SARS-CoV-2 infection causes COVID-19. Several clinical reports have linked COVID-19 during pregnancy to negative birth outcomes and placentitis. However, the pathophysiological mechanisms ...underpinning SARS-CoV-2 infection during placentation and early pregnancy are not clear. Here, to shed light on this, we used induced trophoblast stem cells to generate an in vitro early placenta infection model. We identified that syncytiotrophoblasts could be infected through angiotensin-converting enzyme 2 (ACE2). Using a co-culture model of vertical transmission, we confirmed the ability of the virus to infect syncytiotrophoblasts through a previous endometrial cell infection. We further demonstrated transcriptional changes in infected syncytiotrophoblasts that led to impairment of cellular processes, reduced secretion of HCG hormone and morphological changes vital for syncytiotrophoblast function. Furthermore, different antibody strategies and antiviral drugs restore these impairments. In summary, we have established a scalable and tractable platform to study early placental cell types and highlighted its use in studying strategies to protect the placenta.
Abstract
Titin-related myopathies are heterogeneous clinical conditions associated with mutations in TTN. To define their histopathologic boundaries and try to overcome the difficulty in assessing ...the pathogenic role of TTN variants, we performed a thorough morphological skeletal muscle analysis including light and electron microscopy in 23 patients with different clinical phenotypes presenting pathogenic autosomal dominant or autosomal recessive (AR) mutations located in different TTN domains. We identified a consistent pattern characterized by diverse defects in oxidative staining with prominent nuclear internalization in congenital phenotypes (AR-CM) (n = 10), ± necrotic/regenerative fibers, associated with endomysial fibrosis and rimmed vacuoles (RVs) in AR early-onset Emery-Dreifuss-like (AR-ED) (n = 4) and AR adult-onset distal myopathies (n = 4), and cytoplasmic bodies (CBs) as predominant finding in hereditary myopathy with early respiratory failure (HMERF) patients (n = 5). Ultrastructurally, the most significant abnormalities, particularly in AR-CM, were multiple narrow core lesions and/or clear small areas of disorganizations affecting one or a few sarcomeres with M-band and sometimes A-band disruption and loss of thick filaments. CBs were noted in some AR-CM and associated with RVs in HMERF and some AR-ED cases. As a whole, we described recognizable histopathological patterns and structural alterations that could point toward considering the pathogenicity of TTN mutations.
The first aim of this work was to obtain temporal variability patterns for satellite‐derived solar radiation estimations in Zambia. A principal component analysis, in Zambia and the surrounding ...zones, was performed and from this analysis the physical phenomena associated with these patterns were established. According to the results, two temporal variability patterns stand out: the first is associated with the regional global climate characteristics, including both the deterministic and non‐deterministic components of solar radiation, and the other is strictly associated with the influence of the intertropical convergence zone (ITCZ) responsible for the behaviour of solar radiation during October–March. The second aim of the work was to analyse the spatial variability of the irradiance in the study area. For this aim, a clustering analysis based on the interquartile range of the data was performed. The analysis leads to a spatial distribution of the radiation in agreement with the influence of the ITCZ on the territory. Indeed, those stations less affected by the ITCZ, in the south and east of the territory, show a clear diminution of the radiation around June. However, the stations of the northwest zone, the most affected by the belt of low pressure during November–April, do not present this diminution.
The first component of the principal component analysis is associated with the global climate characteristics of the region.
The second component is strictly associated with the influence of the intertropical convergence zone.
A clustering analysis based on the interquartile range divides the territory, in terms of solar radiation variability, into coherent zones.
This analysis could serve to establish a regionalization to improve radiation models or the location of measuring ground stations.
The present study evaluated changes in the incidence of invasive pneumococcal disease (IPD) and the pattern of serotypes isolated in Navarre, Spain, after the introduction and increased coverage of ...the heptavalent pneumococcal conjugate vaccine (PCV7). All cases with isolation of pneumococcus from normally sterile bodily fluids were included. The incidence of IPD in children and adults was compared for the periods 2001–2002 and 2006–2007. By the end of 2002, only 11% of children aged <5 years had received any dose of PCV7, whereas, beginning in 2007, the proportion exceeded 50%. Among the cases of IPD aged <5 years, the percentage of those vaccinated increased from 7% during 2001–2002 to 53% during 2006–2007 (p <0.001). The incidence of IPD from PCV7-serotypes decreased by 85% in children <5 years (p <0.001), by 45% in the population aged 5–64 years (p 0.10) and by 68% in those ≥65 years (p 0.004). By contrast, the incidence of IPD from non-PCV7 serotypes increased by 40% overall (p 0.006). The incidence of IPD from all serotypes did not change significantly in children <5 years (from 83 to 72 per 100 000) or in the total population (from 15.8 to 16.3 per 100 000). The percentage of cases as a result of serotypes 7 and 19A increased significantly in both children and adults. No significant changes were seen in the clinical forms of IPD. The pattern of serotypes causing IPD has changed, in both children and adults, following the increased coverage of PCV7, although the incidence has been reduced only slightly.
Postnatal maturation of the immune system is poorly understood, as is its impact on illnesses afflicting term or preterm infants, such as bronchopulmonary dysplasia (BPD) and BPD-associated pulmonary ...hypertension. These are both cardiopulmonary inflammatory diseases that cause substantial mortality and morbidity with high treatment costs. Here, we characterized blood samples collected from 51 preterm infants longitudinally at five time points, 20 healthy term infants at birth and age 3 to 16 weeks, and 5 healthy adults. We observed strong associations between type 2 immune polarization in circulating CD3
CD4
T cells and cardiopulmonary illness, with odds ratios up to 24. Maternal magnesium sulfate therapy, delayed hepatitis B vaccination, and increasing fetal, but not maternal, chorioamnionitis severity were associated with attenuated type 2 polarization. Blocking type 2 mediators such as interleukin-4 (IL-4), IL-5, IL-13, or signal transducer and activator of transcription 6 (STAT6) in murine neonatal cardiopulmonary disease in vivo prevented changes in cell type composition, increases in IL-1β and IL-13, and losses of pulmonary capillaries, but not gains in larger vessels. Thereby, type 2 blockade ameliorated lung inflammation, protected alveolar and vascular integrity, and confirmed the pathological impact of type 2 cytokines and STAT6. In-depth flow cytometry and single-cell transcriptomics of mouse lungs further revealed complex associations between immune polarization and cardiopulmonary disease. Thus, this work advances knowledge on developmental immunology and its impact on early life disease and identifies multiple therapeutic approaches that may relieve inflammation-driven suffering in the youngest patients.
We explore how to address the challenges of adaptation of water resources systems under changing conditions by supporting flexible, resilient and low-regret solutions, coupled with on-going ...monitoring and evaluation. This will require improved understanding of the linkages between biophysical and social aspects in order to better anticipate the possible future co-evolution of water systems and society. We also present a call to enhance the dialogue and foster the actions of governments, the international scientific community, research funding agencies and additional stakeholders in order to develop effective solutions to support water resources systems adaptation. Finally, we call the scientific community to a renewed and unified effort to deliver an innovative message to stakeholders. Water science is essential to resolve the water crisis, but the effectiveness of solutions depends, inter alia, on the capability of scientists to deliver a new, coherent and technical vision for the future development of water systems.
EDITOR D. Koutsoyiannis; ASSOCIATE EDITOR not assigned
In the light of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, we have developed a porcine respiratory coronavirus (PRCV) model for in depth mechanistic evaluation of the ...pathogenesis, virology and immune responses of this important family of viruses. Pigs are a large animal with similar physiology and immunology to humans and are a natural host for PRCV. Four PRCV strains were investigated and shown to induce different degrees of lung pathology. Importantly, although all four strains replicated equally well in porcine cell lines
and in the upper respiratory tract
, PRCV strains causing more severe lung pathology were also able to replicate in
tracheal organ cultures as well as
in the trachea and lung. The time course of infection of PRCV 135, which caused the most severe pulmonary pathology, was investigated. Virus was shed from the upper respiratory tract until day 10 post infection, with infection of the respiratory mucosa, as well as olfactory and sustentacular cells, providing an excellent model to study upper respiratory tract disease in addition to the commonly known lower respiratory tract disease from PRCV. Infected animals made antibody and T cell responses that cross reacted with the four PRCV strains and Transmissible Gastroenteritis Virus. The antibody response was reproduced
in organ cultures. Comparison of mechanisms of infection and immune control in pigs infected with PRCVs of differing pathogenicity with human data from SARS-CoV-2 infection and from our
organ cultures, will enable key events in coronavirus infection and disease pathogenesis to be identified.
Cyclic block copolymers ( c BCP) are fundamentally intriguing materials, but their synthetic challenges that demand precision in controlling both the monomer sequence and polymer topology limit ...access to AB and ABC block architectures. Here, we show that cyclic ABAB tetra-BCPs ( c ABAB) and their linear counterpart ( l ABAB) can be readily obtained at a speed and scale from one-pot (meth)acrylic monomer mixtures, through coupling the Lewis pair polymerization’s unique compounded-sequence control with its precision in topology control. This approach achieves fast (<15 min) and quantitative (>99%) conversion to tetra-BCPs of predesignated linear or cyclic topology at scale (40 g) in a one-pot procedure, precluding the needs for repeated chain extensions, stoichiometric addition steps, dilute conditions, and postsynthetic modifications, and/or postsynthetic ring-closure steps. The resulting l ABAB and c ABAB have essentially identical molecular weights (M n = 165–168 kg mol–1) and block degrees/symmetry, allowing for direct behavioral comparisons in solution (hydrodynamic volume, intrinsic viscosity, elution time, and refractive indices), bulk (thermal transitions), and film (thermomechanical and rheometric properties and X-ray scattering patterns) states. To further the morphological characterizations, allylic side-chain functionality is exploited via the thiol–ene click chemistry to install crystalline octadecane side chains and promote phase separation between the A and B blocks, allowing visualization of microdomain formation.
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