Pest management and biodiversity in organic fruit production: the case of apple orchards

Numerous pesticide applications are required for orchard protection, regardless of the guidelines. Organic fruit production (OFP) mainly relies on the use of mineral fungicides and microbiological or naturally-occurring insecticides. The environmental impact of this type of production does not significantly differ from that of conventional production when assessed in terms of synthetic indicators. However, the abundance of earthworms, as well as the abundance and specific richness of arthropod pests and beneficials in the orchards and surrounding hedges, is greater in OFP than in conventional orchards. Generalist predators are usually less affected by OFP compounds than by the chemical pesticides applied in conventional orchards. OFP also benefits avian communities, and above all, insectivorous birds, for which organic orchards offer a suitable habitat similar to that of undisturbed natural areas. In addition to this general trend, discrepancies may be observed in the protection responses of different insect groups. The abundance of hymenopteran parasitoids is the lowest in organic orchards in which outbreaks of phytophagous mites are also recorded in relation to the intensive use of sulphur for scab protection. Biological insecticides often act in ways that are similar to those of chemical ones, and the restricted choice of available compounds is likely to induce resistance selection in insect pests. Although maintaining biodiversity is not a direct result of the implementation of OFP guidelines, it seems to be widely considered as an option by organic growers, both alone and as a complementary tool for pest regulation

The Efficacy of Simulation as a Pedagogy in Facilitating Pre-Service Teachers’ Learning About Emotional Self-Regulation and its Relevance to the Teaching Profession

This study was undertaken in response to the imperative of teacher education courses incorporating National Professional Standards for Teachers, in particular Standard 7, which deals with the professional engagement of teachers (AITSL, 2011). It aimed to evaluate the efficacy of simulation and active recall as a learner-centred pedagogy in facilitating pre-service teachers’ learning about their capacity to self-regulate emotionally and its relevance to the profession. A simulated ‘critical incident’ was used in a lecture to guide students (n=106) to analyse and understand their emotional responses to an altercation between the lecturer and a colleague. The evaluation involved both quantitative and qualitative data collection. The study generated six useful insights associated with the efficacy of simulation pedagogy and revealed convincingly that this pedagogy can engage students actively in learning about the importance of emotional self-regulation in relation to their professional role as a teacher

Invited perspectives: Mountain roads in Nepal at a new crossroads

In Nepal and many developing countries around the world, roads are vehicles for development for communities in rural areas. By reducing travel time on foot, opportunities are opened for quicker transportation of goods and better access to employment, education, health care and markets. Roads also fuel migration and numerous social changes, both positive and negative. Poorly constructed roads in mountainous areas of Nepal have increased erosion and landslide risk as they often cut through fragile geology, destabilizing slopes and altering local hydrological conditions, with costs to lives and livelihoods. The convergence of the newly constituted decentralized Nepali government with China's Belt and Road Initiative is likely to bring more roads to rural communities. The new provincial government administrations now have the opportunity to develop policies and practices, which can realign the current trend of poorly engineered, inefficient and hazardous road construction toward a more sustainable trajectory. This commentary provides an overview of some of the obstacles along the way for a more sustainable road network in Nepal and illustrates how good governance, development and landslide risk are intertwined. The opinion presented in this brief commentary lends little hope that Nepal's current pathway of unsustainable road construction will provide the country with the much-needed sustainable road network, unless checks and balances are put in place to curb noncompliance with existing laws and policies.</p

Severe hematopoietic stem cell inflammation compromises chronic granulomatous disease gene therapy

X-linked chronic granulomatous disease (CGD) is associated with defective phagocytosis, life-threatening infections, and inflammatory complications. We performed a clinical trial of lentivirus-based gene therapy in four patients (NCT02757911). Two patients show stable engraftment and clinical benefits, whereas the other two have progressively lost gene-corrected cells. Single-cell transcriptomic analysis reveals a significantly lower frequency of hematopoietic stem cells (HSCs) in CGD patients, especially in the two patients with defective engraftment. These two present a profound change in HSC status, a high interferon score, and elevated myeloid progenitor frequency. We use elastic-net logistic regression to identify a set of 51 interferon genes and transcription factors that predict the failure of HSC engraftment. In one patient, an aberrant HSC state with elevated CEBPβ expression drives HSC exhaustion, as demonstrated by low repopulation in a xenotransplantation model. Targeted treatments to protect HSCs, coupled to targeted gene expression screening, might improve clinical outcomes in CGD

Pediatric-onset Evans syndrome: Heterogeneous presentation and high frequency of monogenic disorders including LRBA and CTLA4 mutations

Evans syndrome (ES) is defined by the combination of autoimmune hemolytic anemia and immune thrombocytopenia. Clinical presentation includes manifestations of immune dysregulation, found in primary immune deficiencies, autoimmune lymphoproliferative syndrome with FAS (ALPS-FAS), Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) and Lipopolysaccharide-Responsive vesicle trafficking Beige-like and Anchor protein (LRBA) defects. We report the clinical history and genetic results of 18 children with ES after excluding ALPS-FAS. Thirteen had organomegaly, five lymphocytic infiltration of non-lymphoid organs, nine hypogammaglobulinemia and fifteen anomalies in lymphocyte phenotyping. Seven patients had genetic defects: three CTLA4 mutations (c.151C&gt;T; c.109+1092_568-512del; c.110-2A&gt;G) identified by Sanger sequencing and four revealed by Next Generation Sequencing: LRBA (c.2450+1C&gt;T), STAT3 gain-of-function (c.2147C&gt;T; c.2144C&gt;T) and KRAS (c.37G&gt;T). No feature emerged to distinguish patients with or without genetic diagnosis. Our data on pediatric-onset ES should prompt physicians to perform extensive screening for mutations in the growing pool of genes involved in primary immune deficiencies with autoimmunity

AKT activity orchestrates marginal zone B cell development in mice and humans.

The signals controlling marginal zone (MZ) and follicular (FO) B cell development remain incompletely understood. Here, we show that AKT orchestrates MZ B cell formation in mice and humans. Genetic models that increase AKT signaling in B cells or abolish its impact on FoxO transcription factors highlight the AKT-FoxO axis as an on-off switch for MZ B cell formation in mice. In humans, splenic immunoglobulin (Ig) D &lt;sup&gt;+&lt;/sup&gt; CD27 &lt;sup&gt;+&lt;/sup&gt; B cells, proposed as an MZ B cell equivalent, display higher AKT signaling than naive IgD &lt;sup&gt;+&lt;/sup&gt; CD27 &lt;sup&gt;-&lt;/sup&gt; and memory IgD &lt;sup&gt;-&lt;/sup&gt; CD27 &lt;sup&gt;+&lt;/sup&gt; B cells and develop in an AKT-dependent manner from their precursors in vitro, underlining the conservation of this developmental pathway. Consistently, CD148 is identified as a receptor indicative of the level of AKT signaling in B cells, expressed at a higher level in MZ B cells than FO B cells in mice as well as humans

Clinical heterogeneity can hamper the diagnosis of patients with ZAP70 deficiency

One of the severe combined immunodeficiencies (SCIDs), which is caused by a genetic defect in the signal transduction pathways involved in T-cell activation, is the ZAP70 deficiency. Mutations in ZAP70 lead to both abnormal thymic development and defective T-cell receptor (TCR) signaling of peripheral T-cells. In contrast to the lymphopenia in most SCID patients, ZAP70-deficient patients have lymphocytosis, despite the selective absence of CD8+ T-cells. The clinical presentation is usually before 2 years of age with typical findings of SCID. Here, we present three new ZAP70-deficient patients who vary in their clinical presentation. One of the ZAP70-deficient patients presented as a classical SCID, the second patient presented as a healthy looking wheezy infant, whereas the third patient came to clinical attention for the eczematous skin lesions simulating atopic dermatitis with eosinophilia and elevated immunoglobulin E (IgE), similar to the Omenn syndrome. This study illustrates that awareness of the clinical heterogeneity of ZAP70 deficiency is of utmost importance for making a fast and accurate diagnosis, which will contribute to the improvement of the adequate treatment of this severe immunodeficiency

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

Eimeripain, a Cathepsin B-Like Cysteine Protease, Expressed throughout Sporulation of the Apicomplexan Parasite Eimeria tenella

The invasion and replication of Eimeria tenella in the chicken intestine is responsible for avian coccidiosis, a disease that has major economic impacts on poultry industries worldwide. E. tenella is transmitted to naïve animals via shed unsporulated oocysts that need contact with air and humidity to form the infectious sporulated oocysts, which contain the first invasive form of the parasite, the sporozoite. Cysteine proteases (CPs) are major virulence factors expressed by protozoa. In this study, we show that E. tenella expresses five transcriptionally regulated genes encoding one cathepsin L, one cathepsin B and three cathepsin Cs. Biot-LC-LVG-CHN2, a cystatin derived probe, tagged eight polypeptides in unsporulated oocysts but only one in sporulated oocysts. CP-dependant activities were found against the fluorescent substrates, Z-FR-AMC and Z-LR-AMC, throughout the sporulation process. These activities corresponded to a cathepsin B-like enzyme since they were inhibited by CA-074, a specific cathepsin B inhibitor. A 3D model of the catalytic domain of the cathepsin B-like protease, based on its sequence homology with human cathepsin B, further confirmed its classification as a papain-like protease with similar characteristics to toxopain-1 from the related apicomplexan parasite, Toxoplasma gondii; we have, therefore, named the E. tenella cathepsin B, eimeripain. Following stable transfection of E. tenella sporozoites with a plasmid allowing the expression of eimeripain fused to the fluorescent protein mCherry, we demonstrated that eimeripain is detected throughout sporulation and has a punctate distribution in the bodies of extra- and intracellular parasites. Furthermore, CA-074 Me, the membrane-permeable derivative of CA-074, impairs invasion of epithelial MDBK cells by E. tenella sporozoites. This study represents the first characterization of CPs expressed by a parasite from the Eimeria genus. Moreover, it emphasizes the role of CPs in transmission and dissemination of exogenous stages of apicomplexan parasites