Global warming and arctic terns: Estimating climate change impacts on the world's longest migration.

Climate change is one of the top three global threats to seabirds, particularly species that visit polar regions. Arctic terns migrate between both polar regions annually and rely on productive marine areas to forage, on sea ice for rest and foraging, and prevailing winds during flight. Here, we report 21st-century trends in environmental variables affecting arctic terns at key locations along their Atlantic/Indian Ocean migratory flyway during the non-breeding seasons, identified through tracking data. End-of-century climate change projections were derived from Earth System Models and multi-model means calculated in two Shared Socioeconomic Pathways: 'middle-of-the-road' and 'fossil-fuelled development' scenarios. Declines in North Atlantic primary production emerge as a major impact to arctic terns likely to affect their foraging during the 21st century under a 'fossil-fuelled development' scenario. Minimal changes are, however, projected at three other key regions visited by arctic terns (Benguela Upwelling, Subantarctic Indian Ocean and the Southern Ocean). Southern Ocean sea ice extent is likely to decline, but the magnitude of change and potential impacts on tern survival are uncertain. Small changes (<1 m s-1 ) in winds are projected in both scenarios, but with minimal likely impacts on migration routes and duration. However, Southern Ocean westerlies are likely to strengthen and contract closer to the continent, which may require arctic terns to shift routes or flight strategies. Overall, we find minor effects of climate change on the migration of arctic terns, with the exception of poorer foraging in the North Atlantic. However, given that arctic terns travel over huge spatial scales and live for decades, they integrate minor changes in conditions along their migration routes such that the sum effect may be greater than the parts. Meeting carbon emission targets is vital to slow these end-of-century climatic changes and minimise extinction risk for a suite of polar species.

Hearing conservation measures of effectiveness across the Department of Defense.

This article summarizes the findings from the first report of the new, standard Measures of Effectiveness developed by the Department of Defense (DoD) Hearing Conservation Program Working Group in 2018. When examining periodic hearing test results of DoD personnel, the overall risk of potential hearing injury/illness was stable from 2012 through 2018. The National Guard and Reserve components showed a higher potential risk of hearing loss, possibly related to lower compliance on follow-up tests when a shift in hearing occurred. Finally, the overall percentage of DoD personnel (who received periodic hearing tests) with hearing impairment decreased over the years presented.

Metabolic inhibitors of bacterial glycan biosynthesis.

The bacterial cell wall is a quintessential drug target due to its critical role in colonization of the host, pathogen survival, and immune evasion. The dense cell wall glycocalyx contains distinctive monosaccharides that are absent from human cells, and proper assembly of monosaccharides into higher-order glycans is critical for bacterial fitness and pathogenesis. However, the systematic study and inhibition of bacterial glycosylation enzymes remains challenging. Bacteria produce glycans containing rare deoxy amino sugars refractory to traditional glycan analysis, complicating the study of bacterial glycans and the creation of glycosylation inhibitors. To ease the study of bacterial glycan function in the absence of detailed structural or enzyme information, we crafted metabolic inhibitors based on rare bacterial monosaccharide scaffolds. Metabolic inhibitors were assessed for their ability to interfere with glycan biosynthesis and fitness in pathogenic and symbiotic bacterial species. Three metabolic inhibitors led to dramatic structural and functional defects in Helicobacter pylori. Strikingly, these inhibitors acted in a bacteria-selective manner. These metabolic inhibitors will provide a platform for systematic study of bacterial glycosylation enzymes not currently possible with existing tools. Moreover, their selectivity will provide a pathway for the development of novel, narrow-spectrum antibiotics to treat infectious disease. Our inhibition approach is general and will expedite the identification of bacterial glycan biosynthesis inhibitors in a range of systems, expanding the glycochemistry toolkit.

Cholesterol Metabolism Is a Druggable Axis that Independently Regulates Tau and Amyloid-ß in iPSC-Derived Alzheimer's Disease Neurons.

Genetic, epidemiologic, and biochemical evidence suggests that predisposition to Alzheimer's disease (AD) may arise from altered cholesterol metabolism, although the molecular pathways that may link cholesterol to AD phenotypes are only partially understood. Here, we perform a phenotypic screen for pTau accumulation in AD-patient iPSC-derived neurons and identify cholesteryl esters (CE), the storage product of excess cholesterol, as upstream regulators of Tau early during AD development. Using isogenic induced pluripotent stem cell (iPSC) lines carrying mutations in the cholesterol-binding domain of APP or APP null alleles, we found that while CE also regulate Aß secretion, the effects of CE on Tau and Aß are mediated by independent pathways. Efficacy and toxicity screening in iPSC-derived astrocytes and neurons showed that allosteric activation of CYP46A1 lowers CE specifically in neurons and is well tolerated by astrocytes. These data reveal that CE independently regulate Tau and Aß and identify a druggable CYP46A1-CE-Tau axis in AD.

Elucidating molecular phenotypes caused by the SORL1 Alzheimer's disease genetic risk factor using human induced pluripotent stem cells.

Predisposition to sporadic Alzheimer's disease (SAD) involves interactions between a person's unique combination of genetic variants and the environment. The molecular effect of these variants may be subtle and difficult to analyze with standard in vitro or in vivo models. Here we used hIPSCs to examine genetic variation in the SORL1 gene and possible contributions to SAD-related phenotypes in human neurons. We found that human neurons carrying SORL1 variants associated with an increased SAD risk show a reduced response to treatment with BDNF, at the level of both SORL1 expression and APP processing. shRNA knockdown of SORL1 demonstrates that the differences in BDNF-induced APP processing between genotypes are dependent on SORL1 expression. We propose that the variation in SORL1 expression induction by BDNF is modulated by common genetic variants and can explain how genetic variation in this one locus can contribute to an individual's risk of developing SAD.

Metabolism of strobilurins by wheat cell suspension cultures.

Strobilurin fungicides are a leading class of antifungal chemicals used today in agricultural applications. Although degradation of some strobilurin fungicides has been assessed in plant residues, little information has appeared in the literature concerning the rates of metabolism of these fungicides in plants. In this study, we explored plant metabolism of three strobilurin fungicides, azoxystrobin, kresoxim-methyl, and trifloxystrobin, using wheat cell suspension cultures. Trifloxystrobin and kresoxim-methyl were completely metabolized within 24 h, whereas the metabolism of azoxystrobin was relatively slow with half-lives up to 48 h depending on specific experimental conditions. Metabolic rates of these fungicides were affected by the amounts of compound and cells added to the media. Structural analysis of metabolites of trifloxystrobin and kresoxim-methyl by high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance spectroscopy (NMR) indicated that trifloxystrobin was first demethylated followed by subsequent hydroxylation, whereas kresoxim-methyl was largely demethylated. In contrast, a number of minor metabolites of azoxystrobin were present suggesting a differential metabolism of strobilurins by wheat cells.

The effects of energetic and informational masking on The Words-in-Noise Test (WIN).

BACKGROUND: In certain masking paradigms, the masker can have two components, energetic and informational. Energetic masking is the traditional peripheral masking, whereas informational masking involves confusions (uncertainty) between the signal and masker that originate more centrally in the auditory system. Sperry et al (1997) used Northwestern University Auditory Test No. 6 (NU-6) words in multitalker babble to study the differential effects of energetic and informational masking using babble played temporally forward (FB) and backward (BB). The FB and BB are the same except BB is void of the contextual and semantic content cues that are available in FB. It is these informational cues that are thought to fuel informational masking. Sperry et al found 15% better recognition performance (∼3 dB) on BB than on FB, which can be interpreted as the presence of informational masking in the FB condition and not in the BB condition (Dirks and Bower, 1969). The Words-in-Noise Test (WIN) (Wilson, 2003; Wilson and McArdle, 2007) uses NU-6 words as the signal and multitalker babble as the masker, which is a combination of stimuli that potentially could produce informational masking. The WIN presents 5 or 10 words at each of seven signal-to-noise ratios (S/N, SNR) from 24 to 0 dB in 4 dB decrements with the 50% correct point being the metric of interest. The same recordings of the NU-6 words and multitalker babble used by Sperry et al are used in the WIN. PURPOSE: To determine whether informational masking was involved with the WIN. RESEARCH DESIGN: Descriptive, quasi-experimental designs were conducted in three experiments using FB and BB in various paradigms in which FB and BB varied from 4.3 sec concatenated segments to essentially continuous. STUDY SAMPLE: Eighty young adults with normal hearing and 64 older adults with sensorineural hearing losses participated in a series of three experiments. DATA COLLECTION AND ANALYSIS: Experiment 1 compared performance on the normal WIN (FB) with performance on the WIN in which the babble segment with each word was reversed temporally (BB). Experiment 2 examined the effects of continuous FB and BB segments on WIN performance. Experiment 3 replicated the Sperry et al (1997) experiment at 4 and 0 dB S/N using NU-6 words in the FB and BB conditions. RESULTS: Experiment 1-with the WIN paradigm, recognition performances on FB and BB were the same for listeners with normal hearing and listeners with hearing loss, except at the 0 dB S/N with the listeners with normal hearing at which performance was significantly better on BB than FB. Experiment 2-recognition performances on FB and BB were the same at all SNRs for listeners with normal hearing using a slightly modified WIN paradigm. Experiment 3-there was no difference in performances on the FB and BB conditions with either of the two SNRs. CONCLUSIONS: Informational masking was not involved in the WIN paradigm. The Sperry et al results were not replicated, which is thought to be related to the way in which the Sperry et al BB condition was produced.