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

Brain matters: unveiling the distinct contributions of region, age, and sex to glia diversity and CNS function

The myelinated white matter tracts of the central nervous system (CNS) are essential for fast transmission of electrical impulses and are often differentially affected in human neurodegenerative diseases across CNS region, age and sex. We hypothesize that this selective vulnerability is underpinned by physiological variation in white matter glia. Using single nucleus RNA sequencing of human post-mortem white matter samples from the brain, cerebellum and spinal cord and subsequent tissue-based validation we found substantial glial heterogeneity with tissue region: we identified region-specific oligodendrocyte precursor cells (OPCs) that retain developmental origin markers into adulthood, distinguishing them from mouse OPCs. Region-specific OPCs give rise to similar oligodendrocyte populations, however spinal cord oligodendrocytes exhibit markers such as SKAP2 which are associated with increased myelin production and we found a spinal cord selective population particularly equipped for producing long and thick myelin sheaths based on the expression of genes/proteins such as HCN2. Spinal cord microglia exhibit a more activated phenotype compared to brain microglia, suggesting that the spinal cord is a more pro-inflammatory environment, a difference that intensifies with age. Astrocyte gene expression correlates strongly with CNS region, however, astrocytes do not show a more activated state with region or age. Across all glia, sex differences are subtle but the consistent increased expression of protein-folding genes in male donors hints at pathways that may contribute to sex differences in disease susceptibility. These findings are essential to consider for understanding selective CNS pathologies and developing tailored therapeutic strategies

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

No Full Tex

A Radio Flare in the Long-lived Afterglow of the Distant Short GRB 210726A: Energy Injection or a Reverse Shock from Shell Collisions?

We present the discovery of the radio afterglow of the short gamma-ray burst (GRB) 210726A, localized to a galaxy at a photometric redshift of z ∼ 2.4. While radio observations commenced ≲1 day after the burst, no radio emission was detected until ∼11 days. The radio afterglow subsequently brightened by a factor of ∼3 in the span of a week, followed by a rapid decay (a “radio flare”). We find that a forward shock afterglow model cannot self-consistently describe the multiwavelength X-ray and radio data, and underpredicts the flux of the radio flare by a factor of ≈5. We find that the addition of substantial energy injection, which increases the isotropic kinetic energy of the burst by a factor of ≈4, or a reverse shock from a shell collision are viable solutions to match the broadband behavior. At z ∼ 2.4, GRB 210726A is among the highest-redshift short GRBs discovered to date, as well as the most luminous in radio and X-rays. Combining and comparing all previous radio afterglow observations of short GRBs, we find that the majority of published radio searches conclude by ≲10 days after the burst, potentially missing these late-rising, luminous radio afterglows

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