Overexpression of SAMDC1 gene in Arabidopsis thaliana increases expression of defense-related genes as well as resistance to Pseudomonas syringae and Hyaloperonospora arabidopsidis

It has been previously described that elevation of endogenous spermine levels in Arabidopsis could be achieved by transgenic overexpression of S-Adenosylmethionine decarboxylase (SAMDC) or Spermine synthase (SPMS). In both cases, spermine accumulation had an impact on the plant transcriptome, with up-regulation of a set of genes enriched in functional categories involved in defense-related processes against both biotic and abiotic stresses. In this work, the response of SAMDC1-overexpressing plants against bacterial and oomycete pathogens has been tested. The expression of several pathogen defense-related genes was induced in these plants as well as in wild type plants exposed to an exogenous supply of spermine. SAMDC1-overexpressing plants showed an increased tolerance to infection by Pseudomonas syringae and by Hyaloperonospora arabidopsidis. Both results add more evidence to the hypothesis that spermine plays a key role in plant resistance to biotic stress

Energy cost and return for hunting in African wild dogs and Cheetahs

African wild dogs (Lycaon pictus) are reported to hunt with energetically costly long chase distances. We used high-resolution GPS and inertial technology to record 1,119 high-speed chases of all members of a pack of six adult African wild dogs in northern Botswana. Dogs performed multiple short, high-speed, mostly unsuccessful chases to capture prey, while cheetahs (Acinonyx jubatus) undertook even shorter, higher-speed hunts. We used an energy balance model to show that the energy return from group hunting and feeding substantially outweighs the cost of multiple short chases, which indicates that African wild dogs are more energetically robust than previously believed. Comparison with cheetah illustrates the trade-off between sheer athleticism and high individual kill rate characteristic of cheetahs, and the energetic robustness of frequent opportunistic group hunting and feeding by African wild dogs

Abundance and Distribution of Enteric Bacteria and Viruses in Coastal and Estuarine Sediments—a Review

The long term survival of fecal indicator organisms (FIOs) and human pathogenic microorganisms in sediments is important from a water quality, human health and ecological perspective. Typically, both bacteria and viruses strongly associate with particulate matter present in freshwater, estuarine and marine environments. This association tends to be stronger in finer textured sediments and is strongly influenced by the type and quantity of clay minerals and organic matter present. Binding to particle surfaces promotes the persistence of bacteria in the environment by offering physical and chemical protection from biotic and abiotic stresses. How bacterial and viral viability and pathogenicity is influenced by surface attachment requires further study. Typically, long-term association with surfaces including sediments induces bacteria to enter a viable-but-non-culturable (VBNC) state. Inherent methodological challenges of quantifying VBNC bacteria may lead to the frequent under-reporting of their abundance in sediments. The implications of this in a quantitative risk assessment context remain unclear. Similarly, sediments can harbor significant amounts of enteric viruses, however, the factors regulating their persistence remains poorly understood. Quantification of viruses in sediment remains problematic due to our poor ability to recover intact viral particles from sediment surfaces (typically <10%), our inability to distinguish between infective and damaged (non-infective) viral particles, aggregation of viral particles, and inhibition during qPCR. This suggests that the true viral titre in sediments may be being vastly underestimated. In turn, this is limiting our ability to understand the fate and transport of viruses in sediments. Model systems (e.g., human cell culture) are also lacking for some key viruses, preventing our ability to evaluate the infectivity of viruses recovered from sediments (e.g., norovirus). The release of particle-bound bacteria and viruses into the water column during sediment resuspension also represents a risk to water quality. In conclusion, our poor process level understanding of viral/bacterial-sediment interactions combined with methodological challenges is limiting the accurate source apportionment and quantitative microbial risk assessment for pathogenic organisms associated with sediments in aquatic environments

Influenza Research Database: An integrated bioinformatics resource for influenza virus research

The Influenza Research Database (IRD) is a U.S. National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Bioinformatics Resource Center dedicated to providing bioinformatics support for influenza virus research. IRD facilitates the research and development of vaccines, diagnostics and therapeutics against influenza virus by providing a comprehensive collection of influenza-related data integrated from various sources, a growing suite of analysis and visualization tools for data mining and hypothesis generation, personal workbench spaces for data storage and sharing, and active user community support. Here, we describe the recent improvements in IRD including the use of cloud and high performance computing resources, analysis and visualization of user-provided sequence data with associated metadata, predictions of novel variant proteins, annotations of phenotype-associated sequence markers and their predicted phenotypic effects, hemagglutinin (HA) clade classifications, an automated tool for HA subtype numbering conversion, linkouts to disease event data and the addition of host factor and antiviral drug components. All data and tools are freely available without restriction from the IRD website at https://www.fludb.org.National Institutes of Health/National Institute for Allergy and Infectious Diseases [HHSN272201400028C]. Funding for open access charge: J. Craig Venter Institute

Protein crystals in adenovirus type 5-infected cells: requirements for intranuclear crystallogenesis, structural and functional analysis

Intranuclear crystalline inclusions have been observed in the nucleus of epithelial cells infected with Adenovirus serotype 5 (Ad5) at late steps of the virus life cycle. Using immuno-electron microscopy and confocal microscopy of cells infected with various Ad5 recombinants modified in their penton base or fiber domains, we found that these inclusions represented crystals of penton capsomers, the heteromeric capsid protein formed of penton base and fiber subunits. The occurrence of protein crystals within the nucleus of infected cells required the integrity of the fiber knob and part of the shaft domain. In the knob domain, the region overlapping residues 489–492 in the FG loop was found to be essential for crystal formation. In the shaft, a large deletion of repeats 4 to 16 had no detrimental effect on crystal inclusions, whereas deletion of repeats 8 to 21 abolished crystal formation without altering the level of fiber protein expression. This suggested a crucial role of the five penultimate repeats in the crystallisation process. Chimeric pentons made of Ad5 penton base and fiber domains from different serotypes were analyzed with respect to crystal formation. No crystal was found when fiber consisted of shaft (S) from Ad5 and knob (K) from Ad3 (heterotypic S5-K3 fiber), but occurred with homotypic S3K3 fiber. However, less regular crystals were observed with homotypic S35-K35 fiber. TB5, a monoclonal antibody directed against the Ad5 fiber knob was found by immunofluorescence microscopy to react with high efficiency with the intranuclear protein crystals in situ. Data obtained with Ad fiber mutants indicated that the absence of crystalline inclusions correlated with a lower infectivity and/or lower yields of virus progeny, suggesting that the protein crystals might be involved in virion assembly. Thus, we propose that TB5 staining of Ad-infected 293 cells can be used as a prognostic assay for the viability and productivity of fiber-modified Ad5 vectors

A 3D individual-based model to investigate the spatially heterogeneous response of bacterial biofilms to antimicrobial agents

The response of bacterial biofilms to treatment with antimicrobial agents is often characterized by the emergence of recalcitrant cellular microcolonies. We present an individual-based model to investigate the biophysical mechanisms of the selective resistance that arises within the biofilm and leads to a spatially heterogeneous response upon treatment with antibiotics. The response occurs in 3 distinct phases. In the first phase, the subpopulation of metabolically active cells diminishes due to antibiotic-induced cell death. Subsequently, in the second phase, increased nutrient availability allows dormant cells in the lower layers of the biofilm to transform into metabolically active cells. In the third phase, survival of the biofilm is governed by the interplay between 2 contrasting factors: (1) rate of antibiotic-induced cell death and (2) rate of transformation of dormant cells into active ones. Metabolically active cells at the distal edge of the biofilm sacrifice themselves to protect the dormant cells in the interior by (1) reducing local antibiotic concentrations and (2) increasing nutrient availability. In the presence of quorum sensing, biofilms exhibit increased tolerance compared with the quorum sensing-negative strains. Extracellular polymeric substance (EPS) forms a protective layer at the top of the biofilm, thereby limiting antibiotic penetration. The surviving cells, in turn, produce EPS resulting in a feedback-like mechanism of resistance. Whereas resistance in QS- biofilms occurs because of transformation of dormant cells into metabolically active cells, this transformation is less pronounced in QS+ biofilms, and resistance is a consequence of the sequestration of the antibiotic by EPS

Design and characterisation of food grade powders and inks for microstructure control using 3D printing

Additive Manufacturing techniques have been previously applied to food materials with direct consumption in mind, as opposed to creating structural ingredients as shown in this study. First, semi-crystalline cellulose was mechanically treated by ball milling to render an amorphous powder, which has been characterised. Requirements for the subsequent recrystallization of this powder with a view to structuring have been determined through the control of moisture and thermal energy. Food inks based on xanthan gum have been formulated to enable successful jetting with a FujiFilm Dimatix ink jet printer. The polymer inks were subsequently jetted onto the amorphous cellulose powder to observe powder-binder interactions. Material combinations and parameters were optimised to produce cohesive geometric structures. The results of this study are promising when looking towards using these materials in a binder jetting additive manufacturing technique using designer particles and inks to create structures for use in food products

The resolution sensitivity of the Asian summer monsoon and its inter-model comparison between MRI-AGCM and MetUM

In this study, we compare the resolution sensitivity of the Asian Summer Monsoon (ASM) in two Atmospheric General Circulation Models (AGCMs): the MRI-AGCM and the MetUM. We analyze the MetUM at three different resolutions, N96 (approximately 200-km mesh on the equator), N216 (90-km mesh) and N512 (40-km mesh), and the MRI-AGCM at TL95 (approximately 180-km mesh on the equator), TL319 (60-km mesh), and TL959 (20-km mesh). The MRI-AGCM and the MetUM both show decreasing precipitation over the western Pacific with increasing resolution, but their precipitation responses differ over the Indian Ocean. In MRI-AGCM, a large precipitation increase appears off the equator (5–20°N). In MetUM, this off-equatorial precipitation increase is less significant and precipitation decreases over the equator. Moisture budget analysis demonstrates that a changing in moisture flux convergence at higher resolution is related to the precipitation response. Orographic effects, intra-seasonal variability and the representation of the meridional thermal gradient are explored as possible causes of the resolution sensitivity. Both high-resolution AGCMs (TL959 and N512) can represent steep topography, which anchors the rainfall pattern over south Asia and the Maritime Continent. In MRI-AGCM, representation of low pressure systems in TL959 also contributes to the rainfall pattern. Furthermore, the seasonal evolution of the meridional thermal gradient appears to be more accurate at higher resolution, particularly in the MRI-AGCM. These findings emphasize that the impact of resolution is only robust across the two AGCMs for some features of the ASM, and highlights the importance of multi-model studies of GCM resolution sensitivity

Expanding the clinical phenotype of IARS2-related mitochondrial disease.

BACKGROUND: IARS2 encodes a mitochondrial isoleucyl-tRNA synthetase, a highly conserved nuclear-encoded enzyme required for the charging of tRNAs with their cognate amino acid for translation. Recently, pathogenic IARS2 variants have been identified in a number of patients presenting broad clinical phenotypes with autosomal recessive inheritance. These phenotypes range from Leigh and West syndrome to a new syndrome abbreviated CAGSSS that is characterised by cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, as well as cataract with no additional anomalies. METHODS: Genomic DNA from Iranian probands from two families with consanguineous parental background and overlapping CAGSSS features were subjected to exome sequencing and bioinformatics analysis. RESULTS: Exome sequencing and data analysis revealed a novel homozygous missense variant (c.2625C > T, p.Pro909Ser, NM_018060.3) within a 14.3 Mb run of homozygosity in proband 1 and a novel homozygous missense variant (c.2282A > G, p.His761Arg) residing in an ~ 8 Mb region of homozygosity in a proband of the second family. Patient-derived fibroblasts from proband 1 showed normal respiratory chain enzyme activity, as well as unchanged oxidative phosphorylation protein subunits and IARS2 levels. Homology modelling of the known and novel amino acid residue substitutions in IARS2 provided insight into the possible consequence of these variants on function and structure of the protein. CONCLUSIONS: This study further expands the phenotypic spectrum of IARS2 pathogenic variants to include two patients (patients 2 and 3) with cataract and skeletal dysplasia and no other features of CAGSSS to the possible presentation of the defects in IARS2. Additionally, this study suggests that adult patients with CAGSSS may manifest central adrenal insufficiency and type II esophageal achalasia and proposes that a variable sensorineural hearing loss onset, proportionate short stature, polyneuropathy, and mild dysmorphic features are possible, as seen in patient 1. Our findings support that even though biallelic IARS2 pathogenic variants can result in a distinctive, clinically recognisable phenotype in humans, it can also show a wide range of clinical presentation from severe pediatric neurological disorders of Leigh and West syndrome to both non-syndromic cataract and cataract accompanied by skeletal dysplasia