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Creators/Authors contains: "Kumar, Sudhir"

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  1. Primates, consisting of apes, monkeys, tarsiers, and lemurs, are among the most charismatic and well-studied animals on Earth, yet there is no taxonomically complete molecular timetree for the group. Combining the latest large-scale genomic primate phylogeny of 205 recognized species with the 400-species literature consensus tree available fromTimeTree.orgyields a phylogeny of just 405 primates, with 50 species still missing despite having molecular sequence data in the NCBI GenBank. In this study, we assemble a timetree of 455 primates, incorporating every species for which molecular data are available. We use a synthetic approach consisting of a literature review for published timetrees,de novodating of untimed trees, and assembly of timetrees from novel alignments. The resulting near-complete molecular timetree of primates allows testing of two long-standing alternate hypotheses for the origins of primate biodiversity: whether species richness arises at a constant rate, in which case older clades have more species, or whether some clades exhibit faster rates of speciation than others, in which case, these fast clades would be more species-rich. Consistent with other large-scale macroevolutionary analyses, we found that the speciation rate is similar across the primate tree of life, albeit with some variation in smaller clades. 
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  2. Abstract Protein sequence evolution in the presence of epistasis makes many previously acceptable amino acid residues at a site unfavorable over time. This phenomenon of entrenchment has also been observed with neutral substitutions using Potts Hamiltonian models. Here, we show that simulations using these models often evolve non-neutral proteins. We introduce a Neutral-with-Epistasis (N×E) model that incorporates purifying selection to conserve fitness, a requirement of neutral evolution. N×E protein evolution revealed a surprising lack of entrenchment, with site-specific amino-acid preferences remaining remarkably conserved, in biologically realistic time frames despite extensive residue coupling. Moreover, we found that the overdispersion of the molecular clock is caused by rate variation across sites introduced by epistasis in individual lineages, rather than by historical contingency. Therefore, substitutional entrenchment and rate contingency may indicate that adaptive and other non-neutral evolutionary processes were at play during protein evolution. 
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  3. When students think of evolution, they might imagine T. rex, or perhaps an abiotic scene of sizzling electrical storms and harsh reducing atmospheres, an Earth that looks like a lunar landscape. Natural selection automatically elicits responses that include “survival of the fittest,” and “descent with modification,” and with these historical biological catch phrases, one conjures up images of large animals battling it out on the Mesozoic plane. Rarely do teachers or students apply these same ideas to cancer and the evolution of somatic cells, which have accrued mutations and epigenetic imprinting and relentlessly survive and proliferate. Our questions in this paper include the following: Can cancer become an important teaching model for students to explore fundamental hypotheses about evolutionary process? Can the multi- step somatic cancer model encourage visualizations that enable students to revisit and reenter previous primary concepts in general biology such as the cell, mitosis, chromosomes, genetic diversity, ecological diversity, immune function, and of course evolution, continually integrating their biology knowledge into process and pattern knowledge? Can the somatic cancer model expose similar patterns and protagonists, linking Darwinian observations of the natural world to our body? And, can the cancer clone model excite critical thinking and student hypotheses about what cancer is as a biological process? Does this visually simple model assist students in recognizing patterns, connecting their biological curriculum dots into a more coherent learning experience? These biological dynamics and intercepting aptitudes of cells are amplified through the cancer model and can help shape the way biology students begin to appreciate the interrelatedness of all biological systems while they continue to explore pivotal points of biological fuzziness, such as the microbiome, limitations of models, and the complex coordination of genomic networks required for the function of even a single cell and the realization of phenotypes. In this paper we use clonal evolution of cancer as a model experience for students to recreate how a single, non-germline cell appears to shadow the classic pattern of natural selection in body cells that have gone awry. With authentic STEAM activities students can easily crossover and revisit previous biological topics and the ubiquitous nature of natural selection as seen in the example of somatic cells that result in a metastasizing tumor, giving students insight into natural selection’s accommodating and tractable patterns throughout the planet. 
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  4. Abstract The brightest gamma-ray burst (GRB) ever, GRB 221009A, displays ultralong GRB (ULGRB) characteristics, with a prompt emission duration exceeding 1000 s. To constrain the origin and central engine of this unique burst, we analyze its prompt and afterglow characteristics and compare them to the established set of similar GRBs. To achieve this, we statistically examine a nearly complete sample of Swift-detected GRBs with measured redshifts. We categorize the sample to bronze, silver, and gold by fitting a Gaussian function to the log-normal ofT90duration distribution and considering three subsamples respectively to 1, 2, and 3 times of the standard deviation to the mean value. GRB 221009A falls into the gold subsample. Our analysis of prompt emission and afterglow characteristics aims to identify trends between the three burst groups. Notably, the gold subsample (a higher likelihood of being ULGRB candidates) suggests a collapsar scenario with a hyperaccreting black hole as a potential central engine, while a few GRBs (GRB 060218, GRB 091024A, and GRB 100316D) in our gold subsample favor a magnetar. Late-time near-IR observations from 3.6 m Devasthal Optical Telescope rule out the presence of any bright supernova associated with GRB 221009A in the gold subsample. To further constrain the physical properties of ULGRB progenitors, we employ the toolMESAto simulate the evolution of low-metallicity massive stars with different initial rotations. The outcomes suggest that rotating (Ω ≥ 0.2 Ωc) massive stars could potentially be the progenitors of ULGRBs within the considered parameters and initial inputs toMESA. 
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  5. We integrate evolutionary predictions based on the neutral theory of molecular evolution with protein dynamics to generate mechanistic insight into the molecular adaptations of the SARS-COV-2 spike (S) protein. With this approach, we first identified candidate adaptive polymorphisms (CAPs) of the SARS-CoV-2 S protein and assessed the impact of these CAPs through dynamics analysis. Not only have we found that CAPs frequently overlap with well-known functional sites, but also, using several different dynamics-based metrics, we reveal the critical allosteric interplay between SARS-CoV-2 CAPs and the S protein binding sites with the human ACE2 (hACE2) protein. CAPs interact far differently with the hACE2 binding site residues in the open conformation of the S protein compared to the closed form. In particular, the CAP sites control the dynamics of binding residues in the open state, suggesting an allosteric control of hACE2 binding. We also explored the characteristic mutations of different SARS-CoV-2 strains to find dynamic hallmarks and potential effects of future mutations. Our analyses reveal that Delta strain-specific variants have non-additive (i.e., epistatic) interactions with CAP sites, whereas the less pathogenic Omicron strains have mostly additive mutations. Finally, our dynamics-based analysis suggests that the novel mutations observed in the Omicron strain epistatically interact with the CAP sites to help escape antibody binding. 
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  6. The primate infraorder Simiiformes, comprising Old and New World monkeys and apes, includes the most well-studied species on earth. Their most comprehensive molecular timetree, assembled from thousands of published studies, is found in the TimeTree database and contains 268 simiiform species. It is, however, missing 38 out of 306 named species in the NCBI taxonomy for which at least one molecular sequence exists in the NCBI GenBank. We developed a three-pronged approach to expanding the timetree of Simiiformes to contain 306 species. First, molecular divergence times were searched and found for 21 missing species in timetrees published across 15 studies. Second, untimed molecular phylogenies were searched and scaled to time using relaxed clocks to add four more species. Third, we reconstructed ten new timetrees from genetic data in GenBank, allowing us to incorporate 13 more species. Finally, we assembled the most comprehensive molecular timetree of Simiiformes containing all 306 species for which any molecular data exists. We compared the species divergence times with those previously imputed using statistical approaches in the absence of molecular data. The latter data-less imputed times were not significantly correlated with those derived from the molecular data. Also, using phylogenies containing imputed times produced different trends of evolutionary distinctiveness and speciation rates over time than those produced using the molecular timetree. These results demonstrate that more complete clade-specific timetrees can be produced by analyzing existing information, which we hope will encourage future efforts to fill in the missing taxa in the global timetree of life. 
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  7. The origin of eukaryotes was among the most important events in the history of life, spawning a new evolutionary lineage that led to all complex multicellular organisms. However, the timing of this event, crucial for understanding its environmental context, has been difficult to establish. The fossil and biomarker records are sparse and molecular clocks have thus far not reached a consensus, with dates spanning 2.1–0.91 billion years ago (Ga) for critical nodes. Notably, molecular time estimates for the last common ancestor of eukaryotes are typically hundreds of millions of years younger than the Great Oxidation Event (GOE, 2.43–2.22 Ga), leading researchers to question the presumptive link between eukaryotes and oxygen. We obtained a new time estimate for the origin of eukaryotes using genetic data of both archaeal and bacterial origin, the latter rarely used in past studies. We also avoided potential calibration biases that may have affected earlier studies. We obtained a conservative interval of 2.2–1.5 Ga, with an even narrower core interval of 2.0–1.8 Ga, for the origin of eukaryotes, a period closely aligned with the rise in oxygen. We further reconstructed the history of biological complexity across the tree of life using three universal measures: cell types, genes, and genome size. We found that the rise in complexity was temporally consistent with and followed a pattern similar to the rise in oxygen. This suggests a causal relationship stemming from the increased energy needs of complex life fulfilled by oxygen. 
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  8. Through the artistic planning tool known to comic book artists and animators as storyboarding, students will embark on comic book–style adventures to plan, describe, and visualize the complex life of genes through the non-Mendelian concept of epistasis. Using storyboard templates, conceptual layouts, sketch booking, and cut-out genetic elements, students will construct their interpretation of the gene-gene interactions of epistasis. The incomplete story of the epistasis of human eye color will serve as the theme for this storyboard, which will also become its own assessment tool, inviting educators into a realm of a true STEAM experience. 
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  9. We introduce biology to the artist’s design tool, the storyboard. This versatile organizing and visualizing artistic platform is introduced into the biology classroom to aid in an inventive and focused discovery process. Almost all biological concepts are dynamic, and storyboards offer biology, lecture, wet and computational labs, flexibility, inventiveness, and an opportunity for students to slow down the so-called steps of biological processes and moderate their observations. Storyboarding is a thoughtful and reflective discovery device with enormous potential to break with traditional biology classroom experiences and return to the root of the educational process: storytelling. It will encourage teachers to embark on the remodeling of the biological curriculum with specific technical skills that students and teachers should consider developing to make the STEAM experience tailored to the uniqueness of biological systems. Storyboards offer hands-on, illustrative, and interactive conversations about biology concepts. They are an “unplugged” and contemplative experiences, organizing frameworks for personal expression focused on biological wonders. 
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