Exploring Human/Animal Intersections: Converging Lines of Evidence in Comparative Models of Aging

At a symposium convened on March 8, 2007 by the Institute on Aging at the University of Pennsylvania, researchers from the University’s Schools of Medicine and Veterinary Medicine explored the convergence of aging research emerging from the two schools. Studies in human patients, animal models, and companion animals have revealed different but complementary aspects of the aging process, ranging from fundamental biologic aspects of aging to the treatment of age-related diseases, both experimentally and in clinical practice. Participants concluded that neither animal nor human research alone will provide answers to most questions about the aging process. Instead, an optimal translational research model supports a bidirectional flow of information from animal models to clinical research

Patterns of abundance across geographical ranges as a predictor for responses to climate change:Evidence from UK rocky shores

Aim: Understanding patterns in the abundance of species across thermal ranges can give useful insights into the potential impacts of climate change. The abundant-centre hypothesis suggests that species will reach peak abundance at the centre of their thermal range where conditions are optimal, but evidence in support of this hypothesis is mixed and limited in geographical and taxonomic scope. We tested the applicability of the abundant-centre hypothesis across a range of intertidal organisms using a large, citizen science-generated data set. Location: UK. Methods: Species' abundance records were matched with their location within their thermal range. Patterns in abundance distribution for individual species, and across aggregated species abundances, were analysed using Kruskal–Wallis tests and quantile general additive models. Results: Individually, invertebrate species showed increasing abundances in the cooler half of the thermal range and decreasing abundances in the warmer half of the thermal range. The overall shape for aggregated invertebrate species abundances reflected a broad peak, with a cool-skewed maximum abundance. Algal species showed little evidence for an abundant-centre distribution individually, but overall the aggregated species abundances suggested a hump-backed abundance distribution. Main Conclusions: Our study follows others in showing mixed support for the abundant-centre hypothesis at an individual species level, but demonstrates an increased predictability in species responses when an aggregated overall response is considered

Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals

During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-2. Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal pseudovirus neutralizing titres: less than 1:50 in 33% and below 1:1,000 in 79%, while only 1% showed titres above 1:5,000. Antibody sequencing revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titres, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC₅₀ values) as low as single digit nanograms per millitre. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Rocky shores as tractable test systems for experimental ecology

Rocky shore ecology has been studied for a long time, starting with qualitative descriptions and becoming more quantitative and experimental over time. Some of the earliest manipulative experimental ecological studies were undertaken on rocky shores. Many, over time, have made considerable contributions to ecological theory, especially highlighting the importance of biological interactions at the community level. The suitability of rocky shores as convenient test systems for ecological experimentation is outlined. Here we consider contributions from rocky shores to the emerging concepts of supply-side ecology, the roles of competition, predation and grazing, disturbance and succession and positive interactions in structuring communities along environmental gradients. We then address alternative stable states, relationships between biodiversity and ecosystem functioning, and bottom-up and top-down control of ecosystems. We briefly consider the feedback and synergies between ecological concepts and experimental work on rocky shores, whilst still emphasizing the traditional values of marine natural history upheld in JMBA since its first publication. The importance of rigorous experimental designs championed by Underwood and co-workers is emphasized. Recent progress taking advantage of new technologies and emerging approaches is considered. We illustrate how experimental studies have shown the importance of biological interactions in modulating species and assemblage-level responses to climate change and informed conservation and management of coastal ecosystems

Rocky shores as tractable test systems for experimental ecology

Rocky shore ecology has been studied for a long time, starting with qualitative descriptions and becoming more quantitative and experimental over time. Some of the earliest manipulative experimental ecological studies were undertaken on rocky shores. Many, over time, have made considerable contributions to ecological theory, especially highlighting the importance of biological interactions at the community level. The suitability of rocky shores as convenient test systems for ecological experimentation is outlined. Here we consider contributions from rocky shores to the emerging concepts of supply-side ecology, the roles of competition, predation and grazing, disturbance and succession and positive interactions in structuring communities along environmental gradients. We then address alternative stable states, relationships between biodiversity and ecosystem functioning, and bottom-up and top-down control of ecosystems. We briefly consider the feedback and synergies between ecological concepts and experimental work on rocky shores, whilst still emphasizing the traditional values of marine natural history upheld in JMBA since its first publication. The importance of rigorous experimental designs championed by Underwood and co-workers is emphasized. Recent progress taking advantage of new technologies and emerging approaches is considered. We illustrate how experimental studies have shown the importance of biological interactions in modulating species and assemblage-level responses to climate change and informed conservation and management of coastal ecosystems