The emergence and spread of SARS-CoV-2 lineage B.1.1.7, first detected in the United Kingdom, has become a global public health concern because of its increased transmissibility. Over 2,500 COVID-19 ...cases associated with this variant have been detected in the United States (US) since December 2020, but the extent of establishment is relatively unknown. Using travel, genomic, and diagnostic data, we highlight that the primary ports of entry for B.1.1.7 in the US were in New York, California, and Florida. Furthermore, we found evidence for many independent B.1.1.7 establishments starting in early December 2020, followed by interstate spread by the end of the month. Finally, we project that B.1.1.7 will be the dominant lineage in many states by mid- to late March. Thus, genomic surveillance for B.1.1.7 and other variants urgently needs to be enhanced to better inform the public health response.
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•Flight data identify that NY, CA, and FL were high risk for importing B.1.1.7•B.1.1.7 was introduced separately to multiple US states starting in December 2020•Phylogenetic analysis shows evidence for domestic spread between regions in US•Exponential growth of B.1.1.7 projects that it will be the dominant lineage
The SARS-CoV-2 variant B.1.1.7 was introduced to the US in early December 2020 and soon became established within many communities. The primary points of entry into the US are identified as New York, California, and Florida, and exponential growth in these states resulted in spread to neighboring states.
A SARS-CoV-2 surveillance program conducted by the National Basketball Association identified 173 newly infected persons. The viral kinetics were systematically studied and are described.
Research on astronaut health and model organisms have revealed six features of spaceflight biology that guide our current understanding of fundamental molecular changes that occur during space ...travel. The features include oxidative stress, DNA damage, mitochondrial dysregulation, epigenetic changes (including gene regulation), telomere length alterations, and microbiome shifts. Here we review the known hazards of human spaceflight, how spaceflight affects living systems through these six fundamental features, and the associated health risks of space exploration. We also discuss the essential issues related to the health and safety of astronauts involved in future missions, especially planned long-duration and Martian missions.
An international group of spaceflight researchers detail how spaceflight affects human biology from the molecular to physiological level and identify key challenges for making space exploration compatible with human health.
This study aims to develop a comprehensive and easily executable histopathologic grading scheme for murine knee osteoarthritis (OA) using specific scoring criteria for both cartilage and ...periarticular changes, which may overcome important limitations of the existing grading systems. The new grading scheme was developed based on mouse knee OA models with observation periods up to 24 months of age (spontaneous OA) or 24‐week post‐injury (posttraumatic OA). Semi‐quantitative assessments of the histopathologic OA changes were applied to all four quadrants per femorotibial joint for 50 joints (200 quadrants) using specific scoring criteria rather than mild to severe grades. Scoring elements per quadrant were as follows: cartilage lesion (0–7), osteophyte (0–3), subchondral bone change (0–3), synovitis (0–3), and ectopic periarticular soft‐tissue chondrogenesis and ossification (0–3). The new histopathologic grading scheme had high intra‐ and interobserver reproducibility (correlation coefficients r > 0.95) across experienced and novice observers. Sensitivity and reliability analyses confirmed the ability of the new scheme to detect minimal but significant OA progression (p < 0.01) within a 2‐week interval and to accurately identify tissue‐ and quadrant‐specific OA severity within the joints. In conclusion, this study presents the first whole‐joint histopathologic grading scheme for murine knee OA that covers all‐stage osteoarthritic changes in all major joint tissues, including periarticular soft‐tissue ossification that is not included in any of the existing OA grading systems. This reproducible scheme is easy to execute and sensitive to minimal OA progression without using computer software, suitable for quick OA severity assessments of the entire femorotibial joint.
The importance of diversity and cellular specialization is clear for many reasons, from population-level diversification, to improved resiliency to unforeseen stresses, to unique functions within ...metazoan organisms during development and differentiation. However, the level of cellular heterogeneity is just now becoming clear through the integration of genome-wide analyses and more cost effective Next Generation Sequencing (NGS). With easy access to single-cell NGS (scNGS), new opportunities exist to examine different levels of gene expression and somatic mutational heterogeneity, but these assays can generate yottabyte scale data. Here, we model the importance of heterogeneity for large-scale analysis of scNGS data, with a focus on the utilization in oncology and other diseases, providing a guide to aid in sample size and experimental design.
Facet joint (FJ) osteoarthritis (FJOA) is a widely prevalent spinal disorder but its pathogenesis remains unclear, largely due to the difficulties in conducting longitudinal human studies and lack of ...spontaneous-FJOA animal models for mechanistic investigations. This study aimed to investigate whether spontaneous FJOA occurs in mice bearing mutant NFAT1 (nuclear factor of activated T cells 1) transcription factor.
The lumbar FJs of 50 NFAT1-mutant mice and of 50 wild-type control mice, of both sexes, were examined by histopathology, quantitative gene expression analysis, semiquantitative immunohistochemistry, and a novel FJOA scoring system for semiquantitative assessment of the histopathologic changes at 2, 6, 12, and 18 months of age. Age-dependent and tissue-specific histopathologic and gene or protein expression changes were analyzed statistically.
FJs in NFAT1-mutant mice displayed significantly increased expression of specific catabolic genes (p < 0.05) and proteins (p < 0.001) in cartilage and synovium as early as 2 months of age, followed by early osteoarthritic structural changes such as articular surface fissuring and chondro-osteophyte formation at 6 months. More severe cartilage lesions, osteophytes, subchondral bone changes, synovitis, and tissue-specific molecular alterations in FJs of NFAT1-mutant mice were observed at 12 and 18 months. Osteoarthritic structural changes were not detected in FJs of wild-type mice at any ages, although age-related cartilage degeneration was observed at 18 months. The novel FJOA scoring system had high intraobserver and interobserver reproducibility (correlation coefficients: r > 0.97). Whole-joint FJOA scoring showed significantly higher OA scores in FJs of NFAT1-mutant mice compared with wild-type mice at all time points (p = 0.0033 at 2 months, p = 0.0001 at 6 months, p < 0.0001 at 12 and 18 months).
This study has identified the NFAT1-mutant mouse as a novel animal model of spontaneous FJOA with age-dependent and slowly progressing osteoarthritic features, developed the first FJOA scoring system, and elucidated the molecular mechanisms of NFAT1 mutation-induced FJOA.
This murine FJOA model resembles the features of human FJOA and may provide new insights into the pathogenesis of and therapeutic strategies for FJOA in humans.
Abstract Future multi-year crewed planetary missions will motivate advances in aerospace nutrition and telehealth. On Earth, the Human Cell Atlas project aims to spatially map all cell types in the ...human body. Here, we propose that a parallel Human Cell Space Atlas could serve as an openly available, global resource for space life science research. As humanity becomes increasingly spacefaring, high-resolution omics on orbit could permit an advent of precision spaceflight healthcare. Alongside the scientific potential, we consider the complex ethical, cultural, and legal challenges intrinsic to the human space omics discipline, and how philosophical frameworks may benefit from international perspectives.
Telomeres, repetitive terminal features of chromosomes essential for maintaining genome integrity, shorten with cell division, lifestyle factors and stresses, and environmental exposures, and so they ...provide a robust biomarker of health, aging, and age-related diseases. We assessed telomere length dynamics (changes over time) in three unrelated astronauts before, during, and after 1-year or 6-month missions aboard the International Space Station (ISS). Similar to our results for National Aeronautics and Space Administration’s (NASA’s) One-Year Mission twin astronaut (Garrett-Bakelman et al., 2019), significantly longer telomeres were observed during spaceflight for two 6-month mission astronauts. Furthermore, telomere length shortened rapidly after return to Earth for all three crewmembers and, overall, telomere length tended to be shorter after spaceflight than before spaceflight. Consistent with chronic exposure to the space radiation environment, signatures of persistent DNA damage responses were also detected, including mitochondrial and oxidative stress, inflammation, and telomeric and chromosomal aberrations, which together provide potential mechanistic insight into spaceflight-specific telomere elongation.
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•Telomere elongation during spaceflight was observed for two 6-month mission astronauts•Telomere elongation was not dependent on mission duration, sample, or measurement type•Chronic space radiation exposure was associated with persistent DNA damage responses•Telomeres shortened rapidly after return to Earth, and long-term individual differences were observed
Consistent with findings first observed for NASA’s One-Year Mission twin astronaut, Luxton et al. report spaceflight-specific telomere elongation in ISS crewmembers on shorter duration missions. Signatures of persistent DNA damage responses in the space radiation environment are also observed, providing potential mechanistic insight into telomere maintenance pathways during spaceflight.
Hematogenous metastasis is initiated by a subset of circulating tumor cells (CTC) shed from primary or metastatic tumors into the blood circulation. Thus, CTCs provide a unique patient biopsy ...resource to decipher the cellular subpopulations that initiate metastasis and their molecular properties. However, one crucial question is whether CTCs derived and expanded
from patients recapitulate human metastatic disease in an animal model. Here, we show that CTC lines established from patients with breast cancer are capable of generating metastases in mice with a pattern recapitulating most major organs from corresponding patients. Genome-wide sequencing analyses of metastatic variants identified semaphorin 4D as a regulator of tumor cell transmigration through the blood-brain barrier and MYC as a crucial regulator for the adaptation of disseminated tumor cells to the activated brain microenvironment. These data provide the direct experimental evidence of the promising role of CTCs as a prognostic factor for site-specific metastasis. SIGNIFICANCE: Interests abound in gaining new knowledge of the physiopathology of brain metastasis. In a direct metastatic tropism analysis, we demonstrated that
-cultured CTCs from 4 patients with breast cancer showed organotropism, revealing molecular features that allow a subset of CTCs to enter and grow in the brain.
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