Association of Allergic Symptoms with Dengue Infection and Severity: A Systematic Review and Meta-analysis

The relationship between the severity of dengue infection and allergy is still obscure. We conducted an electronic search across 12 databases for relevant articles reporting allergic symptoms, dengue infection, and dengue classification. These studies were categorized according to dengue severity and allergy symptoms, and a meta-analysis was performed by pooling the studies in each category. Among the included 57 articles, pruritus was the most common allergic sign followed by non-specified allergy and asthma(28.6%, 13%, and 6.5%, respectively). Despite the reported significant association of dengue with pruritus and total Ig E level(P \ 0.05), in comparison with non-dengue cases and healthy controls, there was no association between the different severe dengue group with pruritus, skin allergy, food allergy or asthma. However,removing the largest study revealed a significant association between asthma with dengue hemorrhagic fever(DHF) rather than dengue fever(DF). In comparison with DF, DHF was associated with Ig E positivity. Furthermore, specific-Ig E level was higher in secondary DF rather than primary DF. There was a possible association between allergy symptoms and dengue severity progression. Further studies are needed to clarify this association.     

GPI7-mediated glycosylphosphatidylinositol anchoring regulates appressorial penetration and immune evasion during infection of Magnaporthe oryzae

Glycosylphosphatidylinositol (GPI) anchoring plays key roles in many biological processes by targeting proteins to the cell wall; however, its roles are largely unknown in plant pathogenic fungi. Here, we reveal the roles of the GPI anchoring in Magnaporthe oryzae during plant infection. The GPI-anchored proteins were found to highly accumulate in appressoria and invasive hyphae. Disruption of GPI7, a GPI anchor-pathway gene, led to a significant reduction in virulence. The Δgpi7 mutant showed significant defects in penetration and invasive growth. This mutant also displayed defects of the cell wall architecture, suggesting GPI7 is required for cell wall biogenesis. Removal of GPI-anchored proteins in the wild-type strain by hydrofluoric acid (HF) pyridine treatment exposed both the chitin and β-1,3-glucans to the host immune system. Exposure of the chitin and β-1,3-glucans was also observed in the Δgpi7 mutant, indicating GPI-anchored proteins are required for immune evasion. The GPI anchoring can regulate subcellular localization of the Gel proteins in the cell wall for appressorial penetration and abundance of which for invasive growth. Our results indicate the GPI anchoring facilitates the penetration of M. oryzae into host cells by affecting the cell wall integrity and the evasion of host immune recognition.     

Soil and root nutrient chemistry structure root-associated fungal assemblages in temperate forests

Root-associated fungi (RAF) link nutrient fluxes between soil and roots and thus play important roles in ecosystem functioning. To enhance our understanding of the factors that control RAF, we fitted statistical models to explain variation in RAF community structure using data from 150 temperate forest sites covering a broad range of environmental conditions and chemical root traits. We found that variation in RAF communities was related to both root traits (e.g., cations, carbohydrates, NO₃⁻) and soil properties (pH, cations, moisture, C/N). The identified drivers were the combined result of distinct response patterns of fungal taxa (determined at the rank of orders) to biotic and abiotic factors. Our results support that RAF community variation is related to evolutionary adaptedness of fungal lineages and consequently, drivers of RAF communities are context-dependent.     

Staphylococcus aureus Lpl protein triggers human host cell invasion via activation of Hsp90 receptor

Staphylococcus aureus is a facultative intracellular pathogen. Recently, it has been shown that the protein part of the lipoprotein‐like lipoproteins (Lpls), encoded by the lpl cluster comprising of 10 lpls paralogue genes, increases pathogenicity, delays the G2/M phase transition, and also triggers host cell invasion. Here, we show that a recombinant Lpl1 protein without the lipid moiety binds directly to the isoforms of the human heat shock proteins Hsp90α and Hsp90ß. Synthetic peptides covering the Lpl1 sequence caused a twofold to fivefold increase of S. aureus invasion in HaCaT cells. Antibodies against Hsp90 decrease S. aureus invasion in HaCaT cells and in primary human keratinocytes. Additionally, inhibition of ATPase function of Hsp90 or silencing Hsp90α expression by siRNA also decreased the S. aureus invasion in HaCaT cells. Although the Hsp90ß is constitutively expressed, the Hsp90α isoform is heat‐inducible and appears to play a major role in Lpl1 interaction. Pre‐incubation of HaCaT cells at 39°C increased both the Hsp90α expression and S. aureus invasion. Lpl1‐Hsp90 interaction induces F‐actin formation, thus, triggering an endocytosis‐like internalisation. Here, we uncovered a new host cell invasion principle on the basis of Lpl‐Hsp90 interaction.     

Combined ipilimumab and nivolumab first‐line and after BRAF‐targeted therapy in advanced melanoma

The combination of ipilimumab and nivolumab is a highly active systemic therapy for metastatic melanoma but can cause significant toxicity. We explore the safety and efficacy of this treatment in routine clinical practice, particularly in the setting of serine/threonine‐protein kinase B‐Raf (BRAF)‐targeted therapy. Consecutive patients with unresectable stage IIIC/IV melanoma commenced on ipilimumab and nivolumab across 10 tertiary melanoma institutions in Australia were identified retrospectively. Data collected included demographics, response and survival outcomes. A total of 152 patients were included for analysis, 39% were treatment‐naïve and 22% failed first‐line BRAF/MEK inhibitors. Treatment‐related adverse events occurred in 67% of patients, grade 3–5 in 38%. The overall objective response rate was 41%, 57% in treatment‐naïve and 21% in BRAF/MEK failure patients. Median progression‐free survival was 4.0 months (95% CI, 3.0–6.0) in the whole cohort, 11.0 months (95% CI, 6.0‐NR) in treatment‐naïve and 2.0 months (95% CI, 1.4–4.6) in BRAF/MEK failure patients. The combination of ipilimumab and nivolumab can be used safely and effectively in a real‐world population. While first‐line efficacy appears comparable to trial populations, BRAF‐mutant patients failing prior BRAF/MEK inhibitors show less response.     

Genetic basis of kernel nutritional traits during maize domestication and improvement

The nutritional traits of maize kernels are important for human and animal nutrition, and these traits have undergone selection to meet the diverse nutritional needs of humans. However, our knowledge of the genetic basis of selecting for kernel nutritional traits is limited. Here, we identified both single and epistatic quantitative trait loci (QTLs) that contributed to the differences of oil and carotenoid traits between maize and teosinte. Over half of teosinte alleles of single QTLs increased the values of the detected oil and carotenoid traits. Based on the pleiotropism or linkage information of the identified single QTLs, we constructed a trait–locus network to help clarify the genetic basis of correlations among oil and carotenoid traits. Furthermore, the selection features and evolutionary trajectories of the genes or loci underlying variations in oil and carotenoid traits revealed that these nutritional traits produced diverse selection events during maize domestication and improvement. To illustrate more, a mutator distance–relative transposable element (TE) in intron 1 of DXS2, which encoded a rate‐limiting enzyme in the methylerythritol phosphate pathway, was identified to increase carotenoid biosynthesis by enhancing DXS2 expression. This TE occurs in the grass teosinte, and has been found to have undergone selection during maize domestication and improvement, and is almost fixed in yellow maize. Our findings not only provide important insights into evolutionary changes in nutritional traits, but also highlight the feasibility of reintroducing back into commercial agricultural germplasm those nutritionally important genes hidden in wild relatives.