Protein storage vacuoles originate by remodelling of pre-existing vacuoles in Arabidopsis thaliana

Protein storage vacuoles (PSV) are the main repository of protein in dicotyledonous seeds. Little is known about the origins of these transient organelles. PSV are hypothesised to either arise de novo or to originate from the pre-existing embryonic vacuole (EV) during seed maturation. We have tested these hypotheses by studying PSV formation in Arabidopsis embryos at different stages of seed maturation and have recapitulated this process in Arabidopsis leaves reprogrammed to an embryogenic fate by inducing expression of the LEAFY COTYLEDON2 transcription factor. Confocal and immunoelectron microscopy indicate that both storage proteins and tonoplast proteins typical of PSV are delivered to the pre-existing EV in embryos or to the lytic vacuole in reprogrammed leaf cells. In addition, sectioning through embryos at several developmental stages using serial block face scanning electron microscopy reveals the 3D architecture of forming PSV. Our results indicate that in Arabidopsis the pre-existing vacuole is reprogrammed to become a PSV

Qualitative impact assessment of land management interventions on ecosystem services (“QEIA”). Report-3 theme-6: carbon sequestration

This project assessed the impacts of 741 potential land management actions, suitable for agricultural land in England, on the Farming & Countryside Programme’s Environmental Objectives (and therefore Environment Act targets and climate commitments) through 53 relevant environmental and cultural service indicators. The project used a combination of expert opinion and rapid evidence reviews, which included 1000+ pages of evidence in 10 separate reports with reference to over 2400 published studies, and an Integrated Assessment comprising expert-derived qualitative impact scores. The project has ensured that ELM schemes are evidence-based, offer good value for money, and contribute to SoS priorities for farming

FCRL5 Delineates Functionally Impaired Memory B Cells Associated with Plasmodium falciparum Exposure.

Exposure to Plasmodium falciparum is associated with circulating "atypical" memory B cells (atMBCs), which appear similar to dysfunctional B cells found in HIV-infected individuals. Functional analysis of atMBCs has been limited, with one report suggesting these cells are not dysfunctional but produce protective antibodies. To better understand the function of malaria-associated atMBCs, we performed global transcriptome analysis of these cells, obtained from individuals living in an area of high malaria endemicity in Uganda. Comparison of gene expression data suggested down-modulation of B cell receptor signaling and apoptosis in atMBCs compared to classical MBCs. Additionally, in contrast to previous reports, we found upregulation of Fc receptor-like 5 (FCRL5), but not FCRL4, on atMBCs. Atypical MBCs were poor spontaneous producers of antibody ex vivo, and higher surface expression of FCRL5 defined a distinct subset of atMBCs compromised in its ability to produce antibody upon stimulation. Moreover, higher levels of P. falciparum exposure were associated with increased frequencies of FCRL5+ atMBCs. Together, our findings suggest that FCLR5+ identifies a functionally distinct, and perhaps dysfunctional, subset of MBCs in individuals exposed to P. falciparum

B cell sub-types following acute malaria and associations with clinical immunity.

BACKGROUND: Repeated exposure to Plasmodium falciparum is associated with perturbations in B cell sub-set homeostasis, including expansion atypical memory B cells. However, B cell perturbations immediately following acute malaria infection have been poorly characterized, especially with regard to their relationship with immunity to malaria. METHODS: To better understand the kinetics of B cell sub-sets following malaria, the proportions of six B cell sub-sets were assessed at five time points following acute malaria in four to 5 years old children living in a high transmission region of Uganda. B cell sub-set kinetics were compared with measures of clinical immunity to malaria-lower parasite density at the time of malaria diagnosis and recent asymptomatic parasitaemia. RESULTS: Atypical memory B cell and transitional B cell proportions increased following malaria. In contrast, plasmablast proportions were highest at the time of malaria diagnosis and rapidly declined following treatment. Increased proportions of atypical memory B cells were associated with greater immunity to malaria, whereas increased proportions of transitional B cells were associated with evidence of less immunity to malaria. CONCLUSIONS: These findings highlight the dynamic changes in multiple B cell sub-sets following acute, uncomplicated malaria, and how these sub-sets are associated with developing immunity to malaria

Land degradation neutrality: testing the indicator in a temperate agricultural landscape

Land degradation directly affects around 25% of land globally, undermining progress on most of the UN Sustainable Development Goals (SDG), particularly target 15.3. To assess land degradation, SDG indicator 15.3.1 combines sub-indicators of productivity, soil carbon and land cover. Over 100 countries have set Land Degradation Neutrality (LDN) targets. Here, we demonstrate application of the indicator for a well-established agricultural landscape using the case study of Great Britain. We explore detection of degradation in such landscapes by: 1) transparently evaluating land cover transitions; 2) comparing assessments using global and national data; 3) identifying misleading trends; and 4) including extra sub-indicators for additional forms of degradation. Our results demonstrate significant impacts on the indicator both from the land cover transition evaluation and choice or availability of data. Critically, we identify a misleading improvement trend due to a trade-off between improvement detected by the productivity sub-indicator, and 30-year soil carbon loss trends in croplands (11% from 1978 to 2007). This carbon loss trend would not be identified without additional data from Countryside Survey (CS). Thus, without incorporating field survey data we risk overlooking the degradation of regulating and supporting ecosystem services (linked to soil carbon), in favour of signals from improving provisioning services (productivity sub-indicator). Relative importance of these services will vary between socioeconomic contexts. Including extra sub-indicators for erosion or critical load exceedance, as additional forms of degradation, produced a switch from net area improving (9%) to net area degraded (58%). CS data also identified additional degradation for soil health, including 44% arable soils exceeding bulk density thresholds and 35% of CS squares exceeding contamination thresholds for metals

A comparative study of the effect of the Time for Dementia programme on medical students

Background Traditional healthcare education typically focuses on short block clinical placements based on acute care, investigations, and technical aspects of diagnosis and treatment. It may therefore fail to build the understanding, compassion, and person‐centred empathy needed to help those with long‐term conditions, like dementia. Time for Dementia was developed to address this. Method Parallel group comparison of two cohorts of UK medical students from universities, one participating in Time for Dementia (intervention group) and one not (control group). In Time for Dementia students visit a person with dementia and their family in pairs for two hours three times a year for two years, the control group received their normal curriculum. Results In an adjusted multilevel model of data (intervention group n=274, control n=112), there was strong evidence supporting improvements for Time for Dementia participants in: total Approaches to Dementia Questionnaire score (coefficient 2.19, p=0.003), and its person‐centredness subscale (1.32, p=0.006), and weaker evidence in its hopefulness subscale (0.78, p=0.070); Dementia Knowledge Questionnaire score (1.63, p<0.001); and Dementia Attitudes Scale (total score 6.55, p<0.001; social comfort subscale 4.15, p<0.001; dementia knowledge subscale 3.38, p=0.001) scores. No differences were observed on the Alzheimer's Disease Knowledge Scale, the Medical Condition Regard Scale, or the Jefferson Scale of Empathy. Discussion Time for Dementia may help improve the attitudes of medical students towards dementia promoting a person‐centred approach and increasing social comfort. Such patient‐focused programmes may be a useful complement to traditional medical education

Are children with Specific Language Impairment competent with the pragmatics and logic of quantification?

Specific Language Impairment (SLI) is understood to be a disorder that predominantly affects phonology, morphosyntax and/or lexical semantics. There is little conclusive evidence on whether children with SLI are challenged with regard to Gricean pragmatic maxims and on whether children with SLI are competent with the logical meaning of quantifying expressions. We use the comprehension of statements quantified with ‘all’, ‘none’, ‘some’, ‘some…not’, ‘most’ and ‘not all’ as a paradigm to study whether Spanish-speaking children with SLI are competent with the pragmatic maxim of informativeness, as well as with the logical meaning of these expressions. Children with SLI performed more poorly than a group of age-matched typically-developing peers, and both groups performed more poorly with pragmatics than with logical meaning. Moreover, children with SLI were disproportionately challenged by pragmatic meaning compared to their age-matched peers. However, the performance of children with SLI was comparable to that of a group of younger language-matched typically-developing children. The findings document that children with SLI do face difficulties with employing the maxim of informativeness, as well as with understanding the logical meaning of quantifiers, but also that these difficulties are in keeping with their overall language difficulties rather than exceeding them. The implications of these findings for SLI, linguistic theory, and clinical practice are discussed

Progression to AIDS in South Africa Is Associated with both Reverting and Compensatory Viral Mutations

We lack the understanding of why HIV-infected individuals in South Africa progress to AIDS. We hypothesised that in end-stage disease there is a shifting dynamic between T cell imposed immunity and viral immune escape, which, through both compensatory and reverting viral mutations, results in increased viral fitness, elevated plasma viral loads and disease progression. We explored how T cell responses, viral adaptation and viral fitness inter-relate in South African cohorts recruited from Bloemfontein, the Free State (n = 278) and Durban, KwaZulu-Natal (n = 775). Immune responses were measured by γ-interferon ELISPOT assays. HLA-associated viral polymorphisms were determined using phylogenetically corrected techniques, and viral replication capacity (VRC) was measured by comparing the growth rate of gag-protease recombinant viruses against recombinant NL4-3 viruses. We report that in advanced disease (CD4 counts <100 cells/µl), T cell responses narrow, with a relative decline in Gag-directed responses (p<0.0001). This is associated with preserved selection pressure at specific viral amino acids (e.g., the T242N polymorphism within the HLA-B*57/5801 restricted TW10 epitope), but with reversion at other sites (e.g., the T186S polymorphism within the HLA-B*8101 restricted TL9 epitope), most notably in Gag and suggestive of “immune relaxation”. The median VRC from patients with CD4 counts <100 cells/µl was higher than from patients with CD4 counts ≥500 cells/µl (91.15% versus 85.19%, p = 0.0004), potentially explaining the rise in viral load associated with disease progression. Mutations at HIV Gag T186S and T242N reduced VRC, however, in advanced disease only the T242N mutants demonstrated increasing VRC, and were associated with compensatory mutations (p = 0.013). These data provide novel insights into the mechanisms of HIV disease progression in South Africa. Restoration of fitness correlates with loss of viral control in late disease, with evidence for both preserved and relaxed selection pressure across the HIV genome. Interventions that maintain viral fitness costs could potentially slow progression