Transgenic avidin maize is resistant to storage insect pests

Avidin is a glycoprotein found in chicken egg white, that sequesters the vitamin biotin. Here we show that when present in maize at levels of ≥100 p.p.m., avidin is toxic to and prevents development of insects that damage grains during storage. Insect toxicity is caused by a biotin deficiency, as shown by prevention of toxicity with biotin supplementation. The avidin maize is not, however, toxic to mice when administered as the sole component of their diet for 21 days. These data suggest that avidin expression in food or feed grain crops can be used as a biopesticide against a spectrum of stored-product insect pests

Shortcomings of short hairpin RNA-based transgenic RNA interference in mouse oocytes

<p>Abstract</p> <p>Background</p> <p>RNA interference (RNAi) is a powerful approach to study a gene function. Transgenic RNAi is an adaptation of this approach where suppression of a specific gene is achieved by expression of an RNA hairpin from a transgene. In somatic cells, where a long double-stranded RNA (dsRNA) longer than 30 base-pairs can induce a sequence-independent interferon response, short hairpin RNA (shRNA) expression is used to induce RNAi. In contrast, transgenic RNAi in the oocyte routinely employs a long RNA hairpin. Transgenic RNAi based on long hairpin RNA, although robust and successful, is restricted to a few cell types, where long double-stranded RNA does not induce sequence-independent responses. Transgenic RNAi in mouse oocytes based on a shRNA offers several potential advantages, including simple cloning of the transgenic vector and an ability to use the same targeting construct in any cell type.</p> <p>Results</p> <p>Here we report our experience with shRNA-based transgenic RNAi in mouse oocytes. Despite optimal starting conditions for this experiment, we experienced several setbacks, which outweigh potential benefits of the shRNA system. First, obtaining an efficient shRNA is potentially a time-consuming and expensive task. Second, we observed that our transgene, which was based on a common commercial vector, was readily silenced in transgenic animals.</p> <p>Conclusions</p> <p>We conclude that, the long RNA hairpin-based RNAi is more reliable and cost-effective and we recommend it as a method-of-choice when a gene is studied selectively in the oocyte.</p

The development of descending projections from the brainstem to the spinal cord in the fetal sheep

<p>Abstract</p> <p>Background</p> <p>Although the fetal sheep is a favoured model for studying the ontogeny of physiological control systems, there are no descriptions of the timing of arrival of the projections of supraspinal origin that regulate somatic and visceral function. In the early development of birds and mammals, spontaneous motor activity is generated within spinal circuits, but as development proceeds, a distinct change occurs in spontaneous motor patterns that is dependent on the presence of intact, descending inputs to the spinal cord. In the fetal sheep, this change occurs at approximately 65 days gestation (G65), so we therefore hypothesised that spinally-projecting axons from the neurons responsible for transforming fetal behaviour must arrive at the spinal cord level shortly before G65. Accordingly we aimed to identify the brainstem neurons that send projections to the spinal cord in the mature sheep fetus at G140 (term = G147) with retrograde tracing, and thus to establish whether any projections from the brainstem were absent from the spinal cord at G55, an age prior to the marked change in fetal motor activity has occurred.</p> <p>Results</p> <p>At G140, CTB labelled cells were found within and around nuclei in the reticular formation of the medulla and pons, within the vestibular nucleus, raphe complex, red nucleus, and the nucleus of the solitary tract. This pattern of labelling is similar to that previously reported in other species. The distribution of CTB labelled neurons in the G55 fetus was similar to that of the G140 fetus.</p> <p>Conclusion</p> <p>The brainstem nuclei that contain neurons which project axons to the spinal cord in the fetal sheep are the same as in other mammalian species. All projections present in the mature fetus at G140 have already arrived at the spinal cord by approximately one third of the way through gestation. The demonstration that the neurons responsible for transforming fetal behaviour in early ontogeny have already reached the spinal cord by G55, an age well before the change in motor behaviour occurs, suggests that the projections do not become fully functional until well after their arrival at the spinal cord.</p

Weight Loss and Mortality in Overweight and Obese Cancer Survivors: A Systematic Review

Background Excess adiposity is a risk factor for poorer cancer survival, but there is uncertainty over whether losing weight reduces the risk. We conducted a critical review of the literature examining weight loss and mortality in overweight or obese cancer survivors. Methods We systematically searched PubMed and EMBASE for articles reporting associations between weight loss and mortality (cancer-specific or all-cause) in overweight/obese patients with obesity-related cancers. Where available, data from the same studies on non-overweight patients were compared. Results Five articles describing observational studies in breast cancer survivors were included. Four studies reported a positive association between weight loss and mortality in overweight/obese survivors, and the remaining study observed no significant association. Results were similar for non-overweight survivors. Quality assessment indicated high risk of bias across studies. Conclusions There is currently a lack of observational evidence that weight loss improves survival for overweight and obese cancer survivors. However, the potential for bias in these studies is considerable and the results likely reflect the consequences of disease-related rather than intentional weight loss. There is a need for stronger study designs, incorporating measures of intentionality of weight loss, and extended to other cancers

Human and mouse essentiality screens as a resource for disease gene discovery.

The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery

An overview of the ORACLES (ObseRvations of Aerosols above CLouds and their intEractionS) project: aerosol–cloud–radiation interactions in the southeast Atlantic basin

This is the final version. Available on open access from the European Geosciences Union via the DOI in this recordData availability: All ORACLES data are accessible via the digital object identifiers (DOIs) provided under ORACLES Science Team (2020a–d) references: https://doi.org/10.5067/Suborbital/ORACLES/P3/2018_V2 (ORACLES Science Team, 2020a), https://doi.org/10.5067/Suborbital/ORACLES/P3/2017_V2 (ORACLES Science Team, 2020b), https://doi.org/10.5067/Suborbital/ORACLES/P3/2016_V2 (ORACLES Science Team, 2020c), and https://doi.org/10.5067/Suborbital/ORACLES/ER2/2016_V2 (ORACLES Science Team, 2020d). The only exceptions are noted as footnotes to Table B2.Southern Africa produces almost a third of the Earth's biomass burning (BB) aerosol particles, yet the fate of these particles and their influence on regional and global climate is poorly understood. ORACLES (ObseRvations of Aerosols above CLouds and their intEractionS) is a 5-year NASA EVS-2 (Earth Venture Suborbital-2) investigation with three intensive observation periods designed to study key atmospheric processes that determine the climate impacts of these aerosols. During the Southern Hemisphere winter and spring (June–October), aerosol particles reaching 3–5 km in altitude are transported westward over the southeast Atlantic, where they interact with one of the largest subtropical stratocumulus (Sc) cloud decks in the world. The representation of these interactions in climate models remains highly uncertain in part due to a scarcity of observational constraints on aerosol and cloud properties, as well as due to the parameterized treatment of physical processes. Three ORACLES deployments by the NASA P-3 aircraft in September 2016, August 2017, and October 2018 (totaling ∼350 science flight hours), augmented by the deployment of the NASA ER-2 aircraft for remote sensing in September 2016 (totaling ∼100 science flight hours), were intended to help fill this observational gap. ORACLES focuses on three fundamental science themes centered on the climate effects of African BB aerosols: (a) direct aerosol radiative effects, (b) effects of aerosol absorption on atmospheric circulation and clouds, and (c) aerosol–cloud microphysical interactions. This paper summarizes the ORACLES science objectives, describes the project implementation, provides an overview of the flights and measurements in each deployment, and highlights the integrative modeling efforts from cloud to global scales to address science objectives. Significant new findings on the vertical structure of BB aerosol physical and chemical properties, chemical aging, cloud condensation nuclei, rain and precipitation statistics, and aerosol indirect effects are emphasized, but their detailed descriptions are the subject of separate publications. The main purpose of this paper is to familiarize the broader scientific community with the ORACLES project and the dataset it produced.NAS

Identification of NAD(P)H Quinone Oxidoreductase Activity in Azoreductases from P. aeruginosa: Azoreductases and NAD(P)H Quinone Oxidoreductases Belong to the Same FMN-Dependent Superfamily of Enzymes

Water soluble quinones are a group of cytotoxic anti-bacterial compounds that are secreted by many species of plants, invertebrates, fungi and bacteria. Studies in a number of species have shown the importance of quinones in response to pathogenic bacteria of the genus Pseudomonas. Two electron reduction is an important mechanism of quinone detoxification as it generates the less toxic quinol. In most organisms this reaction is carried out by a group of flavoenzymes known as NAD(P)H quinone oxidoreductases. Azoreductases have previously been separate from this group, however using azoreductases from Pseudomonas aeruginosa we show that they can rapidly reduce quinones. Azoreductases from the same organism are also shown to have distinct substrate specificity profiles allowing them to reduce a wide range of quinones. The azoreductase family is also shown to be more extensive than originally thought, due to the large sequence divergence amongst its members. As both NAD(P)H quinone oxidoreductases and azoreductases have related reaction mechanisms it is proposed that they form an enzyme superfamily. The ubiquitous and diverse nature of azoreductases alongside their broad substrate specificity, indicates they play a wide role in cellular survival under adverse conditions

Engineering of microfabricated ion traps and integration of advanced on-chip features

Atomic ions trapped in electromagnetic potentials have long been used for fundamental studies in quantum physics. Over the past two decades, trapped ions have been successfully used to implement technologies such as quantum computing, quantum simulation, atomic clocks, mass spectrometers and quantum sensors. Advanced fabrication techniques, taken from other established or emerging disciplines, are used to create new, reliable ion-trap devices aimed at large-scale integration and compatibility with commercial fabrication. This Technical Review covers the fundamentals of ion trapping before discussing the design of ion traps for the aforementioned applications. We overview the current microfabrication techniques and the various considerations behind the choice of materials and processes. Finally, we discuss current efforts to include advanced, on-chip features in next-generation ion traps

Recent advances in studies of polymicrobial interactions in oral biofilms

The oral cavity supports a complex and finely balanced consortium of microbial species, many of which cooperate within structured biofilms. These communities develop through multitudinous synergistic and antagonistic interspecies relationships. Changes in the dynamics of oral microbial populations are associated with the transition from healthy teeth and gums to dental caries, gingivitis and periodontitis. Understanding the ecology of oral biofilm communities, and how different species communicate within a given host, will inform new strategies for treatment and prevention of oral diseases. Advances in sequencing technologies have fuelled an increasing trend towards global genomic and proteomic approaches to determine the key factors that initiate oral diseases. Whilst metabolic profiling seeks to identify phenotypic changes of whole microbial communities, transcriptomic studies are exploring their complex interactions with each other and the host. This review discusses the most recent in vitro and in vivo studies of interspecies interactions within polymicrobial oral biofilms