| 1. |
- Huang, H., et al.
(författare)
-
Extracellular domain shedding of the ALK receptor mediates neuroblastoma cell migration
- 2021
-
Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 36:2
-
Tidskriftsartikel (refereegranskat)abstract
- Although activating mutations of the anaplastic lymphoma kinase (ALK) membrane receptor occur in similar to 10% of neuroblastoma (NB) tumors, the role of the wild-type (WT) receptor, which is aberrantly expressed in most non-mutated cases, is unclear. Both WT and mutant proteins undergo extracellular domain (ECD) cleavage. Here, we map the cleavage site to Asn654-Leu655 and demonstrate that cleavage inhibition of WT ALK significantly impedes NB cell migration with subsequent prolongation of survival in mouse models. Cleavage inhibition results in the downregulation of an epithelial-to-mesenchymal transition (EMT) gene signature, with decreased nuclear localization and occupancy of beta-catenin at EMT gene promoters. We further show that cleavage is mediated by matrix metalloproteinase 9, whose genetic and pharmacologic inactivation inhibits cleavage and decreases NB cell migration. Together, our results indicate a pivotal role forWTALK ECD cleavage in NB pathogenesis, which may be harnessed for therapeutic benefit.
|
|
| 2. |
- Hellerstedt, W. L., et al.
(författare)
-
Are prenatal, obstetric, and infant complications associated with postpartum psychosis among women with pre-conception psychiatric hospitalisations?
- 2013
-
Ingår i: British Journal of Obstetrics and Gynecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 120:4, s. 446-455
-
Tidskriftsartikel (refereegranskat)abstract
- Objective To examine the associations of maternal and infant complications with postpartum hospitalisation for psychosis in women with a pre-conception history of psychiatric hospitalisation. Design Population-based study. Setting Swedish medical birth register. Population Primiparous women who gave birth between 1January1987 and 31December2001, and who had a pre-conception history of psychiatric hospitalisation but who were not hospitalised during pregnancy (n=1842). Methods International Classification of Diseases (ICD) codes were used to identify prenatal, obstetric, postpartum maternal complications, and newborn health conditions. We used multivariable logistic regression to describe the associations between maternal and infant health conditions and the odds for postpartum hospitalisation for psychosis. Main outcome measure Psychiatric hospitalisation within 90days of delivery. Results Compared with women who did not have a postpartum psychiatric hospitalisation, hospitalised women were at 2.3 times higher odds (95%CI 1.04.9) of having non-psychiatric puerperium complications (e.g. infection, lactation problems or venous complications). No other maternal complications were associated with postpartum psychiatric hospitalisation. Although their infants were at no higher odds for health complications, the offspring of women who had a postpartum psychiatric hospitalisation were at 4.1 times higher odds (95%CI 1.312.6) of death within the first 365days of life than those of women who were not hospitalised. Conclusions We found no prenatal indicators of postpartum risk for psychiatric hospitalisation among high-risk women, but they had higher odds of postpartum pregnancy-related medical problems and, rarely, offspring death.
|
|
| 3. |
- Brath, M., et al.
(författare)
-
Retrieval of an ice water path over the ocean from ISMAR and MARSS millimeter and submillimeter brightness temperatures
- 2018
-
Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 11:1, s. 611-632
-
Tidskriftsartikel (refereegranskat)abstract
- A neural-network-based retrieval method to determine the snow ice water path (SIWP), liquid water path (LWP), and integrated water vapor (IWV) from millimeter and submillimeter brightness temperatures, measured by using airborne radiometers (ISMAR and MARSS), is presented. The neural networks were trained by using atmospheric profiles from the ICON numerical weather prediction (NWP) model and by radiative transfer simulations using the Atmospheric Radiative Transfer Simulator (ARTS). The basic performance of the retrieval method was analyzed in terms of offset (bias) and the median fractional error (MFE), and the benefit of using submillimeter channels was studied in comparison to pure microwave retrievals. The retrieval is offset-free for SIWP > 0.01kgm -2 , LWP > 0:1kgm -2 , and IWV > 3kgm -2 . The MFE of SIWP decreases from 100% at SIWPD 0.01kgm -2 to 20% at SIWPD 1kgm -2 and the MFE of LWP from 100% at LWP D 0.05kgm -2 to 30% at LWPD 1kgm -2 . The MFE of IWV for IWV > 3kgm -2 is 5 to 8%. The SIWP retrieval strongly benefits from submillimeter channels, which reduce the MFE by a factor of 2, compared to pure microwave retrievals. The IWV and the LWP retrievals also benefit from submillimeter channels, albeit to a lesser degree. The retrieval was applied to ISMAR and MARSS brightness temperatures from FAAM flight B897 on 18 March 2015 of a precipitating frontal system west of the coast of Iceland. Considering the given uncertainties, the retrieval is in reasonable agreement with the SIWP, LWP, and IWV values simulated by the ICON NWP model for that flight. A comparison of the retrieved IWV with IWV from 12 dropsonde measurements shows an offset of 0:5kgm -2 and an RMS difference of 0:8kgm -2 , showing that the retrieval of IWV is highly effective even under cloudy conditions.
|
|
| 4. |
- Harlow, Bernard L, et al.
(författare)
-
Incidence of hospitalization for postpartum psychotic and bipolar episodes in women with and without prior pregnancy or prenatal psychiatric hospitalizations
- 2007
-
Ingår i: Archives of General Psychiatry. - : American Medical Association (AMA). - 0003-990X .- 1538-3636. ; 64:1, s. 42-48
-
Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Postpartum psychosis occurs in 1 to 2 cases per 1000 live births. Most studies have not distinguished postpartum psychosis from bipolar disorder or the proportion of the incidence attributable to prepregnancy psychiatric morbidity. OBJECTIVE: To determine the incidence of postpartum psychosis and bipolar disorder attributable to previous psychiatric hospitalization. DESIGN: Population-based study using linked registry data to determine postpartum onset of psychotic and bipolar episodes within 90 days after the first birth, by women with and without prepregnancy or prenatal psychiatric hospitalization. We assessed the type, number, and recency of previous hospitalizations on the incidence of hospitalization for postpartum psychotic and bipolar episodes. SETTING: Nationwide Swedish Hospital Discharge and Medical Birth registers. PATIENTS: Swedish women delivering a first live infant between January 1, 1987, and December 31, 2001. MAIN OUTCOME MEASURES: Postpartum hospitalization for psychosis or bipolar disorder. RESULTS: The cumulative incidences for postpartum psychotic and bipolar episodes (adjusted for age at first birth) were 0.07% and 0.03%, respectively. The incidence of psychiatric hospitalizations for postpartum psychotic or bipolar episodes among women without previous psychiatric hospitalizations was 0.04% and 0.01% of first births, respectively; for women with any psychiatric hospitalization before delivery, the incidence was 9.24% and 4.48%, respectively. For postpartum psychotic and bipolar episodes, the risk increased significantly with the recency of prepregnancy hospitalizations, number of previous hospitalizations, and length of most recent hospitalization. More than 40% of women hospitalized during the prenatal period for a bipolar or a psychotic condition were hospitalized again during the postpartum period. Approximately 90% of all postpartum psychotic and bipolar episodes occurred within the first 4 weeks after delivery. CONCLUSIONS: Almost 10% of women hospitalized for psychiatric morbidity before delivery develop postpartum psychosis after their first birth. This underscores the need for obstetricians to assess history of psychiatric symptoms and, with pediatric and psychiatric colleagues, to optimize the treatment of mothers with psychiatric diagnoses through childbirth.
|
|
| 5. |
- Harlow, Bernard L., et al.
(författare)
-
The Association Between Immune-Related Conditions Across the Life-Course and Provoked Vulvodynia
- 2023
-
Ingår i: Journal of Pain. - : Elsevier BV. - 1526-5900 .- 1528-8447. ; 24:8, s. 1415-1422
-
Tidskriftsartikel (refereegranskat)abstract
- Vulvodynia, impacts up to 8% of women by age 40, and is hypothesized to manifest through an altered immune-inflammatory response. To test this hypothesis, we identified all women born in Sweden between 1973 and 1996 diagnosed with localized provoked vulvodynia (N76.3) and/or vaginismus (N94.2 or F52.5) between 2001 and 2018. We matched each case to two women from the same birth year with no vulvar pain ICD codes. As a proxy for immune dysfunction, we used Swedish Registry data to capture 1) immunodeficiencies, 2) single organ and multiorgan autoimmune conditions, 3) allergy and atopies, and 4) malignancies involving immune cells across the life course. Women with vulvodynia, vaginismus or both were more likely to experience immune deficiencies (OR 1.8, 95% CI, 1.2–2.8), single organ (OR 1.4, 95% CI, 1.2–1.6) and/or multi-organ (OR 1.6, 95% CI, 1.3–1.9) immune disorders, and allergy/atopy conditions (OR 1.7, 95% CI, 1.6–1.8) compared to controls. We observed greater risk with increasing numbers of unique immune related conditions (1 code: OR = 1.6, 95% CI, 1.5–1.7; 2 codes: OR = 2.4, 95% CI, 2.1–2.9; 3 or more codes: OR = 2.9, 1.6–5.4). These findings suggest that women with vulvodynia may have a more compromised immune system either at birth or at points across the life course than women with no vulvar pain history.
|
|
| 6. |
- Lees, Matthew J., et al.
(författare)
-
Novel Essential Amino Acid Supplements Following Resistance Exercise Induce Aminoacidemia and Enhance Anabolic Signaling Irrespective of Age : A Proof-of-Concept Trial
- 2020
-
Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 12:7, s. 2067-
-
Tidskriftsartikel (refereegranskat)abstract
- We investigated the effects of ingesting a leucine-enriched essential amino acid (EAA) gel alone or combined with resistance exercise (RE) versus RE alone (control) on plasma aminoacidemia and intramyocellular anabolic signaling in healthy younger (28 +/- 4 years) and older (71 +/- 3 years) adults. Blood samples were obtained throughout the three trials, while muscle biopsies were collected in the postabsorptive state and 2 h following RE, following the consumption of two 50 mL EAA gels (40% leucine, 15 g total EAA), and following RE with EAA (combination (COM)). Protein content and the phosphorylation status of key anabolic signaling proteins were determined via immunoblotting. Irrespective of age, during EAA and COM peak leucinemia (younger: 454 +/- 32 mu M and 537 +/- 111 mu M; older: 417 +/- 99 mu M and 553 +/- 136 mu M) occurred similar to 60-120 min post-ingestion (younger: 66 +/- 6 min and 120 +/- 60 min; older: 90 +/- 13 min and 78 +/- 12 min). In the pooled sample, the area under the curve for plasma leucine and the sum of branched-chain amino acids was significantly greater in EAA and COM compared with RE. For intramyocellular signaling, significant main effects were found for condition (mTOR (Ser2481), rpS6 (Ser235/236)) and age (S6K1 (Thr421/Ser424), 4E-BP1 (Thr37/46)) in age group analyses. The phosphorylation of rpS6 was of similar magnitude (similar to 8-fold) in pooled and age group data 2 h following COM. Our findings suggest that a gel-based, leucine-enriched EAA supplement is associated with aminoacidemia and a muscle anabolic signaling response, thus representing an effective means of stimulating muscle protein anabolism in younger and older adults following EAA and COM.
|
|
| 7. |
- Pfaff, Sebastian, et al.
(författare)
-
Operando Reflectance Microscopy on Polycrystalline Surfaces in Thermal Catalysis, Electrocatalysis, and Corrosion
- 2021
-
Ingår i: ACS applied materials & interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 13:16, s. 19530-19540
-
Tidskriftsartikel (refereegranskat)abstract
- We have developed a microscope with a spatial resolution of 5 μm, which can be used to image the two-dimensional surface optical reflectance (2D-SOR) of polycrystalline samples in operando conditions. Within the field of surface science, operando tools that give information about the surface structure or chemistry of a sample under realistic experimental conditions have proven to be very valuable to understand the intrinsic reaction mechanisms in thermal catalysis, electrocatalysis, and corrosion science. To study heterogeneous surfaces in situ, the experimental technique must both have spatial resolution and be able to probe through gas or electrolyte. Traditional electron-based surface science techniques are difficult to use under high gas pressure conditions or in an electrolyte due to the short mean free path of electrons. Since it uses visible light, SOR can easily be used under high gas pressure conditions and in the presence of an electrolyte. In this work, we use SOR in combination with a light microscope to gain information about the surface under realistic experimental conditions. We demonstrate this by studying the different grains of three polycrystalline samples: Pd during CO oxidation, Au in electrocatalysis, and duplex stainless steel in corrosion. Optical light-based techniques such as SOR could prove to be a good alternative or addition to more complicated techniques in improving our understanding of complex polycrystalline surfaces with operando measurements.
|
|
| 8. |
|
|
| 9. |
- Valdimarsdottir, Unnur, et al.
(författare)
-
Psychotic Illness in First-Time Mothers with No Previous Psychiatric Hospitalizations : A Population-Based Study
- 2009
-
Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 6:2, s. 194-201
-
Tidskriftsartikel (refereegranskat)abstract
- Background Psychotic illness following childbirth is a relatively rare but severe condition with unexplained etiology. The aim of this study was to investigate the impact of maternal background characteristics and obstetric factors on the risk of postpartum psychosis, specifically among mothers with no previous psychiatric hospitalizations. Methods and Findings We investigated incidence rates and potential maternal and obstetric risk factors of psychoses after childbirth in a national cohort of women who were first-time mothers from 1983 through 2000 (n=745,596). Proportional hazard regression models were used to estimate relative risks of psychoses during and after the first 90 d postpartum, among mothers without any previous psychiatric hospitalization and among all mothers. Within 90 d after delivery, 892 women (1.2 per 1,000 births; 4.84 per 1,000 person-years) were hospitalized due to psychoses and 436 of these (0.6 per 1,000 births; 2.38 per 1,000 person-years) had not previously been hospitalized for any psychiatric disorder. During follow-up after the 90 d postpartum period, the corresponding incidence rates per 1,000 person-years were reduced to 0.65 for all women and 0.49 for women not previously hospitalized. During (but not after) the first 90 d postpartum the risk of psychoses among women without any previous psychiatric hospitalization was independently affected by: maternal age (35 y or older versus 19 y or younger; hazard ratio 2.4, 95% confidence interval [CI] 1.2 to 4.7); high birth weight (>= 4,500 g; hazard ratio 0.3, 95% CI 0.1 to 1.0); and diabetes (hazard ratio 0). Conclusions The incidence of psychotic illness peaks immediately following a first childbirth, and almost 50% of the cases are women without any previous psychiatric hospitalization. High maternal age increases the risk while diabetes and high birth weight are associated with reduced risk of first-onset psychoses, distinctly during the postpartum period.
|
|
