Strong plasmonic fluorescence enhancement of individual plant light-harvesting complexes

Plasmonic coupling of metallic nanoparticles and adjacent pigments can dramatically increase the brightness of the pigments due to the enhanced local electric field. Here, we demonstrate that the fluorescence brightness of a single plant light-harvesting complex (LHCII) can be significantly enhanced when coupled to single gold nanorods (AuNRs). The AuNRs utilized in this study were prepared via chemical reactions, and the hybrid system was constructed using a simple and economical spin-assisted layer-by-layer technique. Enhancement of fluorescence brightness of up to 240-fold was observed, accompanied by a 109-fold decrease in the average (amplitude-weighted) fluorescence lifetime from approximately 3.5 ns down to 32 ps, corresponding to an excitation enhancement of 63-fold and emission enhancement of up to 3.8-fold. This large enhancement is due to the strong spectral overlap of the longitudinal localized surface plasmon resonance of the utilized AuNRs and the absorption or emission bands of LHCII. This study provides an inexpensive strategy to explore the fluorescence dynamics of weakly emitting photosynthetic light-harvesting complexes at the single molecule level.Comment: 23 pages, 6 figures, 2 supplementary figures, and supplementary equation

Social Needs and Happiness:A Life Course Perspective

Both the fulfilment of affection, status, and behavioral confirmation needs and their role in happiness may differ along the adult lifespan. We examined age-graded differences in (a) the fulfilment of the need for affection, status, and behavioral confirmation, (b) disharmonious profiles of need fulfillment (e.g., high affection but low status), and (c) the associations between these needs and happiness. Data from 11,406 Dutch respondents (age range 18–87 (M = 44.82, SD = 14.62), 67% female) were collected via hoegekis.nl and categorized over six age groups (early, young, middle-aged and late adults, young-old and oldest-old). Age-graded differences in social need fulfilment and their link to happiness were examined using regression analyses. Need fulfillment profiles were identified with LCA cluster analyses. Age-graded differences in social need fulfilment were virtually absent (Cohen’s d = 0.20 or smaller) and their link with happiness was stable across the age groups. Social need fulfilment profiles were harmonious as people reported either low, middle, or high need fulfilment in general, irrespective of age. The idea that different social needs are more important in different phases of adult life received only weak support in our data. No strategic investment in specific social needs was observed (no substitution-effects).People typically differed in their capacities to fulfil their affection, status, and behavioral confirmation needs in general, regardless of age. The implications of these results for the social production function theory of wellbeing and socioemotional selectivity theory are outlined in the discussion

Investigations of mechanisms of microbial enhanced oil recovery by microbes and their metabolic products

Experiments at NIPER have demonstrated that oil mobilization by microbial formulations is not merely the result of the effects of the metabolic products from the in situ fermentation of nutrient. A combination of two microorganisms, Bacillus licheniformis, NIPER and a Clostridium species (NIPER 6) was determined to be an effective microbial formulation for the recovery of residual crude oil in porous media. Flask tests with various nutrients and environmental conditions were used to evaluate the growth and metabolite production of NIPER 1 and 6. Several interfacial tension (IFT) measurements were conducted using certain metabolic products from the combined microbial cultures NIPER 1 and NIPER 6. Nonane was used as the oil for these experiments, since crude oil from Delaware-Childers field emulsifies very easily. The IFT of a selected microbial formulation were measured with two different crude oils using brines of varying salinities. Comparisons were made with saline brines containing only the nutrient and with microbial metabolite solutions from which the active cells have been removed by filtration to isolate the specific effects of the microbial cells. Etched-glass micromodel studies showed that the microbial formulation effectively mobilized crude oil trapped after waterflooding. Wettability alteration and unsteady-state relative permeability tests were performed in Berea Sandstone cores. 16 refs., 17 figs., 12 tabs

PR3-ANCA:a promising biomarker in primary sclerosing cholangitis (PSC)

BACKGROUND AND AIMS:The only recognized biomarker for primary sclerosing cholangitis (PSC) is atypical anti-neutrophil cytoplasmic antibodies (aANCA), which, in addition to having low sensitivity and specificity, is an indirect immunofluorescence (IIF) test lacking the advantages of high throughput and objectivity. Recent reports have shown that antibodies to proteinase-3 (PR3-ANCA) might add diagnostic value in inflammatory bowel disease (IBD), specifically in ulcerative colitis (UC). As PSC is associated with IBD, the objective of this study was to evaluate the frequency and clinical significance of PR3-ANCA in a large cohort of patients. METHODS:A total of 244 PSC and 254 control [autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), hepatitis C viral infection (HCV), hepatitis B viral infection (HBV), and healthy controls] sera and their clinical correlations were retrospectively analyzed for PR3-ANCA determined by ELISA and a new chemiluminescence immunoassay (CIA). Testing was also performed for aANCA by IIF. RESULTS:When measured by CIA, PR3-ANCA was detected in 38.5% (94/244) of PSC patients compared to 10.6% (27/254) controls (p<0.0001). By ELISA, PR3-ANCA was detected in 23.4% (57/244) of PSC patients compared to 2.7% (6/254) controls (p<0.0001). PR3-ANCA in PSC patients was not associated with the presence or type of underlying IBD, and, in fact, it was more frequent in Crohn's disease (CD) patients with PSC than previously reported in CD alone. PR3-ANCA in PSC measured by CIA correlated with higher liver enzymes. CONCLUSION:PR3-ANCA is detected in a significant proportion of PSC patients compared to other liver diseases including PBC and AIH. PR3-ANCA is associated with higher liver enzyme levels in PSC, and is not solely related to underlying IBD

Small intestinal CD103+ dendritic cells display unique functional properties that are conserved between mice and humans

A functionally distinct subset of CD103+ dendritic cells (DCs) has recently been identified in murine mesenteric lymph nodes (MLN) that induces enhanced FoxP3+ T cell differentiation, retinoic acid receptor signaling, and gut-homing receptor (CCR9 and α4β7) expression in responding T cells. We show that this function is specific to small intestinal lamina propria (SI-LP) and MLN CD103+ DCs. CD103+ SI-LP DCs appeared to derive from circulating DC precursors that continually seed the SI-LP. BrdU pulse-chase experiments suggested that most CD103+ DCs do not derive from a CD103− SI-LP DC intermediate. The majority of CD103+ MLN DCs appear to represent a tissue-derived migratory population that plays a central role in presenting orally derived soluble antigen to CD8+ and CD4+ T cells. In contrast, most CD103− MLN DCs appear to derive from blood precursors, and these cells could proliferate within the MLN and present systemic soluble antigen. Critically, CD103+ DCs with similar phenotype and functional properties were present in human MLN, and their selective ability to induce CCR9 was maintained by CD103+ MLN DCs isolated from SB Crohn's patients. Thus, small intestinal CD103+ DCs represent a potential novel target for regulating human intestinal inflammatory responses

The PKC, HOG and Ca2+ signalling pathways co-ordinately regulate chitin synthesis in Candida albicans

Open Access via PMC2649417Peer reviewedPublisher PD

The NOD2-Smoking Interaction in Crohn's Disease is likely Specific to the 1007fs Mutation and may be Explained by Age at Diagnosis:A Meta-Analysis and Case-Only Study

Background: NOD2 and smoking are risk factors for Crohn's disease. We meta-analyzed NOD2-smoking interactions in Crohn's disease (Phase 1), then explored the effect of age at diagnosis on NOD2-smoking interactions (Phase 2). Methods: Phase 1: MEDLINE and EMBASE were searched for studies (n = 18) providing data on NOD2 and smoking in Crohn's disease. NOD2-smoking interactions were estimated using odds ratios (ORs) and 95% confidence intervals (CIs) calculated using random effects models. Phase 2: A case-only study compared the proportion of smokers and carriers of the 1007 fs variant across ages at diagnosis (≤16, 17–40, >40 years). Findings: Phase 1: Having ever smoked was less common among carriers of the 1007 fs variant of NOD2 (OR 0.74, 95%CI:0.66–0.83). There was no interaction between smoking and the G908R (OR 0.96, 95%CI:0.82–1.13) or the R702W variant (OR 0.89, 95%CI:0.76–1.05). Phase 2: The proportion of patients (n = 627) carrying the 1007 fs variant decreased with age at diagnosis (≤16 years: 15%; 17–40: 12%; >40: 3%; p = 0.003). Smoking was more common in older patients (≤16 years: 4%; 17–40: 48%; >40: 71%; p < 0.001). Interpretation: The negative NOD2-smoking interaction in Crohn's disease is specific to the 1007 fs variant. However, opposing rates of this variant and smoking across age at diagnosis may explain this negative interaction

Safety, tolerability, and efficacy of maralixibat in adults with primary sclerosing cholangitis: Open-label pilot study

BACKGROUND: Primary sclerosing cholangitis (PSC) is frequently associated with pruritus, which significantly impairs quality of life. Maralixibat is a selective ileal bile acid transporter (IBAT) inhibitor that lowers circulating bile acid (BA) levels and reduces pruritus in cholestatic liver diseases. This is the first proof-of-concept study of IBAT inhibition in PSC. METHODS: This open-label study evaluated the safety and tolerability of maralixibat ≤10 mg/d for 14 weeks in adults with PSC. Measures of pruritus, biomarkers of BA synthesis, cholestasis, and liver function were also assessed. RESULTS: Of 27 enrolled participants, 85.2% completed treatment. Gastrointestinal treatment-emergent adverse events (TEAEs) occurred in 81.5%, with diarrhea in 51.9%. TEAEs were mostly mild or moderate (63.0%); 1 serious TEAE (cholangitis) was considered treatment related. Mean serum BA (sBA) levels decreased by 16.7% (-14.84 µmol/L; 95% CI, -27.25 to -2.43; p = 0.0043) by week 14/early termination (ET). In participants with baseline sBA levels above normal (n = 18), mean sBA decreased by 40.0% (-22.3 µmol/L, 95% CI, -40.38 to -4.3; p = 0.004) by week 14/ET. Liver enzyme elevations were not significant; however, increases of unknown clinical significance in conjugated bilirubin levels were observed. ItchRO weekly sum scores decreased from baseline to week 14/ET by 8.4% (p = 0.0495), by 12.6% (p = 0.0275) in 18 participants with pruritus at baseline, and by 70% (p = 0.0078) in 8 participants with ItchRO daily average score ≥3 at baseline. CONCLUSIONS: Maralixibat was associated with reduced sBA levels in adults with PSC. In participants with more severe baseline pruritus, pruritus improved significantly from baseline. TEAEs were mostly gastrointestinal related. These results support further investigation of IBAT inhibitors for adults with PSC-associated pruritus. ClinicalTrials.gov: NCT02061540

The Nonsteroidal Farnesoid X Receptor Agonist Cilofexor (GS-9674) Improves Markers of Cholestasis and Liver Injury in Patients With Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) represents a major unmet medical need. In a phase II double-blind, placebo-controlled study, we tested the safety and efficacy of cilofexor (formerly GS-9674), a nonsteroidal farnesoid X receptor agonist in patients without cirrhosis with large-duct PSC. Patients were randomized to receive cilofexor 100 mg (n = 22), 30 mg (n = 20), or placebo (n = 10) orally once daily for 12 weeks. All patients had serum alkaline phosphatase (ALP) > 1.67 × upper limit of normal and total bilirubin ≤ 2 mg/dL at baseline. Safety, tolerability, pharmacodynamic effects of cilofexor (serum C4 [7α-hydroxy-4-cholesten-3-one] and bile acids), and changes in liver biochemistry and serum fibrosis markers were evaluated. Overall, 52 patients were randomized (median age 43 years, 58% male, 60% with inflammatory bowel disease, 46% on ursodeoxycholic acid). Baseline median serum ALP and bilirubin were 348 U/L (interquartile range 288-439) and 0.7 mg/dL (0.5-1.0), respectively. Dose-dependent reductions in liver biochemistry were observed. At week 12, cilofexor 100 mg led to significant reductions in serum ALP (median reduction -21%; P = 0.029 versus placebo), gamma-glutamyl transferase (-30%; P < 0.001), alanine aminotransferase (ALT) (-49%; P = 0.009), and aspartate aminotransferase (-42%; P = 0.019). Cilofexor reduced serum C4 compared with placebo; reductions in bile acids were greatest with 100 mg. Relative reductions in ALP were similar between ursodeoxycholic acid-treated and untreated patients. At week 12, cilofexor-treated patients with a 25% or more relative reduction in ALP had greater reductions in serum alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, tissue inhibitor of metalloproteinase 1, C-reactive protein, and bile acids than nonresponders. Adverse events were similar between cilofexor and placebo-treated patients. Rates of grade 2 or 3 pruritus were 14% with 100 mg, 20% with 30 mg, and 40% with placebo. Conclusion: In this 12-week, randomized, placebo-controlled study, cilofexor was well tolerated and led to significant improvements in liver biochemistries and markers of cholestasis in patients with PSC