Detection of prostate cancer in unselected young men: prospective cohort nested within a randomised controlled trial

Objective To investigate the feasibility of testing for prostate cancer and the prevalence and characteristics of the disease in unselected young men.Design Prospective cohort nested within a randomised controlled trial, with two years of follow-up.Setting Eight general practices in a UK city.Participants 1299 unselected men aged 45-49.Intervention Prostate biopsies for participants with a prostate specific antigen level of 1.5 ng/ml or more and the possibility of randomisation to three treatments for those with localised prostate cancer.Main outcome measures Uptake of testing for prostate specific antigen; positive predictive value of prostate specific antigen; and prevalence of prostate cancer, TNM disease stage, and histological grade (Gleason score).Results 442 of 1299 men agreed to be tested for prostate specific antigen (34%) and 54 (12%) had a raised level. The positive predictive value for prostate specific antigen was 21.3%. Ten cases of prostate cancer were detected (2.3%) with eight having at least two positive results in biopsy cores and three showing perineural invasion. One tumour was of high volume (cT2c), Gleason score 7, with a positive result on digital rectal examination; nine tumours were cT1c, Gleason score 6, and eight had a negative result on digital rectal examination. Five of the nine eligible participants (55%) agreed to be randomised. No biochemical disease progression in the form of a rising prostate specific antigen level occurred in two years of follow-up.Conclusions Men younger than 50 will accept testing for prostate cancer but at a much lower rate than older men. Using an age based threshold of 1.5 ng/ml, the prevalence of prostate cancer was similar to that in older men (3.0 ng/ml threshold) and some cancers of potential clinical significance were found.Trial registration Current Controlled Trials ISRCTN20141297     

Control of Early Theiler's Murine Encephalomyelitis Virus Replication in Macrophages by Interleukin-6 Occurs in Conjunction with STAT1 Activation and Nitric Oxide Production

During Theiler's murine encephalomyelitis virus (TMEV) infection of macrophages, it is thought that high interleukin-6 (IL-6) levels contribute to the demyelinating disease found in chronically infected SJL/J mice but absent in B10.S mice capable of clearing the infection. Therefore, IL-6 expression was measured in TMEV-susceptible SJL/J and TMEV-resistant B10.S macrophages during their infection with TMEV DA strain or responses to lipopolysaccharide (LPS) or poly(I · C). Unexpectedly, IL-6 production was greater in B10.S macrophages than SJL/J macrophages during the first 24 h after stimulation with TMEV, LPS, or poly(I · C). Further experiments showed that in B10.S, SJL/J, and RAW264.7 macrophage cells, IL-6 expression was dependent on extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) and enhanced by exogenous IL-12. In SJL/J and RAW264.7 macrophages, exogenous IL-6 resulted in decreased TMEV replication, earlier activation of STAT1 and STAT3, production of nitric oxide, and earlier upregulation of several antiviral genes downstream of STAT1. However, neither inhibition of IL-6-induced nitric oxide nor knockdown of STAT1 diminished the early antiviral effect of exogenous IL-6. In addition, neutralization of endogenous IL-6 from SJL/J macrophages with Fab antibodies did not exacerbate early TMEV infection. Therefore, endogenous IL-6 expression after TMEV infection is dependent on ERK MAPK, enhanced by IL-12, but too slow to decrease viral replication during early infection. In contrast, exogenous IL-6 enhances macrophage control of TMEV infection through preemptive antiviral nitric oxide production and antiviral STAT1 activation. These results indicate that immediate-early production of IL-6 could protect macrophages from TMEV infection.     

Two sympatric Byrsonima species (Malpighiaceae) differ in phenological and reproductive patterns

Sympatric and taxonomically related species may present pre- and/or postzygotic mechanisms for reproductive isolation. We compared the phenology and reproductive biology of Byrsonima intermedia and B. pachyphylla, two sympatric Malpighiaceae species, growing in a remnant of Cerrado in Central Brazil. Both species are evergreens and do not have an overlapping flowering period. In both species, dispersal occurs during the rainy season with low and intermediate overlap in the production of immature and mature fruits, respectively. Both species exhibit self-incompatibility (SI), or, in the case of B. intermedia, facultative SI, and, hence, depend on pollinators to compensate for the lack of spontaneous self-pollination. The flowers of the Byrsonima species were visited by fifteen species of bees that collected pollen and/or oil. Based on their more appropriate intrafloral posture, Epicharis flava and Centris varia were the main pollinators of both species, presenting more frequent visits and/or exhibiting trapline foraging behavior, tending to promote outcrossing. Temporal variation in flowering period and total or partial self-incompatibility seem to function as prezygotic isolation mechanisms that form barriers to gene flow between the studied species and probably avoid competition among pollinators. Both species make oil and pollen available to flower visitors and pollinators almost the entire year, but since Byrsonima intermedia has a long flowering time and is very abundant in the study area, it seems to be more important in maintaining flower-visiting bees.     

Photoperiodism and seasonality in neotropical population of Plutella xylostella L. (Lepidoptera: Yponomeutidae)

Neotropical populations of the diamondback moth Plutella xylostella L. have seasonal cycles of growth and decrease, and moth migration plays a fundamental role in generating such population dynamics. Since the oscillation of these populations is predictable, photoperiod might operate as a signal that triggers the migratory behaviour of the insect. Migration in insects is usually preceded by reproductive diapause, a photoperiodic response that can be characterised by morphological, physiological and behavioural alterations that permit to discriminate between migratory and non-migratory forms. In this study, I tested whether the pre-imaginal and reproductive development of P. xylostella from Minas Gerais (Brazil) is affected by artificial day-lengths that are equivalent to the periods of natural population growth or decrease. No evidence of photoperiodic response was found for the insect reared in laboratory on five different constant photoperiods, from 8h to 16h of light per day. There was no significant variation in survival and duration of egg, larva, and pupa stages or in pupal weight, adult size (forewing length), fecundity, and longevity. Although some species have geographically distinct photoperiodic responses, previous assumptions that cosmopolitan P. xylostella responds to photoperiod in temperate regions was questioned. Migratory and population seasonality among neotropical populations of P. xylostella certainly occurs independently of the photoperiodic announcement of seasonal changes in habitat quality.     

Neuromuscular action of venom from the South American colubrid snake Philodryas patagoniensis

Snakes of the opisthoglyphous genus Philodryas are widespread in South America and cause most bites by colubrids in this region. In this study, we examined the neurotoxic and myotoxic effects of venom from Philodryas patagoniensis in biventer cervicis and phrenic nerve-diaphragm preparations and we compared the biochemical activities of venoms from P. patagoniensis and Philodryas olfersii. Philodryas patagoniensis venom (40 microg/mL) had no effect on mouse phrenic nerve-diaphragm preparations but caused time-dependent neuromuscular blockade of chick biventer cervicis preparations. This blockade was not reversed by washing. The highest concentration of venom tested (40 microg/mL) significantly reduced (p<0.05) the contractures to exogenous acetylcholine (55 microM and 110 microM) and K(+) (13.4 mM) after 120 min; lower concentrations of venom had no consistent or significant effect on these responses. Venom caused a concentration- and time-dependent release of creatine kinase (CK) from biventer cervicis preparations. Histological analysis showed contracted muscle fibers at low venom concentrations and myonecrosis at high concentrations. Philodryas venoms had low esterase and phospholipase A(2) but high proteolytic activities compared to the pitviper Bothrops jararaca. SDS-PAGE showed that the Philodryas venoms had similar electrophoretic profiles, with most proteins having a molecular mass of 25-80 kDa. Both of the Philodryas venoms cross-reacted with bothropic antivenom in ELISA, indicating the presence of proteins immunologically related to Bothrops venoms. RP-HPLC of P. patagoniensis venom yielded four major peaks, each of which contained several proteins, as shown by SDS-PAGE. These results indicate that P. patagoniensis venom has neurotoxic and myotoxic components that may contribute to the effects of envenoming by this species.     

Dust and ammonia in horse stalls with different ventilation rates and bedding

Airborne particles and ammonia were monitored in horse stalls managed under four conditions. Two ventilation rates, high (27 air changes per h) and low (5 air changes per h) and two bedding types, paper and straw, were employed. At both ventilation rates, the number of airborne particles generated while the stalls were mucked out was higher with straw than with paper. Particles were more efficiently cleared at the higher ventilation rate in both the straw and paper stalls. Ammonia measurements reflected an accumulation over time. In the stalls with low ventilation, ammonia levels were significantly higher than in those stalls with high ventilation regardless of bedding type. Management decisions and their relationships to respiratory disorders are discussed.     

Actin deficiency induces cofilin phosphorylation: proteome analysis of HeLa cells after beta-actin gene silencing

Actin-binding proteins regulate the dynamic structure and function of actin filaments in the cell. Much is known about how manipulation of the actin-binding proteins affects the structure and function of actin filaments; however, little is known about how manipulation of actin in the cell affects actin-binding proteins. We addressed this question by utilizing two technologies: RNA interference and 2-dimensional gel electrophoresis. We knocked down beta-actin expression in HeLa cells using short interfering RNA and applied 2-DGE to examine alterations in the HeLa cell proteome. We revealed a 2-5 fold increases of four protein spots on 2-D gels and identified these proteins by mass spectrometry. Three of the four proteins were actin-binding proteins, including cofilin, which promotes both disassembly and assembly of actin filaments but becomes inactivated when phosphorylated. Further examination revealed that the cofilin total protein level barely increased, but the phosphorylated cofilin level increased dramatically in HeLa cells after beta-actin siRNA treatment. These results suggest that in response to siRNA-induced beta-actin deficiency HeLa cells inactivate cofilin by phosphorylation rather than down-regulate its protein expression level. This study also demonstrates that the combination of RNA interference and 2-dimensional gel electrophoresis technologies provides a valuable method to study protein interactions in a specific cellular pathway.