Time series of freshwater macroinvertebrate abundances and site characteristics of European streams and rivers.

Freshwater macroinvertebrates are a diverse group and play key ecological roles, including accelerating nutrient cycling, filtering water, controlling primary producers, and providing food for predators. Their differences in tolerances and short generation times manifest in rapid community responses to change. Macroinvertebrate community composition is an indicator of water quality. In Europe, efforts to improve water quality following environmental legislation, primarily starting in the 1980s, may have driven a recovery of macroinvertebrate communities. Towards understanding temporal and spatial variation of these organisms, we compiled the TREAM dataset (Time seRies of European freshwAter Macroinvertebrates), consisting of macroinvertebrate community time series from 1,816 river and stream sites (mean length of 19.2 years and 14.9 sampling years) of 22 European countries sampled between 1968 and 2020. In total, the data include >93 million sampled individuals of 2,648 taxa from 959 genera and 212 families. These data can be used to test questions ranging from identifying drivers of the population dynamics of specific taxa to assessing the success of legislative and management restoration efforts.

Antisera against flagellin A or B inhibits Pseudomonas aeruginosa motility as measured by novel video microscopy assay.

Flagellum-mediated motility is essential to Pseudomonas aeruginosa (P. aeruginosa) virulence. Antibody against flagellin reduces motility and inhibits the spread of the bacteria from the infection site. The standard soft-agar assay to demonstrate anti-flagella motility inhibition requires long incubation times, is difficult to interpret, and requires large amounts of antibody. We have developed a time-lapse video microscopy method to analyze anti-flagellin P. aeruginosa motility inhibition that has several advantages over the soft agar assay. Antisera from mice immunized with flagellin type A or B were incubated with Green Fluorescent Protein (GFP)-expressing P. aeruginosa strain PAO1 (FlaB+) and GFP-expressing P. aeruginosa strain PAK (FlaA+). We analyzed the motion of the bacteria in video taken in ten second time intervals. An easily measurable decrease in bacterial locomotion was observed microscopically within minutes after the addition of small volumes of flagellin antiserum. From data analysis, we were able to quantify the efficacy of anti-flagellin antibodies in the test serum that decreased P. aeruginosa motility. This new video microscopy method to assess functional activity of anti-flagellin antibodies required less serum, less time, and had more robust and reproducible endpoints than the standard soft agar motility inhibition assay.

Developing the Diagnostic Interview for Adolescents and Adults with Mild/Moderate Intellectual Disabilities: An interview schedule of mental disorders (DIAAID).

Introduction: Young people with intellectual disabilities (ID) are at an increased risk for experiencing mental health issues compared to their peers without disabilities. Further, there are limited resources available to help accurately assess mental health disorders and that are accessible for adolescents with ID. Method: This paper describes the iterative development and pilot testing of the Diagnostic Interview for Adolescents and Adults with Intellectual Disabilities (DIAAID). The authors utilized Evidence Center Design and Universal Design principals to develop the DIAAID; a multi-informant diagnostic interview. Results: The DIAAID development resulted in the creation of 15 adolescents disorder interviews and 24 caregiver disorder interviews. Preliminary results suggest that the DIAAID is a feasible and accessible diagnostic interview for adolescents with ID and their caregivers. Discussion: Lessons learned from DIAAID implementation and future areas research are discussed.

Inland navigation and land use interact to impact European freshwater biodiversity.

Inland navigation in Europe is proposed to increase in the coming years, being promoted as a low-carbon form of transport. However, we currently lack knowledge on how this would impact biodiversity at large scales and interact with existing stressors. Here we addressed this knowledge gap by analysing fish and macroinvertebrate community time series across large European rivers comprising 19,592 observations from 4,049 sampling sites spanning the past 32 years. We found ship traffic to be associated with biodiversity declines, that is, loss of fish and macroinvertebrate taxonomic richness, diversity and trait richness. Ship traffic was also associated with increases in taxonomic evenness, which, in concert with richness decreases, was attributed to losses in rare taxa. Ship traffic was especially harmful for benthic taxa and those preferring slow flows. These effects often depended on local land use and riparian degradation. In fish, negative impacts of shipping were highest in urban and agricultural landscapes. Regarding navigation infrastructure, the negative impact of channelization on macroinvertebrates was evident only when riparian degradation was also high. Our results demonstrate the risk of increasing inland navigation on freshwater biodiversity. Integrative waterway management accounting for riparian habitats and landscape characteristics could help to mitigate these impacts.

Multi-decadal improvements in the ecological quality of European rivers are not consistently reflected in biodiversity metrics.

Humans impact terrestrial, marine and freshwater ecosystems, yet many broad-scale studies have found no systematic, negative biodiversity changes (for example, decreasing abundance or taxon richness). Here we show that mixed biodiversity responses may arise because community metrics show variable responses to anthropogenic impacts across broad spatial scales. We first quantified temporal trends in anthropogenic impacts for 1,365 riverine invertebrate communities from 23 European countries, based on similarity to least-impacted reference communities. Reference comparisons provide necessary, but often missing, baselines for evaluating whether communities are negatively impacted or have improved (less or more similar, respectively). We then determined whether changing impacts were consistently reflected in metrics of community abundance, taxon richness, evenness and composition. Invertebrate communities improved, that is, became more similar to reference conditions, from 1992 until the 2010s, after which improvements plateaued. Improvements were generally reflected by higher taxon richness, providing evidence that certain community metrics can broadly indicate anthropogenic impacts. However, richness responses were highly variable among sites, and we found no consistent responses in community abundance, evenness or composition. These findings suggest that, without sufficient data and careful metric selection, many common community metrics cannot reliably reflect anthropogenic impacts, helping explain the prevalence of mixed biodiversity trends.

Social support among English learners with disabilities and other adolescents.

INTRODUCTION: Social support is important for many youth but may be particularly important for English learners (ELs) with disabilities, a population that has historically faced barriers accessing resources to meet their educational needs. The current study investigates social support from parents, peers, teachers, and schools in a nationally representative sample of adolescents. METHOD: Data from the National Longitudinal Transition Study 2012 was used to evaluate potential group differences in social support among participants that included ELs with (n = 440) and without disabilities (n = 100) and non-ELs with (n = 4890) and without disabilities (n = 1090). A multivariate analysis of covariance was conducted to evaluate potential between-group variations in social support among these student groups after controlling for variations in background demographic characteristics. RESULTS AND CONCLUSIONS: Results showed between group differences in parental support and peer connectedness but not in teacher or school support. Parents of students with disabilities reported the highest levels of support, whereas parents of ELs without disabilities reported the lowest levels of support. Students with disabilities reported the lowest levels of peer connectedness among the four groups. Overall, levels of teacher and school supports were high across all four groups of students. These patterns contribute to our understanding of the social support network of ELs with disabilities in comparison to other students. Further investigation is needed to examine the mechanisms that contribute to these differences.

Comparison of four DNA extraction methods for 16s rRNA microbiota profiling of human faecal samples.

OBJECTIVE: Growth in large population-based studies assessing contributions of the gut microbiota to health and disease requires high-throughput sample processing and analysis methods. This study assessed the impact that modifications to a commercially available magnetic bead based, semi-automated DNA extraction kit had on determination of microbial composition, relative to an established in-house method involving a combination of mechanical and chemical lysis. DNA was extracted from faecal samples from healthy adults (n = 12; 34-69 years), microbial composition was determined by V3-V4 16s rRNA sequencing and compared between extraction methods. RESULTS: Diversity metrics did not differ between extraction methods. Differences in the relative abundance of key phyla, including a significantly lower abundance of the Firmicutes (p = 0.004) and higher relative abundance of the Bacteroidetes (p = 0.005) and Proteobacteria (p = 0.008) phyla were noted where the DNA extraction did not include additional chemical and mechanical lysis. Principal coordinate analysis of family and genera level data also suggested a potential for sample pre-processing to impact microbial composition. Observations of the potential for skewed microbial composition profiles from samples prepared using a semi-automated DNA extraction kit without additional sample pre-processing highlights a need for consideration of standardisation of methodological approaches to increase the comparability of microbial compositional data.

Distribution of serotypes and antibiotic resistance of invasive Pseudomonas aeruginosa in a multi-country collection.

BACKGROUND: Pseudomonas aeruginosa is an opportunistic pathogen that causes a wide range of acute and chronic infections and is frequently associated with healthcare-associated infections. Because of its ability to rapidly acquire resistance to antibiotics, P. aeruginosa infections are difficult to treat. Alternative strategies, such as a vaccine, are needed to prevent infections. We collected a total of 413 P. aeruginosa isolates from the blood and cerebrospinal fluid of patients from 10 countries located on 4 continents during 2005-2017 and characterized these isolates to inform vaccine development efforts. We determined the diversity and distribution of O antigen and flagellin types and antibiotic susceptibility of the invasive P. aeruginosa. We used an antibody-based agglutination assay and PCR for O antigen typing and PCR for flagellin typing. We determined antibiotic susceptibility using the Kirby-Bauer disk diffusion method. RESULTS: Of the 413 isolates, 314 (95%) were typed by an antibody-based agglutination assay or PCR (n = 99). Among the 20 serotypes of P. aeruginosa, the most common serotypes were O1, O2, O3, O4, O5, O6, O8, O9, O10 and O11; a vaccine that targets these 10 serotypes would confer protection against more than 80% of invasive P. aeruginosa infections. The most common flagellin type among 386 isolates was FlaB (41%). Resistance to aztreonam (56%) was most common, followed by levofloxacin (42%). We also found that 22% of strains were non-susceptible to meropenem and piperacillin-tazobactam. Ninety-nine (27%) of our collected isolates were resistant to multiple antibiotics. Isolates with FlaA2 flagellin were more commonly multidrug resistant (p = 0.04). CONCLUSIONS: Vaccines targeting common O antigens and two flagellin antigens, FlaB and FlaA2, would offer an excellent strategy to prevent P. aeruginosa invasive infections.

Temporal scope influences ecosystem driver-response relationships: A case study of Lake Erie with implications for ecosystem-based management.

Understanding environmental driver-response relationships is critical to the implementation of effective ecosystem-based management. Ecosystems are often influenced by multiple drivers that operate on different timescales and may be nonstationary. In turn, contrasting views of ecosystem state and structure could arise depending on the temporal perspective of analysis. Further, assessment of multiple ecosystem components (e.g., biological indicators) may serve to identify different key drivers and connections. To explore how the timescale of analysis and data richness can influence the identification of driver-response relationships within a large, dynamic ecosystem, this study analyzed long-term (1969-2018) data from Lake Erie (USA-Canada). Data were compiled on multiple biological, physical, chemical, and socioeconomic components of the ecosystem to quantify trends and identify potential key drivers during multiple time intervals (20 to 50 years duration), using zooplankton, bird, and fish community metrics as indicators of ecosystem change. Concurrent temporal shifts of many variables occurred during the 1980s, but asynchronous dynamics were evident among indicator taxa. The strengths and rank orders of predictive drivers shifted among intervals and were sometimes taxon-specific. Drivers related to nutrient loading and lake trophic status were consistently strong predictors of temporal patterns for all indicators; however, within the longer intervals, measures of agricultural land use were the strongest predictors, whereas within shorter intervals, the stronger predictors were measures of tributary or in-lake nutrient concentrations. Physical drivers also tended to increase in predictive ability within shorter intervals. The results highlight how the time interval examined can filter influences of lower-frequency, slower drivers and higher-frequency, faster drivers. Understanding ecosystem change in support of ecosystem-based management requires consideration of both the temporal perspective of analysis and the chosen indicators, as both can influence which drivers are identified as most predictive of ecosystem trends at that timescale.

Functional traits reveal the dominant drivers of long-term community change across a North American Great Lake.

Ecosystems worldwide have been impacted by multiple anthropogenic stressors, yet efforts to understand and manage these impacts have been hindered by difficulties in disentangling relative stressor effects. Theoretically, the actions of individual stressors can be delineated based on associated changes in functional traits and these relationships should be generalizable across communities comprised of different species. Thus, combining trait perspectives with community composition data could help to identify the relative influence of different stressors. We evaluated the utility of this combined approach by quantifying shifts in fish species and trait composition in Lake Erie during the past 50 years (1969-2018) in relation to human-driven changes in nutrient inputs, climate warming, and biological invasions. Species and trait shifts were also compared between two Lake Erie basins, which differ in their environmental and biological characteristics, to identify trait responses that were generalizable across different ecosystems versus those that were context dependent. Our analyses revealed consistent species changes across basins, and shifts in feeding and thermal traits, that were primarily associated with altered nutrient inputs (oligotrophication followed by eutrophication). We found no or inconsistent trait-based evidence for the effects of warming and two invasive fishes. Context-dependent trait responses were also evident; nutrient inputs were related to shifts in species tolerant of turbidity in the shallow, eutrophic western basin, which contrasted to shifts between benthopelagic and benthic species in the deeper central basin. Our results reveal the dominant effects of specific stressors on a large freshwater lake and offer a framework for combining species-based and trait-based approaches to delineate the impacts of simultaneous stressors on communities of perturbed natural ecosystems.

The International Vertebrate Pet Trade Network and Insights from US Imports of Exotic Pets.

The international trade in exotic vertebrate pets provides key social and economic benefits but also drives associated ecological, ethical, and human health impacts. However, despite its clear importance, we currently lack a full understanding of the structure of the pet trade, hampering efforts to optimize its benefits while mitigating its negative effects. In the present article, we represent and review the structure of the pet trade as a network composed of different market actors (nodes) and trade flows (links). We identify key data gaps in this network that, if filled, would enable network analyses to pinpoint targets for management. As a case study of how data-informed networks can realize this goal, we quantified spatial and temporal patterns in pets imported to the United States. Our framework and case study illustrate how network approaches can help to inform and manage the effects of the growing demand for exotic pets.

Lived experiences of mental health in higher education: A comparative analysis of determinants to supports and services.

Due to increasing incidence of mental health challenges in college students and its relation to poorer student outcomes (e.g., recruitment, retention, graduation), higher education institutions have turned their attention toward the needs of students experiencing mental health challenges (Collins & Mowbray, 2005). In attempts to ameliorate poorer student outcomes, some states have investigated the impact of mental health on those enrolled in higher education as well as the needs for supports and services for those impacted (e.g., Oregon Higher Education Coordinating Commission [OHECC], Office of Academic Policy and Authorization, 2018). However, despite these initiatives, limited empirical research is available related to the lived experiences of individuals with mental health challenges in higher education settings; including the supports and barriers they may experience while navigating these complex settings. This study begins to address this knowledge gap by using qualitative content analysis to examine and compare key stakeholder lived experiences related to mental health challenges in higher education, including the similarities and differences regarding service and support needs, determinants to usage (support and barriers), and recommendations for future research and improving the continuum of care. Considerations for policy, practice, and future research are provided. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Are bicycle lanes effective? The relationship between passing distance and road characteristics.

An on-road observational study of 162 cyclists was conducted in the Australian cities of Melbourne, Perth, Geelong, and Bendigo. Participants had a distance sensor and two video cameras fitted to their bicycle for two weeks while they cycled on their usual routes, producing 46,769 events where a motor vehicle passed a bicycle. This was the largest study to-date to record passing behavior on public roads, and a large number of road and traffic attributes that might affect passing distance were included in the analysis. When drivers pass cyclists on roads with painted bicycle lanes, they tend to give more space than on roads without bicycle lanes. This is true even when controlling for the space available on the roadway. Drivers also travel in a more predictable fashion, with less variability in passing distances when a bicycle lane is present. Protected bicycle lanes completely remove the risk of passing events less than 1 m. However, where it is not possible to build a protected bicycle lane it is preferable to have a painted bicycle lane than no bicycle lane at all. Other protective factors include: wider lanes, single lane roads, smaller vehicles, and the removal of on-street parking.

Projecting the effects of agricultural conservation practices on stream fish communities in a changing climate.

How anticipated climate change might affect long-term outcomes of present-day agricultural conservation practices remains a key uncertainty that could benefit water quality and biodiversity conservation planning. To explore this issue, we forecasted how the stream fish communities in the Western Lake Erie Basin (WLEB) would respond to increasing amounts of agricultural conservation practice (ACP) implementation under two IPCC future greenhouse gas emission scenarios (RCP4.5: moderate reductions; RCP8.5: business-as-usual conditions) during 2020-2065. We used output from 19 General Circulation Models to drive linked agricultural land use (APEX), watershed hydrology (SWAT), and stream fish distribution (boosted regression tree) models, subsequently analyzing how projected changes in habitat would influence fish community composition and functional trait diversity. Our models predicted both positive and negative effects of climate change and ACP implementation on WLEB stream fishes. For most species, climate and ACPs influenced species in the same direction, with climate effects outweighing those of ACP implementation. Functional trait analysis helped clarify the varied responses among species, indicating that more extreme climate change would reduce available habitat for large-bodied, cool-water species with equilibrium life-histories, many of which also are of importance to recreational fishing (e.g., northern pike, smallmouth bass). By contrast, available habitat for warm-water, benthic species with more periodic or opportunistic life-histories (e.g., northern hogsucker, greater redhorse, greenside darter) was predicted to increase. Further, ACP implementation was projected to hasten these shifts, suggesting that efforts to improve water quality could come with costs to other ecosystem services (e.g., recreational fishing opportunities). Collectively, our findings demonstrate the need to consider biological outcomes when developing strategies to mitigate water quality impairment and highlight the value of physical-biological modeling approaches to agricultural and biological conservation planning in a changing climate.

A Survey of Small-Scale Waves and Wave-Like Phenomena in Jupiter's Atmosphere Detected by JunoCam.

In the first 20 orbits of the Juno spacecraft around Jupiter, we have identified a variety of wave-like features in images made by its public-outreach camera, JunoCam. Because of Juno's unprecedented and repeated proximity to Jupiter's cloud tops during its close approaches, JunoCam has detected more wave structures than any previous surveys. Most of the waves appear in long wave packets, oriented east-west and populated by narrow wave crests. Spacing between crests were measured as small as ~30 km, shorter than any previously measured. Some waves are associated with atmospheric features, but others are not ostensibly associated with any visible cloud phenomena and thus may be generated by dynamical forcing below the visible cloud tops. Some waves also appear to be converging, and others appear to be overlapping, possibly at different atmospheric levels. Another type of wave has a series of fronts that appear to be radiating outward from the center of a cyclone. Most of these waves appear within 5° of latitude from the equator, but we have detected waves covering planetocentric latitudes between 20°S and 45°N. The great majority of the waves appear in regions associated with prograde motions of the mean zonal flow. Juno was unable to measure the velocity of wave features to diagnose the wave types due to its close and rapid flybys. However, both by our own upper limits on wave motions and by analogy with previous measurements, we expect that the waves JunoCam detected near the equator are inertia-gravity waves.

Ross River Virus Provokes Differentially Expressed MicroRNA and RNA Interference Responses in Aedes aegypti Mosquitoes.

Alphaviruses are globally distributed and predominately transmitted by mosquitoes. Aedes species are common vectors for the clinically important alphaviruses-Chikungunya, Sindbis, and Ross River (RRV) viruses-with Aedes aegypti also being a vector for the flaviviruses dengue, Yellow Fever, and Zika viruses. Ae. aegypti was putatively implicated in the large 1979-1980 South Pacific Islands outbreak of RRV-the leading cause of arboviral disease in Australia today. The RNA interference (RNAi) defense response in mosquitoes involves a number of small RNAs, with their kinetics induced by alphaviruses being poorly understood, particularly at the tissue level. We compared the small RNA profiles between RRV-infected and noninfected Ae. aegypti midgut and fat body tissues at 2, 6, and 12 days post-inoculation (dpi). RRV induced an incremental RNAi response, yielding short interfering and P-element-induced-wimpy-testis (PIWI)-interacting RNAs. Fourteen host microRNAs were differentially expressed due to RRV with the majority in the fat body at 2 dpi. The largely congruent pattern of microRNA regulation with previous reports for alphaviruses and divergence from those for flaviviruses suggests a degree of conservation, whereas patterns of microRNA expression unique to this study provide novel insights into the tissuespecific hostvirus attributes of Ae. aegypti responses to this previously unexplored oldworld alphavirus.

The Diversity of Lipopolysaccharide (O) and Capsular Polysaccharide (K) Antigens of Invasive Klebsiella pneumoniae in a Multi-Country Collection.

Klebsiella pneumoniae is a common cause of sepsis and is particularly associated with healthcare-associated infections. New strategies are needed to prevent or treat infections due to the emergence of multi-drug resistant K. pneumoniae. The goal of this study was to determine the diversity and distribution of O (lipopolysaccharide) and K (capsular polysaccharide) antigens on a large (>500) global collection of K. pneumoniae strains isolated from blood to inform vaccine development efforts. A total of 645 K. pneumoniae isolates were collected from the blood of patients in 13 countries during 2005-2017. Antibiotic susceptibility was determined using the Kirby-Bauer disk diffusion method. O antigen types including the presence of modified O galactan types were determined by PCR. K types were determined by multiplex PCR and wzi capsular typing. Sequence types of isolates were determined by multilocus sequence typing (MLST) targeting seven housekeeping genes. Among 591 isolates tested for antimicrobial resistance, we observed that 19.3% of isolates were non-susceptible to carbapenems and 62.1% of isolates were multidrug resistant (from as low as 16% in Sweden to 94% in Pakistan). Among 645 isolates, four serotypes, O1, O2, O3, and O5, accounted for 90.1% of K. pneumoniae strains. Serotype O1 was associated with multidrug resistance. Fifty percent of 199 tested O1 and O2 strains were gmlABC-positive, indicating the presence of the modified polysaccharide subunit D-galactan III. The most common K type was K2 by both multiplex PCR and wzi capsular typing. Of 39 strains tested by MLST, 36 strains were assigned to 26 known sequence types of which ST14, ST25, and ST258 were the most common. Given the limited number of O antigen types, diverse K antigen types and the high multidrug resistance, we believe that an O antigen-based vaccine would offer an excellent prophylactic strategy to prevent K. pneumoniae invasive infection.

Stormwater ponds: An overlooked but plentiful urban designer ecosystem provides invasive plant habitat in a subtropical region (Florida, USA).

Designed ecosystems are built as part of ongoing urban expansion, providing a suite of valued ecosystem services. However, these new ecosystems could also promote disservices by facilitating the colonization and spread of invasive species. We conduct the first assessment of the quantity and invasion of an overlooked designed ecosystem: stormwater ponds. These ponds are commonly recommended for managing urban hydrology, but little is known about their ecology or extent of proliferation. Using a broad-scale survey of pond coverage in Florida, USA, we found that over 76,000 stormwater ponds have been built just in this state, forming 2.7% of total urban land cover. This extensive pondscape of manufactured habitats could facilitate species spread throughout urban areas and into nearby natural waterbodies. We also conducted a survey of the severity of plant invasion in 30 ponds in Gainesville, FL, US across two pond types (dry vs. wet), and a gradient of management intensities (low, medium, high) and pond ages. We unexpectedly found a high number of invasive plant species (28 in just 30 ponds). Ninety-six percent of surveyed ponds contained from one to ten of these species, with ponds exhibiting high turnover in invader composition (i.e., high beta diversity). The bank sections of dry unmanaged ponds exhibited the highest mean invasive species richness (5.8 ± 1.3) and the inundated centers of wet medium managed ponds exhibited the highest mean invasive species cover (34 ± 12%). Invasive plant richness and cover also tended to be greater in dry ponds with higher soil nutrient levels, and in older wet ponds. Therefore, we found that highly maintained and younger wet ponds were the least invaded. Nevertheless, common management practices that limit plant invasions may also limit native species establishment and invasion may increase in the decades following pond construction.

Urocortin 3 signalling in the auditory brainstem aids recovery of hearing after reversible noise-induced threshold shift.

KEY POINTS: Ongoing, moderate noise exposure does not instantly damage the auditory system but may cause lasting deficits, such as elevated thresholds and accelerated ageing of the auditory system. The neuromodulatory peptide urocortin-3 (UCN3) is involved in the body's recovery from a stress response, and is also expressed in the cochlea and the auditory brainstem. Lack of UCN3 facilitates age-induced hearing loss and causes permanently elevated auditory thresholds following a single 2 h noise exposure at moderate intensities. Outer hair cell function in mice lacking UCN3 is unaffected, so that the observed auditory deficits are most likely due to inner hair cell function or central mechanisms. Highly specific, rather than ubiquitous, expression of UCN3 in the brain renders it a promising candidate for designing drugs to ameliorate stress-related auditory deficits, including recovery from acoustic trauma. ABSTRACT: Environmental acoustic noise is omnipresent in our modern society, with sound levels that are considered non-damaging still causing long-lasting or permanent changes in the auditory system. The small neuromodulatory peptide urocortin-3 (UCN3) is the endogenous ligand for corticotropin-releasing factor receptor type 2 and together they are known to play an important role in stress recovery. UCN3 expression has been observed in the auditory brainstem, but its role remains unclear. Here we describe the detailed distribution of UCN3 expression in the murine auditory brainstem and provide evidence that UCN3 is expressed in the synaptic region of inner hair cells in the cochlea. We also show that mice with deficient UCN3 signalling experience premature ageing of the auditory system starting at an age of 4.7 months with significantly elevated thresholds of auditory brainstem responses (ABRs) compared to age-matched wild-type mice. Following a single, 2 h exposure to moderate (84 or 94 dB SPL) noise, UCN3-deficient mice exhibited significantly larger shifts in ABR thresholds combined with maladaptive recovery. In wild-type mice, the same noise exposure did not cause lasting changes to auditory thresholds. The presence of UCN3-expressing neurons throughout the auditory brainstem and the predisposition to hearing loss caused by preventing its normal expression suggests UCN3 as an important neuromodulatory peptide in the auditory system's response to loud sounds.

Shiga Toxin Type 1a (Stx1a) Reduces the Toxicity of the More Potent Stx2a In Vivo and In Vitro.

Shiga toxin (Stx)-producing Escherichia coli (STEC) causes foodborne outbreaks of bloody diarrhea. There are two major types of immunologically distinct Stxs: Stx1a and Stx2a. Stx1a is more cytotoxic to Vero cells than Stx2a, but Stx2a has a lower 50% lethal dose (LD50) in mice. Epidemiological data suggest that infections by STEC strains that produce only Stx2a progress more often to a life-threatening sequela of infection called hemolytic-uremic syndrome (HUS) than isolates that make Stx1a only or produce both Stx1a and Stx2a. In this study, we found that an E. coli O26:H11 strain that produces both Stx1a and Stx2a was virulent in streptomycin- and ciprofloxacin-treated mice and that mice were protected by administration of an anti-Stx2 antibody. However, we discovered that in the absence of ciprofloxacin, neutralization of Stx1a enhanced the virulence of the strain, a result that corroborated our previous finding that Stx1a reduces the toxicity of Stx2a by the oral route. We further found that intraperitoneal administration of the purified Stx1a B subunit delayed the mean time to death of mice intoxicated with Stx2a and reduced the cytotoxic effect of Stx2a on Vero cells. Taken together, our data suggest that Stx1a reduces both the pathogenicity of Stx2 in vivo and cytotoxicity in vitro.