The chloroplast RNA helicase ISE2 is required for multiple chloroplast RNA processing steps in Arabidopsis thaliana

INCREASED SIZE EXCLUSION LIMIT2 (ISE2) is a chloroplast-localized RNA helicase that is indispensable for proper plant development. Chloroplasts in leaves with reduced ISE2expression have previously been shown to exhibit reduced thylakoid contents and increased stromal volume, indicative of defective development. It has recently been reported that ISE2 is required for the splicing of group II introns from chloroplast transcripts. The current study extends these findings, and presents evidence for ISE2’s role in multiple aspects of chloroplast RNA processing beyond group II intron splicing. Loss of ISE2 from Arabidopsis thaliana leaves resulted in defects in C-to-U RNA editing, altered accumulation of chloroplast transcripts and chloroplast-encoded proteins, and defective processing of chloroplast ribosomal RNAs. Potential ISE2 substrates were identified by RNA immunoprecipitation followed by next-generation sequencing (RIP-seq), and the diversity of RNA species identified supports ISE2’s involvement in multiple aspects of chloroplast RNA metabolism. Comprehensive phylogenetic analyses revealed that ISE2 is a non-canonical Ski2-like RNA helicase that represents a separate sub-clade unique to green photosynthetic organisms, consistent with its function as an essential protein. Thus ISE2’s evolutionary conservation may be explained by its numerous roles in regulating chloroplast gene expression

Triplet exciton diffusion and phosphorescence quenching in Iridium(III)-Centered dendrimers

A study of triplet-triplet exciton annihilation and nonradiative decay in films of iridium(III)-centered phosphorescent dendrimers is reported. The average separation of the chromophore was tuned by the molecular structure and also by blending with a host material. It was found that triplet exciton hopping is controlled by electron exchange interactions and can be over 600 times faster than phosphorescence quenching. Nonradiative decay occurs by weak dipole-dipole interactions and is independent of exciton diffusion, except in very thin films

A novel fragment derived from the β chain of human fibrinogen, β43–63, is a potent inhibitor of activated endothelial cells in vitro and in vivo

Background: Angiogenesis and haemostasis are closely linked within tumours with many haemostatic proteins regulating tumour angiogenesis. Indeed we previously identified a fragment of human fibrinogen, fibrinogen E-fragment (FgnE) with potent anti-angiogenic properties in vitro and cytotoxic effects on tumour vessels in vivo. We therefore investigated which region of FgnE was mediating vessel cytotoxicity. Methods: Human dermal microvascular endothelial cells (ECs) were used to test the efficacy of peptides derived from FgnE on proliferation, migration, differentiation, apoptosis and adhesion before testing the efficacy of an active peptide on tumour vasculature in vivo. Results: We identified a 20-amino-acid peptide derived from the β chain of FgnE, β43–63, which had no effect on EC proliferation or migration but markedly inhibited the ability of activated ECs to form tubules or to adhere to various constituents of the extracellular matrix – collagen IV, fibronectin and vitronectin. Furthermore, our data show that β43–63 interacts with ECs, in part, by binding to αvβ3, so soluble αvβ3 abrogated β43–63 inhibition of tubule formation by activated ECs. Finally, when injected into mice bearing tumour xenografts, β43–63 inhibited tumour vascularisation and induced formation of significant tumour necrosis. Conclusions: Taken together, these data suggest that β43–63 is a novel anti-tumour peptide whose anti-angiogenic effects are mediated by αvβ3

Genetic Background Can Result in a Marked or Minimal Effect of Gene Knockout (GPR55 and CB2 Receptor) in Experimental Autoimmune Encephalomyelitis Models of Multiple Sclerosis

PMCID: PMC379391

Loved Ones Near and Far: Feinberg's Personal Significance Theory

This paper examines Todd Feinberg's theory of the misidentification syndromes

Mobilizing Crop Biodiversity

Over the past 70 years, the world has witnessed extraordinary growth in crop productivity, 1 enabled by a suite of technological advances, including higher yielding crop varieties, improved farm management, synthetic agrochemicals, and agricultural mechanization. While this “Green Revolution” intensified crop production, and is credited with reducing famine and malnutrition, its benefits were accompanied by several undesirable collateral effects (Pingali, 2012). These include a narrowing of agricultural biodiversity, stemming from increased monoculture and greater reliance on a smaller number of crops and crop varieties for the majority of our calories. This reduction in diversity has created vulnerabilities to pest and disease epidemics, climate variation, and ultimately to human health (Harlan, 1972). The value of crop diversity has long been recognized (Vavilov, 1992). A global system of genebanks (e.g.www.genebanks.org/genebanks/) was established in the 1970s to preserve the abundant genetic variation found in traditional “landrace” varieties of crops and in crop wild relatives (Harlan, 1972). While preserving crop variation is a critical first step, the time has come to make use of this variation to breed more resilient crops. The DivSeek International Network (https://divseekintl.org/) is a scientific, not-for profit organization that aims to accelerate such effort

Angiogenesis is associated with the onset of hyperplasia in human ductal breast disease

BACKGROUND: The precise timing of the angiogenic switch and the role of angiogenesis in the development of breast malignancy is currently unknown. METHODS: Therefore, the expression of CD31 (pan endothelial cells (ECs)), endoglin (actively proliferating ECs), hypoxia-inducible factor-1 (HIF-1alpha), vascular endothelial growth factor-A (VEGF) and tissue factor (TF) were quantified in 140 surgical specimens comprising normal human breast, benign and pre-malignant hyperplastic tissue, in situ and invasive breast cancer specimens. RESULTS: Significant increases in angiogenesis (microvessel density) were observed between normal and benign hyperplastic breast tissue (P<0.005), and between in situ and invasive carcinomas (P<0.0005). In addition, significant increases in proliferating ECs were observed in benign hyperplastic breast compared with normal breast (P<0.05) cancers and in invasive compared with in situ cancers (P<0.005). Hypoxia-inducible factor-1alpha, VEGF and TF expression were significantly associated with increases in both angiogenesis and proliferating ECs (P<0.05). Moreover, HIF-1alpha was expressed by 60-75% of the hyperplastic lesions, and a significant association was observed between VEGF and TF in ECs (P<0.005) and invasive tumour cells (P<0.01). CONCLUSIONS: These findings are the first to suggest that the angiogenic switch, associated with increases in HIF-1alpha, VEGF and TF expression, occurs at the onset of hyperplasia in the mammary duct, although the greatest increase in angiogenesis occurs with the development of invasion

Mechanisms of pulmonary dysfunction after on-pump and off-pump cardiac surgery: a prospective cohort study

BACKGROUND: Pulmonary dysfunction following cardiac surgery is believed to be caused, at least in part, by a lung vascular injury and/or atelectasis following cardiopulmonary bypass (CPB) perfusion and collapse of non-ventilated lungs. METHODS: To test this hypothesis, we studied the postoperative pulmonary leak index (PLI) for (67)Ga-transferrin and (transpulmonary) extravascular lung water (EVLW) in consecutive patients undergoing on-pump (n = 31) and off-pump (n = 8) cardiac surgery. We also studied transfusion history, radiographs, ventilatory and gas exchange variables. RESULTS: The postoperative PLI and EVLW were elevated above normal in 42 and 29% after on-pump surgery and 63 and 37% after off-pump surgery, respectively (ns). Transfusion of red blood cell (RBC) concentrates, PLI, EVLW, occurrence of atelectasis, ventilatory variables and duration of mechanical ventilation did not differ between groups, whereas patients with atelectasis had higher venous admixture and airway pressures than patients without atelectasis (P = 0.037 and 0.049). The PLI related to number of RBC concentrates infused (P = 0.025). CONCLUSION: The lung vascular injury in about half of patients after cardiac surgery is not caused by CPB perfusion but by trauma necessitating RBC transfusion, so that off-pump surgery may not afford a benefit in this respect. However, atelectasis rather than lung vascular injury is a major determinant of postoperative pulmonary dysfunction, irrespective of CPB perfusion

Alcohol use and extramarital sex among men in Cameroon

<p>Abstract</p> <p>Background</p> <p>The spread of HIV in sub-Saharan Africa is believed to be driven by unsafe sex, and identification of modifiable risk factors of the latter is needed for comprehensive HIV prevention programming in the region. Some previous studies suggest an association between alcohol abuse and unsafe sexual behaviour, such as multiple concurrent sexual partnerships and inconsistent condom use in sex with non-spousal non-cohabiting partners. However, most of these studies were conducted in developed countries and the few studies in Africa were conducted among well-defined social groups such as men attending beer halls or sexually transmitted infection clinics. We therefore examined the association between alcohol and extramarital sex (a sign of multiple concurrent sexual partnerships) among men in a population-based survey in Cameroon; a low-income country in sub-Saharan Africa with a high rate of alcohol abuse and a generalised HIV epidemic.</p> <p>Methods</p> <p>We analyzed data from 2678 formally married or cohabiting men aged 15 to 59 years, who participated in the 2004 Cameroon Demographic and Health Survey, using a multivariate regression model.</p> <p>Results</p> <p>A quarter of the men (25.8%) declared having taken alcohol before their last sexual intercourse and 21% indicated that the last sex was with a woman other than their wife or cohabiting partner. After controlling for possible confounding by other socio-demographic characteristics, alcohol use was significantly associated with having extramarital sex: adjusted odds ratio (OR) 1.70, 95% confidence intervals (CI) 1.40 to 2.05. Older age (30–44 years: OR 3.06, 95%CI 2.16–4.27 and 45–59 years: OR 4.10, 95%CI 2.16–4.27), higher education (OR 1.25, 95%CI 1.10–1.45), and wealth (OR 1.71, 95%CI 1.50–1.98) were also significantly associated with higher odds of having extramarital sex. The men were more likely to have used a condom in their last sex if it was extramarital (OR 10.50, 95%CI 8.10–13.66). Older age at first sex (16–19 years: OR 0.81, 95%CI 0.72–0.90 and > 19 years: OR 0.74, 95% CI 0.65–0.87) and being the head of a household (OR 0.17, 95%CI 0.14–0.22) significantly decreased the odds of having sex outside of marriage. Religion and place of residence (whether urban or rural) were not significantly associated with extramarital sex.</p> <p>Conclusion</p> <p>Alcohol use is associated with having multiple concurrent non-spousal sexual partnerships among married men in Cameroon. We cannot infer a causal relationship between alcohol abuse and unsafe sex from this cross-sectional study, as both alcohol use and unsafe sexual behaviour may have a common set of causal personal and social factors. However, given the consistency with results of studies in other settings and the biologic plausibility of the link between alcohol intake and unsafe sex, our findings underscore the need for integrating alcohol abuse and HIV prevention efforts in Cameroon and other African countries with similar social profiles.</p