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Article ; Online: Pegasparaginase treatment alters thrombin generation by modulating the protein C and S system in acute lymphoblastic leukaemia/lymphoma.

Staddon, Jack H / Smock, Kristi J / Schiffman, Joshua D / Fluchel, Mark N / Engel, Michael E / Weyrich, Andrew S / Campbell, Robert A

Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis

2015 Volume 26, Issue 7, Page(s) 840–843

Abstract: ... of thrombomodulin compared with prepegasparaginase, suggesting reduced protein C and S activity. This corresponded ... to a significant decrease in protein C and protein S antigen. Alterations in the protein C and S pathway ...

Abstract	Paediatric patients with acute lymphoblastic leukaemia/lymphoma treated with pegasparaginase are at an increased risk of thrombosis. We evaluated changes in thrombin generation in the presence and absence of thrombomodulin using paired plasma samples collected from paediatric patients treated with pegasparaginase. Postpegasparaginase samples were significantly less sensitive to reductions in thrombin generation in the presence of thrombomodulin compared with prepegasparaginase, suggesting reduced protein C and S activity. This corresponded to a significant decrease in protein C and protein S antigen. Alterations in the protein C and S pathway may contribute to the increased risk of thrombosis in patients treated with pegasparaginase.
MeSH term(s)	Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/therapeutic use ; Asparaginase/administration & dosage ; Asparaginase/therapeutic use ; Child ; Female ; Humans ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Protein C/metabolism ; Protein S/metabolism ; Thrombin/drug effects
Chemical Substances	Antineoplastic Agents ; Protein C ; Protein S ; Thrombin (EC 3.4.21.5) ; Asparaginase (EC 3.5.1.1)
Language	English
Publishing date	2015-10
Publishing country	England
Document type	Journal Article
ZDB-ID	1033551-1
ISSN	1473-5733 ; 0957-5235
ISSN (online)	1473-5733
ISSN	0957-5235
DOI	10.1097/MBC.0000000000000356
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Article: Paternal heat exposure causes DNA methylation and gene expression changes of Stat3 in Wild guinea pig sons

Weyrich, Alexandra / Jewgenow, Katarina

Ecology and evolution, 6(9): 2657–2666

2016

Abstract: ... transmitted to the next generation(s), and whether it regulates mRNA expression. Five (F0) adult male ... heat treatment (as has recently been described in Weyrich et al. [Mol. Ecol., 2015]). Transcription analysis was ...

Institution	Leibniz-Institut für Zoo- und Wildtierforschung (Berlin)
Abstract	Epigenetic mechanisms convey environmental information through generations and can regulate gene expression. Epigenetic studies in wild mammals are rare, but enable understanding adaptation processes as they may occur in nature. In most wild mammal species, males are the dispersing sex and thus often have to cope with differing habitats and thermal changes more rapidly than the often philopatric females. As temperature is a major environmental selection factor, we investigated whether genetically heterogeneous Wild guinea pig (Cavia aperea) males adapt epigenetically to an increase in temperature, whether that response will be transmitted to the next generation(s), and whether it regulates mRNA expression. Five (F0) adult male guinea pigs were exposed to an increased ambient temperature for 2 months, corresponding to the duration of the species' spermatogenesis. To study the effect of heat, we focused on the main thermoregulatory organ, the liver. We analyzed CpG-methylation changes of male offspring (F1) sired before and after the fathers' heat treatment (as has recently been described in Weyrich et al. [Mol. Ecol., 2015]). Transcription analysis was performed for the three genes with the highest number of differentially methylated changes detected: the thermoregulation gene Signal Transducer and Activator of Transcription 3 (Stat3), the proteolytic peptidase gene Cathepsin Z (Ctsz), and Sirtuin 6 (Sirt6) with function in epigenetic regulation. Stat3 gene expression was significantly reduced (P < 0.05), which indicated a close link between CpG-methylation and expression levels for this gene. The two other genes did not show gene expression changes. Our results indicate the presence of a paternal transgenerational epigenetic effect. Quick adaptation to climatic changes may become increasingly relevant for the survival of wildlife species as global temperatures are rising.
Keywords	Adaptation ; DNA methylation ; Paternal effects ; nonmodel species ; thermoregulation ; transgenerational epigenetic inheritance
Language	English
Document type	Article
Database	Repository for Life Sciences

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Article ; Online: Supplemental Screening for Breast Cancer in Women With Dense Breasts: A Systematic Review for the U.S. Preventive Services Task Force.

Melnikow, Joy / Fenton, Joshua J / Whitlock, Evelyn P / Miglioretti, Diana L / Weyrich, Meghan S / Thompson, Jamie H / Shah, Kunal

Annals of internal medicine

2016 Volume 164, Issue 4, Page(s) 268–278

Abstract: Background: Screening mammography has lower sensitivity and specificity in women with dense breasts, who experience higher breast cancer risk.: Purpose: To perform a systematic review of reproducibility of Breast Imaging Reporting and Data System (BI- ...

Abstract	Background: Screening mammography has lower sensitivity and specificity in women with dense breasts, who experience higher breast cancer risk. Purpose: To perform a systematic review of reproducibility of Breast Imaging Reporting and Data System (BI-RADS) density categorization and test performance and clinical outcomes of supplemental screening with breast ultrasonography, magnetic resonance imaging (MRI), and digital breast tomosynthesis (DBT) in women with dense breasts and negative mammography results. Data sources: MEDLINE, PubMed, EMBASE, and Cochrane database from January 2000 to July 2015. Study selection: Studies reporting BI-RADS density reproducibility or supplemental screening results for women with dense breasts. Data extraction: Quality assessment and abstraction of 24 studies from 7 countries; 6 studies were good-quality. Data synthesis: Three good-quality studies reported reproducibility of BI-RADS density; 13% to 19% of women were recategorized between "dense" and "nondense" at subsequent screening. Two good-quality studies reported that sensitivity of ultrasonography for women with negative mammography results ranged from 80% to 83%; specificity, from 86% to 94%; and positive predictive value (PPV), from 3% to 8%. The sensitivity of MRI ranged from 75% to 100%; specificity, from 78% to 94%; and PPV, from 3% to 33% (3 studies). Rates of additional cancer detection with ultrasonography were 4.4 per 1000 examinations (89% to 93% invasive); recall rates were 14%. Use of MRI detected 3.5 to 28.6 additional cancer cases per 1000 examinations (34% to 86% invasive); recall rates were 12% to 24%. Rates of cancer detection with DBT increased by 1.4 to 2.5 per 1000 examinations compared with mammography alone (3 studies). Recall rates ranged from 7% to 11%, compared with 7% to 17% with mammography alone. No studies examined breast cancer outcomes. Limitations: Good-quality evidence was sparse. Studies were small and CIs were wide. Definitions of recall were absent or inconsistent. Conclusion: Density ratings may be recategorized on serial screening mammography. Supplemental screening of women with dense breasts finds additional breast cancer but increases false-positive results. Use of DBT may reduce recall rates. Effects of supplemental screening on breast cancer outcomes remain unclear. Primary funding source: Agency for Healthcare Research and Quality.
MeSH term(s)	Adult ; Aged ; Breast/anatomy & histology ; Breast Density ; Breast Neoplasms/diagnosis ; Early Detection of Cancer/methods ; Female ; Humans ; Magnetic Resonance Imaging ; Mammary Glands, Human/abnormalities ; Mammography ; Mass Screening/methods ; Middle Aged ; Risk Factors ; Ultrasonography, Mammary
Language	English
Publishing date	2016-01-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review ; Systematic Review
ZDB-ID	336-0
ISSN	1539-3704 ; 0003-4819
ISSN (online)	1539-3704
ISSN	0003-4819
DOI	10.7326/M15-1789
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Article ; Online: Studying ancient human oral microbiomes could yield insights into the evolutionary history of noncommunicable diseases.

Gancz, Abigail S / Weyrich, Laura S

F1000Research

2023 Volume 12, Page(s) 109

Abstract: Noncommunicable diseases (NCDs) have played a critical role in shaping human evolution and societies. Despite the exceptional impact of NCDs economically and socially, little is known about the prevalence or impact of these diseases in the past as most ... ...

Abstract	Noncommunicable diseases (NCDs) have played a critical role in shaping human evolution and societies. Despite the exceptional impact of NCDs economically and socially, little is known about the prevalence or impact of these diseases in the past as most do not leave distinguishing features on the human skeleton and are not directly associated with unique pathogens. The inability to identify NCDs in antiquity precludes researchers from investigating how changes in diet, lifestyle, and environments modulate NCD risks in specific populations and from linking evolutionary processes to modern health patterns and disparities. In this review, we highlight how recent advances in ancient DNA (aDNA) sequencing and analytical methodologies may now make it possible to reconstruct NCD-related oral microbiome traits in past populations, thereby providing the first proxies for ancient NCD risk. First, we review the direct and indirect associations between modern oral microbiomes and NCDs, specifically cardiovascular disease, diabetes mellitus, rheumatoid arthritis, and Alzheimer's disease. We then discuss how oral microbiome features associated with NCDs in modern populations may be used to identify previously unstudied sources of morbidity and mortality differences in ancient groups. Finally, we conclude with an outline of the challenges and limitations of employing this approach, as well as how they might be circumvented. While significant experimental work is needed to verify that ancient oral microbiome markers are indeed associated with quantifiable health and survivorship outcomes, this new approach is a promising path forward for evolutionary health research.
MeSH term(s)	Humans ; Noncommunicable Diseases/epidemiology ; Microbiota/genetics ; Diabetes Mellitus/epidemiology ; Diet ; Prevalence
Language	English
Publishing date	2023-01-30
Publishing country	England
Document type	Journal Article ; Review ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2699932-8
ISSN	2046-1402 ; 2046-1402
ISSN (online)	2046-1402
ISSN	2046-1402
DOI	10.12688/f1000research.129036.2
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Article: Commercializing equitable, accessible oral microbiome transplantation therapy.

Weyrich, L S / Nath, S / Jamieson, L M

Community dental health

2024 Volume 41, Issue 1, Page(s) 83–88

Abstract: Chronic oral diseases, such as caries and periodontal disease, may, in future, be treated by oral microbiome transplant (OMT) technology. OMT therapy would involve collecting a donor oral microbiome and transplanting into a recipient to either prevent or ...

Abstract	Chronic oral diseases, such as caries and periodontal disease, may, in future, be treated by oral microbiome transplant (OMT) technology. OMT therapy would involve collecting a donor oral microbiome and transplanting into a recipient to either prevent or treat oral diseases linked to a change (i.e., dysbiosis) in the oral microbiome. Given the great promise of this technology, we must consider the ethical and practical implications of how it is developed to maximise its accessibility and affordability. Here, we examine ways that OMT technology might be commercialized in the context of equity and accessibility in both clinical or do-it-yourself settings. We do this while assuming that the technology can be developed for humans in ways that are safe and effective at the individual and population-levels. We highlight the need for OMT therapy to be 1) cost-effective, 2) understood by end users and clinicians, 3) easy to access even in rural or remote communities, and 4) providing donors equitable compensation for their microbiomes. These key elements will only be achieved through partnerships between scientists, clinicians, investors and stakeholders throughout development. Therefore, proper acknowledgement and equitable evaluation of contributions in this team will also be critical to ensuring that this technology can be globally accessed. While OMT is likely to reshape how we prevent or treat oral disease, consciously guiding its development toward equity and accessibility to all people may significantly aid in improving health for those without access to dental care.
MeSH term(s)	Humans ; Dental Caries/prevention & control ; Periodontal Diseases ; Microbiota ; Mouth Diseases
Language	English
Publishing date	2024-02-29
Publishing country	England
Document type	Journal Article
ZDB-ID	631156-8
ISSN	0265-539X
ISSN	0265-539X
DOI	10.1922/CDH_IADR24Weyrich06
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Zs.A 2169: Show issues

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Article: Using environmental (e)DNA sequencing for aquatic biodiversity surveys: a beginnerâs guide

Shaw, Jennifer L. A / Alan Cooper / Laura Weyrich

Marine & freshwater research. 2017, v. 68, no. 1

2017

Abstract: Biological surveys are needed to monitor and assess the health of ecosystems and the species within them. However, morphology-based biodiversity surveys can be invasive, time consuming and financially expensive. Recently, environmental (e)DNA sequencing ... ...

Abstract	Biological surveys are needed to monitor and assess the health of ecosystems and the species within them. However, morphology-based biodiversity surveys can be invasive, time consuming and financially expensive. Recently, environmental (e)DNA sequencing has been demonstrated as a potential alternative to morphological-based surveys because it enables the rapid and inexpensive detection of multiple taxa from DNA present in the environment. Numerous studies have shown that eDNA-based biodiversity surveys can provide considerable information about aquatic ecosystem function and health. Therefore, this molecular method has the potential to improve how current aquatic biological surveys are conducted. Currently, most eDNA literature is aimed at an audience with a moderate to advanced knowledge of DNA sequencing, creating a barrier for many ecologists who lack DNA sequencing expertise but wish to apply such methods to their research. The aim of this review is to provide guidance to non-geneticists regarding sequencing eDNA for aquatic biodiversity surveys and to highlight the requirements that need to be considered before the technique can be effectively incorporated into biomonitoring programs. Specifically, we provide details and recommendations on some of the major principles, from sample collection to bioinformatic analyses. For those areas where specific recommendations cannot be given, we have provided references to suitable literature.
Keywords	aquatic ecosystems ; biodiversity ; bioinformatics ; DNA ; ecological function ; ecologists ; environmental monitoring ; sequence analysis ; surveys
Language	English
Size	p. 20-33.
Publishing place	CSIRO Publishing
Document type	Article
ZDB-ID	1283028-8
ISSN	1323-1650
ISSN	1323-1650
DOI	10.1071/MF15361
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: The evolutionary history of the human oral microbiota and its implications for modern health.

Weyrich, Laura S

Periodontology 2000

2020 Volume 85, Issue 1, Page(s) 90–100

Abstract: Numerous biological and cultural factors influence the microbial communities (microbiota) that inhabit the human mouth, including diet, environment, hygiene, physiology, health status, genetics, and lifestyle. As oral microbiota can underpin oral and ... ...

Abstract	Numerous biological and cultural factors influence the microbial communities (microbiota) that inhabit the human mouth, including diet, environment, hygiene, physiology, health status, genetics, and lifestyle. As oral microbiota can underpin oral and systemic diseases, tracing the evolutionary history of oral microbiota and the factors that shape its origins will unlock information to mitigate disease today. Despite this, the origins of many oral microbes remain unknown, and the key factors in the past that shaped our oral microbiota are only now emerging. High throughput DNA sequencing of oral microbiota using ancient DNA and comparative anthropological methodologies has been employed to investigate oral microbiota origins, revealing a complex, rich history. Here, I review the current literature on the factors that shaped and guided oral microbiota evolution, both in Europe and globally. In Europe, oral microbiota evolution was shaped by interactions with Neandertals, the adaptation of farming, widespread integration of industrialization, and postindustrial lifestyles that emerged after World War II. Globally, evidence for a multitude of different oral microbiota histories is emerging, likely supporting dissimilarities in modern oral health across discrete human populations. I highlight how these evolutionary changes are linked to the development of modern oral diseases and discuss the remaining factors that need to be addressed to improve this embryonic field of research. I argue that understanding the evolutionary history of our oral microbiota is necessary to identify new treatment and prevention options to improve oral and systemic health in the future.
MeSH term(s)	Diet ; Humans ; Microbiota/genetics ; Mouth Diseases ; Oral Health
Language	English
Publishing date	2020-11-23
Publishing country	Denmark
Document type	Journal Article ; Review
ZDB-ID	1200504-6
ISSN	1600-0757 ; 0906-6713
ISSN (online)	1600-0757
ISSN	0906-6713
DOI	10.1111/prd.12353
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Zs.A 4046: Show issues

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Article: The Oral-Microbiome-Brain Axis and Neuropsychiatric Disorders: An Anthropological Perspective.

Bowland, Grace B / Weyrich, Laura S

Frontiers in psychiatry

2022 Volume 13, Page(s) 810008

Abstract: In the 21st century, neuropsychiatric disorders (NPDs) are on the rise, yet the causal mechanisms behind this global epidemic remain poorly understood. A key to these unknowns may lie within the vast communities of bacteria, fungi, and viruses in the ... ...

Abstract	In the 21st century, neuropsychiatric disorders (NPDs) are on the rise, yet the causal mechanisms behind this global epidemic remain poorly understood. A key to these unknowns may lie within the vast communities of bacteria, fungi, and viruses in the body (microbiota), which are intimately linked with health and disease. NPDs were recently shown to be connected to gut microbiota, which can communicate with and influence the brain through the Gut-Brain-Axis (GBA). Parallel studies examining oral microbiota and their connections to the brain also suggest that microbes in the mouth can similarly influence NPD outcomes. However, the mechanisms and pathways that illuminate how oral microbiota and brain communicate in NPDs remain unknown. Here, we review identified mechanisms and pathways that oral microbiota use to engage the brain, and we lay the theoretical foundation for an oral-microbiota-brain axis (OMBA). Specifically, we examine established neuroinflammatory and immune system activation responses that underpin interactions between the oral microbiota and the central nervous system (CNS), detailing four specific mechanisms: (1) microbial and metabolite escape, (2) neuroinflammation, (3) CNS signaling, and (4) response to neurohormones. We then scrutinize why including the OMBA, in addition to the GBA, is critically needed to elucidate specific causal relationships between microbial dysbiosis and observed NPD development and progression. Furthermore, we argue for comprehensive, interdisciplinary approaches that integrate lab-based microbiome research and population-level studies that examine the OMBA to improve NPDs. We specifically identify key anthropological perspectives that integrate sociocultural, epidemiological, genetic, and environmental factors that shape the oral microbiome and its interactions with NPDs. Together, future studies of the OMBA in conjunction with interdisciplinary approaches can be used to identify NPD risks and improve outcomes, as well as develop novel intervention and treatment strategies.
Language	English
Publishing date	2022-03-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2564218-2
ISSN	1664-0640
ISSN	1664-0640
DOI	10.3389/fpsyt.2022.810008
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Article ; Online: Ancient human dental calculus metadata collection and sampling strategies: Recommendations for best practices.

Gancz, Abigail S / Wright, Sterling L / Weyrich, Laura S

American journal of biological anthropology

2023 Volume 183, Issue 4, Page(s) e24871

Abstract: Objectives: Ancient human dental calculus is a unique, nonrenewable biological resource encapsulating key information about the diets, lifestyles, and health conditions of past individuals and populations. With compounding calls its destructive analysis, ...

Abstract	Objectives: Ancient human dental calculus is a unique, nonrenewable biological resource encapsulating key information about the diets, lifestyles, and health conditions of past individuals and populations. With compounding calls its destructive analysis, it is imperative to refine the ways in which the scientific community documents, samples, and analyzes dental calculus so as to maximize its utility to the public and scientific community. Materials and methods: Our research team conducted an IRB-approved survey of dental calculus researchers with diverse academic backgrounds, research foci, and analytical specializations. Results: This survey reveals variation in how metadata is collected and utilized across different subdisciplines and highlights how these differences have profound implications for dental calculus research. Moreover, the survey suggests the need for more communication between those who excavate, curate, and analyze biomolecular data from dental calculus. Discussion: Challenges in cross-disciplinary communication limit researchers' ability to effectively utilize samples in rigorous and reproducible ways. Specifically, the lack of standardized skeletal and dental metadata recording and contamination avoidance procedures hinder downstream anthropological applications, as well as the pursuit of broader paleodemographic and paleoepidemiological inquiries that rely on more complete information about the individuals sampled. To provide a path forward toward more ethical and standardized dental calculus sampling and documentation approaches, we review the current methods by which skeletal and dental metadata are recorded. We also describe trends in sampling and contamination-control approaches. Finally, we use that information to suggest new guidelines for ancient dental calculus documentation and sampling strategies that will improve research practices in the future.
MeSH term(s)	Humans ; Dental Calculus/epidemiology ; Metadata ; Anthropology ; Communication ; Documentation
Language	English
Publishing date	2023-11-23
Publishing country	United States
Document type	Review ; Journal Article
ISSN	2692-7691
ISSN (online)	2692-7691
DOI	10.1002/ajpa.24871
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Article ; Online: A Standardized Approach for Shotgun Metagenomic Analysis of Ancient Dental Calculus.

Moore, Nicole E / Weyrich, Laura S

Methods in molecular biology (Clifton, N.J.)

2021 Volume 2327, Page(s) 93–118

Abstract: Ancient dental calculus provides a challenging, yet unparalleled, opportunity to reconstruct ancient oral microbial communities and trace the origins of modern microbiota-associated diseases. Metagenomic analysis of ancient dental calculus using high- ... ...

Abstract	Ancient dental calculus provides a challenging, yet unparalleled, opportunity to reconstruct ancient oral microbial communities and trace the origins of modern microbiota-associated diseases. Metagenomic analysis of ancient dental calculus using high-throughput DNA sequencing has proven itself as an effective method to accurately reconstruct microorganisms that once lived in the mouths of ancient humans. Here, we provide the strategy, methodologies, and approaches used to establish an ancient dental calculus project, from project conception, community engagement, sampling, extracting DNA, and preparing shotgun metagenomic DNA libraries for sequencing on an Illumina platform. We also discuss techniques to minimize background or contaminant DNA by monitoring and reducing contamination in calculus data sets, utilizing appropriate protective gear, and employing the use of sample decontamination strategies. In this methodology chapter, we hope to promote transparency in the ancient dental calculus research field and encourage collaboration across the ancient DNA research community.
MeSH term(s)	DNA, Ancient ; Dental Calculus ; High-Throughput Nucleotide Sequencing ; Humans ; Metagenome ; Metagenomics ; Microbiota/genetics ; Sequence Analysis, DNA
Chemical Substances	DNA, Ancient
Language	English
Publishing date	2021-08-19
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1518-8_7
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