The Contribution of Organic Livestock to Sustainable Rural Development in Sensitive Areas

Organic production may contribute positively to rural development. However, there is a gap of knowledge with regard to the livestock sector that the present work is aimed at filling by means of a multidisciplinary and participatory approach. The results suggest that ‘fully organic’ holdings (organic farms that sell products as organic) have the highest potential to contribute to the rural development in the area under study. Nevertheless, its implementation requires higher levels of education and implies higher costs. Due to these difficulties, public subsidies should support such production systems. Moreover, systems with low productivity but high environmental services should be also supported, such as those extensive (either conventional or organic)

Comparative Sustainability Assessment of Extensive Beef Cattle Farms

This chapter analyzes the sustainability of beef cattle systems of the Spanish Rangelands known as “Dehesas”. These are traditional systems of the Iberian Peninsula where native herbaceous vegetation and evergreen species of Quercus provide the basis for extensive livestock farms. These systems are considered as outstanding High Nature Value (HNV) farming systems and the most extensive agroforestry systems in Europe according to CORINE Land Cover. Beef farms in this area show low stocking rates and a small dependence on foodstuff purchases.However, certain changes have occurred in the last decadesdue to the Common Agricultural Policy (CAP). On the one hand, some farms have become more intensified, as a way to maximize the revenues from the CAP subsidies. On the other hand, many farms have turned to organic production, trying to take advantage both of new subsidies and of new market trends. In this regard, the organic livestock farming model is gaining weight as an option for sustainable production since, according to various authors, these systems have advantages over conventional and intensive systems. In fact, organic production in the area has increased substantially in recent years due to several factors, such as the growing interest of the EU towards preserving sensitive ecosystems, the potential role of organic production in the development of rural areas and the growing consumers’ demand for safer and higher quality foods produced under ethical and environmental standards. In this study, we carried out a comparative assessment of the sustainability of different conventional and organic beef production systems located in dehesa rangelands. The systems analyzed were classified as follows. (i) non-organic farms (Conventional); (ii) organic farms that sold calves at weaning age as conventional ones (Organic 1); (iii) organic farms that fattened and sold their calves as organic (Organic 2). An adaptation of the MESMIS multicriteria framework was applied to calculate sustainability indices for each system. The results showed that the Organic 2 farms scored highest on most of the attributes of sustainability, as well as on the environmental and economic dimensions of sustainability. Thus, they were the most sustainable system (66.55%), followed by the Organic 1 (61.04%) and Conventional ones (56.89%). Despite Organic 2 was the most sustainable system, its implementation is complex due to both the high costs of organic inputs and the weak demand for organic beef. The results also showed that all three types of systems need to improve in certain aspects that are crucial in the current and future context of the livestock sector. These aspects are: reducing the dependence on external feed, implementing more environmentally friendly farming practices, and farm diversification

Treating Immunodeficiency through HSC Gene Therapy

Haematopoietic stem cell (HSC) gene therapy has been successfully employed as a therapeutic option to treat specific inherited immune deficiencies, including severe combined immune deficiencies (SCID) over the past two decades. Initial clinical trials using first-generation gamma-retroviral vectors to transfer corrective DNA demonstrated clinical benefit for patients, but were associated with leukemogenesis in a number of cases. Safer vectors have since been developed, affording comparable efficacy with an improved biosafety profile. These vectors are now in Phase I/II clinical trials for a number of immune disorders with more preclinical studies underway. Targeted gene editing allowing precise DNA correction via platforms such as ZFNs, TALENs and CRISPR/Cas9 may now offer promising strategies to improve the safety and efficacy of gene therapy in the future

Perforin gene transfer into hematopoietic stem cells improves immune dysregulation in murine models of perforin deficiency

Defects in perforin lead to the failure of T and NK cell cytotoxicity, hypercytokinemia, and the immune dysregulatory condition known as familial hemophagocytic lymphohistiocytosis (FHL). The only curative treatment is allogeneic hematopoietic stem cell transplantation which carries substantial risks. We used lentiviral vectors (LV) expressing the human perforin gene, under the transcriptional control of the ubiquitous phosphoglycerate kinase promoter or a lineage-specific perforin promoter, to correct the defect in different murine models. Following LV-mediated gene transfer into progenitor cells from perforin-deficient mice, we observed perforin expression in mature T and NK cells, and there was no evidence of progenitor cell toxicity when transplanted into irradiated recipients. The resulting perforin-reconstituted NK cells showed partial recovery of cytotoxicity, and we observed full recovery of cytotoxicity in polyclonal CD8 + T cells. Furthermore, reconstituted T cells with defined antigen specificity displayed normal cytotoxic function against peptide-loaded targets. Reconstituted CD8 + lymphoblasts had reduced interferon-γ secretion following stimulation in vitro, suggesting restoration of normal immune regulation. Finally, upon viral challenge, mice with >30% engraftment of gene-modified cells exhibited reduction of cytokine hypersecretion and cytopenias. This study demonstrates the potential of hematopoietic stem cell gene therapy as a curative treatment for perforin-deficient FHL

Transfer of gene corrected T cells corrects humoral and cytotoxic defects in X-linked lymphoproliferative disease (XLP1)

BACKGROUND: XLP1 arises from mutations in the SH2D1A gene encoding SAP, an adaptor protein expressed in T, NK and NKT cells. Defects lead to abnormalities of T and NK cell cytotoxicity and T cell dependent humoral function. Clinical manifestations include haemophagocytic lymphohistiocytosis (HLH), lymphoma and dysgammaglobulinaemia. Curative treatment is limited to haematopoietic stem cell transplant with outcome reliant on a good donor match. OBJECTIVES: As most symptoms arise from defective T cell function, we investigated whether transfer of SAP gene corrected T cells could reconstitute known effector cell defects. METHODS: CD3+ lymphocytes from sap-deficient mice were transduced with a gammaretroviral vector encoding human SAP cDNA before transfer into sub-lethally irradiated sap-deficient recipients. Following immunisation with the T-dependent antigen NP-CGG, recovery of humoral function was evaluated through germinal centre formation and antigen specific responses. To efficiently transduce patient CD3+ cells, we generated an equivalent lentiviral SAP vector. Functional recovery was demonstrated using in vitro cytotoxicity and TFH cell function assays, alongside tumour clearance in an in vivo LCL lymphoma xenograft model. RESULTS: In sap-deficient mice, 20-40% engraftment of gene modified T cells led to significant recovery of germinal centre formation and NP-specific antibody responses. Gene corrected patient T cells demonstrated improved cytotoxicity and TFH cell function in vitro. Adoptive transfer of gene corrected patient CTLs reduced tumour burden to a level comparable with healthy donor CTLs in an in vivo lymphoma model. CONCLUSIONS: These data demonstrate that autologous T cell gene therapy corrects SAP dependent defects and may offer an alternative therapeutic option for XLP1 patients

Fingerprinting and tracing the sources of soils and sediments: Earth and ocean science, geoarchaeological, forensic, and human health applications

publisher: Elsevier articletitle: Fingerprinting and tracing the sources of soils and sediments: Earth and ocean science, geoarchaeological, forensic, and human health applications journaltitle: Earth-Science Reviews articlelink: http://dx.doi.org/10.1016/j.earscirev.2016.08.012 content_type: article copyright: © 2016 Elsevier B.V. All rights reserved

Comparación de la estructura y rendimientos ganaderos en sistemas de producción tradicional y ecológico de bovino en Extremadura. Comparison of the structure and livestock yields in traditional production systems and ecological bovine Extremadura

The paper analyzes the structure and performance of beef cattle farms in Extremadura: Conventional (n = 50), Organic with no sales of organic products (n = 37) and Organic farms with sales of organic products (n = 11). Regarding stocking rate levels, no significant differences were observed among groups. By contrast, significant differences among the three types of farms regarding racial structure (p <0.05). Similarly, significant differences were found (p <0.1) in relation to farm's area, cattle's reproductive management and performance. The study highlights the similarity between conventional and organic cattle production in Extremadura. This fact could allow a smooth transition of conventional farms to the organic production model

Biallelic JAK1 mutations in immunodeficient patient with mycobacterial infection

Mutations in genes encoding components of the immune system cause primary immunodeficiencies. Here, we study a patient with recurrent atypical mycobacterial infection and early-onset metastatic bladder carcinoma. Exome sequencing identified two homozygous missense germline mutations, P733L and P832S, in the JAK1 protein that mediates signalling from multiple cytokine receptors. Cells from this patient exhibit reduced JAK1 and STAT phosphorylation following cytokine stimulations, reduced induction of expression of interferon-regulated genes and dysregulated cytokine production; which are indicative of signalling defects in multiple immune response pathways including Interferon-γ production. Reconstitution experiments in the JAK1-deficient cells demonstrate that the impaired JAK1 function is mainly attributable to the effect of the P733L mutation. Further analyses of the mutant protein reveal a phosphorylation-independent role of JAK1 in signal transduction. These findings clarify JAK1 signalling mechanisms and demonstrate a critical function of JAK1 in protection against mycobacterial infection and possibly the immunological surveillance of cancer.Wellcome Trust (095198/Z/10/Z and 090233/Z/09/Z); Higher Education Funding Council for England; Great Ormond Street Hospital Children’s Charity; National Institute for Health Research (NIHR); Great Ormond Street Hospital Biomedical Research Centre; NIHR Cambridge Biomedical Research Centre; Alfonso Martin Escudero Foundatio

Long-term lymphoid progenitors independently sustain naïve T and NK cell production in humans.

Our mathematical model of integration site data in clinical gene therapy supported the existence of long-term lymphoid progenitors capable of surviving independently from hematopoietic stem cells. To date, no experimental setting has been available to validate this prediction. We here report evidence of a population of lymphoid progenitors capable of independently maintaining T and NK cell production for 15 years in humans. The gene therapy patients of this study lack vector-positive myeloid/B cells indicating absence of engineered stem cells but retain gene marking in both T and NK. Decades after treatment, we can still detect and analyse transduced naïve T cells whose production is likely maintained by a population of long-term lymphoid progenitors. By tracking insertional clonal markers overtime, we suggest that these progenitors can support both T and NK cell production. Identification of these long-term lymphoid progenitors could be utilised for the development of next generation gene- and cancer-immunotherapies