Specific Alterations in Complement Protein Activity of Little Brown Myotis (Myotis lucifugus) Hibernating in White-Nose Syndrome Affected Sites

White-nose syndrome (WNS) is the most devastating condition ever reported for hibernating bats, causing widespread mortality in the northeastern United States. The syndrome is characterized by cutaneous lesions caused by a recently identified psychrophilic and keratinophylic fungus (Geomyces destructans), depleted fat reserves, atypical behavior, and damage to wings; however, the proximate cause of mortality is still uncertain. To assess relative levels of immunocompetence in bats hibernating in WNS-affected sites compared with levels in unaffected bats, we describe blood plasma complement protein activity in hibernating little brown myotis (Myotis lucifugus) based on microbicidal competence assays using Escherichia coli, Staphylococcus aureus and Candida albicans. Blood plasma from bats collected during mid-hibernation at WNS-affected sites had higher bactericidal ability against E. coli and S. aureus, but lower fungicidal ability against C. albicans when compared with blood plasma from bats collected at unaffected sites. Within affected sites during mid-hibernation, we observed no difference in microbicidal ability between bats displaying obvious fungal infections compared to those without. Bactericidal ability against E. coli decreased significantly as hibernation progressed in bats collected from an affected site. Bactericidal ability against E. coli and fungicidal ability against C. albicans were positively correlated with body mass index (BMI) during late hibernation. We also compared complement activity against the three microbes within individuals and found that the ability of blood plasma from hibernating M. lucifugus to lyse microbial cells differed as follows: E. coli>S. aureus>C. albicans. Overall, bats affected by WNS experience both relatively elevated and reduced innate immune responses depending on the microbe tested, although the cause of observed immunological changes remains unknown. Additionally, considerable trade-offs may exist between energy conservation and immunological responses. Relationships between immune activity and torpor, including associated energy expenditure, are likely critical components in the development of WNS

Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism

SummaryWe have undertaken a genome-wide analysis of rare copy-number variation (CNV) in 1124 autism spectrum disorder (ASD) families, each comprised of a single proband, unaffected parents, and, in most kindreds, an unaffected sibling. We find significant association of ASD with de novo duplications of 7q11.23, where the reciprocal deletion causes Williams-Beuren syndrome, characterized by a highly social personality. We identify rare recurrent de novo CNVs at five additional regions, including 16p13.2 (encompassing genes USP7 and C16orf72) and Cadherin 13, and implement a rigorous approach to evaluating the statistical significance of these observations. Overall, large de novo CNVs, particularly those encompassing multiple genes, confer substantial risks (OR = 5.6; CI = 2.6–12.0, p = 2.4 × 10-7). We estimate there are 130–234 ASD-related CNV regions in the human genome and present compelling evidence, based on cumulative data, for association of rare de novo events at 7q11.23, 15q11.2-13.1, 16p11.2, and Neurexin 1

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Microbicidal ability across the hibernation period.

<p>Microbicidal ability, expressed as percent microbe killed, against <i>E. coli</i> (A) and <i>S. aureus</i> (B) in blood plasma collected from little brown myotis hibernating in the affected Aeolus Cave during the 2008–2009 hibernation period. Bactericidal ability of blood plasma against <i>E. coli</i> varied significantly throughout the hibernation period (early <i>n</i> = 18; mid <i>n</i> = 18; late <i>n</i> = 16; F<i>_{2, 49}</i> = 5.86; <i>p</i> = 0.005; R² = 0.19) and was greater during early hibernation than in late hibernation (<i>p</i> = 0.004). Bactericidal ability of blood plasma against <i>S. aureus</i> also varied significantly throughout the hibernation period (early <i>n</i> = 18; mid <i>n</i> = 18; late <i>n</i> = 17; F<i>_{2, 51}</i> = 31.7; <i>p</i><0.001; R² = 0.55), but was greater in early hibernation compared with mid-hibernation (<i>p</i><0.001) and greater in late hibernation than in early hibernation (<i>p</i> = 0.002) and mid-hibernation (<i>p</i><0.001). Lines indicate mean percent microbe killed ±1 SE.</p

Microbicidal ability of blood plasma from little brown myotis collected in WNS-affected and unaffected sites.

<p>Microbicidal ability, expressed as percent microbe killed, against <i>E. coli</i> (A), <i>S. aureus</i> (B), and <i>C. albicans</i> (C) in <i>M. lucifugus</i> collected from WNS-affected and unaffected sites during the winter of 2008–2009. Significantly more <i>E. coli</i> was killed by plasma collected from bats hibernating in WNS-affected sites compared with plasma collected from bats hibernating in unaffected sites (affected <i>n</i> = 54; unaffected <i>n</i> = 31; F<i>_{1, 80}</i> = 16.22; <i>p</i><0.001; R² = 0.17). Bactericidal ability against <i>S. aureus</i> was also significantly greater in bats collected from affected sites compared with bats from unaffected sites (affected <i>n</i> = 55; unaffected <i>n</i> = 31; F<i>_{1, 81}</i> = 9.05; <i>p</i> = 0.004; R² = 0.10), but fungicidal ability against <i>C. albicans</i> was significantly lower in bats collected at affected sites compared with bats collected at unaffected sites (affected <i>n</i> = 52; unaffected <i>n</i> = 25; Mann-Whitney U = 383; <i>p</i> = 0.004). Lines indicate mean percent microbe killed ±1 SE.</p

Sample sizes for winter 2008–2009 collections across multiple hibernacula and different stages within the hibernation period.

<p>Sample sizes for winter 2008–2009 collections across multiple hibernacula and different stages within the hibernation period.</p

Little brown myotis affected by WNS.

<p>Hibernating little brown myotis (<i>Myotis lucifugus</i>) with and without visible white fungal growth characteristic of white-nose syndrome.</p