Scalar soliton quantization with generic moduli

This article is distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits any use, distribution and reproduction in any medium, provided the original author(s) and source are credArticle funded by SCOAP3. CP is a Royal Society Research Fellow and partly supported by the U.S. Department of Energy under grants DOE-SC0010008, DOE-ARRA-SC0003883 and DOE-DE-SC0007897. ABR is supported by the Mitchell Family Foundation. We would like to thank the Mitchell Institute at Texas A&M and the NHETC at Rutgers University respectively for hospitality during the course of this work. We would also like to acknowledge the Aspen Center for Physics and NSF grant 1066293 for a stimulating research environment which led to questions addressed in this paper

Bridging topological and functional information in protein interaction networks by short loops profiling

Protein-protein interaction networks (PPINs) have been employed to identify potential novel interconnections between proteins as well as crucial cellular functions. In this study we identify fundamental principles of PPIN topologies by analysing network motifs of short loops, which are small cyclic interactions of between 3 and 6 proteins. We compared 30 PPINs with corresponding randomised null models and examined the occurrence of common biological functions in loops extracted from a cross-validated high-confidence dataset of 622 human protein complexes. We demonstrate that loops are an intrinsic feature of PPINs and that specific cell functions are predominantly performed by loops of different lengths. Topologically, we find that loops are strongly related to the accuracy of PPINs and define a core of interactions with high resilience. The identification of this core and the analysis of loop composition are promising tools to assess PPIN quality and to uncover possible biases from experimental detection methods. More than 96% of loops share at least one biological function, with enrichment of cellular functions related to mRNA metabolic processing and the cell cycle. Our analyses suggest that these motifs can be used in the design of targeted experiments for functional phenotype detection.This research was supported by the Biotechnology and Biological Sciences Research Council (BB/H018409/1 to AP, ACCC and FF, and BB/J016284/1 to NSBT) and by the Leukaemia & Lymphoma Research (to NSBT and FF). SSC is funded by a Leukaemia & Lymphoma Research Gordon Piller PhD Studentship

DEP and AFO Regulate Reproductive Habit in Rice

Sexual reproduction is essential for the life cycle of most angiosperms. However, pseudovivipary is an important reproductive strategy in some grasses. In this mode of reproduction, asexual propagules are produced in place of sexual reproductive structures. However, the molecular mechanism of pseudovivipary still remains a mystery. In this work, we found three naturally occurring mutants in rice, namely, phoenix (pho), degenerative palea (dep), and abnormal floral organs (afo). Genetic analysis of them indicated that the stable pseudovivipary mutant pho was a double mutant containing both a Mendelian mutation in DEP and a non-Mendelian mutation in AFO. Further map-based cloning and microarray analysis revealed that dep mutant was caused by a genetic alteration in OsMADS15 while afo was caused by an epigenetic mutation in OsMADS1. Thus, OsMADS1 and OsMADS15 are both required to ensure sexual reproduction in rice and mutations of them lead to the switch of reproductive habit from sexual to asexual in rice. For the first time, our results reveal two regulators for sexual and asexual reproduction modes in flowering plants. In addition, our findings also make it possible to manipulate the reproductive strategy of plants, at least in rice

FHA-Mediated Cell-Substrate and Cell-Cell Adhesions Are Critical for Bordetella pertussis Biofilm Formation on Abiotic Surfaces and in the Mouse Nose and the Trachea

Bordetella spp. form biofilms in the mouse nasopharynx, thereby providing a potential mechanism for establishing chronic infections in humans and animals. Filamentous hemagglutinin (FHA) is a major virulence factor of B. pertussis, the causative agent of the highly transmissible and infectious disease, pertussis. In this study, we dissected the role of FHA in the distinct biofilm developmental stages of B. pertussis on abiotic substrates and in the respiratory tract by employing a murine model of respiratory biofilms. Our results show that the lack of FHA reduced attachment and decreased accumulation of biofilm biomass on artificial surfaces. FHA contributes to biofilm development by promoting the formation of microcolonies. Absence of FHA from B. pertussis or antibody-mediated blockade of surface-associated FHA impaired the attachment of bacteria to the biofilm community. Exogenous addition of FHA resulted in a dose-dependent inhibitory effect on bacterial association with the biofilms. Furthermore, we show that FHA is important for the structural integrity of biofilms formed on the mouse nose and trachea. Together, these results strongly support the hypothesis that FHA promotes the formation and maintenance of biofilms by mediating cell-substrate and inter-bacterial adhesions. These discoveries highlight FHA as a key factor in establishing structured biofilm communities in the respiratory tract

Dcc Regulates Asymmetric Outgrowth of Forebrain Neurons in Zebrafish

The guidance receptor DCC (deleted in colorectal cancer) ortholog UNC-40 regulates neuronal asymmetry development in Caenorhabditis elegans, but it is not known whether DCC plays a role in the specification of neuronal polarity in vertebrates. To examine the roles of DCC in neuronal asymmetry regulation in vertebrates, we studied zebrafish anterior dorsal telencephalon (ADt) neuronal axons. We generated transgenic zebrafish animals expressing the photo-convertible fluorescent protein Kaede in ADt neurons and then photo-converted Kaede to label specifically the ADt neuron axons. We found that ADt axons normally project ventrally. Knock down of Dcc function by injecting antisense morpholino oligonucleotides caused the ADt neurons to project axons dorsally. To examine the axon projection pattern of individual ADt neurons, we labeled single ADt neurons using a forebrain-specific promoter to drive fluorescent protein expression. We found that individual ADt neurons projected axons dorsally or formed multiple processes after morpholino knock down of Dcc function. We further found that knock down of the Dcc ligand, Netrin1, also caused ADt neurons to project axons dorsally. Knockdown of Neogenin1, a guidance receptor closely related to Dcc, enhanced the formation of aberrant dorsal axons in embryos injected with Dcc morpholino. These experiments provide the first evidence that Dcc regulates polarized axon initiation and asymmetric outgrowth of forebrain neurons in vertebrates

Early Evolution of Conserved Regulatory Sequences Associated with Development in Vertebrates

Comparisons between diverse vertebrate genomes have uncovered thousands of highly conserved non-coding sequences, an increasing number of which have been shown to function as enhancers during early development. Despite their extreme conservation over 500 million years from humans to cartilaginous fish, these elements appear to be largely absent in invertebrates, and, to date, there has been little understanding of their mode of action or the evolutionary processes that have modelled them. We have now exploited emerging genomic sequence data for the sea lamprey, Petromyzon marinus, to explore the depth of conservation of this type of element in the earliest diverging extant vertebrate lineage, the jawless fish (agnathans). We searched for conserved non-coding elements (CNEs) at 13 human gene loci and identified lamprey elements associated with all but two of these gene regions. Although markedly shorter and less well conserved than within jawed vertebrates, identified lamprey CNEs are able to drive specific patterns of expression in zebrafish embryos, which are almost identical to those driven by the equivalent human elements. These CNEs are therefore a unique and defining characteristic of all vertebrates. Furthermore, alignment of lamprey and other vertebrate CNEs should permit the identification of persistent sequence signatures that are responsible for common patterns of expression and contribute to the elucidation of the regulatory language in CNEs. Identifying the core regulatory code for development, common to all vertebrates, provides a foundation upon which regulatory networks can be constructed and might also illuminate how large conserved regulatory sequence blocks evolve and become fixed in genomic DNA

The Melbourne epidemic thunderstorm asthma event 2016: an investigation of environmental triggers, effect on health services, and patient risk factors.

BACKGROUND: A multidisciplinary collaboration investigated the world's largest, most catastrophic epidemic thunderstorm asthma event that took place in Melbourne, Australia, on Nov 21, 2016, to inform mechanisms and preventive strategies. METHODS: Meteorological and airborne pollen data, satellite-derived vegetation index, ambulance callouts, emergency department presentations, and data on hospital admissions for Nov 21, 2016, as well as leading up to and following the event were collected between Nov 21, 2016, and March 31, 2017, and analysed. We contacted patients who presented during the epidemic thunderstorm asthma event at eight metropolitan health services (each including up to three hospitals) via telephone questionnaire to determine patient characteristics, and investigated outcomes of intensive care unit (ICU) admissions. FINDINGS: Grass pollen concentrations on Nov 21, 2016, were extremely high (>100 grains/m3). At 1800 AEDT, a gust front crossed Melbourne, plunging temperatures 10°C, raising humidity above 70%, and concentrating particulate matter. Within 30 h, there were 3365 (672%) excess respiratory-related presentations to emergency departments, and 476 (992%) excess asthma-related admissions to hospital, especially individuals of Indian or Sri Lankan birth (10% vs 1%, p<0·0001) and south-east Asian birth (8% vs 1%, p<0·0001) compared with previous 3 years. Questionnaire data from 1435 (64%) of 2248 emergency department presentations showed a mean age of 32·0 years (SD 18·6), 56% of whom were male. Only 28% had current doctor-diagnosed asthma. 39% of the presentations were of Asian or Indian ethnicity (25% of the Melbourne population were of this ethnicity according to the 2016 census, relative risk [RR] 1·93, 95% CI 1·74-2·15, p <0·0001). Of ten individuals who died, six were Asian or Indian (RR 4·54, 95% CI 1·28-16·09; p=0·01). 35 individuals were admitted to an intensive care unit, all had asthma, 12 took inhaled preventers, and five died. INTERPRETATION: Convergent environmental factors triggered a thunderstorm asthma epidemic of unprecedented magnitude, tempo, and geographical range and severity on Nov 21, 2016, creating a new benchmark for emergency and health service escalation. Asian or Indian ethnicity and current doctor-diagnosed asthma portended life-threatening exacerbations such as those requiring admission to an ICU. Overall, the findings provide important public health lessons applicable to future event forecasting, health care response coordination, protection of at-risk populations, and medical management of epidemic thunderstorm asthma. FUNDING: None

Glatiramer acetate reduces the risk for experimental cerebral malaria: a pilot study

<p>Abstract</p> <p>Background</p> <p>Cerebral malaria (CM) is associated with high mortality and morbidity caused by a high rate of transient or persistent neurological sequelae. Studies on immunomodulatory and neuroprotective drugs as ancillary treatment in murine CM indicate promising potential. The current study was conducted to evaluate the efficacy of glatiramer acetate (GA), an immunomodulatory drug approved for the treatment of relapsing remitting multiple sclerosis, in preventing the death of C57Bl/6J mice infected with <it>Plasmodium berghei </it>ANKA.</p> <p>Methods and Results</p> <p>GA treatment led to a statistically significant lower risk for developing CM (57.7% versus 84.6%) in treated animals. The drug had no effect on the course of parasitaemia. The mechanism of action seems to be an immunomodulatory effect since lower IFN-gamma levels were observed in treated animals in the early course of the disease (day 4 post-infection) which also led to a lower number of brain sequestered leukocytes in treated animals. No direct neuro-protective effect such as an inhibition of apoptosis or reduction of micro-bleedings in the brain was found.</p> <p>Conclusion</p> <p>These findings support the important role of the host immune response in the pathophysiology of murine CM and might lead to the development of new adjunctive treatment strategies.</p