Truncation of Plasmodium berghei merozoite surface protein 8 does not affect in vivo blood-stage development

Merozoite surface protein 8 (MSP8) has shown promise as a vaccine candidate in the Plasmodium yoelii rodent malaria model and has a proposed role in merozoite invasion of erythrocytes. However, the temporal expression and localisation of MSP8 are unusual for a merozoite antigen. Moreover, in Plasmodium falciparum the MSP8 gene could be disrupted with no apparent effect on in vitro growth. To address the in vivo function of full-length MSP8, we truncated MSP8 in the rodent parasite Plasmodium berghei. Pb&Delta;MSP8 disruptant parasites displayed a normal blood-stage growth rate but no increase in reticulocyte preference, a phenomenon observed in P. yoelii MSP8 vaccinated mice. Expression levels of erythrocyte surface antigens were similar in P. berghei wild-type and Pb&Delta;MSP8-infected erythrocytes, suggesting that a parasitophorous vacuole function for MSP8 does not involve global trafficking of such antigens. These data demonstrate that a full-length membrane-associated form of PbMSP8 is not essential for blood-stage growth.<br /

The influence of taphonomy on histological and isotopic analyses of treated and untreated buried modern human bone

The chemical (e.g., preservation/embalming) treatment of skeletal remains can reduce overall DNA quality and quantity. The histological and stable isotope examination of treated and untreated human remains improves our understanding of how chemical preservatives impact bone diagenesis and will determine if chemical treatment adversely affects stable isotope ratio analysis of collagen. Fidelity in the application(s) of stable isotope interpretations requires that the isotope delta (δ) values have not been altered postmortem. Re-associated antimeres and refits of chemically treated and untreated rib and long bones from eight casualties [thin-sectioned human bone (n = 43) and collagen extraction/stable isotope analysis (n = 42)] from the World War II Battle of Tarawa were examined to compare skeletal elements from the same individual that had different taphonomic histories. Histological analyses included scoring upon the Oxford Histological Index (OHI) and Birefringence scale, recording microbial invasion, and general observations. The collected data were analyzed via simple descriptive statistics and paired samples t-tests. Treated remains scored higher on the OHI and for Birefringence, indicating that bone quality was good to excellent. The untreated samples scored lower on the OHI and Birefringence scales suggesting poorer preservation than the treated remains. Histology results were supported by the isotope sample preparation results: the collagen % yield was higher for treated bone than untreated bone. Additionally, chemical preservation had no meaningful impact on isotope δ values of treated and untreated remains from the same element or pair-matched elements. Overall, treated remains exhibited good preservation while untreated remains exhibit poorer preservation with significant microfocal destruction to the extent that little histological analyses can be applied. Stable isotope ratio analysis is viable for both treated and untreated remains indicating this testing modality likely can be used for most treated remains, regardless of origin

Tillage energy savings from zone burial of shredded and whole cotton stalks

Two prototypes of a stalk burial implement were tested for energy requirements at the University of California, Shafter Research Station. Both versions of the implement are designed to bury the cotton stalks in a concentrated Zone and reform the bed in the same location. To plow under shredded stalks, both versions of the implement required less energy than a conventional tillage systems typical of the San Joaquin Valley of California. Both stalk burial implements were also used to plow under whole cotton stalks. This offers additional energy savings by eliminating the stalk shredding operation

NaF PET/CT for response assessment of prostate cancer bone metastases treated with single fraction stereotactic ablative body radiotherapy

Introduction: In prostate cancer patients, imaging of bone metastases is enhanced through the use of sodium fluoride positron emission tomography (18F-NaF PET/CT). This imaging technique shows areas of enhanced osteoblastic activity and blood flow. In this work, 18F-NaF PET/CT was investigated for response assessment to single fraction stereotactic ablative body radiotherapy (SABR) to bone metastases in prostate cancer patients. Methods: Patients with bone metastases in a prospective trial treated with single fraction SABR received a 18F-NaF PET/CT scan prior to and 6 months post-SABR. The SUVmax in the tumour was determined and the difference between before and after SABR determined. The change in uptake in the non-tumour bone was also measured as a function of the received SABR dose. Results: Reduction in SUVmax was observed in 29 of 33 lesions 6 months after SABR (mean absolute decrease in SUVmax 17.7, 95% CI 25.8 to - 9.4, p = 0.0001). Of the three lesions with increased SUVmax post-SABR, two were from the same patient and located in the vertebral column. Both were determined to be local progression in addition to one fracture. The third lesion (in a rib) was shown to be controlled locally but suffered from a fracture at 24 months. Progression adjacent to the treated volume was observed in two patients. The non-tumour bone irradiated showed increased loss in uptake with increasing dose, with a median loss in uptake of 23.3% for bone receiving 24 Gy. Conclusion: 18F-NaF PET/CT for response assessment of bone metastases to single fraction SABR indicates high rates of reduction of osteoblastic activity in the tumour and non-tumour bone receiving high doses. The occurrence of marginal recurrence indicates use of larger clinical target volumes may be warranted in treatment of bone metastases. Trial registration: POPSTAR, \u27Pilot Study of patients with Oligometastases from Prostate cancer treated with STereotactic Ablative Radiotherapy\u27, Universal Trial Number U1111-1140-7563, Registered 17th April 2013

Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety

&lt;p&gt;Background: Melatonin is extensively used in the USA in a non-regulated manner for sleep disorders. Prolonged release melatonin (PRM) is licensed in Europe and other countries for the short term treatment of primary insomnia in patients aged 55 years and over. However, a clear definition of the target patient population and well-controlled studies of long-term efficacy and safety are lacking. It is known that melatonin production declines with age. Some young insomnia patients also may have low melatonin levels. The study investigated whether older age or low melatonin excretion is a better predictor of response to PRM, whether the efficacy observed in short-term studies is sustained during continued treatment and the long term safety of such treatment.&lt;/p&gt; &lt;p&gt;Methods: Adult outpatients (791, aged 18-80 years) with primary insomnia, were treated with placebo (2 weeks) and then randomized, double-blind to 3 weeks with PRM or placebo nightly. PRM patients continued whereas placebo completers were re-randomized 1:1 to PRM or placebo for 26 weeks with 2 weeks of single-blind placebo run-out. Main outcome measures were sleep latency derived from a sleep diary, Pittsburgh Sleep Quality Index (PSQI), Quality of Life (World Health Organzaton-5) Clinical Global Impression of Improvement (CGI-I) and adverse effects and vital signs recorded at each visit.&lt;/p&gt; &lt;p&gt;Results: On the primary efficacy variable, sleep latency, the effects of PRM (3 weeks) in patients with low endogenous melatonin (6-sulphatoxymelatonin [6-SMT] ≤8 μg/night) regardless of age did not differ from the placebo, whereas PRM significantly reduced sleep latency compared to the placebo in elderly patients regardless of melatonin levels (-19.1 versus -1.7 min; P = 0.002). The effects on sleep latency and additional sleep and daytime parameters that improved with PRM were maintained or enhanced over the 6-month period with no signs of tolerance. Most adverse events were mild in severity with no clinically relevant differences between PRM and placebo for any safety outcome.&lt;/p&gt; &lt;p&gt;Conclusions: The results demonstrate short- and long-term efficacy and safety of PRM in elderly insomnia patients. Low melatonin production regardless of age is not useful in predicting responses to melatonin therapy in insomnia. The age cut-off for response warrants further investigation.&lt;/p&gt

Safety and efficacy of Taminizer D (dimethylglycine sodium salt) as a feed additive for chickens for fattening

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of Taminizer D (dimethylglycine sodium salt) as a feed additive for chickens for fattening, based on a dossier submitted for the modification of the terms of authorisation of the additive. The product is authorised in the European Union for chickens for fattening at the maximum content of 1,000&nbsp;mg/kg complete feedingstuffs. The applicant proposed the introduction of an additional manufacturing process, which introduces an impurity (dimethylamino-ethanol (DMAE)) in the additive at concentrations up to 0.09%. The EFSA Panel&nbsp;on Additives and Products or Substances used in Animal Feed (FEEDAP) considered that the proposed modification would not substantially affect the previous assessment as related to the safety of the environment and the efficacy of the product. Since the safety of the active substance was established, the current assessment has dealt with the impurity DMAE. Considering the toxicological profile of DMAE, the estimated intake by the target animal and consumers, and making use of the Threshold of Toxicological Concern (TTC) approach, the Panel&nbsp;concluded that Taminizer D, manufactured by the DMAE route, is safe for both chickens for fattening and consumers, up to the maximum level of 1,000 mg/kg feed. The FEEDAP Panel&nbsp;extends its conclusions about Taminizer D produced by the original method to cover also Taminizer D produced by the new DMAE method. There is minimal risk to users from dust produced as a result of normal handling of the additive. Taminizer D is not irritant to skin but may be irritant to eyes; it is regarded as a potential skin sensitiser. The FEEDAP Panel&nbsp;recommended to set a specification for the DMAE content in the additive

Spatial complementarity and the coexistence of species

Coexistence of apparently similar species remains an enduring paradox in ecology. Spatial structure has been predicted to enable coexistence even when population-level models predict competitive exclusion if it causes each species to limit its own population more than that of its competitor. Nevertheless, existing hypotheses conflict with regard to whether clustering favours or precludes coexistence. The spatial segregation hypothesis predicts that in clustered populations the frequency of intra-specific interactions will be increased, causing each species to be self-limiting. Alternatively, individuals of the same species might compete over greater distances, known as heteromyopia, breaking down clusters and opening space for a second species to invade. In this study we create an individual-based model in homogeneous two-dimensional space for two putative sessile species differing only in their demographic rates and the range and strength of their competitive interactions. We fully characterise the parameter space within which coexistence occurs beyond population-level predictions, thereby revealing a region of coexistence generated by a previously-unrecognised process which we term the triadic mechanism. Here coexistence occurs due to the ability of a second generation of offspring of the rarer species to escape competition from their ancestors. We diagnose the conditions under which each of three spatial coexistence mechanisms operates and their characteristic spatial signatures. Deriving insights from a novel metric — ecological pressure — we demonstrate that coexistence is not solely determined by features of the numerically-dominant species. This results in a common framework for predicting, given any pair of species and knowledge of the relevant parameters, whether they will coexist, the mechanism by which they will do so, and the resultant spatial pattern of the community. Spatial coexistence arises from complementary combinations of traits in each species rather than solely through self-limitation

Safety and efficacy of Kelforce \uae (l-glutamic acid, N,N-diacetic acid, tetrasodium salt (GLDA-Na 4 )) as a feed additive for chickens for fattening

l-Glutamic acid, N,N-diacetic acid, tetrasodium salt (GLDA-Na 4 ) (Kelforce \uae ) is sought to be used as a zootechnical feed additive in chickens for fattening to improve the absorption of zinc from feed, reducing zinc emissions through manure and thus, affecting favourably the environment. The product has not been authorised in the European Union as a feed additive. Kelforce \uae is intended to be marketed as a liquid and solid formulation, containing 65&nbsp;47% and 65&nbsp;30% of GLDA-Na 4 , respectively. Kelforce \uae is safe for chickens for fattening at the maximum level of 1,000&nbsp;mg GLDA-Na 4 /kg complete feed. Based on the toxicological profile of GLDA-Na 4 and the consumer exposure to GLDA-Na 4 and to nitrilotriacetic acid trisodium salt (NTA-Na 3 ; an impurity of the additive), the use of Kelforce \uae at the maximum proposed level in feed of chickens for fattening is of no concern for consumer safety. Due to its low inhalation toxicity, the exposure to GLDA-Na 4 is unlikely to pose a risk by inhalation. However, owing to the high-dusting potential of the solid formulation, a risk from such high level of dust, even if toxicologically inert, cannot be excluded. Kelforce \uae is not a skin/eye irritant or skin sensitiser. No risks for the terrestrial compartment were identified at the maximum use level of the additive. Risks for the aquatic compartment cannot be excluded based on the secondary effect of the additive on green algae. In the absence of data, the Panel&nbsp;cannot conclude on the safety for the sediment compartment or the possible ground water contamination. The risk of bioaccumulation and secondary poisoning caused by the additive is considered very low. Owing to the inconsistent and conflicting results from the studies assessed, the Panel&nbsp;on Additives and Products or Substances used in Animal Feed (FEEDAP) cannot conclude on the efficacy of the additive. The Panel&nbsp;made a recommendation regarding the levels of formaldehyde and cyanide in the active substance

Safety and efficacy of a preparation of algae interspaced bentonite as a feed additive for all animal species

Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP Panel) was asked to deliver a scientific opinion on the safety and efficacy of a preparation of algae interspaced bentonite when used as aflatoxin B1 binder for all animal species. The additive is composed of bentonite and algae belonging to Ulva spp. The additive is considered safe for weaned piglets, dairy cows and chickens for fattening at the maximum recommended dose of 125 mg/kg complete feed (a wide margin of safety is established in weaned piglets and dairy cows); this conclusion is extrapolated to all animal species. The additive is not genotoxic. As bentonite is essentially not absorbed from the gut lumen and algae from Ulva spp. are not expected to be of concern for human consumption, the FEEDAP Panel considers that the use of the additive in animal nutrition is safe for consumers. The additive is not an irritant to the skin or the eyes and it is considered to have low inhalation toxicity. However, the additive has a high dusting potential and contains a high proportion of fine particles. A high level of inhalation exposure to an inert dust may be hazardous. In the absence of data, the Panel could not conclude on dermal sensitisation. As the components of the additive are of natural origin (soil and marine environment), it is not expected that the use of the additive in animal nutrition would adversely affect the environment. The FEEDAP Panel could not conclude on the efficacy of the additive for all animal species