Human L-Ficolin (Ficolin-2) and Its Clinical Significance

Human L-ficolin (P35, ficolin-2) is synthesised in the liver and secreted into the bloodstream where it is one of the major pattern recognition molecules of plasma/serum. Like other ficolins, it consists of a collagen-like tail region linked to a fibrinogen-related globular head; a basic triplet subunit arises via a collagen-like triple helix, and this then forms higher multimers (typically a 12-mer, Mr 400K). Unlike other ficolins, it has a complex set of binding sites arranged within an internal cleft enabling it to recognise a variety of molecular patterns including acetylated sugars and certain 1,3-β-glucans. It is one of the few molecules known to activate the lectin pathway of complement. Recently, some disease association studies (at either the DNA or protein level) have implicated L-ficolin in innate immunity, where it might cooperate with pentraxins and collectins. Emerging lines of evidence point to a role for L-ficolin in respiratory immunity, where its affinity for Pseudomonas aeruginosa could be significant

DISTRIBUTION AND PREVALENCE OF ELAEOPHORA SCHNEIDERI IN MOOSE IN WYOMING

Elaeophora schneideri causes disease in aberrant hosts such as moose. Documented E. schneideri infections in moose are relatively rare, yet noteworthy enough that individual cases describing morbidity and mortality have been the norm for reporting. Surveillance efforts for E. schneideri in Wyoming moose in the 1970s found zero cases, but since 2000 several moose in Wyoming discovered dead or showing clinical signs of elaeophorosis have been found infected with E. schneideri. In 2009 we searched for worms in the carotid arteries of 168 hunter-harvested moose from across Wyoming to determine the prevalence and distribution of E. schneideri in moose; 82 (48.8%; 95% CI: 41.4-56.3%) were positive for E. schneideri. Prevalence did not differ between sexes or among age classes but there was difference in prevalence among herd units (range = 5-82.6%). Intensity of infection (range = 1-26 worms) did not differ between sexes, among age classes, or among herd units. Our findings indicate that moose do not succumb to the parasite to the extent previously thought. Prevalence and intensity were constant across age classes, suggesting that infected moose are surviving and an acquired, immunological resistance to further infection develops. In addition, moose might sometimes act as natural hosts to the parasite, as indicated by 1) high prevalence of infection in moose in areas where sympatric mule deer had much lower prevalence of infection, and 2) preliminary necropsy findings that revealed microfilariae in skin samples from 3 moose. However, negative impacts to moose and moose populations cannot be ruled out entirely, as this study was limited to apparently healthy hunter-harvested animals. While moose appear to often survive infection with E. schneideri, prevalence of ~50% is still cause for concern because it is unknown to what extent this parasite causes subclinical effects in moose that might impact recruitment or productivity. Subsequent research on moose herds where E. schneideri occurs should consider the effects of elaeophorosis and attempt to clarify its role

Multi-Messenger Astronomy with Extremely Large Telescopes

The field of time-domain astrophysics has entered the era of Multi-messenger Astronomy (MMA). One key science goal for the next decade (and beyond) will be to characterize gravitational wave (GW) and neutrino sources using the next generation of Extremely Large Telescopes (ELTs). These studies will have a broad impact across astrophysics, informing our knowledge of the production and enrichment history of the heaviest chemical elements, constrain the dense matter equation of state, provide independent constraints on cosmology, increase our understanding of particle acceleration in shocks and jets, and study the lives of black holes in the universe. Future GW detectors will greatly improve their sensitivity during the coming decade, as will near-infrared telescopes capable of independently finding kilonovae from neutron star mergers. However, the electromagnetic counterparts to high-frequency (LIGO/Virgo band) GW sources will be distant and faint and thus demand ELT capabilities for characterization. ELTs will be important and necessary contributors to an advanced and complete multi-messenger network.Comment: White paper submitted to the Astro2020 Decadal Surve

Moving Beyond Too Little, Too Late: Managing Emerging Infectious Diseases in Wild Populations Requires International Policy and Partnerships

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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum