SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Novikova J.) "

Sökning: WFRF:(Novikova J.)

  • Resultat 1-45 av 45
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Tabiri, S, et al. (författare)
  • 2021
  • swepub:Mat__t
  •  
2.
  • 2017
  • swepub:Mat__t
  •  
3.
  • Bravo, L, et al. (författare)
  • 2021
  • swepub:Mat__t
  •  
4.
  •  
5.
  •  
6.
  •  
7.
  •  
8.
  • Zaborowski, AM, et al. (författare)
  • Microsatellite instability in young patients with rectal cancer: molecular findings and treatment response
  • 2022
  • Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 109:3, s. 251-255
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study of 400 patients with early-onset rectal cancer, 12.5 per cent demonstrated microsatellite instability (MSI). MSI was associated with a reduced likelihood of nodal positivity, an increased rate of pathological complete response, and improved disease-specific survival.
  •  
9.
  •  
10.
  •  
11.
  •  
12.
  • Al Moubayed, Samer, et al. (författare)
  • Human-robot Collaborative Tutoring Using Multiparty Multimodal Spoken Dialogue
  • 2014
  • Konferensbidrag (refereegranskat)abstract
    • In this paper, we describe a project that explores a novel experi-mental setup towards building a spoken, multi-modally rich, and human-like multiparty tutoring robot. A human-robotinteraction setup is designed, and a human-human dialogue corpus is collect-ed. The corpus targets the development of a dialogue system platform to study verbal and nonverbaltutoring strategies in mul-tiparty spoken interactions with robots which are capable of spo-ken dialogue. The dialogue task is centered on two participants involved in a dialogueaiming to solve a card-ordering game. Along with the participants sits a tutor (robot) that helps the par-ticipants perform the task, and organizes and balances their inter-action. Differentmultimodal signals captured and auto-synchronized by different audio-visual capture technologies, such as a microphone array, Kinects, and video cameras, were coupled with manual annotations. These are used build a situated model of the interaction based on the participants personalities, their state of attention, their conversational engagement and verbal domi-nance, and how that is correlated with the verbal and visual feed-back, turn-management, and conversation regulatory actions gen-erated by the tutor. Driven by the analysis of the corpus, we will show also the detailed design methodologies for an affective, and multimodally rich dialogue system that allows the robot to meas-ure incrementally the attention states, and the dominance for each participant, allowing the robot head Furhat to maintain a well-coordinated, balanced, and engaging conversation, that attempts to maximize the agreement and the contribution to solve the task. This project sets the first steps to explore the potential of us-ing multimodal dialogue systems to build interactive robots that can serve in educational, team building, and collaborative task solving applications.
  •  
13.
  • Al Moubayed, Samer, et al. (författare)
  • Tutoring Robots: Multiparty Multimodal Social Dialogue With an Embodied Tutor
  • 2014
  • Konferensbidrag (refereegranskat)abstract
    • This project explores a novel experimental setup towards building spoken, multi-modally rich, and human-like multiparty tutoring agent. A setup is developed and a corpus is collected that targets the development of a dialogue system platform to explore verbal and nonverbal tutoring strategies in multiparty spoken interactions with embodied agents. The dialogue task is centered on two participants involved in a dialogue aiming to solve a card-ordering game. With the participants sits a tutor that helps the participants perform the task and organizes and balances their interaction. Different multimodal signals captured and auto-synchronized by different audio-visual capture technologies were coupled with manual annotations to build a situated model of the interaction based on the participants personalities, their temporally-changing state of attention, their conversational engagement and verbal dominance, and the way these are correlated with the verbal and visual feedback, turn-management, and conversation regulatory actions generated by the tutor. At the end of this chapter we discuss the potential areas of research and developments this work opens and some of the challenges that lie in the road ahead.
  •  
14.
  • Alonso-Blanco, Carlos, et al. (författare)
  • 1,135 Genomes Reveal the Global Pattern of Polymorphism in Arabidopsis thaliana
  • 2016
  • Ingår i: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 166:2, s. 481-491
  • Tidskriftsartikel (refereegranskat)abstract
    • Arabidopsis thaliana serves as a model organism for the study of fundamental physiological, cellular, and molecular processes. It has also greatly advanced our understanding of intraspecific genome variation. We present a detailed map of variation in 1,135 high-quality re-sequenced natural inbred lines representing the native Eurasian and North African range and recently colonized North America. We identify relict populations that continue to inhabit ancestral habitats, primarily in the Iberian Peninsula. They have mixed with a lineage that has spread to northern latitudes from an unknown glacial refugium and is now found in a much broader spectrum of habitats. Insights into the history of the species and the fine-scale distribution of genetic diversity provide the basis for full exploitation of A. thaliana natural variation through integration of genomes and epigenomes with molecular and non-molecular phenotypes.
  •  
15.
  •  
16.
  •  
17.
  • Kawakatsu, Taiji, et al. (författare)
  • Epigenomic Diversity in a Global Collection of Arabidopsis thaliana Accessions
  • 2016
  • Ingår i: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 166:2, s. 492-505
  • Tidskriftsartikel (refereegranskat)abstract
    • The epigenome orchestrates genome accessibility, functionality, and three-dimensional structure. Because epigenetic variation can impact transcription and thus phenotypes, it may contribute to adaptation. Here, we report 1,107 high-quality single-base resolution methylomes and 1,203 transcriptomes from the 1001 Genomes collection of Arabidopsis thaliana. Although the genetic basis of methylation variation is highly complex, geographic origin is a major predictor of genome-wide DNA methylation levels and of altered gene expression caused by epialleles. Comparison to cistrome and epicistrome datasets identifies associations between transcription factor binding sites, methylation, nucleotide variation, and co-expression modules. Physical maps for nine of the most diverse genomes reveal how transposons and other structural variants shape the epigenome, with dramatic effects on immunity genes. The 1001 Epigenomes Project provides a comprehensive resource for understanding how variation in DNA methylation contributes to molecular and non-molecular phenotypes in natural populations of the most studied model plant.
  •  
18.
  • Novikova, P. Y., et al. (författare)
  • Sequencing of the genus Arabidopsis identifies a complex history of nonbifurcating speciation and abundant trans-specific polymorphism
  • 2016
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:9, s. 1077-1082
  • Tidskriftsartikel (refereegranskat)abstract
    • The notion of species as reproductively isolated units related through a bifurcating tree implies that gene trees should generally agree with the species tree and that sister taxa should not share polymorphisms unless they diverged recently and should be equally closely related to outgroups. It is now possible to evaluate this model systematically. We sequenced multiple individuals from 27 described taxa representing the entire Arabidopsis genus. Cluster analysis identified seven groups, corresponding to described species that capture the structure of the genus. However, at the level of gene trees, only the separation of Arabidopsis thaliana from the remaining species was universally supported, and, overall, the amount of shared polymorphism demonstrated that reproductive isolation was considerably more recent than the estimated divergence times. We uncovered multiple cases of past gene flow that contradict a bifurcating species tree. Finally, we showed that the pattern of divergence differs between gene ontologies, suggesting a role for selection. © 2016 Nature America, Inc. All rights reserved.
  •  
19.
  • Banas, Indra, et al. (författare)
  • Spatio-functional organization in virocells of small uncultivated archaea from the deep biosphere
  • 2023
  • Ingår i: The ISME Journal. - : Springer Nature. - 1751-7362 .- 1751-7370. ; 17, s. 1789-1792
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite important ecological roles posited for virocells (i.e., cells infected with viruses), studying individual cells in situ is technically challenging. We introduce here a novel correlative microscopic approach to study the ecophysiology of virocells. By conducting concerted virusFISH, 16S rRNA FISH, and scanning electron microscopy interrogations of uncultivated archaea, we linked morphologies of various altiarchaeal cells to corresponding phylogenetic signals and indigenous virus infections. While uninfected cells exhibited moderate separation between fluorescence signals of ribosomes and DNA, virocells displayed complete cellular segregation of chromosomal DNA from viral DNA, the latter co-localizing with host ribosome signals. A similar spatial separation was observed in dividing cells, with viral signals congregating near ribosomes at the septum. These observations suggest that replication of these uncultivated viruses occurs alongside host ribosomes, which are used to generate the required proteins for virion assembly. Heavily infected cells sometimes displayed virus-like particles attached to their surface, which agree with virus structures in cells observed via transmission electron microscopy. Consequently, this approach is the first to link genomes of uncultivated viruses to their respective structures and host cells. Our findings shed new light on the complex ecophysiology of archaeal virocells in deep subsurface biofilms and provide a solid framework for future in situ studies of virocells.
  •  
20.
  • Brachi, B., et al. (författare)
  • Plant genetic effects on microbial hubs impact host fitness in repeated field trials
  • 2022
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:30
  • Tidskriftsartikel (refereegranskat)abstract
    • Although complex interactions between hosts and microbial associates are increasingly well documented, we still know little about how and why hosts shape microbial communities in nature. In addition, host genetic effects on microbial communities vary widely depending on the environment, obscuring conclusions about which microbes are impacted and which plant functions are important. We characterized the leaf microbiota of 200 Arabidopsis thaliana genotypes in eight field experiments and detected consistent host effects on specific, broadly distributed microbial species (operational taxonomic unit [OTUs]). Host genetic effects disproportionately influenced central ecological hubs, with heritability of particular OTUs declining with their distance from the nearest hub within the microbial network. These host effects could reflect either OTUs preferentially associating with specific genotypes or differential microbial success within them. Host genetics associated with microbial hubs explained over 10% of the variation in lifetime seed production among host genotypes across sites and years. We successfully cultured one of these microbial hubs and demonstrated its growth-promoting effects on plants in sterile conditions. Finally, genome-wide association mapping identified many putatively causal genes with small effects on the relative abundance of microbial hubs across sites and years, and these genes were enriched for those involved in the synthesis of specialized metabolites, auxins, and the immune system. Using untargeted metabolomics, we corroborate the consistent association between variation in specialized metabolites and microbial hubs across field sites. Together, our results reveal that host genetic variation impacts the microbial communities in consistent ways across environments and that these effects contribute to fitness variation among host genotypes. 
  •  
21.
  •  
22.
  • Jones, Iwan, et al. (författare)
  • Regenerative effects of human embryonic stem cell-derived neural crest cells for treatment of peripheral nerve injury
  • 2018
  • Ingår i: Journal of Tissue Engineering and Regenerative Medicine. - : Hindawi Limited. - 1932-6254 .- 1932-7005. ; 12:4, s. E2099-E2109
  • Tidskriftsartikel (refereegranskat)abstract
    • Surgical intervention is the current gold standard treatment following peripheral nerve injury. However, this approach has limitations, and full recovery of both motor and sensory modalities often remains incomplete. The development of artificial nerve grafts that either complement or replace current surgical procedures is therefore of paramount importance. An essential component of artificial grafts is biodegradable conduits and transplanted cells that provide trophic support during the regenerative process. Neural crest cells are promising support cell candidates because they are the parent population to many peripheral nervous system lineages. In this study, neural crest cells were differentiated from human embryonic stem cells. The differentiated cells exhibited typical stellate morphology and protein expression signatures that were comparable with native neural crest. Conditioned media harvested from the differentiated cells contained a range of biologically active trophic factors and was able to stimulate in vitro neurite outgrowth. Differentiated neural crest cells were seeded into a biodegradable nerve conduit, and their regeneration potential was assessed in a rat sciatic nerve injury model. A robust regeneration front was observed across the entire width of the conduit seeded with the differentiated neural crest cells. Moreover, the up-regulation of several regeneration-related genes was observed within the dorsal root ganglion and spinal cord segments harvested from transplanted animals. Our results demonstrate that the differentiated neural crest cells are biologically active and provide trophic support to stimulate peripheral nerve regeneration. Differentiated neural crest cells are therefore promising supporting cell candidates to aid in peripheral nerve repair.
  •  
23.
  • Jonsson, Samuel, et al. (författare)
  • Effect of delayed peripheral nerve repair on nerve regeneration, Schwann cell function and target muscle recovery
  • 2013
  • Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite advances in surgical techniques for peripheral nerve repair, functional restitution remains incomplete. The timing of surgery is one factor influencing the extent of recovery but it is not yet clearly defined how long a delay may be tolerated before repair becomes futile. In this study, rats underwent sciatic nerve transection before immediate (0) or 1, 3, or 6 months delayed repair with a nerve graft. Regeneration of spinal motoneurons, 13 weeks after nerve repair, was assessed using retrograde labeling. Nerve tissue was also collected from the proximal and distal stumps and from the nerve graft, together with the medial gastrocnemius (MG) muscles. A dramatic decline in the number of regenerating motoneurons and myelinated axons in the distal nerve stump was observed in the 3- and 6-months delayed groups. After 3 months delay, the axonal number in the proximal stump increased 2-3 folds, accompanied by a smaller axonal area. RT-PCR of distal nerve segments revealed a decline in Schwann cells (SC) markers, most notably in the 3 and 6 month delayed repair samples. There was also a progressive increase in fibrosis and proteoglycan scar markers in the distal nerve with increased delayed repair time. The yield of SC isolated from the distal nerve segments progressively fell with increased delay in repair time but cultured SC from all groups proliferated at similar rates. MG muscle at 3- and 6-months delay repair showed a significant decline in weight (61% and 27% compared with contra-lateral side). Muscle fiber atrophy and changes to neuromuscular junctions were observed with increased delayed repair time suggestive of progressively impaired reinnervation. This study demonstrates that one of the main limiting factors for nerve regeneration after delayed repair is the distal stump. The critical time point after which the outcome of regeneration becomes too poor appears to be 3-months.
  •  
24.
  • Karalija, Amar, et al. (författare)
  • Neuroprotective Effects of N-Acetyl-Cysteine and Acetyl-L-Carnitine after Spinal Cord Injury in Adult Rats
  • 2012
  • Ingår i: PLOS ONE. - San Fransisco : Public library of Science. - 1932-6203. ; 7:7, s. e41086-
  • Tidskriftsartikel (refereegranskat)abstract
    • Following the initial acute stage of spinal cord injury, a cascade of cellular and inflammatory responses will lead to progressive secondary damage of the nerve tissue surrounding the primary injury site. The degeneration is manifested by loss of neurons and glial cells, demyelination and cyst formation. Injury to the mammalian spinal cord results in nearly complete failure of the severed axons to regenerate. We have previously demonstrated that the antioxidants N-acetyl-cysteine (NAC) and acetyl-L-carnitine (ALC) can attenuate retrograde neuronal degeneration after peripheral nerve and ventral root injury. The present study evaluates the effects of NAC and ALC on neuronal survival, axonal sprouting and glial cell reactions after spinal cord injury in adult rats. Tibial motoneurons in the spinal cord were pre-labeled with fluorescent tracer Fast Blue one week before lumbar L5 hemisection. Continuous intrathecal infusion of NAC (2.4 mg/day) or ALC (0.9 mg/day) was initiated immediately after spinal injury using Alzet 2002 osmotic minipumps. Neuroprotective effects of treatment were assessed by counting surviving motoneurons and by using quantitative immunohistochemistry and Western blotting for neuronal and glial cell markers 4 weeks after hemisection. Spinal cord injury induced significant loss of tibial motoneurons in L4-L6 segments. Neuronal degeneration was associated with decreased immunostaining for microtubular-associated protein-2 (MAP2) in dendritic branches, synaptophysin in presynaptic boutons and neurofilaments in nerve fibers. Immunostaining for the astroglial marker GFAP and microglial marker OX42 was increased. Treatment with NAC and ALC rescued approximately half of the motoneurons destined to die. In addition, antioxidants restored MAP2 and synaptophysin immunoreactivity. However, the perineuronal synaptophysin labeling was not recovered. Although both treatments promoted axonal sprouting, there was no effect on reactive astrocytes. In contrast, the microglial reaction was significantly attenuated. The results indicate a therapeutic potential for NAC and ALC in the early treatment of traumatic spinal cord injury.
  •  
25.
  • Karalija, Amar, et al. (författare)
  • The effects of N-acetyl-cysteine and acetyl-l-carnitine on neural survival, neuroinflammation and regeneration following spinal cord injury
  • 2014
  • Ingår i: Neuroscience. - : Elsevier BV. - 0306-4522 .- 1873-7544. ; 269, s. 143-151
  • Tidskriftsartikel (refereegranskat)abstract
    • Traumatic spinal cord injury induces a long-standing inflammatory response in the spinal cord tissue, leading to a progressive apoptotic death of spinal cord neurons and glial cells. We have recently demonstrated that immediate treatment with the antioxidants N-acetyl-cysteine (NAC) and acetyl-l-carnitine (ALC) attenuates neuroinflammation, induces axonal sprouting, and reduces the death of motoneurons in the vicinity of the trauma zone 4weeks after initial trauma. The objective of the current study was to investigate the effects of long-term antioxidant treatment on the survival of descending rubrospinal neurons after spinal cord injury in rats. It also examines the short- and long-term effects of treatment on apoptosis, inflammation, and regeneration in the spinal cord trauma zone. Spinal cord hemisection performed at the level C3 induced a significant loss of rubrospinal neurons 8weeks after injury. At 2weeks, an increase in the expression of the apoptosis-associated markers BCL-2-associated X protein (BAX) and caspase 3, as well as the microglial cell markers OX42 and ectodermal dysplasia 1 (ED1), was seen in the trauma zone. After 8weeks, an increase in immunostaining for OX42 and the serotonin marker 5HT was detected in the same area. Antioxidant therapy reduced the loss of rubrospinal neurons by approximately 50%. Treatment also decreased the expression of BAX, caspase 3, OX42 and ED1 after 2weeks. After 8weeks, treatment decreased immunoreactivity for OX42, whereas it was increased for 5HT. In conclusion, this study provides further insight in the effects of treatment with NAC and ALC on descending pathways, as well as short- and long-term effects on the spinal cord trauma zone.
  •  
26.
  • Kingham, Paul J, et al. (författare)
  • Stimulating the neurotrophic and angiogenic properties of human adipose-derived stem cells enhances nerve repair
  • 2014
  • Ingår i: Stem Cells and Development. - : Mary Ann Liebert Inc. - 1547-3287 .- 1557-8534. ; 23:7, s. 741-754
  • Tidskriftsartikel (refereegranskat)abstract
    • In future, adipose-derived stem cells (ASC) might be used to treat neurological disorders. In this study, the neurotrophic and angiogenic properties of human ASC were evaluated, and their effects in a peripheral nerve injury model were determined. In vitro growth factor stimulation of the cells resulted in increased secretion of brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), vascular endothelial growth factor-A (VEGF-A), and angiopoietin-1 proteins. Conditioned medium from stimulated cells increased neurite outgrowth of dorsal root ganglia (DRG) neurons. Similarly, stimulated cells showed an enhanced ability to induce capillary-like tube formation in an in vitro angiogenesis assay. ASC were seeded into a fibrin conduit that was used to bridge a 10 mm rat nerve gap. After 2 weeks, the animals treated with control or stimulated ASC showed an enhanced axon regeneration distance. Stimulated cells evoked more total axon growth. Analysis of regeneration and apoptosis-related gene expression showed that both ASC and stimulated ASC enhanced GAP-43 and activating transcription factor 3 (ATF-3) expression in the spinal cord and reduced c-jun expression in the DRG. Caspase-3 expression in the DRG was reduced by stimulated ASC. Both ASC and stimulated ASC also increased the vascularity of the fibrin nerve conduits. Thus, ASC produce functional neurotrophic and angiogenic factors, creating a more desirable microenvironment for nerve regeneration.
  •  
27.
  • Kolar, Mallappa K, et al. (författare)
  • The therapeutic effects of human adipose derived stem cells in a rat cervical spinal cord injury model
  • 2014
  • Ingår i: Stem Cells and Development. - : Mary Ann Liebert. - 1547-3287 .- 1557-8534. ; 23:14, s. 1659-1674
  • Tidskriftsartikel (refereegranskat)abstract
    • Spinal cord injury triggers a cascade of degenerative changes leading to cell death and cavitation. Severed axons fail to regenerate across the scar tissue and are only capable of limited sprouting. In this study we investigated the effects of adult human adipose derived stem cells (ASC) on axonal regeneration following transplantation into the injured rat cervical spinal cord. ASC did not induce activation of astrocytes in culture and supported neurite outgrowth from adult rat sensory DRG neurons. After transplantation into the lateral funiculus 1mm rostral and caudal to the cervical C3-C4 hemisection, ASC continued to express BDNF, VEGF and FGF-2 for 3 weeks but only in animals treated with cyclosporine A. Transplanted ASC stimulated extensive ingrowth of 5HT-positive raphaespinal axons into the trauma zone with some terminal arborisations reaching the caudal spinal cord. In addition, ASC induced sprouting of raphaespinal terminals in C2 contralateral ventral horn and C6 ventral horn on both sides. Transplanted cells also changed the structure of the lesion scar with numerous astrocytic processes extended into the middle of the trauma zone in a chain-like pattern and in close association with regenerating axons. The density of the astrocytic network was also significantly decreased. Although the transplanted cells had no effect on the density of capillaries around the lesion site, the activity of OX42-positive microglial cells was markedly reduced. However, ASC did not support recovery of forelimb function. The results suggest that transplanted ASC can modify the structure of the glial scar and stimulate axonal sprouting.
  •  
28.
  • Kumar Kuna, Vijay, et al. (författare)
  • Efficacy of Nerve-Derived Hydrogels to Promote Axon Regeneration Is Influenced by the Method of Tissue Decellularization
  • 2022
  • Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 23:15
  • Tidskriftsartikel (refereegranskat)abstract
    • Injuries to large peripheral nerves are often associated with tissue defects and require reconstruction using autologous nerve grafts, which have limited availability and result in donor site morbidity. Peripheral nerve-derived hydrogels could potentially supplement or even replace these grafts. In this study, three decellularization protocols based on the ionic detergents sodium dodecyl sulfate (P1) and sodium deoxycholate (P2), or the organic solvent tri-n-butyl phosphate (P3), were used to prepare hydrogels. All protocols resulted in significantly decreased amounts of genomic DNA, but the P2 hydrogel showed the best preservation of extracellular matrix proteins, cytokines, and chemokines, and reduced levels of sulfated glycosaminoglycans. In vitro P1 and P2 hydrogels supported Schwann cell viability, secretion of VEGF, and neurite outgrowth. Surgical repair of a 10 mm-long rat sciatic nerve gap was performed by implantation of tubular polycaprolactone conduits filled with hydrogels followed by analyses using diffusion tensor imaging and immunostaining for neuronal and glial markers. The results demonstrated that the P2 hydrogel considerably increased the number of axons and the distance of regeneration into the distal nerve stump. In summary, the method used to decellularize nerve tissue affects the efficacy of the resulting hydrogels to support regeneration after nerve injury.
  •  
29.
  • Louw, Andrew M, et al. (författare)
  • Chitosan polyplex mediated delivery of miRNA-124 reduces activation of microglial cells in vitro and in rat models of spinal cord injury
  • 2016
  • Ingår i: Nanomedicine. - : Elsevier BV. - 1549-9634 .- 1549-9642. ; 12:3, s. 643-653
  • Tidskriftsartikel (refereegranskat)abstract
    • Traumatic injury to the central nervous system (CNS) is further complicated by an increase in secondary neuronal damage imposed by activated microglia/macrophages. MicroRNA-124 (miR-124) is responsible for mouse monocyte quiescence and reduction of their inflammatory cytokine production. We describe the formulation and ex vivo transfection of chitosan/miR-124 polyplex particles into rat microglia and the resulting reduction of reactive oxygen species (ROS) and TNF-α and lower expression of MHC-II. Upon microinjection into uninjured rat spinal cords, particles formed with Cy3-labeled control sequence RNA, were specifically internalized by OX42 positive macrophages and microglia cells. Alternatively particles injected in the peritoneum were transported by macrophages to the site of spinal cord injury 72h post injection. Microinjections of chitosan/miR-124 particles significantly reduced the number of ED-1 positive macrophages in the injured spinal cord. Taken together, these data present a potential treatment technique to reduce inflammation for a multitude of CNS neurodegenerative conditions.
  •  
30.
  • McGrath, Aleksandra M, et al. (författare)
  • Fibrin conduit supplemented with human mesenchymal stem cells and immunosuppressive treatment enhances regeneration after peripheral nerve injury
  • 2012
  • Ingår i: Neuroscience Letters. - : Elsevier. - 0304-3940 .- 1872-7972. ; 516:2, s. 171-176
  • Tidskriftsartikel (refereegranskat)abstract
    • To address the need for the development of bioengineered replacement of a nerve graft, a novel two component fibrin glue conduit was combined with human mesenchymal stem cells (MSC) and immunosupressive treatment with cyclosporine A. The effects of MSC on axonal regeneration in the conduit and reaction of activated macrophages were investigated using sciatic nerve injury model. A 10mm gap in the sciatic nerve of a rat was created and repaired either with fibrin glue conduit containing diluted fibrin matrix or fibrin glue conduit containing fibrin matrix with MSC at concentration of 80×10(6)cells/ml. Cells were labeled with PKH26 prior to transplantation. The animals received daily injections of cyclosporine A. After 3 weeks the distance of regeneration and area occupied by regenerating axons and ED1 positives macrophages was measured. MSC survived in the conduit and enhanced axonal regeneration only when transplantation was combined with cyclosporine A treatment. Moreover, addition of cyclosporine A to the conduits with transplanted MSC significantly reduced the ED1 macrophage reaction.
  •  
31.
  • McGrath, Aleksandra M., et al. (författare)
  • Long-Term Effects of Fibrin Conduit with Human Mesenchymal Stem Cells and Immunosuppression after Peripheral Nerve Repair in a Xenogenic Model
  • 2018
  • Ingår i: Cell Medicine. - : SAGE Publications. - 2155-1790. ; 10, s. 1-13
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Previously we showed that a fibrin glue conduit with human mesenchymal stem cells (hMSCs) and cyclosporine A (CsA) enhanced early nerve regeneration. In this study long term effects of this conduit are investigated. Methods: In a rat model, the sciatic nerve was repaired with fibrin conduit containing fibrin matrix, fibrin conduit containing fibrin matrix with CsA treatment and fibrin conduit containing fibrin matrix with hMSCs and CsA treatment, and also with nerve graft as control. Results: At 12 weeks 34% of motoneurons of the control group regenerated axons through the fibrin conduit. CsA treatment alone or with hMSCs resulted in axon regeneration of 67% and 64% motoneurons respectively. The gastrocnemius muscle weight was reduced in the conduit with fibrin matrix. The treatment with CsA or CsA with hMSCs induced recovery of the muscle weight and size of fast type fibers towards the levels of the nerve graft group. Discussion: The transplantation of hMSCs for peripheral nerve injury should be optimized to demonstrate their beneficial effects. The CsA may have its own effect on nerve regeneration.
  •  
32.
  • Mårdh, Per-Anders, et al. (författare)
  • Facts and myths on recurrent vulvovaginal candidosis-a review on epidemiology, clinical manifestations, diagnosis, pathogenesis and therapy.
  • 2002
  • Ingår i: International Journal of STD and AIDS. - 0956-4624. ; 13:8, s. 522-539
  • Forskningsöversikt (refereegranskat)abstract
    • Approximately three-quarters of all women will experience an episode of vulvovaginal candidosis at least once in their life and 5-10% of them will have more than one attack. Women suffering from three to four attacks within 12 months will be diagnosed with recurrent vulvovaginal candidosis (RVVC). This review covers the large number of proposed aetiological factors for RVVC. The diagnosis of the condition made by conventional means by health providers is often false and is also often misdiagnosed by the affected woman herself. The review covers various methods of diagnosing RVVC and the current knowledge on potential pathogenetic mechanisms proposed for genital candida infections. Treatment of RVVC, including local and systemic antimicrobial therapy and behaviour modification to decrease the risk of recurrences, are discussed. Recent knowledge on drug resistance in candida is also included.
  •  
33.
  • Novikov, Lev N, et al. (författare)
  • Exogenous brain-derived neurotrophic factor regulates the synaptic composition of axonally lesioned and normal adult rat motoneurons
  • 2000
  • Ingår i: Neuroscience. - : Elsevier. - 0306-4522 .- 1873-7544. ; 100:1, s. 171-181
  • Tidskriftsartikel (refereegranskat)abstract
    • Brain-derived neurotrophic factor has previously been shown to promote survival and axonal regeneration in injured spinal motoneurons and, also, to modulate synaptic transmission and regulate the density of synaptic innervation in a variety of neurons. The present light and electron microscopic study demonstrates synaptotrophic effects of exogenously applied brain-derived neurotrophic factor on the synaptic composition of both normal and axonally lesioned adult rat spinal motoneurons. After L5-L6 ventral root avulsion, a massive loss of all types of boutons occurred on the somata of the lesioned motoneurons which persisted for at least 12 weeks postoperatively. We found that (i) intrathecal infusion of brain-derived neurotrophic factor during the first postoperative week did not prevent the synaptic detachment and activation of glial cells; (ii) prolonged treatment for four weeks restored synaptic covering and significantly reduced microglial reaction; (iii) the synaptotrophic effect remained significant for at least eight weeks after cessation of the treatment; (iv) brain-derived neurotrophic factor mainly supported F-type boutons with presumably inhibitory function, while it had little effect on S-type boutons associated with excitatory action; and (v) in normal unlesioned motoneurons, four weeks of treatment with brain-derived neurotrophic factor induced sprouting of F-type boutons, a loss of S-type boutons and motoneuron atrophy. The present data show that exogenous neurotrophins not only help to restore synaptic circuitry in axonally injured motoneurons, but also strongly influence the synaptic composition in normal motoneurons.
  •  
34.
  •  
35.
  • Novikova, G, et al. (författare)
  • Integration of Alzheimer's disease genetics and myeloid genomics identifies disease risk regulatory elements and genes
  • 2021
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 1610-
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have identified more than 40 loci associated with Alzheimer’s disease (AD), but the causal variants, regulatory elements, genes and pathways remain largely unknown, impeding a mechanistic understanding of AD pathogenesis. Previously, we showed that AD risk alleles are enriched in myeloid-specific epigenomic annotations. Here, we show that they are specifically enriched in active enhancers of monocytes, macrophages and microglia. We integrated AD GWAS with myeloid epigenomic and transcriptomic datasets using analytical approaches to link myeloid enhancer activity to target gene expression regulation and AD risk modification. We identify AD risk enhancers and nominate candidate causal genes among their likely targets (including AP4E1, AP4M1, APBB3, BIN1, MS4A4A, MS4A6A, PILRA, RABEP1, SPI1, TP53INP1, and ZYX) in twenty loci. Fine-mapping of these enhancers nominates candidate functional variants that likely modify AD risk by regulating gene expression in myeloid cells. In the MS4A locus we identified a single candidate functional variant and validated it in human induced pluripotent stem cell (hiPSC)-derived microglia and brain. Taken together, this study integrates AD GWAS with multiple myeloid genomic datasets to investigate the mechanisms of AD risk alleles and nominates candidate functional variants, regulatory elements and genes that likely modulate disease susceptibility.
  •  
36.
  • Novikova, Liudmila N, et al. (författare)
  • BDNF abolishes the survival effect of NT-3 in axotomized Clarke neurons of adult rats
  • 2000
  • Ingår i: Journal of Comparative Neurology. - : Wiley-Liss, Inc.. - 0021-9967 .- 1096-9861. ; 428:4, s. 671-680
  • Tidskriftsartikel (refereegranskat)abstract
    • Neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) have previously been shown to support survival and axonal regeneration in various types of neurons. Also, synergistic neuroprotective effects of these neurotrophins have been reported in descending rubrospinal neurons after cervical spinal cord injury (Novikova et al., [2000] Eur. J. Neurosci. 12:776-780). The present study investigates the effects of intrathecally delivered NT-3 and BDNF on the survival and atrophy of ascending spinocerebellar neurons of Clarke nucleus (CN) after cervical spinal cord injury in adult rats. At 8 weeks after cervical spinal cord hemisection, 40% of the axotomized CN neurons had been lost, and the remaining cells exhibited marked atrophy. Microglial activity was significantly increased in CN of the operated side. Intrathecal infusion of NT-3 for 8 weeks postoperatively resulted in 91% cell survival and a reduction in cell atrophy, but did not reduce microglial activity. In spite of the fact that the CN neurons expressed both TrkC and TrkB receptors, only NT-3 had a neuroprotective effect, whereas BDNF was ineffective. Furthermore, when a combination of BDNF and NT-3 was administered, the neuroprotective effect of NT-3 was lost. The present results indicate a therapeutic potential for NT-3 in the treatment of spinal cord injury, but also demonstrate that in certain neuronal populations the neuroprotection obtained by a combination of neurotrophic factors may be less than that of a single neurotrophin.
  •  
37.
  • Novikova, Liudmila N, et al. (författare)
  • Neuroprotective and growth-promoting effects of bone marrow stromal cells after cervical spinal cord injury in adult rats
  • 2011
  • Ingår i: Cytotherapy. - : Elsevier BV. - 1465-3249 .- 1477-2566. ; 13:7, s. 873-887
  • Tidskriftsartikel (refereegranskat)abstract
    • Background aims. Bone marrow stromal cells (BMSC) have been shown to provide neuroprotection after transplantation into the injured central nervous system. The present study investigated whether adult rat BMSC differentiated along a Schwann cell lineage could increase production of trophic factors and support neuronal survival and axonal regeneration after transplantation into the injured spinal cord. Methods. After cervical C4 hemi-section, 5-bromo-2-deoxyuridine (BrdU)/green fluorescent protein (GFP)-labeled BMSC were injected into the lateral funiculus at 1 mm rostral and caudal to the lesion site. Spinal cords were analyzed 2-13 weeks after transplantation. Results and Conclusions. Treatment of native BMSC with Schwann cell-differentiating factors significantly increased production of brain-derived neurotrophic factor in vitro. Transplanted undifferentiated and differentiated BMSC remained at the injection sites, and in the trauma zone were often associated with neurofilament-positive fibers and increased levels of vascular endothelial growth factor. BMSC promoted extensive in-growth of serotonin-positive raphaespinal axons and calcitonin gene-related peptide (CGRP)-positive dorsal root sensory axons into the trauma zone, and significantly attenuated astroglial and microglial cell reactions, but induced aberrant sprouting of CGRP-immunoreactive axons in Rexed's lamina III. Differentiated BMSC provided neuroprotection for axotomized rubrospinal neurons and increased the density of rubrospinal axons in the dorsolateral funiculus rostral to the injury site. The present results suggest that BMSC induced along the Schwann cell lineage increase expression of trophic factors and have neuroprotective and growth-promoting effects after spinal cord injury.
  •  
38.
  • Novikova, Liudmila N, et al. (författare)
  • Survival effects of BDNF and NT-3 on axotomized rubrospinal neurons depend on the temporal pattern of neurotrophin administration
  • 2000
  • Ingår i: European Journal of Neuroscience. - : Wiley-Blackwell. - 0953-816X .- 1460-9568. ; 12:2, s. 776-780
  • Tidskriftsartikel (refereegranskat)abstract
    • This study shows that both BDNF and NT-3 can prevent cell death in axotomized adult rat rubrospinal neurons (RSNs), but that the efficacy of neuroprotection depends on the temporal pattern of treatment. At 8 weeks after cervical spinal cord injury, 51% of the RSNs had died. Subarachnoidal BDNF infusion into the cisterna magna for 4 weeks resulted in neuronal hypertrophy and 71% survival. Continuous infusion for 8 weeks into the lumbar subarachnoidal space with either BDNF or NT-3 gave similar survival rates, while a combination of BDNF and NT-3 resulted in 96% survival, although the cells were atrophic. When administration of either BDNF or NT-3 was delayed and performed during postoperative weeks 5-8, the number of surviving neurons was increased compared to early treatment. Delayed treatment with a combination of BDNF and NT-3 resulted in complete survival and a reduction in neuronal atrophy. A decreased expression of TrkB receptors and microtubule-associated protein-2 in the RSNs after axotomy was counteracted by BDNF and NT-3. Microglial activity remained increased even when complete cell survival was achieved. Thus, the combination of neurotrophins as well as the temporal pattern of treatment need to be adequately defined to optimize survival of injured spinal tract neurons.
  •  
39.
  • Novikova, Liudmila N., et al. (författare)
  • Trimethylene carbonate-caprolactone conduit with poly-p-dioxanone microfilaments to promote regeneration after spinal cord injury
  • 2018
  • Ingår i: Acta Biomaterialia. - : Elsevier. - 1742-7061 .- 1878-7568. ; 66, s. 177-191
  • Tidskriftsartikel (refereegranskat)abstract
    • Spinal cord injury (SCI) is often associated with scarring and cavity formation and therefore bridging strategies are essential to provide a physical substrate for axonal regeneration. In this study we investigated the effects of a biodegradable conduit made from trimethylene carbonate and c-caprolactone (TC) containing poly-p-dioxanone microfilaments (PDO) with longitudinal grooves on regeneration after SCI in adult rats. In vitro studies demonstrated that different cell types including astrocytes, meningeal fibroblasts, Schwann cells and adult sensory dorsal root ganglia neurons can grow on the TC and PDO material. For in vivo experiments, the TC/PDO conduit was implanted into a small 2-3 mm long cavity in the C3-C4 cervical segments immediately after injury (acute SCI) or at 2-5 months after initial surgery (chronic SCI). At 8 weeks after implantation into acute SCI, numerous 5HT-positive descending raphaespinal axons and sensory CGRP-positive axons regenerated across the conduit and were often associated with PDO microfilaments and migrated host cells. Implantation into chronically injured SCI induced regeneration mainly of the sensory CGRP-positive axons. Although the conduit had no effect on the density of OX42-positive microglial cells when compared with SCI control, the activity of GFAP-positive astrocytes was reduced. The results suggest that a TC/PDO conduit can support axonal regeneration after acute and chronic SCI even without addition of exogenous glial or stem cells.
  •  
40.
  • Podlesny-Drabiniok, A, et al. (författare)
  • BHLHE40/41 regulate macrophage/microglia responses associated with Alzheimer's disease and other disorders of lipid-rich tissues
  • 2023
  • Ingår i: bioRxiv : the preprint server for biology. - : Cold Spring Harbor Laboratory.
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • BackgroundGenetic and experimental evidence strongly implicates myeloid cells in the etiology of AD and suggests that AD-associated alleles and genes may modulate disease risk by altering the transcriptional and cellular responses of macrophages (like microglia) to damage of lipid-rich tissues (like the brain). Specifically, recent single-cell/nucleus RNA sequencing (sc/nRNA-seq) studies identified a transcriptionally distinct state of subsets of macrophages in aging or degenerating brains (usually referred to as disease- associated microglia or DAM) and in other diseased lipid-rich tissues (e.g., obese adipose tissue, fatty liver, and atherosclerotic plaques). We collectively refer to these subpopulations as lipid-associated macrophages or LAMs. Importantly, this particular activation state is characterized by increased expression of genes involved in the phagocytic clearance of lipid-rich cellular debris (efferocytosis), including several AD risk genes.MethodsWe used sc/nRNA-seq data from human and mouse microglia from healthy and diseased brains and macrophages from other lipid-rich tissues to reconstruct gene regulatory networks and identify transcriptional regulators whose regulons are enriched for LAM response genes (LAM TFs) across species. We then used gene knock- down/knock-out strategies to validate some of these LAM TFs in human THP-1 macrophages and iPSC-derived microgliain vitro, as well as mouse microgliain vivo.ResultsWe nominate 11 strong candidate LAM TFs shared across human and mouse networks (BHLHE41,HIF1A,ID2,JUNB,MAF,MAFB,MEF2A,MEF2C,NACA, POU2F2andSPI1). We also demonstrate a strong enrichment of AD risk alleles in the cistrome ofBHLHE41(and its close homologBHLHE40), thus implicating its regulon in the modulation of disease susceptibility. Loss or reduction ofBHLHE40/41expression in human THP-1 macrophages and iPSC-derived microglia, as well as loss ofBhlhe40/41in mouse microglia led to increased expression of LAM response genes, specifically those involved in cholesterol clearance and lysosomal processing, with a concomitant increase in cholesterol efflux and storage, as well as lysosomal mass and degradative capacity.ConclusionsTaken together, this study nominates transcriptional regulators of the LAM response, experimentally validates BHLHE40/41 in human and mouse macrophages/microglia, and provides novel targets for therapeutic modulation of macrophage/microglia function in AD and other disorders of lipid-rich tissues.Graphical abstract
  •  
41.
  •  
42.
  • Steg, Linda, et al. (författare)
  • A method to identify barriers to and enablers of implementing climate change mitigation options
  • 2022
  • Ingår i: One Earth. - : Elsevier BV. - 2590-3330 .- 2590-3322. ; 5:11, s. 1216-1227
  • Forskningsöversikt (refereegranskat)abstract
    • Mitigation option are not yet being implemented at the scale required to limit global warming to well below 2°C. Various factors have been identified that inhibit the implementation of specific mitigation options. Yet, an integrated assessment of key barriers and enablers is lacking. Here we present a comprehensive framework to assess which factors inhibit and enable the implementation of mitigation options. The framework comprises six dimensions, each encompassing different criteria: geophysical, environmental-ecological, technological, economic, sociocultural, and institutional feasibility. We demonstrate the approach by assessing to what extent each criterion and dimension affects the feasibility of six mitigation options. The assessment reveals that institutional factors inhibit the implementation of many options that need to be addressed to increase their feasibility. Of all the options assessed, many factors enable the implementation of solar energy, while only a few barriers would need to be addressed to implement solar energy at scale.
  •  
43.
  • Wiberg, Rebecca, 1988-, et al. (författare)
  • A Morphological and Molecular Characterization of the Spinal Cord after Ventral Root Avulsion or Distal Peripheral Nerve Axotomy Injuries in Adult Rats
  • 2017
  • Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 34:3, s. 652-660
  • Tidskriftsartikel (refereegranskat)abstract
    • Retrograde cell death in sensory dorsal root ganglion cells following peripheral nerve injury is well established. However, available data regarding the underlying mechanism behind injury induced motoneuron death are conflicting. By comparing morphological and molecular changes in spinal motoneurons after L4-L5 ventral root avulsion (VRA) and distal peripheral nerve axotomy (PNA) 7 and 14 days postoperatively, we aimed to gain more insight about the mechanism behind injury-induced motoneuron degeneration. Morphological changes in spinal cord were assessed by using quantitative immunohistochemistry. Neuronal degeneration was revealed by decreased immunostaining for microtubuleassociated protein-2 in dendrites and synaptophysin in presynaptic boutons after both VRA and PNA. Significant motoneuron atrophy was already observed at 7 days post-injury, independently of injury type. Immunostaining for ED1 reactive microglia was significantly elevated in all experimental groups, as well as the astroglial marker glial fibrillary acidic protein (GFAP). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis of the ventral horn from L4-L5 spinal cord segments revealed a significant upregulation of genes involved in programmed cell death including caspase-3, caspase-8, and related death receptors TRAIL-R, tumor necrosis factor (TNF)-R, and Fas following VRA. In contrast, following PNA, caspase-3 and the death receptor gene expression levels did not differ from the control, and there was only a modest increased expression of caspase-8. Moreover, the altered gene expression correlated with protein changes. These results show that the spinal motoneurons reacted in a similar fashion with respect to morphological changes after both proximal and distal injury. However, the increased expression of caspase-3, caspase-8, and related death receptors after VRA suggest that injury- induced motoneuron degeneration is mediated through an apoptotic mechanism, which might involve both the intrinsic and the extrinsic pathways.
  •  
44.
  • Wiberg, Rebecca, et al. (författare)
  • Evaluation of apoptotic pathways in dorsal root ganglion neurons following peripheral nerve injury
  • 2018
  • Ingår i: NeuroReport. - : Lippincott Williams & Wilkins. - 0959-4965 .- 1473-558X. ; , s. 779-785
  • Tidskriftsartikel (refereegranskat)abstract
    • Peripheral nerve injuries induce significant sensory neuronal cell death in the dorsal root ganglia (DRG); however, the role of specific apoptotic pathways is still unclear. In this study, we performed peripheral nerve transection on adult rats, after which the corresponding DRGs were harvested at 7, 14, and 28 days after injury for subsequent molecular analyses with quantitative reverse transcription-PCR, western blotting, and immunohistochemistry. Nerve injury led to increased levels of caspase-3 mRNA and active caspase-3 protein in the DRG. Increased expression of caspase-8, caspase-12, caspase-7, and calpain suggested that both the extrinsic and the endoplasmic reticulum (ER) stress-mediated apoptotic pathways were activated. Phosphorylation of protein kinase R-like ER kinase further implied the involvement of ER-stress in the DRG. Phosphorylated protein kinase R-like ER kinase was most commonly associated with isolectin B4 (IB4)-positive neurons in the DRG and this may provide an explanation for the increased susceptibility of these neurons to die following nerve injury, likely in part because of an activation of the ER-stress response.
  •  
45.
  • Wiberg, Rebecca, 1988-, et al. (författare)
  • Investigation of the Expression of Myogenic Transcription Factors, microRNAs and Muscle-Specific E3 Ubiquitin Ligases in the Medial Gastrocnemius and Soleus Muscles following Peripheral Nerve Injury
  • 2015
  • Ingår i: PLOS ONE. - San Francisco : Public Library Science. - 1932-6203. ; 10:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite surgical innovation, the sensory and motor outcome after a peripheral nerve injury remains incomplete. One contributing factor to the poor outcome is prolonged denervation of the target organ, leading to apoptosis of both mature myofibres and satellite cells with subsequent replacement of the muscle tissue with fibrotic scar and adipose tissue. In this study, we investigated the expression of myogenic transcription factors, muscle specific microRNAs and muscle-specific E3 ubiquitin ligases at several time points following denervation in two different muscles, the gastrocnemius (containing predominantly fast type fibres) and soleus (slow type) muscles, since these molecules may influence the degree of atrophy following denervation. Both muscles exhibited significant atrophy (compared with the contra-lateral sides) at 7 days following either a nerve transection or crush injury. In the crush model, the soleus muscle showed significantly increased muscle weights at days 14 and 28 which was not the case for the gastrocnemius muscle which continued to atrophy. There was a significantly more pronounced up-regulation of MyoD expression in the denervated soleus muscle compared with the gastrocnemius muscle. Conversely, myogenin was more markedly elevated in the gastrocnemius versus soleus muscles. The muscles also showed significantly contrasting transcriptional regulation of the microRNAs miR-1 and miR-206. MuRF1 and Atrogin-1 showed the highest levels of expression in the denervated gastrocnemius muscle. This study provides further insights regarding the intracellular regulatory molecules that generate and maintain distinct patterns of gene expression in different fibre types following peripheral nerve injury.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-45 av 45

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy