Coscinaraea marshae corals that have survived prolonged bleaching exhibit signs of increased heterotrophic feeding

Colonies of Coscinaraea marshae corals from Rottnest Island, Western Australia have survived for more than 11 months in various bleached states following a severe heating event in the austral summer of 2011. These colonies are situated in a high-latitude, mesophotic environment, which has made their long-term survival of particular interest as such environments typically suffer from minimal thermal pressures. We have investigated corals that remain unbleached, moderately bleached, or severely bleached to better understand potential survival mechanisms utilised in response to thermal stress. Specifically, Symbiodinium (algal symbiont) density and genotype, chlorophyll-a concentrations, and δ¹³C and δ¹⁵N levels were compared between colonies in the three bleaching categories. Severely bleached colonies housed significantly fewer Symbiodinium cells (p < 0.05) and significantly reduced chlorophyll-a concentrations (p < 0.05), compared with unbleached colonies. Novel Symbiodinium clade associations were observed for this coral in both severely and moderately bleached colonies, with clade C and a mixed clade population detected. In unbleached colonies, only clade B was observed. Levels of δ¹⁵N indicate that severely bleached colonies are utilising heterotrophic feeding mechanisms to aid survival whilst bleached. Collectively, these results suggest that these C. marshae colonies can survive with low symbiont and chlorophyll densities, in response to prolonged thermal stress and extended bleaching, and increase heterotrophic feeding levels sufficiently to meet energy demands, thus enabling some colonies to survive and recover over long time frames. This is significant as it suggests that corals in mesophotic and high-latitude environments may possess considerable plasticity and an ability to tolerate and adapt to large environmental fluctuations, thereby improving their chances of survival as climate change impacts coral ecosystems worldwide.     

美、欧、日三国药物审批趋势解读（2004—2013 年）

2014 年5 月汤森路透集团的科学创新监管中心（CIRS）发表了一份“R&D Briefing 54”的报告。基于该报告对新活性物质的统计数据,分析美、欧、日三个药物审批机构,即美国食品与药品管理局、欧洲药物管理局和日本药品与医疗器械管理局的新药审批趋势。     

临床试验进展：大数据方法在临床试验中的应用

药物研发的复杂性与日俱增,而大数据时代的到来使得临床试验的进展大大加快。本期“临床试验进展”讨论了皮肤病学新创试验中面向数据的亮点,探讨了现实采用的大数据方法,剖析了对风险导向监察的新兴方法学。此外还汇总了银屑病和特应性皮炎新疗法的临床研究报告,揭示了这些疾病的影响以及Ⅱ期和Ⅲ期研究中已经取得成功的候选药。     

Interpreting biological degradative processes acting on mammalian hair in the living and the dead: which ones are taphonomic?

Although the taphonomic (post-mortem) degradation processes relevant to teeth and bones have been well described, those taking place with regards to mammalian hairs have not been characterized to the same extent. This present article describes, in detail, microscopic changes resulting from the actions of biological agents that digest and degrade hairs. The most noteworthy and prevalent agents responsible for the destruction of hair structure are fungi, which use a range of strategies to invade and digest hairs. One of the most important finds to emerge from this study is that taphonomic structures and processes can easily be interpreted by the unwary as ‘real’, or as class characteristics for a particular animal taxon. Moreover, under certain conditions, ‘taphonomic’ processes normally associated with the dead are also present on the hairs of the living. This work will improve the reliability of hair examinations in forensic, archaeological and palaeontological applications—in addition, the finding has relevance in the protection of mammalian collections susceptible to infestation. This article also addresses the popular myth that ancient peoples were often red-haired and discusses phenomena responsible for this observation. Insights gained from detailed characterization of taphonomic processes in 95 hairs from a variety of species demonstrate the range and breadth of degradative effects on hair structure and colour. Lastly, the study demonstrates that hairs often tell a story and that there is value of extracting as much morphological data as possible from hairs, prior to destructive sampling for biomolecules.     

Inducible Resistance to Maize Streak Virus

Maize streak virus (MSV), which causes maize streak disease (MSD), is the major viral pathogenic constraint on maize production in Africa. Type member of the Mastrevirus genus in the family Geminiviridae, MSV has a 2.7 kb, single-stranded circular DNA genome encoding a coat protein, movement protein, and the two replication-associated proteins Rep and RepA. While we have previously developed MSV-resistant transgenic maize lines constitutively expressing “dominant negative mutant” versions of the MSV Rep, the only transgenes we could use were those that caused no developmental defects during the regeneration of plants in tissue culture. A better transgene expression system would be an inducible one, where resistance-conferring transgenes are expressed only in MSV-infected cells. However, most known inducible transgene expression systems are hampered by background or “leaky” expression in the absence of the inducer. Here we describe an adaptation of the recently developed INPACT system to express MSV-derived resistance genes in cell culture. Split gene cassette constructs (SGCs) were developed containing three different transgenes in combination with three different promoter sequences. In each SGC, the transgene was split such that it would be translatable only in the presence of an infecting MSV’s replication associated protein. We used a quantitative real-time PCR assay to show that one of these SGCs (pSPLITrep^III-Rb-Ubi) inducibly inhibits MSV replication as efficiently as does a constitutively expressed transgene that has previously proven effective in protecting transgenic maize from MSV. In addition, in our cell-culture based assay pSPLITrep ^III-Rb-Ubi inhibited replication of diverse MSV strains, and even, albeit to a lesser extent, of a different mastrevirus species. The application of this new technology to MSV resistance in maize could allow a better, more acceptable product.     

Time Series Analysis of Trends in Malaria Cases and Deaths at Hospitals and the Effect of Antimalarial Interventions, 2001–2011, Ethiopia

Background

The Government of Ethiopia and its partners have deployed artemisinin-based combination therapies (ACT) since 2004 and long-lasting insecticidal nets (LLINs) since 2005. Malaria interventions and trends in malaria cases and deaths were assessed at hospitals in malaria transmission areas during 2001–2011.

Methods

Regional LLINs distribution records were used to estimate the proportion of the population-at-risk protected by LLINs. Hospital records were reviewed to estimate ACT availability. Time-series analysis was applied to data from 41 hospitals in malaria risk areas to assess trends of malaria cases and deaths during pre-intervention (2001–2005) and post-interventions (2006–2011) periods.

Findings

The proportion of the population-at-risk potentially protected by LLINs increased to 51% in 2011. The proportion of facilities with ACTs in stock exceeded 87% during 2006–2011. Among all ages, confirmed malaria cases in 2011 declined by 66% (95% confidence interval [CI], 44–79%) and SPR by 37% (CI, 20%–51%) compared to the level predicted by pre-intervention trends. In children under 5 years of age, malaria admissions and deaths fell by 81% (CI, 47%–94%) and 73% (CI, 48%–86%) respectively. Optimal breakpoint of the trendlines occurred between January and June 2006, consistent with the timing of malaria interventions. Over the same period, non-malaria cases and deaths either increased or remained unchanged, the number of malaria diagnostic tests performed reflected the decline in malaria cases, and rainfall remained at levels supportive of malaria transmission.

Conclusions

Malaria cases and deaths in Ethiopian hospitals decreased substantially during 2006–2011 in conjunction with scale-up of malaria interventions. The decrease could not be accounted for by changes in hospital visits, malaria diagnostic testing or rainfall. However, given the history of variable malaria transmission in Ethiopia, more data would be required to exclude the possibility that the decrease is due to other factors.     

Using Mobile Health (mHealth) and Geospatial Mapping Technology in a Mass Campaign for Reactive Oral Cholera Vaccination in Rural Haiti

Background

In mass vaccination campaigns, large volumes of data must be managed efficiently and accurately. In a reactive oral cholera vaccination (OCV) campaign in rural Haiti during an ongoing epidemic, we used a mobile health (mHealth) system to manage data on 50,000 participants in two isolated communities.

Methods

Data were collected using 7-inch tablets. Teams pre-registered and distributed vaccine cards with unique barcodes to vaccine-eligible residents during a census in February 2012. First stored on devices, data were uploaded nightly via Wi-fi to a web-hosted database. During the vaccination campaign between April and June 2012, residents presented their cards at vaccination posts and their barcodes were scanned. Vaccinee data from the census were pre-loaded on tablets to autopopulate the electronic form. Nightly analysis of the day''s community coverage informed the following day''s vaccination strategy. We generated case-finding reports allowing us to identify those who had not yet been vaccinated.

Results

During 40 days of vaccination, we collected approximately 1.9 million pieces of data. A total of 45,417 people received at least one OCV dose; of those, 90.8% were documented to have received 2 doses. Though mHealth required up-front financial investment and training, it reduced the need for paper registries and manual data entry, which would have been costly, time-consuming, and is known to increase error. Using Global Positioning System coordinates, we mapped vaccine posts, population size, and vaccine coverage to understand the reach of the campaign. The hardware and software were usable by high school-educated staff.

Conclusion

The use of mHealth technology in an OCV campaign in rural Haiti allowed timely creation of an electronic registry with population-level census data, and a targeted vaccination strategy in a dispersed rural population receiving a two-dose vaccine regimen. The use of mHealth should be strongly considered in mass vaccination campaigns in future initiatives.     

Inhibitory Synapse Formation in a Co-culture Model Incorporating GABAergic Medium Spiny Neurons and HEK293 Cells Stably Expressing GABAA Receptors

Inhibitory neurons act in the central nervous system to regulate the dynamics and spatio-temporal co-ordination of neuronal networks. GABA (γ-aminobutyric acid) is the predominant inhibitory neurotransmitter in the brain. It is released from the presynaptic terminals of inhibitory neurons within highly specialized intercellular junctions known as synapses, where it binds to GABA_A receptors (GABA_ARs) present at the plasma membrane of the synapse-receiving, postsynaptic neurons. Activation of these GABA-gated ion channels leads to influx of chloride resulting in postsynaptic potential changes that decrease the probability that these neurons will generate action potentials. During development, diverse types of inhibitory neurons with distinct morphological, electrophysiological and neurochemical characteristics have the ability to recognize their target neurons and form synapses which incorporate specific GABA_ARs subtypes. This principle of selective innervation of neuronal targets raises the question as to how the appropriate synaptic partners identify each other. To elucidate the underlying molecular mechanisms, a novel in vitro co-culture model system was established, in which medium spiny GABAergic neurons, a highly homogenous population of neurons isolated from the embryonic striatum, were cultured with stably transfected HEK293 cell lines that express different GABA_AR subtypes. Synapses form rapidly, efficiently and selectively in this system, and are easily accessible for quantification. Our results indicate that various GABA_AR subtypes differ in their ability to promote synapse formation, suggesting that this reduced in vitro model system can be used to reproduce, at least in part, the in vivo conditions required for the recognition of the appropriate synaptic partners and formation of specific synapses. Here the protocols for culturing the medium spiny neurons and generating HEK293 cells lines expressing GABA_ARs are first described, followed by detailed instructions on how to combine these two cell types in co-culture and analyze the formation of synaptic contacts.