Unconventional miR-122 binding stabilizes the HCV genome by forming a trimolecular RNA structure.

MicroRNAs (miRNAs) typically downregulate protein expression from target mRNAs through limited base-pairing interactions between the 5' 'seed' region of the miRNA and the mRNA 3' untranslated region (3'UTR). In contrast to this established mode of action, the liver-specific human miR-122 binds at two sites within the hepatitis C viral (HCV) 5'UTR, leading to increased production of infectious virions. We show here that two copies of miR-122 interact with the HCV 5'UTR at partially overlapping positions near the 5' end of the viral transcript to form a stable ternary complex. Both miR-122 binding sites involve extensive base pairing outside of the seed sequence; yet, they have substantially different interaction affinities. Structural probing reveals changes in the architecture of the HCV 5'UTR that occur on interaction with miR-122. In contrast to previous reports, however, results using both the recombinant cytoplasmic exonuclease Xrn1 and liver cell extracts show that miR-122-mediated protection of the HCV RNA from degradation does not correlate with stimulation of viral propagation in vivo. Thus, the miR-122:HCV ternary complex likely functions at other steps critical to the viral life cycle

EFFECTS OF ASPIRATION VERSUS NEUROTOXIC LESIONS OF THE AMYGDALA ON EMOTIONAL RESPONSES IN MONKEYS

All previous reports describing alterations in emotional reactivity after amygdala damage in monkeys were based on aspiration or radiofrequency lesions which likely disrupted fibers of passage coursing to and from adjacent ventral and medial temporal cortical areas. To determine whether this associated indirect damage was responsible for some or all of the changes described earlier, we compared the changes induced by aspiration of the amygdala to those induced by fiber-sparing neurotoxic lesions. Four different stimuli, two with and two without a social component, were used to evaluate the expression of Defense, Aggression, Submission, and Approach responses. In unoperated controls, Defense and Approach behaviors were elicited by all four stimuli, "social" and inanimate alike, whereas Aggression and Submission responses occurred only in the presence of the two "social" stimuli. Furthermore, all Defense reactions were reduced with an attractive inanimate item, while Freezing was selectively increased with an aversive one. Relative to controls, monkeys with neurotoxic amygdala lesions showed the same array of behavioral changes as those with aspiration lesions, namely reduced fear and aggression, increased submission, and excessive manual and oral exploration. Even partial neurotoxic lesions involving less than two-thirds of the amygdala significantly altered fear and manual exploration. These findings convincingly demonstrate that the amygdala is crucial for the normal regulation of emotions in monkeys. Nevertheless, since some of the symptoms observed after neurotoxic lesions were less marked than those seen after aspiration lesions, the emotional disorders described earlier after amygdalectomy in monkeys were likely exacerbated by the attendant fiber damage

Benzo-pyrones for reducing and controlling lymphoedema of the limbs.

Background Lymphoedema is the accumulation of excess fluid in the body caused by obstruction of the lymphatic drainage mechanisms. Treatment with Benzo-pyrones is thought to reduce fluid forming in the subcutaneous tissues and reduce pain and discomfort of the affected area. Objectives To assess the effectiveness of benzo-pyrones compared to placebo in the management of lymphoedema. Search strategy We searched the Cochrane Breast Cancer Group register (September 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4,2003), MEDLINE, EMBASE, CINAHL, UnCover, PASCAL, SIGLE, reference lists produced by The British Lymphology Society, the National Research Register (NRR) and The International Society of Lymphology congress proceedings. Selection criteria Randomised controlled trials comparing Benzo-pyrones with placebo. Data collection and analysis Trials were selected for eligibility and tested for quality by two blinded reviewers who independently extracted data. Meta-analysis was not performed due to the poor quality of the trials. Main results Fifteen trials were included. Three oxerutin trials tested the same dose over 6 months against placebo and included a total of 127 participants (data were available for 81). There were insufficient data from these to calculate the per cent reduction or increase in baseline excess limb volume. One trial testing Cyclo 3 Fort (approved name) was found (57 participants) but insufficient data was provided to allow a proper analysis of its findings. A single trial of Daflon (approved name) was found (104 participants) but this also provided insufficient information to reach a conclusion about the effectiveness of the drug. Three trials of coumarin combined with troxerutin were found which tested two different doses of the drug against each other with no placebo, however participant numbers and baseline data were not provided. Eight trials of coumarin were identified. Two of these reported the same trial and the other potentially also referred to the same trial but this could not be confirmed. A further two papers also appeared to refer to the same trial but again this was unconfirmed. Five studies added anti-filarial drugs to the interventions tested. Participant data could not be extracted and the reporting of outcome measures in most was unclear. Loprinzi's 1999 trial was reported in more detail but its conclusions were very much at odds with other findings. Authors' conclusions It is not possible to draw conclusions about the effectiveness of Benzopyrones in the management of lymphoedema from the current available trials

Improved weed management for transplanted aman rice

Rainfed transplanted rice grown in the monsoon aman season accounts for more than 50% of the total area planted to rice in Bangladesh. Because of rising input costs, including labor, farmers are searching for ways to maintain income, by either increasing yields or reducing costs or both. On-farm trials in the High Barind Tract indicated that one-third of the farmers would be able to gain 0.5 t ha–1 or more additional grain by undertaking more intensive or timelier weeding than is usual under current management practices. Higher yields were observed on-farm from a preemergence application of butachlor(1.25 kg a.i. ha–1) compared with hand weeding twice. In Comilla District, trials of a range of weed management practices demonstrated that the yield advantage over the farmers’ practice, either one or two hand weedings, was on average 355 ± 18 kg ha–1 for Rifit (pretilachlor), 281 ± 39 kg ha–1 for Machete (butachlor), and 210 ± 34 kg ha–1 for Ronstar (oxadiazon), each followed by one hand weeding in aman 2003. Partial budgets calculated for inputs and returns showed that hand weeding was less profitable than herbicides in rainfed rice,incurring US$72 ha–1 lower return. Use of a push weeder plus one hand weeding was less profitable than herbicides, incurring$49 ha–1 lower return. To date, herbicides have been largely promoted for irrigated rice in Bangladesh. The trial results demonstrate that under rainfed conditions early in the aman season, water levels are adequate for herbicides to work effectively. The use of herbicides allows timely weed control when there is a shortage of labor and avoids transaction costs, such as the provision of meals and time needed to source laborers. Herbicides are likely to be adopted by growers experiencing labor shortages, particularly on large farms and for farmers seeking to reduce input costs. Sharecroppers and tenant farmers who pay rent are primarily concerned about obtaining a high aman yield, so innovations that raise aman yields (such as herbicides that will have a similar effect as a timely first weeding) are also likely to be adopted on sharecropped plots, even when costs are not shared between the landlord and tenant

The effect of ocean acidification on organic and inorganic speciation of trace metals

Rising concentrations of atmospheric carbon dioxide are causing acidification of the oceans. 20 This results in changes to the concentrations of key chemical species such as hydroxide, 21 carbonate and bicarbonate ions. These changes will affect the distribution of different forms 22 of trace metals. Using IPCC data for pCO2 and pH under four future emissions scenarios (to 23 the year 2100) we use a chemical speciation model to predict changes in the distribution of 24 organic and inorganic forms of trace metals. Under a scenario where emissions peak after 25 the year 2100, predicted free ion Al, Fe, Cu and Pb concentrations increase by factors of up 26 to approximately 21, 2.4, 1.5 and 2.0 respectively. Concentrations of organically complexed 27 metal typically have a lower sensitivity to ocean acidification induced changes. 28 Concentrations of organically-complexed Mn, Cu, Zn and Cd fall by up to 10%, while those 29 of organically-complexed Fe, Co and Ni rise by up to 14%. Although modest, these changes 30 may have significance for the biological availability of metals given the close adaptation of 31 marine microorganisms to their environment

Understanding the mobilisation of metal pollution associated with historical mining in a carboniferous upland catchment

Point and diffuse pollution from metal mining has led to severe environmental damage worldwide. Mine drainage is a significant problem for riverine ecosystems, it is commonly acidic (AMD), but neutral mine drainage (NMD) can also occur. A representative environment for studying metal pollution from NMD is provided by Carboniferous catchments characterised by a circumneutral pH and high concentrations of carbonates, supporting the formation of secondary metal-minerals as potential sinks of metals. The present study focuses on understanding the mobility of metal pollution associated with historical mining in a Carboniferous upland catchment. In the uplands of the UK, river water, sediments and spoil wastes were collected over a period of fourteen months, samples were chemically analysed to identify the main metal sources and their relationships with geological and hydrological factors. Correlation tests and principal component analysis suggest that the underlying limestone bedrock controls pH and weathering reactions. Significant metal concentrations from mining activities were measured for zinc (4.3mg/l), and lead (0.3 mg/l), attributed to processes such as oxidation of mined ores (e.g. sphalerite, galena) or dissolution of precipitated secondary metal-minerals (e.g. cerussite, smithsonite). Zinc and lead mobility indicated strong dependence on biogeochemistry and hydrological conditions (e.g. pH and flow) at specific locations in the catchment. Annual loads of zinc and lead (2.9 and 0.2 tonnes/year) demonstrate a significant source of both metals to downstream river reaches. Metal pollution results in a large area of catchment having a depleted chemical status with likely effects on the aquatic ecology. This study provides an improved understanding of geological and hydrological processes controlling water chemistry, which is critical to assessing metal sources and mobilization, especially in neutral mine drainage areas

Seven exercises planned to stimulate the flow of ideas in creative composition

Thesis (Ed.M.)--Boston Universit

Two RNA-binding motifs in eIF3 direct HCV IRES-dependent translation.

The initiation of protein synthesis plays an essential regulatory role in human biology. At the center of the initiation pathway, the 13-subunit eukaryotic translation initiation factor 3 (eIF3) controls access of other initiation factors and mRNA to the ribosome by unknown mechanisms. Using electron microscopy (EM), bioinformatics and biochemical experiments, we identify two highly conserved RNA-binding motifs in eIF3 that direct translation initiation from the hepatitis C virus internal ribosome entry site (HCV IRES) RNA. Mutations in the RNA-binding motif of subunit eIF3a weaken eIF3 binding to the HCV IRES and the 40S ribosomal subunit, thereby suppressing eIF2-dependent recognition of the start codon. Mutations in the eIF3c RNA-binding motif also reduce 40S ribosomal subunit binding to eIF3, and inhibit eIF5B-dependent steps downstream of start codon recognition. These results provide the first connection between the structure of the central translation initiation factor eIF3 and recognition of the HCV genomic RNA start codon, molecular interactions that likely extend to the human transcriptome