The genome of the green anole lizard and a comparative analysis with birds and mammals

The evolution of the amniotic egg was one of the great evolutionary innovations in the history of life, freeing vertebrates from an obligatory connection to water and thus permitting the conquest of terrestrial environments. Among amniotes, genome sequences are available for mammals and birds, but not for non-avian reptiles. Here we report the genome sequence of the North American green anole lizard, Anolis carolinensis. We find that A. carolinensis microchromosomes are highly syntenic with chicken microchromosomes, yet do not exhibit the high GC and low repeat content that are characteristic of avian microchromosomes. Also, A. carolinensis mobile elements are very young and diverse—more so than in any other sequenced amniote genome. The GC content of this lizard genome is also unusual in its homogeneity, unlike the regionally variable GC content found in mammals and birds. We describe and assign sequence to the previously unknown A. carolinensis X chromosome. Comparative gene analysis shows that amniote egg proteins have evolved significantly more rapidly than other proteins. An anole phylogeny resolves basal branches to illuminate the history of their repeated adaptive radiations.National Science Foundation (U.S.) (NSF grant DEB-0920892)National Science Foundation (U.S.) (NSF grant DEB-0844624)National Human Genome Research Institute (U.S.

Efficacy of Messenger RNA-1273 Against Severe Acute Respiratory Syndrome Coronavirus 2 Acquisition in Young Adults From March to December 2021

BACKGROUND: The efficacy of messenger RNA (mRNA)-1273 against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is not well defined, particularly among young adults. METHODS: Adults aged 18-29 years with no known history of SARS-CoV-2 infection or prior vaccination for coronavirus disease 2019 (COVID-19) were recruited from 44 US sites from 24 March to 13 September 2021 and randomized 1:1 to immediate vaccination (receipt of 2 doses of mRNA-1273 vaccine at months 0 and 1) or the standard of care (receipt of COVID-19 vaccine). Randomized participants were followed up for SARS-CoV-2 infection measured by nasal swab testing and symptomatic COVID-19 measured by nasal swab testing plus symptom assessment and assessed for the primary efficacy outcome. A vaccine-declined observational group was also recruited from 16 June to 8 November 2021 and followed up for SARS-CoV-2 infection as specified for the randomized participants. RESULTS: The study enrolled 1149 in the randomized arms and 311 in the vaccine-declined group and collected >122 000 nasal swab samples. Based on randomized participants, the efficacy of 2 doses of mRNA-1273 vaccine against SARS-CoV-2 infection was 52.6% (95% confidence interval, -14.1% to 80.3%), with the majority of infections due to the Delta variant. Vaccine efficacy against symptomatic COVID-19 was 71.0% (95% confidence interval, -9.5% to 92.3%). Precision was limited owing to curtailed study enrollment and off-study vaccination censoring. The incidence of SARS-CoV-2 infection in the vaccine-declined group was 1.8 times higher than in the standard-of-care group. CONCLUSIONS: mRNA-1273 vaccination reduced the incidence of SARS-CoV-2 infection from March to September 2021, but vaccination was only one factor influencing risk. CLINICAL TRIALS REGISTRATION: NCT04811664

GA4GH: International policies and standards for data sharing across genomic research and healthcare.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits

The genome of the green anole lizard and a comparative analysis with birds and mammals

The evolution of the amniotic egg was one of the great evolutionary innovations in the history of life, freeing vertebrates from an obligatory connection to water and thus permitting the conquest of terrestrial environments1. Among amniotes, genome sequences are available for mammals2 and birds3–5, but not for non-avian reptiles. Here we report the genome sequence of the North American green anole lizard, Anolis carolinensis. We find that A. carolinensis microchromosomes are highly syntenic with chicken microchromosomes, yet do not exhibit the high GC and low repeat content that are characteristic of avian microchromosomes3. Also, A. carolinensis mobile elements are very young and diverse – more so than in any other sequenced amniote genome. This lizard genome’s GC content is also unusual in its homogeneity, unlike the regionally variable GC content found in mammals and birds6. We describe and assign sequence to the previously unknown A. carolinensis X chromosome. Comparative gene analysis shows that amniote egg proteins have evolved significantly more rapidly than other proteins. An anole phylogeny resolves basal branches to illuminate the history of their repeated adaptive radiations

A practical guide to single-cell RNA-sequencing for biomedical research and clinical applications.

RNA sequencing (RNA-seq) is a genomic approach for the detection and quantitative analysis of messenger RNA molecules in a biological sample and is useful for studying cellular responses. RNA-seq has fueled much discovery and innovation in medicine over recent years. For practical reasons, the technique is usually conducted on samples comprising thousands to millions of cells. However, this has hindered direct assessment of the fundamental unit of biology-the cell. Since the first single-cell RNA-sequencing (scRNA-seq) study was published in 2009, many more have been conducted, mostly by specialist laboratories with unique skills in wet-lab single-cell genomics, bioinformatics, and computation. However, with the increasing commercial availability of scRNA-seq platforms, and the rapid ongoing maturation of bioinformatics approaches, a point has been reached where any biomedical researcher or clinician can use scRNA-seq to make exciting discoveries. In this review, we present a practical guide to help researchers design their first scRNA-seq studies, including introductory information on experimental hardware, protocol choice, quality control, data analysis and biological interpretation

Local and systemic responses to SARS-CoV-2 infection in children and adults.

It is not fully understood why COVID-19 is typically milder in children1-3. Here, to examine the differences between children and adults in their response to SARS-CoV-2 infection, we analysed paediatric and adult patients with COVID-19 as well as healthy control individuals (total n = 93) using single-cell multi-omic profiling of matched nasal, tracheal, bronchial and blood samples. In the airways of healthy paediatric individuals, we observed cells that were already in an interferon-activated state, which after SARS-CoV-2 infection was further induced especially in airway immune cells. We postulate that higher paediatric innate interferon responses restrict viral replication and disease progression. The systemic response in children was characterized by increases in naive lymphocytes and a depletion of natural killer cells, whereas, in adults, cytotoxic T cells and interferon-stimulated subpopulations were significantly increased. We provide evidence that dendritic cells initiate interferon signalling in early infection, and identify epithelial cell states associated with COVID-19 and age. Our matching nasal and blood data show a strong interferon response in the airways with the induction of systemic interferon-stimulated populations, which were substantially reduced in paediatric patients. Together, we provide several mechanisms that explain the milder clinical syndrome observed in children

Investigating Memory Reactivity with a Within-Participant Manipulation of Judgments of Learning

When learners make judgments of learning (JOLs) for some word pairs but not others, how and why is recall performance affected? Participants studied related and unrelated word pairs and made JOLs for a randomly selected half of the pairs. We evaluated two hypotheses. The changed-goal hypothesis states that making JOLs leads learners to notice differences in pair difficulty and to change their learning goal. Because JOLs are manipulated within participants, such a goal change should influence how all (judged or non-judged) pairs are processed on the list, which should lead to no JOL reactivity. The cue-strengthening hypothesis predicts greater positive reactivity (i.e., higher recall for judged versus non-judged pairs) for related than unrelated pairs, because making a JOL strengthens the relationship between the two words in a pair, which would be more beneficial for pairs with an a priori relationship. Across experiments, we found positive reactivity for both related and unrelated pairs (albeit to a lesser degree for the latter). We also found no evidence that learners make qualitative changes in their reported strategy use when judging pairs. Making JOLs for some pairs on a list influenced memory performance and the pattern of reactivity provided support for the cue-strengthening hypothesis

Judgments of Learning Enhance Recall for Category-Cued but not Letter-Cued Items

Making immediate judgments of learning (JOLs) during study influence later memory performance, with a common outcome being that JOLs improve cued-recall performance for related word pairs (i.e., positive reactivity) and do not impact memory for unrelated pairs (i.e., no reactivity). The cue-strengthening hypothesis proposes that JOL reactivity will be observed when a criterion test is sensitive to the cues used to inform JOLs (Soderstrom et al., 2015; J Expt Psych: Learn, Mem, Cogn). Across four experiments, we evaluated this hypothesis with novel material: category-cued items (e.g., A type of gem–Jade) and letter-cued items (e.g., Ja – Jade). Participants studied a list comprised of both pair types and did (or did not) make JOLs and then completed a cued-recall test (Experiments 1a/b). Consistent with predictions from the cue-strengthening hypothesis, positive reactivity occurred for category pairs and no reactivity occurred for letter pairs. We also evaluated and ruled out alternative explanations for this pattern of effects: (a) that they arose due to overall differences in recall performance for the two pair types (Experiment 2), (b) that they would also occur even when the processing at encoding does not match requirements of the criterion test (Experiment 3), and (c) that JOLs increased memory strength for the targets (Experiment 4). Thus, the current experiments rule out plausible accounts of reactivity effects and provide further, converging evidence for the cue-strengthening hypothesis

Exploring the role of attentional reorienting in the reactive effects of judgments of learning on memory performance

Making judgments of learning (JOLs) while studying related word pairs can enhance performance on tests that rely on cue-target associations (e.g., cued recall) compared to studying alone. One possible explanation for this positive JOL reactivity effect is that the prompt to make JOLs, which typically occurs halfway through the presentation of each pair, may encourage learners to devote more attention to the pair during the second half of the encoding episode, which may contribute to enhanced recall performance. To investigate this idea, an online sample of participants (Experiment 1) and undergraduate students (Experiment 2) studied a set of moderately related word pairs (e.g., dairy–cow) in preparation for a cued recall test. Some participants made JOLs for each pair halfway through the presentation, whereas other participants did not. Also, some participants were presented with a fixation point halfway through the presentation, whereas other participants were not. The goal of this fixation point was to simulate the possible “reorienting” effect of a JOL prompt halfway through each encoding episode. In both an unsupervised online context and a supervised laboratory context, cued recall performance was higher for participants who made JOLs compared to those who did not make JOLs. However, presenting a fixation point halfway through the presentation of each pair did not lead to reactive effects on memory. Thus, JOLs are more effective than a manipulation that reoriented participants to the word pairs in another way (i.e., via a fixation point), which provides some initial evidence that positive reactivity for related pairs is not solely driven by attentional reorienting during encoding