Replication and Meta-Analysis of GWAS Identified Susceptibility Loci in Kawasaki Disease Confirm the Importance of B Lymphoid Tyrosine Kinase (BLK) in Disease Susceptibility

The BLK and CD40 loci have been associated with Kawasaki disease (KD) in two genome-wide association studies (GWAS) conducted in a Taiwanese population of Han Chinese ancestry (Taiwanese) and in Japanese cohorts. Here we build on these findings with replication studies of the BLK and CD40 loci in populations of Korean and European descent. The BLK region was significantly associated with KD susceptibility in both populations. Within the BLK gene the rs2736340-located linkage disequilibrium (LD ) comprising the promoter and first intron was strongly associated with KD, with the combined results of Asian studies including Taiwanese, Japanese, and Korean populations (2,539 KD patients and 7,021 controls) providing very compelling evidence of association (rs2736340, OR = 1.498, 1.354–1.657; P = 4.74×10⁻³¹). We determined the percentage of B cells present in the peripheral blood mononuclear cell (PBMC) population and the expression of BLK in the peripheral blood leukocytes (leukocytes) of KD patients during the acute and convalescent stages. The percentage of B cells in the PBMC population and the expression of BLK in leukocytes were induced in patients in the acute stage of KD. In B cell lines derived from KD patients, and in purified B cells from KD patients obtained during the acute stage, those with the risk allele of rs2736340 expressed significantly lower levels of BLK. These results suggest that peripheral B cells play a pathogenic role during the acute stage of KD. Decreased BLK expression in peripheral blood B cells may alter B cell function and predispose individuals to KD. These associative data suggest a role for B cells during acute KD. Understanding the functional implications may facilitate the development of B cell-mediated therapy for KD.     

Disturbance and the role of refuges in mediterranean climate streams

Refuges protect plant and animal populations from disturbance. Knowledge of refuges from disturbance in mediterranean climate rivers (med-rivers) has increased the last decade. We review disturbance processes and their relationship to refuges in streams in mediterranean climate regions (med-regions). Med-river fauna show high endemicity and their populations are often exposed to disturbance; hence the critical importance of refuges during (both seasonal and supraseasonal) disturbances. Disturbance pressures are increasing in med-regions, in particular from climatic change, salinisation, sedimentation, water extraction, hydropower generation, supraseasonal drought, and wildfire. Med-rivers show annual cycles of constrained precipitation and predictable seasonal drying, causing the biota to depend on seasonal refuges, in particular, those that are spatially predictable. This creates a spatial and temporal mosaic of inundation that determines habitat extent and refuge function. Refuges of sufficient size and duration to maintain populations, such as perennially flowing reaches, sustain biodiversity and may harbour relict populations, particularly during increasing aridification, where little other suitable habitat remains in landscapes. Therefore, disturbances that threaten perennial flows potentially cascade disproportionately to reduce regional scale biodiversity in med-regions. Conservation approaches for med-river systems need to conserve both refuges and refuge connectivity, reduce the impact of anthropogenic disturbances and sustain predictable, seasonal flow patterns.     

Comparison of power output by rice (Oryza sativa) and an associated weed (Echinochloa glabrescens) in vascular plant bio-photovoltaic (VP-BPV) systems

Vascular plant bio-photovoltaics (VP-BPV) is a recently developed technology that uses higher plants to harvest solar energy and the metabolic activity of heterotrophic microorganisms in the plant rhizosphere to generate electrical power. In the present study, electrical output and maximum power output variations were investigated in a novel VP-BPV configuration using the crop plant rice (Oryza sativa L.) or an associated weed, Echinochloa glabrescens (Munro ex Hook. f.). In order to compare directly the physiological performances of these two species in VP-BPV systems, plants were grown in the same soil and glasshouse conditions, while the bio-electrochemical systems were operated in the absence of additional energy inputs (e.g. bias potential, injection of organic substrate and/or bacterial pre-inoculum). Diurnal oscillations were clearly observed in the electrical outputs of VP-BPV systems containing the two species over an 8-day growth period. During this 8-day period, O. sativa generated charge ～6 times faster than E. glabrescens. This greater electrogenic activity generated a total charge accumulation of 6.75?±?0.87 Coulombs for O. sativa compared to 1.12?±?0.16 for E. glabrescens. The average power output observed over a period of about 30 days for O. sativa was significantly higher (0.980?±?0.059 GJ?ha^?1?year^?1) than for E. glabrescens (0.088?±?0.008 GJ?ha^?1?year^?1). This work indicates that electrical power can be generated in both VP-BPV systems (O. sativa and E. glabrescens) when bacterial populations are self-forming. Possible reasons for the differences in power outputs between the two plant species are discussed.     

The role of proteins in C(3) plants prior to their recruitment into the C(4) pathway

Our most productive crops and native vegetation use a modified version of photosynthesis known as the C(4) pathway. Leaves of C(4) crops have increased nitrogen and water use efficiencies compared with C(3) species. Although the modifications to leaves of C(4) plants are complex, their faster growth led to the proposal that C(4) photosynthesis should be installed in C(3) crops in order to increase yield potential. Typically, a limited set of proteins become restricted to mesophyll or bundle sheath cells, and this allows CO(2) to be concentrated around the primary carboxylase RuBisCO. The role that these proteins play in C(3) species prior to their recruitment into the C(4) pathway is addressed here. Understanding the role of these proteins in C(3) plants is likely to be of use in predicting how the metabolism of a C(3) leaf will alter as components of the C(4) pathway are introduced as part of efforts to install characteristics of C(4) photosynthesis in leaves of C(3) crops.     

Transient expression of green fluorescent protein in various plastid types following microprojectile bombardment

The green fluorescent protein gene ( gfp ) is a widely used reporter in both animals and plants. Fusions between the plastid rrn promoter or the Escherichia coli trc promoter and the gfp coding region have been delivered to chloroplasts using gold or tungsten microprojectiles, and fluorescence from GFP was visible in individual tobacco chloroplasts and in the abnormally large chloroplasts of the arc 6 mutant of Arabidopsis thaliana 2–4 days after bombardment. The fusion of the gfp coding region to the bacterial trc promoter demonstrated that a bacterial promoter is active in chloroplasts in vivo . GFP was also detectable in amyloplasts of potato tubers and in chromoplasts of marigold petals, carrot roots and pepper fruits 4 days after bombardment. This demonstrates that GFP can be used as a reporter for transient gene expression in chloroplasts and in non-photosynthetic plastids in a range of higher plants.     

Enhancement of anti-tumor CD8 immunity by IgG1-mediated targeting of Fc receptors

Dendritic cells (DCs) function as professional antigen presenting cells and are critical for linking innate immune responses to the induction of adaptive immunity. Many current cancer DC vaccine strategies rely on differentiating DCs, feeding them tumor antigens ex vivo, and infusing them into patients. Importantly, this strategy relies on prior knowledge of suitable “tumor-specific” antigens to prime an effective anti-tumor response. DCs express a variety of receptors specific for the Fc region of immunoglobulins, and antigen uptake via Fc receptors is highly efficient and facilitates antigen presentation to T cells. Therefore, we hypothesized that expression of the mouse IgG1 Fc region on the surface of tumors would enhance tumor cell uptake by DCs and other myeloid cells and promote the induction of anti-tumor T cell responses. To test this, we engineered a murine lymphoma cell line expressing surface IgG1 Fc and discovered that such tumor cells were taken up rapidly by DCs, leading to enhanced cross-presentation of tumor-derived antigen to CD8+ T cells. IgG1-Fc tumors failed to grow in vivo and prophylactic vaccination of mice with IgG1-Fc tumors resulted in rejection of unmanipulated tumor cells. Furthermore, IgG1-Fc tumor cells were able to slow the growth of an unmanipulated primary tumor when used as a therapeutic tumor vaccine. Our data demonstrate that engagement of Fc receptors by tumors expressing the Fc region of IgG1 is a viable strategy to induce efficient and protective anti-tumor CD8+ T cell responses without prior knowledge of tumor-specific antigens.     

The early clinical features of dengue in adults: challenges for early clinical diagnosis

Background

The emergence of dengue throughout the tropical world is affecting an increasing proportion of adult cases. The clinical features of dengue in different age groups have not been well examined, especially in the context of early clinical diagnosis.

Methodology/Principal Findings

We structured a prospective study of adults (≥18 years of age) presenting with acute febrile illness within 72 hours from illness onset upon informed consent. Patients were followed up over a 3–4 week period to determine the clinical outcome. A total of 2,129 adults were enrolled in the study, of which 250 (11.7%) had dengue. Differences in the rates of dengue-associated symptoms resulted in high sensitivities when the WHO 1997 or 2009 classification schemes for probable dengue fever were applied to the cohort. However, when the cases were stratified into age groups, fewer older adults reported symptoms such as myalgia, arthralgia, retro-orbital pain and mucosal bleeding, resulting in reduced sensitivity of the WHO classification schemes. On the other hand, the risks of severe dengue and hospitalization were not diminshed in older adults, indicating that this group of patients can benefit from early diagnosis, especially when an antiviral drug becomes available. Our data also suggests that older adults who present with fever and leukopenia should be tested for dengue, even in the absence of other symptoms.

Conclusion

Early clinical diagnosis based on previously defined symptoms that are associated with dengue, even when used in the schematics of both the WHO 1997 and 2009 classifications, is difficult in older adults.