| 1. |
- Dunn, R. J. H., et al.
(författare)
-
GLOBAL CLIMATE : State of the Climate in 2020
- 2021
-
Ingår i: Bulletin of the American Meteorological Society. - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 102:8
-
Tidskriftsartikel (refereegranskat)
|
|
| 2. |
- Ades, M., et al.
(författare)
-
GLOBAL CLIMATE
- 2020
-
Ingår i: BULLETIN OF THE AMERICAN METEOROLOGICAL SOCIETY. - 0003-0007 .- 1520-0477. ; 101:8
-
Tidskriftsartikel (refereegranskat)
|
|
| 3. |
- Charney, A. W., et al.
(författare)
-
Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder
- 2017
-
Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 7:1
-
Tidskriftsartikel (refereegranskat)abstract
- We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed with prior results from the Psychiatric Genomics Consortium Bipolar Disorder Working Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P = 3.28 x 10(-8)) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P (XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and investigate their genetic overlap with schizophrenia and major depressive disorder. We found a significant difference in heritability of the two most common forms of BD (BD I SNP-h(2) = 0.35; BD II SNP-h(2) = 0.25; P = 0.02). The genetic correlation between BD I and BD II was 0.78, whereas the genetic correlation was 0.97 when BD cohorts containing both types were compared. In addition, we demonstrated a significantly greater load of polygenic risk alleles for schizophrenia and BD in patients with BD I compared with patients with BD II, and a greater load of schizophrenia risk alleles in patients with the bipolar type of schizoaffective disorder compared with patients with either BD I or BD II. These results point to a partial difference in the genetic architecture of BD subtypes as currently defined.
|
|
| 4. |
- Gastineau, R., et al.
(författare)
-
Haslea ostrearia-like Diatoms: Biodiversity out of the Blue
- 2014
-
Ingår i: Advances in Botanical Research. - London : Academic Press Ltd-Elsevier Science Ltd. - 0065-2296. ; 71, s. 441-465
-
Tidskriftsartikel (refereegranskat)abstract
- Diatoms are usually referred to as golden-brown microalgae, due to the colour of their plastids and to their pigment composition, mainly carotenoids (fucoxanthin, diadinoxanthin, diatoxanthin), which mask chlorophylls a and c. The species Haslea ostrearia Gaillon/Bory (Simonsen) appears unique because of its extraplastidial bluish colour, a consequence of the presence of a water-soluble blue pigment at cell apices, marennine. When released in seawater, marenbine can be fixed on gills of oysters and other bivalves, which turn green. This greening phenomenon is economically exploited in Southwestern France, as it gives an added value to oysters. For decades, this singularity ascribed a worldwide distribution to H. ostrearia, first as Vibrio ostrearius, then Navicula ostrearia, last as H. ostrearia, when the genus Haslea was proposed by R. Simonsen (1974). Indeed, this 'birthmark' (presence of blue apices) made H. ostrearia easily recognisable without further scrutiny and identification of the microalga as well as its presence easily deduced from the greening of bivalves. Consequently, the widely admitted cosmopolitan character of H. ostrearia has only been questioned recently, following the discovery in 2008, of a new species of blue diatom in the Black Sea, Haslea karadagensis. The biodiversity of blue diatoms suddenly increased with the finding of other blue species in the Mediterranean Sea, the Canary Islands, etc., the taxonomic characterization of which is in progress. This review thus focuses on the unsuspected biodiversity of blue diatoms within the genus Haslea. Methods for species determination (morphometrics, chemotaxonomy, genomics), as well as a new species, are presented and discussed.
|
|
| 5. |
- Bocci, G., et al.
(författare)
-
Virtual and in Vitro Antiviral Screening Revive Therapeutic Drugs for COVID-19
- 2020
-
Ingår i: ACS Pharmacology and Translational Science. - : American Chemical Society (ACS). - 2575-9108. ; 3:6, s. 1278-1292
-
Tidskriftsartikel (refereegranskat)abstract
- The urgent need for a cure for early phase COVID-19 infected patients critically underlines drug repositioning strategies able to efficiently identify new and reliable treatments by merging computational, experimental, and pharmacokinetic expertise. Here we report new potential therapeutics for COVID-19 identified with a combined virtual and experimental screening strategy and selected among already approved drugs. We used hydroxychloroquine (HCQ), one of the most studied drugs in current clinical trials, as a reference template to screen for structural similarity against a library of almost 4000 approved drugs. The top-ranked drugs, based on structural similarity to HCQ, were selected for in vitro antiviral assessment. Among the selected drugs, both zuclopenthixol and nebivolol efficiently block SARS-CoV-2 infection with EC50 values in the low micromolar range, as confirmed by independent experiments. The anti-SARS-CoV-2 potential of ambroxol, amodiaquine, and its active metabolite (N-monodesethyl amodiaquine) is also discussed. In trying to understand the "hydroxychloroquine"mechanism of action, both pKa and the HCQ aromatic core may play a role. Further, we show that the amodiaquine metabolite and, to a lesser extent, zuclopenthixol and nebivolol are active in a SARS-CoV-2 titer reduction assay. Given the need for improved efficacy and safety, we propose zuclopenthixol, nebivolol, and amodiaquine as potential candidates for clinical trials against the early phase of the SARS-CoV-2 infection and discuss their potential use as adjuvant to the current (i.e., remdesivir and favipiravir) COVID-19 therapeutics. © 2020 American Chemical Society. All rights reserved.
|
|
| 6. |
- Charney, Alexander W, et al.
(författare)
-
Contribution of Rare Copy Number Variants toBipolar Disorder Risk Is Limited to Schizoaffective Cases.
- 2019
-
Ingår i: Biological psychiatry. - : Elsevier BV. - 1873-2402 .- 0006-3223. ; 86:2, s. 110-119
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic risk for bipolar disorder (BD) is conferred through many common alleles, while a role for rare copy number variants (CNVs) is less clear. Subtypes of BD including schizoaffective disorder bipolar type (SAB), bipolar I disorder (BD I), and bipolar II disorder (BD II) differ according to the prominence and timing of psychosis, mania, and depression. The genetic factors contributing to the combination of symptoms among these subtypes are poorly understood.Rare large CNVs were analyzed in 6353 BD cases (3833 BD I [2676 with psychosis, 850 without psychosis, and 307 with unknown psychosis history], 1436 BD II, 579 SAB, and 505 BD not otherwise specified) and 8656 controls. CNV burden and a polygenic risk score (PRS) for schizophrenia were used to evaluate the relative contributions of rare and common variants to risk of BD, BD subtypes, and psychosis.CNV burden did not differ between BD and controls when treated as a single diagnostic entity. However, burden in SAB was increased relative to controls (p= .001), BD I (p= .0003), and BD II (p= .0007). Burden and schizophrenia PRSs were increased in SAB compared with BD I with psychosis (CNV p= .0007, PRS p= .004), and BD I without psychosis (CNV p= .0004, PRS p= 3.9× 10-5). Within BD I, psychosis was associated with increased schizophrenia PRSs (p= .005) but not CNV burden.CNV burden in BD is limited to SAB. Rare and common genetic variants may contribute differently to risk for psychosis and perhaps other classes of psychiatric symptoms.
|
|
| 7. |
- Davis, K., et al.
(författare)
-
Altered groundwater discharge and associated carbon fluxes in a wetland-drained coastal canal
- 2020
-
Ingår i: Estuarine, Coastal and Shelf Science. - : Elsevier BV. - 0272-7714. ; 235
-
Tidskriftsartikel (refereegranskat)abstract
- Residential canal systems are becoming increasingly popular with the rising demand for absolute coastal waterfront properties. We hypothesize that canals alter groundwater-surface water connectivity and related carbon fluxes into coastal surface waters. Here, we quantified submarine groundwater discharge (SGD) in a residential canal system on Bribie Island (Australia) and associated carbon fluxes. SGD rates estimated from a radon (222Rn) mass balance model were 3.1 ± 1.5 cm d−1. These fluxes delivered 68 ± 44 and 70 ± 48 mmol m−2 d−1 of dissolved inorganic carbon (DIC) and dissolved organic carbon (DOC) into the canal, respectively. Carbon dioxide (CO2) emissions to the atmosphere ranged from 15 to 28 mmol m−2 d−1. Multiple lines of evidence, including flux estimates and groundwater observations, converge to the conclusion that SGD was a major source of DOC and free CO2, but not carbonate alkalinity nor DIC to canal surface waters. In comparison to mangrove tidal creeks that often precede canals, the canal had (1) lower tidally-driven saline groundwater exchange rates but higher fresh groundwater discharge, (2) lower CO2 emissions to the atmosphere; and (3) acted as a driver rather than a buffer of local ocean acidification. These differences seem to be driven by the replacement of intertidal wetland vegetation with urban areas that prevent soil carbon accumulation and related biogeochemical processes around the canals. We suggest that decisions on canal construction should consider potential changes to groundwater-derived soil carbon losses and carbon cycling in receiving coastal waters. © 2020 Elsevier Ltd
|
|
| 8. |
- Wu, Hao, et al.
(författare)
-
Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug
- 2017
-
Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 23:7
-
Tidskriftsartikel (refereegranskat)abstract
- Metformin is widely used in the treatment of type 2 diabetes (T2D), but its mechanism of action is poorly defined. Recent evidence implicates the gut microbiota as a site of metformin action. In a double-blind study, we randomized individuals with treatment-naive T2D to placebo or metformin for 4 months and showed that metformin had strong effects on the gut microbiome. These results were verified in a subset of the placebo group that switched to metformin 6 months after the start of the trial. Transfer of fecal samples (obtained before and 4 months after treatment) from metformin-treated donors to germ-free mice showed that glucose tolerance was improved in mice that received metformin-altered microbiota. By directly investigating metformin-microbiota interactions in a gut simulator, we showed that metformin affected pathways with common biological functions in species from two different phyla, and many of the metformin-regulated genes in these species encoded metalloproteins or metal transporters. Our findings provide support for the notion that altered gut microbiota mediates some of metformin's antidiabetic effects.
|
|
| 9. |
- Devarakonda, Sravani, et al.
(författare)
-
Low-grade intestinal inflammation two decades after pelvic radiotherapy.
- 2023
-
Ingår i: EBioMedicine. - 2352-3964. ; 94
-
Tidskriftsartikel (refereegranskat)abstract
- Radiotherapy is effective in the treatment of cancer but also causes damage to non-cancerous tissue. Pelvic radiotherapy may produce chronic and debilitating bowel symptoms, yet the underlying pathophysiology is still undefined. Most notably, although pelvic radiotherapy causes an acute intestinal inflammation there is no consensus on whether the late-phase pathophysiology contains an inflammatory component or not. To address this knowledge gap, we examined the potential presence of a chronic inflammation in mucosal biopsies from irradiated pelvic cancer survivors.We biopsied 24 cancer survivors two to 20 years after pelvic radiotherapy, and four non-irradiated controls. Using tandem mass tag (TMT) mass spectrometry and mRNA sequencing (mRNA-seq), we charted proteomic and transcriptomic profiles of the mucosal tissue previously exposed to a high or a low/no dose of radiation. Changes in the immune cell populations were determined with flow cytometry. The integrity of the protective mucus layers were determined by permeability analysis and 16S rRNA bacterial detection.942 proteins were differentially expressed in mucosa previously exposed to a high radiation dose compared to a low radiation dose. The data suggested a chronic low-grade inflammation with neutrophil activity, which was confirmed by mRNA-seq and flow cytometry and further supported by findings of a weakened mucus barrier with bacterial infiltration.Our results challenge the idea that pelvic radiotherapy causes an acute intestinal inflammation that either heals or turns fibrotic without progression to chronic inflammation. This provides a rationale for exploring novel strategies to mitigate chronic bowel symptoms in pelvic cancer survivors.This study was supported by the King Gustav V Jubilee Clinic Cancer Foundation (CB), The Adlerbertska Research Foundation (CB), The Swedish Cancer Society (GS), The Swedish State under the ALF agreement (GS and CB), Mary von Sydow's foundation (MA and VP).
|
|
| 10. |
- Koh, Ara, et al.
(författare)
-
Microbial Imidazole Propionate Affects Responses to Metformin through p38 gamma-Dependent Inhibitory AMPK Phosphorylation
- 2020
-
Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131. ; 32:4
-
Tidskriftsartikel (refereegranskat)abstract
- Metformin is the first-line therapy for type 2 diabetes, but there are large inter-individual variations in responses to this drug. Its mechanism of action is not fully understood, but activation of AMP-activated protein kinase (AMPK) and changes in the gut microbiota appear to be important. The inhibitory role of microbial metabolites on metformin action has not previously been investigated. Here, we show that concentrations of the microbial metabolite imidazole propionate are higher in subjects with type 2 diabetes taking metformin who have high blood glucose. We also show that metformin-induced glucose lowering is not observed in mice pretreated with imidazole propionate. Furthermore, we demonstrate that imidazole propionate inhibits AMPK activity by inducing inhibitory AMPK phosphorylation, which is dependent on imidazole propionate-induced basal Akt activation. Finally, we identify imidazole propionate-activated p38 gamma as a novel kinase for Akt and demonstrate that p38 gamma kinase activity mediates the inhibitory action of imidazole propionate on metformin.
|
|
