41 research outputs found

    The Control of Carbon Translocation in a Sea Anemone-Dinoflagellate Symbiosis from New Zealand

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    Anthopleura aureoradiata, a common sea anemone of New Zealand's intertidal mudflats and rocky shores, hosts symbiotic dinoflagellates of the genus Symbiodinium. This study investigated the control of photosynthetic carbon translocation in this symbiosis, and in particular the presence and operation of socalled 'host release factor' (HRF). Evidence for HRF exists in a number other algalinvertebrate symbioses, where tissue extracts of the host stimulate carbon release by isolated algal symbionts. However, its identity remains elusive and it has never been studied before in A. aureoradiata. Translocation of photosynthetically-fixed carbon in the intact symbiosis and in the presence of host tissue extract was measured using a 14C label. Zooxanthellae in the intact symbiosis released around 40% of their photosynthetically-fixed carbon to the anemone. Isolated zooxanthellae, however, translocated only 8%, even less than the amount of photosynthate liberated by zooxanthellae in FSW alone (11%). Photosynthetic rates per algal cell were similar in the intact symbiosis and both host homogenate and FSW incubations, meaning that the total amount of photosynthetically-fixed carbon released (in pg C/cell/h) by the zooxanthellae in these different situations reflected the %translocation values. Given the failure of homologous zooxanthellae (i.e. those from A. aureoradiata) to respond to homogenized host tissue, it was tested whether zooxanthellae from other host species (i.e. cultured heterologous algae) responded. Heterologous zooxanthellae representing 5 clades (A-E) of Symbiodinium were incubated in host tissue homogenate and photosynthate release again measured with 14C. The %translocation varied from 12-51% in A. aureoradiata homogenate and 17-67% in FSW, again suggesting a lack of an active HRF in the homogenized tissues of this sea anemone. Photosynthetic rates amongst the different heterologous algae also varied widely with, for instance, freshly isolated zooxanthellae from A. aureoradiata having 6-fold higher photosynthetic rates than cultured algae from the same clade (clade A). The zooxanthellae of A. aureoradiata are known to be N-sufficient in the field, and studies with other species have demonstrated that N-deficient zooxanthellae release more photosynthate in response to HRF than do N-sufficient ones. Therefore, induction of an HRF effect was attempted by starving sea anemones, and hence their zooxanthellae, prior to incubation of freshly isolated zooxanthellae in homogenized tissue. However, even after 8 weeks of starvation, the zooxanthellae showed no signs of N-deficiency (as indicated by the extent to which ammonium enhanced the rate of dark 14C fixation), meaning that the relationship with HRF activity could not be examined. The ability of these temperate zooxanthellae to maintain their Nsufficiency, even after relatively long periods of food deprivation, may indicate a lower reliance on host feeding for nitrogen than is seen in tropical zooxanthellae, or a greater capacity to use internal stores of nitrogen. The lack of photosynthate release by both homologous and heterologous zooxanthellae in host homogenate, as opposed to substantial carbon released in the intact symbiosis, suggests that control of carbon translocation in A. aureoradiata is not related to the activity of an HRF; alternatively, if an HRF is present, its activity is hindered when the symbiosis is disrupted. Further study is needed to determine what is responsible for the control of photosynthate translocation in the A. aureoradiata-Symbiodinium symbiosis

    Do cravings predict smoking cessation in smokers calling a national quit line: secondary analyses from a randomised trial for the utility of ‘urges to smoke’ measures

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    BACKGROUND: Single-item urges to smoke measures have been contemplated as important measures of nicotine dependence This study aimed to prospectively determine the relationships between measures of craving to smoke and smoking cessation, and compare their ability to predict cessation with the Heaviness of Smoking Index, an established measure of nicotine dependence. METHODS: We conducted a secondary analysis of data from the randomised controlled PORTSSS trial. Measures of nicotine dependence, ascertained before making a quit attempt, were the HSI, frequency of urges to smoke (FUTS) and strength of urges to smoke (SUTS). Self-reported abstinence at six months after quitting was the primary outcome measure. Multivariate logistic regression and Receiver Operating Characteristic (ROC) analysis were used to assess associations and abilities of the nicotine dependence measures to predict smoking cessation. RESULTS: Of 2,535 participants, 53.5% were female; the median (Interquartile range) age was 38 (28–50) years. Both FUTS and HSI were inversely associated with abstinence six months after quitting; for each point increase in HSI score, participants were 16% less likely to have stopped smoking (OR 0.84, 95% C.I 0.78-0.89, p < 0.0001). Compared to participants with the lowest possible FUTS scores, those with greater scores had generally lower odds of cessation (p across frequency of urges categories=0.0026). SUTS was not associated with smoking cessation. ROC analysis suggested the HSI and FUTS had similar predictive validity for cessation. CONCLUSIONS: Higher FUTS and HSI scores were inversely associated with successful smoking cessation six months after quit attempts began and both had similar validity for predicting cessation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13011-015-0011-8) contains supplementary material, which is available to authorized users

    Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters

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    Transcription of long noncoding RNAs (lncRNAs) within gene regulatory elements can modulate gene activity in response to external stimuli, but the scope and functions of such activity are not known. Here we use an ultrahigh-density array that tiles the promoters of 56 cell-cycle genes to interrogate 108 samples representing diverse perturbations. We identify 216 transcribed regions that encode putative lncRNAs, many with RT-PCR–validated periodic expression during the cell cycle, show altered expression in human cancers and are regulated in expression by specific oncogenic stimuli, stem cell differentiation or DNA damage. DNA damage induces five lncRNAs from the CDKN1A promoter, and one such lncRNA, named PANDA, is induced in a p53-dependent manner. PANDA interacts with the transcription factor NF-YA to limit expression of pro-apoptotic genes; PANDA depletion markedly sensitized human fibroblasts to apoptosis by doxorubicin. These findings suggest potentially widespread roles for promoter lncRNAs in cell-growth control.National Institutes of Health (U.S.)National Institute of Arthritis and Musculoskeletal and Skin Diseases (U.S.) (NIAMS) (K08-AR054615))National Cancer Institute (U.S.) (NIH/(NCI) (R01-CA118750))National Cancer Institute (U.S.) (NIH/(NCI) R01-CA130795))Juvenile Diabetes Research Foundation InternationalAmerican Cancer SocietyHoward Hughes Medical Institute (Early career scientist)Stanford University (Graduate Fellowship)National Science Foundation (U.S.) (Graduate Research Fellowship)United States. Dept. of Defense (National Defense Science and Engineering Graduate Fellowship

    Stimulant Reduction Intervention using Dosed Exercise (STRIDE) - CTN 0037: Study protocol for a randomized controlled trial

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    <p>Abstract</p> <p>Background</p> <p>There is a need for novel approaches to the treatment of stimulant abuse and dependence. Clinical data examining the use of exercise as a treatment for the abuse of nicotine, alcohol, and other substances suggest that exercise may be a beneficial treatment for stimulant abuse, with direct effects on decreased use and craving. In addition, exercise has the potential to improve other health domains that may be adversely affected by stimulant use or its treatment, such as sleep disturbance, cognitive function, mood, weight gain, quality of life, and anhedonia, since it has been shown to improve many of these domains in a number of other clinical disorders. Furthermore, neurobiological evidence provides plausible mechanisms by which exercise could positively affect treatment outcomes. The current manuscript presents the rationale, design considerations, and study design of the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) CTN-0037 Stimulant Reduction Intervention using Dosed Exercise (STRIDE) study.</p> <p>Methods/Design</p> <p>STRIDE is a multisite randomized clinical trial that compares exercise to health education as potential treatments for stimulant abuse or dependence. This study will evaluate individuals diagnosed with stimulant abuse or dependence who are receiving treatment in a residential setting. Three hundred and thirty eligible and interested participants who provide informed consent will be randomized to one of two treatment arms: Vigorous Intensity High Dose Exercise Augmentation (DEI) or Health Education Intervention Augmentation (HEI). Both groups will receive TAU (i.e., usual care). The treatment arms are structured such that the quantity of visits is similar to allow for equivalent contact between groups. In both arms, participants will begin with supervised sessions 3 times per week during the 12-week acute phase of the study. Supervised sessions will be conducted as one-on-one (i.e., individual) sessions, although other participants may be exercising at the same time. Following the 12-week acute phase, participants will begin a 6-month continuation phase during which time they will attend one weekly supervised DEI or HEI session.</p> <p>Clinical Trials Registry</p> <p>ClinicalTrials.gov, <a href="http://www.clinicaltrials.gov/ct2/show/NCT01141608">NCT01141608</a></p> <p><url>http://clinicaltrials.gov/ct2/show/NCT01141608?term=Stimulant+Reduction+Intervention+using+Dosed+Exercise&rank=1</url></p

    The Control of Carbon Translocation in a Sea Anemone-Dinoflagellate Symbiosis from New Zealand

    No full text
    Anthopleura aureoradiata, a common sea anemone of New Zealand's intertidal mudflats and rocky shores, hosts symbiotic dinoflagellates of the genus Symbiodinium. This study investigated the control of photosynthetic carbon translocation in this symbiosis, and in particular the presence and operation of socalled 'host release factor' (HRF). Evidence for HRF exists in a number other algalinvertebrate symbioses, where tissue extracts of the host stimulate carbon release by isolated algal symbionts. However, its identity remains elusive and it has never been studied before in A. aureoradiata. Translocation of photosynthetically-fixed carbon in the intact symbiosis and in the presence of host tissue extract was measured using a 14C label. Zooxanthellae in the intact symbiosis released around 40% of their photosynthetically-fixed carbon to the anemone. Isolated zooxanthellae, however, translocated only 8%, even less than the amount of photosynthate liberated by zooxanthellae in FSW alone (11%). Photosynthetic rates per algal cell were similar in the intact symbiosis and both host homogenate and FSW incubations, meaning that the total amount of photosynthetically-fixed carbon released (in pg C/cell/h) by the zooxanthellae in these different situations reflected the %translocation values. Given the failure of homologous zooxanthellae (i.e. those from A. aureoradiata) to respond to homogenized host tissue, it was tested whether zooxanthellae from other host species (i.e. cultured heterologous algae) responded. Heterologous zooxanthellae representing 5 clades (A-E) of Symbiodinium were incubated in host tissue homogenate and photosynthate release again measured with 14C. The %translocation varied from 12-51% in A. aureoradiata homogenate and 17-67% in FSW, again suggesting a lack of an active HRF in the homogenized tissues of this sea anemone. Photosynthetic rates amongst the different heterologous algae also varied widely with, for instance, freshly isolated zooxanthellae from A. aureoradiata having 6-fold higher photosynthetic rates than cultured algae from the same clade (clade A). The zooxanthellae of A. aureoradiata are known to be N-sufficient in the field, and studies with other species have demonstrated that N-deficient zooxanthellae release more photosynthate in response to HRF than do N-sufficient ones. Therefore, induction of an HRF effect was attempted by starving sea anemones, and hence their zooxanthellae, prior to incubation of freshly isolated zooxanthellae in homogenized tissue. However, even after 8 weeks of starvation, the zooxanthellae showed no signs of N-deficiency (as indicated by the extent to which ammonium enhanced the rate of dark 14C fixation), meaning that the relationship with HRF activity could not be examined. The ability of these temperate zooxanthellae to maintain their Nsufficiency, even after relatively long periods of food deprivation, may indicate a lower reliance on host feeding for nitrogen than is seen in tropical zooxanthellae, or a greater capacity to use internal stores of nitrogen. The lack of photosynthate release by both homologous and heterologous zooxanthellae in host homogenate, as opposed to substantial carbon released in the intact symbiosis, suggests that control of carbon translocation in A. aureoradiata is not related to the activity of an HRF; alternatively, if an HRF is present, its activity is hindered when the symbiosis is disrupted. Further study is needed to determine what is responsible for the control of photosynthate translocation in the A. aureoradiata-Symbiodinium symbiosis.</p

    Pseudomonas aeruginosa-induced nociceptor activation increases susceptibility to infection

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    We report a rapid reduction in blink reflexes during in vivo ocular Pseudomonas aeruginosa infection, which is commonly attributed and indicative of functional neuronal damage. Sensory neurons derived in vitro from trigeminal ganglia (TG) were able to directly respond to P. aeruginosa but reacted significantly less to strains of P. aeruginosa that lacked virulence factors such as pili, flagella, or a type III secretion system. These observations led us to explore the impact of neurons on the host's susceptibility to P. aeruginosa keratitis. Mice were treated with Resiniferatoxin (RTX), a potent activator of Transient Receptor Potential Vanilloid 1 (TRPV1) channels, which significantly ablated corneal sensory neurons, exhibited delayed disease progression that was exemplified with decreased bacterial corneal burdens and altered neutrophil trafficking. Sensitization to disease was due to the increased frequencies of CGRP-induced ICAM-1(+) neutrophils in the infected corneas and reduced neutrophil bactericidal activities. These data showed that sensory neurons regulate corneal neutrophil responses in a tissue-specific matter affecting disease progression during P. aeruginosa keratitis. Hence, therapeutic modalities that control nociception could beneficially impact anti-infective therapy. Author summary Many of the molecular mechanisms behind bacterial keratitis induced nociception activation and specifically, how pathogen-sensing sensory neurons impact the outcome of infection have yet to be discovered, Elucidating the molecular and cellular mechanisms of nociceptor activation during bacterial keratitis can have a profound impact on treatment approaches. In this study, we established that P. aeruginosa can directly induce calcium influx in neurons and this induction is dependent on several virulence factors. Further, we demonstrated that Resiniferatoxin (RTX), a toxin that overactivates TRPV1 channels leading to chemical ablation of neurons, induces significant loss of sensory neurons in the cornea and this improves temporarily local innate responses to P. aeruginosa
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