Submicron fibers as a morphological improvement of amorphous zirconium oxide particles and their utilization in antimonate (Sb(v)) removal

Mesoporous and large surface area zirconium oxide aggregate granules with good adsorption properties were synthesized using a simple precipitation method. Since utilization of these small and fragile particles is considered rather difficult in larger scale column operation, the product was formed into a fibrous form to improve its usability. The submicron fibers were obtained from an optimized electroblowing synthesis that resulted in elastic and uniform fibers with a tetragonal structure and high length-to-diameter ratio. In antimonate (Sb(v)) adsorption experiments, the higher calcination temperature (350 °C) of the fibers did not seem to decrease the Sb(v) adsorption capacity excessively since the high theoretical adsorption capacities were 113 mg g⁻¹ and 58 mg g⁻¹ for the aggregate and fibers, respectively. Both materials had fast kinetics, fibers being faster in the beginning of the reaction. Moreover, both materials offered efficient Sb(v) removal in the studied pH range from 1 to 11 by reaching over 99.9% adsorption in the optimal pH range. X-ray absorption near edge spectroscopy (XANES) revealed that Sb(v) stays as pentavalent antimony after being adsorbed by these materials and based on the isoelectric point shifts in the zeta potential measurement, adsorption occurs mainly by an inner-sphere complexation reaction. Finally, our study showed that pressure buildup in a flow-through column packed with zirconium oxide fibers was significantly lower than in a column packed with aggregates. Thus, zirconium oxide aggregates can be formed into submicron fibers with enhanced column operation properties without a too large compromise in the adsorption properties.

Zirconium oxide was formed into submicron fibers to improve the Sb(v) separation performance compared to a conventional aggregate material.     

Increasing circulating levels of Tenascin C in response to the Wingate anaerobic test

Aim

Tenascin C (TNC) is a large extracellular matrix glycoprotein. It is involved in development and upregulated both during tissue repair and in several pathological conditions, including cardiovascular disease. Extracellular matrix proteins play a role in promoting exercise responses, leading to adaptation, regeneration, and repair. The main goal of this study was to investigate whether a short anaerobic effort leads to increased levels of TNC in serum.

Methods

Thirty-nine healthy men performed a Wingate test followed by a muscle biopsy. Myoblasts were isolated from the muscle biopsies and differentiated to myotubes ex vivo. TNC RNA was quantified in the biopsies, myotubes and myoblasts using RNA sequencing. Blood samples were drawn before and 5 min after the Wingate test. Serum TNC levels were measured using enzyme-linked immunosorbent assay.

Results

After the Wingate test, serum TNC increased on average by 23% [15–33], median [interquartile range]; P_Wilcoxon < 0.0001. This increase is correlated with peak power output and power drop, but not with VO_2max. TNC RNA expression is higher in myoblasts and myotubes compared to skeletal muscle tissue.

Conclusion

TNC is secreted systemically as a response to the Wingate anaerobic test in healthy males. The response was positively correlated with peak power and power drop, but not with VO_2max which implicates a relation to mechanical strain and/or blood flow. With higher expression in undifferentiated myoblast cells than muscle tissue, it is likely that TNC plays a role in muscle tissue remodelling in humans. Our findings open for research on how TNC contributes to exercise adaptation.     

Theiler’s virus infection provokes the overexpression of genes coding for the chemokine Ip10 (CXCL10) in SJL/J murine astrocytes,which can be inhibited by modulators of estrogen receptors

Theiler’s murine encephalomyelitis virus (TMEV) induces demyelination in susceptible strains of mice (SJL/J) through an immunopathological process that is mediated by CD4⁺ Th1 T cell. These T cells are chemoattracted to the central nervous system by chemokines. Hence, in this study, we focused on the production of the chemokine “interferon-gamma-inducible protein 10 kDa,” or IP-10/CXCL10, by cultured SJL/J mouse astrocytes infected with the BeAn strain of TMEV and its capacity to attract activated T cells. The analysis of the whole murine genome by DNA hybridization with cRNAs from mock- and TMEV-infected cultures revealed the upregulation of six sequences that potentially encode for CXCL10. This increased CXCL10 expression was validated by PCR and qPCR. The presence of this chemokine was further demonstrated by enzyme-linked immunoassay (ELISA). Significantly, astrocytes from BALB/c mice, a strain resistant to demyelination, did not produce CXCL10. The secreted CXCL10 was biologically active, inducing chemoattraction of activated lymphocytes. The inflammatory cytokines, IL-1α, IFN-γ, and TNF-α, were strong inducers of CXCL10 in astrocytes. Serum from TMEV-infected SJL/J but not BALB/c mice contains CXCL10, the levels of which peak at the onset of the clinical disease. Finally, this in vitro inflammation model was fully inhibited by 17β-estradiol and four selective estrogen receptor modulators, as demonstrated by ELISA and qPCR.     

Bayesian Latent Variable Collapsing Model for Detecting Rare Variant Interaction Effect in Twin Study

By analyzing more next‐generation sequencing data, researchers have affirmed that rare genetic variants are widespread among populations and likely play an important role in complex phenotypes. Recently, a handful of statistical models have been developed to analyze rare variant (RV) association in different study designs. However, due to the scarce occurrence of minor alleles in data, appropriate statistical methods for detecting RV interaction effects are still difficult to develop. We propose a hierarchical Bayesian latent variable collapsing method (BLVCM), which circumvents the obstacles by parameterizing the signals of RVs with latent variables in a Bayesian framework and is parameterized for twin data. The BLVCM can tackle nonassociated variants, allow both protective and deleterious effects, capture SNP‐SNP synergistic effect, provide estimates for the gene level and individual SNP contributions, and can be applied to both independent and various twin designs. We assessed the statistical properties of the BLVCM using simulated data, and found that it achieved better performance in terms of power for interaction effect detection compared to the Granvil and the SKAT. As proof of practical application, the BLVCM was then applied to a twin study analysis of more than 20,000 gene regions to identify significant RVs associated with low‐density lipoprotein cholesterol level. The results show that some of the findings are consistent with previous studies, and we identified some novel gene regions with significant SNP–SNP synergistic effects.     

Terminal Deletion of 11q with Significant Late-Onset Combined Immune Deficiency

Purpose

We report a 45-year old female adult patient with terminal deletion of chromosome 11q resulting in clinical phenotype of late-onset combined immunodeficiency.

Methods

We describe the clinical phenotype and discuss the similarities between our patient and those with chromosome 22q11.2 deletion syndrome. Immunological evaluation included immunoglobulin levels, vaccine responses, number and function of T, NK and B cell subsets and comparative genomic hybridization test of blood and fibroblasts.

Results

The patient suffered from recurrent pneumococcal pneumonia and genital and cutaneous condylomas. She had a history of learning difficulties, dysmorphic features, autoimmune thyroiditis, chronic thrombocytopenia and severe asthma. We found Paris-Trousseau type thrombocytopenia, B-, T- and NK-lymphopenia, T cell oligoclonality and IgG hypogammaglobulinemia with inability to respond to pneumococcal polysaccharide, tetanus and diphtheria vaccines. A terminal deletion of chromosome 11q compatible with partial Jacobsen syndrome was found.

Conclusions

This confirms Jacobsen syndrome as a chromosome deletion syndrome able to cause combined immunodeficiency.     

Long-term outcomes after ascending aortic replacement and aortic root replacement for type A aortic dissection

 Open in a separate windowOBJECTIVESWe investigated whether the selective use of supracoronary ascending aorta replacement achieves late outcomes comparable to those of aortic root replacement for acute Stanford type A aortic dissection (TAAD).METHODSPatients who underwent surgery for acute type A aortic dissection from 2005 to 2018 at the Helsinki University Hospital, Finland, were included in this analysis. Late mortality was evaluated with the Kaplan–Meier method and proximal aortic reoperation, i.e. operation on the aortic root or aortic valve, with the competing risk method.RESULTSOut of 309 patients, 216 underwent supracoronary ascending aortic replacement and 93 had aortic root replacement. At 10 years, mortality was 33.8% after aortic root replacement and 35.2% after ascending aortic replacement (P = 0.806, adjusted hazard ratio 1.25, 95% confidence interval, 0.77–2.02), and the cumulative incidence of proximal aortic reoperation was 6.0% in the aortic root replacement group and 6.2% in the ascending aortic replacement group (P = 0.65; adjusted subdistributional hazard ratio 0.53, 95% confidence interval 0.15–1.89). Among 71 propensity score matched pairs, 10-year survival was 34.4% after aortic root replacement and 36.2% after ascending aortic replacement surgery (P = 0.70). Cumulative incidence of proximal aortic reoperation was 7.0% after aortic root replacement and 13.0% after ascending aortic replacement surgery (P = 0.22). Among 102 patients with complete imaging data [mean follow-up, 4.7 (3.2) years], the estimated growth rate of the aortic root diameter was 0.22 mm/year, that of its area 7.19 mm²/year and that of its perimeter 0.43 mm/year.CONCLUSIONSWhen stringent selection criteria were used to determine the extent of proximal aortic reconstruction, aortic root replacement and ascending aortic replacement for type A aortic dissection achieved comparable clinical outcomes.     

Copolymers of bipyridinium and metal (Zn & Ni) porphyrin derivatives; theoretical insights and electrochemical activity towards CO2

This study reports the electropolymerization of novel keto functionalized octaethyl metal porphyrins (Zn²⁺ and Ni²⁺) in the presence of 4,4′-bipyridine (4,4′-bpy) as a bridging nucleophile. The polymer films were characterized by electrochemical, spectroscopic (UV-Vis, XPS, FT-IR and Raman spectroscopy) and imaging (AFM and SEM) techniques. The absorption and electronic spectra confirm the presence of both porphyrin and 4,4′-bipyridine units in the film. The surface morphology reveals homogeneous film deposition with average roughness values of approx. 8 nm. The theoretical studies performed offered insights into the interplay of different metal centres (Zn²⁺ and Ni²⁺) and the keto functionality of the porphyrin unit in the formation of copolymer films. The electrochemical interaction of polymer films with CO₂ suggests a reversible trap and release of CO₂ with low energy barriers for both the polymers.

Electropolymerization of keto functionalized porphyrins and 4,4′-bipyridine.     

Noncoding RET variants explain the strong association with Hirschsprung disease in patients without rare coding sequence variant

The pathogenesis of Hirschsprung disease is complex. Although the RET proto-oncogene is the most frequently affected gene in Hirschsprung disease, rare coding sequence variants explain only a small part of Hirschsprung disease cases. We aimed to assess the genetic background of Hirschsprung disease using a genome-wide association analysis combined with sequencing all RET exons in samples from 105 Hirschsprung disease cases (30 familial and 75 sporadic) and 386 controls.As expected, variants in or near RET showed the strongest overall association with Hirschsprung disease and the most statistically significant association was observed when using a recessive genetic model (rs2435357, NC_000010.10:g.43582056T?>?C; genotype TT, OR?=?17.31, P?=?1.462?×?10^?21). Previously published associations in variants in SEMA (rs11766001, NC_000007.13:g.84145202A?>?C; allele C, OR?=?2.268, P?=?0.009533) and NRG1 (rs4541858, NC_000008.10:g.32410309A?>?G; allele G, OR?=?1.567, P?=?0.015; rs7835688, NC_000008.10:g.32411499G?>?C; allele C, OR?=?1.567, P?=?0.015) were also replicated in the genome-wide association analysis. Sequencing revealed a total of 12 exonic RET rare variants. Of these, eight amino acid changing rare variants and two frameshift variants caused or possibly caused Hirschsprung disease.Only a minority of the Hirschsprung disease cases (9/30 familial; 7/75 sporadic) carried one of the rare variants. Excluding the rare variant carriers from the genome-wide association analysis did not appreciably change the association of rs2435357 with Hirschsprung disease. We estimate that approximately two thirds of the sporadic cases may be statistically attributed to the recessive action of the common non-coding RET variants. Thus, even though most cases do not carry rare RET variants, combinations of rare variants and the common non-coding RET variant cause the majority of the cases in our population.     

Spatial aspects of oncogenic signalling determine the response to combination therapy in slice explants from Kras‐driven lung tumours

A key question in precision medicine is how functional heterogeneity in solid tumours informs therapeutic sensitivity. We demonstrate that spatial characteristics of oncogenic signalling and therapy response can be modelled in precision‐cut slices from Kras‐driven non‐small‐cell lung cancer with varying histopathologies. Unexpectedly, profiling of in situ tumours demonstrated that signalling stratifies mostly according to histopathology, showing enhanced AKT and SRC activity in adenosquamous carcinoma, and mitogen‐activated protein kinase (MAPK) activity in adenocarcinoma. In addition, high intertumour and intratumour variability was detected, particularly of MAPK and mammalian target of rapamycin (mTOR) complex 1 activity. Using short‐term treatment of slice explants, we showed that cytotoxic responses to combination MAPK and phosphoinositide 3‐kinase–mTOR inhibition correlate with the spatially defined activities of both pathways. Thus, whereas genetic drivers determine histopathology spectra, histopathology‐associated and spatially variable signalling activities determine drug sensitivity. Our study is in support of spatial aspects of signalling heterogeneity being considered in clinical diagnostic settings, particularly to guide the selection of drug combinations. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.