Angiosperm phylogeny: 17 genes, 640 taxa Soltis, Douglas E.; Smith, Stephen A.; Cellinese, Nico ...
American journal of botany,
April 2011, Letnik:
98, Številka:
4
Journal Article
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Premise of the study. Recent analyses employing up to five genes have provided numerous insights into angiosperm phylogeny, but many relationships have remained unresolved or poorly supported. In the ...hope of improving our understanding of angiosperm phylogeny, we expanded sampling of taxa and genes beyond previous analyses. Methods: We conducted two primary analyses based on 640 species representing 330 families. The first included 25260 aligned base pairs (bp) from 17 genes (representing all three plant genomes, i. e., nucleus, plastid, and mitochondrion). The second included 19846 aligned bp from 13 genes (representing only the nucleus and plastid). Key results: Many important questions of deep-level relationships in the nonmonocot angiosperms have now been resolved with strong support. Amborellaceae, Nymphaeales, and Austrobaileyales are successive sisters to the remaining angiosperms (Mesangiospermae), which are resolved into Chloranthales + Magnoliidae as sister to Monocotyledoneae + Ceratophyllaceae + Eudicotyledoneae. Eudicotyledoneae contains a basal grade subtending Gunneridae. Within Gunneridae, Gunnerales are sister to the remainder (Pentapetalae), which comprises (1) Superrosidae, consisting of Rosidae (including Vitaceae) and Saxifragales; and (2) Superasteridae, comprising Berberidopsidales, Santalales, CaryophyHales, Asteridae, and, based on this study, Dilleniaceae (although other recent analyses disagree with this placement). Within the major subclades of Pentapetalae, most deep-level relationships are resolved with strong support. Conclusions: Our analyses confirm that with large amounts of sequence data, most deep-level relationships within the angiosperms can be resolved. We anticipate that this well-resolved angiosperm tree will be of broad utility for many areas of biology, including physiology, ecology, paleobiology, and genomics.
Abstract
Antibody-drug conjugates (ADCs) are complex engineered therapeutics consisting of monoclonal antibodies, directed toward tumor-associated antigens, to which highly potent cytotoxic agents ...are attached using chemical linkers. This targeted drug delivery strategy couples the precision of the antibody targeting moiety with the cytocidal activity of the payload, which is generally too toxic on its own to be systemically administered. In this manner, ADCs confer a means to reduce off-target toxicities in patients by limiting the exposure of normal tissues to the payload, thus broadening the potential therapeutic window compared with traditional chemotherapy. The pace of ADC development is accelerating, with the number of investigational agents in human trials having more than tripled over the past 5 years, underscoring the enthusiasm for this transformative approach to cancer treatment. Here, we review the key structural elements of ADC design (antibody, linker, and payload), highlighting critical aspects and technological advances that have affected the clinical effectiveness of this class of biopharmaceuticals. The ADC field continues to evolve, including ongoing efforts aimed at improving target selection, developing payloads with varied mechanisms of action and increased potency, designing innovative bioconjugation strategies, as well as maximizing efficacy and tolerability in patients. An overview of the current clinical trial landscape is provided, with emphasis on the clinical experience of the four ADCs to have received regulatory approval to date, as well as additional promising candidates currently in late-stage clinical development in both solid tumor and hematological malignancies.
Historical biogeography is increasingly studied from an explicitly statistical perspective, using stochastic models to describe the evolution of species range as a continuous-time Markov process of ...dispersal between and extinction within a set of discrete geographic areas. The main constraint of these methods is the computational limit on the number of areas that can be specified. We propose a Bayesian approach for inferring biogeographic history that extends the application of biogeographic models to the analysis of more realistic problems that involve a large number of areas. Our solution is based on a "data-augmentation" approach, in which we first populate the tree with a history of biogeographic events that is consistent with the observed species ranges at the tips of the tree. We then calculate the likelihood of a given history by adopting a mechanistic interpretation of the instantaneous-rate matrix, which specifies both the exponential waiting times between biogeographic events and the relative probabilities of each biogeographic change. We develop this approach in a Bayesian framework, marginalizing over all possible biogeographic histories using Markov chain Monte Carlo (MCMC). Besides dramatically increasing the number of areas that can be accommodated in a biogeographic analysis, our method allows the parameters of a given biogeographic model to be estimated and different biogeographic models to be objectively compared. Our approach is implemented in the program, BayArea.
The COVID-19 outbreak has highlighted our vulnerability to novel infections. Faced with this threat and no effective treatment, in line with many other countries, the UK adopted enforced social ...distancing (lockdown) to reduce transmission-successfully reducing the reproductive number R below one. However, given the large pool of susceptible individuals that remain, complete relaxation of controls is likely to generate a substantial further outbreak. Vaccination remains the only foreseeable means of both containing the infection and returning to normal interactions and behaviour. Here, we consider the optimal targeting of vaccination within the UK, with the aim of minimising future deaths or quality adjusted life year (QALY) losses. We show that, for a range of assumptions on the action and efficacy of the vaccine, targeting older age groups first is optimal and may be sufficient to stem the epidemic if the vaccine prevents transmission as well as disease.
Significant evidence supports the view that dopamine shapes learning by encoding reward prediction errors. However, it is unknown whether striatal targets receive tailored dopamine dynamics based on ...regional functional specialization. Here, we report wave-like spatiotemporal activity patterns in dopamine axons and release across the dorsal striatum. These waves switch between activational motifs and organize dopamine transients into localized clusters within functionally related striatal subregions. Notably, wave trajectories were tailored to task demands, propagating from dorsomedial to dorsolateral striatum when rewards are contingent on animal behavior and in the opponent direction when rewards are independent of behavioral responses. We propose a computational architecture in which striatal dopamine waves are sculpted by inference about agency and provide a mechanism to direct credit assignment to specialized striatal subregions. Supporting model predictions, dorsomedial dopamine activity during reward-pursuit signaled the extent of instrumental control and interacted with reward waves to predict future behavioral adjustments.
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•Dorsal striatum receives wave-like dopamine dynamics•Motif flow patterns produce delayed DA transients across striatal subregions•Opponent DA wave directions predict behavioral control of reward•Computational model links multi-timescale DA signals: transients, ramps, and waves
Dopamine axon activity and release across the dorsal striatum in mice exhibits wave-like spatiotemporal patterns that are tailored to task demands and predict an animal’s behavioral adjustments.
The optimal chemotherapy regimen administered concurrently with preoperative radiation therapy (RT) for patients with rectal cancer is unknown. National Surgical Adjuvant Breast and Bowel Project ...trial R-04 compared four chemotherapy regimens administered concomitantly with RT.
Patients with clinical stage II or III rectal cancer who were undergoing preoperative RT (45 Gy in 25 fractions over 5 weeks plus a boost of 5.4 Gy to 10.8 Gy in three to six daily fractions) were randomly assigned to one of the following chemotherapy regimens: continuous intravenous infusional fluorouracil (CVI FU; 225 mg/m(2), 5 days per week), with or without intravenous oxaliplatin (50 mg/m(2) once per week for 5 weeks) or oral capecitabine (825 mg/m(2) twice per day, 5 days per week), with or without oxaliplatin (50 mg/m(2) once per week for 5 weeks). Before random assignment, the surgeon indicated whether the patient was eligible for sphincter-sparing surgery based on clinical staging. The surgical end points were complete pathologic response (pCR), sphincter-sparing surgery, and surgical downstaging (conversion to sphincter-sparing surgery).
From September 2004 to August 2010, 1,608 patients were randomly assigned. No significant differences in the rates of pCR, sphincter-sparing surgery, or surgical downstaging were identified between the CVI FU and capecitabine regimens or between the two regimens with or without oxaliplatin. Patients treated with oxaliplatin experienced significantly more grade 3 or 4 diarrhea (P < .001).
Administering capecitabine with preoperative RT achieved similar rates of pCR, sphincter-sparing surgery, and surgical downstaging compared with CVI FU. Adding oxaliplatin did not improve surgical outcomes but added significant toxicity. The definitive analysis of local tumor control, disease-free survival, and overall survival will be performed when the protocol-specified number of events has occurred.
Plastome (plastid genome) sequences provide valuable information for understanding the phylogenetic relationships and evolutionary history of plants. Although the rapid development of high-throughput ...sequencing technology has led to an explosion of plastome sequences, annotation remains a significant bottleneck for plastomes. User-friendly batch annotation of multiple plastomes is an urgent need.
We introduce Plastid Genome Annotator (PGA), a standalone command line tool that can perform rapid, accurate, and flexible batch annotation of newly generated target plastomes based on well-annotated reference plastomes. In contrast to current existing tools, PGA uses reference plastomes as the query and unannotated target plastomes as the subject to locate genes, which we refer to as the reverse query-subject BLAST search approach. PGA accurately identifies gene and intron boundaries as well as intron loss. The program outputs GenBank-formatted files as well as a log file to assist users in verifying annotations. Comparisons against other available plastome annotation tools demonstrated the high annotation accuracy of PGA, with little or no post-annotation verification necessary. Likewise, we demonstrated the flexibility of reference plastomes within PGA by annotating the plastome of
using that of
as a reference. The program, user manual and example data sets are freely available at https://github.com/quxiaojian/PGA.
PGA facilitates rapid, accurate, and flexible batch annotation of plastomes across plants. For projects in which multiple plastomes are generated, the time savings for high-quality plastome annotation are especially significant.
Abstract
North Atlantic right whales (Eubalaena glacialis) risk extinction unless conservation measures not only reduce mortality but also enhance reproduction. Vessel collisions injure and kill by ...spinning propeller cuts or being hit with a blunt structure resulting in bone and soft tissue damage. Entanglement trauma includes sublethal injuries that can reduce their ability to reproduce, while lethal events include drowning, deep constricting wounds, and emaciation leading to death over months or years. Current regulations attempt to reduce mortality from vessel strikes and fishing gear entanglement off the eastern shores of the United States and Canada. However, sub-lethal stressors, especially entanglement, have exacerbated impacts from climate-driven food supply changes, resulting in a serious reduction in growth of individuals and calving rates. If consumers demand that their ship-borne goods and bottom-caught seafood be procured without serious welfare and health concerns for the whales, recovery is possible. We need the will to widely employ the tools of vessel speed restrictions and acoustic retrieval of bottom traps and nets without a persistent vertical line in the water column to reduce sub-lethal as well as lethal trauma. Thus, consumers should pressure legislators, endangered species managers, and suppliers for far broader protections than currently exist.
One-sentence summary: With ∼340 left, North Atlantic right whales are close to extinction: for every calf born, three animals die. We know how to fix this; we just need to do it.
Although Pentapetalae (comprising all core eudicots except Gunnerales) include almost equal to70% of all angiosperms, the origin of and relationships among the major lineages of this clade have ...remained largely unresolved. Phylogenetic analyses of 83 protein-coding and rRNA genes from the plastid genome for 86 species of seed plants, including new sequences from 25 eudicots, indicate that soon after its origin, Pentapetalae diverged into three clades: (i) a "superrosid" clade consisting of Rosidae, Vitaceae, and Saxifragales; (ii) a "superasterid" clade consisting of Berberidopsidales, Santalales, Caryophyllales, and Asteridae; and (iii) Dilleniaceae. Maximum-likelihood analyses support the position of Dilleniaceae as sister to superrosids, but topology tests did not reject alternative positions of Dilleniaceae as sister to Asteridae or all remaining Pentapetalae. Molecular dating analyses suggest that the major lineages within both superrosids and superasterids arose in as little as 5 million years. This phylogenetic hypothesis provides a crucial historical framework for future studies aimed at elucidating the underlying causes of the morphological and species diversity in Pentapetalae.
The dynamics of vaccination against SARS-CoV-2 are complicated by age-dependent factors, changing levels of infection, and the relaxation of non-pharmaceutical interventions (NPIs) as the perceived ...risk declines, necessitating the use of mathematical models. Our aims were to use epidemiological data from the UK together with estimates of vaccine efficacy to predict the possible long-term dynamics of SARS-CoV-2 under the planned vaccine rollout.
In this study, we used a mathematical model structured by age and UK region, fitted to a range of epidemiological data in the UK, which incorporated the planned rollout of a two-dose vaccination programme (doses 12 weeks apart, protection onset 14 days after vaccination). We assumed default vaccine uptake of 95% in those aged 80 years and older, 85% in those aged 50–79 years, and 75% in those aged 18–49 years, and then varied uptake optimistically and pessimistically. Vaccine efficacy against symptomatic disease was assumed to be 88% on the basis of Pfizer-BioNTech and Oxford-AstraZeneca vaccines being administered in the UK, and protection against infection was varied from 0% to 85%. We considered the combined interaction of the UK vaccination programme with multiple potential future relaxations (or removals) of NPIs, to predict the reproduction number (R) and pattern of daily deaths and hospital admissions due to COVID-19 from January, 2021, to January, 2024.
We estimate that vaccination alone is insufficient to contain the outbreak. In the absence of NPIs, even with our most optimistic assumption that the vaccine will prevent 85% of infections, we estimate R to be 1·58 (95% credible intervals CI 1·36–1·84) once all eligible adults have been offered both doses of the vaccine. Under the default uptake scenario, removal of all NPIs once the vaccination programme is complete is predicted to lead to 21 400 deaths (95% CI 1400–55 100) due to COVID-19 for a vaccine that prevents 85% of infections, although this number increases to 96 700 deaths (51 800–173 200) if the vaccine only prevents 60% of infections. Although vaccination substantially reduces total deaths, it only provides partial protection for the individual; we estimate that, for the default uptake scenario and 60% protection against infection, 48·3% (95% CI 48·1–48·5) and 16·0% (15·7–16·3) of deaths will be in individuals who have received one or two doses of the vaccine, respectively.
For all vaccination scenarios we investigated, our predictions highlight the risks associated with early or rapid relaxation of NPIs. Although novel vaccines against SARS-CoV-2 offer a potential exit strategy for the pandemic, success is highly contingent on the precise vaccine properties and population uptake, both of which need to be carefully monitored.
National Institute for Health Research, Medical Research Council, and UK Research and Innovation.
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