| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
|
|
| 6. |
- Zhang, Huai, et al.
(författare)
-
A global survey on the use of the international classification of diseases codes for metabolic dysfunction-associated fatty liver disease.
- 2024
-
Ingår i: Hepatology international. - 1936-0541.
-
Tidskriftsartikel (refereegranskat)abstract
- With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11.Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members.A total of 890 international experts in various fields from 61 countries responded to the survey. We also achieved full coverage of provincial-level administrative regions in China. 77.1% of respondents agreed that MAFLD should be represented in ICD-11 by updating NAFLD, with no significant regional differences (77.3% in Asia and 76.6% in non-Asia, p=0.819). Over 80% of respondents agreed or somewhat agreed with the need to assign specific codes for progressive stages of MAFLD (i.e. steatohepatitis) (92.2%), MAFLD combined with comorbidities (84.1%), or MAFLD subtypes (i.e., lean, overweight/obese, and diabetic) (86.1%).This global survey by a collaborative panel of clinical, coding, health management and policy experts, indicates agreement that MAFLD should be coded in ICD-11. The data serves as a foundation for corresponding adjustments in the ICD-11 revision.
|
|
| 7. |
- Ablikim, M., et al.
(författare)
-
Observation of the decay psi(3686) -> Lambda(Sigma)over-bar(+/-) pi(-/+) + c.c
- 2013
-
Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 88:11, s. 112007-
-
Tidskriftsartikel (refereegranskat)abstract
- Using a sample of 1:06 X 10(8) psi(3686) events collected with the BESIII detector, we present the first observation of the decays of psi(3686) -> Lambda(Sigma) over bar (+) pi(-) + c.c. and psi(3686) -> Lambda(Sigma) over bar (-) pi(+) + c.c. The branching fractions are measured to be B(psi(3686) -> Lambda(Sigma) over bar (+) pi(-) + c.c.) = (1.40 +/- 0.03 +/- 0.13) X 10(-4) and B(psi(3686) -> Lambda (Sigma) over bar (-) pi(+) + c.c.) = (1.54 +/- 0.04 +/- 0.13) X 10(-4) where the first errors are statistical and the second ones systematic.
|
|
| 8. |
- Ablikim, M., et al.
(författare)
-
Search for eta(c)(2S)h(c) -> p(p)over-bar decays and measurements of the chi(cJ) -> p(p)over-bar branching fractions
- 2013
-
Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 88:11, s. 112001-
-
Tidskriftsartikel (refereegranskat)abstract
- Using a sample of 1.06 x 10(8)psi(3686) events collected with the BESIII detector at BEPCII, the decays eta(c)(2S) -> p (p) over bar and h(c) -> p (p) over bar are searched for, where eta(c)(2S) and h(c) are reconstructed in the decay chains psi(3686) -> gamma eta(c)(2S), eta(c)(2S) -> p (p) over bar and psi(3686) -> pi(0)h(c), h(c) -> p (p) over bar, respectively. No significant signals are observed. The upper limits of the product branching fractions are determined to be B(psi(3686) -> gamma eta(c)(2S)) x B(eta(c)(2S) -> p (p) over bar) < 1.4 x 10(-6) and B(psi(3686) -> pi(0)h(c)) x B(h(c) -> p<(p)over bar>) < 1.3 x 10(-7) at the 90% C.L.. The branching fractions for chi(cJ) -> p<(p)over bar> (J = 0, 1, 2) are also measured to be (24.5 +/- 0.8 +/- 1.3, 8.6 +/- 0.5 +/- 0.5, 8.4 +/- 0.5 +/- 0.5) x 10(-5), which are the world's most precise measurements.
|
|
| 9. |
- An, Junghwa, et al.
(författare)
-
Permanent Genetic Resources added to Molecular Ecology Resources Database 1 October 2009-30 November 2009
- 2010
-
Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:2, s. 404-408
-
Tidskriftsartikel (refereegranskat)abstract
- This article documents the addition of 411 microsatellite marker loci and 15 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Acanthopagrus schlegeli, Anopheles lesteri, Aspergillus clavatus, Aspergillus flavus, Aspergillus fumigatus, Aspergillus oryzae, Aspergillus terreus, Branchiostoma japonicum, Branchiostoma belcheri, Colias behrii, Coryphopterus personatus, Cynogolssus semilaevis, Cynoglossus semilaevis, Dendrobium officinale, Dendrobium officinale, Dysoxylum malabaricum, Metrioptera roeselii, Myrmeciza exsul, Ochotona thibetana, Neosartorya fischeri, Nothofagus pumilio, Onychodactylus fischeri, Phoenicopterus roseus, Salvia officinalis L., Scylla paramamosain, Silene latifo, Sula sula, and Vulpes vulpes. These loci were cross-tested on the following species: Aspergillus giganteus, Colias pelidne, Colias interior, Colias meadii, Colias eurytheme, Coryphopterus lipernes, Coryphopterus glaucofrenum, Coryphopterus eidolon, Gnatholepis thompsoni, Elacatinus evelynae, Dendrobium loddigesii Dendrobium devonianum, Dysoxylum binectariferum, Nothofagus antarctica, Nothofagus dombeyii, Nothofagus nervosa, Nothofagus obliqua, Sula nebouxii, and Sula variegata. This article also documents the addition of 39 sequencing primer pairs and 15 allele specific primers or probes for Paralithodes camtschaticus.
|
|
| 10. |
- Li, Yifei, et al.
(författare)
-
Can Nup88 expression be associated with atypical endometrial hyperplasia and endometrial cancer? A preliminary study
- 2016
-
Ingår i: Pathology, Research and Practice. - : ELSEVIER GMBH, URBAN & FISCHER VERLAG. - 0344-0338 .- 1618-0631. ; 212:4, s. 274-278
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Nup88 is overexpressed in a number of types of carcinomas and is associated with myometrial invasion, but its exact expression pattern in endometrial cancer and premalignant lesions is unknown. Aims: To evaluate the role of Nup88 in endometrial cancers and atypical endometrial hyperplasia and its clinicopathological significance. Methods: Nup88 expression was examined by immunohistochemistry in samples from 104 endometrial cancers, 21 atypical endometrial hyperplasia lesions, and 40 normal endometria. All samples were from patients who underwent surgery at the First Hospital of Hebei Medical University (Shijiazhuang, China) between April 2006 and December 2009. Nup88 expression was compared between the groups and associations were assessed between Nup88 and clinicopathological characteristics of the subjects. Results: Nup88 expression in cancer (76% of samples) and atypical hyperplasia (91%) was significantly higher compared to normal endometrium (33%, both P < 0.001), but there was no significant difference between endometrial cancer and atypical hyperplasia (P = 0.237). The expression of Nup88 increased significantly with increasing exposure time to estrogen (P = 0.033). Conclusions: Nup88 may be related to the occurrence of endometrial cancers and premalignant lesions. Nup88 might be a useful biomarker for pre-malignant lesions and early-stage endometrial cancer. (C) 2016 Elsevier GmbH. All rights reserved.
|
|
| 11. |
- Li, Yifei, et al.
(författare)
-
Expression and clinical significance of FXYD3 in endometrial cancer
- 2014
-
Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 8:2, s. 517-522
-
Tidskriftsartikel (refereegranskat)abstract
- FXYD3 expression is upregulated in numerous cancer cell types. The present study compared the FXDY3 expression in normal endometrium, premalignant lesion and endometrial cancer tissue samples, and investigated the correlation between FXDY3 expression and clinicopathological features. FXYD3 expression was analyzed by streptavidin-peroxidase immunohistochemistry in 21 normal endometrial tissue samples, 18 atypical endometrial hyperplasia samples and 50 tissues obtained from patients diagnosed with endometrial cancer. The percentage of FXYD3-positive cell expression in the normal endometrium, atypical hyperplasia and endometrial cancer tissues samples was 0, 22, and 26%, respectively. The differences between the atypical hyperplasia and endometrial cancer groups were statistically significant when compared with the normal group (P=0.007 and P=0.037, respectively). There was no significant difference between the atypical hyperplasia and endometrial cancer groups. The percentage of FXYD3-positive cells correlated with the fertility frequency (Pless than0.05). In conclusion, FXYD3 is a potential biomarker for endometrial cancer, and its upregulation may be an early event in endometrial carcinoma progression. In addition, FXYD3 expression in endometrial carcinoma correlates with fertility frequency.
|
|
| 12. |
- Zhu, Jing-Jing, et al.
(författare)
-
Fiber-Optic High-Temperature Sensor Based on Thin-Core Fiber Modal Interferometer
- 2010
-
Ingår i: IEEE Sensors Journal. - 1530-437X .- 1558-1748. ; 10:9, s. 1415-1418
-
Tidskriftsartikel (refereegranskat)abstract
- We present a new fiber-optic high-temperature sensor based on a thin-core fiber (TCF) modal interferometer. A thin-core fiber, whose core radius is about half of the radius of a standard single-mode fiber (SMF), is inserted between standard SMFs to form an extremely simple in-fiber modal interferometer. The wavelength of the transmission dip increases linearly with the temperature. Experimental demonstration shows that it can be used to sense temperature up to 850 degrees C with a sensitivity of about 18.3 pm/degrees C.
|
|
| 13. |
- Ahmadi, Mahboobah, et al.
(författare)
-
Human extraocular muscles in ALS
- 2010
-
Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 51:7, s. 3494-3501
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To investigate the general morphology, fiber type content, and myosin heavy chain (MyHC) composition of extraocular muscles (EOMs) from postmortem donors with amyotrophic lateral sclerosis (ALS) and to evaluate whether EOMs are affected or truly spared in this disease. METHODS. EOM and limb muscle samples obtained at autopsy from ALS donors and EOM samples from four control donors were processed for immunohistochemistry with monoclonal antibodies against distinct MyHC isoforms and analyzed by SDS-PAGE. In addition, hematoxylin and eosin staining and nicotinamide tetrazolium reductase (NADH-TR) activity were studied. RESULTS. Wide heterogeneity was observed in the appearance of the different EOMs from each single donor and between donors, irrespective of ALS type or onset. Pathologic morphologic findings in ALS EOMs included presence of atrophic and hypertrophic fibers, either clustered in groups or scattered; increased amounts of connective tissue; and areas of fatty replacement. The population of fibers stained with anti-MyHCslow tonic was smaller than that of MyHCIpositive fibers and was mostly located in the orbital layer in most of the ALS EOM samples, whereas an identical staining pattern for both fiber populations was observed in the control specimens. MyHCembryonic was notably absent from the ALS EOMs. CONCLUSIONS. The EOMs showed signs of involvement with altered fiber type composition, contractile protein content, and cellular architecture. However, when compared to the limb muscles, the EOMs were remarkably preserved. EOMs are a useful model for the study of the pathophysiology of ALS.
|
|
| 14. |
- Behzadi, Arvin, et al.
(författare)
-
Myofiber type shift in extraocular muscles in amyotrophic lateral sclerosis
- 2023
-
Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 64:5
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate changes in myofiber composition in the global layer (GL) and orbital layer (OL) of extraocular muscles (EOMs) from terminal amyotrophic lateral sclerosis (ALS) donors.Methods: Medial recti muscles collected postmortem from spinal-onset ALS, bulbar-onset ALS, and healthy control donors were processed for immunofluorescence with antibodies against myosin heavy chain (MyHC) IIa, MyHCI, MyHCeom, laminin, neurofilaments, synaptophysin, acetylcholine receptor γ-subunit, and α-bungarotoxin.Results: The proportion of myofibers containing MyHCIIa was significantly smaller and MyHCeom was significantly larger in the GL of spinal-onset ALS and bulbar-onset ALS donors compared to control donors. Changes in the GL were more prominent in the bulbar-onset ALS donors, with a significantly larger proportion of myofibers containing MyHCeom being present compared to spinal-onset ALS donors. There were no significant differences in the myofiber composition in the OL. In the spinal-onset ALS donors, the proportions of myofibers containing MyHCIIa in the GL and MyHCeom in the OL were significantly correlated with the disease duration. Neurofilament and synaptophysin were present at motor endplates of myofibers containing MyHCeom in ALS donors.Conclusions: The EOMs of terminal ALS donors displayed changes in the fast-type myofiber composition in the GL, with a more pronounced alteration in bulbar-onset ALS donors. Our results align with the worse prognosis and subclinical changes in eye movement function previously observed in bulbar-onset ALS patients and suggest that the myofibers in the OL might be more resistant to the pathological process in ALS.
|
|
| 15. |
- Bennett, Joanne M., et al.
(författare)
-
Land use and pollinator dependency drives global patterns of pollen limitation in the Anthropocene
- 2020
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Land use change, by disrupting the co-evolved interactions between plants and their pollinators, could be causing plant reproduction to be limited by pollen supply. Using a phylogenetically controlled meta-analysis on over 2200 experimental studies and more than 1200 wild plants, we ask if land use intensification is causing plant reproduction to be pollen limited at global scales. Here we report that plants reliant on pollinators in urban settings are more pollen limited than similarly pollinator-reliant plants in other landscapes. Plants functionally specialized on bee pollinators are more pollen limited in natural than managed vegetation, but the reverse is true for plants pollinated exclusively by a non-bee functional group or those pollinated by multiple functional groups. Plants ecologically specialized on a single pollinator taxon were extremely pollen limited across land use types. These results suggest that while urbanization intensifies pollen limitation, ecologically and functionally specialized plants are at risk of pollen limitation across land use categories. An insufficient amount of pollen transfer by pollinators (pollen limitation) could reduce plant reproduction in human-impacted landscapes. Here the authors conduct a global meta-analysis and find that pollen limitation is high in urban environments and depends of plant traits such as pollinator dependency.
|
|
| 16. |
- Burns, Jean H., et al.
(författare)
-
Plant traits moderate pollen limitation of introduced and native plants : a phylogenetic meta-analysis of global scale
- 2019
-
Ingår i: New Phytologist. - : WILEY. - 0028-646X .- 1469-8137. ; 223:4, s. 2063-2075
-
Tidskriftsartikel (refereegranskat)abstract
- The role of pollination in the success of invasive plants needs to be understood because invasives have substantial effects on species interactions and ecosystem functions. Previous research has shown both that reproduction of invasive plants is often pollen limited and that invasive plants can have high seed production, motivating the questions: How do invasive populations maintain reproductive success in spite of pollen limitation? What species traits moderate pollen limitation for invaders? We conducted a phylogenetic meta-analysis with 68 invasive, 50 introduced noninvasive and 1931 native plant populations, across 1249 species. We found that invasive populations with generalist pollination or pollinator dependence were less pollen limited than natives, but invasives and introduced noninvasives did not differ. Invasive species produced 3x fewer ovules/flower and >250x more flowers per plant, compared with their native relatives. While these traits were negatively correlated, consistent with a tradeoff, this did not differ with invasion status. Invasive plants that produce many flowers and have floral generalisation are able to compensate for or avoid pollen limitation, potentially helping to explain the invaders' reproductive successes.
|
|
| 17. |
- Carlsson-Jonsson, Anna, et al.
(författare)
-
N-terminal truncations of substance P1-7 amide affect its action on spinal cord injury-induced mechanical allodynia in rats
- 2014
-
Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999 .- 1879-0712. ; 738, s. 319-325
-
Tidskriftsartikel (refereegranskat)abstract
- Central neuropathic pain can arise from injury of the spinal cord and can become chronic. Treatment is difficult and, because complete pain relief is currently very hard to achieve, there is a need for new, more effective treatment options. In this study we used an animal model of spinal cord injury to evaluate the potency of a bioactive fragment of substance P (SP), i.e. SP1-7, in alleviating signs of allodynia and acute pain. SP1-7 is known from earlier studies to possess antinociceptive properties. We also studied the effects of intraperitoneal injection of an amidated analog of this heptapeptide and of its truncated analogs, all of which had high affinity to the SP1-7 binding site, to evaluate the importance of the removed amino acids for the bioclistribution and stability of the peptides. Most of the examined compounds alleviated mechanical alloclynia without any signs of sedation or motor impairment in the rats. In contrast, the response threshold to acute nociceptive stimulation was not affected by arty of the compounds tested. Most of the amino acids in the heptapepticle structure were essential for retaining the biological effect after peripheral injection. These observations suggest that the heptapepticle and its N-Lerminal truncated hexa- and pentapeptide analogs could be of interest for further development of analgesics in the management of mechanical allodynia.
|
|
| 18. |
- Chandra, Naresh, 1987-, et al.
(författare)
-
Sulfated Glycosaminoglycans as Viral Decoy Receptors for Human Adenovirus Type 37
- 2019
-
Ingår i: Viruses. - : MDPI. - 1999-4915. ; 11:3
-
Tidskriftsartikel (refereegranskat)abstract
- Glycans on plasma membranes and in secretions play important roles in infection by many viruses. Species D human adenovirus type 37 (HAdV-D37) is a major cause of epidemic keratoconjunctivitis (EKC) and infects target cells by interacting with sialic acid (SA)-containing glycans via the fiber knob domain of the viral fiber protein. HAdV-D37 also interacts with sulfated glycosaminoglycans (GAGs), but the outcome of this interaction remains unknown. Here, we investigated the molecular requirements of HAdV-D37 fiber knob:GAG interactions using a GAG microarray and demonstrated that fiber knob interacts with a broad range of sulfated GAGs. These interactions were corroborated in cell-based assays and by surface plasmon resonance analysis. Removal of heparan sulfate (HS) and sulfate groups from human corneal epithelial (HCE) cells by heparinase III and sodium chlorate treatments, respectively, reduced HAdV-D37 binding to cells. Remarkably, removal of HS by heparinase III enhanced the virus infection. Our results suggest that interaction of HAdV-D37 with sulfated GAGs in secretions and on plasma membranes prevents/delays the virus binding to SA-containing receptors and inhibits subsequent infection. We also found abundant HS in the basement membrane of the human corneal epithelium, which may act as a barrier to sub-epithelial infection. Collectively, our findings provide novel insights into the role of GAGs as viral decoy receptors and highlight the therapeutic potential of GAGs and/or GAG-mimetics in HAdV-D37 infection.
|
|
| 19. |
- Chen, Jie, et al.
(författare)
-
Bidirectional Mendelian Randomisation Analysis Provides Evidence for the Causal Involvement of Dysregulation of CXCL9, CCL11 and CASP8 in the Pathogenesis of Ulcerative Colitis
- 2023
-
Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 17:5, s. 777-785
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Aims Systemic inflammation is well recognised to be associated with ulcerative colitis [UC], but whether these effects are causal or consequential remains unclear. We aimed to define potential causal relationship of cytokine dysregulation with different tiers of evidence. Methods We first synthesised serum proteomic profiling data from two multicentred observational studies, in which a panel of systemic inflammatory proteins was analysed to examine their associations with UC risk. To further dissect observed associations, we then performed a bidirectional two-sample Mendelian randomisation [TSMR] analysis from both forward and reverse directions using five genome-wide association study [GWAS] summary level data for serum proteomic profiles and the largest GWAS of 28 738 European-ancestry individuals for UC risk. Results Pooled analysis of serum proteomic data identified 14 proteins to be associated with the risk of UC. Forward MR analysis using only cis-acting protein quantitative trait loci [cis-pQTLs] or trans-pQTLs further validated causal associations of two chemokines and the increased risk of UC: C-X-C motif chemokine ligand 9 [CXCL9] [OR 1.45, 95% CI 1.08, 1.95, p = 0.012] and C-C motif chemokine ligand 11 [CCL11] [OR 1.14, 95% CI 1.09, 1.18, p = 3.89 x 10(-10)]. Using both cis- and trans-acting pQTLs, an association of caspase-8 [CASP8] [OR 1.04, 95% CI 1.03, 1.05, p = 7.63 x 10(-19)] was additionally identified. Reverse MR did not find any influence of genetic predisposition to UC on any of these three inflammation proteins. Conclusion Pre-existing elevated levels of CXCL9, CCL11 and CASP8 may play a role in the pathogenesis of UC.
|
|
| 20. |
- Dennhag, Nils, et al.
(författare)
-
Absence of Desmin in Myofibers of the Zebrafish Extraocular Muscles
- 2020
-
Ingår i: Translational Vision Science & Technology. - : Association for Research in Vision and Ophthalmology. - 2164-2591. ; 9:10
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To study the medial rectus (MR) muscle of zebrafish (Danio rerio) with respect to the pattern of distribution of desmin and its correlation to distinct types of myofibers and motor endplates.Methods: The MRs of zebrafish were examined using confocal microscopy in whole-mount longitudinal specimens and in cross sections processed for immunohistochemistry with antibodies against desmin, myosin heavy chain isoforms, and innervation markers. Desmin patterns were correlated to major myofiber type and type of innervation. A total of 1382 myofibers in nine MR muscles were analyzed.Results: Four distinct desmin immunolabeling patterns were found in the zebrafish MRs. Approximately a third of all slow myofibers lacked desmin, representing 8.5% of the total myofiber population. The adult zebrafish MR muscle displayed en grappe, en plaque, and multiterminal en plaque neuromuscular junctions (NMJs) with intricate patterns of desmin immunolabeling.Conclusions: The MRs of zebrafish showed important similarities with the human extraocular muscles with regard to the pattern of desmin distribution and presence of the major types of NMJs and can be regarded as an adequate model to further study the role of desmin and the implications of heterogeneity in cytoskeletal protein composition.Translational Relevance: The establishment of a zebrafish model to study the cytoskeleton in muscles that are particularly resistant to muscle disease opens new avenues to understand human myopathies and muscle dystrophies and may provide clues to new therapies.
|
|
| 21. |
|
|
| 22. |
- Dennhag, Nils, 1989-, et al.
(författare)
-
fhl2b mediates extraocular muscle protection in zebrafish models of muscular dystrophies and its ectopic expression ameliorates affected body muscles
- 2024
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
-
Tidskriftsartikel (refereegranskat)abstract
- In muscular dystrophies, muscle fibers loose integrity and die, causing significant suffering and premature death. Strikingly, the extraocular muscles (EOMs) are spared, functioning well despite the disease progression. Although EOMs have been shown to differ from body musculature, the mechanisms underlying this inherent resistance to muscle dystrophies remain unknown. Here, we demonstrate important differences in gene expression as a response to muscle dystrophies between the EOMs and trunk muscles in zebrafish via transcriptomic profiling. We show that the LIM-protein Fhl2 is increased in response to the knockout of desmin, plectin and obscurin, cytoskeletal proteins whose knockout causes different muscle dystrophies, and contributes to disease protection of the EOMs. Moreover, we show that ectopic expression of fhl2b can partially rescue the muscle phenotype in the zebrafish Duchenne muscular dystrophy model sapje, significantly improving their survival. Therefore, Fhl2 is a protective agent and a candidate target gene for therapy of muscular dystrophies.
|
|
| 23. |
- Ding, Xue Bing, et al.
(författare)
-
Impaired meningeal lymphatic drainage in patients with idiopathic Parkinson’s disease
- 2021
-
Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:3, s. 411-418
-
Tidskriftsartikel (refereegranskat)abstract
- Animal studies implicate meningeal lymphatic dysfunction in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease (PD). However, there is no direct evidence in humans to support this role1–5. In this study, we used dynamic contrast-enhanced magnetic resonance imaging to assess meningeal lymphatic flow in cognitively normal controls and patients with idiopathic PD (iPD) or atypical Parkinsonian (AP) disorders. We found that patients with iPD exhibited significantly reduced flow through the meningeal lymphatic vessels (mLVs) along the superior sagittal sinus and sigmoid sinus, as well as a notable delay in deep cervical lymph node perfusion, compared to patients with AP. There was no significant difference in the size (cross-sectional area) of mLVs in patients with iPD or AP versus controls. In mice injected with α-synuclein (α-syn) preformed fibrils, we showed that the emergence of α-syn pathology was followed by delayed meningeal lymphatic drainage, loss of tight junctions among meningeal lymphatic endothelial cells and increased inflammation of the meninges. Finally, blocking flow through the mLVs in mice treated with α-syn preformed fibrils increased α-syn pathology and exacerbated motor and memory deficits. These results suggest that meningeal lymphatic drainage dysfunction aggravates α-syn pathology and contributes to the progression of PD.
|
|
| 24. |
- Dominguez, Cecilia A, et al.
(författare)
-
Genetic analysis of neuropathic pain-like behavior following peripheral nerve injury suggests a role of the major histocompatibility complex in development of allodynia
- 2008
-
Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 1872-6623 .- 0304-3959. ; 136:3, s. 313-319
-
Tidskriftsartikel (refereegranskat)abstract
- Neuropathic pain is a common consequence of damage to the nervous system. We here report a genetic analysis of development of neuropathic pain-like behaviors after unilateral photochemically-induced ischemic sciatic nerve injury in a panel of inbred rat strains known to display different susceptibility to autoimmune neuroinflammation. Pain behavior was initially characterized in Dark-Agouti (DA; RT1(avl)), Piebald Virol Glaxo (PVG; RT1(c)), and in the major histocompatibility complex (MHC)-congenic strain PVG-RT1(avl). All strains developed mechanical hypersensitivity (allodynia) following nerve injury. However, the extent and duration of allodynia varied significantly among the strains, with PVG displaying more severe allodynia compared to DA rats. Interestingly, the response of PVG-RT1(avR1) was similar to that of DA, suggesting regulation by the MHC locus. This notion was subsequently confirmed in an F2 cohort derived from crossing of the PVG and PVG-RT1(avl) strains, where allodynia was reduced in homozygous or heterozygous carriers of the RT1(avl) allele in comparison to rats homozygous for the RT1(c) allele. These results indicate that certain allelic variants of the MHC could influence susceptibility to develop and maintain neuropathic pain-like behavior following peripheral nerve injury in rats.
|
|
| 25. |
- Dong, Xiao Xia, et al.
(författare)
-
Carrier-envelope-phase measurement of sub-cycle UV pulses using angular photofragment distributions
- 2022
-
Ingår i: Communications Physics. - : Springer Nature. - 2399-3650. ; 5:1
-
Tidskriftsartikel (refereegranskat)abstract
- Carrier-envelope-phase (CEP) of sub-cycle ultraviolet (UV) pulse strongly influences the dynamics of quantum systems, but its characterization is not accessible experimentally. Here we investigate photodissociation of a diatomic molecule from its ground-rovibrational state in a linearly polarized weak sub-cycle UV pulse with a controlled CEP. The angular distribution of photofragments shows an asymmetric profile deviating from the well-known cos(2-) or sin(2)-like ones, which can be identified as a way to imprint CEP. We unveil that such an effect stems from the temporal neighboring rotational excitation by molecular permanent dipole interaction through the joint contributions between counter-rotating and rotating terms. This in turn, opens different pathways in photodissociation dynamics. Given that the temporal excitation between various states with close energies can be manipulated by CEP of subcycle UV pulses, our results pave ways for understanding and manipulating electron, nuclear and their joint dynamics with variation of CEP of attosecond pulses.
|
|
| 26. |
- Dun, Xiaoling, et al.
(författare)
-
Neofunctionalization of Duplicated Tic40 Genes Caused a Gain-of-Function Variation Related to Male Fertility in Brassica oleracea Lineages
- 2014
-
Ingår i: Plant Physiology. - : Oxford University Press (OUP). - 0032-0889 .- 1532-2548. ; 166:3, s. 1403-1419
-
Tidskriftsartikel (refereegranskat)abstract
- Gene duplication followed by functional divergence in the event of polyploidization is a major contributor to evolutionary novelties. The Brassica genus evolved from a common ancestor after whole-genome triplication. Here, we studied the evolutionary and functional features of Brassica spp. homologs to Tic40 (for translocon at the inner membrane of chloroplasts with 40 kDa). Four Tic40 loci were identified in allotetraploid Brassica napus and two loci in each of three basic diploid Brassica spp. Although these Tic40 homologs share high sequence identities and similar expression patterns, they exhibit altered functional features. Complementation assays conducted on Arabidopsis thaliana tic40 and the B. napus male-sterile line 7365A suggested that all Brassica spp. Tic40 homologs retain an ancestral function similar to that of AtTic40, whereas BolC9.Tic40 in Brassica oleracea and its ortholog in B. napus, BnaC9.Tic40, in addition, evolved a novel function that can rescue the fertility of 7365A. A homologous chromosomal rearrangement placed bnac9.tic40 originating from the A genome (BraA10.Tic40) as an allele of BnaC9.Tic40 in the C genome, resulting in phenotypic variation for male sterility in the B. napus near-isogenic two-type line 7365AB. Assessment of the complementation activity of chimeric B. napus Tic40 domain-swapping constructs in 7365A suggested that amino acid replacements in the carboxyl terminus of BnaC9.Tic40 cause this functional divergence. The distribution of these amino acid replacements in 59 diverse Brassica spp. accessions demonstrated that the neofunctionalization of Tic40 is restricted to B. oleracea and its derivatives and thus occurred after the divergence of the Brassica spp. A, B, and C genomes.
|
|
| 27. |
- Guo, Ziyin, et al.
(författare)
-
In Situ Formation of a LiBO2 Coating Layer and Spinel Phase for Ni-Rich Cathode Materials from a Boric Acid-Etched Precursor
- 2024
-
Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 16:1, s. 731-741
-
Tidskriftsartikel (refereegranskat)abstract
- Ni-rich cathode materials exhibit superior energy densities and have attracted interest among both research and industrial fields; whereas, their practical application is hindered by the intrinsic drawbacks brought by the high nickel content such as structural instability and rapid capacity fading. Herein, in situ formation of a LiBO2 coating layer and spinel phase layer is achieved on the surface of a Ni-rich cathode material via a boric acid etching method at the precursor state. The spinel phase is considered to have a 3D lithium diffusion tunnel and hence faster diffusion kinetics. Moreover, the LiBO2 layer possesses excellent (electro)-chemical inertness and can suppress electrolyte decomposition, resulting in a more inorganic and stable cathode-electrolyte interface. The surface reconstructed sample exhibits better cyclic stability (93.3% capacity retention vs 85.3% for the pristine sample at 1 C for 100 cycles) and rate performance. The superiority of this surface reconstruction is demonstrated by a series of electrochemical techniques and characterization methods including high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM), post-mortem X-ray photoelectron spectroscopy (XPS) analysis, and density functional theory (DFT) calculations.
|
|
| 28. |
- Harandi, Vahid M, et al.
(författare)
-
Unchanged neurotrophic factors and their receptors correlate with sparing in extraocular muscles in amyotrophic lateral sclerosis
- 2016
-
Ingår i: Investigative Ophthalmology and Visual Science. - Rockville : The association for research in vision and ophthalmology. - 0146-0404 .- 1552-5783. ; 57:15, s. 6831-6842
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate the impact of amyotrophic lateral sclerosis (ALS) on the extraocular muscles (EOMs) by examining the distribution of neurotrophic factors (NTFs) and their receptors in EOMs and limb muscles from ALS transgenic mice.Methods: Muscle samples collected from transgenic mice overexpressing human superoxide dismutase type 1 mutations (SOD1G93A, the most widely used mouse model of ALS) at 50 and 150 days as well as age-matched controls were analyzed with immunohistochemistry using antibodies against brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4/5 (NT-4), glial cell line-derived neurotrophic factor (GDNF), and the neurotrophin receptors p75NTR, tyrosine kinase (Trk) receptor TrkB and TrkC, and GDNF family receptor alpha-1 (GFRα-1).Results: There was an intrinsic difference in NTF expression between EOMs and limb muscles in control mice: EOMs presented significantly lower number of neuromuscular junctions (NMJs) labeled for BDNF and NT-4 at 50 days, and for BDNF and GDNF at 150 days, compared with the control limb muscles of corresponding age. In ALS transgenic mice at 150 days, NTF expression in limb muscles was significantly changed but not in EOMs: the limb muscles presented a significant decline in the number of NMJs labeled for BDNF, NT-4, GDNF, p75NTR, TrkB, and TrkC, which was not observed in EOMs.Conclusions: The significant differences in expression of NTFs on NMJs between EOMs and limb muscles in both control and ALS transgenic mice suggest that NTF may be involved in the pathogenesis of ALS and the resistance of EOMs to the disease.
|
|
| 29. |
- He, Youjun, et al.
(författare)
-
Poly(4,8-bis(2-ethylhexyloxy)benzo[1,2-b:4,5-b ]dithiophene vinylene): Synthesis, Optical and Photovoltaic Properties
- 2010
-
Ingår i: JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY. - : John Wiley and Sons, Ltd. - 0887-624X .- 1099-0518. ; 48:8, s. 1822-1829
-
Tidskriftsartikel (refereegranskat)abstract
- A new benzodithiophene (BDT)-based polymer, poly(4,8-bis(2-ethylhexyloxy)benzo[1,2-b:4,5-b]dithiophene vinylene) (PBDTV), was synthesized by Pd-catalyzed Stille-coupling method. The polymer is soluble in common organic solvents and possesses high thermal stability. PBDTV film shows a broad absorption band covering from 350 nm to 618 nm, strong photoluminescence peaked at 545 nm and high hole mobility of 4.84 x 10(-3) cm(2)/Vs. Photovoltaic properties of PBDTV were studied by fabricating the polymer solar cells based on PBDTV as donor and PC70BM as acceptor. With the weight ratio of PBDTV: PC70BM of 1:4 and the active layer thickness of 65 nm, the power conversion efficiency of the device reached 2.63% with V-oc = 0.71 V, I-sc = 6.46 mA/cm(2), and FF = 0.57 under the illumination of AM1.5, 100 mW/cm(2).
|
|
| 30. |
- Hu, Xia-lin, et al.
(författare)
-
Evaluating the impacts of some environmentally relevant factors on the availability of bisphenol A with negligible-depletion SPME
- 2006
-
Ingår i: Chemosphere. - : Elsevier BV. - 1879-1298 .- 0045-6535. ; 65:11, s. 1935-1941
-
Tidskriftsartikel (refereegranskat)abstract
- The effect of some environmentally relevant factors including salinity, pH, and humic acids on the availability of bisphenol A (BPA) was evaluated by using the negligible-depletion solid-phase microextraction (nd-SPME) biomimetic method. With the variation of salinity (0-500 mM NaCl) and pH (5.0-8.5) of aqueous solutions, the partition coefficients of BPA between the nd-SPME fiber and the aqueous solution varied in the range of logD = 3.55-3.86, which indicates that the salinity and pH can influence the availability of BPA. By using Acros humic acid as model dissolved organic matter (DOM), it was also demonstrated that the environmental factors such as salinity and pH could affect the partitioning of BPA between DOM and aqueous solutions. The determined partition coefficients of BPA between dissolved organic carbon (DOC) and aqueous solutions were in the range of log D-DOC = 4.03-5.60 for Acros humic acid solutions with 1-50 mg l(-1) DOC. The influence of salinity and pH on log D-DOC was more significant at low concentration (0-5 mg l(-1)) of DOC. (c) 2006 Elsevier Ltd. All rights reserved.
|
|
| 31. |
- Huang, Kun, et al.
(författare)
-
Enhanced peak growth of global vegetation and its key mechanisms
- 2018
-
Ingår i: Nature Ecology and Evolution. - : Springer Science and Business Media LLC. - 2397-334X. ; 2:12, s. 1897-1905
-
Tidskriftsartikel (refereegranskat)abstract
- The annual peak growth of vegetation is critical in characterizing the capacity of terrestrial ecosystem productivity and shaping the seasonality of atmospheric CO2 concentrations. The recent greening of global lands suggests an increasing trend of terrestrial vegetation growth, but whether or not the peak growth has been globally enhanced still remains unclear. Here, we use two global datasets of gross primary productivity (GPP) and a satellite-derived Normalized Difference Vegetation Index (NDVI) to characterize recent changes in annual peak vegetation growth (that is, GPPmax and NDVImax). We demonstrate that the peak in the growth of global vegetation has been linearly increasing during the past three decades. About 65% of the NDVImax variation is evenly explained by expanding croplands (21%), rising CO2 (22%) and intensifying nitrogen deposition (22%). The contribution of expanding croplands to the peak growth trend is substantiated by measurements from eddy-flux towers, sun-induced chlorophyll fluorescence and a global database of plant traits, all of which demonstrate that croplands have a higher photosynthetic capacity than other vegetation types. The large contribution of CO2 is also supported by a meta-analysis of 466 manipulative experiments and 15 terrestrial biosphere models. Furthermore, we show that the contribution of GPPmax to the change in annual GPP is less in the tropics than in other regions. These multiple lines of evidence reveal an increasing trend in the peak growth of global vegetation. The findings highlight the important roles of agricultural intensification and atmospheric changes in reshaping the seasonality of global vegetation growth.
|
|
| 32. |
- Jing Xiong, Jiang, et al.
(författare)
-
A two-year family-based behaviour treatment for obese children
- 2005
-
Ingår i: Archives of Disease in Childhood. - : BMJ. - 0003-9888 .- 1468-2044. ; 90:12, s. 1235-8
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Childhood obesity has become a nutritional problem in China since the 1990s. Aims: A family based behavioural treatment was developed and tested, to see if its use was feasible in China and to evaluate its impact on obese schoolchildren. Methods: In a single school in Beijing, 33 obese children were randomly assigned to a treatment group and 35 to a control group. The treatment group participated in a family based behavioural treatment programme for two years. Height and weight were measured every six months for all participants. Blood pressure, cholesterol, and triglyceride levels were measured at baseline and after two years of programme implementation. Results: Body mass index (BMI, kg/m2) was significantly reduced in the treatment group (from 26.6 (1.7) to 24.0 (0.9), 95% CI 2.06 to 3.18) but not in the control group (from 26.1 (1.5) to 26.0 (1.6)). Total cholesterol decreased 5.5% and triglycerides 9.7% in the treatment group. There was a significant correlation between change in BMI and change in triglycerides. There were no significant changes in plasma lipids in the controls. Blood pressure values also decreased significantly in the treatment, but not the control group. Conclusions: A family based behavioural intervention was feasible to use in treating obesity in schoolchildren in Beijing, China. After two years of implementation, it successfully decreased the degree of obesity, reduced levels of blood pressure, and decreased serum lipids in treatment; there were no significant changes among control children.
|
|
| 33. |
- Kahsay, Abraha, et al.
(författare)
-
Obscurin maintains myofiber identity in extraocular muscles
- 2024
-
Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 65:2
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: The cytoskeleton of the extraocular muscles (EOMs) is significantly different from that of other muscles. We aimed to investigate the role of obscurin, a fundamental cytoskeletal protein, in the EOMs.Methods: The distribution of obscurin in human and zebrafish EOMs was compared using immunohistochemistry. The two obscurin genes in zebrafish, obscna and obscnb, were knocked out using CRISPR/Cas9, and the EOMs were investigated using immunohistochemistry, qPCR, and in situ hybridization. The optokinetic reflex (OKR) in five-day-old larvae and adult obscna−/−;obscnb−/− and sibling control zebrafish was analyzed. Swimming distance was recorded at the same age.Results: The obscurin distribution pattern was similar in human and zebrafish EOMs. The proportion of slow and fast myofibers was reduced in obscna−/−;obscnb−/− zebrafish EOMs but not in trunk muscle, whereas the number of myofibers containing cardiac myosin myh7 was significantly increased in EOMs of obscurin double mutants. Loss of obscurin resulted in less OKRs in zebrafish larvae but not in adult zebrafish.Conclusions: Obscurin expression is conserved in normal human and zebrafish EOMs. Loss of obscurin induces a myofiber type shift in the EOMs, with upregulation of cardiac myosin heavy chain, myh7, showing an adaptation strategy in EOMs. Our model will facilitate further studies in conditions related to obscurin.
|
|
| 34. |
- Kanoni, Stavroula, et al.
(författare)
-
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
-
Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
|
|
| 35. |
- Li, Lili, et al.
(författare)
-
Heparanase overexpression reduces carrageenan-induced mechanical and cold hypersensitivity in mice
- 2012
-
Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 511:1, s. 4-7
-
Tidskriftsartikel (refereegranskat)abstract
- Heparanase controls the structure and functions of extracellular matrix (ECM) by degrading heparan sulfate proteoglycans. Heparanase is involved in inflammatory process through modulating the functions of inflammatory cytokines. The present study aimed to find out whether overexpression of heparanase in mice affects carrageenan-induced localized inflammation and inflammatory hyperalgesia. Without challenge, the heparanase overexpression did not significantly affect the mice in response to mechanical, cold and heat stimulation. Unilateral subcutaneous administration of carrageenan produced hypersensitivity to mechanical and cold in both wildtype and the heparanase overexpression (Hpa-tg) mice 24h after treatment. In comparison to wildtype animals, the Hpa-tg mice showed significantly reduced mechanical and cold hypersensitivity. This may, at least partially, due to the reduced mast cell infiltration at the site of inflammation in Hpa-tg mice. These data support a role for heparanase that reduces localized inflammation and inflammatory hyperalgesia in mice.
|
|
| 36. |
- Li, Qian, et al.
(författare)
-
Novel AQP2 Mutations and Clinical Characteristics in Seven Chinese Families With Congenital Nephrogenic Diabetes Insipidus
- 2021
-
Ingår i: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Mutations in AQP2 (aquaporin-2) lead to rare congenital nephrogenic diabetes insipidus (NDI), which has been limitedly studied in Chinese population.Methods: Twenty-five subjects from seven families with NDI in a department (Beijing, PUMCH) were screened for AQP2 mutations. Clinical characteristics were described and genotype-phenotype correlation analysis was performed.Results: We identified 9 AQP2 mutations in 13 patients with NDI, including 3 novel AQP2 mutations (p.G165D, p.Q255RfsTer72 and IVS3-3delC). Missense mutations were the most common mutation type, followed by splicing mutations, and frameshift mutations caused by small deletion or insertion. The onset-age in our patients was younger than 1 year old. Common manifestations included polydipsia, polyuria (7/7) and intermittent fever (6/7). Less common presentations included short stature (3/7) and mental impairment (1/7). High osmotic hypernatremia and low osmotic urine were the main biochemical features. Dilation of the urinary tract was a common complication of NDI (3/6). Level of serum sodium in NDI patients with compound het AQP2 mutations was higher than non-compound het mutations.Conclusion: In the first and largest case series of NDI caused by AQP2 mutation in Chinese population, we identified 9 AQP2 mutations, including 3 novel mutations. Phenotype was found to correlate with genotypes, revealed by higher level of serum sodium in patients with compound het AQP2 mutations than non-compound het mutations. This knowledge broadens genotypic and phenotypic spectrum for rare congenital NDI and provided basis for studying molecular biology of AQP2.
|
|
| 37. |
- Li, Q., et al.
(författare)
-
Novel AVPR2 mutations and clinical characteristics in 28 Chinese families with congenital nephrogenic diabetes insipidus
- 2021
-
Ingår i: Journal of Endocrinological Investigation. - : Springer Nature. - 0391-4097 .- 1720-8386. ; 44:12, s. 2777-2783
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: To investigate genotype and phenotype of congenital nephrogenic diabetes insipidus caused by AVPR2 mutations, which is rare and limitedly studied in Chinese population.Methods: 88 subjects from 28 families with NDI in a department (Beijing, PUMCH) were screened for AVPR2 mutations. Medical records were retrospectively reviewed and characterized. Genotype and phenotype analysis was performed.Results: 23 AVPR2 mutations were identified, including six novel mutations (p.Y117D, p.W208R, p.L313R, p.S127del, p.V162Sfs*30 and p.G251Pfs*96). The onset-age ranged from 1 week to 3 years. Common presentations were polydipsia and polyuria (100%) and intermittent fever (57%). 21% and 14% of patients had short stature and mental impairment. Urine SG and osmolality were decreased, while serum osmolality and sodium were high. Urological ultrasonography results showed hydronephrosis of the kidney (52%), dilation of the ureter (48%), and thickened bladder wall or increased residual urine (32%), led to intermittent urethral catheterization (7%), cystostomy (11%) and binary nephrostomy (4%). Urological defects were developed in older patients. Genotype and phenotype analysis revealed patients with non-missense mutations had higher levels of serum sodium than missense mutations.Conclusion: In the first and largest case series of NDI caused by AVPR2 mutations in Chinese population, we established genetic profile and characterized clinical data, reporting six novel mutations. Further, we found genotype was associated with phenotype. This knowledge broadens genotype and phenotype spectrum of rare congenital NDI caused by AVPR2 mutations, and provides basis for studying molecular biology of AVPR2.
|
|
| 38. |
- Li, Shenpan, et al.
(författare)
-
Hepatic injury and ileitis associated with gut microbiota dysbiosis in mice upon F–53B exposure
- 2024
-
Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 248
-
Tidskriftsartikel (refereegranskat)abstract
- Chlorinated polyfluorinated ether sulfonate (F–53B), a substitute of perfluorooctane sulfonic acid (PFOS), has attracted significant attention for its link to hepatotoxicity and enterotoxicity. Nevertheless, the underlying mechanisms of F–53B-induced enterohepatic toxicity remain incompletely understood. This study aimed to explore the role of F–53B exposure on enterohepatic injury based on the gut microbiota, pathological and molecular analysis in mice. Here, we exposed C57BL/6 mice to F–53B (0, 4, 40, and 400 μg/L) for 28 days. Our findings revealed a significant accumulation of F–53B in the liver, followed by small intestines, and feces. In addition, F–53B induced pathological collagen fiber deposition and lipoid degeneration, up-regulated the expression of fatty acid β-oxidation-related genes (PPARα and PPARγ, etc), while simultaneously down-regulating pro-inflammatory genes (Nlrp3, IL-1β, and Mcp1) in the liver. Meanwhile, F–53B induced ileal mucosal barrier damage, and an up-regulation of pro-inflammatory genes and mucosal barrier-related genes (Muc1, Muc2, Claudin1, Occludin, Mct1, and ZO-1) in the ileum. Importantly, F–53B distinctly altered gut microbiota compositions by increasing the abundance of Akkermansia and decreasing the abundance of Prevotellaceae_NK3B31_group in the feces. F–53B-altered microbiota compositions were significantly associated with genes related to fatty acid β-oxidation, inflammation, and mucosal barrier. In summary, our results demonstrate that F–53B is capable of inducing hepatic injury, ileitis, and gut microbiota dysbiosis in mice, and the gut microbiota dysbiosis may play an important role in the F–53B-induced enterohepatic toxicity.
|
|
| 39. |
- Li, Wanxin, et al.
(författare)
-
Exploring the Complex Relationship between Gut Microbiota and Risk of Colorectal Neoplasia Using Bidirectional Mendelian Randomization Analysis
- 2023
-
Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association For Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 32:6, s. 809-817
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Human gut microbiome has complex relation-ships with the host, contributing to metabolism, immunity, and carcinogenesis.Methods: Summary-level data for gut microbiota and metabo-lites were obtained from MiBioGen, FINRISK and human meta-bolome consortia. Summary-level data for colorectal cancer were derived from a genome-wide association study meta-analysis. In forward Mendelian randomization (MR), we employed genetic instrumental variables (IV) for 24 gut microbiota taxa and six bacterial metabolites to examine their causal relationship with colorectal cancer. We also used a lenient threshold for nine apriori gut microbiota taxa as secondary analyses. In reverse MR, we explored association between genetic liability to colorectal neoplasia and abundance of microbiota studied above using 95, 19, and 7 IVs for colorectal cancer, adenoma, and polyps, respectively.Results: Forward MR did not find evidence indicating causal relationship between any of the gut microbiota taxa or six bacterial metabolites tested and colorectal cancer risk. However, reverse MR supported genetic liability to colorectal adenomas was causally related with increased abundance of two taxa: Gammaproteobacteria (b = 0.027, which represents a 0.027 increase in log-transformed relative abundance values of Gam-maproteobacteria for per one-unit increase in log OR of adenoma risk; P = 7.06x10-8), Enterobacteriaceae (b = 0.023, P = 1.29x10-5).Conclusions: We find genetic liability to colorectal neoplasia may be associated with abundance of certain microbiota taxa. It is more likely that subset of colorectal cancer genetic liability variants changes gut biology by influencing both gut microbiota and colo-rectal cancer risk.Impact: This study highlights the need of future complemen-tary studies to explore causal mechanisms linking both host genetic variation with gut microbiome and colorectal cancer susceptibility.
|
|
| 40. |
- Li, Wei, et al.
(författare)
-
Soluble Immune Checkpoints Are Dysregulated in COVID-19 and Heavy Alcohol Users With HIV Infection
- 2022
-
Ingår i: FRONTIERS IN IMMUNOLOGY. - : Frontiers Media SA. - 1664-3224. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Immune checkpoints (ICPs) consist of paired receptor-ligand molecules that exert inhibitory or stimulatory effects on immune defense, surveillance, regulation, and self-tolerance. ICPs exist in both membrane and soluble forms in vivo and in vitro. Imbalances between inhibitory and stimulatory membrane-bound ICPs (mICPs) in malignant cells and immune cells in the tumor immune microenvironment (TIME) have been well documented. Blockades of inhibitory mICPs have emerged as an immense breakthrough in cancer therapeutics. However, the origin, structure, production regulation, and biological significance of soluble ICPs (sICPs) in health and disease largely remains elusive. Soluble ICPs can be generated through either alternative mRNA splicing and secretion or protease-mediated shedding from mICPs. Since sICPs are found in the bloodstream, they likely form a circulating immune regulatory system. In fact, there is increasing evidence that sICPs exhibit biological functions including (1) regulation of antibacterial immunity, (2) interaction with their mICP compartments to positively or negatively regulate immune responses, and (3) competition with their mICP compartments for binding to the ICP blocking antibodies, thereby reducing the efficacy of ICP blockade therapies. Here, we summarize current data of sICPs in cancer and infectious diseases. We particularly focus on sICPs in COVID-19 and HIV infection as they are the two ongoing global pandemics and have created the world's most serious public health challenges. A "storm" of sICPs occurs in the peripheral circulation of COVID-19 patients and is associated with the severity of COVID-19. Similarly, sICPs are highly dysregulated in people living with HIV (PLHIV) and some sICPs remain dysregulated in PLHIV on antiretroviral therapy (ART), indicating these sICPs may serve as biomarkers of incomplete immune reconstitution in PLHIV on ART. We reveal that HIV infection in the setting of alcohol misuse exacerbates sICP dysregulation as PLHIV with heavy alcohol consumption have significantly elevated plasma levels of many sICPs. Thus, both stimulatory and inhibitory sICPs are present in the bloodstream of healthy people and their balance can be disrupted under pathophysiological conditions such as cancer, COVID-19, HIV infection, and alcohol misuse. There is an urgent need to study the role of sICPs in immune regulation in health and disease.
|
|
| 41. |
- Lin, Shangrong, et al.
(författare)
-
Underestimated Interannual Variability of Terrestrial Vegetation Production by Terrestrial Ecosystem Models
- 2023
-
Ingår i: Global Biogeochemical Cycles. - 0886-6236. ; 37:4
-
Tidskriftsartikel (refereegranskat)abstract
- Vegetation gross primary production (GPP) is the largest terrestrial carbon flux and plays an important role in regulating the carbon sink. Current terrestrial ecosystem models (TEMs) are indispensable tools for evaluating and predicting GPP. However, to which degree the TEMs can capture the interannual variability (IAV) of GPP remains unclear. With large data sets of remote sensing, in situ observations, and predictions of TEMs at a global scale, this study found that the current TEMs substantially underestimate the GPP IAV in comparison to observations at global flux towers. Our results also showed the larger underestimations of IAV in GPP at nonforest ecosystem types than forest types, especially in arid and semiarid grassland and shrubland. One cause of the underestimation is that the IAV in GPP predicted by models is strongly dependent on canopy structure, that is, leaf area index (LAI), and the models underestimate the changes of canopy physiology responding to climate change. On the other hand, the simulated interannual variations of LAI are much less than the observed. Our results highlight the importance of improving TEMs by precisely characterizing the contribution of canopy physiological changes on the IAV in GPP and of clarifying the reason for the underestimated IAV in LAI. With these efforts, it may be possible to accurately predict the IAV in GPP and the stability of the global carbon sink in the context of global climate change.
|
|
| 42. |
- Liu, Jing-fu, et al.
(författare)
-
Equilibrium sampling of freely dissolved alkylphenols into a thin film of 1-octanol supported on a hollow fiber membrane
- 2006
-
Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 1520-6882 .- 0003-2700. ; 78:24, s. 8526-8534
-
Tidskriftsartikel (refereegranskat)abstract
- A new negligible depletion extraction procedure was proposed for equilibrium sampling of 4-tert-octylphenol (OP) and 4-nonylphenol (NP) into a thin film of 1-octanol supported on a hollow fiber membrane. This thin liquid film extraction technique was directed at the determination of ( 1) freely dissolved concentrations, ( 2) distribution coefficients to 1-octanol (D-ow), and ( 3) binding to dissolved organic matter (D-DOC). The sampling device was prepared by dipping pieces of polypropylene microporous hollow fiber membrane (10-mm length, 30-mu m wall thickness, 240-mu m inner diameter) into 1-octanol for a few seconds to impregnate the pores of the hollow fiber wall. After stirring in 100 mL of sample solution for 24 h, the sampling device was harvested and desorbed with 30 mu L of methanol, of which 20 mu L was injected for HPLC analysis. With the measured Dow of a chemical and its equilibrium concentration in the 1-octanol sampling phase (C-octanol), the freely dissolved concentration (C-free) was calibrated based on C-free = C-octanol/D-ow. Measured log D-ow values of OP (4.32 +/- 0.06) and NP (4.79 +/- 0.02) were independent of the chemical concentration, only minimally affected by the environmentally relevant pH, buffering capacity, and salinity of samples, and agreed well with reported values. Log D-DOC values of OP (4.89 +/- 0.43) and NP (5.14 +/- 0.37), determined in Aldrich humic acid solution, agreed with reported partition coefficients to organic carbon ( log K-oc) for particles in river water and effluent wastewater. Short equilibration times and high enrichment factors were obtained for both analytes due to the high surface to volume ratio of the new sampler. The technique was successfully applied to determine C-free of OP and NP in real water samples and to study their association with humic acids and bovine albumin.
|
|
| 43. |
|
|
| 44. |
- Liu, Jing-Xia, et al.
(författare)
-
A novel type of multiterminal motor endplate in human extraocular muscles
- 2018
-
Ingår i: Investigative Ophthalmology and Visual Science. - Rockville : The Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 59:1, s. 539-548
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate the relation between type of motor endplate, acetylcholine receptor (AChR) subunit composition, and fiber types in human extraocular muscles (EOMs).Methods: EOM samples collected from subjects aged 34 to 82 years were serially sectioned and processed for immunohistochemistry, with specific antibodies against different myosin heavy chain (MyHC) isoforms, neurofilament, synaptophysin, and adult epsilon (ε) and fetal gamma (γ) AChR subunits as well as α-bungarotoxin.Results: A novel type of motor endplate consisting of large, multiterminal en plaque endings was found in human EOMs, in addition to the previously well-described single en plaque and multiple en grappe endplates. Such novel endplates were abundant but exclusively observed in myofibers lacking MyHC slow and fast IIa but containing MyHC extraocular (MyHCeom), isoforms. Multiple en grappe endings were found only in myofibers containing MyHC slow-tonic isoform and contained fetal γ AChR subunit. Adult ε and fetal γ AChR subunits, alone or combined, were found in the multiterminal endplates. Distinct AChR subunits were present in adjacent motor endplates of a given myofiber containing MyHCeom.Conclusions: Human EOMs have a more complex innervation pattern than previously described, comprising also a novel type of multiterminal motor endplate present in myofibers containing MyHCeom. The heterogeneity in AChR subunit composition in a given myofiber suggests the possible presence of polyneuronal innervation in human EOMs.
|
|
| 45. |
- Liu, Jing-Xia, et al.
(författare)
-
Complex Correlations Between Desmin Content, Myofiber Types, and Innervation Patterns in the Human Extraocular Muscles
- 2020
-
Ingår i: Investigative Ophthalmology and Visual Science. - : The Association for Research in Vision and Ophthalmology, Inc. (ARVO). - 0146-0404 .- 1552-5783. ; 61:3
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To investigate whether the distribution of intermediate filament protein desmin is related to the different patterns of innervation in the human extraocular muscles (EOMs).METHODS. EOM samples were analyzed with immunohistochemistry using antibodies against desmin, vimentin, different myosin heavy chain (MyHC) isoforms, and fetal and adult acetylcholine receptor (AChR) subunits. Neuromuscular junctions (NMJs) were identified with alpha-bungarotoxin or with antibodies against neurofilament and synaptophysin.RESULTS. Desmin was present in the vast majority of myofibers, but it was weakly present or absent in a limited area in the close vicinity of the single en plaque NMJs in less than half of these myofibers. Desmin was either present or lacking in MyHCsto/I myofibers displaying multiple en grappe endings but present in MyHCsto/I myofibers receiving spiral nerve endings. In MyHCeom myofibers displaying multiterminal en plaque endings, desmin was either present or absent irrespective of AChR subunits or EOM layer. Vimentin did not substitute for the lack of desmin.CONCLUSIONS. The results indicate that the human EOMs have a more complex cytoskeletal organization than other muscles and suggest additional signalling mechanisms from the NMJs to the myofibers.
|
|
| 46. |
- Liu, Jing-Xia, et al.
(författare)
-
Cytoskeletal Proteins in Myotendinous Junctions of Human Extraocular Muscles
- 2021
-
Ingår i: Investigative Ophthalmology and Visual Science. - : ARVO journals. - 0146-0404 .- 1552-5783. ; 62:2, s. 1-10
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this study was to investigate the cytoskeletal composition of myotendinous junctions (MTJs) in the human extraocular muscles (EOMs). Desmin and other major cytoskeletal proteins are enriched at the MTJs of ordinary myofibers, where they are proposed to be of particular importance for force transmission and required to maintain myofiber integrity. Methods: EOM and limb muscle samples were analyzed with immunohistochemistry using antibodies against the intermediate filament proteins desmin, nestin, keratin 19, vimentin, and different myosin heavy chain (MyHC) isoforms. MTJs were identified by labeling with antibodies against laminin or tenascin. Results: In contrast to MTJs in lumbrical muscle where desmin, nestin, and keratin 19 were always present, approximately one-third of the MTJs in the EOMs lacked either desmin and/or nestin, and all MTJs lacked keratin 19. Approximately 6% of the MTJs in the EOMs lacked all of these key cytoskeletal proteins. Conclusions: The cytoskeletal protein composition of MTJs in human EOMs differed significantly from that of MTJs in limb muscles. These differences in cytoskeletal protein composition may indicate particular adaptation to meet the functional requirements of the EOMs.
|
|
| 47. |
- Liu, Jing-Xia, et al.
(författare)
-
Different impact of ALS on laminin isoforms in human extraocular muscles versus limb muscles
- 2011
-
Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 52:7, s. 4842-4852
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose. To determ ine the impact of amyotrophic lateral sclerosis (ALS) on the extraocular muscles (EOMs) by examining the laminin isoform composition of the basement membranes (BMs) in EOMs and limb muscles from donors with ALS.Methods. Muscle samples collected at autopsy from ALS donors and from transgenic mice overexpressing human SOD1 mutations (D90A or G93A), and age-matched controls were analyzed with immunohistochemistry using antibodies against laminin chain α2 (Lnα2), Lnα4, Lnα5, Lnβ1, Lnβ2 and Lnγ1. Neuromuscular junctions (NMJs) were identified with α-bungarotoxin.Results. Lnα2, the hallmark chain of skeletal muscle, and Lnβ2 were absent or partially absent from the BMs in a variable number of muscle fibers in most of the ALS EOMs. Three ALS donors showed dramatic decrease in the levels of these chains around their muscle fibers and NMJs. Changes in Lnα2 were not age-related and were also present in EOMs of ALS mouse models. Lnα4 was preserved in the majority of NMJs in EOM but absent in the majority of NMJs in limb muscle of ALS. The BMs around muscle fibers, NMJs, nerves and blood vessels of the majority of EOMs of ALS donors had rather normal appearance and laminin composition, but heterogeneity was observed among EOM samples of individual ALS donors and between ALS donors.Conclusions. The present study showed distinct impact of ALS on EOMs as compared to limb muscles. The EOMs maintained a normal laminin composition in their NMJs which may be instrumental for the fact that they are not typically affected in ALS.
|
|
| 48. |
- Liu, Jing-Xia, et al.
(författare)
-
Distinct changes in synaptic protein composition at neuromuscular junctions of extraocular muscles versus limb muscles of ALS donors
- 2013
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:2, s. e57473-
-
Tidskriftsartikel (refereegranskat)abstract
- The pathophysiology of amyotrophic lateral sclerosis (ALS) is very complex and still rather elusive but in recent years evidence of early involvement of the neuromuscular junctions (NMJs) has accumulated. We have recently reported that the human extraocular muscles (EOMs) are far less affected than limb muscles at the end-stage of ALS from the same donor. The present study aimed to compare the differences in synaptic protein composition at NMJ and in nerve fibers between EOM and limb muscles from ALS donors and controls. Neurofilament light subunit and synaptophysin decreased significantly at NMJs and in nerve fibers in limb muscles with ALS whereas they were maintained in ALS EOMs. S100B was significantly decreased at NMJs and in nerve fibers in both EOMs and limb muscles of ALS donors, but other markers confirmed the presence of terminal Schwann cells in these NMJs. p75 neurotrophin receptor was present in nerve fibers but absent at NMJs in ALS limb muscles. The EOMs were able to maintain the integrity of their NMJs to a very large extent until the end-stage of ALS, in contrast to the limb muscles. Changes in Ca2+ homeostasis, reflected by altered S100B distribution, might be involved in the breakdown of nerve-muscle contact at NMJs in ALS.
|
|
| 49. |
- Liu, Jing-Xia, et al.
(författare)
-
Distribution of SERCA isoforms in human intrafusal fibers
- 2003
-
Ingår i: Histochemistry and Cell Biology. - : Springer. - 0948-6143 .- 1432-119X. ; 120:4, s. 299-306
-
Tidskriftsartikel (refereegranskat)abstract
- The sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) is a membrane protein that plays a crucial role in muscle relaxation by transporting cytosolic Ca2+ into the lumen of the sarco/endoplasmic reticulum. In this study, the presence of SERCA1 and SERCA2 was investigated in human intrafusal fibers by immunocytochemistry. Nuclear bag1 fibers contained both SERCA1 and SERCA2 isoforms, with predominant staining seen with SERCA2 in the A and B regions. Most nuclear bag2 fibers also contained SERCA1 and SERCA2 isoforms and their coexistence frequently occurred in the A region. SERCA1 was present whereas SERCA2 was generally absent in the nuclear chain fibers. The staining intensity seen with the SERCA1 monoclonal antibody varied in the order of chain>bag1>bag2. The expression of SERCA1 isoform was found to correlate with the presence of fast myosin heavy chain (MyHC) isoform in nuclear chain fibers, whereas for nuclear bag fibers there was no such apparent correlation between patterns of expression of SERCA and MyHC isoforms. The phenotype revealed for the human bag fibers was very sophisticated and adapted to attain a very wide range of contraction and relaxation velocities.
|
|
| 50. |
- Liu, Jing-Xia, et al.
(författare)
-
Fiber content and myosin heavy chain composition of muscle spindles in aged human biceps brachii
- 2005
-
Ingår i: Journal of Histochemistry and Cytochemistry. - Baltimore : Williams & Wilkins Co.. - 0022-1554 .- 1551-5044. ; 53:4, s. 445-454
-
Tidskriftsartikel (refereegranskat)abstract
- The present study investigated potential age-related changes in human muscle spindles with respect to the intrafusal fiber-type content and myosin heavy chain (MyHC) composition in biceps brachii muscle. The total number of intrafusal fibers per spindle decreased significantly with aging, due to a significant reduction in the number of nuclear chain fibers. Nuclear chain fibers in old spindles were short and some showed novel expression of MyHC alpha-cardiac. The expression of MyHC alpha-cardiac in bag1 and bag2 fibers was greatly decreased in the A region. The expression of slow MyHC was increased in nuclear bag1 fibers and that of fetal MyHC decreased in bag2 fibers whereas the patterns of distribution of the remaining MyHC isoforms were generally not affected by aging. We conclude that aging appears to have an important impact on muscle spindle composition. These changes in muscle spindle phenotype may reflect an age-related deterioration in sensory and motor innervation and are likely to have an impact in motor control in the elderly.
|
|
