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"Mitchell, Emily"
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The letters of Emily Dickinson
\"The Letters of Emily Dickinson collects, redates, and recontextualizes all of the poet's extant letters, including dozens newly discovered or never before anthologized. Insightful annotations emphasize not the reclusive poet of myth but rather an artist firmly embedded in the political and literary currents of her time\"-- Provided by publisher.
BOOK
Metacommunity analyses show an increase in ecological specialisation throughout the Ediacaran period
The first animals appear during the late Ediacaran (572 to 541 Ma); an initial diversity increase was followed reduction in diversity, often interpreted as catastrophic mass extinction. We investigate Ediacaran ecosystem structure changes over this time period using the “Elements of Metacommunity Structure” framework to assess whether this diversity reduction in the Nama was likely caused by an external mass extinction, or internal metacommunity restructuring. The oldest metacommunity was characterised by taxa with wide environmental tolerances, and limited specialisation or intertaxa associations. Structuring increased in the second oldest metacommunity, with groups of taxa sharing synchronous responses to environmental gradients, aggregating into distinct communities. This pattern strengthened in the youngest metacommunity, with communities showing strong environmental segregation and depth structure. Thus, metacommunity structure increased in complexity, with increased specialisation and resulting in competitive exclusion, not a catastrophic environmental disaster, leading to diversity loss in the terminal Ediacaran. These results reveal that the complex eco-evolutionary dynamics associated with Cambrian diversification were established in the Ediacaran.
Journal Article
From organisms to biodiversity: the ecology of the Ediacaran/Cambrian transition
The Ediacaran/Cambrian transition (ECT; ~575–500 Ma) captures the early diversification of animals, including the oldest crown-group taxa of most major animal phyla alive today. Key to understanding the drivers underneath the ECT macroevolutionary patterns are the interactions of animals with one another and their environment, and how these interactions scale up to global diversity patterns. Understanding the ecology of ECT organisms is enabled by the abundance of Lagerstätten over this time period, with a relatively large proportion of soft-bodied organisms preserved, often within the communities in which they lived. Here, we review our understanding of organismal, community, and macroecology of the ECT, and how these different scales of ecological analyses relate to the macroevolutionary diversification patterns we see over this 75 Myr time period. Across all ecological scales, we find clear trends, starting with stochastic ecosystem dynamics dominated by generalist taxa in the first Ediacaran communities, to more structured, niche-driven specialist dynamics by Cambrian Epoch 2. These trends are reflected in organism functional morphology, the complexity and strength of organisms’ interactions within their communities, and large-scale metacommunity, biogeographic, and biodiversity patterns. Yet there is often a time delay between the origination of a new type of ecological interaction and when it is observed to impact the ecosystem as a whole. As such, while many modern ecological innovations were in place by the end of the Cambrian, the knock-on effects and complexity of these interactions continued to build up throughout the Phanerozoic, leading to the complex biosphere we have today.
Journal Article
في الغياب : أعمال طارق الغصين الفوتوغرافية
يتناول كتاب (في الغياب : أعمال طارق الغصين الفوتوغرافية) والذي قام بتأليفه (طارق الغصين) في حوالي (146) صفحة من القطع المتوسط موضوع (التصوير الفوتوغرافي) مستعرضا المحتويات التالية : اللوحات : 1- سلسلة Self portrait series حوار مع الفنان مع جاسر املي، 2 سلسلة A + B series بلا عنوان لا مكان للقريب بقلم سوزان كوتر، 3- سلسلة C series بلا عنوان الزمان والمكان بقلم أنتوتيا كارفر ... إلخ.
BOOK
Clonal dynamics of haematopoiesis across the human lifespan
Age-related change in human haematopoiesis causes reduced regenerative capacity
1
, cytopenias
2
, immune dysfunction
3
and increased risk of blood cancer
4
–
6
, but the reason for such abrupt functional decline after 70 years of age remains unclear. Here we sequenced 3,579 genomes from single cell-derived colonies of haematopoietic cells across 10 human subjects from 0 to 81 years of age. Haematopoietic stem cells or multipotent progenitors (HSC/MPPs) accumulated a mean of 17 mutations per year after birth and lost 30 base pairs per year of telomere length. Haematopoiesis in adults less than 65 years of age was massively polyclonal, with high clonal diversity and a stable population of 20,000–200,000 HSC/MPPs contributing evenly to blood production. By contrast, haematopoiesis in individuals aged over 75 showed profoundly decreased clonal diversity. In each of the older subjects, 30–60% of haematopoiesis was accounted for by 12–18 independent clones, each contributing 1–34% of blood production. Most clones had begun their expansion before the subject was 40 years old, but only 22% had known driver mutations. Genome-wide selection analysis estimated that between 1 in 34 and 1 in 12 non-synonymous mutations were drivers, accruing at constant rates throughout life, affecting more genes than identified in blood cancers. Loss of the Y chromosome conferred selective benefits in males. Simulations of haematopoiesis, with constant stem cell population size and constant acquisition of driver mutations conferring moderate fitness benefits, entirely explained the abrupt change in clonal structure in the elderly. Rapidly decreasing clonal diversity is a universal feature of haematopoiesis in aged humans, underpinned by pervasive positive selection acting on many more genes than currently identified.
Haematopoiesis has high clonal diversity up to about 65 years of age, after which diversity drops precipitously owing to positive selection acting on a handful of clones that expand exponentially throughout adulthood.
Journal Article
Increases in reef size, habitat and metacommunity complexity associated with Cambrian radiation oxygenation pulses
Oxygenation during the Cambrian Radiation progressed via a series of short-lived pulses. However, the metazoan biotic response to this episodic oxygenation has not been quantified, nor have the causal evolutionary processes been constrained. Here we present ecological analyses of Cambrian archaeocyath sponge reef communities on the Siberian Platform (525–514 Ma). During the oxic pulse at ~521–519 Ma, we quantify reef habitat expansion coupled to an increase in reef size and metacommunity complexity, from individual within-community reactions to their local environment, to ecologically complex synchronous community-wide response, accompanied by an increase in rates of origination. Subsequently, reef and archaeocyath body size are reduced in association with increased rates of extinction due to inferred expanded marine anoxia (~519–516.5 Ma). A later oxic pulse at ~515 Ma shows further reef habitat expansion, increased archaeocyath body size and diversity, but weaker community-wide environmental responses. These metrics confirm that oxygenation events created temporary pulses of evolutionary diversification and enhanced ecosystem complexity, potentially via the expansion of habitable space, and increased archaeocyath individual and reef longevity in turn leading to niche differentiation. Most notably, we show that progression towards increasing biodiversity and ecosystem complexity was episodic and discontinuous, rather than linear, during the Cambrian Radiation.
During the Cambrian Radiation, oxygenation occurred in a series of short pulses. Here, the authors quantify episodic changes in reef size, extent of habitat and in metacommunity ecological complexity associated with these oxygenation pulses by examining archaeocyath sponges.
Journal Article
Life histories of myeloproliferative neoplasms inferred from phylogenies
Mutations in cancer-associated genes drive tumour outgrowth, but our knowledge of the timing of driver mutations and subsequent clonal dynamics is limited
1
–
3
. Here, using whole-genome sequencing of 1,013 clonal haematopoietic colonies from 12 patients with myeloproliferative neoplasms, we identified 580,133 somatic mutations to reconstruct haematopoietic phylogenies and determine clonal histories. Driver mutations were estimated to occur early in life, including the in utero period.
JAK2
V617F
was estimated to have been acquired by 33 weeks of gestation to 10.8 years of age in 5 patients in whom
JAK2
V617F
was the first event.
DNMT3A
mutations were acquired by 8 weeks of gestation to 7.6 years of age in 4 patients, and a
PPM1D
mutation was acquired by 5.8 years of age. Additional genomic events occurred before or following
JAK2
V617F
acquisition and as independent clonal expansions. Sequential driver mutation acquisition was separated by decades across life, often outcompeting ancestral clones. The mean latency between
JAK2
V617F
acquisition and diagnosis was 30 years (range 11–54 years). Estimated historical rates of clonal expansion varied substantially (3% to 190% per year), increased with additional driver mutations, and predicted latency to diagnosis. Our study suggests that early driver mutation acquisition and life-long growth and evolution underlie adult myeloproliferative neoplasms, raising opportunities for earlier intervention and a new model for cancer development.
Whole-genome sequencing of 1,013 clonal haematopoietic colonies from myeloproliferative neoplasms of 12 individuals reveals haematopoietic phylogenies and indicates that driver mutations are acquired sequentially, starting early in life.
Journal Article
TopoQual polishes circular consensus sequencing data and accurately predicts quality scores
Background
Pacific Biosciences (PacBio) circular consensus sequencing (CCS), also known as high fidelity (HiFi) technology, has revolutionized modern genomics by producing long (10 + kb) and highly accurate reads. This is achieved by sequencing circularized DNA molecules multiple times and combining them into a consensus sequence. Currently, the accuracy and quality value estimation provided by HiFi technology are more than sufficient for applications such as genome assembly and germline variant calling. However, there are limitations in the accuracy of the estimated quality scores when it comes to somatic variant calling on single reads.
Results
To address the challenge of inaccurate quality scores for somatic variant calling, we introduce TopoQual, a novel tool designed to enhance the accuracy of base quality predictions. TopoQual leverages techniques including partial order alignments (POA), topologically parallel bases, and deep learning algorithms to polish consensus sequences. Our results demonstrate that TopoQual corrects approximately 31.9% of errors in PacBio consensus sequences. Additionally, it validates base qualities up to q59, which corresponds to one error in 0.9 million bases. These improvements will significantly enhance the reliability of somatic variant calling using HiFi data.
Conclusion
TopoQual represents a significant advancement in genomics by improving the accuracy of base quality predictions for PacBio HiFi sequencing data. By correcting a substantial proportion of errors and achieving high base quality validation, TopoQual enables confident and accurate somatic variant calling. This tool not only addresses a critical limitation of current HiFi technology but also opens new possibilities for precise genomic analysis in various research and clinical applications.
Journal Article
The longitudinal dynamics and natural history of clonal haematopoiesis
Clonal expansions driven by somatic mutations become pervasive across human tissues with age, including in the haematopoietic system, where the phenomenon is termed clonal haematopoiesis
1
–
4
. The understanding of how and when clonal haematopoiesis develops, the factors that govern its behaviour, how it interacts with ageing and how these variables relate to malignant progression remains limited
5
,
6
. Here we track 697 clonal haematopoiesis clones from 385 individuals 55 years of age or older over a median of 13 years. We find that 92.4% of clones expanded at a stable exponential rate over the study period, with different mutations driving substantially different growth rates, ranging from 5% (
DNMT3A
and
TP53
) to more than 50% per year (
SRSF2
P95H
). Growth rates of clones with the same mutation differed by approximately ±5% per year, proportionately affecting slow drivers more substantially. By combining our time-series data with phylogenetic analysis of 1,731 whole-genome sequences of haematopoietic colonies from 7 individuals from an older age group, we reveal distinct patterns of lifelong clonal behaviour.
DNMT3A
-mutant clones preferentially expanded early in life and displayed slower growth in old age, in the context of an increasingly competitive oligoclonal landscape. By contrast, splicing gene mutations drove expansion only later in life, whereas
TET2
-mutant clones emerged across all ages. Finally, we show that mutations driving faster clonal growth carry a higher risk of malignant progression. Our findings characterize the lifelong natural history of clonal haematopoiesis and give fundamental insights into the interactions between somatic mutation, ageing and clonal selection.
A long-term study of 385 human donors reports that driver gene mutations and age determine the lifelong dynamics of clonal haematopoiesis
Journal Article