| 1. |
- Ackerley, Rochelle, 1980, et al.
(författare)
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Differential effects of radiant and mechanically applied thermal stimuli on human C-tactile afferent firing patterns.
- 2018
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Ingår i: Journal of neurophysiology. - : American Physiological Society. - 1522-1598 .- 0022-3077. ; 120:4, s. 1885-1892
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Tidskriftsartikel (refereegranskat)abstract
- C-tactile (CT) afferents respond to gentle tactile stimulation, but only a handful of studies in humans and animals have investigated whether their firing is modified by temperature. We describe the effects of radiant thermal stimuli, and of stationary and very slowly moving mechanothermal stimuli, on CT afferent responses. We find that CT afferents are primarily mechanoreceptors, as they fired little during radiant thermal stimuli, but they exhibited different patterns of firing during combined mechano-cool stimulation compared with warming. CTs fired optimally to gentle, very slowly moving, or stationary mechanothermal stimuli delivered at neutral temperature (~32°C, normal skin temperature), but they responded with fewer spikes (median 67% decrease) and at significantly lower rates (47% decrease) during warm (~42°C) tactile stimuli. During cool tactile stimuli (~18°C), their mean instantaneous firing frequency significantly decreased by 35%, but they often fired a barrage of afterdischarge spikes at a low frequency (~5 Hz) that outlasted the mechanical stimulus. These effects were observed under a variety of stimulus conditions, including during stationary and slowly moving touch (0.1 cm/s), and we complemented these tactile approaches using a combined electrical-thermal stimulation experiment where we found a suppression of spiking during warming. Overall, CT afferents are exquisitely sensitive to tactile events, and we show that their firing is modulated with touch temperatures above and below neutral skin temperature. Warm touch consistently decreased their propensity to fire, whereas cool touch produced lower firing rates but afterdischarge spiking. NEW & NOTEWORTHY C-tactile (CT) afferents are thought to underpin pleasant touch, and previous work has shown that they respond optimally to a slow caress delivered at typical (neutral) skin temperature. Here, we show that, although CTs are primarily mechanoreceptive afferents, they are modified by temperature: warm touch decreases their firing, whereas cool touch produces lower firing rates but long-lasting spiking, frequently seen as afterdischarges. This has implications for the encoding of affective sensory events in human skin.
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| 2. |
- Andersson, Ulrika, et al.
(författare)
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A comprehensive study of the association between the EGFR and ERBB2 genes and glioma risk
- 2010
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Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 12, s. 17-17
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Tidskriftsartikel (refereegranskat)abstract
- Glioma is the most common type of adult brain tumor and glioblastoma, its most aggressive form, has a dismal prognosis. Receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR, ERBB2, ERBB3, ERBB4) family, and the vascular endothelial growth factor receptor (VEGFR), play a central role in tumor progression. We investigated the genetic variants of EGFR, ERBB2, VEGFR and their ligands, EGF and VEGF on glioma and glioblastoma risk. In addition, we evaluated the association of genetic variants of a newly discovered family of genes known to interact with EGFR: LRIG2 and LRIG3 with glioma and glioblastoma risk. Methods. We analyzed 191 tag single nucleotide polymorphisms (SNPs) capturing all common genetic variation of EGF, EGFR, ERBB2, LRIG2, LRIG3, VEGF and VEGFR2 genes. Material from four case-control studies with 725 glioma patients (329 of who were glioblastoma patients) and their 1 610 controls was used. Haplotype analyses were conducted using SAS/Genetics software. Results. Fourteen of the SNPs were significantly associated with glioma risk at p< 0.05, and 17 of the SNPs were significantly associated with glioblastoma risk at p< 0.05. In addition, we found that one EGFR haplotype was related to increased glioblastoma risk at p=0.009, Odds Ratio [OR] = 1.67 (95% confidence interval (CI): 1.14, 2.45). The Bonferroni correction made all p-values non-significant. One SNP, rs4947986 next to the intron/exon boundary of exon 7 in EGFR, was validated in an independent data set of 713 glioblastoma and 2 236 controls, [OR] = 1.42 (95% CI: 1.06,1.91). Discussion. Previous studies show that regulation of the EGFR pathway plays a role in glioma progression but the present study is the first to find that certain genotypes of the EGFR gene may be related to glioblastoma risk. Further studies are required to reinvestigate these findings and evaluate the functional significance.
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| 3. |
- Aulestia, Shane, et al.
(författare)
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Effect of increased vertical stress on the state of grains in tailings
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The mining industry has experienced rapid growth, leading to the accumulation of substantial mine waste, commonly referred to as tailings. Tailings are typically stored in tailings storage facilities, conventionally consisting of an impoundment surrounded by tailings dams. The construction of tailings dams can involve various methods, with the upstream method being commonly used in the industry. It is crucial to comprehend the long-term mechanical and geochemical behavior of deposited tailings to ensure the safety of upstream constructed tailings dams. The mineral composition, particle size distribution, and particle shape all affect the susceptibility to particle breakage or physical alternation. Therefore, there is an interest in understanding how grain size and grain shape relate to mineral composition and potential particle breakage to ensure the understanding of the long-term mechanical behavior. This study focuses on characterizing deposited tailings from various depths and investigates the impact of increased vertical stress on tailings, particularly examining the potential for crushing effects. The findings highlight the importance of considering these factors for a comprehensive understanding of tailings behavior and their implications for the long-term safety of tailings dams.
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| 4. |
- Bergh, Jonas, et al.
(författare)
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FACT : An Open-Label Randomized Phase III Study of Fulvestrant and Anastrozole in Combination Compared With Anastrozole Alone as First-Line Therapy for Patients With Receptor-Positive Postmenopausal Breast Cancer
- 2012
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Ingår i: Journal of Clinical Oncology. - Alexandria, VA : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 30:16, s. 1919-1925
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To compare the effect of therapy with anastrozole versus a combination of fulvestrant and anastrozole in women in first relapse of endocrine-responsive breast cancer. Patients and Methods: Postmenopausal women, or premenopausal women receiving a gonadotropin-releasing hormone agonist, with estrogen receptor– and/or progesterone receptor–positive disease at first relapse after primary treatment of localized disease were open-label randomly assigned to a fulvestrant loading dose (LD) regimen followed by monthly injection plus 1 mg of anastrozole daily or to 1 mg of anastrozole daily alone. The primary end point was time to progression (TTP). Results: In all, 514 women were randomly assigned to fulvestrant plus anastrozole (experimental arm; n = 258) or anastrozole (standard arm; n = 256). Approximately two thirds had received adjuvant antiestrogens, but only eight individuals had received an aromatase inhibitor. Median TTP was 10.8 and 10.2 months in the experimental versus standard arm, respectively (hazard ratio [HR] = 0.99; 95% CI, 0.81 to 1.20; P = .91); median overall survival was 37.8 and 38.2 months, respectively (HR = 1.0; 95% CI, 0.76 to 1.32; P = 1.00). Incidences of prespecified adverse events (AEs) were similar. Hot flashes were more common in the experimental arm: 63 patients (24.6%) versus 35 patients (13.8%) in the standard arm (P = .0023). Death owing to AEs was reported in 11 (4.3%) and five patients (2.0%) in the experimental versus standard arm, respectively. Conclusion: Fulvestrant (250 mg + LD regimen) in combination with anastrozole offered no clinical efficacy advantage over anastrozole monotherapy in this population of individuals with a relatively high proportion of previous adjuvant antiestrogen exposure.
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| 5. |
- Boman, Jesper, et al.
(författare)
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Evolution of hybrid inviability associated with chromosome fusions
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Chromosomal rearrangements, such as inversions, have received considerable attention in the speciation literature due to their hampering effects on recombination. However, less is known about how other rearrangements, such as chromosome fissions and fusions, can affect the evolution of reproductive isolation. Here, we used crosses between populations of the wood white butterfly (Leptidea sinapis) with different karyotypes to identify genomic regions associated with hybrid inviability. We mapped candidate loci for hybrid inviability by contrasting allele frequencies between F2 hybrids that survived until the adult stage with individuals of the same cohort that succumbed to hybrid incompatibilities. Hybrid inviability factors were predominantly found in fast-evolving regions with reduced recombination rates, especially in regions where chromosome fusions have occurred. By analyzing sequencing coverage, we excluded aneuploidies as a direct link between hybrid inviability and chromosome fusions. Instead, our results point to an indirect relationship between hybrid inviability and chromosome fusions, possibly related to reductions in recombination rate caused by fusions. These results highlight that the extensive variation in chromosome numbers observed across the tree of life does not only distinguish species but can also be involved in speciation by being hotspots for the early evolution of postzygotic reproductive isolation.
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| 6. |
- Boman, Jesper, et al.
(författare)
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Meiotic drive against chromosome fusions in butterfly hybrids
- 2024
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Ingår i: Chromosome Research. - : Springer. - 0967-3849 .- 1573-6849. ; 32:2
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Tidskriftsartikel (refereegranskat)abstract
- Species frequently differ in the number and structure of chromosomes they harbor, but individuals that are heterozygous for chromosomal rearrangements may suffer from reduced fitness. Chromosomal rearrangements like fissions and fusions can hence serve as a mechanism for speciation between incipient lineages, but their evolution poses a paradox. How can rearrangements get fixed between populations if heterozygotes have reduced fitness? One solution is that this process predominantly occurs in small and isolated populations, where genetic drift can override natural selection. However, fixation is also more likely if a novel rearrangement is favored by a transmission bias, such as meiotic drive. Here, we investigate chromosomal transmission distortion in hybrids between two wood white (Leptidea sinapis) butterfly populations with extensive karyotype differences. Using data from two different crossing experiments, we uncover that there is a transmission bias favoring the ancestral chromosomal state for derived fusions, a result that shows that chromosome fusions actually can fix in populations despite being counteracted by meiotic drive. This means that meiotic drive not only can promote runaway chromosome number evolution and speciation, but also that it can be a conservative force acting against karyotypic change and the evolution of reproductive isolation. Based on our results, we suggest a mechanistic model for why chromosome fusion mutations may be opposed by meiotic drive and discuss factors contributing to karyotype evolution in Lepidoptera.
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| 7. |
- Höök, Lars, et al.
(författare)
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Dualistic dosage compensation and rapid evolution of expression balance in response to W chromosome degeneration in Leptidea butterflies
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The evolution of dimorphic sex chromosomes from initially homologous autosomes is generally explained by sex-specific selection to maintain linkage between a sex determining locus and genes that are beneficial to the same sex. While initially beneficial, the strong linkage and reduced recombination causes differentiation and degeneration of many initially shared genes. Reduced copy numbers can have severe consequences for the balance of gene expression levels between sex-linked genes and the rest of the genome. Consequently, dosage compensation has evolved independently in different lineages to mitigate the detrimental effects of unbalanced expression of sex-linked genes in the heterogametic sex. However, the variation in sex chromosome regulation in different lineages, puts the need to restore expression to ancestral levels into question. In particular, a general difference has been observed between male- (XY) and female-heterogametic (ZW) systems. In contrast to the X chromosome upregulation in heterogametic males in the XY-systems, the Z chromosomes are rarely upregulated in the heterogametic females in organisms with ZW-systems. Instead, the Z chromosomes are often downregulated in the homogametic males to achieve inter-sexual balance. Although progress has been made to understand what causes this discrepancy, comparative approaches are limited by long divergence times and ancient sex chromosome systems. An attractive approach is therefore to study the evolution of gene regulation on recently derived neo-sex chromosomes, formed through fusions between ancestral sex chromosomes and autosomes. Here, we investigated dosage compensation of neo-sex chromosomes in three closely related butterflies in the cryptic wood white clade (Leptidea). Importantly, the species have acquired multiple sex chromosomes, and dosage compensation could therefore have evolved repeatedly in the clade. Our analyses reveal a mixture of gene expression patterns which suggests that distinct modes of dosage compensation have evolved on the different Z chromosomes. In addition, we detect evidence that dosage balancing mechanisms have been rapidly recruited to the youngest neo-Z chromosome, to counteract an ongoing degeneration of neo-W gametologs. The results add to a growing list of examples where diverse dosage compensation mechanisms can evolve within a single species, and suggests that various regulatory mechanisms are not restricted to specific sex chromosome systems.
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| 8. |
- Höök, Lars, et al.
(författare)
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High-density linkage maps and chromosome level genome assemblies unveil direction and frequency of extensive structural rearrangements in wood white butterflies (Leptidea spp.)
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Tidskriftsartikel (refereegranskat)abstract
- Karyotypes are generally conserved between closely related species and large chromosome rearrangements typically have negative fitness consequences in heterozygotes, potentially driving speciation. In the order Lepidoptera, most investigated species have the ancestral karyotype and gene synteny is often conserved across deep divergence, although examples of extensive genome reshuffling have recently been demonstrated. The genus Leptidea has an unusual level of chromosome variation and rearranged sex chromosomes, but the extent of restructuring across the rest of the genome is so far unknown. To explore the genomes of the wood white (Leptidea) species complex, we generated eight genome assemblies using a combination of 10X linked reads and HiC data, and improved them using linkage maps for two populations of the common wood white (L. sinapis) with distinct karyotypes. Synteny analysis revealed an extensive amount of rearrangements, both compared to the ancestral karyotype and between the Leptidea species, where only one of the three Z chromosomes was conserved across all comparisons. Most restructuring was explained by fissions and fusions, while translocations appear relatively rare. We further detected several examples of segregating rearrangement polymorphisms supporting a highly dynamic genome evolution in this clade. Fusion breakpoints were enriched for LINEs and LTR elements, which suggests that ectopic recombination might be an important driver in the formation of new chromosomes. Our results show that chromosome count alone may conceal the extent of genome restructuring and we propose that the amount of genome evolution in Lepidoptera might still be underestimated due to lack of taxonomic sampling.
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| 9. |
- Höök, Lars, 1980-, et al.
(författare)
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Temporal dynamics of faster neo-Z evolution in butterflies
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The faster-Z/X hypothesis predicts that sex-linked genes should diverge faster than autosomal genes and may therefore play important roles in speciation. However, studies across different lineages have shown mixed support for this effect, a variation that has been explained by various evolutionary mechanisms. So far, most analyses have focused on systems with old and well differentiated sex chromosomes, but less is known about divergence of more recently acquired neo-sex chromosomes. In the female heterogametic order Lepidoptera (moths and butterflies), fusions between the ancestral Z chromosome and autosomes are relatively frequent, but the evolutionary dynamics of neo Z-linked genes have not been explored in detail. Here, we analysed the faster-Z effect in Leptidea sinapis, a butterfly with an exceptionally reorganized genome and three Z chromosomes. We show that the neo-Z chromosomes have been acquired in a stepwise fashion, resulting in distinct strata of differentiation and masculinization. While Z-linked divergence generally seems to have been driven by adaptive processes, the relative effects of selection and drift showed a temporal trend where selection has been more prevalent for genes located on older Z linked regions, causing increased divergence of Z-linked genes with female-biased expression. In contrast, the intensity of selection on genes located on the most recently acquired neo-Z chromosome (Z3) appears to have been hampered by the presence of gametologs on the largely intact, homologous neo-W chromosome. However, the intermediately aged neo-Z chromosome (Z2), which is completely differentiated from W gametologs, showed less evolutionary constraint than the ancestral Z, resulting in particularly fast evolution. Our results therefore support that neo-sex chromosomes can constitute temporary hot-spots of adaptation and divergence. The underlying dynamics are likely causally linked to shifts in selective constraints, evolution of gene expression and the degeneration of W-linked gametologs which gradually expose Z-linked genes to selection.
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| 10. |
- Höök, Lars, et al.
(författare)
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Temporal dynamics of faster neo-Z evolution in butterflies
- 2024
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Ingår i: Evolution. - 0014-3820 .- 1558-5646.
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Tidskriftsartikel (refereegranskat)abstract
- The faster-Z/X hypothesis predicts that sex-linked genes should diverge faster than autosomal genes. However, studies across different lineages have shown mixed support for this effect. So far, most analyses have focused on old and well-differentiated sex chromosomes, but less is known about the divergence of more recently acquired neo-sex chromosomes. In Lepidoptera (moths and butterflies), Z-autosome fusions are frequent, but the evolutionary dynamics of neo-Z chromosomes have not been explored in detail. Here, we analyzed the faster-Z effect in Leptidea sinapis, a butterfly with three Z chromosomes. We show that the neo-Z chromosomes have been acquired stepwise, resulting in strata of differentiation and masculinization. While all Z chromosomes showed evidence of the faster-Z effect, selection for genes on the youngest neo-Z chromosome (Z3) appears to have been hampered by a largely intact, homologous neo-W chromosome. However, the intermediately aged neo-Z chromosome (Z2), which lacks W gametologs, showed fewer evolutionary constraints, resulting in particularly fast evolution. Our results therefore support that neo-sex chromosomes can constitute temporary hot-spots of adaptation and divergence. The underlying dynamics are likely causally linked to shifts in selective constraints, evolution of gene expression, and degeneration of W-linked gametologs which gradually expose Z-linked genes to selection.
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