| 1. |
- Santangelo, James S., et al.
(författare)
-
Global urban environmental change drives adaptation in white clover
- 2022
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
-
Tidskriftsartikel (refereegranskat)abstract
- Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
|
|
| 2. |
- Alessandro, B., et al.
(författare)
-
Vector boson scattering : Recent experimental and theory developments
- 2018
-
Ingår i: Reviews in Physics. - : Elsevier BV. - 2405-4283. ; 3, s. 44-63
-
Tidskriftsartikel (refereegranskat)abstract
- This document summarises the talks and discussions happened during the VBSCan Split17 workshop, the first general meeting of the VBSCan COST Action network. This collaboration is aiming at a consistent and coordinated study of vector-boson scattering from the phenomenological and experimental point of view, for the best exploitation of the data that will be delivered by existing and future particle colliders.
|
|
| 3. |
- Aggelopoulos, Christos A., et al.
(författare)
-
Cold Atmospheric Plasma Attenuates Breast Cancer Cell Growth Through Regulation of Cell Microenvironment Effectors
- 2022
-
Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Breast cancer exists in multiple subtypes some of which still lack a targeted and effective therapy. Cold atmospheric plasma (CAP) has been proposed as an emerging anti-cancer treatment modality. In this study, we investigated the effects of direct and indirect CAP treatment driven by the advantageous nanosecond pulsed discharge on breast cancer cells of different malignant phenotypes and estrogen receptor (ER) status, a major factor in the prognosis and therapeutic management of breast cancer. The main CAP reactive species in liquid (i.e. H2O2, NO2−/NO3−) and gas phase were determined as a function of plasma operational parameters (i.e. treatment time, pulse voltage and frequency), while pre-treatment with the ROS scavenger NAC revealed the impact of ROS in the treatment. CAP treatment induced intense phenotypic changes and apoptosis in both ER+ and ER- cells, which is associated with the mitochondrial pathway as evidenced by the increased Bax/Bcl-2 ratio and cleavage of PARP-1. Interestingly, CAP significantly reduced CD44 protein expression (a major cancer stem cell marker and matrix receptor), while differentially affected the expression of proteases and inflammatory mediators. Collectively, the findings of the present study suggest that CAP suppresses breast cancer cell growth and regulates several effectors of the tumor microenvironment and thus it could represent an efficient therapeutic approach for distinct breast cancer subtypes.
|
|
| 4. |
- Arner, P., et al.
(författare)
-
Circulating Carnosine Dipeptidase 1 associates with weight loss and poor prognosis in gastrointestinal cancer
- 2015
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:4
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Cancer cachexia (CC) is linked to poor prognosis. Although the mechanisms promoting this condition are not known, several circulating proteins have been proposed to contribute. We analyzed the plasma proteome in cancer subjects in order to identify factors associated with cachexia. Design/Subjects: Plasma was obtained from a screening cohort of 59 patients, newly diagnosed with suspected gastrointestinal cancer, with (n = 32) or without (n = 27) cachexia. Samples were subjected to proteomic profiling using 760 antibodies (targeting 698 individual proteins) from the Human Protein Atlas project. The main findings were validated in a cohort of 93 patients with verified and advanced pancreas cancer. Results: Only six proteins displayed differential plasma levels in the screening cohort. Among these, Carnosine Dipeptidase 1 (CNDP1) was confirmed by sandwich immunoassay to be lower in CC (p = 0.008). In both cohorts, low CNDP1 levels were associated with markers of poor prognosis including weight loss, malnutrition, lipid breakdown, low circulating albumin/IGF1 levels and poor quality of life. Eleven of the subjects in the discovery cohort were finally diagnosed with non-malignant disease but omitting these subjects from the analyses did not have any major influence on the results. Conclusions: In gastrointestinal cancer, reduced plasma levels of CNDP1 associate with signs of catabolism and poor outcome. These results, together with recently published data demonstrating lower circulating CNDP1 in subjects with glioblastoma and metastatic prostate cancer, suggest that CNDP1 may constitute a marker of aggressive cancer and CC.
|
|
| 5. |
- Bainbridge, Matthew N, et al.
(författare)
-
Germline mutations in shelterin complex genes are associated with familial glioma
- 2015
-
Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 107:1
-
Tidskriftsartikel (refereegranskat)abstract
- Gliomas are the most common brain tumor, with several histological subtypes of various malignancy grade. The genetic contribution to familial glioma is not well understood. Using whole exome sequencing of 90 individuals from 55 families, we identified two families with mutations in POT1 (p.G95C, p.E450X), a member of the telomere shelterin complex, shared by both affected individuals in each family and predicted to impact DNA binding and TPP1 binding, respectively. Validation in a separate cohort of 264 individuals from 246 families identified an additional mutation in POT1 (p.D617Efs), also predicted to disrupt TPP1 binding. All families with POT1 mutations had affected members with oligodendroglioma, a specific subtype of glioma more sensitive to irradiation. These findings are important for understanding the origin of glioma and could have importance for the future diagnostics and treatment of glioma.
|
|
| 6. |
- Demichev, Vadim, et al.
(författare)
-
A proteomic survival predictor for COVID-19 patients in intensive care
- 2022
-
Ingår i: PLOS Digital Health. - : Public Library of Science (PLoS). - 2767-3170. ; 1:1 January
-
Tidskriftsartikel (refereegranskat)abstract
- Global healthcare systems are challenged by the COVID-19 pandemic. There is a need to optimize allocation of treatment and resources in intensive care, as clinically established risk assessments such as SOFA and APACHE II scores show only limited performance for predicting the survival of severely ill COVID-19 patients. Additional tools are also needed to monitor treatment, including experimental therapies in clinical trials. Comprehensively capturing human physiology, we speculated that proteomics in combination with new data-driven analysis strategies could produce a new generation of prognostic discriminators. We studied two independent cohorts of patients with severe COVID-19 who required intensive care and invasive mechanical ventilation. SOFA score, Charlson comorbidity index, and APACHE II score showed limited performance in predicting the COVID-19 outcome. Instead, the quantification of 321 plasma protein groups at 349 timepoints in 50 critically ill patients receiving invasive mechanical ventilation revealed 14 proteins that showed trajectories different between survivors and non-survivors. A predictor trained on proteomic measurements obtained at the first time point at maximum treatment level (i.e. WHO grade 7), which was weeks before the outcome, achieved accurate classification of survivors (AUROC 0.81). We tested the established predictor on an independent validation cohort (AUROC 1.0). The majority of proteins with high relevance in the prediction model belong to the coagulation system and complement cascade. Our study demonstrates that plasma proteomics can give rise to prognostic predictors substantially outperforming current prognostic markers in intensive care.
|
|
| 7. |
- Demichev, Vadim, et al.
(författare)
-
A time-resolved proteomic and prognostic map of COVID-19
- 2021
-
Ingår i: Cell Systems. - : Elsevier BV. - 2405-4712 .- 2405-4720. ; 12:8, s. 780-794.e7
-
Tidskriftsartikel (refereegranskat)abstract
- COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.
|
|
| 8. |
- Jalali, Ali, et al.
(författare)
-
Targeted sequencing in chromosome 17q linkage region identifies familial glioma candidates in the Gliogene Consortium
- 2015
-
Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 5, s. 8278-
-
Tidskriftsartikel (refereegranskat)abstract
- Glioma is a rare, but highly fatal, cancer that accounts for the majority of malignant primary brain tumors. Inherited predisposition to glioma has been consistently observed within non-syndromic families. Our previous studies, which involved non-parametric and parametric linkage analyses, both yielded significant linkage peaks on chromosome 17q. Here, we use data from next generation and Sanger sequencing to identify familial glioma candidate genes and variants on chromosome 17q for further investigation. We applied a filtering schema to narrow the original list of 4830 annotated variants down to 21 very rare (<0.1% frequency), non-synonymous variants. Our findings implicate the MYO19 and KIF18B genes and rare variants in SPAG9 and RUNDC1 as candidates worthy of further investigation. Burden testing and functional studies are planned.
|
|
| 9. |
- Karalis, Theodoros T, et al.
(författare)
-
Salicylate suppresses the oncogenic hyaluronan network in metastatic breast cancer cells.
- 2020
-
Ingår i: Matrix biology plus. - : Elsevier BV. - 2590-0285. ; 6-7
-
Tidskriftsartikel (refereegranskat)abstract
- The oncogenic role of hyaluronan in several aspects of tumor biology has been well established. Recent studies by us and others suggest that inhibition of hyaluronan synthesis could represent an emerging therapeutic approach with significant clinical relevance in controlling different breast cancer subtypes, including triple-negative breast cancer. Epidemiological and preclinical studies have revealed the therapeutic potential of aspirin (acetyl salicylate), a classical anti-inflammatory drug, in patients with cancer. However, the underlying molecular mechanisms remain unknown. The present study demonstrates that salicylate, a break down product of aspirin in vivo, alters the organization of hyaluronan matrices by affecting the expression levels of hyaluronan synthesizing (HAS1, 2, 3) and degrading (HYAL-1, -2) enzymes, and that of hyaluronan receptor CD44. In particular, salicylate was found to potently activate AMPK, a kinase known to inhibit HAS2 activity, and caused a dose-dependent decrease of cell associated (intracellular and membrane-bound) as well as secreted hyaluronan, followed by the down-regulation of HAS2 and the induction of HYAL-2 and CD44 in metastatic breast cancer cells. These salicylate-mediated effects were associated with the redistribution of CD44 and actin cytoskeleton that resulted in a less motile cell phenotype. Interestingly, salicylate inhibited metastatic breast cancer cell proliferation and growth by inducing cell growth arrest without signs of apoptosis as evidenced by the substantial decrease of cyclin D1 protein and the absence of cleaved caspase-3, respectively. Collectively, our study offers a possible direction for the development of new matrix-based targeted treatments of metastatic breast cancer subtypes via inhibition of hyaluronan, a pro-angiogenic, pro-inflammatory and tumor promoting glycosaminoglycan.
|
|
| 10. |
- Karalis, Theodoros T., et al.
(författare)
-
Tumor-suppressive functions of 4-MU on breast cancer cells of different ER status : Regulation of hyaluronan/HAS2/CD44 and specific matrix effectors
- 2019
-
Ingår i: Matrix Biology. - : ELSEVIER SCIENCE BV. - 0945-053X .- 1569-1802. ; 78-79, s. 118-138
-
Tidskriftsartikel (refereegranskat)abstract
- The malignant phenotype of various cancers is linked to enhanced expression of hyaluronan, a proangiogenic glycosaminoglycan whose expression is suppressed by 4-methylumbelliferone (4-MU), a non-toxic oral agent used as a dietary supplement to improve health and combat prostate cancer. In this study, we investigated the role of 4-MU in mammary carcinoma cells with distinct malignant phenotypes and estrogen receptor (ER) status, a major prognostic factor in the clinical management of breast cancers. We focused on two breast cancer cell lines, the low metastatic and ER alpha+ MCF-7 cells, and the highly-aggressive and ER alpha-MDA-MB-231 cells. Treatment with 4-MU caused a dose-dependent decrease of hyaluronan accumulation in the extracellular matrix as well as within the breast cancer cells, most prevalent in cells lacking ER alpha. This decrease in hyaluronan was accompanied by suppression of Hyaluronan Synthase 2 (HAS2), the major enzyme responsible for the synthesis of hyaluronan, and by induction of hyaluronidases (HYALs) -1 and -2. Moreover, 4-MU induced intense phenotypic changes and substantial loss of CD44, a major hyaluronan receptor, from cell protrusions. Importantly, 4-MU evoked differential effects depending on the absence or presence of ER alpha. Only the ER alpha+ cells showed signs of apoptosis, as determined by cleaved PARP-1, and anoikis as shown by concurrent loss of E-cadherin and beta-catenin. Interestingly, 4-MU significantly reduced migration, adhesion and invasion of ER alpha- breast cancer cells, and concurrently reduced the expression and activity of several matrix degrading enzymes and pro-inflammatory molecules with tumor-promoting functions. Collectively, our findings suggest that 4-MU could represent a novel therapeutic for specific breast cancer subtypes with regard to their ER status via suppression of hyaluronan synthesis and regulation of HAS2, CD44, matrix-degrading enzymes and inflammatory mediators.
|
|
