The tumor microenvironment of cholangiocarcinoma (CCA) is composed of numerous cells, including mast cells (MCs). MCs release histamine, which increases CCA progression and angiogenesis. ...Cholangiocytes secrete stem cell factor, which functions via the MC growth factor receptor c-Kit. Here, we show that cholangiocytes express histidine decarboxylase and its inhibition reduces CCA growth. MC recruitment in the tumor microenvironment increased CCA growth. MC infiltration and MC markers were detected by toluidine blue staining and real-time PCR in human biopsies and in tumors from athymic mice treated with saline, histamine, histidine decarboxylase inhibitor, or cromolyn sodium. Tumor growth, angiogenesis, and epithelial-mesenchymal transition (EMT)/extracellular matrix (ECM) markers were measured in mice treated with cromolyn sodium. In vitro , human CCA cells were treated with MC supernatant fluids before evaluating angiogenesis and EMT/ECM expression. Migration assays were performed with CCA cells treated with the stem cell factor inhibitor. MC supernatant fluids increased CCA histidine decarboxylase, vascular endothelial growth factor, and MC/EMT/ECM expression that decreased with pretreatment of cromolyn sodium. MCs were found in human biopsies. In mice treated with cromolyn sodium, MC infiltration and tumor growth decreased. Inhibition of CCA stem cell factor blocked MC migration and MC/EMT/ECM in CCA. MCs migrate into CCA tumor microenvironment via c-Kit/stem cell factor and increase tumor progression, angiogenesis, EMT switch, and ECM degradation.
The COVID-19 pandemic continues to spread around the world and remains a major public health threat. Vaccine inefficiency, vaccination breakthroughs and lack of supply, especially in developing ...countries, as well as the fact that a non-negligible part of the population either refuse vaccination or cannot be vaccinated due to age, pre-existing illness or non-response to existing vaccines intensify this issue. This might also contribute to the emergence of new variants, being more efficiently transmitted, more virulent and more capable of escaping naturally acquired and vaccine-induced immunity. Hence, the need of effective and viable prevention options to reduce viral transmission is of outmost importance. In this study, we investigated the antiviral effect of iota-, lambda- and kappa-carrageenan, sulfated polysaccharides extracted from red seaweed, on SARS-CoV-2 Wuhan type and the spreading variants of concern (VOCs) Alpha, Beta, Gamma and Delta. Carrageenans as part of broadly used nasal and mouth sprays as well as lozenges have the potential of first line defense to inhibit the infection and transmission of SARS-CoV-2. Here, we demonstrate by using a SARS-CoV-2 spike pseudotyped lentivirus particles (SSPL) system and patient-isolated SARS-CoV-2 VOCs to infect transgenic A549ACE2/TMPRSS2 and Calu-3 human lung cells that all three carrageenan types exert antiviral activity. Iota-carrageenan exhibits antiviral activity with comparable IC
values against the SARS-CoV-2 Wuhan type and the VOCs. Altogether, these results indicate that iota-carrageenan might be effective for prophylaxis and treatment of SARS-CoV-2 infections independent of the present and potentially future variants.
Abstract
Bacterial growth rate (µ) depends on the protein synthesis capacity of the cell and thus on the number of active ribosomes and their translation elongation rate. The relationship between ...these fundamental growth parameters have only been described for few bacterial species, in particular
Escherichia coli
. Here, we analyse the growth-rate dependency of ribosome abundance and translation elongation rate for
Corynebacterium glutamicum
, a gram-positive model species differing from
E. coli
by a lower growth temperature optimum and a lower maximal growth rate. We show that, unlike in
E. coli
, there is little change in ribosome abundance for µ <0.4 h
−1
in
C. glutamicum
and the fraction of active ribosomes is kept above 70% while the translation elongation rate declines 5-fold. Mathematical modelling indicates that the decrease in the translation elongation rate can be explained by a depletion of translation precursors.
Inconsistent findings between laboratories are hampering scientific progress and are of increasing public concern. Differences in laboratory environment is a known factor contributing to poor ...reproducibility of findings between research sites, and well-controlled multisite efforts are an important next step to identify the relevant factors needed to reduce variation in study outcome between laboratories. Through harmonization of apparatus, test protocol, and aligned and non-aligned environmental variables, the present study shows that behavioral pharmacological responses in Shank2 knockout (KO) rats, a model of synaptic dysfunction relevant to autism spectrum disorders, were highly replicable across three research centers. All three sites reliably observed a hyperactive and repetitive behavioral phenotype in KO rats compared to their wild-type littermates as well as a dose-dependent phenotype attenuation following acute injections of a selective mGluR1 antagonist. These results show that reproducibility in preclinical studies can be obtained and emphasizes the need for high quality and rigorous methodologies in scientific research. Considering the observed external validity, the present study also suggests mGluR1 as potential target for the treatment of autism spectrum disorders.
Living organisms compartmentalize their catalytic reactions in membranes for increased efficiency and selectivity. To mimic the organelles of eukaryotic cells, we develop a mild approach for in situ ...encapsulating enzymes in aqueous‐core silica nanocapsules. In order to confine the sol‐gel reaction at the water/oil interface of miniemulsion, we introduce an aminosilane to the silica precursors, which serves as both catalyst and an amphiphilic anchor that electrostatically assembles with negatively charged hydrolyzed alkoxysilanes at the interface. The semi‐permeable shell protects enzymes from proteolytic attack, and allows the transport of reactants and products. The enzyme‐carrying nanocapsules, as synthetic nano‐organelles, are able to perform cascade reactions when enveloped in a polymer vesicle, mimicking the hierarchically compartmentalized reactions in eukaryotic cells. This in situ encapsulation approach provides a versatile platform for the delivery of biomacromolecules.
To mimic the compartmentalization of enzyme reactions in living organisms, in this study we developed an efficient and safe method for in situ encapsulating enzymes in aqueous‐core mesoporous nanocapsules. The enzyme‐carrying nanocapsules, as synthetic nano‐organelles, were able to successfully perform cascade reactions when enveloped in a polymer vesicle, mimicking the hierarchically compartmentalized reactions in the eukaryotic cells.
Military personnel deployed to the Amazon Basin are at high risk for cutaneous leishmaniasis (CL). We responded to an outbreak among Peruvian Army personnel returning from short-term training in the ...Amazon, conducting active case detection, lesion sample collection, and risk factor assessment. The attack rate was 25% (76/303); the incubation period was 2-36 weeks (median = 8). Most cases had one lesion (66%), primarily ulcerative (49%), and in the legs (57%). Real-time polymerase chain reaction (PCR) identified Leishmania (Viannia) braziliensis (59/61 = 97%) and L. (V.) guyanensis (2/61 = 3%). Being male (risk ratio RR = 4.01; P = 0.034), not wearing long-sleeve clothes (RR = 1.71; P = 0.005), and sleeping in open rooms (RR = 1.80; P = 0.009) were associated with CL. Sodium stibogluconate therapy had a 41% cure rate, less than previously reported in Peru (~70%; P < 0.001). After emphasizing pre-deployment education and other basic prevention measures, trainees in the following year had lower incidence (1/278 = 0.4%; P < 0.001). Basic prevention can reduce CL risk in deployed militaries.
To date, the 12-lead electrocardiogram (ECG) is the gold standard for cardiological diagnosis in clinical settings. With the advancements in technology, a growing number of smartphone apps and ...gadgets for recording, visualizing, and evaluating physical performance as well as health data is available. Although this new smart technology is innovative and time- and cost-efficient, less is known about its diagnostic accuracy and reliability.
This study aimed to examine the agreement between the mobile single-lead ECG measurements of the Kardia Mobile App and the Apple Watch 4 compared to the 12-lead gold standard ECG in healthy adults under laboratory conditions. Furthermore, it assessed whether the measurement error of the devices increases with an increasing heart rate.
This study was designed as a prospective quasi-experimental 1-sample measurement, in which no randomization of the sampling was carried out. In total, ECGs at rest from 81 participants (average age 24.89, SD 8.58 years; n=58, 72% male) were recorded and statistically analyzed. Bland-Altman plots were created to graphically illustrate measurement differences. To analyze the agreement between the single-lead ECGs and the 12-lead ECG, Pearson correlation coefficient (r) and Lin concordance correlation coefficient (CCC
) were calculated.
The results showed a higher agreement for the Apple Watch (mean deviation QT: 6.85%; QT interval corrected for heart rate using Fridericia formula QTcF: 7.43%) than Kardia Mobile (mean deviation QT: 9.53%; QTcF: 9.78%) even if both tend to underestimate QT and QTcF intervals. For Kardia Mobile, the QT and QTcF intervals correlated significantly with the gold standard (r
=0.857 and r
=0.727; P<.001). CCC
corresponded to an almost complete heuristic agreement for the QT interval (0.835), whereas the QTcF interval was in the range of strong agreement (0.682). Further, for the Apple Watch, Pearson correlations were highly significant and in the range of a large effect (r
=0.793 and r
=0.649; P<.001). CCC
corresponded to a strong heuristic agreement for both the QT (0.779) and QTcF (0.615) intervals. A small negative correlation between the measurement error and increasing heart rate could be found of each the devices and the reference.
Smart technology seems to be a promising and reliable approach for nonclinical health monitoring. Further research is needed to broaden the evidence regarding its validity and usability in different target groups.
Urbanization is one of the most intense forms of landscape change, and it is likely to increase in the coming years. Although there is a consensus that urbanization has drastic effects on ...biodiversity, recent discussions on the conservation of urban plant-pollinator interactions have not properly included biodiverse tropical regions. Here, we investigate how the structure of plant-pollinator networks changes along the urbanization gradient. We examined changes in structure of 21 plant-pollinator networks along six urbanization gradients. We also accessed the centrality of
Apis mellifera
(an exotic bee) and
Trigona spinipes
(a native bee), both generalist species, highly abundant and tolerant to urban environments. Finally, we identified important species of plants in urban pollination networks. We found that connectance and interaction evenness increases with urbanization, probably due to the loss of bee species. Complementary specialization (H2’) and modularity were not affected by the urban landscape. Closeness centrality of
A. mellifera
increased with increasing impermeable cover reinforcing the hypothesis that invasive and super-generalist species are generally more central in more urbanized areas. In contrast, eigenvector centrality of
T. spinipes
decreased with the increase in urbanization, suggesting a decrease in the importance of this species for the network as urban areas get denser. Our results support to understand the effects of urbanization on mutualistic networks in tropical environments and can contribute to the protection of native biodiversity against urban expansion.
Implications for insect conservation:
Our results show that plant-bee interactions networks become simplified as urbanization increases. We also show that the invasive non-native bee Apis mellifera dominate urban plant-bee interactions in neotropical cities. To improve insect conservation in cities, it is recommended to plant native plant species and manage invasive non-native species.
To benefit allergy patients and the medical practitioners, pollen information should be available in both a reliable and timely manner; the latter is only recently possible due to automatic ...monitoring. To evaluate the performance of all currently available automatic instruments, an international intercomparison campaign was jointly organised by the EUMETNET AutoPollen Programme and the ADOPT COST Action in Munich, Germany (March–July 2021).
The automatic systems (hardware plus identification algorithms) were compared with manual Hirst-type traps. Measurements were aggregated into 3-hourly or daily values to allow comparison across all devices. We report results for total pollen as well as for Betula, Fraxinus, Poaceae, and Quercus, for all instruments that provided these data. The results for daily averages compared better with Hirst observations than the 3-hourly values. For total pollen, there was a considerable spread among systems, with some reaching R2 > 0.6 (3 h) and R2 > 0.75 (daily) compared with Hirst-type traps, whilst other systems were not suitable to sample total pollen efficiently (R2 < 0.3). For individual pollen types, results similar to the Hirst were frequently shown by a small group of systems. For Betula, almost all systems performed well (R2 > 0.75 for 9 systems for 3-hourly data). Results for Fraxinus and Quercus were not as good for most systems, while for Poaceae (with some exceptions), the performance was weakest. For all pollen types and for most measurement systems, false positive classifications were observed outside of the main pollen season. Different algorithms applied to the same device also showed different results, highlighting the importance of this aspect of the measurement system. Overall, given the 30 % error on daily concentrations that is currently accepted for Hirst-type traps, several automatic systems are currently capable of being used operationally to provide real-time observations at high temporal resolutions. They provide distinct advantages compared to the manual Hirst-type measurements.
Display omitted
•Daily results compared better with the Hirst observations than the 3-hourly values.•For individual pollen types, results similar to the Hirst were frequently shown by a few systems.•Automatic systems performed best for Betula, then Quercus and Fraxinus, while worst for Poaceae.•Different algorithms applied to the same device also showed different results.•Some automatic systems are capable of being used operationally to provide real time observations.
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