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- Kennedy, S. A., et al.
(författare)
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Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRASG13D
- 2020
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Protein-protein-interaction networks (PPINs) organize fundamental biological processes, but how oncogenic mutations impact these interactions and their functions at a network-level scale is poorly understood. Here, we analyze how a common oncogenic KRAS mutation (KRASG13D) affects PPIN structure and function of the Epidermal Growth Factor Receptor (EGFR) network in colorectal cancer (CRC) cells. Mapping >6000 PPIs shows that this network is extensively rewired in cells expressing transforming levels of KRASG13D (mtKRAS). The factors driving PPIN rewiring are multifactorial including changes in protein expression and phosphorylation. Mathematical modelling also suggests that the binding dynamics of low and high affinity KRAS interactors contribute to rewiring. PPIN rewiring substantially alters the composition of protein complexes, signal flow, transcriptional regulation, and cellular phenotype. These changes are validated by targeted and global experimental analysis. Importantly, genetic alterations in the most extensively rewired PPIN nodes occur frequently in CRC and are prognostic of poor patient outcomes.
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| 4. |
- Gross, Sean M., et al.
(författare)
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A multi-omic analysis of MCF10A cells provides a resource for integrative assessment of ligand-mediated molecular and phenotypic responses
- 2022
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Ingår i: Communications Biology. - : Springer Nature. - 2399-3642. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- The phenotype of a cell and its underlying molecular state is strongly influenced by extracellular signals, including growth factors, hormones, and extracellular matrix proteins. While these signals are normally tightly controlled, their dysregulation leads to phenotypic and molecular states associated with diverse diseases. To develop a detailed understanding of the linkage between molecular and phenotypic changes, we generated a comprehensive dataset that catalogs the transcriptional, proteomic, epigenomic and phenotypic responses of MCF10A mammary epithelial cells after exposure to the ligands EGF, HGF, OSM, IFNG, TGFB and BMP2. Systematic assessment of the molecular and cellular phenotypes induced by these ligands comprise the LINCS Microenvironment (ME) perturbation dataset, which has been curated and made publicly available for community-wide analysis and development of novel computational methods ( synapse.org/LINCS_MCF10A ). In illustrative analyses, we demonstrate how this dataset can be used to discover functionally related molecular features linked to specific cellular phenotypes. Beyond these analyses, this dataset will serve as a resource for the broader scientific community to mine for biological insights, to compare signals carried across distinct molecular modalities, and to develop new computational methods for integrative data analysis.
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- Butler, Eadaoin M., et al.
(författare)
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A prediction model for childhood obesity in New Zealand
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Several early childhood obesity prediction models have been developed, but none for New Zealand's diverse population. We aimed to develop and validate a model for predicting obesity in 4-5-year-old New Zealand children, using parental and infant data from the Growing Up in New Zealand (GUiNZ) cohort. Obesity was defined as body mass index (BMI) for age and sex >= 95th percentile. Data on GUiNZ children were used for derivation (n=1731) and internal validation (n=713). External validation was performed using data from the Prevention of Overweight in Infancy Study (POI, n=383) and Pacific Islands Families Study (PIF, n=135) cohorts. The final model included: birth weight, maternal smoking during pregnancy, maternal pre-pregnancy BMI, paternal BMI, and infant weight gain. Discrimination accuracy was adequate [AUROC=0.74 (0.71-0.77)], remained so when validated internally [AUROC=0.73 (0.68-0.78)] and externally on PIF [AUROC=0.74 [0.66-0.82)] and POI [AUROC=0.80 (0.71-0.90)]. Positive predictive values were variable but low across the risk threshold range (GUiNZ derivation 19-54%; GUiNZ validation 19-48%; and POI 8-24%), although more consistent in the PIF cohort (52-61%), all indicating high rates of false positives. Although this early childhood obesity prediction model could inform early obesity prevention, high rates of false positives might create unwarranted anxiety for families.
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- Ilhan, Emre, et al.
(författare)
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What is the definition of acute episodic and chronic pain in critically ill neonates and infants? A global, four-stage consensus and validation study
- 2022
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To define and validate types of pain in critically ill neonates and infants by researchers and clinicians working in the neonatal intensive care unit (NICU) and high dependency unit (HDU).Design: A qualitative descriptive mixed-methods design.Procedure/s: Each stage of the study was built on and confirmed the previous stages. Stage 1 was an expert panel to develop definitions; stage 2 was a different expert panel made up of neonatal clinicians to propose clinical characteristics associated with the definitions from stage 1; stage 3 was a focus group of neonatal clinicians to provide clinical case scenarios associated with each definition and clinical characteristics; and stage 4 was a survey administered to neonatal clinicians internationally to test the validity of the definitions using the clinical case scenarios.Results: In stage 1, the panel (n=10) developed consensus definitions for acute episodic pain and chronic pain in neonates and infants. In stage 2, a panel (n=8) established clinical characteristics that may be associated with each definition. In stage 3, a focus group (n=11) created clinical case scenarios of neonates and infants with acute episodic pain, chronic pain and no pain using the definitions and clinical characteristics. In stage 4, the survey (n=182) revealed that the definitions allowed an excellent level of discrimination between case scenarios that described neonates and infants with acute episodic pain and chronic pain (area under the receiver operating characteristic=0.87 and 0.89, respectively).Conclusions: This four-stage study enabled the development of consensus-based and clinically valid definitions of acute episodic pain and chronic pain. There is a need to define and validate other pain types to inform a taxonomy of pain experienced by neonates and infants in the NICU and HDU.
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- Meethal, Sruthi Meledath, et al.
(författare)
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Asymmetric dual species copper(II/I) electrolyte dye-sensitized solar cells with 35.6% efficiency under indoor light
- 2024
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Ingår i: Journal of Materials Chemistry A. - : Royal Society of Chemistry. - 2050-7488 .- 2050-7496. ; 12:2, s. 1081-1093
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Tidskriftsartikel (refereegranskat)abstract
- Indoor photovoltaics (IPV) using dye-sensitized solar cells (DSCs) is one among the most promising ambient energy harvesting technologies used to realize self-powered Internet of Things (IoT), consumer electronics and portable devices. The emergence of new generation Cu(II/I) redox electrolytes used with co-sensitized organic dyes enables DSCs to realize higher open circuit photovoltages (Voc) and power conversion efficiencies (PCE) under indoor/ambient illumination. Even though Cu(II/I) electrolytes are promising candidates, the recombination of electrons from the conduction band and sub-bandgap states to the oxidized Cu(II) species and slower regeneration of Cu(II) at the counter electrode limit their performance. Taking inspiration from the asymmetric redox behaviour exhibited by the conventional iodide/triiodide electrolyte, which is efficient in inhibiting the undesirable recombination process, we introduced an alternative strategy of modifying the coordination environment of Cu(II) metal center using the 2,9-dimethyl-1,10-phenanthroline (dmp) ligand. The resulting dual species [Cu(II)(dmp)2Cl]+/[Cu(I)(dmp)2]+ electrolyte exhibited an improved lifetime both under full sun and indoor illumination and better regeneration at the counter electrode. Employing this asymmetric dual species Cu(II)/Cu(I) electrolyte with the co-sensitized D35:XY1 dyes, we realized a record PCE of 35.6% under 1000 lux warm white CFL illumination.
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| 8. |
- Pillai, Rajath S, et al.
(författare)
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Assessment of Somatosensory and Psychosocial Function of Patients With Trigeminal Nerve Damage
- 2020
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Ingår i: Clinical Journal of Pain. - : Lippincott Williams & Wilkins. - 1536-5409 .- 0749-8047. ; 36:5, s. 321-335
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The present study assessed somatosensory changes related to trigeminal nerve damage using extensive evaluation tools and assessed the effect of such damage on the patients' psychosocial status and quality of life compared with healthy participants.METHODS: In 37 patients with intraorally or extraorally presenting trigeminal nerve damage diagnosed as painful or nonpainful posttraumatic trigeminal neuropathy, psychophysical tests like quantitative sensory testing (QST) and qualitative sensory testing and the electrophysiological "nociceptive-specific" blink reflex were performed. The patients and 20 healthy participants completed a set of questionnaires assessing their psychosocial status and quality of life.RESULTS: A loss or gain of somatosensory function was seen in at least 1 QST parameter in >88.9% of the patients. Patients in whom extraoral QST was performed showed an overall loss of somatosensory function, whereas intraoral QST showed a general gain of somatosensory function. Qualitative sensory testing identified a side-to-side difference in the tactile and pinprick stimulation in >77% of the patients. An abnormal "nociceptive-specific" blink reflex response was seen in 42.1% to 71.4% of patients dependent on the trigeminal branch stimulated, though comparisons with healthy reference values showed ambiguous results. Compared with the healthy participants, patients showed higher scores for pain catastrophizing, symptoms of depression and anxiety, limited jaw function, more somatic symptoms, and significantly impaired oral health-related quality of life (all P<0.038).DISCUSSION: The results from the present study showed presence of varied somatosensory abnormalities when assessed using psychophysical and electrophysiological investigations and a significantly impaired psychosocial status.
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| 9. |
- Pomara, N., et al.
(författare)
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Plasma Amyloid-beta dynamics in late-life major depression: a longitudinal study
- 2022
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Depressed individuals are twice as likely to develop Alzheimer's disease (AD) as compared to controls. Brain amyloid-beta (A beta) deposition is believed to have a major role in AD pathogenesis but studies also suggest associations of A beta dynamics and depression. The aim of this study was to test if plasma A beta levels are longitudinally associated to late-life depression. We measured plasma levels of amyloid-beta(1-40) (A beta 40) and amyloid-beta(1-42) (A beta 42) peptides longitudinally for three consecutive years in 48 cognitively intact elderly subjects with late-life major depressive disorder (LLMD) and 45 age-matched cognitively healthy controls. We found that the A beta 42/A beta 40 plasma ratio was significantly and steadily lower in depressed subjects compared to controls (p < 0.001). At screening, A beta 42/A beta 40 plasma did not correlate with depression severity (as measured with Hamilton Depression Scale) or cognitive performance (as measured with Mini-Mental State Examination) but was associated to depression severity at 3 years after adjustment for age, education, cognitive performance, and antidepressants use. This study showed that reduced plasma A beta 42/A beta 40 ratio is consistently associated with LLMD diagnosis and that increased severity of depression at baseline predicted low A beta 42/A beta 40 ratio at 3 years. Future studies are needed to confirm these findings and examine if the consistently lower plasma A beta 42/A beta 40 ratio in LLMD reflects increased brain amyloid deposition, as observed in AD subjects, and an increased risk for progressive cognitive decline and AD.
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| 10. |
- Tang, Jiexiong, et al.
(författare)
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Neural Outlier Rejection For Self-Supervised Keypoint Learning
- 2020
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Ingår i: <em>8th International Conference on Learning Representations, ICLR 2020</em>. - : International Conference on Learning Representations, ICLR.
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Konferensbidrag (refereegranskat)abstract
- Identifying salient points in images is a crucial component for visual odometry, Structure-from-Motion or SLAM algorithms. Recently, several learned keypoint methods have demonstrated compelling performance on challenging benchmarks. However, generating consistent and accurate training data for interest-point detection in natural images still remains challenging, especially for human annotators. We introduce IO-Net (i.e. InlierOutlierNet), a novel proxy task for the self-supervision of keypoint detection, description and matching. By making the sampling of inlier-outlier sets from point-pair correspondences fully differentiable within the keypoint learning framework, we show that are able to simultaneously self-supervise keypoint description and improve keypoint matching. Second, we introduce KeyPointNet, a keypoint-network architecture that is especially amenable to robust keypoint detection and description. We design the network to allow local keypoint aggregation to avoid artifacts due to spatial discretizations commonly used for this task, and we improve fine-grained keypoint descriptor performance by taking advantage of efficient sub-pixel convolutions to upsample the descriptor feature-maps to a higher operating resolution. Through extensive experiments and ablative analysis, we show that the proposed self-supervised keypoint learning method greatly improves the quality of feature matching and homography estimation on challenging benchmarks over the state-of-the-art.
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