The basement membrane complex (BMC) is a critical component of the extracellular matrix (ECM) that supports and facilitates the growth of cells. This study investigates four detergents commonly used ...in the process of tissue decellularization and their effect upon the BMC. The BMC of porcine urinary bladder was subjected to 3% Triton-X 100, 8mM 3-(3-cholamidopropyl)dimethylammonio-1-propanesulfonate (CHAPS), 4% sodium deoxycholate or 1% sodium dodecyl sulfate (SDS) for 24h. The BMC structure for each treatment group was assessed by immunolabeling, scanning electron microscopy (SEM) and second harmonic generation (SHG) imaging of the fiber network. The composition was assessed by quantification of dsDNA, glycosaminoglycans (GAG) and collagen content. The results showed that collagen fibers within samples treated with 1% SDS and 8mM CHAPS were denatured, and the ECM contained fewer GAG compared with samples treated with 3% Triton X-100 or 4% sodium deoxycholate. Human microvascular endothelial cells (HMEC) were seeded onto each BMC and cultured for 7days. Cell–ECM interactions were investigated by immunolabeling for integrin β-1, SEM imaging and semi-quantitative assessment of cellular infiltration, phenotype and confluence. HMEC cultured on a BMC treated with 3% Triton X-100 were more confluent and had a normal phenotype compared with HMEC cultured on a BMC treated with 4% sodium deoxycholate, 8mM CHAPS and 1% SDS. Both 8mM CHAPS and 1% SDS damaged the BMC to the extent that seeded HMEC were able to infiltrate the damaged sub-basement membrane tissue, showed decreased confluence and an atypical phenotype. The choice of detergents used for tissue decellularization can have a marked effect upon the integrity of the BMC of the resultant bioscaffold.
Pulmonary aspiration of gastric contents during the perioperative period in infants and children may be associated with postoperative mortality or pulmonary morbidity. There has not been a recent ...determination of the frequency of this event and its outcomes in infants and children.
The authors prospectively identified all cases of pulmonary aspiration of gastric contents during the perioperative courses of 56,138 consecutive patients younger than 18 yr of age who underwent 63,180 general anesthetics for procedures performed in all surgical specialties from July 1985 through June 1997 at the Mayo Clinic.
Pulmonary aspiration occurred in 24 patients (1: 2,632 anesthetics; 0.04%). Children undergoing emergency procedures had a greater frequency of pulmonary aspiration compared to those undergoing elective procedures (1:373 vs. 1:4,544, P < 0.001). Fifteen of the 24 children who aspirated gastric contents did not develop respiratory symptoms within 2 h of aspiration, and none of these 15 developed pulmonary sequelae. Five of these nine children who aspirated and in whom respiratory symptoms developed within 2 h subsequently had pulmonary complications treated with respiratory support (P < 0.003). Three children were treated with mechanical ventilation for more than 48 h, but no child died of sequelae of pulmonary aspiration.
In this study population, the frequency of perioperative pulmonary aspiration in children was quite low. Serious respiratory morbidity was rare, and there were no associated deaths. Infants and children with clinically apparent pulmonary aspiration in whom symptoms did not develop within 2 h did not have respiratory sequelae.
Arctic-breeding geese acquire resources for egg production from overwintering grounds, spring stopover sites and breeding grounds, where pollutant exposure may differ. We investigated the effect of ...migration strategy on pollutant occurrence of lipophilic polychlorinated biphenyls (PCBs) and protein-associated poly- and perfluoroalkyl substances (PFASs) and mercury (Hg) in eggs of herbivorous barnacle geese (Branta leucopsis) from an island colony on Svalbard. Stable isotopes (δ13C and δ15N) in eggs and vegetation collected along the migration route were similar. Pollutant concentrations in eggs were low, reflecting their terrestrial diet (∑PCB = 1.23 ± 0.80 ng/g ww; ∑PFAS = 1.21 ± 2.97 ng/g ww; Hg = 20.17 ± 7.52 ng/g dw). PCB concentrations in eggs increased with later hatch date, independent of lipid content which also increased over time. Some females may remobilize and transfer more PCBs to their eggs, by delaying migration several weeks, relying on more polluted and stored resources, or being in poor body condition when arriving at the breeding grounds. PFAS and Hg occurrence in eggs did not change throughout the breeding season, suggesting migration has a greater effect on lipophilic pollutants. Pollutant exposure during offspring production in arctic-breeding migrants may result in different profiles, with effects becoming more apparent with increasing trophic levels.
Patients with advanced salivary gland mucoepidermoid carcinoma (MEC) are treated with surgery and radiotherapy, as current systemic therapies are largely ineffective. As such, current treatment ...frequently leads to poor long-term survival due to locoregional recurrence or metastases. We have shown that salivary gland cancer stem cells (CSCs) are resistant to platinum-based chemotherapy and drive tumor progression. The purpose of this study was to investigate the effect of therapeutic inhibition of mTOR (mechanistic target of rapamycin) on resistance of CSCs to cisplatin, a prototypic platinum-based chemotherapeutic agent. Viability assays determined the effect of several inhibitors of PI3k/mTOR signaling (e.g., temsirolimus, BKM120, AZD8055, PF4708671) and/or cisplatin on survival of human MEC cells. The impact of mTOR inhibitors and/or cisplatin on MEC stemness was examined with salisphere assays, flow cytometry for ALDH/CD44 (CSC markers for MEC), and Western blots for Bmi-1 expression (marker of stem cell self-renewal). Salivary gland MEC patient-derived xenografts were used to examine the effect of cisplatin and/or temsirolimus on CSCs in vivo. We observed that cisplatin induced mTOR and S6K1 phosphorylation, increased the number and size of MEC salispheres, and induced Bmi-1 expression and the fraction of CSCs in MEC models in vitro. Cisplatin also increased the fraction of CSCs in vivo. In contrast, mTOR inhibition (e.g., temsirolimus) blocked cisplatin-induced Bmi-1 expression and salisphere formation in vitro. Remarkably, temsirolimus slowed down tumor growth and decreased the fraction of CSCs (P < 0.05) even in presence of cisplatin in a short-term in vivo experiment. Collectively, these results demonstrate that therapeutic inhibition of mTOR ablates cytotoxic-resistant CSCs, and they suggest that a combination of an mTOR inhibitor and platinum-based chemotherapy might be beneficial to patients with salivary gland mucoepidermoid carcinoma.
Multiple genetic loci confer susceptibility to breast and ovarian cancers. We have previously developed a model (BOADICEA) under which susceptibility to breast cancer is explained by mutations in ...BRCA1 and BRCA2, as well as by the joint multiplicative effects of many genes (polygenic component). We have now updated BOADICEA using additional family data from two UK population-based studies of breast cancer and family data from BRCA1 and BRCA2 carriers identified by 22 population-based studies of breast or ovarian cancer. The combined data set includes 2785 families (301 BRCA1 positive and 236 BRCA2 positive). Incidences were smoothed using locally weighted regression techniques to avoid large variations between adjacent intervals. A birth cohort effect on the cancer risks was implemented, whereby each individual was assumed to develop cancer according to calendar period-specific incidences. The fitted model predicts that the average breast cancer risks in carriers increase in more recent birth cohorts. For example, the average cumulative breast cancer risk to age 70 years among BRCA1 carriers is 50% for women born in 1920-1929 and 58% among women born after 1950. The model was further extended to take into account the risks of male breast, prostate and pancreatic cancer, and to allow for the risk of multiple cancers. BOADICEA can be used to predict carrier probabilities and cancer risks to individuals with any family history, and has been implemented in a user-friendly Web-based program (http://www.srl.cam.ac.uk/genepi/boadicea/boadicea_home.html).
Genetic parameters were estimated for a range of meat quality traits recorded on Australian lamb meat. Data were collected from Merino and crossbred progeny of Merino, terminal and maternal meat ...breed sires of the Information Nucleus programme. Lambs born between 2007 and 2010 (n=8968) were slaughtered, these being the progeny of 372 sires and 5309 dams. Meat quality traits were found generally to be of moderate heritability (estimates between 0.15 and 0.30 for measures of meat tenderness, meat colour, polyunsaturated fat content, mineral content and muscle oxidative capacity), with notable exceptions of intramuscular fat (0.48), ultimate pH (0.08) and fresh meat colour a* (0.08) and b* (0.10) values. Genetic correlations between hot carcass weight and the meat quality traits were low. The genetic correlation between intramuscular fat and shear force was high (−0.62). Several measures of meat quality (fresh meat redness, retail meat redness, retail oxy/met value and iron content) appear to have potential for inclusion in meat sheep breeding objectives.
•Genetic parameters were estimated among a range of meat quality traits in lamb meat.•Moderate heritability of many traits showed that they can be altered via selection.•Selection to improve IMF or tenderness associated with reduced meat colour stability•Meat redness and iron content could possibly be included in sheep breeding programmes.
Aims
Improving glycaemic control in people with Type 1 diabetes is known to reduce complications. Our aim was to compare glycaemic control among people with Type 1 diabetes using data gathered in ...regional or national registries.
Methods
Data were obtained for children and/or adults with Type 1 diabetes from the following countries (or regions): Western Australia, Austria, Denmark, England, Champagne‐Ardenne (France), Germany, Epirus, Thessaly and Thessaloniki (Greece), Galway (Ireland), several Italian regions, Latvia, Rotterdam (The Netherlands), Otago (New Zealand), Norway, Northern Ireland, Scotland, Sweden, Volyn (Ukraine), USA and Wales) from population or clinic‐based registries. The sample size with available data varied from 355 to 173 880. Proportions with HbA1c < 58 mmol/mol (< 7.5%) and ≥ 75 mmol/mol (≥ 9.0%) were compared by age and sex.
Results
Data were available for 324 501 people. The proportions with HbA1c 58 mmol/mol (< 7.5%) varied from 15.7% to 46.4% among 44 058 people aged < 15 years, from 8.9% to 49.5% among 50 766 people aged 15–24 years and from 20.5% to 53.6% among 229 677 people aged ≥ 25 years. Sex differences in glycaemic control were small. Proportions of people using insulin pumps varied between the 12 sources with data available.
Conclusion
These results suggest that there are substantial variations in glycaemic control among people with Type 1 diabetes between the data sources and that there is room for improvement in all populations, especially in young adults.
What's new?
We present HbA1c data from registries in 19 different countries describing control in 324 501 people with Type 1 diabetes, across all age groups.
These data are the best representation of diabetes care available and therefore describe the ‘state of the art’.
We show clearly that Type 1 diabetes control is not as good as suggested in guidelines, but that some healthcare systems appear to result in better control than others.
These data present a challenge to diabetes services. Leaders in diabetes units/service can compare their local data to our data and encourage improvement.
Heteroatom doping into polyaromatic hydrocarbons (PAHs) is a powerful approach for modifying key physical properties, however, there are extremely few modular routes that enable facile formation of ...B-, B
- and B,N-(specifically not containing direct B-N bonds) doped PAHs despite the growing importance of these materials. Sequential, one pot borylative cyclisation/intramolecular electrophilic C-H borylation of naphthyl-alkynes provides a simple new route to access novel B-, B,N- and B
-doped (PAHs). The initial products, dihydronaphthalene/dihydroquinoline B-mesityl PAHs, were reacted with Ph
CBF
/pyridyl base to form the oxidised B-, and B,N-doped PAHs. However, for B-triisopropylphenyl (Trip) PAH congeners oxidation has to be performed prior to Trip installation due to preferential oxidation of an isopropylaryl moiety to the styrene. This alternative sequence enables access to Trip-B-PAHs and to structurally constrained B and B
-PAHs. Analysis of the solid state structures and optoelectronic properties of these PAHs confirm that frontier orbital energies, extended packing structures, Stokes shift and quantum yields all can be rationally modified using this methodology. The simplicity of this synthetic approach makes it a powerful tool for rapidly generating novel bench stable boron doped PAHs, which is important for facilitating further structure-property relationship studies and the wider utilisation of these materials in optoelectronic applications.
Key message
Elite wheat pollinators are critical for successful hybrid breeding. We identified
Rht
-
B1
and
Ppd
-
D1
loci affecting multiple pollinator traits and therefore represent major targets ...for improving hybrid seed production.
Hybrid breeding has a great potential to significantly boost wheat yields. Ideal male pollinators would be taller in stature, contain many spikelets well-spaced along the spike and exhibit high extrusion of large anthers. Most importantly, flowering time would match with that of the female parent. Available genetic resources for developing an elite wheat pollinator are limited, and the genetic basis for many of these traits is largely unknown. Here, we report on the genetic analysis of pollinator traits using biparental mapping populations. We identified two anther extrusion QTLs of medium effect, one on chromosome 1BL and the other on 4BS coinciding with the semi-dwarfing
Rht
-
B1
locus. The effect of
Rht
-
B1
alleles on anther extrusion is genotype dependent, while tall plant
Rht
-
B1a
allele is consistently associated with large anthers. Multiple QTLs were identified at the
Ppd
-
D1
locus for anther length, spikelet number and spike length, with the photoperiod-sensitive
Ppd
-
D1b
allele associated with favourable pollinator traits in the populations studied. We also demonstrated that homeoloci,
Rht
-
D1
and
Ppd
-
B1
, influence anther length among other traits. These results suggest that combinations of
Rht
-
B1
and
Ppd
-
D1
alleles control multiple pollinator traits and should be major targets of hybrid wheat breeding programs.
In terrestrial systems it is well known that the spatial patterns of grazing by herbivores can influence the structure of primary producer communities. On coral reefs, the consequences of varied ...space use by herbivores on benthic community structure are not well understood, nor are the relative influences of bottom-up (resource abundance and quality), horizontal (competition), and top-down (predation risk) factors in affecting spatial foraging behaviors of mobile herbivorous fishes. In the current study we quantified space use and feeding rates of the parrotfish, Chlorurus spilurus, across a strong gradient of food resources and predator and competitor abundance across two islands with drastically different fisheries management schemes. We found evidence that while feeding rates of this species are affected by direct interference competition and chronic predation risk, space use appears to be primarily related to exploitative competition with the surrounding herbivore community. We found no evidence that predation risk influences diurnal foraging space use in this small bodied parrotfish species. Additionally, we found the influence of chronic predation risk on feeding rates of this species to be less dramatic than the results of recent studies that used model predators to measure acute behavioral responses of other species of herbivorous fishes. Our results indicate that the non-consumptive effects of predators on the foraging behaviors of coral reef herbivores may be less dramatic than previously thought.
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