Are agricultural researchers working on the right crops to enable food and nutrition security under future climates?

This study examined how crop-specific agricultural research investments can be prioritised to anticipate climate change impact on crops and to enable the production of more nutritious food. We used a simple crop modelling approach to derive expected future changes in regional climate suitability for crops. To determine if different starch-rich and pulse crops are currently underresearched or overresearched, we examined the global relation between crop-specific research output (number of publications) and the total nutrient output available for human consumption. Our analysis shows that current research investments are mostly associated with the current energy output of crops. Other things equal, investment levels tend to be slightly lower for crops better adapted to future climates and tend to decrease as crop nutrient richness increases. Among starch-rich crops, maize, barley, and rice receive substantially more research investment than justified by their current nutrient output. Sweetpotato, potato, and wheat show substantial current research deficits. Sweetpotato is most strongly underresearched in regions with improving climate suitability. For potato, research deficits occur in regions where these crops will experience less suitable climate conditions. For wheat, the deficits are distributed equally across regions with negative and positive climate effects. Three crops are significantly over-researched, namely maize, rice, and barley. Among pulses, cowpea, and lupin are generally overresearched. Common bean is highly underresearched, but these deficits concentrate in areas where it will likely suffer from climate change. Lentil, broad bean, and chickpea are underresearched, with deficits concentrating in regions where these crops will tend to benefit from future climates. Agricultural research investment allocations will need to consider additional factors not taken into account in this study, but our findings suggest that current allocations need reconsideration to support climate adaptation and enhance healthy human nutrition

Cryopreservation of Paramecium bursaria Chlorella Virus-1 during an active infection cycle of its host

Best practices in laboratory culture management often include cryopreservation of microbiota, but this can be challenging with some virus particles. By preserving viral isolates researchers can mitigate genetic drift and laboratory-induced selection, thereby maintaining genetically consistent strains between experiments. To this end, we developed a method to cryopreserve the model, green-alga infecting virus, Paramecium bursaria Chlorella virus 1 (PBCV-1). We explored cryotolerance of the infectivity of this virus particle, whereby freezing without cryoprotectants was found to maintain the highest infectivity (~2.5%). We then assessed the cryopreservation potential of PBCV-1 during an active infection cycle in its Chlorella variabilisNC64A host, and found that virus survivorship was highest (69.5 ± 16.5%) when the infected host is cryopreserved during mid-late stages of infection (i.e., coinciding with virion assembly). The most optimal condition for cryopreservation was observed at 240 minutes post-infection. Overall, utilizing the cell as a vehicle for viral cryopreservation resulted in 24.9–30.1 fold increases in PBCV-1 survival based on 95% confidence intervals of frozen virus particles and virus cryopreserved at 240 minutes post-infection. Given that cryoprotectants are often naturally produced by psychrophilic organisms, we suspect that cryopreservation of infected hosts may be a reliable mechanism for virus persistence in non-growth permitting circumstances in the environment, such as ancient permafrosts

\u3ci\u3eParamecium bursaria\u3c/i\u3e Chlorella Virus 1 Encodes a Polyamine Acetyltransferase

Background: PBCV-1 gene a654l encodes a protein with sequence similarity to GCN5 histone acetyltransferases. Results: A crystal structure of A654L bound to coenzyme A reveals how A654L acetylates polyamines, not histone lysines. Conclusion: A654L functions as a polyamine acetyltransferase. Significance: As the first viral polyamine acetyltransferase, A654L has a possible role in host polyamine catabolism in viral replication. Paramecium bursaria chlorella virus 1 (PBCV-1), a large DNA virus that infects green algae, encodes a histone H3 lysine 27-specific methyltransferase that functions in global transcriptional silencing of the host. PBCV-1 has another gene a654l that encodes a protein with sequence similarity to the GCN5 family histone acetyltransferases. In this study, we report a 1.5A˚ crystal structure of PBCV-1 A654L in a complex with coenzyme A. The structure reveals a unique feature of A654L that precludes its acetylation of histone peptide substrates. We demonstrate that A654L, hence named viral polyamine acetyltransferase (vPAT), acetylates polyamines such as putrescine, spermidine, cadaverine, and homospermidine present in both PBCV-1 and its host through a reaction dependent upon a conserved glutamate 27. Our study suggests that as the first virally encoded polyamine acetyltransferase, vPAT plays a possible key role in the regulation of polyamine catabolism in the host during viral replication. Includes Supplemental Material

Protein-rich legume and pseudo-cereal crop suitability under present and future European climates

Open Access Article; Published online: 29 Nov 2019.Replacing animal proteins with plant proteins in diets has been demonstrated to have both health and environmental advantages, driving a debate about the potential of protein-rich crops as dietary replacements for animal products. However, there is a lack of knowledge on how climate change could influence the potential for producing protein-rich crops. This study addresses this knowledge gap for the European Union. We analysed 13 protein-rich crops, using the crop suitability model EcoCrop and climate projections for the 2050s, based on 30 Global Circulation Models, under the Representative Concentration Pathway 4.5. The results suggest that current protein-rich crop distributions reflect climatic suitability. We demonstrate the heterogeneous impacts of climate change on crop suitability. In general, conditions in northern Europe were modelled to become more favourable for protein-rich crops, while in southern Europe modelled future climates limit the production of traditional protein-rich crops commonly grown there, including chickpea and lentil. Model results show an expanded area of high suitability for quinoa. Our results confirm the need for concerted breeding and research planning strategies to improve the tolerance of faba bean, lentil, and chickpea to the abiotic stresses that are predicted to become more common with climate change. At the same time, production in northern Europe can benefit from experimentation with protein-rich crops predicted to become more suitable there. Production planning and agricultural policy should consider these likely impacts, to encourage shifts that follow the emerging geographic patterns of crop suitability, and to support the resilience of protein-rich crop production in regions that may be negatively impacted by climate change

\u3ci\u3eParamecium bursaria\u3c/i\u3e Chlorella Virus 1 Encodes a Polyamine Acetyltransferase

Background: PBCV-1 gene a654l encodes a protein with sequence similarity to GCN5 histone acetyltransferases. Results: A crystal structure of A654L bound to coenzyme A reveals how A654L acetylates polyamines, not histone lysines. Conclusion: A654L functions as a polyamine acetyltransferase. Significance: As the first viral polyamine acetyltransferase, A654L has a possible role in host polyamine catabolism in viral replication. Paramecium bursaria chlorella virus 1 (PBCV-1), a large DNA virus that infects green algae, encodes a histone H3 lysine 27-specific methyltransferase that functions in global transcriptional silencing of the host. PBCV-1 has another gene a654l that encodes a protein with sequence similarity to the GCN5 family histone acetyltransferases. In this study, we report a 1.5A˚ crystal structure of PBCV-1 A654L in a complex with coenzyme A. The structure reveals a unique feature of A654L that precludes its acetylation of histone peptide substrates. We demonstrate that A654L, hence named viral polyamine acetyltransferase (vPAT), acetylates polyamines such as putrescine, spermidine, cadaverine, and homospermidine present in both PBCV-1 and its host through a reaction dependent upon a conserved glutamate 27. Our study suggests that as the first virally encoded polyamine acetyltransferase, vPAT plays a possible key role in the regulation of polyamine catabolism in the host during viral replication. Includes Supplemental Material

Comparative genomics, transcriptomics, and physiology distinguish symbiotic from free-living \u3ci\u3eChlorella\u3c/i\u3e strains

Most animal–microbe symbiotic interactions must be advantageous to the host and provide nutritional benefits to the endosymbiont. When the host provides nutrients, it can gain the capacity to control the interaction, promote self-growth, and increase its fitness. Chlorella-like green algae engage in symbiotic relationships with certain protozoans, a partnership that significantly impacts the physiology of both organisms. Consequently, it is often challenging to grow axenic Chlorella cultures after isolation from the host because they are nutrient fastidious and often susceptible to virus infection. We hypothesize that the establishment of a symbiotic relationship resulted in natural selection for nutritional and metabolic traits that differentiate symbiotic algae from their free-living counterparts. Here, we compare metabolic capabilities of 5 symbiotic and 4 free-living Chlorella strains by determining growth levels on combinations of nitrogen and carbon sources. Data analysis by hierarchical clustering revealed clear separation of the symbiotic and free-living Chlorella into two distinct clades. Symbiotic algae did not grow on nitrate but did grow on two symbiont-specific amino acids (Asn and Ser) on which the free-living strains did not grow. The use of these amino acids was exclusively affected by the presence/absence of Ca2+ in the medium, and the differences were magnified if galactose was provided rather than sucrose or glucose. In addition, Chlorella variabilis NC64A genomic and differential expression analysis confirmed the presence of abundant amino acid transporter protein motifs, some of which were expressed constitutively both axenically and within the host. Significantly, all 5 symbiotic strains exhibited similar physiological phenotypes even though they were isolated as symbionts from different host organisms. Such similarities indicate a parallel coevolution of shared metabolic pathways across multiple independent symbiotic events. Collectively, our results suggest that physiological changes drive the Chlorella symbiotic phenotype and contribute to their natural fitness. Includes Supplementary materials

Comparative genomics, transcriptomics, and physiology distinguish symbiotic from free-living \u3ci\u3eChlorella\u3c/i\u3e strains

Most animal–microbe symbiotic interactions must be advantageous to the host and provide nutritional benefits to the endosymbiont. When the host provides nutrients, it can gain the capacity to control the interaction, promote self-growth, and increase its fitness. Chlorella-like green algae engage in symbiotic relationships with certain protozoans, a partnership that significantly impacts the physiology of both organisms. Consequently, it is often challenging to grow axenic Chlorella cultures after isolation from the host because they are nutrient fastidious and often susceptible to virus infection. We hypothesize that the establishment of a symbiotic relationship resulted in natural selection for nutritional and metabolic traits that differentiate symbiotic algae from their free-living counterparts. Here, we compare metabolic capabilities of 5 symbiotic and 4 free-living Chlorella strains by determining growth levels on combinations of nitrogen and carbon sources. Data analysis by hierarchical clustering revealed clear separation of the symbiotic and free-living Chlorella into two distinct clades. Symbiotic algae did not grow on nitrate but did grow on two symbiont-specific amino acids (Asn and Ser) on which the free-living strains did not grow. The use of these amino acids was exclusively affected by the presence/absence of Ca2+ in the medium, and the differences were magnified if galactose was provided rather than sucrose or glucose. In addition, Chlorella variabilis NC64A genomic and differential expression analysis confirmed the presence of abundant amino acid transporter protein motifs, some of which were expressed constitutively both axenically and within the host. Significantly, all 5 symbiotic strains exhibited similar physiological phenotypes even though they were isolated as symbionts from different host organisms. Such similarities indicate a parallel coevolution of shared metabolic pathways across multiple independent symbiotic events. Collectively, our results suggest that physiological changes drive the Chlorella symbiotic phenotype and contribute to their natural fitness. Includes Supplementary materials

What are the characteristics of excellent physicians and residents in the clinical workplace? A systematic review.

OBJECTIVES: In order to recognise and facilitate the development of excellent medical doctors (physicians and residents), it is important to first identify the characteristics of excellence. Failure to recognising excellence causes loss of talent, loss of role models and it lowers work ethos. This causes less than excellent patient care and lack of commitment to improve the healthcare system. DESIGN: Systematic review performed according to the Association for Medical Education in Europe guideline. INFORMATION SOURCES: We searched Medline, Embase, Psycinfo, ERIC and CINAHL until 14 March 2022. ELIGIBILITY CRITERIA: We included original studies describing characteristics of excellent medical doctors, using a broad approach as to what is considered excellence. Assuming that excellence will be viewed differently depending on the interplay, and that different perspectives (peers, supervisors and patients) will add to a complete picture of the excellent medical doctor, we did not limit this review to a specific perspective. DATA EXTRACTION AND SYNTHESIS: Data extraction and quality assessment were performed independently by two researchers. We used the Quality Assessment Tool for Different Designs for quality assessment. RESULTS: Eleven articles were eligible and described the characteristics from different perspectives: (1) physicians on physicians, (2) physicians on residents, (3) patients on physicians and (4) mixed group (diverse sample of participants on physicians). The included studies showed a wide range of characteristics, which could be grouped into competencies (communication, professionalism and knowledge), motivation (directed to learning and to patient care) and personality (flexibility, empathy). CONCLUSIONS: In order to define excellence of medical doctors three clusters seem important: competence, motivation and personality. This is in line with Renzulli’s model of gifted behaviour. Our work adds to this model by specifying the content of these clusters, and as such provides a basis for definition and recognition of medical excellence

Nitric oxide synthase inhibition results in synergistic anti-tumour activity with melphalan and tumour necrosis factor alpha-based isolated limb perfusions

Nitric oxide (NO) is an important molecule in regulating tumour blood flow and stimulating tumour angiogenesis. Inhibition of NO synthase by L-NAME might induce an anti-tumour effect by limiting nutrients and oxygen to reach tumour tissue or affecting vascular growth. The anti-tumour effect of L-NAME after systemic administration was studied in a renal subcapsular CC531 adenocarcinoma model in rats. Moreover, regional administration of L-NAME, in combination with TNF and melphalan, was studied in an isolated limb perfusion (ILP) model using BN175 soft-tissue sarcomas. Systemic treatment with L-NAME inhibited growth of adenocarcinoma significantly but was accompanied by impaired renal function. In ILP, reduced tumour growth was observed when L-NAME was used alone. In combination with TNF or melphalan, L-NAME increased response rates significantly compared to perfusions without L-NAME (0–64% and 0–63% respectively). An additional anti-tumour effect was demonstrated when L-NAME was added to the synergistic combination of melphalan and TNF (responses increased from 70 to 100%). Inhibition of NO synthase reduces tumour growth both after systemic and regional (ILP) treatment. A synergistic anti-tumour effect of L-NAME is observed in combination with melphalan and/or TNF using ILP. These results indicate a possible role of L-NAME for the treatment of solid tumours in a systemic or regional setting. © 2000 Cancer Research Campaig

SMRT Sequencing of Paramecium Bursaria Chlorella Virus-1 Reveals Diverse Methylation Stability in Adenines Targeted by Restriction Modification Systems

Chloroviruses (family Phycodnaviridae) infect eukaryotic, freshwater, unicellular green algae. A unique feature of these viruses is an abundance of DNA methyltransferases, with isolates dedicating up to 4.5% of their protein coding potential to these genes. This diversity highlights just one of the long-standing values of the chlorovirus model system; where group-wide epigenomic characterization might begin to elucidate the function(s) of DNA methylation in large dsDNA viruses. We characterized DNA modifications in the prototype chlorovirus, PBCV-1, using single-molecule real time (SMRT) sequencing (aka PacBio). Results were compared to total available sites predicted in silico based on DNA sequence alone. SMRT-software detected N6-methyl-adenine (m6A) at GATC and CATG recognition sites, motifs previously shown to be targeted by PBCV-1 DNA methyltransferases M.CviAI and M. CviAII, respectively. At the same time, PacBio analyses indicated that 10.9% of the PBCV-1 genome had large interpulse duration ratio (ipdRatio) values, the primary metric for DNA modification identification. These events represent 20.6x more sites than can be accounted for by all available adenines in GATC and CATG motifs, suggesting base or backbone modifications other than methylation might be present. To define methylation stability, we cross-compared methylation status of each GATC and CATG sequence in three biological replicates and found ∼81% of sites were stably methylated, while ∼2% consistently lack methylation. The remaining 17% of sites were stochastically methylated. When methylation status was analyzed for both strands of each target, we show that palindromes existed in completely non-methylated states, fully-methylated states, or hemi-methylated states, though GATC sites more often lack methylation than CATG sequences. Given that both sequences are targeted by not just methyltransferases, but by restriction endonucleases that are together encoded by PBCV-1 as virus-originating restriction modification (RM) systems, there is strong selective pressure to modify all target sites. The finding that most instances of non-methylation are associated with hemi-methylation is congruent with observations that hemi-methylated palindromes are resistant to cleavage by restriction endonucleases. However, sites where hemi-methylation is conserved might represent a unique regulatory function for PBCV-1. This study serves as a baseline for future investigation into the epigenomics of chloroviruses and their giant virus relatives