The discovery of 2-fluoro-N-(3-fluoro-4-(5-((4-morpholinobutyl)amino)-1,3,4-oxadiazol-2-yl)phenyl)benzamide, a full agonist of the alpha-7 nicotinic acetylcholine receptor showing efficacy in the novel object recognition model of cognition enhancement

A series of α7 nicotinic acetylcholine receptor full agonists with a 1,3,4-oxadiazol-2-amine core has been discovered. Early lead 1 was found to have a limited therapeutic index with respect to its potential for cardiovascular side effects. Further optimisation of this series led to the identification of 22 a potent full agonist showing efficacy at a dose of 0.1mg/kg in the novel object recognition model of cognition enhancement. Comparison of 1 with 22 demonstrated the latter to have an improved oral pharmacokinetic profile and cardiovascular therapeutic index.     

Diet selection of African elephant over time shows changing optimization currency

Multiple factors determine diet selection of herbivores. However, in many diet studies selection of single nutrients is studied or optimization models are developed using only one currency. In this paper, we use linear programming to explain diet selection by African elephant based on plant availability and nutrient and deterrent content over time. Our results indicate that elephant at our study area maximized intake of phosphorus throughout the year, possibly in response to the deficiency of this nutrient in the region. After adjusting the model to incorporate the effects of this deficiency, elephant were found to maximize nitrogen intake during the wet season and energy during the dry season. We reason that the increased energy requirements during the dry season can be explained by seasonal changes in water availability and forage abundance. As forage abundance decrease into the dry season, elephant struggle to satisfy their large absolute food requirements. Adding to this restriction is the simultaneous decrease in plant and surface water availability, which force the elephant to seek out scarce surface water sources at high energy costs. During the wet season when food becomes more abundant and energy requirements are satisfied easier, elephant aim to maximize nitrogen intake for growth and reproduction. Our study contributes to the emerging theory on understanding foraging for multiple resources.     

After the epidemic: follow up study of HIV seroprevalence and changing patterns of drug use.

OBJECTIVE--To follow up known intravenous drug users to determine current health state and drug use, compare characteristics with those of recent drug users, and examine HIV exposure and serostate. DESIGN--Subjects were identified from conventional general practice records and recruited from 1980 to the end of 1985; they were followed up during 1987 and 1988 and compared with drug users identified in the same way but recruited after 1985. SETTING--General practice and community in north west Edinburgh. Follow up conducted throughout the United Kingdom. SUBJECTS--Subjects known to have injected illegal drugs before 1986 (n = 203) and since that time. MAIN OUTCOME MEASURES--Mortality from and prevalence of HIV seropositivity and various parameters indicative of abstinence. RESULTS--Of the 203 subjects in the follow up group, 189 (93%) were traced; 16 (8%) had died and the remaining 173 (85%) were interviewed. In all, 146 (72% of the follow up cohort) had been tested for HIV antibodies, 94 (64%) having positive and 52 (36%) negative results; 57 (28%) had not been tested. Of the 65 subjects in the recently recruited group, 51 (79%) had been tested for HIV, 15 (29%) having positive results. A further 21 (43%) were currently negative for HIV antibody but still at risk. Thirty three (19%) of those followed up were confirmed abstinent, although more (about half) showed evidence of diminished drug injecting. Age correlated strongly with abstinence (p less than 0.001). One third of the group currently used cannabis, buprenorphine, dihydrocodeine, or diazepam. When the two groups were analysed together there was a strong association between the date of starting injecting and HIV seropositivity (chi 3 = 23.81, df = 2, p less than 0.001), with a peak around 1980-3. CONCLUSIONS--Although only a fifth of the followed up group were convincingly abstinent, a much larger group showed evidence of prolonged periods of remission. Overall, much use of oral drugs was confirmed and worrying trends towards taking buprenorphine and benzodiazepines were evident. The peak incidence of starting drug use and the comparatively low seroprevalence of HIV in the newer drug users probably explain the anomalous high seroprevalence in Edinburgh drug users during 1980-5. The epidemic of HIV during the first half of the 1980s in the group suggests that the virus was probably being transmitted because of a pattern of behaviour. Changing patterns of HIV transmission suggest a need to concentrate on heterosexual transmission as the main problem in the future.     

Diversity, abundance, and potential activity of nitrifying and nitrate-reducing microbial assemblages in a subglacial ecosystem

Subglacial sediments sampled from beneath Robertson Glacier (RG), Alberta, Canada, were shown to harbor diverse assemblages of potential nitrifiers, nitrate reducers, and diazotrophs, as assessed by amoA, narG, and nifH gene biomarker diversity. Although archaeal amoA genes were detected, they were less abundant and less diverse than bacterial amoA, suggesting that bacteria are the predominant nitrifiers in RG sediments. Maximum nitrification and nitrate reduction rates in microcosms incubated at 4°C were 280 and 18.5 nmol of N per g of dry weight sediment per day, respectively, indicating the potential for these processes to occur in situ. Geochemical analyses of subglacial sediment pore waters and bulk subglacial meltwaters revealed low concentrations of inorganic and organic nitrogen compounds. These data, when coupled with a C/N atomic ratio of dissolved organic matter in subglacial pore waters of ~210, indicate that the sediment communities are N limited. This may reflect the combined biological activities of organic N mineralization, nitrification, and nitrate reduction. Despite evidence of N limitation and the detection of nifH, we were unable to detect biological nitrogen fixation activity in subglacial sediments. Collectively, the results presented here suggest a role for nitrification and nitrate reduction in sustaining microbial life in subglacial environments. Considering that ice currently covers 11% of the terrestrial landmass and has covered significantly greater portions of Earth at times in the past, the demonstration of nitrification and nitrate reduction in subglacial environments furthers our understanding of the potential for these environments to contribute to global biogeochemical cycles on glacial-interglacial timescales.     

Microbial metabolism in ice and brine at -5°C

Metabolic activity, but not growth, has been observed in ice at temperatures from -5°C to -32°C. To improve understanding of metabolism in ice, we simultaneously examined various aspects of metabolism ((14) C-acetate utilization, macromolecule syntheses and viability via reduction of CTC) of the glacial isolates Sporosarcina sp. B5 and Chryseobacterium sp. V3519-10 during incubation in nutrient-rich ice and brine at -5°C for 50 days. Measured rates of acetate utilization and macromolecule syntheses were high in the first 20 days suggesting adjustment to the lower temperatures and higher salt concentrations of both the liquid vein network in the ice and the brine. Following this adjustment, reproductive growth of both organisms was evident in brine, and suggested for Sporosarcina sp. B5 in ice by increases in cell numbers and biomass. Chryseobacterium sp. V3519-10 cells incubated in ice remained active. These data indicate that neither low temperature nor high salt concentrations prohibit growth in ice, but some other aspect of living within ice slows growth to within the detection limits of current methodologies. These results imply that microbial growth is plausible in natural ice systems with comparable temperatures and sufficient nutrients, such as debris-rich basal ices of glaciers and ice masses.     

Molecular evidence for an active endogenous microbiome beneath glacial ice

Geologic, chemical and isotopic evidence indicate that Earth has experienced numerous intervals of widespread glaciation throughout its history, with roughly 11% of present day Earth''s land surface covered in ice. Despite the pervasive nature of glacial ice both today and in Earth''s past and the potential contribution of these systems to global biogeochemical cycles, the composition and phylogenetic structure of an active microbial community in subglacial systems has yet to be described. Here, using RNA-based approaches, we demonstrate the presence of active and endogenous archaeal, bacterial and eukaryal assemblages in cold (0–1 °C) subglacial sediments sampled from Robertson Glacier, Alberta, Canada. Patterns in the phylogenetic structure and composition of subglacial sediment small subunit (SSU) ribosomal RNA (rRNA) assemblages indicate greater diversity and evenness than in glacial surface environments, possibly due to facilitative or competitive interactions among populations in the subglacial environment. The combination of phylogenetically more even and more diverse assemblages in the subglacial environment suggests minimal niche overlap and optimization to capture a wider spectrum of the limited nutrients and chemical energy made available from weathering of bedrock minerals. The prevalence of SSU rRNA affiliated with lithoautotrophic bacteria, autotrophic methane producing archaea and heterotrophic eukarya in the subglacial environment is consistent with this hypothesis and suggests an active contribution to the global carbon cycle. Collectively, our findings demonstrate that subglacial environments harbor endogenous active ecosystems that have the potential to impact global biogeochemical cycles over extended periods of time.     

African Elephants Loxodonta africana Amplify Browse Heterogeneity in African Savanna

There is a growing concern that the feeding habits of the African elephant, which include pushing over, uprooting and snapping trees, may have a negative impact on other herbivores. Browsed trees are known to respond by either increasing production (shoots and leaves) or defence (secondary compounds). It is not clear, however, what proportion of the browsed biomass can be made available at lower feeding heights after a tree is pushed over or snapped; thus, it is also unclear how the forage quality is affected. In a field survey in Kruger National Park, South Africa, 708 Mopane trees were measured over four elephant utilization categories: snapped trees, pushed‐over trees, uprooted trees and control trees. The elephants' impact on the leaf biomass distribution was quantified, and the forage quality (Ca, P, K and Mg, N, digestibility and condensed tannin [CT] concentrations) were analyzed. Pushed‐over and uprooted trees had the maximum leaf biomass at lower heights (<1 m), snapped trees at medium heights (1–2 m) and control trees at higher heights (>2 m). In all three utilization categories, the minimum leaf biomass was seven times higher than it was for control trees at a height of below 1 m. Leaf nitrogen content increased in all three categories and was significantly higher in snapped trees. CT concentrations increased slightly in all trees that were utilized by elephants, especially on granitic soils in the dry season. The results provide the insight that elephants facilitate the redistribution and availability of browse and improve the quality, which may positively affect small browsing herbivores.     

Effectiveness of Personal Protective Equipment for Healthcare Workers Caring for Patients with Filovirus Disease: A Rapid Review

Background

A rapid review, guided by a protocol, was conducted to inform development of the World Health Organization’s guideline on personal protective equipment in the context of the ongoing (2013–present) Western African filovirus disease outbreak, with a focus on health care workers directly caring for patients with Ebola or Marburg virus diseases.

Methods

Electronic databases and grey literature sources were searched. Eligibility criteria initially included comparative studies on Ebola and Marburg virus diseases reported in English or French, but criteria were expanded to studies on other viral hemorrhagic fevers and non-comparative designs due to the paucity of studies. After title and abstract screening (two people to exclude), full-text reports of potentially relevant articles were assessed in duplicate. Fifty-seven percent of extraction information was verified. The Grading of Recommendations Assessment, Development and Evaluation framework was used to inform the quality of evidence assessments.

Results

Thirty non-comparative studies (8 related to Ebola virus disease) were located, and 27 provided data on viral transmission. Reporting of personal protective equipment components and infection prevention and control protocols was generally poor.

Conclusions

Insufficient evidence exists to draw conclusions regarding the comparative effectiveness of various types of personal protective equipment. Additional research is urgently needed to determine optimal PPE for health care workers caring for patients with filovirus.