| 1. |
- Horger, B A, et al.
(författare)
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Neurturin exerts potent actions on survival and function of midbrain dopaminergic neurons
- 1998
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Ingår i: The Journal of Neuroscience. - 1529-2401. ; 18:13, s. 4929-4937
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Tidskriftsartikel (refereegranskat)abstract
- Glial cell line-derived neurotrophic factor (GDNF) exhibits potent effects on survival and function of midbrain dopaminergic (DA) neurons in a variety of models. Although other growth factors expressed in the vicinity of developing DA neurons have been reported to support survival of DA neurons in vitro, to date none of these factors duplicate the potent and selective actions of GDNF in vivo. We report here that neurturin (NTN), a homolog of GDNF, is expressed in the nigrostriatal system, and that NTN exerts potent effects on survival and function of midbrain DA neurons. Our findings indicate that NTN mRNA is sequentially expressed in the ventral midbrain and striatum during development and that NTN exhibits survival-promoting actions on both developing and mature DA neurons. In vitro, NTN supports survival of embryonic DA neurons, and in vivo, direct injection of NTN into the substantia nigra protects mature DA neurons from cell death induced by 6-OHDA. Furthermore, administration of NTN into the striatum of intact adult animals induces behavioral and biochemical changes associated with functional upregulation of nigral DA neurons. The similarity in potency and efficacy of NTN and GDNF on DA neurons in several paradigms stands in contrast to the differential distribution of the receptor components GDNF Family Receptor alpha1 (GFRalpha1) and GFRalpha2 within the ventral mesencephalon. These results suggest that NTN is an endogenous trophic factor for midbrain DA neurons and point to the possibility that GDNF and NTN may exert redundant trophic influences on nigral DA neurons acting via a receptor complex that includes GFRalpha1.
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| 2. |
- Nunez, J. C. B., et al.
(författare)
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Footprints of natural selection at the mannose-6-phosphate isomerase locus in barnacles
- 2020
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 117:10, s. 5376-5385
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Tidskriftsartikel (refereegranskat)abstract
- The mannose-6-phosphate isomerase (Mpi) locus in Semibalanus balanoides has been studied as a candidate gene for balancing selection for more than two decades. Previous work has shown that Mpi allozyme genotypes (fast and slow) have different fre-quencies across Atlantic intertidal zones due to selection on post-settlement survival (i.e., allele zonation). We present the complete gene sequence of the Mpi locus and quantify nucleotide polymor-phism in S. balanoides, as well as divergence to its sister taxon Semibalanus cariosus. We show that the slow allozyme contains a derived charge-altering amino acid polymorphism, and both allo-zyme classes correspond to two haplogroups with multiple internal haplotypes. The locus shows several footprints of balancing selec-tion around the fast/slow site: an enrichment of positive Tajima's D for nonsynonymous mutations, an excess of polymorphism, and a spike in the levels of silent polymorphism relative to silent diver-gence, as well as a site frequency spectrum enriched for midfre-quency mutations. We observe other departures from neutrality across the locus in both coding and noncoding regions. These in-clude a nonsynonymous trans-species polymorphism and a recent mutation under selection within the fast haplogroup. The latter suggests ongoing allelic replacement of functionally relevant amino acid variants. Moreover, predicted models of Mpi protein structure provide insight into the functional significance of the putatively selected amino acid polymorphisms. While footprints of selection are widespread across the range of S. balanoides, our data show that intertidal zonation patterns are variable across both spatial and temporal scales. These data provide further evidence for heteroge-neous selection on Mpi.
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| 3. |
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| 4. |
- Nemlander, E., et al.
(författare)
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A machine learning tool for identifying non-metastatic colorectal cancer in primary care
- 2023
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 182, s. 100-106
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Tidskriftsartikel (refereegranskat)abstract
- Background: Primary health care (PHC) is often the first point of contact when diagnosing colorectal cancer (CRC). Human limitations in processing large amounts of information warrant the use of machine learning as a diagnostic prediction tool for CRC. Aim: To develop a predictive model for identifying non-metastatic CRC (NMCRC) among PHC patients using diagnostic data analysed with machine learning. Design and setting: A case-control study containing data on PHC visits for 542 patients >18 years old diagnosed with NMCRC in the Vastra Gotaland Region, Sweden, during 2011, and 2,139 matched controls. Method: Stochastic gradient boosting (SGB) was used to construct a model for predicting the presence of NMCRC based on diagnostic codes from PHC consultations during the year before the date of cancer diagnosis and the total number of consultations. Variables with a normalised relative influence (NRI) >1% were considered having an important contribution to the model. Risks of having NMCRC were calculated using odds ratios of marginal effects. Results: Of the 361 variables used as predictors in the stochastic gradient boosting model, 184 had non-zero influence, with 16 variables having NRI >1% and a combined NRI of 63.3%. Variables representing anaemia and bleeding had a combined NRI of 27.6%. The model had a sensitivity of 73.3% and a specificity of 83.5%. Change in bowel habit had the highest odds ratios of marginal effects at 28.8. Conclusion: Machine learning is useful for identifying variables of importance for predicting NMCRC in PHC. Malignant diagnoses may be hidden behind benign symptoms such as haemorrhoids. 2023 The Author(s). Published by Elsevier Ltd.
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| 5. |
- Nilsson, O G, et al.
(författare)
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Spatial learning impairments in rats with selective immunolesion of the forebrain cholinergic system
- 1992
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Ingår i: NeuroReport. - 0959-4965. ; 3:11, s. 8-1005
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Tidskriftsartikel (refereegranskat)abstract
- A monoclonal antibody to the low-affinity NGF receptor, 192 IgG, coupled to a cytotoxin, saporin, was recently introduced as an efficient selective neurotoxin for the NGFr-bearing cholinergic neurones in the rat basal forebrain. In the present study we report that an intracerebroventricular injection of this 192 IgG-saporin conjugate induces a severe, long-lasting spatial learning impairment, as assessed in the Morris water-maze task. This behavioural impairment was associated with 65-90% depletion of choline acetyltransferase activity (ChAT) in the hippocampus and cortex. ChAT activity associated with other cholinergic neurone systems in the brain (striatum, mesencephalon, spinal cord), was left virtually unaffected. This new immunotoxin holds great promise as a tool for selective and efficient lesions of the forebrain cholinergic system in functional and behavioural studies.
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| 6. |
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| 7. |
- Nunez, J. C. B., et al.
(författare)
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From tides to nucleotides: Genomic signatures of adaptation to environmental heterogeneity in barnacles
- 2021
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Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 30:23, s. 6417-6433
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Tidskriftsartikel (refereegranskat)abstract
- The northern acorn barnacle (Semibalanus balanoides) is a robust system to study the genetic basis of adaptations to highly heterogeneous environments. Adult barnacles may be exposed to highly dissimilar levels of thermal stress depending on where they settle in the intertidal (i.e., closer to the upper or lower tidal boundary). For instance, barnacles near the upper tidal limit experience episodic summer temperatures above recorded heat coma levels. This differential stress at the microhabitat level is also dependent on the aspect of sun exposure. In the present study, we used pool-seq approaches to conduct a genome wide screen for loci responding to intertidal zonation across the North Atlantic basin (Maine, Rhode Island, and Norway). Our analysis discovered 382 genomic regions containing SNPs which are consistently zonated (i.e., SNPs whose frequencies vary depending on their position in the rocky intertidal) across all surveyed habitats. Notably, most zonated SNPs are young and private to the North Atlantic. These regions show high levels of genetic differentiation across ecologically extreme microhabitats concomitant with elevated levels of genetic variation and Tajima's D, suggesting the action of non-neutral processes. Overall, these findings support the hypothesis that spatially heterogeneous selection is a general and repeatable feature for this species, and that natural selection can maintain functional genetic variation in heterogeneous environments.
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| 8. |
- Rosenblad, Carl, et al.
(författare)
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In vivo protection of nigral dopamine neurons by lentiviral gene transfer of the novel GDNF-family member neublastin/artemin
- 2000
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Ingår i: Molecular and Cellular Neuroscience. - : Elsevier BV. - 1044-7431. ; 15:2, s. 199-214
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Tidskriftsartikel (refereegranskat)abstract
- The glial cell line-derived neurotrophic factor (GDNF)-family of neurotrophic factors consisted until recently of three members, GDNF, neurturin, and persephin. We describe here the cloning of a new GDNF-family member, neublastin (NBN), identical to artemin (ART), recently published (Baloh et al., 1998). Addition of NBN/ART to cultures of fetal mesencephalic dopamine (DA) neurons increased the number of surviving tyrosine hydroxylase (TH)-immunoreactive neurons by approximately 70%, similar to the maximal effect obtained with GDNF. To investigate the neuroprotective effects in vivo, lentiviral vectors carrying the cDNA for NBN/ART or GDNF were injected into the striatum and ventral midbrain. Three weeks after an intrastriatal 6-hydroxydopamine lesion only about 20% of the nigral DA neurons were left in the control group, while 80-90% of the DA neurons remained in the NBN/ART and GDNF treatment groups, and the striatal TH-immunoreactive innervation was partly spared. We conclude that NBN/ART, similarly to GDNF, is a potent neuroprotective factor for the nigrostriatal DA neurons in vivo.
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| 9. |
- Abramova, Anna, 1990, et al.
(författare)
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Sensory receptor repertoire in cyprid antennules of the barnacle Balanus improvisus
- 2019
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:5
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Tidskriftsartikel (refereegranskat)abstract
- - Barnacle settlement involves sensing of a variety of exogenous cues. A pair of antennules is the main sensory organ that the cyprid larva uses to explore the surface. Antennules are equipped with a number of setae that have both chemo- and mechanosensing function. The current study explores the repertoire of sensory receptors in Balanus improvisus cyprid antennules with the goal to better understand sensory systems involved in the settling behavior of this species. We carried out transcriptome sequencing of dissected B. improvisus cyprid antennules. The generated transcriptome assembly was used to search for sensory receptors using HMM models. Among potential chemosensory genes, we identified the ionotropic receptors IR25a, IR8a and IR93a, and several divergent IR candidates to be expressed in the cyprid antennules. We found one gustatory-like receptor but no odorant receptors, chemosensory or odorant-binding proteins. Apart from chemosensory receptors, we also identified 13 potential mechanosensory genes represented by several transient receptor potential channels (TRP) subfamilies. Furthermore, we analyzed changes in expression profiles of IRs and TRPs during the B. improvisus settling process. Several of the sensory genes were differentially expressed during the course of larval settlement. This study gives expanded knowledge about the sensory systems present in barnacles, a taxonomic group for which only limited information about receptors is currently available. It furthermore serves as a starting point for more in depth studies of how sensory signaling affects settling behavior in barnacles with implications for preventing biofouling. © 2019 Abramova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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| 10. |
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