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1
SHAFIEE, M. "2-PLECTIC MANIFOLDS AND ITS RELATION WITH COURANT ALGEBROIDS." International Journal of Geometric Methods in Modern Physics 09, no. 03 (May 2012): 1250015. http://dx.doi.org/10.1142/s0219887812500156.
Анотація:
In this paper we study the relation between 2-plectic manifolds and Courant algebroids. We establish a relation between 2-Lagrangian submanifolds of 2-plectic manifolds and subbundles of Courant algebroids. Also we show that an action of a compact Lie group G on a 2-plectic manifold (M, ω) can be extended to an action of G on an exact Courant algebroid E over M if and only if G is a subgroup of Hamiltonian group of (M, ω).
2
SÄMANN, CHRISTIAN, and RICHARD J. SZABO. "GROUPOIDS, LOOP SPACES AND QUANTIZATION OF 2-PLECTIC MANIFOLDS." Reviews in Mathematical Physics 25, no. 03 (April 2013): 1330005. http://dx.doi.org/10.1142/s0129055x13300057.
Анотація:
We describe the quantization of 2-plectic manifolds as they arise in the context of the quantum geometry of M-branes and non-geometric flux compactifications of closed string theory. We review the groupoid approach to quantizing Poisson manifolds in detail, and then extend it to the loop spaces of 2-plectic manifolds, which are naturally symplectic manifolds. In particular, we discuss the groupoid quantization of the loop spaces of ℝ3, 𝕋3and S3, and derive some interesting implications which match physical expectations from string theory and M-theory.
3
Shafiee, Mohammad. "A note on $2$-plectic homogeneous manifolds." Journal of Geometric Mechanics 7, no. 3 (July 2015): 389–94. http://dx.doi.org/10.3934/jgm.2015.7.389.
4
Rogers, Christopher L. "2-Plectic geometry, Courant algebroids, and categorified prequantization." Journal of Symplectic Geometry 11, no. 1 (2013): 53–91. http://dx.doi.org/10.4310/jsg.2013.v11.n1.a4.
5
Shafiee, Mohammad. "The 2-plectic structures induced by the Lie bialgebras." Journal of Geometric Mechanics 9, no. 1 (2017): 83–90. http://dx.doi.org/10.3934/jgm.2017003.
6
Shafiee, Mohammad. "On compact semisimple Lie groups as 2-plectic manifolds." Journal of Geometry 105, no. 3 (April 21, 2014): 615–23. http://dx.doi.org/10.1007/s00022-014-0223-5.
7
Krepski, Derek. "Lie 2-algebras of symmetries of U(1)-bundle gerbes." Journal of Physics: Conference Series 2667, no. 1 (December 1, 2023): 012035. http://dx.doi.org/10.1088/1742-6596/2667/1/012035.
Анотація:
Abstract This is a brief survey of some recent results on infinitesimal symmetries of bundle gerbes and their relation to three Lie 2-algebras associated to manifolds equipped with a closed 3-form, such as 2-plectic manifolds: the Poisson Lie 2-algebra of local observables, the Lie 2-algebra of sections of an associated exact Courant algebroid, and the Atiyah Lie 2-algebra.
8
Bunk, Severin. "Gerbes in Geometry, Field Theory, and Quantisation." Complex Manifolds 8, no. 1 (January 1, 2021): 150–82. http://dx.doi.org/10.1515/coma-2020-0112.
Анотація:
Abstract This is a mostly self-contained survey article about bundle gerbes and some of their recent applications in geometry, field theory, and quantisation. We cover the definition of bundle gerbes with connection and their morphisms, and explain the classification of bundle gerbes with connection in terms of differential cohomology. We then survey how the surface holonomy of bundle gerbes combines with their transgression line bundles to yield a smooth bordism-type field theory. Finally, we exhibit the use of bundle gerbes in geometric quantisation of 2-plectic as well as 1- and 2-shifted symplectic forms. This generalises earlier applications of gerbes to the prequantisation of quasi-symplectic groupoids.
9
Xu, Rushuang, Shan He, Di Ma, Rui Liang, Qing Luo, and Guanbin Song. "Plectin Downregulation Inhibits Migration and Suppresses Epithelial Mesenchymal Transformation of Hepatocellular Carcinoma Cells via ERK1/2 Signaling." International Journal of Molecular Sciences 24, no. 1 (December 21, 2022): 73. http://dx.doi.org/10.3390/ijms24010073.
Анотація:
Plectin, as a cytoskeleton-related protein, is involved in various physiological and pathological processes of many cell types. Studies have found that plectin affects cancer cell invasion and metastasis, but the exact mechanism is not fully understood. In this study, we aim to investigate the role of plectin in the migration of hepatocellular carcinoma (HCC) cells and explore its relevant molecular mechanism. Herein, we found that the expression of plectin in HCC tissue and cells was significantly increased compared with normal liver tissue and cells. After downregulation of plectin, the migration ability of HCC cells was significantly lower than that of the control group. Moreover, the expression of E-cadherin was upregulated and the expression of N-cadherin and vimentin was downregulated, suggesting that plectin downregulation suppresses epithelial mesenchymal transformation (EMT) of HCC cells. Mechanically, we found that plectin downregulation repressed the extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. Activation of ERK1/2 recovered the plectin downregulation-inhibited migration and EMT of HCC cells. Taken together, our results demonstrate that downregulation of plectin inhibits HCC cell migration and EMT through ERK1/2 signaling, which provides a novel prognostic biomarker and potential therapeutic target for HCC.
10
Foisner, R., B. Feldman, L. Sander, and G. Wiche. "Monoclonal antibody mapping of structural and functional plectin epitopes." Journal of Cell Biology 112, no. 3 (February 1, 1991): 397–405. http://dx.doi.org/10.1083/jcb.112.3.397.
Анотація:
To map structural and functional epitopes of the cytomatrix protein plectin, a set of mAbs was prepared by immunization of mice. Using immunoblot analysis of plectin fragments obtained after limited digestion with various proteases, two groups of mAbs were distinguished. The epitopes of one group (1) were located on a 130-kD terminal segment of the plectin 300-kD polypeptide chain, whereas those of the other group (2) bound within a 40kD segment confined to a central domain of the polypeptide chain. Domains containing the epitopes of group 2 mAbs were shown to include in vitro phosphorylation sites for kinase A, whereas kinase C phosphorylation sites were found on the same terminal segment that contained group 1 mAb epitopes. Rotary shadowing EM of mAb (Fab fragment) -decorated plectin molecules at various states of aggregation, ranging from characteristic dumbbell-shaped single molecules to highly complex multimeric structures, revealed that the epitopes of group 1 as well as those of group 2 mAbs were located on plectin's roughly 200-nm long rod domain interlinking its two globular end domains. Epitopes of group 1 mAbs were localized within a region near the center of the rod, those of group 2 in more peripheral sections near the globular end domains. Solid-phase binding assays carried out in the presence of Fab fragments of mAbs demonstrated an interference of certain group 1 mAbs in the interactions of plectin with vimentin and lamin B. On the other hand, plectin's self-interaction was inhibited mainly by Fab fragments with epitopes in the peripheral rod domain (group 2 mAbs). Together, these results suggested that the molecular binding sites of plectin for vimentin and lamin B, as well as the phosphorylation sites for kinase C, were confined to a defined central section of plectin's rod domain. In addition, they suggest an involvement of peripheral rod sections in plectin self-association.
11
Litjens, Sandy H. M., Jan Koster, Ingrid Kuikman, Sandra van Wilpe, José M. de Pereda та Arnoud Sonnenberg. "Specificity of Binding of the Plectin Actin-binding Domain to β4 Integrin". Molecular Biology of the Cell 14, № 10 (жовтень 2003): 4039–50. http://dx.doi.org/10.1091/mbc.e03-05-0268.
Анотація:
Plectin is a major component of the cytoskeleton and links the intermediate filament system to hemidesmosomes by binding to the integrin β4 subunit. Previously, a binding site for β4 was mapped on the actin-binding domain (ABD) of plectin and binding of β4 and F-actin to plectin was shown to be mutually exclusive. Here we show that only the ABDs of plectin and dystonin bind to β4, whereas those of other actin-binding proteins do not. Mutations of the ABD of plectin-1C show that Q131, R138, and N149 are critical for tight binding of the ABD to β4. These residues form a small cavity, occupied by a well-ordered water molecule in the crystal structure. The β4 binding pocket partly overlaps with the actin-binding sequence 2 (ABS2), previously shown to be essential for actin binding. Therefore, steric interference may render binding of β4 and F-actin to plectin mutually exclusive. Finally, we provide evidence indicating that the residues preceding the ABD in plectin-1A and -1C, although unable to mediate binding to β4 themselves, modulate the binding activity of the ABD for β4. These studies demonstrate the unique property of the plectin-ABD to bind to both F-actin and β4, and explain why several other ABD-containing proteins that are expressed in basal keratinocytes are not recruited into hemidesmosomes.
12
Osmanagic-Myers, Selma, Martin Gregor, Gernot Walko, Gerald Burgstaller, Siegfried Reipert, and Gerhard Wiche. "Plectin-controlled keratin cytoarchitecture affects MAP kinases involved in cellular stress response and migration." Journal of Cell Biology 174, no. 4 (August 14, 2006): 557–68. http://dx.doi.org/10.1083/jcb.200605172.
Анотація:
Plectin is a major intermediate filament (IF)–based cytolinker protein that stabilizes cells and tissues mechanically, regulates actin filament dynamics, and serves as a scaffolding platform for signaling molecules. In this study, we show that plectin deficiency is a cause of aberrant keratin cytoskeleton organization caused by a lack of orthogonal IF cross-linking. Keratin networks in plectin-deficient cells were more susceptible to osmotic shock–induced retraction from peripheral areas, and their okadaic acid–induced disruption (paralleled by stress-activated MAP kinase p38 activation) proceeded faster. Basal activities of the MAP kinase Erk1/2 and of the membrane-associated upstream protein kinases c-Src and PKCδ were significantly elevated, and increased migration rates, as assessed by in vitro wound-closure assays and time-lapse microscopy, were observed. Forced expression of RACK1, which is the plectin-binding receptor protein for activated PKCδ, in wild-type keratinocytes elevated their migration potential close to that of plectin-null cells. These data establish a link between cytolinker-controlled cytoarchitecture/scaffolding functions of keratin IFs and specific MAP kinase cascades mediating distinct cellular responses.
13
Fujiwara, S., and N. Takeo. "051 Carboxy-terminal structure of plectin-2." Journal of Dermatological Science 15, no. 2 (August 1997): 111. http://dx.doi.org/10.1016/s0923-1811(97)81755-0.
14
Nievers, M. G., I. Kuikman, D. Geerts, I. M. Leigh, and A. Sonnenberg. "Formation of hemidesmosome-like structures in the absence of ligand binding by the (alpha)6(beta)4 integrin requires binding of HD1/plectin to the cytoplasmic domain of the (beta)4 integrin subunit." Journal of Cell Science 113, no. 6 (March 15, 2000): 963–73. http://dx.doi.org/10.1242/jcs.113.6.963.
Анотація:
Hemidesmosomes are adhesion structures that mediate anchorage of epithelial cells to the underlying basement membrane. We have previously shown that the (alpha)6(beta)4 integrin can induce the assembly of these multi-protein structures independent of binding to its ligand laminin-5 (ligand-independent formation of hemidesmosomes). Our results suggested a role for HD1/plectin, which binds to the cytoplasmic domain of the (beta)4 integrin subunit, in controlling the clustering of hemidesmosomal components at the basal side of the cell. Using keratinocytes derived from patients lacking HD1/plectin, we now show that ligand-independent formation of hemidesmosomal clusters indeed requires HD1/plectin, in contrast to the ligand-dependent assembly of hemidesmosomes. No clustering of the (alpha)6(beta)4 integrin, or of the bullous pemphigoid antigens BP180 and BP230, was seen when HD1/plectin-deficient keratinocytes were plated on fibronectin or type IV collagen. In (β)4-deficient keratinocytes, expression of an interleukin 2 receptor (IL2R) transmembrane chimera containing the (beta)4 cytoplasmic tail with the mutation R1281W, which abrogates HD1/plectin binding, resulted in a diffuse distribution of the chimeric receptor. In contrast, a (beta)4(R1281W) mutant that can associate with (alpha)6 and bind ligand, was found to be directed to the basal surface of the cells, at sites where laminin-5 was deposited. In addition, this mutant induced clustering of BP180 and BP230 at these sites. Together, these results show that the formation of hemidesmosomes requires binding of either ligand or HD1/plectin to the (beta)4 integrin subunit. Intriguingly, we found that IL2R/(beta)4 chimeras become localized in pre-existing hemidesmosomes of HD1/plectin-deficient keratinocytes, and that this localization requires a domain in the (beta)4 cytoplasmic tail that is also required for HD1/plectin binding (residues 1115–1356). Because this part of (beta)4 lacks the BP180 binding site, and since we show in this study that it is unable to interact with the same part on another (beta)4 molecule, we suggest that the chimera becomes incorporated into hemidesmosomes of HD1/plectin-deficient keratinocytes by interacting with an as yet unidentified hemidesmosomal component.
15
Wilhelmsen, Kevin, Sandy H. M. Litjens, Ingrid Kuikman, Ntambua Tshimbalanga, Hans Janssen, Iman van den Bout, Karine Raymond, and Arnoud Sonnenberg. "Nesprin-3, a novel outer nuclear membrane protein, associates with the cytoskeletal linker protein plectin." Journal of Cell Biology 171, no. 5 (December 5, 2005): 799–810. http://dx.doi.org/10.1083/jcb.200506083.
Анотація:
Despite their importance in cell biology, the mechanisms that maintain the nucleus in its proper position in the cell are not well understood. This is primarily the result of an incomplete knowledge of the proteins in the outer nuclear membrane (ONM) that are able to associate with the different cytoskeletal systems. Two related ONM proteins, nuclear envelope spectrin repeat (nesprin)–1 and –2, are known to make direct connections with the actin cytoskeleton through their NH2-terminal actin-binding domain (ABD). We have now isolated a third member of the nesprin family that lacks an ABD and instead binds to the plakin family member plectin, which can associate with the intermediate filament (IF) system. Overexpression of nesprin-3 results in a dramatic recruitment of plectin to the nuclear perimeter, which is where these two molecules are colocalized with both keratin-6 and -14. Importantly, plectin binds to the integrin α6β4 at the cell surface and to nesprin-3 at the ONM in keratinocytes, suggesting that there is a continuous connection between the nucleus and the extracellular matrix through the IF cytoskeleton.
16
HOLOVACHOV, OLEKSANDR. "Swedish Plectida (Nematoda). Part 2. The genus Antomicron Cobb, 1920." Zootaxa 3380, no. 1 (July 5, 2012): 39. http://dx.doi.org/10.11646/zootaxa.3380.1.3.
Анотація:
Two new species of Antomicron are described from bottom sediments collected in Gullmarn Fjord, west coast of Sweden.A. quindecimpapillatus sp. n. is particularly characterised by the 1390–1459 µm long body; elongate doughnut-shapedamphid; straight vagina with drop-shaped sclerotizations; female without sensilla in pharyngeal region and without sup-plements; male with two pairs of setiform sensilla in pharyngeal region, 15 tubular and no alveolar supplements, one pairof precloacal and four pairs of caudal setae, 26.0–29.5 µm long spicules. A. lorenzeni sp. n. is particularly characterisedby the 603–676 µm long body; an inverted U-shaped amphid; straight vagina without sclerotizations; female without sen-silla in pharyngeal region and without supplements; male without sensilla in pharyngeal region, two tubular and nine al-veolar supplements, one pair of precloacal and four pairs of caudal setae, 23 µm long spicules. Additional information onthe males of Antomicron pellucidum, A. elegans, A. pratense and A. intermedius is provided. A taxonomic review, tabular compendium and identification key of species of the genus Antomicron are also given.
17
Song, Jae-Geun, Julius Kostan, Friedel Drepper, Bettina Knapp, Euripedes de Almeida Ribeiro, Petr V. Konarev, Irina Grishkovskaya та ін. "Structural Insights into Ca 2+ -Calmodulin Regulation of Plectin 1a-Integrin β4 Interaction in Hemidesmosomes". Structure 23, № 3 (березень 2015): 558–70. http://dx.doi.org/10.1016/j.str.2015.01.011.
18
Yin, Huadong, Shunshun Han, Can Cui, Yan Wang, Diyan Li, and Qing Zhu. "Plectin regulates Wnt signaling mediated-skeletal muscle development by interacting with Dishevelled-2 and antagonizing autophagy." Gene 783 (May 2021): 145562. http://dx.doi.org/10.1016/j.gene.2021.145562.
19
Henzler, Tanja, Abdallah Harmache, Harald Herrmann, Herbert Spring, Marie Suzan, Gilles Audoly, Therese Panek, and Valerie Bosch. "Fully functional, naturally occurring and C-terminally truncated variant human immunodeficiency virus (HIV) Vif does not bind to HIV Gag but influences intermediate filament structure." Journal of General Virology 82, no. 3 (March 1, 2001): 561–73. http://dx.doi.org/10.1099/0022-1317-82-3-561.
Анотація:
A variant human immunodeficiency virus type 1 (HIV-1) vif gene, vifA45-2, which encodes a protein lacking 19 amino acids at the C terminus but which is fully functional in supporting HIV replication in non-permissive cells has been described previously. By employing newly generated anti-VifA45 serum, further properties of VifA45 and its full-length counterpart, VifA45open, in comparison to Vif from HIV strain BH10 are reported in permissive HeLa and COS-7 cells. The results obtained using confocal microscopic localization studies and in vitro binding assays do not support a requirement for the direct interaction of HIV Gag with Vif. Furthermore and in contrast to previous conclusions, detergent solubility analyses do not demonstrate a role for the C terminus of Vif in mediating localization to the fraction containing cellular membrane proteins. Localization of Vif from HIV strain BH10 to perinuclear aggregates in a small fraction (about 10%) of transfected HeLa cells has been previously reported. The intermediate filament protein vimentin colocalizes to these structures. In contrast, VifA45 and VifA45open form perinuclear aggregates in nearly all transfected HeLa cells; vimentin as well as the cytoskeletal-bridging protein plectin, but not the microtubular protein tubulin, become relocalized to these structures. Interestingly, in COS-7 cells, all of the functional Vif proteins tested (Vif from strain BH10, VifA45 and VifA45open) predominantly localize in the cytoplasm but still induce dramatic aggregation of vimentin and plectin, i.e. in these cells the respective Vif proteins are influencing intermediate filament structure in the absence of colocalization.
20
Nievers, M. G., R. Q. Schaapveld, L. C. Oomen, L. Fontao, D. Geerts, and A. Sonnenberg. "Ligand-independent role of the beta 4 integrin subunit in the formation of hemidesmosomes." Journal of Cell Science 111, no. 12 (June 15, 1998): 1659–72. http://dx.doi.org/10.1242/jcs.111.12.1659.
Анотація:
Recently, we have shown that a region within the beta4 cytoplasmic domain, encompassing the second fibronectin type III (FNIII) repeat and the first 27 amino acids of the connecting segment, is critical for the localization of alpha6 beta4 in hemidesmosomes. In addition, this region was shown to regulate the distribution of HD1/plectin in transfected cells. In order to investigate the function of the beta4 extracellular and cytoplasmic domains in the assembly and integrity of hemidesmosomes, we have constructed chimeric receptors consisting of the extracellular and transmembrane domains of the interleukin 2 receptor (IL2R), fused to different parts of the beta4 cytoplasmic domain. These chimeras are expressed as single subunits at the plasma membrane. The results show that the first and the second FNIII repeat, together with the first part of the connecting segment (in total a stretch of 241 amino acids spanning amino acids 1,115 to 1,356) are both essential and sufficient for the localization of beta4 in pre-existing hemidesmosomes. Moreover, expression of the IL2R/beta4 chimeric constructs in COS-7 and CHO cells, which do not express alpha6 beta4 or the bullous pemphigoid (BP) antigens but do express HD1/plectin, revealed that the stretch of 241 amino acids is sufficient for inducing the formation of type II hemidesmosomes. Expression of the IL2R/beta4 chimeras in a keratinocyte cell line derived from a patient lacking beta4 expression, showed that amino acids 1,115 to 1,356 can also induce the formation of type I hemidesmosomes. We further demonstrate that type I and II hemidesmosomes can also be formed upon adhesion of alpha6 beta4-expressing cells to fibronectin. These findings establish that the beta4 extracellular domain is not essential for the induction of hemidesmosome assembly. Moreover, they demonstrate that binding of alpha6 beta4 to ligand, and heterodimerization of alpha6 with beta4, are not required for hemidesmosome formation. This indicates that the assembly of hemidesmosomes can be regulated from within the cell.
21
Dong, Wenyu, Zhi Cai, Jing Pang, Jingjing Wang, Ningyuan Tang, Weiran Zhang, Feng Wang, et al. "Radiotherapy Enhancement for Human Pancreatic Carcinoma Using a Peptide-Gold Nanoparticle Hybrid." Journal of Biomedical Nanotechnology 16, no. 3 (March 1, 2020): 352–63. http://dx.doi.org/10.1166/jbn.2020.2898.
Анотація:
Pancreatic ductal adenocarcinoma (PDAC) is radioresistant. Due to their strong X-ray absorption capacity, gold nanoparticles (AuNPs) have been used as radiosensitizers for cancer therapeutics. Herein, we describe a novel conjugate complex consisting of a peptide for targeting plectin-1 (PTP) specifically expressed on the PDAC cell membrane and AuNPs, termed AuNP-PTP, to be used for PDAC radiotherapy in vitro and in vivo. Previous studies revealed that compared with unmodified AuNPs, AuNP-PTP along with relevant low-energy X-ray irradiation of 6 MV at a dose of 2 Gy (RF) increased the targeting efficiency and induced apoptosis in treated PANC-1 cells and tumours. Importantly, extensive histopathological examination did not reveal evidence of acute or chronic injury in mice due to AuNPs or AuNP-PTP for up to six weeks despite the presence of X-ray exposure. The delicate AuNP-PTP hybrid provides a novel strategy to enhance radiotherapy efficiency in PDAC treatment.
22
Arshad, Jahanzaib, Kelvin K. H. Tong, Sanam Movassaghi, Tilo Söhnel, Stephen M. F. Jamieson, Muhammad Hanif, and Christian G. Hartinger. "Impact of the Metal Center and Leaving Group on the Anticancer Activity of Organometallic Complexes of Pyridine-2-carbothioamide." Molecules 26, no. 4 (February 5, 2021): 833. http://dx.doi.org/10.3390/molecules26040833.
Анотація:
RuII(cym)Cl (cym = η6-p-cymene) complexes of pyridinecarbothioamides have shown potential for development as orally active anticancer metallodrugs, underlined by their high selectivity towards plectin as the molecular target. In order to investigate the impact of the metal center on the anticancer activity and their physicochemical properties, the Os(cym), Rh- and Ir(Cp*) (Cp* = pentamethylcyclopentadienyl) analogues of the most promising and orally active compound plecstatin 2 were prepared and characterized by spectroscopic techniques and X-ray diffraction analysis. Dissolution in aqueous medium results in quick ligand exchange reactions; however, over time no further changes in the 1H NMR spectra were observed. The Rh- and Ir(Cp*) complexes were investigated for their reactions with amino acids, and while they reacted with Cys, no reaction with His was observed. Studies on the in vitro anticancer activity identified the Ru derivatives as the most potent, independent of their halido leaving group, while the Rh derivative was more active than the Ir analogue. This demonstrates that the metal center has a significant impact on the anticancer activity of the compound class.
23
Koh, Timothy J., and Joel Escobedo. "Cytoskeletal disruption and small heat shock protein translocation immediately after lengthening contractions." American Journal of Physiology-Cell Physiology 286, no. 3 (March 2004): C713—C722. http://dx.doi.org/10.1152/ajpcell.00341.2003.
Анотація:
The purposes of this study were to determine whether, immediately after lengthening contractions, 1) levels of specific force-transmitting cytoskeletal elements are reduced in skeletal muscle cells and 2) cytosolic small heat shock proteins (HSPs) translocate to structures prone to disruption. Western blot analysis demonstrated decreased concentrations of z-disk proteins α-actinin and plectin and membrane scaffolding proteins dystrophin and β-spectrin in muscle exposed to lengthening contractions compared with contralateral control muscle. Lengthening contractions also resulted in immediate translocation of constitutively expressed HSP25 and αB-crystallin from the soluble to the insoluble fraction of muscle homogenates, and cryosections showed translocation from a diffuse, cytosolic localization to striations that corresponded to z-disks. Lengthening contraction-induced translocation of HSP25 and αB-crystallin was associated with phosphorylation of these small HSPs, which may trigger their protective activity. In summary, these findings demonstrate loss of z-disk and membrane scaffolding proteins immediately after lengthening contractions, and concomitant translocation of HSP25 and αB-crystallin to the z-disk, which may help to stabilize or repair cytoskeletal elements at this site.
24
Ketema, Mirjam, and Arnoud Sonnenberg. "Nesprin-3: a versatile connector between the nucleus and the cytoskeleton." Biochemical Society Transactions 39, no. 6 (November 21, 2011): 1719–24. http://dx.doi.org/10.1042/bst20110669.
Анотація:
The cytoskeleton is connected to the nuclear interior by LINC (linker of nucleoskeleton and cytoskeleton) complexes located in the nuclear envelope. These complexes consist of SUN proteins and nesprins present in the inner and outer nuclear membrane respectively. Whereas SUN proteins can bind the nuclear lamina, members of the nesprin protein family connect the nucleus to different components of the cytoskeleton. Nesprin-1 and -2 can establish a direct link with actin filaments, whereas nesprin-4 associates indirectly with microtubules through its interaction with kinesin-1. Nesprin-3 is the only family member known that can link the nuclear envelope to intermediate filaments. This indirect interaction is mediated by the binding of nesprin-3 to the cytoskeletal linker protein plectin. Furthermore, nesprin-3 can connect the nucleus to microtubules by its interactions with BPAG1 (bullous pemphigoid antigen 1) and MACF (microtubule–actin cross-linking factor). In contrast with the active roles that nesprin-1, -2 and -4 have in actin- and microtubule-dependent nuclear positioning, the role of nesprin-3 is likely to be more passive. We suggest that it helps to stabilize the anchorage of the nucleus within the cytoplasm and maintain the structural integrity and shape of the nucleus.
25
Sommerhalder, David, Sarina A. Piha-Paul, Meredith Pelster, Mitesh J. Borad, Andrae Lavon Vandross, Alexander I. Spira, Samantha Perez, et al. "A phase 1/2, first-in-human trial of ZB131, a novel antibody targeting cancer-specific plectin (CSP) in advanced solid tumors." Journal of Clinical Oncology 41, no. 16_suppl (June 1, 2023): 3083. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.3083.
Анотація:
3083 Background: Cancer-Specific Plectin (CSP) is a novel pro-tumorigenic target that is selectively expressed on the surface of tumors, while absent from benign tissue. CSP is highly expressed in many solid cancers, particularly pancreatic (PC), cholangiocarcinoma (CCA), and ovarian (OC). ZB131 (Zielbio), is a humanized anti-CSP IgG1 monoclonal antibody that binds specifically to CSP on the surface of tumor cells, rapidly internalizes and modulates key proliferative and cytoskeletal remodeling signaling pathways to decrease cancer cell growth and increase the recruitment of anti-tumor immune infiltrates. Methods: The dose escalation (3+3 design) and expansion are enrolling adult patients (pts) with advanced treatment-refractory solid tumors. ZB131 was administered IV over 60 minutes (without premedication) weekly. The starting dose of ZB131 is 0.3 mg/kg followed by 1,3, 9, 15 and 30 mg/kg. Primary objectives are safety, tolerability, and maximum tolerated dose/determination of Phase 2 dose. Secondary objectives are preliminary efficacy (RECIST v1.1), Pharmacokinetic (PK) and pharmacodynamic parameters in blood and paired tumor biopsies. Results: As of 31 Jan 2023, 24 pts had enrolled (9 PC, 6 CCA, 4 OC, 5 other). The median age was 59.5 yr (range, 35 – 84) with a median of 4 prior lines of therapy. The median ZB131 treatment duration is 5.3 weeks (range, 1 – 33). No dose-limiting toxicities were observed up to the dose of 30 mg/kg which is currently enrolling. Treatment-related adverse events (TRAEs) were grade 1/ 2: nausea (n=6), fatigue (n=5), anemia (n=3), diarrhea (n=2), flulike symptoms (n=2), and vomiting (n=2). Mild flu-like symptoms and nausea/vomiting were observed during or following infusion at doses of 9 mg/kg and above. Except for one episode of Gr 3 neutropenia at the 30 mg/kg dose, no other drug-related grade 3/4 TRAE’s were reported. Five pts had stable disease range, 12 – 33 weeks (2 PC, 1 CCA, 2 OC), with a 43% decrease in CA-125 observed in one OC pt. The PKs are linear and dose-proportional for all dose levels evaluated (estimated T½ of 6-9 days). No antidrug antibodies have been detected. Conclusions: Interim data from dose-escalation of this first-in-class, anti CSP antibody, demonstrates good tolerability with encouraging signs of activity and target engagement in heavily pretreated pts. Results support further clinical evaluation of ZB131 in dose-expansion cohorts including OC and including combination therapy with gemcitabine. Clinical trial information: NCT 05074472 .
26
Filiou, Michaela D., Larysa Teplytska, Markus Nussbaumer, David-M. Otte, Andreas Zimmer, and Christoph W. Turck. "Multi-Omics Analysis Reveals Myelin, Presynaptic and Nicotinate Alterations in the Hippocampus of G72/G30 Transgenic Mice." Journal of Personalized Medicine 12, no. 2 (February 9, 2022): 244. http://dx.doi.org/10.3390/jpm12020244.
Анотація:
The primate-specific G72/G30 gene locus has been associated with major psychiatric disorders, such as schizophrenia and bipolar disorder. We have previously generated transgenic mice which carry the G72/G30 locus and express the longest G72 splice variant (LG72) protein encoded by this locus with schizophrenia-related symptoms. Here, we used a multi-omics approach, including quantitative proteomics and metabolomics to investigate molecular alterations in the hippocampus of G72/G30 transgenic (G72Tg) mice. Our proteomics analysis revealed decreased expression of myelin-related proteins and NAD-dependent protein deacetylase sirtuin-2 (Sirt2) as well as increased expression of the scaffolding presynaptic proteins bassoon (Bsn) and piccolo (Pclo) and the cytoskeletal protein plectin (Plec1) in G72Tg compared to wild-type (WT) mice. Metabolomics analysis indicated decreased levels of nicotinate in G72Tg compared to WT hippocampi. Decreased hippocampal protein expression for selected proteins, namely myelin oligodentrocyte glycoprotein (Mog), Cldn11 and myelin proteolipid protein (Plp), was confirmed with Western blot in a larger population of G72Tg and WT mice. The identified molecular pathway alterations shed light on the hippocampal function of LG72 protein in the context of neuropsychiatric phenotypes.
27
Preisz, Klaudia, and Sarolta Kárpáti. "Paraneoplastic pemphigus." Orvosi Hetilap 148, no. 21 (May 1, 2007): 979–83. http://dx.doi.org/10.1556/oh.2007.27955.
Анотація:
A paraneoplasticus pemphigus malignus vagy benignus tumorokhoz társuló autoimmun hólyagos megbetegedés diagnosztikus és immunológiai kritériumait 1990-ben fektette le Anhalt . Klinikailag súlyos, fájdalmas, mélyre terjedő bőr- és nyálkahártyatünetek jellemzik. A bőrtünetek polimorf jellegűek, általában dominál a hólyagképződés. Egyes esetekben, az ún. „graft-versus-host-disease” formákban előfordul, hogy kizárólag papulosus, lichenoid bőrtünetek észlelhetők, hólyagképződés nincs, vagy csak később jelenik meg. Elsősorban ezen alcsoport betegeiben a bőr- és nyálkahártyatünetek mellett súlyos dyspnoét okozó pulmonalis érintettség is kialakul, melynek hátterében bronchiolitis obliterans áll. A paraneoplasticus pemphigus diagnosztikájában alapvető fontosságú a bőr/nyálkahártyák direkt immunfluoreszcens, továbbá a szérum indirekt immunhisztológiai és immunoblot vizsgálata. Az eddig azonosított autoantigének döntő többsége a plakincsalád tagja: envoplakin (210 kDa), periplakin (190 kDa), plectin (~500 kDa), desmoplakin I (250 kDa), desmoplakin II (210 kDa), bullosus pemphigoid antigén 1 (230 kDa). A plakinok mellett a desmosomalis cadherinek közé sorolt desmoglein 1 és 3 a bullosus pemphigoid antigén 2 (180 kDa), a desmocollin 2 és 3, továbbá egy még nem azonosított, 170 kDa molekulatömegű transzmembrán fehérje szintén autoantigénje a kórképnek. A paraneoplasticus pemphigus nagy mortalitású kórkép, az esetek több mint 90%-ában halálos kimenetelű. A háttérben álló tumor eltávolítása mellett a bázisterápia továbbra is a nagy dózisú szisztémás szteroidkezelés, melyet citosztatikumok, immunmodulánsok adásával egészítenek ki. Szóba jön ezenkívül plasmapheresis, plazmacsere, photopheresis, nagy dózisú intravénás immunglobulin és anti-CD20 monoklonális antitest (rituximab) adása is.
28
Zhylina, T. M., та V. L. Shevchenko. "УГРУПОВАННЯ ПІДСТИЛКОВИХ НЕМАТОД ЛІСІВ МЕЗИНСЬКОГО НАЦІОНАЛЬНОГО ПРИРОДНОГО ПАРКУ". Scientific Issue Ternopil Volodymyr Hnatiuk National Pedagogical University. Series: Biology 77, № 3 (24 вересня 2019): 13–17. http://dx.doi.org/10.25128/2078-2357.19.3.2.
Анотація:
The taxonomic structure of the nematodes and the thickness in the forest litter of the Mezin National Nature Park were studied. Samples were collected during 2008-2010 and 2014 (June – July) in 21 forest ecosystems. Nematodes were extracted by a modified Baermann's method from the sample of 5 g. The exposition time was 48 h. Extracted nematodes were fixed in the triethanolamine–formalin (TAF, 2 % triethanolamine, 7 % formaldehyde solution, 91 % water), and mounted on the temporary hydroglyceric slides.
To describe the taxonomic structure of nematode communities we calculated the proportion of each order (family) in the community as the ratio (in %) of the individuals of each order (family) to the total number of nematodes.
46 nematode species belonging to 36 genera, 21 families and 10 orders were identified. The average number of nematodes was 4256 per 100 g of substrate. The number of nematodes varied from 220 to 11920 specimens per 100 g in separate samples.
Most of the identified species (78.26 %) belong to the four orders: Tylenchida (10 species), Plectida (9 species), Rhabditida (9 species), Dorylaimida (8 species) or 21.74 %, 19.57 %, 19.57 % and 17.39 % of the species composition, respectively. The orders of Enoplida, Triplonchida, Araeolaimida, Mononchida, Monhysterida and Teratocephalida are represented by 1 to 2 species (4.35 – 2.17 % of the total number of identified species).
In terms of quantitative representation, species of Plectida are dominant (proportion in the community 43.15 %). This proportion was 2.5 times higher than the number of representatives of Tylenchida (17.07 %), Dorylaimida (17.01 %) and Rhabditida (16.44 %).
Comparatively, the largest number of species found belong to the families Plectidae (9 species), Cephalobidae (6 species), and Tylenchidae (5 species).
Only six nematode families were represented in the forest litter samples, namely: Plectidae (with proportion in the community 43.15 %), Dorylaimidae (with proportion in the community 13.74 %), Aphelenchoididae (with 8.99 %), Panagrolaimidae (with 8.17 %), Tylenchidae (with 5.90 %), Mesorhabditidae (with 5.48 %).
29
Herrmann, H., and G. Wiche. "Plectin and IFAP-300K are homologous proteins binding to microtubule-associated proteins 1 and 2 and to the 240-kilodalton subunit of spectrin." Journal of Biological Chemistry 262, no. 3 (January 1987): 1320–25. http://dx.doi.org/10.1016/s0021-9258(19)75789-5.
30
Sun, D., C. L. Leung, and R. K. Liem. "Characterization of the microtubule binding domain of microtubule actin crosslinking factor (MACF): identification of a novel group of microtubule associated proteins." Journal of Cell Science 114, no. 1 (January 1, 2001): 161–72. http://dx.doi.org/10.1242/jcs.114.1.161.
Анотація:
MACF (microtubule actin cross-linking factor) is a large, 608-kDa protein that can associate with both actin microfilaments and microtubules (MTs). Structurally, MACF can be divided into 3 domains: an N-terminal domain that contains both a calponin type actin-binding domain and a plakin domain; a rod domain that is composed of 23 dystrophin-like spectrin repeats; and a C-terminal domain that includes two EF-hand calcium-binding motifs, as well as a region that is homologous to two related proteins, GAR22 and Gas2. We have previously demonstrated that the C-terminal domain of MACF binds to MTs, although no homology was observed between this domain and other known microtubule-binding proteins. In this report, we describe the characterization of this microtubule-binding domain of MACF by transient transfection studies and in vitro binding assays. We found that the C-terminus of MACF contains at least two microtubule-binding regions, a GAR domain and a domain containing glycine-serine-arginine (GSR) repeats. In transfected cells, the GAR domain bound to and partially stabilized MTs to depolymerization by nocodazole. The GSR-containing domain caused MTs to form bundles that are still sensitive to nocodazole-induced depolymerization. When present together, these two domains acted in concert to bundle MTs and render them stable to nocodazole treatment. Recently, a study has shown that the N-terminal half of the plakin domain (called the M1 domain) of MACF also binds MTs. We therefore examined the microtubule binding ability of the M1 domain in the context of the entire plakin domain with and without the remaining N-terminal regions of two different MACF isoforms. Interestingly, in the presence of the surrounding sequences, the M1 domain did not bind MTs. In addition to MACF, cDNA sequences encoding the GAR and GSR-containing domains are also found in the partial human EST clone KIAA0728, which has high sequence homology to the 3′ end of the MACF cDNA; hence, we refer to it as MACF2. The C-terminal domain of mouse MACF2 was cloned and characterized. The microtubule-binding properties of MACF2 C-terminal domain are similar to that of MACF. The GAR domain was originally found in Gas 2 protein and here we show that it can associate with MTs in transfected cells. Plectin and desmoplakin have GSR-containing domains at their C-termini and we further demonstrate that the GSR-containing domain of plectin, but not desmoplakin, can bind to MTs in vivo.
31
Papineni, Rao V., Amitava Adhikary, and Santanu Bhattacharya. "Abstract 219: Towards targeted-gold nanoparticle enhanced chemoradiation therapy of pancreatic cancer." Cancer Research 82, no. 12_Supplement (June 15, 2022): 219. http://dx.doi.org/10.1158/1538-7445.am2022-219.
Анотація:
Abstract The goal of this project is to develop a unique pancreatic cancer treatment platform where, X-ray excited Targeted-Gold nanoparticles (T-GNPs) trigger and enhance drug action (I-RaGAZ, Integrated radiation combined with T-GNP and 2-Azido-2-deoxy-D-glucose (2-AZ-2-DG)). Herein, we plan to utilize a novel three stage nanotechnology-chemoradiation combinatorial approach for enhancing catastrophic cell death in pancreatic tumors and reducing normal tissue toxicity. T-GNP has cytotoxic effect at tumor site and can specifically sensitize tumor tissue for radiation. In this work, we used our GNP-based pancreatic ductal adenocarcinoma (PDAC) -specific drug delivery platform using a plectin-1-targeting peptide (PTP) (patent: US2018/0333432 A1) to demonstrate the cytotoxicity of the nanocomplex in vitro. In PANC-1 cancer cell model, using traditional gold-standard clonogenic assay, we show 2-AZ-2-DG has radiation-mediated cytotoxicity which is further augmented by T-GNP. These results align with our hypothesis and the electron spin resonance (ESR) spectroscopy electron-induced aminyl radical production data presented here. This radiation-produced auger electrons from T-GNP likely increased formation of RNH• which result in enhanced cell kill. This via H-atom abstraction reactions that might cause DNA-strand breaks and/or crosslink formation leading to lesions that could induce apoptosis of cancer cells. This nanotool paraphrased as I-RaGAZ, Integrated radiation induced T-GNP - 2-AZ-2-DG anti-tumor action, will be very useful for treating deep-seated tumors with minimum collateral damage. This approach, integrated radiation-mediated azido tumor cure (I-RaGAZ), has vast global cancer treatment potential considering the dual mode of damaging the tumor tissues and protecting the normal tissues/organs. Citation Format: Rao V. Papineni, Amitava Adhikary, Santanu Bhattacharya. Towards targeted-gold nanoparticle enhanced chemoradiation therapy of pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 219.
32
Nguyen, Jordan, Tze Wei Chong, Hafsa Elmi, Jiani Ma, John Madi, Asha Mamgain, Eileen Melendez, et al. "Role of Hemidesmosomes in Oral Carcinogenesis: A Systematic Review." Cancers 15, no. 9 (April 28, 2023): 2533. http://dx.doi.org/10.3390/cancers15092533.
Анотація:
Background: Oral cancers have limited diagnostic tools to aid clinical management. Current evidence indicates that alterations in hemidesmosomes, the adhesion complexes primarily involved in epithelial attachment to the basement membrane, are correlated to cancer phenotype for multiple cancers. This systematic review aimed to assess the experimental evidence for hemidesmosomal alterations, specifically in relation to oral potentially malignant disorders and oral squamous cell carcinomas. Methods: We conducted a systemic review to summarise the available literature on hemidesmosomal components and their role in oral pre-cancer and cancer. Relevant studies were retrieved from a comprehensive search of Scopus, Ovid MEDLINE, Ovid Embase and Web of Science. Results: 26 articles met the inclusion criteria, of which 19 were in vitro studies, 4 in vivo studies, 1 in vitro and in vivo study, and 2 in vitro and cohort studies. Among them, 15 studies discussed individual alpha-6 and/or beta-4 subunits, 12 studies discussed the alpha-6 beta-4 heterodimers, 6 studies discussed the entire hemidesmosome complex, 5 studies discussed bullous pemphigoid-180, 3 studies discussed plectin, 3 studies discussed bullous pemphigoid antigen-1 and 1 study discussed tetraspanin. Conclusion: Heterogeneity in cell type, experimental models, and methods were observed. Alterations in hemidesmosomal components were shown to contribute to oral pre-cancer and cancer. We conclude that there is sufficient evidence for hemidesmosomes and their components to be potential biomarkers for evaluating oral carcinogenesis.
33
Harris, T. J., D. R. Jones, C. M. Brenin, K. A. Kelly, K. George, and C. A. Moskaluk. "Evaluation of plectin-1 immunohistochemical staining in human non-small cell lung cancer." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e22118-e22118. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e22118.
Анотація:
e22118 Background: Plectin-1 (PLEC1), a known scaffolding protein, impacts signaling pathways and has been found to be up-regulated and redistributed to the cell membrane in tumor cells. The redistribution of PLEC1 has shown promise as a novel molecular imaging biomarker in experimental systems. The purpose of this study was to examine the variation of PLEC1 staining in human non-small cell lung cancer (NSCLC). Methods: 142 NSCLC samples from 2001–2003 were obtained from pathology archives and placed into tissue microarray (TMA) format. TMA sections were stained with anti-PLEC1 antibody. A total PLEC1 immunohistochemical (IHC) staining score was obtained by multiplying the intensity of PLEC1 staining, scored 0 through 3, by the percent of tumor cells showing membrane staining, scored 1 for <25%, 2 for 25%-75% and 3 for >75%. The samples were then grouped into low (0–2), intermediate (3–5) or high (6- 9) membrane expression and analyzed for clinical correlations to tumor type and pathological staging. Results: A total of 125 samples were successfully stained for PLEC1. In all NSCLC subgroups, there was variability of PLEC1 staining. Approximately 50% of cases showed intermediate to high staining. There was a trend of lower PLEC1 staining as the tumor stage advanced (p=0.1). There appeared to be no significant variations of PLEC1 staining when compared to gender of the patients. Conclusions: These findings are the first to show that a significant number of human NSCLC exhibit strong expression of PLEC1 in the cell membrane. As this biomarker is being developed for molecular imaging modalities in other tumor types, it may have potential to be of use in the non-invasive detection of disease or therapeutic efficacy monitoring in NSCLC. [Table: see text] No significant financial relationships to disclose.
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Kannarkat, G. J., T. Harris, K. Kelly, P. Fracasso, and C. Moskaluk. "Evaluation of plectin-1 immunohistochemical expression in human colon cancer tumor progression." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e22132-e22132. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e22132.
Анотація:
e22132 Background: Plectin-1 (PLEC1), a known scaffolding protein, was recently discovered to be upregulated and redistributed to the cell membrane in multiple cancers, thereby providing a molecular imaging biomarker for disease detection. The purpose of this study was to examine PLEC1 staining in the tumor progression of human colorectal carcinoma. Methods: A tissue microarray of colonic neoplastic progression was stained with antibody to PLEC1. A total PLEC1 immunohistochemical (IHC) staining score was obtained by multiplying the intensity of PLEC1 membrane staining, scored 1 to 3, by the percent of target cells stained, scored 1 (<25%), 2 ( 25%-75%) and 3 (>75%). Each specimen was grouped into low (0–2), intermediate (3–5) or high (6–9) expression. The mean IHC score and group distribution were obtained for each tissue type. Results: Normal colonic tissue showed the lowest membrane expression of PLEC1 with a mean IHC score of 2.24. Approximately 80% of cases were in the low group. Colonic adenomas had a slightly higher mean IHC score, 2.57, with more cases falling in the intermediate group. Invasive colorectal cancer as a whole had a mean IHC score of 3.96 with a third of cases falling into the high expression group. Inflamed colonic tissue (ulcerative colitis) stained the highest with a mean IHC score of 4.83 and all cases falling in the intermediate or high group. Conclusions: There is increasing membrane expression of PLEC1 in colonic epithelium through tumor progression. The observation of a difference in IHC staining of normal and malignant tissue requires larger confirmatory studies, but the redistribution of PLEC1 to the cell surface is a potential biomarker for molecular imaging of cancer and potential target for novel therapeutic agents. However, our finding of increased PLEC1 membrane staining in actively inflamed tissue may indicate an important caveat in the use and implementation of this biomarker in certain clinical situations. [Table: see text] No significant financial relationships to disclose.
35
Tran, Thai Thanh, Nguyen Le Que Lam, Nguyen Thi My Yen, Pham Thanh Luu, Tran Thi Hoang Yen, Nguyen Thi Huynh, Lam Van Tan, and Ngo Xuan Quang. "Using free-living nematode communities as biological monitoring of environmental quality status in Ben Tre city." Science and Technology Development Journal - Natural Sciences 4, no. 4 (November 1, 2020): First. http://dx.doi.org/10.32508/stdjns.v4i4.866.
Анотація:
Nematode communities were used as a tool to assess the environmental quality status of sediment of the water bodies in Ben Tre city. Eight locations in the main canals and river in the city were surveyed during the rainy season (September). The study recorded 51 genera belonging to 33 families, 10 orders (Araeolaimida, Chromadorida, Desmodorida, Dorylaimida, Enoplida, Monhysterida, Mononchida, Plectida, Rhabditida, and Triplonchida), 2 classes (Chromadorea and Enoplia). The density of nematode communities at most survey locations is quite high, ranging from 29.88 +/- 38.01 to 1172.08 +/- 659.74 individuals/10 cm2. However, the biodiversity is quite low, species richness index (S) ranged from 5.33 1.15 to 18.33 4.72, and Shannon diversity index (H') from 1.28 +/- 0.12 to 3.19 +/- 0.50 and Pielou's evenness index (J') from 0.47 +/- 0.04 to 0.93 +/- 0.04. The Maturity Index (MI) of nematode communities was applied to assess the environmental quality status of sediment. The results showed that the environmental quality status of sediment recorded disturbances, classified as bad to moderate. The colonizer-persister (c-p) combined with the MI is a potential tool in biological monitoring of environmental quality status. However, to increase the reliability of evaluation conclusions, the combination of MI and biological indicators as well as physical-chemical parameters is necessary.
36
Pozuelo Rubio, Mercedes, David G. Campbell, Nicholas A. Morrice, and Carol Mackintosh. "Phosphodiesterase 3A binds to 14-3-3 proteins in response to PMA-induced phosphorylation of Ser428." Biochemical Journal 392, no. 1 (November 8, 2005): 163–72. http://dx.doi.org/10.1042/bj20051103.
Анотація:
PDE3A (phosphodiesterase 3A) was identified as a phosphoprotein that co-immunoprecipitates with endogenous 14-3-3 proteins from HeLa cell extracts, and binds directly to 14-3-3 proteins in a phosphorylation-dependent manner. Among cellular stimuli tested, PMA promoted maximal binding of PDE3A to 14-3-3 proteins. While p42/p44 MAPK (mitogen-activated protein kinase), SAPK2 (stress-activated protein kinase 2)/p38 and PKC (protein kinase C) were all activated by PMA in HeLa cells, the PMA-induced binding of PDE3A to 14-3-3 proteins was inhibited by the non-specific PKC inhibitors Ro 318220 and H-7, but not by PD 184352, which inhibits MAPK activation, nor by SB 203580 and BIRB0796, which inhibit SAPK2 activation. Binding of PDE3A to 14-3-3 proteins was also blocked by the DNA replication inhibitors aphidicolin and mimosine, but the PDE3A–14-3-3 interaction was not cell-cycle-regulated. PDE3A isolated from cells was able to bind to 14-3-3 proteins after in vitro phosphorylation with PKC isoforms. Using MS/MS of IMAC (immobilized metal ion affinity chromatography)-enriched tryptic phosphopeptides and phosphospecific antibodies, at least five sites on PDE3A were found to be phosphorylated in vivo, of which Ser428 was selectively phosphorylated in response to PMA and dephosphorylated in cells treated with aphidicolin and mimosine. Phosphorylation of Ser428 therefore correlated with 14-3-3 binding to PDE3A. Ser312 of PDE3A was phosphorylated in an H-89-sensitive response to forskolin, indicative of phosphorylation by PKA (cAMP-dependent protein kinase), but phosphorylation at this site did not stimulate 14-3-3 binding. Thus 14-3-3 proteins can discriminate between sites in a region of multisite phosphorylation on PDE3A. An additional observation was that the cytoskeletal cross-linker protein plectin-1 coimmunoprecipitated with PDE3A independently of 14-3-3 binding.
37
Sharma, Vipra, Sabyasachi Bandyopadhyay, Kapil Sikka, Aanchal Kakkar, Gururao Hariprasad, and Sundararajan Baskar Singh. "Label-Free Proteomics of Oral Mucosa Tissue to Identify Potential Biomarkers That Can Flag Predilection of Precancerous Lesions to Oral Cell Carcinoma: A Preliminary Study." Disease Markers 2023 (February 1, 2023): 1–16. http://dx.doi.org/10.1155/2023/1329061.
Анотація:
Oral squamous cell carcinomas are mostly preceded by precancerous lesions such as leukoplakia and erythroplakia. Our study is aimed at identifying potential biomarker proteins in precancerous lesions of leukoplakia and erythroplakia that can flag their transformation to oral cancer. Four biological replicate samples from clinical phenotypes of healthy control, leukoplakia, erythroplakia, and oral carcinoma were annotated based on clinical screening and histopathological evaluation of buccal mucosa tissue. Differentially expressed proteins were delineated using a label-free quantitative proteomic experiment done on an Orbitrap Fusion Tribrid mass spectrometer in three technical replicate sets of samples. Raw files were processed using MaxQuant version 2.0.1.0, and downstream analysis was done via Perseus version 1.6.15.0. Validation included functional annotation based on biological processes and pathways using the ClueGO plug-in of Cytoscape. Hierarchical clustering and principal component analysis were performed using the ClustVis tool. Across control, leukoplakia, and cancer, L-lactate dehydrogenase A chain, plectin, and WD repeat-containing protein 1 were upregulated, whereas thioredoxin 1 and spectrin alpha chain, nonerythrocytic 1 were downregulated. Across control, erythroplakia, and cancer, L-lactate dehydrogenase A chain was upregulated whereas aldehyde dehydrogenase 2, peroxiredoxin 1, heat shock 70 kDa protein 1B, and spectrin alpha chain, nonerythrocytic 1 were downregulated. We found that proteins involved in leukoplakia were associated with alteration in cytoskeletal disruption and glycolysis, while in erythroplakia, they were associated with alteration in response to oxidative stress and glycolysis across phenotypes. Hierarchical clustering subgrouped half of precancerous samples under the main branch of the control and the remaining half under carcinoma. Similarly, principal component analysis identified segregated clusters of control, precancerous lesions, and cancer, but erythroplakia phenotypes, in particular, overlapped more with the cancer cluster. Qualitative and quantitative protein signatures across control, precancer, and cancer phenotypes explain possible functional outcomes that dictate malignant transformation to oral carcinoma.
38
Жиліна, Тетяна, та Валентина Шевченко. "ФАУНА ГРУНТОВИХ НЕМАТОД ПРИБЕРЕЖНИХ СМУГ РІЧОК ЧЕРНІГІВСЬКОГО ПОЛІССЯ". Biota. Human. Technology, № 3 (6 березня 2023): 26–35. http://dx.doi.org/10.58407/bht.3.22.3.
Анотація:
Мета роботи. Одержати відомості про таксономічну структуру угруповань ґрунтових нематод прибережних смуг річок Чернігівського Полісся. Методологія. Зразки ґрунту відбирали у 5 лучних екосистемах, які розташовані у прибережних смугах річок Ревна, Снов, Свишень, Десна та Дніпро у червні та липні 2014 року. Виділення нематод проводили лійковим методом Бермана з наважки 20 г. Експозиція становила 48 год., після чого нематод фіксували ТАФом (триетаноламін+формалін+вода у співвідношенні 2:7:91). Виготовляли тимчасові водно-гліцеринові мікропрепарати. Перерахунок чисельності здійснювали на 100 г абсолютно сухого субстрату. Розраховували частку участі кожного виду у складі фауни (домінування, D), як відношення (%) кількості особин цього виду до загальної кількості нематод та коефіцієнт трапляння (F), як відношення, у %, кількості зразків, в яких вид виявлений, до загальної кількості зразків. Наукова новизна. Вперше вивчена фауна ґрунтових нематод прибережних смуг річок Чернігівського Полісся, проведений її таксономічний аналіз. Зареєстровано 59 видів, які належать до 9 рядів, 31 родини, 48 родів. Для фауни Чернігівського Полісся виявлені нові види нематод, а саме: Hirschmaniella gracilis та Bastianiа sp. Висновки. Середня щільність нематод в угрупованнях ґрунтових нематод прибережних смуг річок становила 672 особини/100 г. Виявлені 59 видів належать до 9 рядів: Enoplida, Triplonchida, Dorylaimida, Mononchida, Monhysterida, Plectida, Rhabditida, Aphelenchida та Tylenchida. За видовим багатством та чисельністю домінують три ряди: Tylenchida, Dorylaimida та Rhabditida, в яких кількість зареєстрованих видів разом складає 37 або 62,6 %, а чисельність їхніх представників в угрупованнях становить 87,9 % від загальної. Більш різноманітними виявилися родини Plectidae та Cephalobidae (по 7 видів або 11,9 % від загальної кількості видів), більш чисельними були Tylenchidae та Cephalobidae (24,7 % та 17,3 % від загальної чисельності, відповідно). У ґрунтових пробах прибережних смуг річок найбільш часто траплялися та були більш чисельними в угрупованнях нематод Aglenchus agricola та Acrobeloides bűtschlii.
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Perez, Samantha M., Brian P. Murphy, Danielle B. Heckert, Sarah Hall, Abby L. Colvin, Molly F. Owens, Ben R. Verfurth, et al. "Abstract 6299: ZB131 antibody-drug conjugates induce potent antitumor activity." Cancer Research 83, no. 7_Supplement (April 4, 2023): 6299. http://dx.doi.org/10.1158/1538-7445.am2023-6299.
Анотація:
Abstract Antibody-drug conjugates (ADCs) have become increasingly adopted clinically, with 13 drugs FDA-approved and over 100 under clinical development. Despite this momentum and major advances in payload and linker technology, ADCs are limited by off-cancer target-mediated toxicities incurred by currently available targets. In contrast to genomic and proteomic strategies, our unique drug discovery approach accounts for a disease’s native context. This led to the identification of cancer-specific plectin (CSP) as not only overexpressed in malignant tissue compared to healthy, but exclusively present on the surface of cancer cells and absent in normal or pre-malignant tissue. A Phase 0 imaging trial (Biodistribution of Novel Imaging for Resectable Pancreatic Cancer - NCT01962909) evaluating a radiolabeled CSP-targeted peptide has revealed that CSP is bioavailable and abundant, with over a million CSP molecules per cancer cell in pancreatic cancer. Previously, we generated ZB131, a humanized monoclonal antibody that targets CSP. ZB131 demonstrated potent monotherapy efficacy in pancreatic, ovarian, and bile duct preclinical cancer models, indications that have high CSP expression and are being evaluated in a first-in-human Phase 1/2 clinical trial (NCT05074472). Here, we show that CSP is an ideal target for an ADC: it is abundantly and selectively expressed in many indications, bioavailable, and its inhibition is predicted to synergize with FDA-approved payloads. ZB131 binds specifically to CSP, rapidly internalizes, displays linear pharmacokinetics in pre-clinical models, and demonstrates a strong safety profile. We describe the development of two ZB131 ADCs, ZB131-MMAE (monomethyl auristatin E) and ZB131-DXd (Deruxtecan), with drug-to-antibody ratios of 3 – 4 and 7 – 8, respectively. After binding, both ADCs are rapidly and specifically internalized by CSP-positive cells resulting in drug payload release and enhancing cancer cell death compared to ZB131 alone. Moreover, we characterize cytotoxic activity in high and low CSP cell lines to evaluate ADC activity in relation to CSP abundance. In preclinical xenograft models, ZB131-ADC enhanced tumor regression compared to controls at clinically relevant doses. Furthermore, anti-huIgG staining revealed selective target engagement by ZB131-ADC. Taken together, these data show that ZB131-ADCs demonstrate potent antitumor activity and support their evaluation in a Phase 1 clinical trial. Citation Format: Samantha M. Perez, Brian P. Murphy, Danielle B. Heckert, Sarah Hall, Abby L. Colvin, Molly F. Owens, Ben R. Verfurth, Julien Dimastromatteo, Jiang He, Reid B. Adams, Yelena Kovtun, Lindsey T. Brinton, Kimberly A. Kelly. ZB131 antibody-drug conjugates induce potent antitumor activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6299.
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von der Heide, Eva, Sebastian Vosberg, Martin Neumann, Liliana H. Mochmann, Alva Rani James, Jutta Ortiz Tanchez, Cornelia Schlee, et al. "Molecular Alterations in Bone Marrow Mesenchymal Stroma Cells of AML Patients." Blood 124, no. 21 (December 6, 2014): 699. http://dx.doi.org/10.1182/blood.v124.21.699.699.
Анотація:
Abstract It is increasingly recognized that the tumor microenvironment plays a pivotal role in cancer initiation and progression. In mouse models it was shown that a genetically altered bone marrow (BM) micro milieu was sufficient to induce leukemia (Raaijmakers, Nature 2010); however, the pathogenic role and contribution of the BM stroma in leukemia initiation and during disease progression warrants further investigation. To address this, we have performed gene expression, methylation, RNAseq, whole exome sequencing (WES) in BM mesenchymal stroma cells (BM-MSC) and leukemic cells from AML patients (pts) to unravel underlying molecular alterations. We collected BM hematopoietic cells (BM-HC) as well as plastic-adherent BM-MSC from aspirates from AML pts and healthy donors (HD). BM-MSC were expanded to passage 4 and defined as CD73+/CD105+/CD271+/low/CD45-/CD33-. We investigated gene expression profiles (Affymetrix) of BM-MSC from newly diagnosed AML pts (n=20) and compared these to BM-MSC from HD (n=4). BM-MSC from AML pts displayed an altered expression signature with 191and 175genesbeingsignificantly 2-fold over- and under-expressed. KEGG analysis of differentially expressed genes in BM-MSC from AML pts exhibited enrichment for TGF-ß signalling, whereas downregulated genes were enriched for cytokine receptor interactions. Several of these candidates were validated in a larger set of BM-MSC samples by RT-PCR. One putative stroma-leukemia interaction molecule, lumican (LUM) was highly overexpressed in BM-MSC (n=60) from AML pts compared to HD (n=5; p value =0.019) indicating that LUM may affect the BM niche in AML. To explore the altered expression pattern in AML BM-MSC compared to HD BM-MSC, global methylation analyses (Illumina Infinium HumanMethylation 450 bead chip arrays) were performed in 5 AML pts where we had collected BM-HC and BM-MSC at 3 sequential time points [initial diagnosis (ID), remission (CR), relapse (REL); n=30] as well as in BM-HC and BM-MSC from HDs (n=6). A significantly different methylation profile was evident comparing AML BM-HC to the corresponding AML BM-MSC samples, the latter showing a homogenous pattern during the course of disease. When AML BM-MSC were compared to a set of HD BM-MSC, we identified 2416 differentially methylated CpG sites (p value <0.01) indicating that an epigenetic deregulation contributes to the altered gene expression profile observed in AML BM-MSC. These 30 AML BM-MSC/BM-HC samples were subsequently analyzed by WES to unravel genetic alterations in the compartments of the mesenchymal and hematopoietic cell fractions. In WES (HiSeq2000, 100bp paired-end), we obtained an average of 100 reads for the target region; more than 90% of the exome target region was covered at least 30-fold. When the AML BM-HC CR sample was used as germline control, a median of 3 SNVs were detected in AML BM-MSC samples. The only BM-MSC-specific alteration present in one AML patient at all time points (ID, CR, REL) was a mutation in the plectin gene (PLEC). This mutation in the ROD domain of this cytoskeletal linker protein is located in the hot spot for mutations described in epidermolysis bullosa. This mutation was validated by Sanger sequencing, however in a larger cohort of 50 AML ID BM-MSC, no additional PLEC mutation at the same position was found. The set of AML BM-MSC (n=15) samples further allowed us to identify lesions (SNVs, Indels) in the corresponding BM-HC (n=15). When we used the AML BM-MSC as germline control we identified in total 43 lesions in the AML BM-HC fractions, which were not found when the corresponding BM-HC CR sample was used as germline control. This unraveled pre-leukemic lesions present in the AML BM-HC at remission: importantly using this approach, lesions in ASXL1 (Y591*) and DNMT3A (R882H), and in another patient a DNMT3A (M880V) mutation were revealed. In conclusion, the altered gene expression profile and methylation signature of AML BM-MSC provide novel insights into the pathogenic role of the leukemic BM microenvironment. Genetic alterations explored by WES revealed only very few genetic hits that will require further functional exploration. However, the low number of genetic alterations suggests that the transcriptional and epigenetic alterations are directed by extrinsic factors. At the same time, AML BM-MSC provides a non-hematopoietic derived germline control that allows to unravel pre-leukemic lesions in BM-HC. Disclosures No relevant conflicts of interest to declare.
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Bajo, Ignacio, and Saïd Benayadi. "Quadratic Lie algebras with 2-plectic structures." Journal of Geometry and Physics, August 2023, 104958. http://dx.doi.org/10.1016/j.geomphys.2023.104958.
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Sevestre, Gabriel, and Tilmann Wurzbacher. "On the Prequantisation Map for 2-Plectic Manifolds." Mathematical Physics, Analysis and Geometry 24, no. 2 (June 2021). http://dx.doi.org/10.1007/s11040-021-09391-5.
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Mizuta, Kana, Takuma Matsubara, Akino Goto, William N. Addison, Mitsushiro Nakatomi, Kou Matsuo, Yukiyo Tada-Shigeyama, et al. "Plectin promotes tumor formation by B16 mouse melanoma cells via regulation of Rous sarcoma oncogene activity." BMC Cancer 22, no. 1 (August 30, 2022). http://dx.doi.org/10.1186/s12885-022-10033-4.
Анотація:
Abstract Background Melanoma is a malignant tumor characterized by high proliferation and aggressive metastasis. To address the molecular mechanisms of the proto-oncogene, Rous sarcoma oncogene (Src), which is highly activated and promotes cell proliferation, migration, adhesion, and metastasis in melanoma. Plectin, a cytoskeletal protein, has recently been identified as a Src-binding protein that regulates Src activity in osteoclasts. Plectin is a candidate biomarker of certain tumors because of its high expression and the target of anti-tumor reagents such as ruthenium pyridinecarbothioamide. The molecular mechanisms by which plectin affects melanoma is still unclear. In this study, we examined the role of plectin in melanoma tumor formation. Methods We used CRISPR/Cas9 gene editing to knock-out plectin in B16 mouse melanoma cells. Protein levels of plectin and Src activity were examined by western blotting analysis. In vivo tumor formation was assessed by subcutaneous injection of B16 cells into nude mice and histological analysis performed after 2 weeks by Hematoxylin-Eosin (H&E) staining. Cell proliferation was evaluated by direct cell count, cell counting kit-8 assays, cyclin D1 mRNA expression and Ki-67 immunostaining. Cell aggregation and adhesion were examined by spheroid formation, dispase-based dissociation assay and cell adhesion assays. Results In in vivo tumor formation assays, depletion of plectin resulted in low-density tumors with large intercellular spaces. In vitro experiments revealed that plectin-deficient B16 cells exhibit reduced cell proliferation and reduced cell-to-cell adhesion. Since Src activity is reduced in plectin-deficient melanomas, we examined the relationship between plectin and Src signaling. Src overexpression in plectin knockout B16 cells rescued cell proliferation and improved cell-to-cell adhesion and cell to extracellular matrix adhesion. Conclusion These results suggest that plectin plays critical roles in tumor formation by promoting cell proliferation and cell-to-cell adhesion through Src signaling activity in melanoma cells.
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Song, Byeong Geun, Wooil Kwon, Hyemin Kim, Eun Mi Lee, Young Min Han, Hongbeom Kim, Yoonhyeong Byun, et al. "Detection of Circulating Tumor Cells in Resectable Pancreatic Ductal Adenocarcinoma: A Prospective Evaluation as a Prognostic Marker." Frontiers in Oncology 10 (February 18, 2021). http://dx.doi.org/10.3389/fonc.2020.616440.
Анотація:
Circulating tumor cells (CTCs) are useful biomarkers of many solid tumors, but are infrequently detected in early stage pancreatic ductal adenocarcinomas (PDACs). The first drainage of pancreatic venous blood flow come to portal vein and pass through the liver, and they finally go out for peripheral blood. We thought that comparing CTCs from portal vein and peripheral blood could enable us to understand the clinical meaning of CTCs from each different site in PDACs. Therefore, we aimed to determine 1) whether CTCs could be reliably identified in early stages (operable) of PDACs, 2) if there are any differences in the detected number of CTC in portal vein blood and peripheral blood, and 3) whether CTCs can be sensitive biomarkers for the prognosis of resectable PDAC patients. Newly diagnosed PDAC patients who underwent operation with curative intention between 2013 and 2015 were prospectively enrolled. Blood draws from portal and peripheral vein ran through the microfabricated porous filter, and anti-epithelial cell adhesion molecule (EpCAM) and anti-Plectin-1 antibodies were used for CTC identification. Baseline clinical characteristics, tumor characteristics, treatment, and clinical outcomes were assessed. The clinical stages of the 32 enrolled patients were as follows: IA/IB 1 (3.1%); IIA 9 (28.1%); IIB 17 (53.1%); III 5 (15.6%). Twenty-seven patients (84.4%) received R0 resection, while five patients (15.6%) received R1 resection. EpCAM+ CTCs were detected in 20 portal blood (62.5%) and 22 peripheral blood (68.8%). Plectin-1+ CTCs were identified in 14 portal blood (43.8%) and 16 peripheral blood (50%). Plectin-1-expressing CTCs were picked from CTC platform (microfabricated porous filter) and we could find out all KRAS mutation. Patients with detectable EpCAM+ CTC less than one in peripheral blood showed longer overall survival (OS) compared to patients with detectable CTCs more than one (35.5 months vs. 16.0 months). EpCAM and Plectin-1 successfully identified CTCs at the early stage of PDACs. Also, the number of CTCs could be a prognostic marker for survival in resectable PDACs.
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Stenvall, Carl-Gustaf A., Joel H. Nyström, Ciarán Butler-Hallissey, Theresia Jansson, Taina Heikkilä, Stephen A. Adam, Roland Foisner, Robert D. Goldman, Karen M. Ridge, and Diana M. Toivola. "Cytoplasmic keratins couple with and maintain nuclear envelope integrity in colonic epithelial cells." Molecular Biology of the Cell, August 24, 2022. http://dx.doi.org/10.1091/mbc.e20-06-0387.
Анотація:
Keratin intermediate filaments convey mechanical stability and protection against stress to epithelial cells. Keratins are essential for colon health, as seen in keratin 8 knockout (K8‒/‒) mice exhibiting colitis phenotype. We hypothesized that keratins contribute to the nuclear structure and lamina in colonocytes. K8‒/‒ colonocytes in vivo exhibit significantly decreased levels of lamins A/C, B1, and B2 in a colon-specific and cell-intrinsic manner. CRISPR/Cas9- or siRNA-mediated K8 knockdown in Caco-2 cells similarly decreased lamin levels, which recovered after re-expression of K8 following siRNA treatment. Nuclear area was not decreased, and roundness was only marginally increased in cells without K8. Downregulation of K8 in adult K8flox/flox;Villin-Cre-Ert2 mice following tamoxifen administration significantly decreased lamin levels at day 4 when K8 levels had reduced to 40%. K8 loss also led to reduced levels of plectin, LINC complex, and lamin-associated proteins. While keratins were not seen in the nucleoplasm without or with leptomycin B treatment, keratins were found intimately located at the nuclear envelope and complexed with SUN2 and lamin A. Furthermore, K8 loss in Caco-2 cells compromised nuclear membrane integrity basally and after shear stress. In conclusion, colonocyte K8 couples with the nuclear lamina, and contributes to nuclear membrane integrity. [Media: see text] [Media: see text] [Media: see text]
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Liu, Weizhuo, Bo Hu, Yuliang Wang, Xiaobin Zhang, Miao Zhu, Yu Shi, Changfa Guo, and Yangyang Zhang. "Multiple targets related to mitochondrial function unveiled by metabolomics and proteomics profiles of hearts from atrial fibrillation patients." Frontiers in Physiology 14 (April 4, 2023). http://dx.doi.org/10.3389/fphys.2023.1123391.
Анотація:
Background: The prominent mitochondrial metabolic changes of the atrium reportedly have significant impact on electrical signals and structural remodeling which play important roles in the occurrence and development of atrial fibrillation (AF). However, the mechanism is not completely known.Objective: This study was aimed to explore the mitochondrial metabolism reprogrammed in AF patients by integrating metabolomics as well as proteomics of human atrium tissues.Methods and Results: Left atrial tissue samples were harvested from 10 non-valvular AF patients and 10 matched samples from healthy donors for transplantation. In metabolomics analysis, 113 metabolites were upregulated and 10 metabolites were downregulated in AF, where multiple pathways related to mitochondrial energy metabolism were enriched. Correlation analysis between the differentially expressed proteins and metabolites identified several hub proteins related to mitochondrial function including Glycerol-3-phosphate dehydrogenase 2 (GPD2), Synemin (SYNM), Plectin (PLEC), with MCC score of 27, 17, 16, respectively, which have the most interactions with the dysregulated metabolites and ranked at the top in network string interactions scored by MCC method. All 330 differentially expressed proteins including 225 upregulated and 105 downregulated molecules were revealed and analyzed, which identified the downregulation of GPD2 (p = 0.02 and FC = 0.77), PLEC (p < 0.001 and FC = 0.71) and SYNM (p = 0.04 and FC = 0.76) in AF patients. Gene Set Variation Analysis (GSEA) showed mitochondrial metabolism-associated pathways including oxidative phosphorylation (NES: −1.73) and ATP biosynthetic process (NES: −2.29), were dramatically diversified in human AF. In GSVA, the expression levels of GPD2, PLEC, and SYNM were demonstrated to be associated with multiple metabolic pathways related to mitochondrial function (e.g., lipid metabolism and AMP activated protein kinase signaling) and cardiac structural and electrical remodeling (e.g., contractile fiber, ion homeostasis), which were proven vital in the development and maintenance of AF.Conclusion: In all, this study provides new insights into understanding the mechanisms of AF progression, especially the reprogramming mitochondrial metabolism, and identifies several genes related to mitochondrial function as novel targets for AF, which may be involved in the occurrence and development of AF.