4,685 research outputs found
Tissue-specific immunoregulatory mechanisms in solid tumours
No full textTumour infiltrating lymphocytes are detected in many patients with solid tumours and it is well established in colorectal cancer (CRC) that they have a direct correlation with survival. However it is not clear why this beneficial immune response is impaired in some patients. Since T regulatory cell (Tregs) infiltrates are common to multiple solid tumour types, where their presence has been associated with poor prognosis, we hypothesized that Tregs infiltrating colorectal tumours functionally contribute to pro-tumour immunity and thereby promote colorectal tumour progression. Using multicolour flow cytometry, we characterised the immune infiltrate in blood, colorectal tumour tissue and liver metastases from patients with colorectal cancer. We found that whilst the CD4+CD2Shi fraction was significantly increased in the peripheral blood of CRC patients, the CD4+Foxp3+ fraction that represents the true T regulatory cells, were not increased in patients as compared to disease- free controls. In marked contrast, the CD4+Foxp3+ T regulatory cells were significantly increased in the colorectal tumour and in the metastatic tumour tissue (hepatic metastases) relative to the adjacent normal tissue obtained from the patients. Using an in vitro microculture system to assess T regulatory cell function, we revealed the differential suppressive ability of the T regulatory cells from different compartments such as the blood and tumour tissue and the differential susceptibility of the T effector cells to be suppressed by Tregs from these compartments. Both the blood-derived Tregs and the tumour-infiltrating Tregs suppressed proliferation of autologous tumour effectors in 7 out of 9 CRC patients and suppressed interferon-y production in 7 out of S patients. In order to determine the functional significance of Tregs in vivo, we utilised a transgenic mouse model of solid tumour development, namely, CC 1 O-TAg. We found that CD4+Foxp3+ Tregs were enriched within mouse tumours and that endogenous anti-tumour CDS+ T cell responses were critical in controlling tumour growth. Using anti-CD25 depleting antibodies that effectively deplete CD25- expressing CD4+FoxP3+ Tregs in CCIO-TAg mice at an early stage of tumour development, we found a significant reduction in tumour burden relative to control mice. This was accompanied by increased infiltration of tumours with cytotoxic CDS' T cells that were characterized by enhanced gene expression of cytotoxic molecules, granzy me A, granZ) me B and perforin. In addition, both CD4' effector T cells and CDS' cytotoxic T cells displayed up-regulation of interferon-y expression following Treg depletion, all of which culminated in increased tumour cell apoptosis. We further tested the therapeutic potential of Treg depletion in combination with chemotherapy (carboplatin) in the more clinically relevant established tumours and demonstrated significant extension of survival in tumour- bearing mice. Taken together, our data have important application in designing novel immunotherapeutic strategies that target Tregs for the treatment of cancer.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Characterization of uncertainties in atmospheric trace gas inversions using hierarchical Bayesian methods
Get PDFWe present a hierarchical Bayesian method for atmospheric trace gas
inversions. This method is used to estimate emissions of trace gases as well
as "hyper-parameters" that characterize the probability density functions
(PDFs) of the a priori emissions and model-measurement covariances. By
exploring the space of "uncertainties in uncertainties", we show that the
hierarchical method results in a more complete estimation of emissions and
their uncertainties than traditional Bayesian inversions, which rely heavily
on expert judgment. We present an analysis that shows the effect of
including hyper-parameters, which are themselves informed by the data, and
show that this method can serve to reduce the effect of errors in assumptions
made about the a priori emissions and model-measurement uncertainties. We
then apply this method to the estimation of sulfur hexafluoride (SF6)
emissions over 2012 for the regions surrounding four Advanced Global
Atmospheric Gases Experiment (AGAGE) stations. We find that improper
accounting of model representation uncertainties, in particular, can lead to
the derivation of emissions and associated uncertainties that are unrealistic
and show that those derived using the hierarchical method are likely to be
more representative of the true uncertainties in the system. We demonstrate
through this SF6 case study that this method is less sensitive to
outliers in the data and to subjective assumptions about a priori emissions
and model-measurement uncertainties than traditional methods
Potential supporting materials from polysaccharide (aero)gels
No full textVariety of approaches for the production and product design of polysaccharide aerogels will be presented. Aerogels of polysaccharides are one of the classes of light-weight open porous materials. Unlike other classical aerogels, they have randomly interconnected nanofibrillar networks and a wide range of pore sizes ranging from 2 to 1000 nm. Aerogels of cellulose, chitin, chitosan, alginate, pectin and carrageenan are of great interests in our studies [1-6]. We have designed the products physically in order to improve the transport of guest atoms or molecules. The products were also chemically modified in order to functionalize the surface adsorbing properties. These product designs can match the requirements for specific applications such as template or supporting materials for bio-composites preparation, separation and purification techniques and tissue engineering.
References
[1] K. Ganesan, A. Barowski and L. Ratke, Molecules, 2019, 24, 2688.
[2] K. Ganesan, A. Barowski, L. Ratke and B. Milow, J. Sol-Gel Sci. Technol., 2019, 89, 156-165.
[3] K. Ganesan, T. Budtova, L. Ratke, P. Gurikov, V. Baudron, I. Preibisch, P. Niemeyer, I. Smirnova and B. Milow, Materials, 2018, 11, 2144.
[4] K. Ganesan, M. Heyer, L. Ratke and B. Milow, Chem. Eur. J., 2018, 24, 19332-19340.
[5] K. Ganesan, A. Dennstedt, A. Barowski and L. Ratke, Mater. Design, 2016, 92, 345-355.
[6] K. Ganesan and L. Ratke, Soft Matter, 2014, 10, 3218-3224
Localising re-entry in atrial fibrillation: Anatomical clues to the substrate of rotors
No full textAnand N. Ganesan, Prashanthan Sander
The human homologue of unc-93 maps to chromosome 6q27 - characterisation and analysis in sporadic epithelial ovarian cancer
No full textBackground: In sporadic ovarian cancer, we have previously reported allele loss at D6S193 (62%) on chromosome 6q27, which suggested the presence of a putative tumour suppressor gene. Based on our data and that from another group, the minimal region of allele loss was between D6S264 and D6S149 (7.4 cM). To identify the putative tumour suppressor gene, we established a physical map initially with YACs and subsequently with PACs/BACs from D6S264 to D6S149. To accelerate the identification of genes, we sequenced the entire contig of approximately 1.1 Mb. Seven genes were identified within the region of allele loss between D6S264 and D6S149.Results: The human homologue of unc-93 (UNC93A) in C. elegans was identified to be within the interval of allele loss centromeric to D6S149. This gene is 24.5 kb and comprises of 8 exons. There are two transcripts with the shorter one due to splicing out of exon 4. It is expressed in testis, small intestine, spleen, prostate, and ovary. In a panel of 8 ovarian cancer cell lines, UNC93A expression was detected by RT-PCR which identified the two transcripts in 2/8 cell lines. The entire coding sequence was examined for mutations in a panel of ovarian tumours and ovarian cancer cell lines. Mutations were identified in exons 1, 3, 4, 5, 6 and 8. Only 3 mutations were identified specifically in the tumour. These included a c. 452G>A (W151X) mutation in exon 3, c.676C>T (R226X) in exon 5 and c.1225G>A(V409I) mutation in exon 8. However, the mutations in exon 3 and 5 were also present in 6% and 2% of the normal population respectively. The UNC93A cDNA was shown to express at the cell membrane and encodes for a protein of 60 kDa.Conclusions: These results suggest that no evidence for UNC93A as a tumour suppressor gene in sporadic ovarian cancer has been identified and further research is required to evaluate its normal function and role in the pathogenesis of ovarian cancer
Heterologous biosynthesis of natural product naringenin by co-culture engineering
No full textCo-culture engineering is an emerging approach for microbial biosynthesis of a variety of biochemicals. In this study, E. coli-E. coli co-cultures were developed for heterologous biosynthesis of the natural product naringenin. The co-cultures were composed of two independent E. coli strains dedicated to functional expression of different portions of the biosynthetic pathway, respectively. The co-culture biosynthesis was optimized by investigating the effect of carbon source, E. coli strain selection, timing of IPTG induction and the inoculation ratio between the co-culture strains. Compared with the monoculture strategy, the utilization of the designed co-cultures significantly improved the naringenin production, largely due to the reduction of metabolic stress, employment of proper hosts for improving pathway enzyme activities, and flexible adjustment of the relative biosynthetic strength between the coculture strains. The findings of this study extend the applicability of co-culture engineering in complex natural product biosynthesis.Peer reviewe
Clinical and radiological recurrence after childhood arterial ischemic stroke
No full textBackground: Data on rates and risk factors for clinical and radiological recurrence of childhood arterial ischemic stroke (AIS) might inform secondary prevention strategies.
Methods and Results: Consecutive Great Ormond Street Hospital patients with first AIS were identified retrospectively (1978–1990) and prospectively (1990–2000). Patients underwent repeat neuroimaging at the time of clinical recurrence or, if asymptomatic, at least 1 year after AIS. Cox and logistic regression analyses were used to explore the relationships between risk factors and clinical and radiological recurrence, respectively. A total of 212 patients were identified, of whom 97 had another prior diagnosis. Seventy-nine children had a clinical recurrence (29 strokes, 46 transient ischemic attacks [TIAs], 4 deaths with reinfarction 1 day to 11.5 years (median 267 days) later); after 5 years, 59% (95% confidence interval, 51% to 67%) were recurrence free. Moyamoya on angiography and low birth weight were independently associated with clinical recurrence in the whole group. Genetic thrombophilia was associated with clinical recurrence in previously healthy patients, independent of the presence of moyamoya. Sixty of 179 patients who had repeat neuroimaging had radiological reinfarction, which was clinically silent in 20. Previous TIA, bilateral infarction, prior diagnosis (specifically immunodeficiency), and leukocytosis were independently associated with reinfarction. Previous TIA and leukocytosis were also independently associated with clinically silent reinfarction.
Conclusions: Clinical and radiological recurrence are common after childhood AIS. The risk of clinical recurrence is increased in children with moyamoya and, in previously healthy patients, in those with genetic thrombophilia. Preexisting pathology, including immunodeficiency, and persistent leukocytosis are risk factors for radiological recurrence, which suggests a potential role for chronic infection
Mechanisms of ischaemic stroke after chickenpox
No full textIschaemic stroke is a recognised complication of chickenpox. Seven cases of ischaemic stroke in children after recent varicella infection are discussed in detail to emphasise that there are several mechanisms by which this may arise.</p
Noonan syndrome and moyamoya
No full textWe report a patient with Noonan syndrome and asymptomatic cardiac disease (supravalvular aortic stenosis and pulmonary valvular stenosis) who had frequent transient ischemic attacks. Bilateral moyamoya was evident; in addition, he manifested activated protein C resistance and was heterozygous for the factor V Leiden mutation. Anticoagulation abolished his episodes and, despite extensive cerebrovascular disease, he has no permanent neurologic deficits. The association between Noonan syndrome and moyamoya has not previously been described. Disruption of vascular development in prenatal life may have resulted in both cardiac and cerebrovascular disease in this child.</p
Sirodotia assamica Necchi, N. L. Rossignolo, F. Yasmin, J. A. West & Ganesan
No full text<i>Sirodotia assamica</i> Necchi, N.L.Rossignolo, F.Yasmin, J.A.West & Ganesan (Fig. 4 A-E) <p> <i>Phytotaxa</i> 437: 125 (2020).</p> <p>TYPE. — F. Yasmin, 25.II.2019 (holo-, SJRP [SJRP 32584]).</p> <p>TYPE LOCALITY. — India, Assam, Nagaon District, Chapanalla; 26°19’13.7”N, 92°10’16.5”E.</p> <p>ADDITIONAL SPECIMENS EXAMINED. — SJRP 32583, SJRP 32585 (Appendix 1).</p> <p>DISTRIBUTION. — Asia, India (northeastern).</p> <p> REPRESENTATIVE DNA SEQUENCES. — COI-5P (MN508239, MN508240) and <i>rbc</i> L (MN496129, MN496130).</p> <i>Description</i> <p>Plants dioecious or monoecious; whorls 400-665 µm in diameter; primary fascicles, 6-11(-12) cells; proximal cells cylindrical or ellipsoidal; distal cells obovoidal or ellipsoidal; secondary fascicles abundant, covering the entire internode; spermatangia spherical, arranged in clusters on primary or secondary fascicles, 6-8 µm in diameter; carpogonial branches straight or slightly curved, short, composed of 1-5(-6) discor barrel shaped cells; arising from periaxial cells of primary fascicles, 7-23 µm in length; carpogonia with sessile, elongate cylindrical, ellipsoidal or lageniform trichogynes, 37-64 µm in length, 10-14(-16) µm in diameter; gonimoblast initial developing from the protuberant side of the carpogonium; gonimoblast filaments with erect branches of 1-4 cells; carposporangia obovoidal, 11-14 µm in length, 6-8 µm in diameter.</p> <i>Remarks</i> <p> A distinguishing feature of <i>Sirodotia assamica</i> is the occurrence of spermatangia arranged in clusters, thus far not confirmed for any other species of <i>Sirodotia.</i> It is most closely comparable to <i>S. delicatula</i> based on other vegetative and reproductive characteristics and its occurrence in or near India (Appendix 6). <i>Sirodotia assamica</i> differs from <i>S. delicatula</i> in having spermatangia in clusters, larger whorls (400-665 µm versus 137-433 µm in diameter), distal fascicles cells ellipsoidal or obovoid (L/D 1.3-2.1) in <i>S. assamica</i> and subspherical or obovoid (L/D 1.1-1.7) in <i>S. delicatula</i> and the known geographic distribution restricted to northeastern India.</p>Published as part of <i>Rossignolo, Natalia L., Vis, Morgan L., Paiano, Monica O., Eloranta, Pertti, West, John A., Ganesan, E. K., Yasmin, Farishta, Lim, Phaik-Eem & Necchi, Orlando Jr, 2021, Revision of the genus Sirodotia Kylin (Batrachospermales, Rhodophyta) with description of four new species, pp. 93-127 in Cryptogamie, Algologie 20 (8)</i> on page 102, DOI: 10.5252/cryptogamie-algologie2021v42a8, <a href="http://zenodo.org/record/7828571">http://zenodo.org/record/7828571</a>
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