Generation of neutralizing antibodies and divergence of SIVmac239 in cynomolgus macaques following short-term early antiretroviral therapy.

Neutralizing antibodies (NAb) able to react to heterologous viruses are generated during natural HIV-1 infection in some individuals. Further knowledge is required in order to understand the factors contributing to induction of cross-reactive NAb responses. Here a well-established model of experimental pathogenic infection in cynomolgus macaques, which reproduces long-lasting HIV-1 infection, was used to study the NAb response as well as the viral evolution of the highly neutralization-resistant SIVmac239. Twelve animals were infected intravenously with SIVmac239. Antiretroviral therapy (ART) was initiated ten days post-inoculation and administered daily for four months. Viral load, CD4(+) T-cell counts, total IgG levels, and breadth as well as strength of NAb in plasma were compared simultaneously over 14 months. In addition, envs from plasma samples were sequenced at three time points in all animals in order to assess viral evolution. We report here that seven of the 12 animals controlled viremia to below 10(4) copies/ml of plasma after discontinuation of ART and that this control was associated with a low level of evolutionary divergence. Macaques that controlled viral load developed broader NAb responses early on. Furthermore, escape mutations, such as V67M and R751G, were identified in virus sequenced from all animals with uncontrolled viremia. Bayesian estimation of ancestral population genetic diversity (PGD) showed an increase in this value in non-controlling or transient-controlling animals during the first 5.5 months of infection, in contrast to virus-controlling animals. Similarly, non- or transient controllers displayed more positively-selected amino-acid substitutions. An early increase in PGD, resulting in the generation of positively-selected amino-acid substitutions, greater divergence and relative high viral load after ART withdrawal, may have contributed to the generation of potent NAb in several animals after SIVmac239 infection. However, early broad NAb responses correlated with relatively preserved CD4(+) T-cell numbers, low viral load and limited viral divergence

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

EUREC⁴A

The science guiding the EUREC⁴A campaign and its measurements is presented. EUREC⁴A comprised roughly 5 weeks of measurements in the downstream winter trades of the North Atlantic – eastward and southeastward of Barbados. Through its ability to characterize processes operating across a wide range of scales, EUREC⁴A marked a turning point in our ability to observationally study factors influencing clouds in the trades, how they will respond to warming, and their link to other components of the earth system, such as upper-ocean processes or the life cycle of particulate matter. This characterization was made possible by thousands (2500) of sondes distributed to measure circulations on meso- (200 km) and larger (500 km) scales, roughly 400 h of flight time by four heavily instrumented research aircraft; four global-class research vessels; an advanced ground-based cloud observatory; scores of autonomous observing platforms operating in the upper ocean (nearly 10 000 profiles), lower atmosphere (continuous profiling), and along the air–sea interface; a network of water stable isotopologue measurements; targeted tasking of satellite remote sensing; and modeling with a new generation of weather and climate models. In addition to providing an outline of the novel measurements and their composition into a unified and coordinated campaign, the six distinct scientific facets that EUREC⁴A explored – from North Brazil Current rings to turbulence-induced clustering of cloud droplets and its influence on warm-rain formation – are presented along with an overview of EUREC⁴A's outreach activities, environmental impact, and guidelines for scientific practice. Track data for all platforms are standardized and accessible at https://doi.org/10.25326/165 (Stevens, 2021), and a film documenting the campaign is provided as a video supplement

EUREC⁴A

The science guiding the EUREC⁴A campaign and its measurements is presented. EUREC⁴A comprised roughly 5 weeks of measurements in the downstream winter trades of the North Atlantic – eastward and southeastward of Barbados. Through its ability to characterize processes operating across a wide range of scales, EUREC⁴A marked a turning point in our ability to observationally study factors influencing clouds in the trades, how they will respond to warming, and their link to other components of the earth system, such as upper-ocean processes or the life cycle of particulate matter. This characterization was made possible by thousands (2500) of sondes distributed to measure circulations on meso- (200 km) and larger (500 km) scales, roughly 400 h of flight time by four heavily instrumented research aircraft; four global-class research vessels; an advanced ground-based cloud observatory; scores of autonomous observing platforms operating in the upper ocean (nearly 10 000 profiles), lower atmosphere (continuous profiling), and along the air–sea interface; a network of water stable isotopologue measurements; targeted tasking of satellite remote sensing; and modeling with a new generation of weather and climate models. In addition to providing an outline of the novel measurements and their composition into a unified and coordinated campaign, the six distinct scientific facets that EUREC⁴A explored – from North Brazil Current rings to turbulence-induced clustering of cloud droplets and its influence on warm-rain formation – are presented along with an overview of EUREC⁴A's outreach activities, environmental impact, and guidelines for scientific practice. Track data for all platforms are standardized and accessible at https://doi.org/10.25326/165 (Stevens, 2021), and a film documenting the campaign is provided as a video supplement

Multidisciplinary treatment for traumatized refugees in a naturalistic setting: symptom courses and predictors

Background: Multidisciplinary treatment approaches are commonly used in specialized psychosocial centres for the treatment of traumatized refugees, but empirical evidence for their efficacy is inconsistent. Objective: In order to obtain more evidence on the development of mental health and well-being of traumatized refugees who receive multidisciplinary treatment, symptom courses of posttraumatic stress disorder (PTSD), anxiety, depression and somatoform symptoms as well as in the subjective quality of life were investigated in the course of a multidisciplinary treatment. In addition, it was analysed if sociodemographic variables were predictors for possible changes in symptomatology and quality of life. Method: N = 76 patients of the outpatient clinic of a psychosocial centre for traumatized refugees receiving regular multidisciplinary treatment were surveyed using standardized questionnaires at three measurement points (at the beginning of treatment, and after an average of 7 and 14 months of treatment) in a single-group design. Results: Multilevel analysis showed significant improvements of symptoms of PTSD (p < .001), depression (p < .001), anxiety (p < .001), and somatoform symptoms (p = .002) as well as of the subjective quality of life (p < .001) over time. Among the tested predictors (gender, age, country of origin), age was a significant predictor for the course of somatoform symptoms (p < .05). Younger patients showed greater improvements in symptomatology over time than older ones. Conclusions: The results suggest that the received multidisciplinary treatment had a positive effect on trauma-related symptoms as well as on quality of life of traumatized refugees. There was no indication that sociodemographic characteristics predicted the symptom courses of the patients, except for somatoform symptoms. Younger patients benefitted more from multidisciplinary treatment than older ones

Unraveling tumor-immune heterogeneity in advanced ovarian cancer uncovers immunogenic effect of chemotherapy.

In metastatic cancer, the degree of heterogeneity of the tumor microenvironment (TME) and its molecular underpinnings remain largely unstudied. To characterize the tumor-immune interface at baseline and during neoadjuvant chemotherapy (NACT) in high-grade serous ovarian cancer (HGSOC), we performed immunogenomic analysis of treatment-naive and paired samples from before and after treatment with chemotherapy. In treatment-naive HGSOC, we found that immune-cell-excluded and inflammatory microenvironments coexist within the same individuals and within the same tumor sites, indicating ubiquitous variability in immune cell infiltration. Analysis of TME cell composition, DNA copy number, mutations and gene expression showed that immune cell exclusion was associated with amplification of Myc target genes and increased expression of canonical Wnt signaling in treatment-naive HGSOC. Following NACT, increased natural killer (NK) cell infiltration and oligoclonal expansion of T cells were detected. We demonstrate that the tumor-immune microenvironment of advanced HGSOC is intrinsically heterogeneous and that chemotherapy induces local immune activation, suggesting that chemotherapy can potentiate the immunogenicity of immune-excluded HGSOC tumors

Identification of the Signal Directing Tim9 and Tim10 into the Intermembrane Space of Mitochondria

The intermembrane space of mitochondria contains the specific mitochondrial intermembrane space assembly (MIA) machinery that operates in the biogenesis pathway of precursor proteins destined to this compartment. The Mia40 component of the MIA pathway functions as a receptor and binds incoming precursors, forming an essential early intermediate in the biogenesis of intermembrane space proteins. The elements that are crucial for the association of the intermembrane space precursors with Mia40 have not been determined. In this study, we found that a region within the Tim9 and Tim10 precursors, consisting of only nine amino acid residues, functions as a signal for the engagement of substrate proteins with the Mia40 receptor. Furthermore, the signal contains sufficient information to facilitate the transfer of proteins across the outer membrane to the intermembrane space. Thus, here we have identified the mitochondrial intermembrane space sorting signal required for delivery of proteins to the mitochondrial intermembrane space