Fibrodysplasia ossificans progressive (FOP) is an ultra-rare genetic disorder that is caused by a mutation in the ACVR1 gene and provokes severe heterotopic ossification. Since flares of the disease ...are associated with inflammation, it is assumed that JAK inhibitors can control active FOP due to blocking multiple signaling pathways. Keywords: Fibrodysplasia ossificans progressiva, FOP, Heterotopic ossification, Tofacitinib, Autoinflammation, Spondyloarthritis-like disease, ACVR1 gene, Bone morphogenetic protein, BMP
Abstract
Passive transfer of antithyroid antibodies in mice leads to reproductive disorders. The purpose was to assess the placental tissue of experimental animals under the influence of the ...circulating thyroperoxidase antibodies. We performed an immunohistochemical examination of murine placentae after a passive transfer of thyroperoxidase antibodies. Placentae of mice that passively transferred IgG from healthy donors were used as control samples. For histological examination, 30 placental samples were selected from mice from the anti-TPO group and 40 placental samples were taken from mice from the IgG group. Immunostaining for VEGFR1, THBS 1, Laminin, CD31, CD34, FGF-β, CD56, CD14, TNF-α, kisspeptin, MCL 1, and Annexin V was performed. There is a significant decrease in the relative area of the expression of VEGFR1 (23.42 ± 0.85 vs. 33.44 ± 0.35, P < 0.01), thrombospondin 1 (31.29 ± 0.83 vs. 34.51 ± 0.75, P < 0.01), CD14 (25.80 ± 0.57 vs. 32.07 ± 0.36, P < .01), CD56 (30.08 ± 0.90 vs. 34.92 ± 0.15, P < 0.01), kisspeptin (25.94 ± 0.47 vs. 31.27 ± 0.57, P < 0.01), MCL 1 (29.24 ± 1.06 vs. 38.57 ± 0.79, P < 0.01) in the labyrinth zone of the placentae of mice from the anti-TPO group compared with control group. A significant increase in the relative expression of laminin and FGF-β was noted in the group of mice to which antibodies to thyroperoxidase were transferred, compared with the control group (36.73 ± 1.38 vs. 29.83 ± 0.94, P < 0.01 and 23.26 ± 0.61 vs. 16.38 ± 1.01, P < 0.01respectively). Our study exposed an imbalance of pro- and anti-angiogenic factors, decreased representation of placental macrophages and NK cells, abnormal trophoblast invasion processes, and insufficient expression of antiapoptotic factors in the placentae of mice in which anti-TPO antibodies were passively transferred.
We performed an immunohistochemical examination of murine placentae after a passive transfer of thyroperoxidase antibodies. Our study exposed an imbalance of pro- and anti-angiogenic factors, decreased representation of placental macrophages and NK cells, abnormal trophoblast invasion processes, and insufficient expression of antiapoptotic factors in the placentae of mice in which anti-TPO antibodies were passively transferred.
Graphical Abstract
Graphical Abstract
Problem
Antibody‐mediated autoimmune diseases, such as autoimmune thyroid diseases (ATD), systemic lupus erythematosus (SLE), and antiphospholipid syndrome (APS), often are associated with recurrent ...fetal loss. One of the ATD is Hashimoto's thyroiditis which recently showed association with complications of pregnancy with increased levels of circulating autoantibodies reactive with epitopes on thyroid tissue such as thyroid peroxidase (anti‐TPO). In retrospective study of sera analyses in patients with Hashimoto's thyroiditis, all patients had mainly elevated circulating anti‐TPO autoantibodies.
Aim
We assessed the potential of human anti‐TPO highly positive IgG, derived from patients with Hashimoto's thyroiditis sera associated with complications of pregnancy, to cause directly complications of pregnancy in murine model.
Method of study
Naïve ICR female mice, infused intravenously with 100 μg of anti‐TPO‐positive IgG, showed increased fetal loss and embryo small for date (P < .001) in comparison with mice passively transferred with commercial IgG or PBS. Moreover, we observed embryos small for date in the mice passively transferred with anti‐TPO‐positive IgG, exemplified by reduced weight of embryos and placentae (P = .001). Histopathological examination revealed delay in fetal development in 50% cases of anti‐TPO‐positive IgG‐treated mice. Importantly, pathological changes in the transition zone, state of glycogen cells, and significant structural changes in the labyrinth part of placenta were observed in all anti‐TPO‐positive IgG samples.
Conclusion
The current study shows in the first time, a direct proof of concept, on the association of human TPO‐positive IgG from Hashimoto's thyroiditis patients on fetal loss induction in murine model.
Universities are vulnerable to infectious disease outbreaks, making them ideal environments to study transmission dynamics and evaluate mitigation and surveillance measures. Here, we analyze ...multimodal COVID-19-associated data collected during the 2020–2021 academic year at Colorado Mesa University and introduce a SARS-CoV-2 surveillance and response framework.
We analyzed epidemiological and sociobehavioral data (demographics, contact tracing, and WiFi-based co-location data) alongside pathogen surveillance data (wastewater and diagnostic testing, and viral genomic sequencing of wastewater and clinical specimens) to characterize outbreak dynamics and inform policy. We applied relative risk, multiple linear regression, and social network assortativity to identify attributes or behaviors associated with contracting SARS-CoV-2. To characterize SARS-CoV-2 transmission, we used viral sequencing, phylogenomic tools, and functional assays.
Athletes, particularly those on high-contact teams, had the highest risk of testing positive. On average, individuals who tested positive had more contacts and longer interaction durations than individuals who never tested positive. The distribution of contacts per individual was overdispersed, although not as overdispersed as the distribution of phylogenomic descendants. Corroboration via technical replicates was essential for identification of wastewater mutations.
Based on our findings, we formulate a framework that combines tools into an integrated disease surveillance program that can be implemented in other congregate settings with limited resources.
This work was supported by the National Science Foundation, the Hertz Foundation, the National Institutes of Health, the Centers for Disease Control and Prevention, the Massachusetts Consortium on Pathogen Readiness, the Howard Hughes Medical Institute, the Flu Lab, and the Audacious Project.
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•Surveillance of SARS-CoV-2 transmission at a public university•Wi-Fi co-location data identified social behaviors associated with infection•Overdispersion in virus transmission consists of both social and biological components•Concurrent clinical sample sequencing led to wastewater variant-calling criteria
Understanding the factors that influence the transmission of SARS-CoV-2 and other pathogens is critical to mitigate outbreaks. Here, researchers at Colorado Mesa University and at the Broad Institute of MIT and Harvard designed and assessed an infectious disease surveillance program that included diagnostic testing and symptom reporting, wastewater surveillance, and digital contact tracing of students at a university. Viral spread on campus was a result of social behaviors, such as the number of contacts and the types of interactions an infected person had, and biological factors, such as the SARS-CoV-2 variant an infected person harbored. The authors’ findings highlight the need to design surveillance programs that capture social behaviors and viral lineage information in congregate communities.
Petros et al. studied SARS-CoV-2 transmission at a university by integrating epidemiological metadata, Wi-Fi-based location data, and viral sequences from wastewater and clinical samples. They identified a novel viral lineage and used digital contact tracing, genomics, and functional assays to delineate the social and biological factors contributing to its expansion.
We study a class of dynamical systems which generalizes and unifies some models arising in the analysis of switched flow systems in manufacturing. The general properties of these dynamical systems, ...called pseudo billiards, as well as some of their perturbations are discussed.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Solid fullerenes C
60
and C
70
have been treated at high pressure of 15 GPa and high temperatures of 520 - 1820 K for a time of exposure of 60 s and a quenching rate of 300 K s
−1
using a toroid-type ...apparatus. X-ray diffraction and Raman spectra confirm the realization of 3D-polymerized phases in these solids at 15 GPa. The pressure/temperature maps of synthesis of metastable carbon phases on the basis of C
60
and C
70
have thus been extended to 15 GPa. The longitudinal and shear sound wave velocities were measured by acoustic microscopy techniques. A maximum sound wave velocity of (21±1)×10
5
m s
−1
was observed in the sample synthesized from C
60
at T = 1170 K. The elastic constants were calculated using experimental data. The acoustic microscopy images of experimental samples have been investigated.
Solid fullerenes C
and C
have been treated at high pressure of 15 GPa and high temperatures of 520 - 1820 K for a time of exposure of 60 s and a quenching rate of 300 K s
using a toroid-type ...apparatus. X-ray diffraction and Raman spectra confirm the realization of 3D-polymerized phases in these solids at 15 GPa. The pressure/temperature maps of synthesis of metastable carbon phases on the basis of C
and C
have thus been extended to 15 GPa. The longitudinal and shear sound wave velocities were measured by acoustic microscopy techniques. A maximum sound wave velocity of (21±1)×10
m s
was observed in the sample synthesized from C
at T = 1170 K. The elastic constants were calculated using experimental data. The acoustic microscopy images of experimental samples have been investigated.
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