Accidental Intracranial Hyperalimentation Infusion

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141658/1/jpen0532.pd

Genomic Consequences of Fragmentation in the Endangered Fennoscandian Arctic Fox (Vulpes lagopus)

Accelerating climate change is causing severe habitat fragmentation in the Arctic, threatening the persistence of many cold-adapted species. The Scandinavian arctic fox (V. lagopus) is highly fragmented, with a once continuous, circumpolar distribution, it struggled to recover from a demographic bottleneck in the late 19th century. The future persistence of the entire Scandinavian population is highly dependent on the northernmost Fennoscandian subpopulations (Scandinavia and the Kola Peninsula), to provide a link to the viable Siberian population. By analyzing 43 arctic fox genomes, we quantified genomic variation and inbreeding in these populations. Signatures of genome erosion increased from Siberia to northern Sweden indicating a stepping-stone model of connectivity. In northern Fennoscandia, runs of homozygosity (ROH) were on average ~1.47-fold longer than ROH found in Siberia, stretching almost entire scaffolds. Moreover, consistent with recent inbreeding, northern Fennoscandia harbored more homozygous deleterious mutations, whereas Siberia had more in heterozygous state. This study underlines the value of documenting genome erosion following population fragmentation to identify areas requiring conservation priority. With the increasing fragmentation and isolation of Arctic habitats due to global warming, understanding the genomic and demographic consequences is vital for maintaining evolutionary potential and preventing local extinctions. inbreeding; runs of homozygosity; bottleneck; fragmentation; mutational load; conservatio

The Panchromatic Hubble Andromeda Treasury II. Tracing the Inner M31 Halo with Blue Horizontal Branch Stars

We attempt to constrain the shape of M31's inner stellar halo by tracing the surface density of blue horizontal branch (BHB) stars at galactocentric distances ranging from 2 kpc to 35 kpc. Our measurements make use of resolved stellar photometry from a section of the Panchromatic Hubble Andromeda Treasury (PHAT) survey, supplemented by several archival Hubble Space Telescope observations. We find that the ratio of BHB to red giant stars is relatively constant outside of 10 kpc, suggesting that the BHB is as reliable a tracer of the halo population as the red giant branch. In the inner halo, we do not expect BHB stars to be produced by the high metallicity bulge and disk, making BHB stars a good candidate to be a reliable tracer of the stellar halo to much smaller galactocentric distances. If we assume a power-law profile r^(-\alpha) for the 2-D projected surface density BHB distribution, we obtain a high-quality fit with a 2-D power-law index of \alpha=2.6^{+0.3}_{-0.2} outside of 3 kpc, which flattens to \alpha<1.2 inside of 3 kpc. This slope is consistent with previous measurements but is anchored to a radial baseline that extends much farther inward. Finally, assuming azimuthal symmetry and a constant mass-to-light ratio, the best-fitting profile yields a total halo stellar mass of 2.1^{+1.7}_{-0.4} x 10^9 M_sun. These properties are comparable with both simulations of stellar halo formation formed by satellite disruption alone, and with simulations that include some in situ formation of halo stars.Comment: 15 pages, 1 table, 5 figures, accepted for publication in Ap

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Multidimensional signals and analytic flexibility: Estimating degrees of freedom in human speech analyses

Recent empirical studies have highlighted the large degree of analytic flexibility in data analysis which can lead to substantially different conclusions based on the same data set. Thus, researchers have expressed their concerns that these researcher degrees of freedom might facilitate bias and can lead to claims that do not stand the test of time. Even greater flexibility is to be expected in fields in which the primary data lend themselves to a variety of possible operationalizations. The multidimensional, temporally extended nature of speech constitutes an ideal testing ground for assessing the variability in analytic approaches, which derives not only from aspects of statistical modeling, but also from decisions regarding the quantification of the measured behavior. In the present study, we gave the same speech production data set to 46 teams of researchers and asked them to answer the same research question, resulting insubstantial variability in reported effect sizes and their interpretation. Using Bayesian meta-analytic tools, we further find little to no evidence that the observed variability can be explained by analysts’ prior beliefs, expertise or the perceived quality of their analyses. In light of this idiosyncratic variability, we recommend that researchers more transparently share details of their analysis, strengthen the link between theoretical construct and quantitative system and calibrate their (un)certainty in their conclusions

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

The Bacterial (Vibrio alginolyticus) Production of Tetrodotoxin in the Ribbon Worm Lineus longissimus-Just a False Positive?

We test previous claims that the bacteria Vibrio alginolyticus produces tetrodotoxin (TTX) when living in symbiosis with the nemertean Lineus longissimus by a setup with bacteria cultivation for TTX production. Toxicity experiments on the shore crab, Carcinus maenas, demonstrated the presence of a paralytic toxin, but evidence from LC-MS and electrophysiological measurements of voltage-gated sodium channel-dependent nerve conductance in male Wistar rat tissue showed conclusively that this effect did not originate from TTX. However, a compound of similar molecular weight was found, albeit apparently non-toxic, and with different LC retention time and MS/MS fragmentation pattern than those of TTX. We conclude that C. maenas paralysis and death likely emanate from a compound &lt;5 kDa, and via a different mechanism of action than that of TTX. The similarity in mass between TTX and the Vibrio-produced low-molecular-weight, non-toxic compound invokes that thorough analysis is required when assessing TTX production. Based on our findings, we suggest that re-examination of some published claims of TTX production may be warranted