Hyperspectral signals in the soil: Plant-soil hydraulic connection and disequilibrium as mechanisms of drought tolerance and rapid recovery.

Predicting soil water status remotely is appealing due to its low cost and large-scale application. During drought, plants can disconnect from the soil, causing disequilibrium between soil and plant water potentials at pre-dawn. The impact of this disequilibrium on plant drought response and recovery is not well understood, potentially complicating soil water status predictions from plant spectral reflectance. This study aimed to quantify drought-induced disequilibrium, evaluate plant responses and recovery, and determine the potential for predicting soil water status from plant spectral reflectance. Two species were tested: sweet corn (Zea mays), which disconnected from the soil during intense drought, and peanut (Arachis hypogaea), which did not. Sweet corn's hydraulic disconnection led to an extended 'hydrated' phase, but its recovery was slower than peanut's, which remained connected to the soil even at lower water potentials (-5 MPa). Leaf hyperspectral reflectance successfully predicted the soil water status of peanut consistently, but only until disequilibrium occurred in sweet corn. Our results reveal different hydraulic strategies for plants coping with extreme drought and provide the first example of using spectral reflectance to quantify rhizosphere water status, emphasizing the need for species-specific considerations in soil water status predictions from canopy reflectance.

Streamlining differential exon and 3' UTR usage with diffUTR.

BACKGROUND: Despite the importance of alternative poly-adenylation and 3' UTR length for a variety of biological phenomena, there are limited means of detecting UTR changes from standard transcriptomic data. RESULTS: We present the diffUTR Bioconductor package which streamlines and improves upon differential exon usage (DEU) analyses, and leverages existing DEU tools and alternative poly-adenylation site databases to enable differential 3' UTR usage analysis. We demonstrate the diffUTR features and show that it is more flexible and more accurate than state-of-the-art alternatives, both in simulations and in real data. CONCLUSIONS: diffUTR enables differential 3' UTR analysis and more generally facilitates DEU and the exploration of their results.

Empirical and Earth system model estimates of boreal nitrogen fixation often differ: A pathway toward reconciliation.

The impacts of global environmental change on productivity in northern latitudes will be contingent on nitrogen (N) availability. In circumpolar boreal ecosystems, nonvascular plants (i.e., bryophytes) and associated N2 -fixing diazotrophs provide one of the largest known N inputs but are rarely accounted for in Earth system models. Instead, most models link N2 -fixation with the functioning of vascular plants. Neglecting nonvascular N2 -fixation may be contributing toward high uncertainty that currently hinders model predictions in northern latitudes, where nonvascular N2 -fixing plants are more common. Adequately accounting for nonvascular N2 -fixation and its drivers could subsequently improve predictions of future N availability and ultimately, productivity, in northern latitudes. Here, we review empirical evidence of boreal nonvascular N2 -fixation responses to global change factors (elevated CO2 , N deposition, warming, precipitation, and shading by vascular plants), and compare empirical findings with model predictions of N2 -fixation using nine Earth system models. The majority of empirical studies found positive effects of CO2 , warming, precipitation, or light on nonvascular N2 -fixation, but N deposition strongly downregulated N2 -fixation in most empirical studies. Furthermore, we found that the responses of N2 -fixation to elevated CO2 were generally consistent between models and very limited empirical data. In contrast, empirical-model comparisons suggest that all models we assessed, and particularly those that scale N2 -fixation with net primary productivity or evapotranspiration, may be overestimating N2 -fixation under increasing N deposition. Overestimations could generate erroneous predictions of future N stocks in boreal ecosystems unless models adequately account for the drivers of nonvascular N2 -fixation. Based on our comparisons, we recommend that models explicitly treat nonvascular N2 -fixation and that field studies include more targeted measurements to improve model structures and parameterization.

Understanding stoichiometric mechanisms of nutrient retention in wetland macrophytes: stoichiometric homeostasis along a nutrient gradient in a subtropical wetland.

Nutrient homeostasis relates ambient stoichiometric conditions in an environment to the stoichiometry of living entities of that ecosystem. Plant nutrient sequestration in wetland ecosystems is a key process for downstream water quality. However, few studies have examined stoichiometric homeostasis of aquatic vegetation despite the importance of stoichiometry to plant nutrient uptake efficiency. This study investigated stoichiometric homeostasis of dominant emergent and submerged aquatic vegetation (EAV and SAV, respectively) within two treatment flow-ways of Everglades Stormwater Treatment Area 2 (STA-2). These flow-ways encompass a large gradient in plant nutrient availability. This study hypothesizes that wetland vegetation is homeostatic relative to ambient nutrients and consequently nutrient resorption does not vary along the nutrient gradient. We developed a framework to investigate how vegetation uptake and resorption of nutrients contribute separately to homeostasis. Overall, we determined that the wetland vegetation in this study was non-homeostatic with respect to differential uptake of nitrogen (N) versus phosphorus (P). In EAV, P resorption was relatively high and N resorption was moderate, and resorption efficiency did not vary significantly along the gradient. In separating the proportional contribution of resorption and uptake to the degree of homeostasis, resorption did not affect overall homeostatic status in EAV.

Global soil nitrous oxide emissions since the preindustrial era estimated by an ensemble of terrestrial biosphere models: Magnitude, attribution, and uncertainty.

Our understanding and quantification of global soil nitrous oxide (N2 O) emissions and the underlying processes remain largely uncertain. Here, we assessed the effects of multiple anthropogenic and natural factors, including nitrogen fertilizer (N) application, atmospheric N deposition, manure N application, land cover change, climate change, and rising atmospheric CO2 concentration, on global soil N2 O emissions for the period 1861-2016 using a standard simulation protocol with seven process-based terrestrial biosphere models. Results suggest global soil N2 O emissions have increased from 6.3 ± 1.1 Tg N2 O-N/year in the preindustrial period (the 1860s) to 10.0 ± 2.0 Tg N2 O-N/year in the recent decade (2007-2016). Cropland soil emissions increased from 0.3 Tg N2 O-N/year to 3.3 Tg N2 O-N/year over the same period, accounting for 82% of the total increase. Regionally, China, South Asia, and Southeast Asia underwent rapid increases in cropland N2 O emissions since the 1970s. However, US cropland N2 O emissions had been relatively flat in magnitude since the 1980s, and EU cropland N2 O emissions appear to have decreased by 14%. Soil N2 O emissions from predominantly natural ecosystems accounted for 67% of the global soil emissions in the recent decade but showed only a relatively small increase of 0.7 ± 0.5 Tg N2 O-N/year (11%) since the 1860s. In the recent decade, N fertilizer application, N deposition, manure N application, and climate change contributed 54%, 26%, 15%, and 24%, respectively, to the total increase. Rising atmospheric CO2 concentration reduced soil N2 O emissions by 10% through the enhanced plant N uptake, while land cover change played a minor role. Our estimation here does not account for indirect emissions from soils and the directed emissions from excreta of grazing livestock. To address uncertainties in estimating regional and global soil N2 O emissions, this study recommends several critical strategies for improving the process-based simulations.

Rate of warming affects temperature sensitivity of anaerobic peat decomposition and greenhouse gas production.

Temperature sensitivity of anaerobic carbon mineralization in wetlands remains poorly represented in most climate models and is especially unconstrained for warmer subtropical and tropical systems which account for a large proportion of global methane emissions. Several studies of experimental warming have documented thermal acclimation of soil respiration involving adjustments in microbial physiology or carbon use efficiency (CUE), with an initial decline in CUE with warming followed by a partial recovery in CUE at a later stage. The variable CUE implies that the rate of warming may impact microbial acclimation and the rate of carbon-dioxide (CO2 ) and methane (CH4 ) production. Here, we assessed the effects of warming rate on the decomposition of subtropical peats, by applying either a large single-step (10°C within a day) or a slow ramping (0.1°C/day for 100 days) temperature increase. The extent of thermal acclimation was tested by monitoring CO2 and CH4 production, CUE, and microbial biomass. Total gaseous C loss, CUE, and MBC were greater in the slow (ramp) warming treatment. However, greater values of CH4 -C:CO2 -C ratios lead to a greater global warming potential in the fast (step) warming treatment. The effect of gradual warming on decomposition was more pronounced in recalcitrant and nutrient-limited soils. Stable carbon isotopes of CH4 and CO2 further indicated the possibility of different carbon processing pathways under the contrasting warming rates. Different responses in fast vs. slow warming treatment combined with different endpoints may indicate alternate pathways with long-term consequences. Incorporations of experimental results into organic matter decomposition models suggest that parameter uncertainties in CUE and CH4 -C:CO2 -C ratios have a larger impact on long-term soil organic carbon and global warming potential than uncertainty in model structure, and shows that particular rates of warming are central to understand the response of wetland soils to global climate change.

Use of locally delivered dequalinium chloride in the treatment of vaginal infections: a review.

BACKGROUND: Vaginal infections are responsible for a large proportion of gynaecological outpatient visits. Those are bacterial vaginosis (BV), vulvovaginal candidosis (VVC), aerobic vaginitis (AV) associated with aerobic bacteria, and mixed infections. Usual treatments show similar acceptable short-term efficacy, but frequent recurrences and increasing microbial resistance are unsolved issues. Furthermore, vaginal infections are associated with a variety of serious adverse outcomes in pregnancy and generally have a major impact on quality of life. Identifying the correct therapy can be challenging for the clinician, particularly in mixed infections. FINDINGS: Dequalinium chloride (DQC) is an anti-microbial antiseptic agent with a broad bactericidal and fungicidal activity. Systemic absorption after vaginal application of DQC is very low and systemic effects negligible. Vaginal DQC (Fluomizin vaginal tablets) has been shown to have equal clinical efficacy as clindamycin in the treatment of BV. Its broad antimicrobial activity makes it appropriate for the treatment of mixed vaginal infections and in case of uncertain diagnosis. Moreover, resistance of pathogens is unlikely due to its multiple mode of action, and vaginal DQC provides also a reduced risk for post-treatment vaginal infections. CONCLUSIONS: Vaginal DQC (10 mg) as 6-day therapy offers a safe and effective option for empiric therapy of different vaginal infections in daily practice. This review summarizes the available and relevant pharmacological and clinical data for the therapy of vaginal infections with vaginal DQC and provides the rationale for its use in daily gynaecologic practice.

Nitrogen limitation on land: how can it occur in Earth system models?

The representation of the nitrogen (N) cycle in Earth system models (ESMs) is strongly motivated by the constraint N poses on the sequestration of anthropogenic carbon (C). Models typically implement a stoichiometric relationship between C and N in which external supply and assimilation by organisms are adjusted to maintain their internal stoichiometry. N limitation of primary productivity thus occurs if the N supply from uptake and fixation cannot keep up with the construction of tissues allowed by C assimilation. This basic approach, however, presents considerable challenges in how to faithfully represent N limitation. Here, we review how N limitation is currently implemented and evaluated in ESMs and highlight challenges and opportunities in their future development. At or near steady state, N limitation is governed by the magnitude of losses from the plant-unavailable pool vs. N fixation and there are considerable differences in how models treat both processes. In nonsteady-state systems, the accumulation of N in pools with slow turnover rates reduces N available for plant uptake and can be challenging to represent when initializing ESM simulations. Transactional N limitation occurs when N is incorporated into various vegetation and soil pools and becomes available to plants only after it is mineralized, the dynamics of which depends on how ESMs represent decomposition processes in soils. Other challenges for ESMs emerge when considering seasonal to interannual climatic oscillations as they create asynchronies between C and N demand, leading to transient alternations between N surplus and deficit. Proper evaluation of N dynamics in ESMs requires conceptual understanding of the main levers that trigger N limitation, and we highlight key measurements and observations that can help constrain these levers. Two of the biggest challenges are the mechanistic representation of plant controls on N availability and turnover, including N fixation and organic matter decomposition processes.

Complex response of the forest nitrogen cycle to climate change.

Climate exerts a powerful influence on biological processes, but the effects of climate change on ecosystem nutrient flux and cycling are poorly resolved. Although rare, long-term records offer a unique opportunity to disentangle effects of climate from other anthropogenic influences. Here, we examine the longest and most complete record of watershed nutrient and climate dynamics available worldwide, which was collected at the Hubbard Brook Experimental Forest in the northeastern United States. We used empirical analyses and model calculations to distinguish between effects of climate change and past perturbations on the forest nitrogen (N) cycle. We find that climate alone cannot explain the occurrence of a dramatic >90% drop in watershed nitrate export over the past 46 y, despite longer growing seasons and higher soil temperatures. The strongest climate influence was an increase in soil temperature accompanied by a shift in paths of soil water flow within the watershed, but this effect explained, at best, only ∼40% of the nitrate decline. In contrast, at least 50-60% of the observed change in the N export could be explained by the long-lasting effect of forest cutting in the early 1900s on the N cycle of the soil and vegetation pools. Our analysis shows that historic events can obscure the influence of modern day stresses on the N cycle, even when analyses have the advantage of being informed by 0.5-century-long datasets. These findings raise fundamental questions about interpretations of long-term trends as a baseline for understanding how climate change influences complex ecosystems.

Titration of Syntaxin1 in mammalian synapses reveals multiple roles in vesicle docking, priming, and release probability.

Synaptic vesicles undergo sequential steps in preparation for neurotransmitter release. Individual SNARE proteins and the SNARE complex itself have been implicated in these processes. However, discrete effects of SNARE proteins on synaptic function have been difficult to assess using complete loss-of-function approaches. We therefore used a genetic titration technique in cultured mouse hippocampal neurons to evaluate the contribution of the neuronal SNARE protein Syntaxin1 (Stx1) in vesicle docking, priming, and release probability. We generated graded reductions of total Stx1 levels by combining two approaches, namely, endogenous hypomorphic expression of the isoform Stx1B and RNAi-mediated knockdown. Proximity of synaptic vesicles to the active zone was not strongly affected. However, overall release efficiency of affected neurons was severely impaired, as demonstrated by a smaller readily releasable pool size, slower refilling rate of primed vesicles, and lower release probability. Interestingly, dose-response fitting of Stx1 levels against readily releasable pool size and vesicular release probability showed similar Kd (dissociation constant) values at 18% and 19% of wild-type Stx1, with cooperativity estimates of 3.4 and 2.5, respectively. This strongly suggests that priming and vesicle fusion share the same molecular stoichiometry, and are governed by highly related mechanisms.

Scaling of physical constraints at the root-soil interface to macroscopic patterns of nutrient retention in ecosystems.

Nutrient limitation in terrestrial ecosystems is often accompanied with maintaining a nearly closed vegetation-soil nutrient cycle. The ability to retain nutrients in an ecosystem requires the capacity of the plant-soil system to draw down nutrient levels in soils effectually such that export concentrations in soil solutions remain low. Here we address the physical constraints of plant nutrient uptake that may be limited by the diffusive movement of nutrients in soils, by the uptake at the root/mycorrhizal surface, and from interactions with soil water flow. We derive an analytical framework of soil nutrient transport and uptake and predict levels of plant available nutrient concentration and residence time. Our results, which we evaluate for nitrogen, show that the physical environment permits plants to lower soil solute concentration substantially. Our analysis confirms that plant uptake capacities in soils are considerable, such that water movement in soils is generally too small to significantly erode dissolved plant-available nitrogen. Inorganic nitrogen concentrations in headwater streams are congruent with the prediction of our theoretical framework. Our framework offers a physical-based parameterization of nutrient uptake in ecosystem models and has the potential to serve as an important tool toward scaling biogeochemical cycles from individual roots to landscapes.

Thermal acclimation of leaf respiration of tropical trees and lianas: response to experimental canopy warming, and consequences for tropical forest carbon balance.

Climate warming is expected to increase respiration rates of tropical forest trees and lianas, which may negatively affect the carbon balance of tropical forests. Thermal acclimation could mitigate the expected respiration increase, but the thermal acclimation potential of tropical forests remains largely unknown. In a tropical forest in Panama, we experimentally increased nighttime temperatures of upper canopy leaves of three tree and two liana species by on average 3 °C for 1 week, and quantified temperature responses of leaf dark respiration. Respiration at 25 °C (R25 ) decreased with increasing leaf temperature, but acclimation did not result in perfect homeostasis of respiration across temperatures. In contrast, Q10 of treatment and control leaves exhibited similarly high values (range 2.5-3.0) without evidence of acclimation. The decrease in R25 was not caused by respiratory substrate depletion, as warming did not reduce leaf carbohydrate concentration. To evaluate the wider implications of our experimental results, we simulated the carbon cycle of tropical latitudes (24°S-24°N) from 2000 to 2100 using a dynamic global vegetation model (LM3VN) modified to account for acclimation. Acclimation reduced the degree to which respiration increases with climate warming in the model relative to a no-acclimation scenario, leading to 21% greater increase in net primary productivity and 18% greater increase in biomass carbon storage over the 21st century. We conclude that leaf respiration of tropical forest plants can acclimate to nighttime warming, thereby reducing the magnitude of the positive feedback between climate change and the carbon cycle.

Piccolo and bassoon maintain synaptic vesicle clustering without directly participating in vesicle exocytosis.

Piccolo and bassoon are highly homologous multidomain proteins of the presynaptic cytomatrix whose function is unclear. Here, we generated piccolo knockin/knockout mice that either contain wild-type levels of mutant piccolo unable to bind Ca(2+) (knockin), approximately 60% decreased levels of piccolo that is C-terminally truncated (partial knockout), or <5% levels of piccolo (knockout). All piccolo mutant mice were viable and fertile, but piccolo knockout mice exhibited increased postnatal mortality. Unexpectedly, electrophysiology and electron microscopy of piccolo-deficient synapses failed to uncover a major phenotype either in acute hippocampal slices or in cultured cortical neurons. To unmask potentially redundant functions of piccolo and bassoon, we thus acutely knocked down expression of bassoon in wild-type and piccolo knockout neurons. Despite a nearly complete loss of piccolo and bassoon, however, we still did not detect an electrophysiological phenotype in cultured piccolo- and bassoon-deficient neurons in either GABAergic or glutamatergic synaptic transmission. In contrast, electron microscopy revealed a significant reduction in synaptic vesicle clustering in double bassoon/piccolo-deficient synapses. Thus, we propose that piccolo and bassoon play a redundant role in synaptic vesicle clustering in nerve terminals without directly participating in neurotransmitter release.

Eribulin as first-line treatment in older patients with advanced breast cancer: A multicenter phase II trial [SAKK 25/14].

INTRODUCTION: Standard-dose eribulin mesylate (1.4 mg/m2 d1 + 8) achieves clinical benefit rates of 26%-52% in patients with metastatic breast cancer (mBC). <10% of patients in the registration trial were ≥ 70 years old; dose reductions were common in these older patients. MATERIALS AND METHODS: This single-arm phase II trial explored the efficacy of reduced starting dosing of first-line eribulin at 1 mg/m2 d1 + 8 q3 weeks in patients with mBC aged ≥70 years. The primary endpoint was a disease control rate (DCR) ≥55%. The secondary endpoints were objective response (OR), progression-free survival (PFS), overall survival (OS), and patient-reported neurotoxicity. RESULTS: Overall, 77 patients were accrued; their median age was 76 years and Eastern Cooperative Oncology Group performance status was 0-1 in 90%. The DCR was 40% (90% confidence interval [CI]: 31-50); therefore, the primary endpoint was not reached. The overall response rate was 22% (95%CI: 13-33), median PFS 5.4 months (95%CI: 4.5-7.7), and median OS 16.1 months (95%CI: 13.5-26.9). Dose modifications were necessary in 35% of patients. In nine patients, more than fifteen cycles were given; 48 patients (62%) experienced at least one grade 3 toxicity. Median patient-reported neurotoxicity scores remained stable for at least fifteen cycles. The main reason for treatment discontinuation was disease progression (57%). DISCUSSION: We report the first prospective data on first-line eribulin in older patients. The reduced starting dose of 1.1 mg/m2 was safe, with prolonged treatment and DC achieved in a considerable proportion of patients (but less than the 55% assumed), without cumulative neurotoxicity. The reduced dose was apparently within the range of the minimal effective dose, as shown by the efficacy lack in patients requiring further dose reductions. Thus, our results do not support the approach of a reduced starting dose for older patients.

Large losses of inorganic nitrogen from tropical rainforests suggest a lack of nitrogen limitation.

Inorganic nitrogen losses from many unpolluted mature tropical forests are over an order of magnitude higher than losses from analogous temperate forests. This pattern could either reflect a lack of N limitation or accelerated plant-soil N cycling under tropical temperatures and moisture. We used a simple analytical framework of the N cycle and compared our predictions with data of N in stream waters of temperate and tropical rainforests. While the pattern could be explained by differences in N limitation, it could not be explained based on up-regulation of the internal N cycle without invoking the unlikely assumption that tropical plants are two to four times less efficient at taking up N than temperate plants. Our results contrast with the idea that a tropical climate promotes and sustains an up-regulated and leaky - but N-limited - internal N cycle. Instead, they are consistent with the notion that many tropical rainforests exist in a state of N saturation.

A comparison of dequalinium chloride vaginal tablets (Fluomizin®) and clindamycin vaginal cream in the treatment of bacterial vaginosis: a single-blind, randomized clinical trial of efficacy and safety.

AIMS: To investigate if vaginal application of dequalinium chloride (DQC, Fluomizin®) is as effective as vaginal clindamycin (CLM) in the treatment of bacterial vaginosis (BV). METHODS: This was a multinational, multicenter, single-blind, randomized trial in 15 centers, including 321 women. They were randomized to either vaginal DQC tablets or vaginal CLM cream. Follow-up visits were 1 week and 1 month after treatment. Clinical cure based on Amsel's criteria was the primary outcome. Secondary outcomes were rate of treatment failures and recurrences, incidence of post-treatment vulvovaginal candidosis (VVC), lactobacillary grade (LBG), total symptom score (TSC), and safety. RESULTS: Cure rates with DQC (C1: 81.5%, C2: 79.5%) were as high as with CLM (C1: 78.4%, C2: 77.6%). Thus, the treatment with DQC had equal efficacy as CLM cream. A trend to less common post-treatment VVC in the DQC-treated women was observed (DQC: 2.5%, CLM: 7.7%; p = 0.06). Both treatments were well tolerated with no serious adverse events occurring. CONCLUSION: Vaginal DQC has been shown to be equally effective as CLM cream, to be well tolerated with no systemic safety concerns, and is therefore a valid alternative therapy for women with BV [ClinicalTrials.gov, Med380104, NCT01125410].

Predictive risk factors for persistent pain following total prosthetic temporomandibular joint replacement.

The aim of this study was to determine the rate of persistent pain following total TMJ replacement and to identify potential predictive risk factors. A retrospective review of case notes treated by a single surgeon in a tertiary unit was performed. For each patient a number of variables were recorded including visual analogue pain scores (0 to 10) and opioid usage pre surgery and at 12 months or last follow up beyond 12 months. Persistent pain scores of 5 to 7 were regarded as moderate and 8 to 10 as severe. The mean pain score at last follow-up was significantly lower than preoperatively (2.1 vs. 6.3, p < 0.001) with a mean follow-up time of 40.1 months (range 12-44). 16.4% of the patients reported moderate to severe pain and 13.7% were still on regular opioids at the last follow-up. Therefore 15 patients (20.5%) suffered from chronic postoperative pain after TMJ replacement surgery. Patients reporting severe preoperative pain scores (p = 0.04), regular opioid use (p = 0.001) or multiple previous open TMJ surgeries (p = 0.03) were more likely to suffer from chronic persistent pain and these should be regarded as predictive risk factors. The identification of these factors allows for better risk stratification of patients, informed consent and the agreement of expected outcomes. Patients with true articular disease and a single failed surgery should be considered for early total TMJ replacement to minimise multifactorial persistent pain.

Association of moderate alcohol use and binge drinking during pregnancy with neonatal health.

BACKGROUND: Heavy drinking and smoking during pregnancy are known to have a negative impact on the unborn child. However, the impact of low-to-moderate alcohol consumption and binge drinking has been debated recently. The aim of this study was to examine the relationship of moderate prenatal drinking and binge drinking with birthweight, being small for gestational age (SGA) at birth, preterm birth, and neonatal asphyxia. METHODS: Moderate alcohol drinking, binge drinking, and several possible confounders were assessed in 1,258 pregnant women; information on neonatal health was obtained at birth. RESULTS: Results indicate that 30.8% of the women drank at low levels (<2 glasses/wk), 7.9% drank moderately (2 to 4 glasses/wk), and 0.9% showed higher levels of drinking (5 glasses/wk); 4.7% reported binge drinking (defined as 3 glasses/occasion). 6.4% of the children were SGA (<10th percentile of birthweight adjusted for gestational age), 4.6% were preterm (<37th week of gestation), and 13.0% showed asphyxia (arterial cord pH <7.10 and/or arterial cord lactate >6.35 mmol and/or Apgar score <7 at 5 minutes). When controlling for maternal age, citizenship, occupational status, parity, smoking, use of prescription/over-the-counter drugs, illicit drug use, and child gender moderate drinking was related to lower birthweight (p < 0.01), and moderate drinking and binge drinking were associated with neonatal asphyxia at trend level (p = 0.06 and p = 0.09). Moderate drinking and binge drinking were not related to length of gestation. CONCLUSIONS: In contrast to recent reviews in the field, our results assume that moderate drinking and binge drinking are risk factors for neonatal health.

Aerosol immunization with NYVAC and MVA vectored vaccines is safe, simple, and immunogenic.

Each year, approximately five million people die worldwide from putatively vaccine-preventable mucosally transmitted diseases. With respect to mass vaccination campaigns, one strategy to cope with this formidable challenge is aerosol vaccine delivery, which offers potential safety, logistical, and cost-saving advantages over traditional vaccination routes. Additionally, aerosol vaccination may elicit pivotal mucosal immune responses that could contain or eliminate mucosally transmitted pathogens in a preventative or therapeutic vaccine context. In this current preclinical non-human primate investigation, we demonstrate the feasibility of aerosol vaccination with the recombinant poxvirus-based vaccine vectors NYVAC and MVA. Real-time in vivo scintigraphy experiments with radiolabeled, aerosol-administered NYVAC-C (Clade C, HIV-1 vaccine) and MVA-HPV vaccines revealed consistent mucosal delivery to the respiratory tract. Furthermore, aerosol delivery of the vaccines was safe, inducing no vaccine-associated pathology, in particular in the brain and lungs, and was immunogenic. Administration of a DNA-C/NYVAC-C prime/boost regime resulted in both systemic and anal-genital HIV-specific immune responses that were still detectable 5 months after immunization. Thus, aerosol vaccination with NYVAC and MVA vectored vaccines constitutes a tool for large-scale vaccine efforts against mucosally transmitted pathogens.

Fast Retrograde Access to Projection Neuron Circuits Underlying Vocal Learning in Songbirds.

Understanding the structure and function of neural circuits underlying speech and language is a vital step toward better treatments for diseases of these systems. Songbirds, among the few animal orders that share with humans the ability to learn vocalizations from a conspecific, have provided many insights into the neural mechanisms of vocal development. However, research into vocal learning circuits has been hindered by a lack of tools for rapid genetic targeting of specific neuron populations to meet the quick pace of developmental learning. Here, we present a viral tool that enables fast and efficient retrograde access to projection neuron populations. In zebra finches, Bengalese finches, canaries, and mice, we demonstrate fast retrograde labeling of cortical or dopaminergic neurons. We further demonstrate the suitability of our construct for detailed morphological analysis, for in vivo imaging of calcium activity, and for multi-color brainbow labeling.