An individual-based model to explore the impacts of lesser-known social dynamics on wolf populations

The occurrence of wolf populations in human-dominated landscapes is challenging worldwide because of conflicts with human activities. Modeling is an important tool to project wolf dynamics and expansion, and help in decision making concerning management and conservation. However, some individual behaviors and pack dynamics of the wolf life cycle are still unclear to ecologists. Here we present an individual-based model (IBM) to project wolf populations while exploring the lesser-known processes of the wolf life cycle. IBMs are bottom-up models that simulate the fate of individuals interacting with each other, with population-level properties emerging from the individual-level simulations. IBMs are particularly adapted to represent social species such as the wolf that exhibits complex individual interactions. Our IBM projects wolf demography including fine-scale individual behavior and pack dynamics based on up-to-date scientific literature. We explore four processes of the wolf life cycle whose consequences on population dynamics are still poorly understood: the pack dissolution following the loss of a breeder, the adoption of young dispersers by packs, the establishment of new packs through budding, and the different breeder replacement strategies. While running different versions of the IBM to explore these processes, we also illustrate the modularity and flexibility of our model, an asset to model wolf populations experiencing different ecological and demographic conditions. The different parameterization of pack dissolution, territory establishment by budding, and breeder replacement processes influence the projections of wolf populations. As such, these processes require further field investigation to be better understood. The adoption process has a lesser impact on model projections. Being coded in R to facilitate its understanding, we expect that our model will be used and further adapted by ecologists for their own specific applications

Antibiotic-related gut dysbiosis induces lung immunodepression and worsens lung infection in mice.

Gut dysbiosis due to the adverse effects of antibiotics affects outcomes of lung infection. Previous murine models relied on significant depletion of both gut and lung microbiota, rendering the analysis of immune gut-lung cross-talk difficult. Here, we study the effects of antibiotic-induced gut dysbiosis without lung dysbiosis on lung immunity and the consequences on acute P. aeruginosa lung infection. C57BL6 mice received 7 days oral vancomycin-colistin, followed by normal regimen or fecal microbial transplant or Fms-related tyrosine kinase 3 ligand (Flt3-Ligand) over 2 days, and then intra-nasal P. aeruginosa strain PAO1. Gut and lung microbiota were studied by next-generation sequencing, and lung infection outcomes were studied at 24 h. Effects of vancomycin-colistin on underlying immunity and bone marrow progenitors were studied in uninfected mice by flow cytometry in the lung, spleen, and bone marrow. Vancomycin-colistin administration induces widespread cellular immunosuppression in both the lung and spleen, decreases circulating hematopoietic cytokine Flt3-Ligand, and depresses dendritic cell bone marrow progenitors leading to worsening of P. aeruginosa lung infection outcomes (bacterial loads, lung injury, and survival). Reversal of these effects by fecal microbial transplant shows that these alterations are related to gut dysbiosis. Recombinant Flt3-Ligand reverses the effects of antibiotics on subsequent lung infection. These results show that gut dysbiosis strongly impairs monocyte/dendritic progenitors and lung immunity, worsening outcomes of P. aeruginosa lung infection. Treatment with a fecal microbial transplant or immune stimulation by Flt3-Ligand both restore lung cellular responses to and outcomes of P. aeruginosa following antibiotic-induced gut dysbiosis

Retrieval of H₂O abundance in Titan's stratosphere:A (re)analysis of CIRS/Cassini and PACS/Herschel observations

Since its first measurement 20 years ago by the Infrared Space Observatory (ISO), the water (H2O) mole fraction in Titan’s stratosphere remains uncertain due to large differences between the determinations from available measurements. More particularly, the recent measurements made from the Herschel observatory (PACS and HIFI) estimated the H2O mole fraction to be 0.023 ppb at 12.1 mbar. A mixing ratio of 0.14 ppb at 10.7 mbar was, however, retrieved from nadir spatially-resolved observations of Cassini/CIRS. At the same pressure level (10.7 mbar), this makes a difference of a factor of 5.5 between PACS and CIRS measurements, and this has notably prevented current models from fully constraining the oxygen flux flowing into Titan’s atmosphere. In this work, we try to understand the differences between the H2O mole fractions estimated from Herschel/PACS and Cassini/CIRS observations. The strategy for this is to 1) analyse recent disc-averaged observations of CIRS to investigate if the observation geometry could explain the previous observed differences, and 2) (re)analyse the three types of observation with the same retrieval scheme to assess if previous differences in retrieval codes/methodology could be responsible for the previous discrepancies. With this analysis, we show that using the same retrieval method better reconcile the previous measurements of these instruments. However, the addition of the disc-averaged CIRS observations, instead of confirming the consistency between the different datasets, reveals discrepancies between one of the CIRS disc-averaged set of observations and PACS measurements. This raises new questions regarding the possibility of latitudinal variations of H2O, which could be triggered by seasonal changes of the meridional circulation. As it has already been shown for nitriles and hydrocarbons, this circulation could potentially impact the latitudinal distribution of H2O through the subsidence or upwelling of air rich in H2O. The possible influence of spatial/time variations of the OH/H2O input flux in Titan’s atmosphere is also discussed. The analysis of more observations will be needed in future work to address the questions arising from this work and to improve the understanding of the sources of H2O in Titan’s atmosphere

J Virol

In this placebo-controlled phase II randomized clinical trial, 103 HIV-1 infected patients under c-ART (combined antiretroviral treatment) were randomized 2:1 to receive 3 doses of DNA GTU-MultiHIV B (coding for Rev, Nef, Tat, Gag and gp160) at Week (W)0, W4 and W12 followed by 2 doses of LIPO-5 vaccine containing long peptides from Gag, Pol and Nef at W20 and W24 or placebos. Analytical treatment interruption (ATI) was performed between W36 to W48.At W28, vaccinees experienced an increase in functional CD4(+) T cell responses measured (P\textbackslashtextless0.001 for each cytokine compared to W0) predominantly against Gag and Pol/Env and an increase in HIV-specific CD8(+) T cells producing IL-2 and TNF-α (P=0.001 and 0.013, respectively), predominantly against Pol/Env and Nef. However, analysis of T cell subsets by mass cytometry in a subpopulation showed an increase of W28/W0 ratio for memory CD8(+) T cells co-expressing exhaustion and senescence markers such as PD-1/TIGIT (P=0.004) and CD27/CD57 (P=0.044) in vaccinees compared to placebo. During ATI, all patients experienced viral rebound with a maximum observed HIV RNA level at W42 (median: 4.63 log(10) cp/ml; IQR 4.00-5.09) without any difference between arms. No patient resumed c-ART for CD4 cell count drop. Globally, the vaccine strategy was safe. However, a secondary HIV transmission during ATI was observed.These data show that the prime-boost combination of DNA and LIPO-5 vaccines elicited broad and polyfunctional T cells. The contrast between the quality of immune responses and the lack of potent viral control underscores the need of combined immunomodulatory strategies.IMPORTANCE In this placebo-controlled phase II randomized clinical trial, we evaluated the safety and immunogenicity of a therapeutic prime-boost vaccine strategy using a recombinant DNA vaccine (GTU®-MultiHIV B clade) followed by a boost vaccination by a lipopeptide vaccine (HIV-LIPO-5) in HIV-infected patients while on combined antiretroviral therapy. We show that this prime-boost strategy is well tolerated, consistently with previous studies in HIV-1 infected individuals and healthy volunteers who received each vaccine component individually. Compared to placebo group, vaccines elicited strong and polyfunctional HIV-specific CD4(+) and CD8(+) T cell responses. However, these immune responses presenting some qualitative defects were not able to control viremia following antiretroviral treatment interruption as no difference in HIV viral rebound was observed in vaccine and placebo groups. Several lessons were learned from these results pointing out the urgent need to combine the vaccine strategies with other immune-based interventions

Genetic underpinnings of sociability in the general population

Levels of sociability are continuously distributed in the general population, and decreased sociability represents an early manifestation of several brain disorders. Here, we investigated the genetic underpinnings of sociability in the population. We performed a genome-wide association study (GWAS) of a sociability score based on four social functioning-related self-report questions from 342,461 adults in the UK Biobank. Subsequently we performed gene-wide and functional follow-up analyses. Robustness analyses were performed in the form of GWAS split-half validation analyses, as well as analyses excluding neuropsychiatric cases. Using genetic correlation analyses as well as polygenic risk score analyses we investigated genetic links of our sociability score to brain disorders and social behavior outcomes. Individuals with autism spectrum disorders, bipolar disorder, depression, and schizophrenia had a lower sociability score. The score was significantly heritable (SNP h(2) of 6%). We identified 18 independent loci and 56 gene-wide significant genes, including genes like ARNTL, DRD2, and ELAVL2. Many associated variants are thought to have deleterious effects on gene products and our results were robust. The sociability score showed negative genetic correlations with autism spectrum, disorders, depression, schizophrenia, and two sociability-related traits-loneliness and social anxiety-but not with bipolar disorder or Alzheimer's disease. Polygenic risk scores of our sociability GWAS were associated with social behavior outcomes within individuals with bipolar disorder and with major depressive disorder. Variation in population sociability scores has a genetic component, which is relevant to several psychiatric disorders. Our findings provide clues towards biological pathways underlying sociability.Stress-related psychiatric disorders across the life spa

Major Role for Amphotericin B–Flucytosine Combination in Severe Cryptococcosis

BACKGROUND: The Infectious Diseases Society of America published in 2000 practical guidelines for the management of cryptococcosis. However, treatment strategies have not been fully validated in the various clinical settings due to exclusion criteria during therapeutic trials. We assessed here the optimal therapeutic strategies for severe cryptococcosis using the observational prospective CryptoA/D study after analyzing routine clinical care of cryptococcosis in university or tertiary care hospitals. METHODOLOGY/PRINCIPAL FINDINGS: Patients were enrolled if at least one culture grew positive with Cryptococcus neoformans. Control of sterilization was warranted 2 weeks (Wk2) and 3 months (Mo3) after antifungal therapy onset. 208 HIV-positive or -negative adult patients were analyzed. Treatment failure (death or mycological failure) at Wk2 and Mo3 was the main outcome measured. Combination of amphotericin B+flucytosine (AMB+5FC) was the best regimen for induction therapy in patients with meningoencephalitis and in all patients with high fungal burden and abnormal neurology. In those patients, treatment failure at Wk2 was 26% in the AMB+5FC group vs. 56% with any other treatments (p<0.001). In patients treated with AMB+5FC, factors independently associated with Wk2 mycological failure were high serum antigen titer (OR [95%CI] = 4.43[1.21-16.23], p = 0.025) and abnormal brain imaging (OR = 3.89[1.23-12.31], p = 0.021) at baseline. Haematological malignancy (OR = 4.02[1.32-12.25], p = 0.015), abnormal neurology at baseline (OR = 2.71[1.10-6.69], p = 0.030) and prescription of 5FC for less than 14 days (OR = 3.30[1.12-9.70], p = 0.030) were independently associated with treatment failure at Mo3. CONCLUSION/SIGNIFICANCE: Our results support the conclusion that induction therapy with AMB+5FC for at least 14 days should be prescribed rather than any other induction treatments in all patients with high fungal burden at baseline regardless of their HIV serostatus and of the presence of proven meningoencephalitis

Significant Reduction of Antibiotic Use in the Community after a Nationwide Campaign in France, 2002–2007

Didier Guillemot and colleagues describe the evaluation of a nationwide programme in France aimed at decreasing unnecessary outpatient prescriptions for antibiotics. The campaign was successful, particularly in reducing prescriptions for children

Strong constraints on aerosol-cloud interactions from volcanic eruptions.

Aerosols have a potentially large effect on climate, particularly through their interactions with clouds, but the magnitude of this effect is highly uncertain. Large volcanic eruptions produce sulfur dioxide, which in turn produces aerosols; these eruptions thus represent a natural experiment through which to quantify aerosol-cloud interactions. Here we show that the massive 2014-2015 fissure eruption in Holuhraun, Iceland, reduced the size of liquid cloud droplets-consistent with expectations-but had no discernible effect on other cloud properties. The reduction in droplet size led to cloud brightening and global-mean radiative forcing of around -0.2 watts per square metre for September to October 2014. Changes in cloud amount or cloud liquid water path, however, were undetectable, indicating that these indirect effects, and cloud systems in general, are well buffered against aerosol changes. This result will reduce uncertainties in future climate projections, because we are now able to reject results from climate models with an excessive liquid-water-path response

Water Vapor Vertical Profiles on Mars in Dust Storms Observed by TGO/NOMAD

It has been suggested that dust storms efficiently transport water vapor from the near‐surface to the middle atmosphere on Mars. Knowledge of the water vapor vertical profile during dust storms is important to understand water escape. During Martian Year 34, two dust storms occurred on Mars: a global dust storm (June to mid‐September 2018) and a regional storm (January 2019). Here we present water vapor vertical profiles in the periods of the two dust storms (Ls = 162–260° and Ls = 298–345°) from the solar occultation measurements by Nadir and Occultation for Mars Discovery (NOMAD) onboard ExoMars Trace Gas Orbiter (TGO). We show a significant increase of water vapor abundance in the middle atmosphere (40–100 km) during the global dust storm. The water enhancement rapidly occurs following the onset of the storm (Ls~190°) and has a peak at the most active period (Ls~200°). Water vapor reaches very high altitudes (up to 100 km) with a volume mixing ratio of ~50 ppm. The water vapor abundance in the middle atmosphere shows high values consistently at 60°S‐60°N at the growth phase of the dust storm (Ls = 195°–220°), and peaks at latitudes greater than 60°S at the decay phase (Ls = 220°–260°). This is explained by the seasonal change of meridional circulation: from equinoctial Hadley circulation (two cells) to the solstitial one (a single pole‐to‐pole cell). We also find a conspicuous increase of water vapor density in the middle atmosphere at the period of the regional dust storm (Ls = 322–327°), in particular at latitudes greater than 60°S