ORCID Profile
0000-0002-9502-1749
Current Organisations
Mohamed bin Zayed University of Artificial Intelligence
,
Australian National University
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Springer Science and Business Media LLC
Date: 11-2016
Publisher: Portland Press Ltd.
Date: 30-11-2017
DOI: 10.1042/ETLS20170042
Abstract: Microbial communities of the urogenital tract have long been recognised to play an important role in disease states. A revolution in methodological approaches is permitting the assessment of complex urogenital tract microbiota–host interactions and the metabolic and protein milieu of the mucosal interface. There is now great potential for significant advances in biomarker discovery and disease risk stratification, and for the elucidation of mechanisms underpinning the microbial community dynamics involved in urogenital tract pathology. Microbiota–host interactions in the female genital tract have a particular significance, because unlike in the male, there is direct communication between the external genitalia, the uterus and the peritoneal cavity. This review examines the microbial community composition at differing sites of the female urogenital tract and its relationship with health and disease. Key factors involved in the modulation of vaginal microbiome stability and structure, such as endocrine, immune and inflammatory pathways, are considered in the context of a woman's life cycle and disease pathogenesis.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2022
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 09-2017
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2022
Publisher: Association for Computing Machinery (ACM)
Date: 31-01-2022
DOI: 10.1145/3505244
Abstract: Astounding results from Transformer models on natural language tasks have intrigued the vision community to study their application to computer vision problems. Among their salient benefits, Transformers enable modeling long dependencies between input sequence elements and support parallel processing of sequence as compared to recurrent networks, e.g., Long short-term memory. Different from convolutional networks, Transformers require minimal inductive biases for their design and are naturally suited as set-functions. Furthermore, the straightforward design of Transformers allows processing multiple modalities (e.g., images, videos, text, and speech) using similar processing blocks and demonstrates excellent scalability to very large capacity networks and huge datasets. These strengths have led to exciting progress on a number of vision tasks using Transformer networks. This survey aims to provide a comprehensive overview of the Transformer models in the computer vision discipline. We start with an introduction to fundamental concepts behind the success of Transformers, i.e., self-attention, large-scale pre-training, and bidirectional feature encoding. We then cover extensive applications of transformers in vision including popular recognition tasks (e.g., image classification, object detection, action recognition, and segmentation), generative modeling, multi-modal tasks (e.g., visual-question answering, visual reasoning, and visual grounding), video processing (e.g., activity recognition, video forecasting), low-level vision (e.g., image super-resolution, image enhancement, and colorization), and three-dimensional analysis (e.g., point cloud classification and segmentation). We compare the respective advantages and limitations of popular techniques both in terms of architectural design and their experimental value. Finally, we provide an analysis on open research directions and possible future works. We hope this effort will ignite further interest in the community to solve current challenges toward the application of transformer models in computer vision.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 10-2016
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.MCE.2015.11.012
Abstract: Oxytocin (OT) plays an important role in the onset of human labour by stimulating uterine contractions and promoting prostaglandin/inflammatory cytokine synthesis in amnion via oxytocin receptor (OTR) coupling. The OTR-antagonist, Atosiban, is widely used as a tocolytic for the management of acute preterm labour. We found that in primary human amniocytes, Atosiban (10 μM) signals via PTX-sensitive Gαi to activate transcription factor NF-κB p65, ERK1/2, and p38 which subsequently drives upregulation of the prostaglandin synthesis enzymes, COX-2 and phospho-cPLA2 and excretion of prostaglandins (PGE2) (n = 6 p < 0.05, ANOVA). Moreover, Atosiban treatment increased expression and excretion of the inflammatory cytokines, IL-6 and CCL5. We also showed that OT-simulated activation of NF-κB, ERK1/2, and p38 and subsequent prostaglandin and inflammatory cytokine synthesis is via Gαi-2 and Gαi-3 but not Gαq, and is not inhibited by Atosiban. Activation or exacerbation of inflammation is not a desirable effect of tocolytics. Therefore therapeutic modulation of the OT/OTR system for clinical management of term reterm labour should consider the effects of differential G-protein coupling of the OTR and the role of OT or selective OTR agonists/antagonists in activating proinflammatory pathways.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 07-2016
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2022
Publisher: American Association for the Advancement of Science (AAAS)
Date: 03-08-2016
DOI: 10.1126/SCITRANSLMED.AAG1026
Abstract: Cervical cerclage using braided suture material disrupts vaginal microbial stability and increases inflammation.
Publisher: American Chemical Society (ACS)
Date: 04-10-2017
DOI: 10.1021/ACS.JPROTEOME.7B00568
Abstract: Lower urinary tract symptoms (LUTS), including urinary incontinence, urgency and nocturia, affect approximately half of women worldwide. Current diagnostic methods for LUTS are invasive and costly, while available treatments are limited by side effects leading to poor patient compliance. In this study, we aimed to identify urine metabolic signatures associated with LUTS using proton nuclear magnetic resonance (
Publisher: Wiley
Date: 09-2015
Abstract: To assess the effect of gestational age (GA) and cervical length (CL) measurements at transvaginal ultrasound (TVUS) in the prediction of preterm birth in twin pregnancy. In idual patient data (IPD) meta-analysis. International multicentre study. Asymptomatic twin pregnancy. MEDLINE and EMBASE searches were performed and IPD obtained from authors of relevant studies. Multinomial logistic regression analysis determined probabilities for birth at ≤28(+0) , 28(+1) to 32(+0) , 32(+1) to 36(+0) , and ≥36(+1) weeks as a function of GA at screening and CL measurements. Predicted probabilities for preterm birth at ≤28(+0) , 28(+1) to 32(+0) , and 32(+1) to 36(+0) . A total of 6188 CL measurements were performed on 4409 twin pregnancies in 12 studies. Both GA at screening and CL had a significant and non-linear effect on GA at birth. The best prediction of birth at ≤28(+0) weeks was provided by screening at ≤18(+0) weeks (P < 0.001), whereas the best prediction of birth between 28(+1) and 36(+0) weeks was provided by screening at ≥24(+0) weeks (P < 0.001). Negative prediction value of 100% for birth at ≤28(+0) weeks is achieved at CL 65 mm and 43 mm at ultrasound GA at ≤18(+0) weeks and at 22(+1) to 24(+0) weeks, respectively. In twin pregnancies, prediction of preterm birth depends on both CL and the GA at screening. When CL is 22(+0) weeks is most predictive of delivery at 28(+1) to 36(+0) weeks. In twins, we recommend CL screening in twins to commence from ≤18(+0) weeks. An in idual patient meta-analysis assessing gestation and CL in the prediction of preterm birth in twins.
Publisher: Springer Science and Business Media LLC
Date: 17-11-2015
DOI: 10.1038/SREP16865
Abstract: Persistent infection with oncogenic Human Papillomavirus (HPV) is necessary for cervical carcinogenesis. Although evidence suggests that the vaginal microbiome plays a functional role in the persistence or regression of HPV infections, this has yet to be described in women with cervical intra-epithelial neoplasia (CIN). We hypothesised that increasing microbiome ersity is associated with increasing CIN severity. llumina MiSeq sequencing of 16S rRNA gene licons was used to characterise the vaginal microbiota of women with low-grade squamous intra-epithelial lesions (LSIL n = 52), high-grade (HSIL n = 92), invasive cervical cancer (ICC n = 5) and healthy controls (n = 20). Hierarchical clustering analysis revealed an increased prevalence of microbiomes characterised by high- ersity and low levels of Lactobacillus spp. (community state type-CST IV) with increasing disease severity, irrespective of HPV status (Normal = 2/20,10% LSIL = 11/52,21% HSIL = 25/92,27% ICC = 2/5,40%). Increasing disease severity was associated with decreasing relative abundance of Lactobacillus spp. The vaginal microbiome in HSIL was characterised by higher levels of Sneathia sanguinegens (P 0.01), Anaerococcus tetradius (P 0.05) and Peptostreptococcus anaerobius (P 0.05) and lower levels of Lactobacillus jensenii (P 0.01) compared to LSIL. Our results suggest advancing CIN disease severity is associated with increasing vaginal microbiota ersity and may be involved in regulating viral persistence and disease progression.
Publisher: Springer International Publishing
Date: 2021
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 03-2022
Publisher: Springer Science and Business Media LLC
Date: 24-04-2020
DOI: 10.1038/S41467-020-15856-Y
Abstract: Emerging evidence suggests associations between the vaginal microbiota (VMB) composition, human papillomavirus (HPV) infection, and cervical intraepithelial neoplasia (CIN) however, causal inference remains uncertain. Here, we use bacterial DNA sequencing from serially collected vaginal s les from a cohort of 87 adolescent and young women aged 16–26 years with histologically confirmed, untreated CIN2 lesions to determine whether VMB composition affects rates of regression over 24 months. We show that women with a Lactobacillus- dominant microbiome at baseline are more likely to have regressive disease at 12 months. Lactobacillus spp. depletion and presence of specific anaerobic taxa including Megasphaera, Prevotella timonensis and Gardnerella vaginalis are associated with CIN2 persistence and slower regression. These findings suggest that VMB composition may be a future useful biomarker in predicting disease outcome and tailoring surveillance, whilst it may offer rational targets for the development of new prevention and treatment strategies.
Publisher: Springer International Publishing
Date: 2019
Publisher: Springer International Publishing
Date: 2019
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2021
Publisher: Springer Science and Business Media LLC
Date: 13-06-2016
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 08-2018
Publisher: Oxford University Press (OUP)
Date: 10-10-2019
Abstract: In our earlier work, we found that intrauterine (i.u.) and intraperitoneal (i.p.) injection of LPS (10-μg serotype 0111:B4) induced preterm labor (PTL) with high pup mortality, marked systemic inflammatory response and hypotension. Here, we used both i.u. and i.p. LPS models in pregnant wild-type (wt) and CCR2 knockout (CCR2−/−) mice on E16 to investigate the role played by the CCL2/CCR2 system in the response to LPS. Basally, lower numbers of monocytes and macrophages and higher numbers of neutrophils were found in the myometrium, placenta, and blood of CCR2−/− vs. wt mice. After i.u. LPS, parturition occurred at 14 h in both groups of mice. At 7 h post-injection, 70% of wt pups were dead vs. 10% of CCR2−/− pups, but at delivery 100% of wt and 90% of CCR2−/− pups were dead. Myometrial and placental monocytes and macrophages were generally lower in CCR2−/− mice, but this was less consistent in the circulation, lung, and liver. At 7 h post-LPS, myometrial ERK activation was greater and JNK and p65 lower and the mRNA levels of chemokines were higher and of inflammatory cytokines lower in CCR2−/− vs. wt mice. Pup brain and placental inflammation were similar. Using the IP LPS model, we found that all measures of arterial pressure increased in CCR2−/− but declined in wt mice. These data suggest that the CCL2/CCR2 system plays a critical role in the cardiovascular response to LPS and contributes to pup death but does not influence the onset of inflammation-induced PTL.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 11-2018
Publisher: Springer Science and Business Media LLC
Date: 24-01-2018
Publisher: Bioscientifica
Date: 08-2014
DOI: 10.1530/REP-13-0587
Abstract: Preterm birth occurs in 10–12% of pregnancies and is the primary cause of neonatal mortality and morbidity. Tocolytic therapies have long been the focus for the prevention of preterm labour, yet they do not significantly improve neonatal outcome. A direct causal link exists between infection-induced inflammation and preterm labour. As inflammation and infection are independent risk factors for poor neonatal outcome, recent research focus has been shifted towards exploring the potential for anti-inflammatory strategies. Nuclear factor kappa B (NFκB) is a transcription factor that controls the expression of many labour-associated genes including PTGS2 ( COX2 ), prostaglandins ( PG s) and the oxytocin receptor ( OXTR ) as well as key inflammatory genes. Targeting the inhibition of NFκB is therefore an attractive therapeutic approach for both the prevention of preterm labour and for reducing neonatal exposure to inflammation. While PGs are considered to be pro-labour and pro-inflammatory, the cyclopentenone PG 15-deoxy-Δ 12,14 PGJ 2 (15d-PGJ 2 ) exhibits anti-inflammatory properties via the inhibition of NFκB in human amniocytes, myocytes and peripheral blood mononuclear cells in vitro . 15d-PGJ 2 also delays inflammation-induced preterm labour in the mouse and significantly increases pup survival. This review examines the current understanding of inflammation in the context of labour and discusses how anti-inflammatory PGs may hold promise for the prevention of preterm labour and improved neonatal outcome.
Publisher: Springer Science and Business Media LLC
Date: 19-01-2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2018
DOI: 10.1161/HYPERTENSIONAHA.118.11092
Abstract: Preecl sia and fetal growth restriction during pregnancy are associated with increased risk of maternal cardiovascular disease later in life. It is unclear whether this association is causal or driven by similar antecedent risk factors. Clarification requires recruitment before conception which is methodologically difficult with high attrition rates and loss of outcome numbers to nonconception/miscarriage. Few prospective studies have, therefore, been adequately powered to address these questions. We recruited 530 healthy women (mean age: 35.0 years) intending to conceive and assessed cardiac output, cardiac index, stroke volume, total peripheral resistance, mean arterial pressure, and heart rate before pregnancy. Participants were followed to completion of subsequent pregnancy with repeat longitudinal assessments. Of 356 spontaneously conceived pregnancies, 15 (4.2%) were affected by preecl sia and fetal growth restriction. Women who subsequently developed preecl sia/fetal growth restriction had lower preconception cardiac output (4.9 versus 5.8 L/min P =0.002) and cardiac index (2.9 versus 3.3 L/min per meter 2 P =0.031) while mean arterial pressure (87.1 versus 82.3 mm Hg P =0.05) and total peripheral resistance (1396.4 versus 1156.1 dynes sec cm − 5 P .001) were higher. Longitudinal trajectories for cardiac output and total peripheral resistance were similar between affected and healthy pregnancies, but the former group showed a more exaggerated fall in mean arterial pressure in the first trimester, followed by a steeper rise and a steeper fall to postpartum values. Significant relationships were observed between cardiac output, total peripheral resistance, and mean arterial pressure and gestational epoch. We conclude that in healthy women, an altered prepregnancy hemodynamic phenotype is associated with the subsequent development of preecl sia/fetal growth restriction.
Publisher: Oxford University Press (OUP)
Date: 19-10-2016
Publisher: Wiley
Date: 10-03-2019
Publisher: Elsevier
Date: 2016
Publisher: Wiley
Date: 08-08-2019
Abstract: Women with congenital absolute uterine factor infertility (AUFI) often need vaginal restoration to optimise sexual function. Given their lack of procreative ability, little consideration has previously been given to the resultant vaginal microbiome (VM). Uterine transplantation (UTx) now offers the opportunity to restore these women's reproductive potential. The structure of the VM is associated with clinical and reproductive implications that are intricately intertwined with the process of UTx. Consideration of how vaginal restoration methods impact VM is now warranted and assessment of the VM in future UTx procedures is essential to understand the interrelation of the VM and clinical and reproductive outcomes. TWEETABLE ABSTRACT: The vaginal microbiome has numerous implications for clinical and reproductive outcomes in the context of uterine transplantation.
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.YMETH.2018.04.022
Abstract: There is increasing appreciation of the role that vaginal microbiota play in health and disease throughout a woman's lifespan. This has been driven partly by molecular techniques that enable detailed identification and characterisation of microbial community structures. However, these methods do not enable assessment of the biochemical and immunological interactions between host and vaginal microbiota involved in pathophysiology. This review examines our current knowledge of the relationships that exist between vaginal microbiota and the host at the level of the vaginal mucosal interface. We also consider methodological approaches to microbiomic, immunologic and metabolic profiling that permit assessment of these interactions. Integration of information derived from these platforms brings the potential for biomarker discovery, disease risk stratification and improved understanding of the mechanisms regulating vaginal microbial community dynamics in health and disease.
Publisher: Springer Nature Switzerland
Date: 15-10-2023
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 11-2022
Publisher: Elsevier BV
Date: 03-2015
DOI: 10.1016/J.MCE.2014.11.008
Abstract: Human labour, both at term and preterm, is preceded by NF-κB-mediated inflammatory activation within the uterus, leading to myometrial activation, fetal membrane remodelling and cervical ripening. The stimuli triggering inflammatory activation in normal human parturition are not fully understood. We show that the neurohypophyseal peptide, oxytocin (OT), activates NF-κB and stimulates downstream inflammatory pathways in human gestational tissues. OT stimulation (1 pM-100 nM) specifically via its receptor (OTR) in human myometrial and amnion primary cells led to MAPK and NF-κB activation within 15 min and maximal p65-subunit nuclear translocation within 30 min. Both in human myometrium and amnion, OT-induced activation of the canonical NF-κB pathway upregulated key inflammatory labour-associated genes including IL-8, CCL5, IL-6 and COX-2. IKKβ inhibition (TPCA1 10 µM) suppressed OT-induced NF-κB-p65 phosphorylation, whereas p65-siRNA knockdown reduced basal and OT-induced COX-2 levels in myometrium and amnion. In both gestational tissues, MEK1/2 (U0126 10 µM) or p38 inhibition (SB203580 10 µM) suppressed OT-induced COX-2 expression, but OT-induced p65-phosphorylation was only inhibited in amnion, suggesting OT activation of NF-κB in amnion is MAPK-dependent. Our data provide new insight into the OT/OTR system in human parturition and suggest that its therapeutic modulation could be a strategy for regulating both contractile and inflammatory pathways in the clinical context of term reterm labour.
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9CC05607F
Abstract: Low-cost detection of miRNA biomarkers from maternal blood is achieved via a highly sequence-specific templated reaction on nitrocellulose paper strips to enable early prediction of preterm birth in a minimally invasive manner.
Publisher: Elsevier BV
Date: 05-2018
Publisher: Springer Science and Business Media LLC
Date: 11-03-2015
DOI: 10.1038/SREP08988
Abstract: The composition and structure of the pregnancy vaginal microbiome may influence susceptibility to adverse pregnancy outcomes. Studies on the pregnant vaginal microbiome have largely been limited to Northern American populations. Using MiSeq sequencing of 16S rRNA gene licons, we characterised the vaginal microbiota of a mixed British cohort of women (n = 42) who experienced uncomplicated term delivery and who were s led longitudinally throughout pregnancy (8–12, 20–22, 28–30 and 34–36 weeks gestation) and 6 weeks postpartum. We show that vaginal microbiome composition dramatically changes postpartum to become less Lactobacillus spp. dominant with increased alpha- ersity irrespective of the community structure during pregnancy and independent of ethnicity. While the pregnancy vaginal microbiome was characteristically dominated by Lactobacillus spp. and low alpha- ersity, unlike Northern American populations, a significant number of pregnant women this British population had a L. jensenii -dominated microbiome characterised by low alpha- ersity. L. jensenii was predominantly observed in women of Asian and Caucasian ethnicity whereas L. gasseri was absent in s les from Black women. This study reveals new insights into biogeographical and ethnic effects upon the pregnancy and postpartum vaginal microbiome and has important implications for future studies exploring relationships between the vaginal microbiome, host health and pregnancy outcomes.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 12-2022
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2020
Publisher: Oxford University Press (OUP)
Date: 14-11-2017
Abstract: The role of progesterone (P4) in the regulation of the local (uterine) and systemic innate immune system, myometrial expression of connexin 43 (Cx-43) and cyclooxygenase 2 (COX-2), and the onset of parturition was examined in (i) naïve mice delivering at term (ii) E16 mice treated with RU486 (P4-antagonist) to induce preterm parturition and (iii) in mice treated with P4 to prevent term parturition. In naïve mice, myometrial neutrophil and monocyte numbers peaked at E18 and declined with the onset of parturition. In contrast, circulating monocytes did not change and although neutrophils were increased with pregnancy, they did not change across gestation. The myometrial mRNA and protein levels of most chemokines/cytokines, Cx-43, and COX-2 increased with, but not before, parturition. With RU486-induced parturition, myometrial and systemic neutrophil numbers increased before and myometrial monocyte numbers increased with parturition only. Myometrial chemokine/cytokine mRNA abundance increased with parturition, but protein levels peaked earlier at between 4.5 and 9 h post-RU486. Cx-43, but not COX-2, mRNA expression and protein levels increased prior to the onset of parturition. In mice treated with P4, the gestation-linked increase in myometrial monocyte, but not neutrophil, numbers was prevented, and expression of Cx-43 and COX-2 was reduced. On E20 of P4 supplementation, myometrial chemokine/cytokine and leukocyte numbers, but not Cx-43 and COX-2 expression, increased. These data show that during pregnancy P4 controls myometrial monocyte infiltration, cytokine and prolabor factor synthesis via mRNA-dependent and independent mechanisms and, with prolonged P4 supplementation, P4 action is repressed resulting in increased myometrial inflammation.
Publisher: Springer Science and Business Media LLC
Date: 30-08-2023
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 09-2021
Publisher: Elsevier BV
Date: 07-2015
DOI: 10.1016/J.AJOG.2015.03.015
Abstract: MicroRNAs (miRNAs) play a modulatory role in pathways that lead to labor onset, although oxytocin is known to modulate gene expression within the myometrium. We aimed to identify miRNAs whose expression is regulated by oxytocin in pregnant human myometrium. Myometrial miRNA expression profiles were compared between s les collected from women at term before the onset of labor (no labor n = 8) and after labor onset after early exogenous oxytocin treatment (n = 8). Multivariate modelling was used to assess differences in miRNA profiles. Biologic validation was undertaken on 3 independent patient cohorts (no labor, n = 10 labor induced with oxytocin, n = 8 and spontaneous labor with no oxytocin treatment, n = 10). In vitro studies that used primary myocytes were undertaken to assess target miRNA expression after oxytocin treatment. Target genes of candidate miRNAs were identified in silico and cross-referenced with genes that are known to be associated with labor or expressed in myometrium. In total, 1309 miRNAs were analyzed by microarray, of which 494 were detected in human myometrium. Multivariate modeling identified 12 target miRNAs the differential expression of which was most responsible for the observed separation of the 2 patient populations in the primary discovery cohorts. Biologic validation in the independent secondary s le cohorts showed that oxytocin independently regulated 5 miRNAs (hsa-miR-146b-3p, hsa-miR-196b-3p, hsa-miR-223-3p, hsa-miR-873-5p, and hsa-miR-876-5p). Additionally, hsa-miR-146b-3p was increased both in labor that was induced with oxytocin and in myometrium from spontaneous labor with no oxytocin treatment compared with no labor s les. Four of the validated miRNAs (hsa-miR-146a-5p, hsa-miR-146b-3p, hsa-miR-196b-3p, and hsa-miR-876-5p) were expressed in primary human myocytes oxytocin treatment of these cells replicated the directional changes that were observed in vivo. Oxytocin alters the expression of a unique set of myometrial miRNAs. These results suggest a further role for oxytocin as a signaling molecule that is involved in the regulation of gene expression during parturition.
Publisher: Wiley
Date: 31-10-2019
Publisher: Public Library of Science (PLoS)
Date: 03-11-2016
Publisher: Wiley
Date: 03-11-2015
DOI: 10.1111/IMM.12534
Publisher: Wiley
Date: 04-02-2014
DOI: 10.1096/FJ.13-247783
Abstract: Activation of uterine inflammatory pathways leads to preterm labor (PTL), associated with high rates of neonatal mortality and morbidity. The transcription factors nuclear factor κB (NFκB) and activator protein 1 (AP-1) regulate key proinflammatory and procontractile genes involved in normal labor and PTL. Here we show that NFκB activation normally occurs in the mouse myometrium at gestation day E18, prior to labor, whereas AP-1 and JNK activation occurs at labor onset. Where labor was induced using the progesterone receptor antagonist RU486, NFkB and AP-1/JNK activation both occurred at the time of labor (20 h compared to 60 h in DMSO-treated controls). Using an LPS (Escherichia coli: serotype O111)-induced PTL model that selectively activates AP-1 but not NFkB, we show that myometrial AP-1 activation drives production of cytokines (Il-6, Il-8, and Il-1β), metalloproteinases (Mmp3 and Mmp10), and procontractile proteins (Cox-2 and Cx43) resulting in PTL after 7 h. Protein levels of CX43 and IL-1β, and IL-1β cleavage, were increased following LPS-induced activation of AP-1. Inhibition of JNK by SP600125 (30 mg/kg) delayed PTL by 6 h (7.5 vs. 13.5 h P<0.05). Our data reveal that NFκB activation is not a functional requirement for infection/inflammation-induced preterm labor and that AP-1 activation is sufficient to drive inflammatory pathways that cause PTL.
Publisher: Elsevier BV
Date: 02-2015
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 11-2023
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2020
Publisher: Oxford University Press (OUP)
Date: 30-11-2016
DOI: 10.1093/BIOINFORMATICS/BTW705
Abstract: KODAMA, a novel learning algorithm for unsupervised feature extraction, is specifically designed for analysing noisy and high-dimensional datasets. Here we present an R package of the algorithm with additional functions that allow improved interpretation of high-dimensional data. The package requires no additional software and runs on all major platforms. KODAMA is freely available from the R archive CRAN (cran.r-project.org). The software is distributed under the GNU General Public License (version 3 or later). Supplementary data are available at Bioinformatics online.
Publisher: Elsevier BV
Date: 09-2015
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 02-2023
Publisher: Bioscientifica
Date: 10-2015
DOI: 10.1530/REP-15-0258
Abstract: Preterm labour (PTL) is commonly associated with infection and/or inflammation. Lipopolysaccharide (LPS) from different bacteria can be used to independently or mutually activate Jun N-terminal kinase (JNK)/AP1- or NF-κB-driven inflammatory pathways that lead to PTL. Previous studies using Salmonella abortus LPS, which activates both JNK/AP-1 and NF-κB, showed that selective inhibition of NF-κB delays labour and improves pup outcome. Where labour is induced using Escherichia coli LPS (O111), which upregulates JNK/AP-1 but not NF-κB, inhibition of JNK/AP-1 activation also delays labour. In this study, to determine the potential role of JNK as a therapeutic target in PTL, we investigated the specific contribution of JNK signalling to S. Abortus LPS-induced PTL in mice. Intrauterine administration of S. Abortus LPS to pregnant mice resulted in the activation of JNK in the maternal uterus and fetal brain, upregulation of pro-inflammatory proteins COX-2, CXCL1, and CCL2, phosphorylation of cPLA2 in myometrium, and induction of PTL. Specific inhibition of JNK by co-administration of specific D-JNK inhibitory peptide (D-JNKI) delayed LPS-induced preterm delivery and reduced fetal mortality. This is associated with inhibition of myometrial cPLA2 phosphorylation and proinflammatory proteins synthesis. In addition, we report that D-JNKI inhibits the activation of JNK/JNK3 and caspase-3, which are important mediators of neural cell death in the neonatal brain. Our data demonstrate that specific inhibition of TLR4-activated JNK signalling pathways has potential as a therapeutic approach in the management of infection/inflammation-associated PTL and prevention of the associated detrimental effects to the neonatal brain.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2023
Publisher: American Chemical Society (ACS)
Date: 11-01-2017
DOI: 10.1021/ACS.ANALCHEM.6B03405
Abstract: Medical swabs are routinely used worldwide to s le human mucosa for microbiological screening with culture methods. These are usually time-consuming and have a narrow focus on screening for particular microorganism species. As an alternative, direct mass spectrometric profiling of the mucosal metabolome provides a broader window into the mucosal ecosystem. We present for the first time a minimal effort/minimal-disruption technique for augmenting the information obtained from clinical swab analysis with mucosal metabolome profiling using desorption electrospray ionization mass spectrometry (DESI-MS) analysis. Ionization of mucosal biomass occurs directly from a standard rayon swab mounted on a rotating device and analyzed by DESI MS using an optimized protocol considering swab-inlet geometry, tip-s le angles and distances, rotation speeds, and reproducibility. Multivariate modeling of mass spectral fingerprints obtained in this way readily discriminate between different mucosal surfaces and display the ability to characterize biochemical alterations induced by pregnancy and bacterial vaginosis (BV). The method was also applied directly to bacterial biomass to confirm the ability to detect intact bacterial species from a swab. These results highlight the potential of direct swab analysis by DESI-MS for a wide range of clinical applications including rapid mucosal diagnostics for microbiology, immune responses, and biochemistry.
Publisher: Proceedings of the National Academy of Sciences
Date: 16-03-2020
Abstract: Clearance of surgical margins in cervical cancer prevents the need for adjuvant chemoradiation and allows fertility preservation. In this study, we determined the capacity of the rapid evaporative ionization mass spectrometry (REIMS), also known as intelligent knife (iKnife), to discriminate between healthy, preinvasive, and invasive cervical tissue. Cervical tissue s les were collected from women with healthy, human papilloma virus (HPV) ± cervical intraepithelial neoplasia (CIN), or cervical cancer. A handheld diathermy device generated surgical aerosol, which was transferred into a mass spectrometer for subsequent chemical analysis. Combination of principal component and linear discriminant analysis and least absolute shrinkage and selection operator was employed to study the spectral differences between groups. Significance of discriminatory m/z features was tested using univariate statistics and tandem MS performed to elucidate the structure of the significant peaks allowing separation of the two classes. We analyzed 87 s les (normal = 16, HPV ± CIN = 50, cancer = 21 patients). The iKnife discriminated with 100% accuracy normal (100%) vs. HPV ± CIN (100%) vs. cancer (100%) when compared to histology as the gold standard. When comparing normal vs. cancer s les, the accuracy was 100% with a sensitivity of 100% (95% CI 83.9 to 100) and specificity 100% (79.4 to 100). Univariate analysis revealed significant MS peaks in the cancer-to-normal separation belonging to various classes of complex lipids. The iKnife discriminates healthy from premalignant and invasive cervical lesions with high accuracy and can improve oncological outcomes and fertility preservation of women treated surgically for cervical cancer. Larger in vivo research cohorts are required to validate these findings.
Publisher: Springer Science and Business Media LLC
Date: 29-08-2017
DOI: 10.1038/S41598-017-09844-4
Abstract: Evidence suggests the vaginal microbiota (VM) may influence risk of persistent Human Papillomavirus (HPV) infection and cervical carcinogenesis. Established cytology biobanks, typically collected with a cytobrush, constitute a unique resource to study such associations longitudinally. It is plausible that compared to rayon swabs the most commonly used s ling devices, cytobrushes may disrupt biofilms leading to variation in VM composition. Cervico-vaginal s les were collected with cytobrush and rayon swabs from 30 women with high-grade cervical precancer. Quantitative PCR was used to compare bacterial load and Illumina MiSeq sequencing of the V1-V3 regions of the 16S rRNA gene used to compare VM composition. Cytobrushes collected a higher total bacterial load. Relative abundance of bacterial species was highly comparable between s ling devices (R 2 = 0.993). However, in women with a Lactobacillus -depleted, high- ersity VM, significantly less correlation in relative species abundance was observed between devices when compared to those with a Lactobacillus species-dominant VM (p = 0.0049). Cytobrush and swab s ling provide a comparable VM composition. In a small proportion of cases the cytobrush was able to detect underlying high- ersity community structure, not realized with swab s ling. This study highlights the need to consider s ling devices as potential confounders when comparing multiple studies and datasets.
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9CC90472G
Abstract: Correction for ‘Oligonucleotide-templated lateral flow assays for lification-free sensing of circulating microRNAs’ by Suraj Pavagada et al. , Chem. Commun. , 2019, 55 , 12451–12454.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2023
Location: United Arab Emirates
Location: United Arab Emirates
No related grants have been discovered for Salman Hameed Khan.