Epigenetic 'clocks' based on DNA methylation have emerged as the most robust and widely used aging biomarkers, but conventional methods for applying them are expensive and laborious. Here we develop tagmentation-based indexing for methylation sequencing (TIME-seq), a highly multiplexed and scalable method for low-cost epigenetic clocks. Using TIME-seq, we applied multi-tissue and tissue-specific epigenetic clocks in over 1,800 mouse DNA samples from eight tissue and cell types.
View Article and Find Full Text PDFDomoic acid produced by toxigenic Pseudo-nitzschia species is the main toxin threat from harmful algal blooms in Monterey Bay and the larger California Current region on the West Coast of the United States. Toxin monitoring in Monterey Bay includes a long-running time series of weekly measurements of domoic acid from water samples, sentinel mussels, and solid phase adsorption toxin tracking (SPATT) at the Santa Cruz Municipal Wharf (SCW). The SCW sampling site is unusual because of its position in the Monterey Bay upwelling shadow in the north bay.
View Article and Find Full Text PDFHeterochronic parabiosis (HPB) is known for its functional rejuvenation effects across several mouse tissues. However, its impact on biological age and long-term health is unknown. Here we performed extended (3-month) HPB, followed by a 2-month detachment period of anastomosed pairs.
View Article and Find Full Text PDFHealthcare delivery in the United States has been characterized as overly reactive and dependent on emergency department care for safety net coverage, with opportunity for improvement around discharge planning and high readmissions and emergency department bounce-back rates. Community paramedicine is a recent healthcare innovation that enables proactive visitation of patients at home, often shortly after emergency department and hospital discharge. We establish the first optimization-based framework to study efficiencies in the management and operation of a community paramedicine program.
View Article and Find Full Text PDFDNA methylation dynamics emerged as a promising biomarker of mammalian aging, with multivariate machine learning models ('epigenetic clocks') enabling measurement of biological age in bulk tissue samples. However, intrinsically sparse and binarized methylation profiles of individual cells have so far precluded the assessment of aging in single-cell data. Here, we introduce , a statistical framework for epigenetic age profiling at single-cell resolution, and validate our approach in mice.
View Article and Find Full Text PDFIntroduction: recurrence rates for primary hernia repair range from 0.5 to 15 percent depending upon the hernia site, type of repair, and clinical circumstances. Many risk factors are known and they must be considered before the procedure.
View Article and Find Full Text PDFRibozymes are RNA molecules that catalyze biochemical reactions. Self-cleaving ribozymes are a common naturally occurring class of ribozymes that catalyze site-specific cleavage of their own phosphodiester backbone. In addition to their natural functions, self-cleaving ribozymes have been used to engineer control of gene expression because they can be designed to alter RNA processing and stability.
View Article and Find Full Text PDFHuman trafficking is a widespread and compound social, economic, and human rights issue occurring in every region of the world. While there have been an increasing number of anti-human trafficking studies from the Operations Research and Analytics domains in recent years, no systematic review of this literature currently exists. We fill this gap by providing a systematic literature review that identifies and classifies the body of Operations Research and Analytics research related to the anti-human trafficking domain, thereby illustrating the collective impact of the field to date.
View Article and Find Full Text PDFNaked mole rats (NMRs) are the longest-lived rodents yet their stem cell characteristics remain enigmatic. Here, we comprehensively mapped the NMR hematopoietic landscape and identified unique features likely contributing to longevity. Adult NMRs form red blood cells in spleen and marrow, which comprise a myeloid bias toward granulopoiesis together with decreased B-lymphopoiesis.
View Article and Find Full Text PDFThe functionality of phonon-based quantum devices largely depends on the efficiency of the interaction of phonons with other excitations. For phonon frequencies above 20 GHz, generation and detection of the phonon quanta can be monitored through photons. The photon-phonon interaction can be enormously strengthened by involving an intermediate resonant quasiparticle, e.
View Article and Find Full Text PDFThe naked mole-rat (NMR) is an exceptionally long-lived rodent that shows no increase of mortality with age, defining it as a demographically non-aging mammal. Here, we perform bisulfite sequencing of the blood of > 100 NMRs, assessing > 3 million common CpG sites. Unsupervised clustering based on sites whose methylation correlates with age reveals an age-related methylome remodeling, and we also observe a methylome information loss, suggesting that NMRs age.
View Article and Find Full Text PDFSeveral interventions have recently emerged that were proposed to reverse rather than just attenuate aging, but the criteria for what it takes to achieve rejuvenation remain controversial. Distinguishing potential rejuvenation therapies from other longevity interventions, such as those that slow down aging, is challenging, and these anti-aging strategies are often referred to interchangeably. We suggest that the prerequisite for a rejuvenation intervention is a robust, sustained, and systemic reduction in biological age, which can be assessed by biomarkers of aging, such as epigenetic clocks.
View Article and Find Full Text PDFImmunosenescence is a hallmark of aging and manifests as increased susceptibility to infection, autoimmunity, and cancer in the elderly. One component of immunosenescence is thymic involution, age-associated shrinkage of the thymus, observed in all vertebrates studied to date. The naked mole rat (Heterocephalus glaber) has become an attractive animal model in aging research due to its extreme longevity and resistance to disease.
View Article and Find Full Text PDFBackground: Clinical signs and their progression in Beagles with Lafora disease are poorly described.
Objectives: To describe clinical signs in Beagles with Lafora disease.
Animals: Twenty-eight Beagles with Lafora disease confirmed by genetic testing or histopathology.
Objective: The sudden COVID-19 outbreak has changed our health system. Physicians had to face the challenge of treating a large number of critically ill patients with a new disease and also maintain the essential healthcare services functioning properly. To prevent disease dissemination, authorities instructed people to stay at home and seek medical care only if they experienced respiratory distress.
View Article and Find Full Text PDFA fundamental understanding of the protein retention mechanism in preparative ion exchange (IEX) chromatography columns is essential for a model-based process development approach. For the past three decades, the mechanistic description of protein retention has been based predominantly on the steric mass action (SMA) model. In recent years, however, retention profiles of proteins have been reported more frequently for preparative processes that are not consistent with the mechanistic understanding relying on the SMA model.
View Article and Find Full Text PDFThe notion that the germ line does not age goes back to the 19th-century ideas of August Weismann. However, being metabolically active, the germ line accumulates damage and other changes over time, i.e.
View Article and Find Full Text PDFBackground: A preliminary national audit of real fasting times including 3324 children showed that the fasting times for clear fluids and light meals were frequently shorter than recommended in current guidelines, but the sample size was too small for subgroup analyses.
Aims: Therefore, the primary aim of this extended study with more participating centers and a larger sample size was to determine whether shortened fasting times for clear fluids or light meals have an impact on the incidence of regurgitation or pulmonary aspiration during general anesthesia in children. The secondary aim was to evaluate the impact of age, emergent status, ASA classification, induction method, airway management or surgical procedure.
Background: Prolonged fasting before anesthesia is still common in children. Shortened fasting times may improve the metabolic and hemodynamic condition during induction of anesthesia and the perioperative experience for parents and children and simplify perioperative management. As a consequence, some centers in Germany have reduced fasting requirements, but the national guidelines are still unchanged.
View Article and Find Full Text PDFSASE1 is the first beamline of the European XFEL that became operational in 2017. It consists of the SASE1 undulator system, the beam transport system, and the two scientific experiment stations: Single Particles, Clusters, and Biomolecules and Serial Femtosecond Crystallography (SPB/SFX), and Femtosecond X-ray Experiments (FXE). The beam transport system comprises mirrors to offset and guide the beam to the instruments and a set of X-ray optical components to align, manipulate and diagnose the beam.
View Article and Find Full Text PDFContextual memory is susceptible to the effects of aging and its impairment compromises episodic memories and quality of life in older adults. Compare the effects of cognitive support on incidental contextual memory free recall and recognition with a naturalistic experimental paradigm and explore the association of encoding strategies and physical activity on memory improvement. Subjects (≥60 years, n = 52) were assigned to one of two encoding conditions for the contextual memory task: with or without an incidental associative instruction to encourage association of an item to its spatial context.
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