Monthly Archives: April 2024

Schrer, O. D. Nucleotide excision repair in Eukaryotes. Cold Spring Harb. Perspect. Biol. 5, a012609 (2013).

Article PubMed PubMed Central Google Scholar

Marteijn, J. A., Lans, H., Vermeulen, W. & Hoeijmakers, J. H. J. Understanding nucleotide excision repair and its roles in cancer and ageing. Nat. Rev. Mol. Cell Biol. 15, 465481 (2014).

Article CAS PubMed Google Scholar

Mu, H., Geacintov, N. E., Broyde, S., Yeo, J. E. & Schrer, O. D. Molecular basis for damage recognition and verification by XPC-RAD23B and TFIIH in nucleotide excision repair. DNA Repair 71, 3342 (2018). vol.

Article CAS PubMed PubMed Central Google Scholar

Sugasawa, K. Molecular mechanisms of DNA damage recognition for mammalian nucleotide excision repair. DNA Repair (Amst.) 44, 110117 (2016).

Article CAS PubMed Google Scholar

Lans, H., Hoeijmakers, J. H. J., Vermeulen, W. & Marteijn, J. A. The DNA damage response to transcription stress. Nat. Rev. Mol. Cell Biol. 20, 766784 (2019).

Article CAS PubMed Google Scholar

Jia, N. et al. Dealing with transcription-blocking DNA damage: Repair mechanisms, RNA polymerase II processing and human disorders. DNA Repair (Amst.) 106, 103192 (2021).

Article CAS PubMed Google Scholar

Theil, A. F., Hckes, D. & Lans, H. TFIIH central activity in nucleotide excision repair to prevent disease. DNA Repair (Amst.) 132, 103568 (2023).

Article CAS PubMed Google Scholar

Bernardes de Jesus, B. M., Bjrs, M., Coin, F. & Egly, J. M. Dissection of the Molecular Defects Caused by Pathogenic Mutations in the DNA Repair Factor XPC. Mol. Cell. Biol. 28, 72257235 (2008).

Article CAS PubMed PubMed Central Google Scholar

Okuda, M., Nakazawa, Y., Guo, C., Ogi, T. & Nishimura, Y. Common TFIIH recruitment mechanism in global genome and transcription-coupled repair subpathways. Nucleic Acids Res. 45, 1304313055 (2017).

Article CAS PubMed PubMed Central Google Scholar

Oksenych, V., De Jesus, B. B., Zhovmer, A., Egly, J. M. & Coin, F. Molecular insights into the recruitment of TFIIH to sites of DNA damage. EMBO J. 28, 29712980 (2009).

Article CAS PubMed PubMed Central Google Scholar

van der Weegen, Y. et al. The cooperative action of CSB, CSA, and UVSSA target TFIIH to DNA damage-stalled RNA polymerase II. Nat. Commun. 11, 116 (2020).

Google Scholar

Ribeiro-Silva, C. et al. Ubiquitin and TFIIH-stimulated DDB2 dissociation drives DNA damage handover in nucleotide excision repair. Nat. Commun. 11, 4868 (2020).

Article CAS PubMed PubMed Central Google Scholar

Coin, F., Oksenych, V. & Egly, J. M. Distinct Roles for the XPB/p52 and XPD/p44 Subcomplexes of TFIIH in Damaged DNA Opening during Nucleotide Excision Repair. Mol. Cell 26, 245256 (2007).

Article CAS PubMed Google Scholar

Sugasawa, K., Akagi, Jichi, Nishi, R., Iwai, S. & Hanaoka, F. Two-step recognition of DNA damage for mammalian nucleotide excision repair: directional binding of the XPC complex and DNA strand scanning. Mol. Cell 36, 642653 (2009).

Article CAS PubMed Google Scholar

Li, C. L. et al. Tripartite DNA lesion recognition and verification by XPC, TFIIH, and XPA in nucleotide excision repair. Mol. Cell 59, 10251034 (2015).

Article CAS PubMed PubMed Central Google Scholar

De Laat, W. L. et al. DNA-binding polarity of human replication protein A positions nucleases in nucleotide excision repair. Genes Dev. 12, 25982609 (1998).

Article PubMed PubMed Central Google Scholar

Matsunaga, T., Park, C. H., Bessho, T., Mu, D. & Sancar, A. Replication protein A confers structure-specific endonuclease activities to the XPF-ERCC1 and XPG subunits of human DNA repair excision nuclease. J. Biol. Chem. 271, 1104711050 (1996).

Article CAS PubMed Google Scholar

Sugitani, N., Sivley, R. M., Perry, K. E., Capra, J. A. & Chazin, W. J. XPA: A key scaffold for human nucleotide excision repair. DNA Repair 44, 123135 (2016).

Article CAS PubMed PubMed Central Google Scholar

Kokic, G. et al. Structural basis of TFIIH activation for nucleotide excision repair. Nat. Commun. 10, 2885 (2019).

Article PubMed PubMed Central Google Scholar

Coin, F. et al. Nucleotide Excision Repair Driven by the Dissociation of CAK from TFIIH. Mol. Cell 31, 920 (2008).

Article CAS PubMed Google Scholar

Staresincic, L. et al. Coordination of dual incision and repair synthesis in human nucleotide excision repair. EMBO J. 28, 11111120 (2009).

Article CAS PubMed PubMed Central Google Scholar

Fagbemi, A. F., Orelli, B. & Schrer, O. D. Regulation of endonuclease activity in human nucleotide excision repair. DNA Repair (Amst.) 10, 722729 (2011).

Article CAS PubMed Google Scholar

Muniesa-Vargas, A. et al. XPG: a multitasking genome caretaker. Cell. Mol. Life Sci. 79, 120 (2022).

Article Google Scholar

van Toorn, M. et al. Active DNA damage eviction by HLTF stimulates nucleotide excision repair. Mol. Cell 82, 13431358.e8 (2022).

Article PubMed PubMed Central Google Scholar

Ogi, T. et al. Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells. Mol. Cell 37, 714727 (2010).

Article CAS PubMed Google Scholar

Ferri, D., Orioli, D. & Botta, E. Heterogeneity and overlaps in nucleotide excision repair disorders. Clin. Genet. 97, 1224 (2020).

Article CAS PubMed Google Scholar

Lehmann, A. R., McGibbon, D. & Stefanini, M. Xeroderma pigmentosum. Orphanet J. Rare Dis. 6, 70 (2011).

Article PubMed PubMed Central Google Scholar

Natale, V. A comprehensive description of the severity groups in Cockayne syndrome. Am. J. Med. Genet. A 155A, 10811095 (2011).

Article PubMed Google Scholar

Natale, V. & Raquer, H. Xeroderma pigmentosum-Cockayne syndrome complex. Orphanet J. Rare Dis. 12, 65 (2017).

Article PubMed PubMed Central Google Scholar

Kraemer, K. H. et al. Xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome: A complex genotype-phenotype relationship. Neuroscience 145, 13881396 (2007).

Article CAS PubMed Google Scholar

Theil, A. F., Hoeijmakers, J. H. J. & Vermeulen, W. TTDA: big impact of a small protein. Exp. Cell Res. 329, 6168 (2014).

Article CAS PubMed Google Scholar

Stefanini, M., Botta, E., Lanzafame, M. & Orioli, D. Trichothiodystrophy: From basic mechanisms to clinical implications. DNA Repair 9, 210 (2010).

Article CAS PubMed Google Scholar

Rahbar, Z. & Naraghi, M. De Sanctis-Cacchione syndrome: A case report and literature review. Int. J. Womens Dermatol. 1, 136139 (2015).

Article Google Scholar

Karikkineth, A. C., Scheibye-Knudsen, M., Fivenson, E., Croteau, D. L. & Bohr, V. A. Cockayne syndrome: Clinical features, model systems and pathways. Ageing Res. Rev. 33, 317 (2017).

Article CAS PubMed Google Scholar

Wang, Y. et al. Dysregulation of gene expression as a cause of cockayne syndrome neurological disease. Proc. Natl Acad. Sci. Usa. 111, 1445414459 (2014).

Article CAS PubMed PubMed Central Google Scholar

Vlez-Cruz, R. & Egly, J. M. Cockayne syndrome group B (CSB) protein: At the crossroads of transcriptional networks. Mech. Ageing Dev. 134, 234242 (2013).

Article PubMed Google Scholar

Sabatella, M. et al. Repair protein persistence at DNA lesions characterizes XPF defect with Cockayne syndrome features. Nucleic Acids Res. 46, 95639577 (2018).

Article CAS PubMed PubMed Central Google Scholar

Lans, H. & Vermeulen, W. Tissue specific response to DNA damage: C. elegans as role model. DNA Repair (Amst.) 32, 141148 (2015).

Article CAS PubMed Google Scholar

Hoogstraten, D. et al. Rapid switching of TFIIH between RNA polymerase I and II transcription and DNA repair in vivo. Mol. Cell 10, 11631174 (2002).

Article CAS PubMed Google Scholar

Vermeulen, W. Dynamics of mammalian NER proteins. DNA Repair (Amst.) 10, 760771 (2011).

Article CAS PubMed Google Scholar

Fassihi, H. et al. Deep phenotyping of 89 xeroderma pigmentosum patients reveals unexpected heterogeneity dependent on the precise molecular defect. Proc. Natl Acad. Sci. Usa. 113, E1236E1245 (2016).

Article CAS PubMed PubMed Central Google Scholar

Kashiyama, K. et al. Malfunction of nuclease ERCC1-XPF results in diverse clinical manifestations and causes Cockayne syndrome, xeroderma pigmentosum, and Fanconi anemia. Am. J. Hum. Genet. 92, 807819 (2013).

Article CAS PubMed PubMed Central Google Scholar

Sijbers, A. M. et al. Xeroderma pigmentosum group F caused by a defect in a structure-specific DNA repair endonuclease. Cell 86, 811822 (1996).

Article CAS PubMed Google Scholar

Ahmad, A. et al. Mislocalization of XPF-ERCC1 nuclease contributes to reduced DNA repair in XP-F patients. PLoS Genet 6, e1000871 (2010).

Article PubMed PubMed Central Google Scholar

Jia, N. et al. A rapid, comprehensive system for assaying DNA repair activity and cytotoxic effects of DNA-damaging reagents. Nat. Protoc. 10, 1224 (2015).

Article CAS PubMed Google Scholar

Llerena Schiffmacher, D. A. et al. Live cell transcription-coupled nucleotide excision repair dynamics revisited. DNA Repair (Amst.) 130, 103566 (2023).

Article CAS PubMed Google Scholar

Geijer, M. E. et al. Elongation factor ELOF1 drives transcription-coupled repair and prevents genome instability. Nat. Cell Biol. 23, 608619 (2021).

Article CAS PubMed PubMed Central Google Scholar

Kim, D. E. et al. Deficiency in the DNA repair protein ERCC1 triggers a link between senescence and apoptosis in human fibroblasts and mouse skin. Aging Cell 19, e13072 (2020).

Article MathSciNet CAS PubMed Google Scholar

Harada, Y.-N. et al. Postnatal Growth Failure, Short Life Span, and Early Onset of Cellular Senescence and Subsequent Immortalization in Mice Lacking the Xeroderma Pigmentosum Group G Gene. Mol. Cell. Biol. 19, 2366 (1999).

Article CAS PubMed PubMed Central Google Scholar

Niedernhofer, L. J. et al. A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis. Nature 444, 10381043 (2006).

Article CAS PubMed Google Scholar

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Persistent TFIIH binding to non-excised DNA damage causes cell and developmental failure - Nature.com

In July 1957, 22 prominent scientists gathered quietly at a private lodge in Pugwash, a small town in Canadas Nova Scotia province. They had answered a call to action by Albert Einstein, inviting scientists to shape guardrails that would contain the danger of nuclear weapons. The Pugwash Conference earned a Nobel Peace Prize, and more importantly, it laid the foundations for the nuclear non-proliferation treaties, which saved our world from risks of annihilation.

Today, governments and businesses are frantically searching for ways to limit the many feared perils of AIespecially those from Artificial General Intelligence (AGI), the next phase of AI evolution. AGI will perform a wide range of cognitive tasks with an efficiency and accuracy far superior to current AI systems. This next stage of A.I., often referred to by Silicon Valley enthusiasts as God-like, is expected to surpass human intelligence and efficiency by a substantial margin. It is rumored that an internal report on the risks of AGI may be what ignited the recent board drama at OpenAI, the maker of ChatGPT. But while the race to build AGI is still in progress, we can be certain that whoever controls it will have enormous sway on society and the economy, potentially exerting influence on the lives of humans everywhere.

In the past year, numerous and uncoordinated efforts by government and business to contain AI sprang across the world, in the U.S., China, the EU, and the U.K. Businesses have been pleading with governments to regulate their AI creations, whilst knowing full well that governments will never succeed in regulating effectively at the speed of A.I. evolution. The EU recently completed a multi-year effort to deliver the AI Act. However, the shifts in generative AI capabilities mean that by the time it is enacted in 2025, the new AI Act may already be outdated.

Governments are not equipped to outgallop fast-moving technologies with effective rules and policiesespecially in the early hyperfast stages of development. Moreover, AI technologies have a transnational borderless reach, limiting the effectiveness of national and regional rule systems to govern them. As for businesses, they are in intense competition to dominate and profit from these technologies. In such a race, fueled by billions of investments, safety guardrails are inevitably a low priority for most businesses.

Ironically, governments and businesses are in fact the two stakeholders who are most in need of guardrails to prevent them from misusing A.I. in surveillance, warfare, and other endeavors to influence or control the public.

A careful analysis of how prior technologies and scientific innovations were tamed in the 20th century offers a clear answer to this dilemma. Guardrails were designed by scientists who know their own creations and understand (better than most) how they might evolve.

At Pugwash, influential scientists came together to develop strategies to mitigate the risks of nuclear weapons, significantly contributing to the formulation of arms control agreements and fostering international dialogue during the tense Cold War era.

In February 1975, at the Asilomar Conference in California, it was again scientists who met and successfully established critical guidelines for the safe and ethical research of DNA, thereby preventing potential biohazards. The Asilomar guidelines not only paved the way for responsible scientific inquiry but also informed regulatory policies worldwide. More recently, it was again the scientists and inventors of the Internet, led by Vint Cerf, who convened and shaped the framework of guardrails and protocols that made the Internet thrive globally.

All these successful precedents are proof that we need businesses and governments to first make space and let A.I. scientists shape a framework of guardrails that contain the risks without limiting the many benefits of A.I. Businesses can then implement such a framework voluntarily, and only when necessary, governments should step in to enforce the implementation by enacting policies and laws based on the scientists framework. This proven approach worked well for nuclear technology, DNA, and the Internet. It should be a blueprint to build safer AI.

A Pugwash Conference for AI scientists is therefore urgently needed. The conference should include no more than two dozen scientists, in the mold of Geoffrey Hinton who chose to quit Google in order to speak his mind on AIs promise and perils.

Like Pugwash, the scientists should be chosen from all the key countries where advanced A.I. technologies are developing, in order to at least strive for a global consensus. Most importantly, the choice of the participants at this seminal A.I. conference must reassure the public that the conferees are shielded from special interests, geopolitical pressures, and profit-centric motives.

While hundreds of government leaders and business bosses will cozy up to discuss A.I. at multiple annual international events, thoughtful and independent A.I. scientists must urgently get together to make A.I. good for all.

Fadi Chehad is chairman, cofounder, and managingpartner of Ethos Capital. He founded several software companies and was a fellow at Harvard and Oxford. From 2012 to 2016 he led ICANN, the technical institution that sets the global rules and policies for the internets key resources.

The opinions expressed in Fortune.com commentary pieces are solely the views of their authors and do not necessarily reflect the opinions and beliefs ofFortune.

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Scientists inspired the right guardrails for nuclear energy, the internet, and DNA research. Let them do the same for AI - Fortune

Strelitzia is a genus of five species of perennial plants, native to South Africa. It belongs to the plant family Strelitziaceae. A common name of the genus is bird of paradise flower/plant, because of a resemblance of its flowers to birds-of-paradise. In South Africa, it is commonly known as a crane flower. Wikipedia

The most up-to-date understanding of the flowering plant tree of life is presented in a new study published today in the journal Nature by an international team of 279 scientists, including three University of Michigan biologists.

Using 1.8 billion letters of genetic code from more than 9,500 species covering almost 8,000 known flowering plant genera (ca. 60%), this achievement sheds new light on the evolutionary history of flowering plants and their rise to ecological dominance on Earth.

Led by scientists at the Royal Botanic Gardens, Kew, the research team believes the data will aid future attempts to identify new species, refine plant classification, uncover new medicinal compounds, and conserve plants in the face of climate change and biodiversity loss.

The major milestone for plant science, involving 138 organizations internationally, was built on 15 times more data than any comparable studies of the flowering plant tree of life. Among the species sequenced for this study, more than 800 have never had their DNA sequenced before.

The sheer amount of data unlocked by this research, which would take a single computer 18 years to process, is a huge stride toward building a tree of life for all 330,000 known species of flowering plantsa massive undertaking by Kews Tree of Life Initiative.

Analyzing this unprecedented amount of data to decode the information hidden in millions of DNA sequences was a huge challenge. But it also offered the unique opportunity to reevaluate and extend our knowledge of the plant tree of life, opening a new window to explore the complexity of plant evolution, said Alexandre Zuntini, a research fellow at Royal Botanic Gardens, Kew.

Tom Carruthers, postdoctoral researcher in the lab of U-M evolutionary biologist Stephen Smith, is co-lead author of the study with Zuntini, who he previously worked with at Kew. U-M plant systematist Richard Rabeler is a co-author.

All 64 orders, all 416 families and 58% (7,923) of genera are represented. The young tree is illustrated here (maximum constraint at the root node of 154Ma), with branch colours representing net diversification rates. Black dots at nodes indicate the phylogenetic placement of fossil calibrations based on the updated AngioCal fossil calibration dataset. Note that calibrated nodes can be older than the age of the corresponding fossils owing to the use of minimum age constraints. Arcs around the tree indicate the main clades of angiosperms as circumscribed in this paper. ANA grade refers to the three consecutively diverging orders Amborellales, Nymphaeales and Austrobaileyales. Plant portraits illustrating key orders were sourced from Curtiss Botanical Magazine (Biodiversity Heritage Library). These portraits, by S. Edwards, W. H. Fitch, W. J. Hooker, J. McNab and M. Smith, were first published between 1804 and 1916 (for a key to illustrations see Supplementary Table 2). A high-resolution version of this figure can be downloaded from https://doi.org/10.5281/zenodo.10778206 (ref. 55).

Flowering plants feed, clothe and greet us whenever we walk into the woods. The construction of a flowering plant tree of life has been a significant challenge and goal for the field of evolutionary biology for more than a century, said Smith, co-author of the study and professor in the U-M Department of Ecology and Evolutionary Biology. This project moves us closer to that goal by providing a massive dataset for most of the genera of flowering plants and offering one strategy to complete this goal.

Smith had two roles on the project. First, members of his labincluding former U-M graduate student Drew Larsontraveled to Kew to help sequence members of a large and diverse plant group called Ericales, which includes blueberries, tea, ebony, azaleas, rhododendrons and Brazil nuts.

Second, Smith supervised the analyses and construction of the project dataset along with William Baker and Felix Forest of the Royal Botanic Gardens, Kew, and Wolf Eisenhardt of Aarhus University.

One of the biggest challenges faced by the team was the unexpected complexity underlying many of the gene regions, where different genes tell different evolutionary histories. Procedures had to be developed to examine these patterns on a scale that hadnt been done before, said Smith, who is also director of the Program in Biology and an associate curator in biodiversity informatics at the U-M Herbarium.

As co-leader of the study, Carruthers main responsibilities included scaling the evolutionary tree to time using 200 fossils, analyzing the different evolutionary histories of the genes underlying the overall evolutionary tree, and estimating rates of diversification in different flowering plant lineages at different times.

Hebarium speciment from 1832 Trepocarpus aethusae RBG Kew

Constructing such a large tree of life for flowering plants, based on so many genes, sheds light on the evolutionary history of this special group, helping us to understand how they came to be such an integral and dominant part of the world, Carruthers said. The evolutionary relationships that are presentedand the data underlying themwill provide an important foundation for a lot of future studies.

The flowering plant tree of life, much like our own family tree, enables us to understand how different species are related to each other. The tree of life is uncovered by comparing DNA sequences between different species to identify changes (mutations) that accumulate over time like a molecular fossil record.

Our understanding of the tree of life is improving rapidly in tandem with advances in DNA sequencing technology. For this study, new genomic techniques were developed to magnetically capture hundreds of genes and hundreds of thousands of letters of genetic code from every sample, orders of magnitude more than earlier methods.

A key advantage of the teams approach is that it enables a wide diversity of plant material, old and new, to be sequenced, even when the DNA is badly damaged. The vast treasure troves of dried plant material in the worlds herbarium collections, which comprise nearly 400 million scientific specimens of plants, can now be studied genetically.

In many ways this novel approach has allowed us to collaborate with the botanists of the past by tapping into the wealth of data locked up in historic herbarium specimens, some of which were collected as far back as the early 19th century, said Baker, senior research leader for Kews Tree of Life Initiative.

Our illustrious predecessors, such as Charles Darwin or Joseph Hooker, could not have anticipated how important these specimens would be in genomic research today. DNA was not even discovered in their lifetimes. Our work shows just how important these incredible botanical museums are to groundbreaking studies of life on Earth. Who knows what other undiscovered science opportunities lie within them?

Across all 9,506 species sequenced, more than 3,400 came from material sourced from 163 herbaria in 48 countries.

Sampling herbarium specimens for the study of plant relationships makes broad sampling from diverse areas of the world much more feasible than if one had to travel to get fresh material from the field, said U-Ms Rabeler, a research scientist emeritus and former collection manager at the U-M Herbarium.

For the tree of life project, Rabeler helped verify the identity of herbarium specimens selected for sampling and analyzed the resulting data.

Flowering plants alone account for about 90% of all known plant life on land and are found virtually everywhere on the planetfrom the steamiest tropics to the rocky outcrops of the Antarctic Peninsula. And yet, our understanding of how these plants came to dominate the scene soon after their origin has baffled scientists for generations, including Darwin.

Flowering plants originated more than 140 million years ago after which they rapidly overtook other vascular plants including their closest living relativesthe gymnosperms (nonflowering plants that have naked seeds, such as cycads, conifers and ginkgo).

Darwin was mystified by the seemingly sudden appearance of such diversity in the fossil record. In an 1879 letter to Hooker, his close confidant and director of the Royal Botanic Gardens, Kew, he wrote: The rapid development as far as we can judge of all the higher plants within recent geological times is an abominable mystery.

Using 200 fossils, the authors scaled their tree of life to time, revealing how flowering plants evolved across geological time. They found that early flowering plants did indeed explode in diversity, giving rise to more than 80% of the major lineages that exist today shortly after their origin.

However, this trend then declined to a steadier rate for the next 100 million years until another surge in diversification about 40 million years ago, coinciding with a global decline in temperatures. These new insights would have fascinated Darwin and will surely help todays scientists grappling with the challenges of understanding how and why species diversify.

Assembling a tree of life this extensive would have been impossible without Kews scientists collaborating with many partners across the globe. In total, 279 authors were involved in the research, representing many different nationalities from 138 organizations in 27 countries.

The plant community has a long history of collaborating and coordinating molecular sequencing to generate a more comprehensive and robust plant tree of life. The effort that led to this paper continues in that tradition but scales up quite significantly, said U-Ms Smith.

The flowering plant tree of life has enormous potential in biodiversity research. This is because, just as one can predict the properties of an element based on its position in the periodic table, the location of a species in the tree of life allows us to predict its properties. The new data will thus be invaluable for enhancing many areas of science and beyond.

To enable this, the tree and all of the data that underpin it have been made openly and freely accessible to both the public and scientific community, including through the Kew Tree of Life Explorer.

Open access will help scientists to make the best use of the data, such as combining it with artificial intelligence to predict which plant species may include molecules with medicinal potential.

Similarly, the tree of life can be used to better understand and predict how pests and diseases are going to affect plants in the future. Ultimately, the authors note, the applications of this data will be driven by the ingenuity of the scientists accessing it.

Phylogenomics and the rise of the Angiosperms, Nature (open access)

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Earth Life Biodiversity: Vast DNA Tree Of life For Flowering Plants Revealed - Astrobiology - Astrobiology News

Suri Cruise inherited more than just her mother Katie Holmess faceher fabulous sense of style was also clearly woven into her DNA. The mother-daughter duo turned a coffee run into a runway, each of them showing off their personal style.

Wearing a very Holmesian outfit, the actor donned a cozy gray crewneck sweater, which she layered over a striped button-up shirt. She paired her layered look with a pair of indigo blue jeans and black Adidas Sambasa stalwart shoe in her closet full of funky loafers and cork wedges. Holmes gave her preppy look a touch of boho chic with her accessorizing, adding a pair of oversized sunglasses and a black leather hobo bag slung over her shoulder.

Cruise, meanwhile, is all in on the boho revival. The freshly minted 18-year-old was too young to fully participate in the last bohemian moment, and is making up for lost time. She wore a tiered maxi dress with a red pattern with a pair of well-worn light brown Frye boots. Layering up on a chilly morning, Cruise layered an olive corduroy jacket underneath a denim overcoat.

Like her daughter, Holmes has also been known to love a good boho moment now and again. A longtime fan of Chlo, shes worn iterations of the brand from Phoebe Philos tenure to Gabriella Hearsts. Chemena Kamali, Chlos new creative director, recently posted a photo on Instagram of her own mother, dubbing her Chlo at heart. Might we suggest Kamali kick off the new Chlo era with a mother-daughter campaign starring, say, Katie Holmes and Suri Cruise?

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Katie Holmes and Suri Cruise Share Some Very Stylish DNA - Vogue

New DNA evidence has led police to arrest a75-year-old Auburn man who allegedly raped an underage victim in the woods near Lee Road 57 over 20 years ago, authorities said.

Bobby Lee Pitts was charged with first-degree kidnapping, rapeand sodomy in the 2003 incident. He is being held in the Lee County Detention Center without bond.

"I hope this sends a powerful message that no matter how much time has passed, we will never relent in our pursuit of justice. Every case matters deeply to us, and we will continue to pursue truth and accountability. Today, we stand firm in our promise," Auburn Police Chief Cedric Anderson said.

Anders said the arrest does more than give thevictim and their family closure.

"Its a testament to the unwavering commitment of our police department," the police chief said.

Auburn police launched an investigation into the incident onOct. 4, 2003. They met with a underaged victim who reported being sexual assaulted in a wooded area near Lee Road 57. The victim told police that theassailant forced them into the woods and subjected them to multiple acts of sexual violence.

At the time of the crime, police couldn't identify a suspect based on the physical evidence and description of the attacker.

APD cold case investigators submitted evidence through the Alabama Department of Forensic Sciences to the FBIs Combined DNA Index System. In January, APD received results fromforensic examinationthat authorities said identified Pitts as the offender.

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DNA evidence leads to arrest of 75-year-old Auburn man - Opelika Auburn News

How do we understand past societies? For centuries, our main sources of information have been pottery sherds, burial sites and ancient texts.

But the study of ancient DNA is changing what we know about the human past, and what we can know. In a new study, we analysed the genetics of hundreds of people who lived in the Carpathian Basin in southeastern central Europe more than 1,000 years ago, revealing detailed family trees, pictures of a complex society, and stories of change over centuries.

The Avars were a nomadic people originating from eastern central Asia. From the 6th to the 9th century CE, they wielded power over much of eastern central Europe.

The Avars are renowned among archaeologists for their distinctive belt garnitures, but their broader legacy has been overshadowed by predecessors such as the Huns. Nevertheless, Avar burial sites provide invaluable insights into their customs and way of life. To date, archaeologists have excavated more than 100,000 Avar graves.

Now, through the lens of archaeogenetics, we can delve even deeper into the intricate web of relationships among individuals who lived more than a millennium ago.

Much of what we know about Avar society comes from descriptions written by their enemies, such as the Byzantines and the Franks, so this work represents a significant leap forward in our understanding.

We combined ancient DNA data with archaeological, anthropological and historical context. As a result, we have been able to reconstruct extensive pedigrees, shedding light on kinship patterns, social practices and population dynamics of this enigmatic period.

We sampled all available human remains from four fully excavated Avar-era cemeteries, including those at Rkczifalva and Hajdnns in what is now Hungary. This resulted in a meticulous analysis of 424 individuals.

Around 300 of these individuals had close relatives buried in the same cemetery. This allowed us to reconstruct multiple extensive pedigrees spanning up to nine generations and 250 years.

Our research uncovered a sophisticated social framework. Our results suggest Avar society ran on a strict system of descent through the fathers line (patrilineal descent).

Following marriage, men typically remained within their paternal community, preserving the lineage continuity. In contrast, women played a crucial role in fostering social ties by marrying outside their familys community. This practice, called female exogamy, underscores the pivotal contribution of women in maintaining social cohesion.

Additionally, our study identified instances where closely related male individuals, such as siblings or a father and son, had offspring with the same female partner. Such couplings are called levirate unions.

Read more: In a Stone Age cemetery, DNA reveals a treasured 'founding father' and a legacy of prosperity for his sons

Despite these practices, we found no evidence of pairings between genetically related people. This suggests Avar societies meticulously preserved an ancestral memory.

These findings align with historical and anthropological evidence from societies of the Eurasian steppe.

Our study also revealed a transition in the main line of descent within Rkczifalva, when one pedigree took over from another. This occurred together with archaeological and dietary shifts likely linked to political changes in the region.

The transition, though significant, cannot be detected from higher-level genetic studies. Our results show an apparent genetic continuity can mask the replacement of entire communities. This insight may have far-reaching implications for future archaeological and genetic research.

Our study, carried out with researchers from the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany and at Etvs Lornd University in Budapest, Hungary, is part of a larger project called HistoGenes funded by the European Research Council.

This project shows we can use ancient DNA to examine entire communities, rather than just individuals. We think there is a lot more we can learn.

Now we aim to deepen our understanding of ancestral Avar society by expanding our research over a wider geographical area within the Avar realm. This broader scope will allow us to investigate the origins of the women who married into the communities we have studied. We hope it will also illuminate the connections between communities in greater detail.

Additionally, we plan to study evidence of pathogens and disease among the individuals in this research, to understand more about their health and lives.

Read more: Ancient DNA reveals children with Down syndrome in past societies. What can their burials tell us about their lives?

Another avenue of research is improving the dating of Avar sites. We are currently analysing multiple radiocarbon dates from individual burials to reveal a more precise timeline of Avar society. This detailed chronology will help us pinpoint significant cultural changes and interactions with neighbouring societies.

The authors would like to acknowledge the contributions to this work of Zsfia Rcz, Tivadar Vida, Johannes Krause and Zuzana Hofmanov.

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Ancient nomads you've probably never heard of disappeared from Europe 1,000 years ago. Now, DNA analysis ... - The Conversation

By Lauren Sausser April 25, 2024

CHARLESTON, S.C. When he recently walked into the dental clinic at the Medical University of South Carolina donning a bright-blue pullover with In Our DNA SC embroidered prominently on the front, Lee Moultrie said, two Black women stopped him to ask questions.

Its a walking billboard, said Moultrie, a health care advocate who serves on the community advisory board for In Our DNA SC, a study underway at the university that aims to enroll 100,000 South Carolinians including a representative percentage of Black people in genetics research. The goal is to better understand how genes affect health risks such as cancer and heart disease.

Moultrie, who is Black and has participated in the research project himself, used the opportunity at the dental clinic to encourage the women to sign up and contribute their DNA. He keeps brochures about the study in his car and at the barbershop he visits weekly for this reason. Its one way he wants to help solve a problem that has plagued the field of genetics research for decades: The data is based mostly on DNA from white people.

Project leaders in Charleston told KFF Health News in 2022 that they hoped to enroll participants who reflect the demographic diversity of South Carolina, where just under 27% of residents identify as Black or African American. To date, though, theyve failed to hit that mark. Only about 12% of the projects participants who provided sociodemographic data identify as Black, while an additional 5% have identified as belonging to another racial minority group.

Wed like to be a lot more diverse, acknowledged Daniel Judge, principal investigator for the study and a cardiovascular genetics specialist at the Medical University of South Carolina.

Lack of diversity in genetics research has real health care implications. Since the completion more than 20 years ago of the Human Genome Project, which mapped most human genes for the first time, close to 90% of genomics studies have been conducted using DNA from participants of European descent, research shows. And while human beings of all races and ancestries are more than 99% genetically identical, even small differences in genes can spell big differences in health outcomes.

Precision medicine is a term used to describe how genetics can improve the way diseases are diagnosed and treated by considering a persons DNA, environment, and lifestyle. But if this emerging field of health care is based on research involving mostly white people, it could lead to mistakes, unknowingly, said Misa Graff, an associate professor in epidemiology at the University of North Carolina and a genetics researcher.

In fact, thats already happening. In 2016, for example, research found that some Black patients had been misdiagnosed with a potentially fatal heart condition because theyd tested positive for a genetic variant thought to be harmful. That variant is much more common among Black Americans than white Americans, the research found, and is considered likely harmless among Black people. Misclassifications can be avoided if even modest numbers of people from diverse populations are included in sequence databases, the authors wrote.

The genetics research project in Charleston requires participants to complete an online consent form and submit a saliva sample, either in person at a designated lab or collection event or by mail. They are not paid to participate, but they do receive a report outlining their DNA results. Those who test positive for a genetic marker linked to cancer or high cholesterol are offered a virtual appointment with a genetics counselor free of charge.

Some research projects require more time from their volunteers, which can skew the pool of participants, Graff said, because not everyone has the luxury of free time. We need to be even more creative in how we obtain people to help contribute to studies, she said.

Moultrie said he recently asked project leaders to reach out to African American media outlets throughout the Palmetto State to explain how the genetics research project works and to encourage Black people to participate. He also suggested that when researchers talk to Black community leaders, such as church pastors, they ought to persuade those leaders to enroll in the study instead of simply passing the message along to their congregations.

We have new ideas. We have ways we can do this, Moultrie said. Well get there.

Other ongoing efforts are already improving diversity in genetics research. At the National Institutes of Health, a program called All of Us aims to analyze the DNA of more than 1 million people across the country to build a diverse health database. So far, that program has enrolled more than 790,000 participants. Of these, more than 560,000 have provided DNA samples and about 45% identify as being part of a racial or ethnic minority group.

Diversity is so important, said Karriem Watson, chief engagement officer for the All of Us research program. When you think about groups that carry the greatest burden of disease, we know that those groups are often from minoritized populations.

Diverse participation in All of Us hasnt come about by accident. NIH researchers strategically partnered with community health centers, faith-based groups, and Black fraternities and sororities to recruit people who have been historically underrepresented in biomedical research.

In South Carolina, for example, the NIH works with Cooperative Health, a network of federally qualified health centers near the state capital that serve many patients who are uninsured and Black, to recruit patients for All of Us. Eric Schlueter, chief medical officer of Cooperative Health, said the partnership works because their patients trust them.

We have a strong history of being integrated into the community. Many of our employees grew up and still live in the same communities that we serve, Schlueter said. That is what is part of our secret sauce.

So far, Cooperative Health has enrolled almost 3,000 people in the research program, about 70% of whom are Black.

Our patients are just like other patients, Schlueter said. They want to be able to provide an opportunity for their children and their childrens children to have better health, and they realize this is an opportunity to do that.

Theoretically, researchers at the NIH and the Medical University of South Carolina may be trying to recruit some of the same people for their separate genetics studies, although nothing would prevent a patient from participating in both efforts.

The researchers in Charleston acknowledge they still have work to do. To date, In Our DNA SC has recruited about half of the 100,000 people it hopes for, and of those, about three-quarters have submitted DNA samples.

Caitlin Allen, a program investigator and a public health researcher at the medical university, acknowledged that some of the programs tactics havent succeeded in recruiting many Black participants.

For example, some patients scheduled to see providers at the Medical University of South Carolina receive an electronic message through their patient portal before an appointment, which includes information about participating in the research project. But studies show that racial and ethnic minorities are less likely to engage with their electronic health records than white patients, Allen said.

We see low uptake with that strategy, she said, because many of the people researchers are trying to engage likely arent receiving the message.

The study involves four research coordinators trained to take DNA samples, but theres a limit to how many people they can talk to face-to-face. Were not necessarily able to go into every single room, Allen said.

That said, in-person community events seem to work well for enrolling diverse participants. In March, In Our DNA SC research coordinators collected more than 30 DNA samples at a bicentennial event in Orangeburg, South Carolina, where more than 60% of residents identify as Black. Between the first and second year of the research project, Allen said, In Our DNA SC doubled the number of these community events that research coordinators attended.

I would love to see it ramp up even more, she said.

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Genetics Studies Have a Diversity Problem That Researchers Struggle To Fix - Kaiser Health News

Ward Raymond Thomas went missing from the Chillicothe VA Medical Center in 1972. Decades later, his family has closure with the help of genetic genealogy testing.

CHILLICOTHE, Ohio Ohio World War II veteran, Ward Raymond Thomas, was laid to rest in April in a traditional military service in Chillicothe.

The path to get to that moment was anything but traditional.

Thomas had been missing for more than 50 years.

In 1942, when Thomas was 24 years old, he joined the U.S. Army at Fort Hayes in Columbus and went to serve overseas in World War II.

He returned home three years later with a long list of accolades, including the Purple Heart, and was honorably discharged from service.

Years later in 1972, Thomas was being treated at the Chillicothe VA Medical Center when he disappeared.

His family searched for him, but for decades, what happened to Thomas would be a mystery, until his niece Carolyn Grandstaff got a phone call last year from investigators at the Ross County Coroners Office.

He asked me if Ward Thomas was my uncle, she said.

The investigator told her about a skull that had been discovered in the Scioto River near the Chillicothe Correctional Institute in 1996.

For years, the identity of the skull was a mystery, labeled John Doe, waiting at the coroners office for technology to catch up.

In our minds, we had done everything we could, until there was technology that came along. It was a cold case, said former Ross County Coroner Dr. John Gabis.

Decades later, Dr. Gabiss successor, Dr. Ben Trotter sent the skull to the state BCI lab for testing.

Technology finally caught up in a way that we could extract DNA from the bone, Dr. Trotter said.

There, scientists extracted enough DNA from a tooth on the skull to look further into its identity.

It was the non-profit, DNA Doe Project, that used genetic genealogy to come up with the name Ward Thomas.

They tracked down his living relatives and Grandstaffs DNA was a perfect match.

Shock, pure shock. I wish my mom was alive and my sisters too to be a part of this because they missed their brother, they loved their brother a lot, she said.

Grandstaff said Ward Thomas was one of 12 siblings. His siblings, wife and stepson have passed away.

For 52 years, the family held on to Thomas military medals, finally reuniting them with the soldier at a funeral organized by the Ross County Veterans Service Office.

Just thankful that he could get this honor. It is wonderful, someone who went to war and fought for our freedoms, it is very important, said Thomas niece, Debbie Riffle.

Lt. Col. Robert Leach organized the service and decided he was going to send off the American hero in the most honorable way possible.

He invited Thomas family, members of the coroner's office, the DNA Doe Project, local law enforcement and anyone who had a part in solving the more than 50-year mystery, even recruiting a local high school student to wear a replica of Thomas military uniform, complete with all of his awards, honors and medals.

What I feel we did today was give a name and a face and a family to Ward Thomas, so now it is more than just an interesting story about science and identification of remains. Now we have laid a World War II decorated combat veteran to rest with his comrades, Lt. Col. Leach said.

Thomas was laid to rest with fellow veterans at Greenlawn Cemetery in Chillicothe. The Ross County Veterans Service Office will place a flag at the site every Memorial Day.

The completed mission to identify a veteran offers hope for the more than 100 John and Jane Does in Ohio. Thomas case is one of the oldest to be solved through DNA at the BCI lab.

When it was sent out it was a smaller amount of DNA than theyre used to for genealogy, and it was successful so just the technology over the last few years in the genealogy world has advanced and its going to keep advancing, said BCI Criminal Intelligence Analyst Jennifer Lester.

Family members of missing persons are encouraged to submit their DNA for free throughProject LINK.

To learn more about the project, and how it could help solve your familys case, contact BCI at 855-BCI-OHIO or email LINK@OhioAttorneyGeneral.gov.

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WWII veteran Ward Thomas identified through genealogy testing - 10TV

A day in the life of DNA can be rough. It gets yanked across a dividing cell, zapped by radiation, and assaulted by chemicals. Luckily, cells have developed a complex set of repair mechanisms to protect vulnerable DNA and fix damage so that the cells genomic instruction manual remains intact. Cells use homologous recombination to stitch double-stranded breaks (DSB) back together and the enzyme telomerase to cap exposed ends of a DNA strand with a repetitive DNA sequence called a telomere.

However, if cells use the wrong repair mechanism for a given situation, it can be disastrous. For example, if telomerase tries to seal up a DSB, it can sever the chromosome, causing the cell to lose key genes. The whole system falls apart, said Titia de Lange, a cell biologist at Rockefeller University.

Scientists have observed that this can happen in yeast and corn, but whether it occurred in humans remained a mystery until now.1,2 de Langes team has finally figured out just how rare this catastrophic event is in humans and how cells keep it in check. In a study published in Science, they revealed that while telomerase occasionally acts at DSB, the ataxia telangiectasia and Rad3-related (ATR) protein typically runs interference to give the cell a chance to repair these breaks.3 The findings shed light on how this type of genomic instability could play a role in diseases such as cancer.

Continue reading below...

If telomeres formed at DSB, de Lange suspected that it would be infrequent, given how few telomerases there are in any cell and how much damage it would cause. We expected that this would be instantly repressed, de Lange said. Cells would not tolerate this.

Starting with immortalized HeLa cells with artificially high levels of telomerase, the researchers cut the cells DNA with Cas9 enzyme to create DSB. They carefully designed the system to target positions in the DNA that telomerase gravitates towards but that are not fatal to the cell when broken. As de Lange expected, telomerase added telomeres at the DSB, but this was very rare; telomerase only created approximately four new telomeres per 1,000 genomes.

I don't know if it's surprising that it occurs, or if it's surprising that it doesn't occur more often, said Nausica Arnoult, a cell biologist at the University of Colorado Boulder who was not involved in this study. It's really well controlled.

To figure out how the cells blocked telomerase from acting at DSB, de Langes team genetically inactivated many different enzymes and repair pathways to see if any of them repressed telomere formation. Eventually, they discovered the genomic guardian: ATR, a protein that senses DNA damage and triggers homologous recombination. When they inhibited ATR, the number of new telomeres nearly tripled.

In the process of pinpointing ATRs role, the researchers stumbled upon other cellular surprises. For example, they knew that certain proteins were required for telomerase to interact with DNA, but reducing those proteins levels didnt seem to block telomere formation at Cas9-induced DSB. They quickly realized that telomerase could act directly on the type of DNA cuts that Cas9 makes, which creates a little wrinkle in the use of CRISPR, de Lange said.

Arnoult agreed. Especially if you consider the therapeutic use of CRISPR-Cas9, we really need to understand if there are some contexts where that misguided action of telomerase is going to be more frequent, she said.

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Much remains for de Lange and her team to reveal about ATR. Although they found that ATR represses telomerase, they dont know how this happens. Arnoult said that she wonders whether there are other redundant pathways that can also influence telomere formation at DSB in other contexts. She pointed to other species where telomeres that form at DSB are a normal part of development.4,5 Studying those species may give us clues of how they can do that very efficiently and why it's prevented in humans, Arnoult said.

de Lange is also thinking about how this process could be involved in cancer. Cancer cells genomes are plagued by DNA breaks, but their survival and proliferation depends on them finding a way to stabilize that damaged DNA; inappropriate telomerase activity may be one tool at their disposal. de Langes team is creating cells with abnormal chromosomes similar to those in cancer to see if telomerase helps these cells survive.

1. Kramer KM, Haber JE. New telomeres in yeast are initiated with a highly selected subset of TG1-3 repeats.Genes Dev. 1993;7(12A):2345-56. 2. McClintock B. The stability of broken ends of chromosomes in Zea Mays.Genetics. 1941;26(2):234-82. 3. Kinzig CG, et al. ATR blocks telomerase from converting DNA breaks into telomeres.Science. 2024;383(6684):763-770. 4. Yu G, Blackburn EH. Developmentally programmed healing of chromosomes by telomerase in tetrahymena.Cell. 1991;67(4):823-32. 5. Mller F, et al. New telomere formation after developmentally regulated chromosomal breakage during the process of chromatin diminution in ascaris lumbricoides. Cell. 1991;67(4):815-22.

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Keeping Telomeres in Their Places - The Scientist

RICHMOND, Va. Dayan Frias was immersed in the world of baseball from a young age. His dads heavy involvement within the sport gave Frias a front row seat of what a career in baseball would look like. Wherever his dad, David, was playing, training players, or managing a team throughout Colombia, Frias was right there watching.

It started with my family, watching them play and listening to them a lot I think thats what made my path toward baseball, he said in Spanish. I told [my dad] that I wanted to be like [the players] some day.

Naturally, the 21-year-old decided to embark on the journey of becoming a professional baseball player. The Cartagena, Colombia native trained with his dad and two-time Gold Glover Orlando Cabrera, played in different academies and attended tryouts and showcases. He didnt stop until he reached the goal of many aspiring ball players: to sign with a team.

The Guardians saw the potential in Frias and signed him as an international free agent in 2018 for $80,000. Having accomplished the goal of signing, the real work of honing his skills and developing his talents to fit the Guardians needs began.

Frias, the Guardians No. 29 prospect per MLB Pipeline, made notable improvements in his first two seasons as a rookie. He slashed .216/.383/.291 in 2019, then in 2021 he slashed .322/.420/.520. The 2020 season was canceled due to COVID.

While he had a good start, Frias struggled in his introduction to full-season ball in 2022, batting .239/.344/.330 and totaling 21 errors. Soon after the season was over, Frias was invited to play for Colombia in the 2023 World Baseball Classic in which he competed with and learned from veterans in the league.

It helped me a lot, getting to play and share moments with veterans in the Major Leagues, the infielder said. I got a lot of advice and I also picked up stuff from them, routines, small things that have helped me in this sport.

He took the advice and good habits with him to the regular season at High-A Lake County and found success in 2023. The switch hitter slashed .260/.356/.426 and recorded 88 hits, 43 runs, and 11 home runs. Defensively at third base, Frias dropped to 13 errors for Lake County. He received Midwest League Player of the Week honors in late July and was named a Caribbean Series All-Star in February.

Frias brought his routines and small things from last season and implemented them into the new season. The advice he received that has been the most impactful, Frias shares with everyone: See it and hit it.

If you dont see anything then you cant hit and nothing happens, he said. I try to find a pitch that I know Im going to hit well and execute it Trying to miss less is what Im looking for at home plate.

He saw results early, collecting two hits and an RBI in five at-bats during his third season in the Cactus League with the Guardians in 2024. His improvements helped the plus defender break into the Guardians Top 30 prospect rankings this season.

As his growth continues, Frias wants to be remembered for his own style of play radiating excitement and passion on and off the field. After all, he has a passion for baseball that has been growing ever since he was introduced to the sport by his dad. He hopes his energy spreads not only within the clubhouse, but to fans as well.

I like to enjoy the game because its what I love, to be here in front of these fans, he said. I play for my team as much as for the fans as well. I love to play with enthusiasm all the time. Youre always going to see me smiling and messing around with the guys, making jokes all the time. I like to be a happy guy and infect my teammates with happiness.

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This Guardians prospect has baseball in his DNA - 1330 WFIN