{p,q,r}$ be the space of Morse functions on $M$ having exactly $p$ critical points of local minima, $q\ge1$ saddle critical points, and $r$ critical points of local maxima, moreover all the points are fixed. Let $F_f$ be the connected component of a function $f\in F$ in $F$. By means of the winding number introduced by Reinhart (1960), a surjection $\pi_0(F)\to{\mathbb Z}^{p+r-1}$ is constructed. In particular, $|\pi_0(F)|=\infty$, and the Dehn twist about the boundary of any disk containing exactly two critical points, exactly one of which is a saddle point, does not preserve $F_f$. Let $\mathscr D$ be the group of orientation preserving diffeomorphisms of $M$ leaving fixed the critical points, ${\mathscr D}^0$ be the connected component of ${\rm id}_M$ in $\mathscr D$, and ${\mathscr D}_f\subset{\mathscr D}$ the set of diffeomorphisms preserving $F_f$. Let ${\mathscr H}_f$ be the subgroup of ${\mathscr D}_f$ generated by ${\mathscr D}^0$ and all diffeomorphisms $h\in{\mathscr D}$ which preserve some functions $f_1\in F_f$, and let ${\mathscr H}_f^{\rm abs}$ be its subgroup generated ${\mathscr D}^0$ and the Dehn twists about the components of level curves of functions $f_1\in F_f$. We prove that ${\mathscr H}_f^{\rm abs}\subsetneq{\mathscr D}_f$ if $q\ge2$, and construct an epimorphism ${\mathscr D}_f/{\mathscr H}_f^{\rm abs}\to{\mathbb Z}_2^{q-1}$, by means of the winding number. A finite polyhedral complex $K=K_{p,q,r}$ associated to the space $F$ is defined. An epimorphism $\mu:\pi_1(K)\to{\mathscr D}_f/{\mathscr H}_f$ and finite generating sets for the groups ${\mathscr D}_f/{\mathscr D}^0$ and ${\mathscr D}_f/{\mathscr H}_f$ in terms of the 2-skeleton of the complex $K$ are constructed.Comment: 12 pages with 2 figures, in Russian, to be published in Vestnik Moskov. Univ., a typo in theorem 1 is correcte

Chief digital officers:An analysis of the presence of a centralized digital transformation role

By appointing a chief digital officer (CDO), firms decide for a central role responsible for their digital transformation. While CDOs have recently appeared in the C-suites of firms across the globe, the current literature lacks insights into the specific antecedents of CDO presence. Grounded in the peculiarities of the digital age, we provide theoretical arguments explaining how the decision to centralize digital transformation responsibilities might be related to transformation urgency and coordination needs. Empirical analyses based on a panel data set of 913 U.S. and European firms support that transformation urgency and coordination needs predict CDO presence. An additional analysis of moderating temporal effects reveals that, over time, the effect of transformation urgency is weakened and the effect of coordination needs on CDO presence is strengthened. We discuss implications for research and practice regarding the antecedents of CDO presence, TMT research more generally, and centralization in the digital age

The degree of acute descending control of spinal nociception in an area of primary hyperalgesia is dependent on the peripheral domain of afferent input

Descending controls of spinal nociceptive processing play a critical role in the development of inflammatory hyperalgesia. Acute peripheral nociceptor sensitization drives spinal sensitization and activates spino–supraspinal–spinal loops leading to descending inhibitory and facilitatory controls of spinal neuronal activity that further modify the extent and degree of the pain state. The afferent inputs from hairy and glabrous skin are distinct with respect to both the profile of primary afferent classes and the degree of their peripheral sensitization. It is not known whether these differences in afferent input differentially engage descending control systems to different extents or in different ways. Injection of complete Freund's adjuvant resulted in inflammation and swelling of hairy hind foot skin in rats, a transient thermal hyperalgesia lasting 72 h). In hairy skin, transient hyperalgesia was associated with sensitization of withdrawal reflexes to thermal activation of either A- or C-nociceptors. The transience of the hyperalgesia was attributable to a rapidly engaged descending inhibitory noradrenergic mechanism, which affected withdrawal responses to both A- and C-nociceptor activation and this could be reversed by intrathecal administration of yohimbine (α-2-adrenoceptor antagonist). In glabrous skin, yohimbine had no effect on an equivalent thermal inflammatory hyperalgesia. We conclude that acute inflammation and peripheral nociceptor sensitization in hind foot hairy skin, but not glabrous skin, rapidly activates a descending inhibitory noradrenergic system. This may result from differences in the engagement of descending control systems following sensitization of different primary afferent classes that innervate glabrous and hairy skin

La pena de treballs en benefici de la comunitat : prevenció i gestió de les incidències en el seu compliment

Aquest estudi té com a objectiu explorar la prevenció i gestió d'incidències que duen a terme els delegats d'execució de mesures per tal d'aconseguir un compliment efectiu, per part dels penats a TBC. Així, a través del marc teòric es vol abordar el compliment en general per tal de comprendre la seva importància des de diferents perspectives així com els elements que la literatura científica mostra com a dificultats en el procés de compliment. El treball de camp recull les aportacions de delegades d'execució de mesures mitjançant una metodologia qualitativa.This study aims to explore the prevention and management of incidents carried out by probation officers aimed at the effective compliance, by those sentenced to community service. Thus, the theoretical framework aims to address compliance in general in order to understand its importance from different perspectives as well as the elements that the scientific literature shows as difficulties in the compliance process. The fieldwork collects the visions of probation officers using a qualitative methodology

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Genomic reconstruction of the SARS-CoV-2 epidemic in England.

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021