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Abstract Meeting the urgent need to protect and restore ecosystems requires effective decision‐making through wisely considering a range of evidence. However, weighing and assessing evidence to make complex decisions is challenging, particularly when evidence is of diverse types, subjects, and sources, and varies greatly in its quality and relevance. To tackle these challenges, we present the Balance Evidence Assessment Method (BEAM), an intuitive way to weigh and assess the evidence relating to the core assumptions underpinning the planning and implementation of conservation projects, strategies, and actions. Our method directly tackles the question of how to bring together diverse evidence whilst assessing its relevance, reliability, and strength of support for a given assumption, which can be mapped, for example to a Theory of Change. We consider how simple principles and safeguards in applying this method could help to respectfully, and equitably, include more local forms of knowledge when assessing assumptions, such as by ensuring diverse groups of individuals contribute and assess evidence. The method can be flexibly applied within existing decision‐making tools, platforms, and frameworks whenever assumptions (i.e., claims and hypotheses) are made. This method could greatly facilitate and improve the weighing of diverse evidence to make decisions in a range of situations, from local projects to global policy platforms.

Abstract Improving the effectiveness of conservation practice requires better use of evidence. Since 2004, researchers from the Conservation Evidence group (University of Cambridge) have engaged with over 1100 named practitioners, policymakers, funders and other academics from across the world to identify needs and develop a range of principles, tools and resources to embed evidence in decision making. The goal of this engagement (the Conservation Evidence Programme) was to deliver improved conservation practice leading to benefits for nature and society. Together, we developed a theory of change with five key strategies for delivering change, alongside a freely available Evidence Toolkit to support decision makers in achieving that change. The authors describe the toolkit, a collection of freely available tools and resources developed by the collaborative programme, and how co‐design, employing different levels of partner engagement, enabled its development. Reflecting on our experiences highlighted a number of insights and recommendations, including the need to identify where deep engagement is a necessary condition for success; the importance of collective agreement of the roles of different partners; the need to consider how to facilitate uptake of new tools or practices, particularly where that requires changes to organisational practices or culture; and the importance of establishing processes/channels for ongoing engagement with stakeholders, with a willingness to be flexible and open to incorporating new suggestions and perspectives as needed. The Conservation Evidence Programme has enabled practitioners, funders and policymakers to become part of a network of forward‐thinking organisations that is working collaboratively to help drive more effective conservation practice through improved evidence use.

Coronary artery bypass graft (CABG) pseudoaneurysms are a rare but often unrecognized clinical entity. They are prone to rupture and hemodynamic compromise and should therefore be on the differential in the appropriate patient. We present a case of a gentleman with a recent CABG surgery who presented with acute onset dyspnea and a large pleural effusion. Imaging revealed a saphenous vein graft pseudoaneurysm embedded in a mediastinal hematoma. Four weeks later, prior to planned stenting, the pseudoaneurysm had spontaneously closed. This case highlights an unusual acute presentation of a CABG pseudoaneurysm and a multidisciplinary approach to its management.

Societal biosecurity – measures built into everyday society to minimize risks from pests and diseases – is an important aspect of managing epidemics and pandemics. We aimed to identify societal options for reducing the transmission and spread of respiratory viruses. We used SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) as a case study to meet the immediate need to manage the COVID-19 pandemic and eventually transition to more normal societal conditions, and to catalog options for managing similar pandemics in the future. We used a ‘solution scanning’ approach. We read the literature; consulted psychology, public health, medical, and solution scanning experts; crowd-sourced options using social media; and collated comments on a preprint. Here, we present a list of 519 possible measures to reduce SARS-CoV-2 transmission and spread. We provide a long list of options for policymakers and businesses to consider when designing biosecurity plans to combat SARS-CoV-2 and similar pathogens in the future. We also developed an online application to help with this process. We encourage testing of actions, documentation of outcomes, revisions to the current list, and the addition of further options.

The purpose of this article is to provide a comment on Simone Weil’s brief but seminal essay ‘Reflections on the Right Use of School Studies with a View to the Love of God.’ It complements an earlier one on Weil’s Lectures on Philosophy . The essay was sent via a letter to her friend and mentor, the Catholic priest, and Dominican friar, Father Joseph-Marie Perrin O.P. It set out her belief that school studies should provide the individual pupil or student with an education in the value and acquisition of attention. This, Weil believed, would be of fundamental value when reaching out to God through prayer. Such a capacity for attention would also enhance the student’s general academic and social learning providing a basis for authentic dialogue with others, and not only teachers and schoolfellows. The article introduces her as a religious philosopher, explains the origins of the essay, and Weil’s friendship with Father Perrin, who was her Christian religious mentor, examines the text itself, considers some critical commentaries, and assesses its relevance to the philosophy and practice of education today.

Abstract How does microbiota research impact our understanding of biological individuality? We summarize the interdisciplinary summer school on “Microbiota, symbiosis and individuality: conceptual and philosophical issues” (July 2019), which was supported by a European Research Council starting grant project “Immunity, DEvelopment, and the Microbiota” (IDEM). The summer school centered around interdisciplinary group work on four facets of microbiota research: holobionts, individuality, causation, and human health. The conceptual discussion of cutting-edge empirical research provided new insights into microbiota and highlights the value of incorporating into meetings experts from other disciplines, such as philosophy and history of science. Video Abstract

We report a case of a 34-year-old woman who presented with an ST-segment elevation myocardial infarction with acute heart failure and a subsequent diagnosis of mosaic Turner syndrome (TS). The report also discusses cardiovascular disease in patients with TS and the current recommendations for screening and follow-up in these patients. (Level of Difficulty: Beginner.)

Background Phytophthora plant pathogens secrete effector proteins that are translocated into host plant cells during infection and collectively contribute to pathogenicity. A subset of these host-translocated effectors can be identified by the amino acid motif RXLR (arginine, any amino acid, leucine, arginine). Bioinformatics analysis has identified hundreds of putative RXLR effector genes in Phytophthora genomes, but the specific molecular function of most remains unknown. Methods Here we describe initial studies to investigate the use of Saccharomyces cerevisiae as a eukaryotic model to explore the function of Phytophthora RXLR effector proteins. Results and Conclusions Expression of individual RXLR effectors in yeast inhibited growth, consistent with perturbation of a highly conserved cellular process. Transcriptome analysis of yeast cells expressing the poorly characterized P. sojae RXLR effector Avh110 identified nearly a dozen yeast genes whose expression levels were altered greater than two-fold compared to control cells. All five of the most down-regulated yeast genes are normally induced under low phosphate conditions via the PHO4 transcription factor, indicating that PsAvh110 perturbs the yeast regulatory network essential for phosphate homeostasis and suggesting likely PsAvh110 targets during P. sojae infection of its soybean host.

ABSTRACT Developing effective assessments of student learning is a challenging task for faculty and even more difficult for those in emerging disciplines that lack readily available resources and standards. With the power of technology-enhanced education and accessible digital learning platforms, instructors are also looking for assessments that work in an online format. This article will be useful for all teachers, but especially for entry-level instructors, in addition to more mature instructors who are looking to become more well versed in assessment, who seek a succinct summary of assessment types to springboard the integration of new forms of assessment of student learning into their courses. In this paper, ten assessment types, all appropriate for face-to-face, blended, and online modalities, are discussed. The assessments are mapped to a set of bioinformatics core competencies with examples of how they have been used to assess student learning. Although bioinformatics is used as the focus of the assessment types, the question types are relevant to many disciplines.

The widely held assumption that any important scientific information would be available in English underlies the underuse of non-English-language science across disciplines. However, non-English-language science is expected to bring unique and valuable scientific information, especially in disciplines where the evidence is patchy, and for emergent issues where synthesising available evidence is an urgent challenge. Yet such contribution of non-English-language science to scientific communities and the application of science is rarely quantified. Here, we show that non-English-language studies provide crucial evidence for informing global biodiversity conservation. By screening 419,679 peer-reviewed papers in 16 languages, we identified 1,234 non-English-language studies providing evidence on the effectiveness of biodiversity conservation interventions, compared to 4,412 English-language studies identified with the same criteria. Relevant non-English-language studies are being published at an increasing rate in 6 out of the 12 languages where there were a sufficient number of relevant studies. Incorporating non-English-language studies can expand the geographical coverage (i.e., the number of 2° × 2° grid cells with relevant studies) of English-language evidence by 12% to 25%, especially in biodiverse regions, and taxonomic coverage (i.e., the number of species covered by the relevant studies) by 5% to 32%, although they do tend to be based on less robust study designs. Our results show that synthesising non-English-language studies is key to overcoming the widespread lack of local, context-dependent evidence and facilitating evidence-based conservation globally. We urge wider disciplines to rigorously reassess the untapped potential of non-English-language science in informing decisions to address other global challenges. Please see the Supporting information files for Alternative Language Abstracts.

Arginyltransferase 1 (ATE1) is an evolutionary-conserved eukaryotic protein that localizes to the cytosol and nucleus. It is the only known enzyme in metazoans and fungi that catalyzes posttranslational arginylation. Lack of arginylation has been linked to an array of human disorders, including cancer, by altering the response to stress and the regulation of metabolism and apoptosis. Although mitochondria play relevant roles in these processes in health and disease, a causal relationship between ATE1 activity and mitochondrial biology has yet to be established. Here, we report a phylogenetic analysis that traces the roots of ATE1 to alpha-proteobacteria, the mitochondrion microbial ancestor. We then demonstrate that a small fraction of ATE1 localizes within mitochondria. Furthermore, the absence of ATE1 influences the levels, organization, and function of respiratory chain complexes in mouse cells. Specifically, ATE1-KO mouse embryonic fibroblasts have increased levels of respiratory supercomplexes I+III2+IVn. However, they have decreased mitochondrial respiration owing to severely lowered complex II levels, which leads to accumulation of succinate and downstream metabolic effects. Taken together, our findings establish a novel pathway for mitochondrial function regulation that might explain ATE1-dependent effects in various disease conditions, including cancer and aging, in which metabolic shifts are part of the pathogenic or deleterious underlying mechanism.

Bioinformatics, a discipline that combines aspects of biology, statistics, mathematics, and computer science, is becoming increasingly important for biological research. However, bioinformatics instruction is not yet generally integrated into undergraduate life sciences curricula. To understand why we studied how bioinformatics is being included in biology education in the US by conducting a nationwide survey of faculty at two- and four-year institutions. The survey asked several open-ended questions that probed barriers to integration, the answers to which were analyzed using a mixed-methods approach. The barrier most frequently reported by the 1,260 respondents was lack of faculty expertise/training, but other deterrents-lack of student interest, overly-full curricula, and lack of student preparation-were also common. Interestingly, the barriers faculty face depended strongly on whether they are members of an underrepresented group and on the Carnegie Classification of their home institution. We were surprised to discover that the cohort of faculty who were awarded their terminal degree most recently reported the most preparation in bioinformatics but teach it at the lowest rate.

Although bioinformatics is becoming increasingly central to research in the life sciences, bioinformatics skills and knowledge are not well integrated into undergraduate biology education. This curricular gap prevents biology students from harnessing the full potential of their education, limiting their career opportunities and slowing research innovation. To advance the integration of bioinformatics into life sciences education, a framework of core bioinformatics competencies is needed. To that end, we here report the results of a survey of biology faculty in the United States about teaching bioinformatics to undergraduate life scientists. Responses were received from 1,260 faculty representing institutions in all fifty states with a combined capacity to educate hundreds of thousands of students every year. Results indicate strong, widespread agreement that bioinformatics knowledge and skills are critical for undergraduate life scientists as well as considerable agreement about which skills are necessary. Perceptions of the importance of some skills varied with the respondent's degree of training, time since degree earned, and/or the Carnegie Classification of the respondent's institution. To assess which skills are currently being taught, we analyzed syllabi of courses with bioinformatics content submitted by survey respondents. Finally, we used the survey results, the analysis of the syllabi, and our collective research and teaching expertise to develop a set of bioinformatics core competencies for undergraduate biology students. These core competencies are intended to serve as a guide for institutions as they work to integrate bioinformatics into their life sciences curricula.

To explore the potential relationship between optic disc haemorrhage, venous pulsation pressure (VPP), ocular perfusion pressures and visual field change in glaucomatous and glaucoma suspect eyes.This prospective observational study examined 155 open angle glaucoma or glaucoma suspect eyes from 78 patients over 5 years. Patients were followed with 3 monthly non-mydriatic disc photographs, 6 monthly standard automated perimetry and annual ophthalmodynamometry. The number of disc haemorrhages in each hemidisc was counted across the study period. Visual field rate of change was calculated using linear regression on the sensitivity of each location over time, then averaged for the matching hemifield. VPP and central retinal artery diastolic pressure (CRADP) were calculated from the measured ophthalmodynanometric forces (ODF). The difference between brachial artery diastolic pressure (DiastBP) and CRADP was calculated as an index of possible flow pathology along the carotid and ophthalmic arteries.Mean age of the cohort was 71.9 ± 7.3 Years. 76 out of 155 eyes (49%) followed for a mean period of 64.2 months had at least 1 disc haemorrhage. 62 (81.6%) of these 76 eyes had recurrent haemorrhages, with a mean of 5.94 recurrences over 64.2 months. Using univariate analysis, rate of visual field change (P

PURPOSE:To explore whether alterations in intraocular pressure (IOP) affect vein pulsation properties using ophthalmodynamometric measures of vein pulsation pressure. PATIENTS AND METHODS:Glaucoma patients had two retinal vein pulsation pressure (VPP) measurements from upper and lower hemiveins performed by ophthalmodynamometry at least 3 months apart. All subjects had VPP and IOP recorded at two visits, with standard automated perimetry, central corneal thickness (CCT) recorded at the initial visit. Where venous pulsation was spontaneous ophthalmodynamometry could not be performed and VPP was considered equal to IOP. Change in VPP was calculated and binarized with reduction in pressure scored 1 and no change or increase scored as 0. Data analysis used a mixed logistic regression model with change in VPP as response variable and change in IOP, visual field loss (mean deviation), CCT and time interval as explanatory variables. RESULTS:31 subjects (20 females) with mean age 60 years (sd 11) were examined with change in VPP being significantly associated with change in IOP (odds ratio 1.6/mmHg, 95% CI 1.2 to 2.1 in the glaucoma patients but not suspect patients (p = 0.0005). CONCLUSION:Change in VPP is strongly associated with change in IOP such that a reduced intraocular pressure is associated with a subsequent reduction in VPP. This indicates that reduced IOP alters some retinal vein properties however the nature and time course of these changes is not known.

PURPOSE:To study the relationship between amplitude of spontaneous retinal venous pulsatility (SRVP) and retinal nerve fibre layer (RNFL) thickness in glaucomatous eyes, and to determine if this parameter may be a potential marker for glaucoma severity. METHOD:85 subjects including 50 glaucoma (21 males, 67±10 yrs) and 35 normals (16 males, 62±11 yrs) were studied. SRVP amplitude was measured using the Dynamic Vessel Analyser (DVA, Imedos, Germany) at four regions of the retina simultaneously within one disc diameter from the optic disc--temporal-superior (TS), nasal-superior (NS), temporal-inferior (TI) and nasal-inferior (NI)). This was followed by RNFL thickness measurement using spectral domain optical coherence tomography (Spectralis OCT). The correlation between SRVP amplitude and corresponding sectoral RNFL thickness was assessed by means of non-linear regression (i.e. logarithmic). Linear regression was also applied and slopes were compared using analysis of covariance (ANCOVA). RESULTS:Greater SRVP amplitude was associated with thicker RNFL. Global SRVP amplitude was significantly lower in glaucoma eyes compared with normals (p0.05). Since the slopes are not significantly different, it is possible to calculate one slope for all the data. The pooled slope equals 10.8 (i.e. RNFL = 10.8SRVP+41). CONCLUSION:While SRVP was present and measurable in all individuals, the amplitude of SRVP is reduced in glaucoma with increasing RNFL loss. Our findings suggest the degree of SRVP may be an additional marker for glaucoma severity. Further studies are needed to determine the mechanism of reduction in SRVP, and whether changes can predict increased risk of progression.

PurposeRetinal venous pulsation detection is a subjective sign, which varies in elevated intracranial pressure, venous obstruction and glaucoma. To date no method can objectively measure and identify pulsating regions.MethodUsing high resolution video-recordings of the optic disk and retina we measured fluctuating light absorption by haemoglobin during pulsation. Pulsation amplitude was calculated from all regions of the retinal image video-frames in a raster pattern. Segmented retinal images were formed by objectively selecting regions with amplitudes above a range of threshold values. These were compared to two observers manually drawing an outline of the pulsating areas while viewing video-clips in order to generate receiver operator characteristics.Results216,515 image segments were analysed from 26 eyes in 18 research participants. Using data from each eye, the median area under the receiver operator curve (AU-ROC) was 0.95. With all data analysed together the AU-ROC was 0.89. We defined the ideal threshold amplitude for detection of any pulsating segment being that with maximal sensitivity and specificity. This was 5 units (95% confidence interval 4.3 to 6.0) compared to 12 units before any regions were missed. A multivariate model demonstrated that ideal threshold amplitude increased with increased variation in video-sequence illumination (p = 0.0119), but between the two observers (p = 0.0919) or other variables.ConclusionThis technique demonstrates accurate identification of retinal vessel pulsating regions with no areas identified manually being missed with the objective technique. The amplitude values are derived objectively and may be a significant advance upon subjective ophthalmodynamometric threshold techniques.

Radial peripapillary capillaries (RPCs) comprise a unique network of capillary beds within the retinal nerve fibre layer (RNFL) and play a critical role in satisfying the nutritional requirements of retinal ganglion cell (RGC) axons. Understanding the topographical and morphological characteristics of these networks through in vivo techniques may improve our understanding about the role of RPCs in RGC axonal health and disease. This study utilizes a novel, non-invasive and label-free optical imaging technique, speckle variance optical coherence tomography (svOCT), for quantitatively studying RPC networks in the human retina. Six different retinal eccentricities from 16 healthy eyes were imaged using svOCT. The same eccentricities were histologically imaged in 9 healthy donor eyes with a confocal scanning laser microscope. Donor eyes were subject to perfusion-based labeling techniques prior to retinal dissection, flat mounting and visualization with the microscope. Capillary density and diameter measurements from each eccentricity in svOCT and histological images were compared. Data from svOCT images were also analysed to determine if there was a correlation between RNFL thickness and RPC density. The results are as follows: (1) The morphological characteristics of RPC networks on svOCT images are comparable to histological images; (2) With the exception of the nasal peripapillary region, there were no significant differences in RPC density measurements between svOCT and histological images; (3) Capillary diameter measurements were significantly greater in svOCT images compared to histology; (4) There is a positive correlation between RPC density and RNFL thickness. The findings in this study suggest that svOCT is a reliable modality for analyzing RPC networks in the human retina. It may therefore be a valuable tool for aiding our understanding about vasculogenic mechanisms that are involved in RGC axonopathies. Further work is required to explore the reason for some of the quantitative differences between svOCT and histology.

It is postulated that secreted soluble factors are important contributors of bystander effect and adaptive responses observed in low dose ionizing radiation. Using multidimensional liquid chromatography-mass spectrometry based proteomics, we quantified the changes of skin tissue secretome--the proteins secreted from a full thickness, reconstituted 3-dimensional skin tissue model 48 hr after exposure to 3, 10 and 200 cGy of X-rays. Overall, 135 proteins showed statistical significant difference between the sham (0 cGy) and any of the irradiated groups (3, 10 or 200 cGy) on the basis of Dunnett adjusted t-test; among these, 97 proteins showed a trend of downregulation and 9 proteins showed a trend of upregulation with increasing radiation dose. In addition, there were 21 and 8 proteins observed to have irregular trends with the 10 cGy irradiated group either having the highest or the lowest level among all three radiated doses. Moreover, two proteins, carboxypeptidase E and ubiquitin carboxyl-terminal hydrolase isozyme L1 were sensitive to ionizing radiation, but relatively independent of radiation dose. Conversely, proteasome activator complex subunit 2 protein appeared to be sensitive to the dose of radiation, as rapid upregulation of this protein was observed when radiation doses were increased from 3, to 10 or 200 cGy. These results suggest that different mechanisms of action exist at the secretome level for low and high doses of ionizing radiation.

Radiation induced genomic instability is a well-studied phenomenon, the underlying mechanisms of which are poorly understood. Persistent oxidative stress, mitochondrial dysfunction, elevated cytokine levels and epigenetic changes are among the mechanisms invoked in the perpetuation of the phenotype. To determine whether epigenetic aberrations affect genomic instability we measured DNA methylation, mRNA and microRNA (miR) levels in well characterized chromosomally stable and unstable clonally expanded single cell survivors of irradiation. While no changes in DNA methylation were observed for the gene promoters evaluated, increased LINE-1 methylation was observed for two unstable clones (LS12 and CS9) and decreased Alu element methylation was observed for the other two unstable clones (115 and Fe5.0-8). These relationships also manifested for mRNA and miR expression. mRNA identified for the LS12 and CS9 clones were most similar to each other (261 mRNA), while the 115 and Fe5.0-8 clones were more similar to each other, and surprisingly also similar to the two stable clones, 114 and 118 (286 mRNA among these four clones). Pathway analysis showed enrichment for pathways involved in mitochondrial function and cellular redox, themes routinely invoked in genomic instability. The commonalities between the two subgroups of clones were also observed for miR. The number of miR for which anti-correlated mRNA were identified suggests that these miR exert functional effects in each clone. The results demonstrate significant genetic and epigenetic changes in unstable cells, but similar changes are almost as equally common in chromosomally stable cells. Possible conclusions might be that the chromosomally stable clones have some other form of instability, or that some of the observed changes represent a sort of radiation signature and that other changes are related to genomic instability. Irrespective, these findings again suggest that a spectrum of changes both drive genomic instability and permit unstable cells to persist and proliferate.

The purpose of this paper is to provide a response to Harrison’s (2012) work. The author highlights the positives associated with many of the academic reform efforts Harrison highlights (i.e., the good); addresses concerns about academic clustering, rewarding teams performing at high academic levels, and athletic administrators’ resistance to upset the status quo (i.e., the problematic); and the strong association between efforts for academic reform and large revenue streams found in men’s basketball and football (i.e., the truly worrisome). Recommendations and conclusions are advanced.

P-glycoprotein (Pgp) and multidrug resistance-associated proteins (MRPs) are ATP-dependent transporters involved in efflux of toxins and xenobiotics from cells. When overexpressed, these transporters can mediate multidrug resistance (MDR) in mammalian cells, and changes in Pgp expression and sequence are associated with drug resistance in helminths. In addition to the role they play in drug efflux, MDR transporters are essential components of normal cellular physiology, and targeting them may prove a useful strategy for development of new therapeutics or of compounds that enhance the efficacy of current anthelmintics. We previously showed that expression of Schistosoma mansoni MDR transporters increases in response to praziquantel (PZQ), the current drug of choice against schistosomiasis, and that reduced PZQ sensitivity correlates with higher levels of these parasite transporters. We have also shown that PZQ inhibits transport by SMDR2, a Pgp orthologue from S. mansoni, and that PZQ is a likely substrate of SMDR2. Here, we examine the physiological roles of SMDR2 and SmMRP1 (the S. mansoni orthologue of MRP1) in S. mansoni adults, using RNAi to knock down expression, and pharmacological agents to inhibit transporter function. We find that both types of treatments disrupt parasite egg deposition by worms in culture. Furthermore, administration of different MDR inhibitors to S. mansoni-infected mice results in a reduction in egg burden in host liver. These schistosome MDR transporters therefore appear to play essential roles in parasite egg production, and can be targeted genetically and pharmacologically. Since eggs are responsible for the major pathophysiological consequences of schistosomiasis, and since they are also the agents for transmission of the disease, these results suggest a potential strategy for reducing disease pathology and spread.

Radiation induced bystander effects and adaptive responses are two phenomena that modulate cellular responses to low doses of ionizing radiation. Bystander effects generally exaggerate the effects of low doses of radiation by eliciting detrimental effects in non-irradiated cells, thus making the target for radiation effects greater than the volume irradiated. Adaptive responses on the other hand indicate that low doses of radiation can reduce damage induced by a second challenging dose. The potential impact of these two low dose effects on the shape of the dose response relationship will be discussed.