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Fulltext Systematic revision of the genus Peronia Fleming, 1822 (Gastropoda, Euthyneura, Pulmonata, Onchidiidae)

Dayrat B, Goulding TC, Apte D, Aslam S, Bourke A, Comendador J, et al.

Zookeys, 2020;972:1-224.
PMID: 33071542 DOI: 10.3897/zookeys.972.52853

The genus Peronia Fleming, 1822 includes all the onchidiid slugs with dorsal gills. Its taxonomy is revised for the first time based on a large collection of fresh material from the entire Indo-West Pacific, from South Africa to Hawaii. Nine species are supported by mitochondrial (COI and 16S) and nuclear (ITS2 and 28S) sequences as well as comparative anatomy. All types available were examined and the nomenclatural status of each existing name in the genus is addressed. Of 31 Peronia species-group names available, 27 are regarded as invalid (twenty-one synonyms, sixteen of which are new, five nomina dubia, and one homonym), and four as valid: Peronia peronii (Cuvier, 1804), Peronia verruculata (Cuvier, 1830), Peronia platei (Hoffmann, 1928), and Peronia madagascariensis (Labbé, 1934a). Five new species names are created: P. griffithsi Dayrat & Goulding, sp. nov., P. okinawensis Dayrat & Goulding, sp. nov., P. setoensis Dayrat & Goulding, sp. nov., P. sydneyensis Dayrat & Goulding, sp. nov., and P. willani Dayrat & Goulding, sp. nov.Peronia species are cryptic externally but can be distinguished using internal characters, with the exception of P. platei and P. setoensis. The anatomy of most species is described in detail here for the first time. All the secondary literature is commented on and historical specimens from museum collections were also examined to better establish species distributions. The genus Peronia includes two species that are widespread across the Indo-West Pacific (P. verruculata and P. peronii) as well as endemic species: P. okinawensis and P. setoensis are endemic to Japan, and P. willani is endemic to Northern Territory, Australia. Many new geographical records are provided, as well as a key to the species using morphological traits.

Matched MeSH terms: Cell Nucleus
Fulltext A new genus of air-breathing marine slugs from South-East Asia (Gastropoda, Pulmonata, Onchidiidae)

Dayrat B, Goulding TC, Khalil M, Comendador J, Xuân QN, Tan SK, et al.

Zookeys, 2019;877:31-80.
PMID: 31592220 DOI: 10.3897/zookeys.877.36698

As part of an ongoing effort to revise the taxonomy of air-breathing, marine, onchidiid slugs, a new genus, Laspionchis Dayrat & Goulding, gen. nov., is described from the mangroves of South-East Asia. It includes two new species, Laspionchis boucheti Dayrat & Goulding, sp. nov., and Laspionchis bourkei Dayrat & Goulding, sp. nov., both distributed from the Malacca Strait to the Philippines and Australia. This study is based on extensive field work in South-East Asia, comparative anatomy, and both mitochondrial (COI and 16S) and nuclear (ITS2 and 28S) DNA sequences. The two new species are found in the same habitat (mud surface in mangrove forests) and are externally cryptic but are distinct anatomically. Both species are also strongly supported by DNA sequences. Three cryptic, least-inclusive, reciprocally-monophyletic units within Laspionchis bourkei are regarded as subspecies: L. bourkei bourkei Dayrat & Goulding, ssp. nov., L. bourkei lateriensis Dayrat & Goulding, ssp. nov., and L. bourkei matangensis Dayrat & Goulding, ssp. nov. The present contribution shows again that species delineation is greatly enhanced by considering comparative anatomy and nuclear DNA sequences in addition to mitochondrial DNA sequences, and that thorough taxonomic revisions are the best and most efficient path to accurate biodiversity knowledge.

Matched MeSH terms: Cell Nucleus
Fulltext Integrative taxonomy of a new and highly-diverse genus of onchidiid slugs from the Coral Triangle (Gastropoda, Pulmonata, Onchidiidae)

Goulding TC, Khalil M, Tan SH, Dayrat B

Zookeys, 2018.
PMID: 29896045 DOI: 10.3897/zookeys.763.21252

A new genus of onchidiid slugs, Wallaconchis Goulding & Dayrat, gen. n., is described, including ten species. Five species were previously described but known only from the type material: Wallaconchis ater (Lesson, 1830), W. graniferum (Semper, 1880), W. nangkauriense (Plate, 1893), W. buetschlii (Stantschinsky, 1907), and W. gracile (Stantschinsky, 1907), all of which were originally classified in Onchidium Buchannan, 1800. Many new records are provided for these five species, which greatly expand their known geographic distributions. Five species are new: Wallaconchis achleitneri Goulding, sp. n., W. comendadori Goulding & Dayrat, sp. n., W. melanesiensis Goulding & Dayrat, sp. n., W. sinanui Goulding & Dayrat, sp. n., and W. uncinus Goulding & Dayrat, sp. n. Nine of the ten Wallaconchis species are found in the Coral Triangle (eastern Indonesia and the Philippines). Sympatry is high, with up to six species found on the island of Bohol (Philippines) and eight species overlapping in northern Sulawesi (Indonesia). Wallaconchis is distinguished from other onchidiids by its bright dorsal colors (red, yellow, orange) but those are extremely variable and not useful for specific identification. Internally, the reproductive system can be used to identify all Wallaconchis species. The copulatory organs of Wallaconchis species are especially diverse compared to other onchidiid genera, and the possible role of reproductive incompatibility in species diversification is discussed. All specimens examined were freshly collected for the purpose of a worldwide revision of the Onchidiidae Rafinesque, 1815. The species are well delineated using DNA sequences and comparative anatomy. Mitochondrial DNA analysis yields thirteen molecular units separated by a large barcode gap, while nuclear DNA yields nine units. By integrating nuclear DNA and mitochondrial DNA with morphology, ten species are recognized. The natural history of each species (e.g., the microhabitat where they are found) is also documented. Nomenclature is addressed thoroughly (the types of all onchidiid species were examined, lectotypes were designated when needed, nomina dubia are discussed). Morphological characters, transitions to new microhabitats, and diversification processes are discussed in the context of a robust molecular phylogeny.

Matched MeSH terms: Cell Nucleus
Fulltext A new species and new records of Onchidium slugs (Gastropoda, Euthyneura, Pulmonata, Onchidiidae) in South-East Asia

Dayrat B, Goulding TC, Khalil M, Apte D, Tan SH

Zookeys, 2019;892:27-58.
PMID: 31824202 DOI: 10.3897/zookeys.892.39524

A new species, Onchidium melakense Dayrat & Goulding, sp. nov., is described, bringing the total to four known species in the genus Onchidium Buchannan, 1800. Onchidium melakense is a rare species with only nine individuals found at three mangrove sites in the Andaman Islands and the Strait of Malacca (western Peninsular Malaysia and eastern Sumatra). The new species is delineated based on mitochondrial (COI and 16S) and nuclear (ITS2 and 28S) DNA sequences as well as comparative anatomy. Each Onchidium species is characterized by a distinct color and can easily be identified in the field, even in the Strait of Malacca where there are three sympatric Onchidium species. An identification key is provided. In addition, Onchidium stuxbergi (Westerlund, 1883) is recorded for the first time from eastern Sumatra, and Onchidium pallidipes Tapparone-Canefri, 1889, of which the type material is described and illustrated here, is regarded as a new junior synonym of O. stuxbergi.

Matched MeSH terms: Cell Nucleus
Computational prediction of Mycoplasma hominis proteins targeting in nucleus of host cell and their implication in prostate cancer etiology

Khan S, Zakariah M, Palaniappan S

Tumour Biol., 2016 Aug;37(8):10805-13.
PMID: 26874727 DOI: 10.1007/s13277-016-4970-9

Cancer has long been assumed to be a genetic disease. However, recent evidence supports the enigmatic connection of bacterial infection with the growth and development of various types of cancers. The cause and mechanism of the growth and development of prostate cancer due to Mycoplasma hominis remain unclear. Prostate cancer cells are infected and colonized by enteroinvasive M. hominis, which controls several factors that can affect prostate cancer growth in susceptible persons. We investigated M. hominis proteins targeting the nucleus of host cells and their implications in prostate cancer etiology. Many vital processes are controlled in the nucleus, where the proteins targeting M. hominis may have various potential implications. A total of 29/563 M. hominis proteins were predicted to target the nucleus of host cells. These include numerous proteins with the capability to alter normal growth activities. In conclusion, our results emphasize that various proteins of M. hominis targeted the nucleus of host cells and were involved in prostate cancer etiology through different mechanisms and strategies.

Matched MeSH terms: Cell Nucleus/metabolism
Fulltext Phylogenetic Relatedness of Several Agarwood-Producing Taxa (Thymelaeaceae) from Indonesia

Lee SY, Turjaman M, Mohamed R

Trop Life Sci Res, 2018 Jul;29(2):13-28.
PMID: 30112138 MyJurnal DOI: 10.21315/tlsr2018.29.2.2

Indonesia is home to several tree taxa that are harvested for agarwood. This highly valuable oleoresin ironically was the cause for some species to become vulnerable due to gluttonous human activity. However, information on the genetic diversity of these endangered trees is limited. In this study, 28 specimens representing eight species from two genera, Aquilaria and Gyrinops, were collected from ex-situ and in-situ populations in Indonesia. Phylogenetic analysis conducted on DNA sequences of the nuclear ribosomal internal transcribed spacer (ITS) and the trnL-trnF intergenic spacer regions, revealed that Aquilaria and Gyrinops are paraphyletic when Aquilaria cumingiana is excluded. The phylogenetic analysis for ITS and trnL-trnF showed capability to categorise agarwood-producing species based on their regions: East Indonesia and West Indonesia, using Wallace's Line as the divider. In addition, we discuss challenges in species identification and taxonomy of agarwood-producing genera, and their conservation efforts in Indonesia.

Matched MeSH terms: Cell Nucleus
Fulltext A transmission electron microscopy study on effects of a modified Glutaraldehyde fixation on Acanthamoeba castellanii

Santhana Raj L, Teh Hamidah Z, Nor Asiha CP, Paramasvaran S

Trop Biomed, 2006 Jun;23(1):69-74.
PMID: 17041554 MyJurnal

Transmission electron microscopy (TEM) can provide high resolution imaging of biological specimens. The study is to establish the effects of a modified glutaraldehyde (GA) compare to the standard GA fixation on Acanthamoeba castellanii from TEM perspectives and thus provide precise and accurate information on the ultrastructure studies of the parasite. By increasing the contrast, the ultrastructures of the parasite were more evident. The TEM images were obtained from parasites fixed with the modified GA and the standard GA and then the area of the nucleus and the gray values of the image of the nucleus of the parasites were measured. The mean areas of the nucleus were found to be significantly reduced in the standard GA fixed parasites (12210.4 nm2) compared to the modified GA fixed parasites (8676.3 nm2) (p < 0.05). The mean gray values of the image were significantly reduced from 2024 in the standard GA fixed parasites (2024) to the modified GA fixed parasites (1636) (p < 0.05). The study shows that the modified GA produced significantly better contrast on TEM images of the A. castellanii compared to the standard GA. This was because the modified GA generated more free water molecules during fixation and the uptake of modified GA by the nucleus of the parasite organizing all protein constituents in the cell into a more closely packed configuration than that of the standard GA. With such properties, the modified GA is a better fixative providing better images for ultrastructures of the parasite.

Matched MeSH terms: Cell Nucleus/ultrastructure
The aminopeptidase inhibitor, z-L-CMK, is toxic and induces cell death in Jurkat T cells through oxidative stress

Yeo EH, Goh WL, Chow SC

Toxicol. Mech. Methods, 2018 Mar;28(3):157-166.
PMID: 28849708 DOI: 10.1080/15376516.2017.1373882

The leucine aminopeptidase inhibitor, benzyloxycarbonyl-leucine-chloromethylketone (z-L-CMK), was found to be toxic and readily induce cell death in Jurkat T cells. Dose-response studies show that lower concentration of z-L-CMK induced apoptosis in Jurkat T cells whereas higher concentration causes necrosis. In z-L-CMK-induced apoptosis, both the initiator caspases (-8 and -9) and effector caspases (-3 and -6) were processed to their respective subunits. However, the caspases remained intact in z-L-CMK-induced necrosis. The caspase inhibitor, z-VAD-FMK inhibited z-L-CMK-mediated apoptosis and caspase processing but has no effect on z-L-CMK-induced necrosis in Jurkat T cells. The high mobility group protein B1 (HMGB1) protein was found to be released into the culture medium by the necrotic cells and not the apoptotic cells. These results indicate that the necrotic cell death mediated by z-L-CMK at high concentrations is via classical necrosis rather than secondary necrosis. We also demonstrated that cell death mediated by z-L-CMK was associated with oxidative stress via the depletion of intracellular glutathione (GSH) and increase in reactive oxygen species (ROS), which was blocked by N-acetyl cysteine. Taken together, the results demonstrated that z-L-CMK is toxic to Jurkat T cells and induces apoptosis at low concentrations, while at higher concentrations the cells die of necrosis. The toxic side effects in Jurkat T cells mediated by z-L-CMK are associated with oxidative stress via the depletion of GSH and accumulation of ROS.

Matched MeSH terms: Cell Nucleus Shape/drug effects
Mitochondrial targeting of bilirubin regulatory enzymes: An adaptive response to oxidative stress

Muhsain SN, Lang MA, Abu-Bakar A

Toxicol Appl Pharmacol, 2015 Jan 1;282(1):77-89.
PMID: 25478736 DOI: 10.1016/j.taap.2014.11.010

The intracellular level of bilirubin (BR), an endogenous antioxidant that is cytotoxic at high concentrations, is tightly controlled within the optimal therapeutic range. We have recently described a concerted intracellular BR regulation by two microsomal enzymes: heme oxygenase 1 (HMOX1), essential for BR production and cytochrome P450 2A5 (CYP2A5), a BR oxidase. Herein, we describe targeting of these enzymes to hepatic mitochondria during oxidative stress. The kinetics of microsomal and mitochondrial BR oxidation were compared. Treatment of DBA/2J mice with 200mgpyrazole/kg/day for 3days increased hepatic intracellular protein carbonyl content and induced nucleo-translocation of Nrf2. HMOX1 and CYP2A5 proteins and activities were elevated in microsomes and mitoplasts but not the UGT1A1, a catalyst of BR glucuronidation. A CYP2A5 antibody inhibited 75% of microsomal BR oxidation. The inhibition was absent in control mitoplasts but elevated to 50% after treatment. An adrenodoxin reductase antibody did not inhibit microsomal BR oxidation but inhibited 50% of mitochondrial BR oxidation. Ascorbic acid inhibited 5% and 22% of the reaction in control and treated microsomes, respectively. In control mitoplasts the inhibition was 100%, which was reduced to 50% after treatment. Bilirubin affinity to mitochondrial and microsomal CYP2A5 enzyme is equally high. Lastly, the treatment neither released cytochrome c into cytoplasm nor dissipated membrane potential, indicating the absence of mitochondrial membrane damage. Collectively, the observations suggest that BR regulatory enzymes are recruited to mitochondria during oxidative stress and BR oxidation by mitochondrial CYP2A5 is supported by mitochondrial mono-oxygenase system. The induced recruitment potentially confers membrane protection.

Matched MeSH terms: Active Transport, Cell Nucleus
A Cross-sectional Study to Evaluate Nuclear Changes in Buccal Mucosa Following Panoramic Radiography

Santhosh K, Manzoor S, Sushanth A, Seralathan S, Rajasekar V, Jacob A

J Contemp Dent Pract, 2020 Nov 01;21(11):1258-1261.
PMID: 33850072

AIM AND OBJECTIVE: To evaluate the possible genotoxic effect of X-rays on buccal mucosa while exposing to dental panoramic radiography using micronucleus test.
MATERIALS AND METHODS: The study group comprised of 30 healthy subjects, 15 males and 15 females, aged between 24 years and 65 years. Samples were obtained from the exfoliated oral mucosa cells of buccal mucosa before and 12 days after exposing the patients to panoramic radiography.
RESULTS: The study reported that there was no significant increase in the number of micronuclei cells present before and after panoramic radiography. Positive correlation existed between age with pre- and postexposure micronuclei.
CONCLUSION: Diagnostic dental panoramic radiograph does not induce micronuclei in the target buccal epithelium cells. A positive correlation between age and micronuclei frequency was established.
CLINICAL SIGNIFICANCE: Panoramic radiographs does not induce cytotoxicity but increase frequency may be vulnerable to genotoxic effects in buccal mucosal cells. Hence, dental radiographs should be prescribed only when necessary.

Matched MeSH terms: Cell Nucleus*
Sex chromatin positive nuclei in the nasal smears of the females

Sen Gupta BN

Med J Malaya, 1968 Sep;23(1):32-4.
PMID: 4237553
Matched MeSH terms: Cell Nucleus*
Fulltext Computer-linked image analysis of nuclear area: is there a use in diagnosis and grading of hepatocellular carcinoma?

Cheah PL, Looi LM

Malays J Pathol, 2007 Jun;29(1):37-40.
PMID: 19105327 MyJurnal

Hepatocellular carcinoma (HCC) ranks as the fifth most common cancer with an increasing frequency worldwide. "Nuclear atypia", one of the critical features in histological diagnosis of malignancy and grading of the tumour, is generally ascertained through eyeballing. A study was conducted at the Department of Pathology, University of Malaya Medical Centre to assess whether nuclear area, (surrogate measure for nuclear size) and standard deviation (surrogate measure for nuclear pleomorphism) when objectively measured via computer-linked image analysis differs between (1) benign and malignant liver cells and (2) different grades of HCC. A 4-microm thick H&E stained section of 52 histologically re-confirmed HCC with 36 having benign, non-dysplastic surrounding liver were analysed using the Leica Q550 CW system. 10 consecutive non-overlapping, non-mitotic and non-apoptotic nuclei of HCC and surrounding benign hepatocytes respectively were manually traced at 400x magnification on the computer monitor and the nuclear area for the particular cell computed in arbitrary units by the Leica QWIN software. A total of 360 benign hepatocytic nuclei, 240 low grade HCC and 280 high grade HCC nuclei were traced. The mean nuclear area of the benign hepatocytes (37.3) was significantly smaller (p < 0.05) than that of both low grade (65.2) and high grade HCC (80.0). In addition, the mean nuclear area of high grade HCC was significantly larger (p < 0.05) than the low grade HCC. SD of the nuclear areas was lowest in benign hepatocytes (9.3), intermediate in low grade HCC (25.0) and highest in high grade HCC (25.6). These findings indicate that computer-linked nuclear measurement may be a useful adjunct in differentiating benign from malignant hepatocytes, in particular in small biopsies of well-differentiated tumours, and in predicting survival after surgical resection and transplant.

Matched MeSH terms: Cell Nucleus/ultrastructure*
Papillary cystic type of acinic cell carcinoma of parotid: fine needle aspiration cytological features of a high grade variant with oncocytic metaplasia

Jayaram G, Othman MA, Kumar M, Krishnan G

Malays J Pathol, 2002 Dec;24(2):107-12.
PMID: 12887170

A 60-year-old female developed a right parotid swelling six months after surgery for intra-oral squamous cell carcinoma. Fine needle aspiration (FNA) cytological smears showed dissociated large and small pleomorphic tumour cells with abundant mitoses and oncocytic features. A cytological diagnosis of parotid acinic cell carcinoma (ACC) was made. Histological study of the subtotal parotidectomy specimen showed a papillary cystic variety of acinic cell carcinoma (ACC-PCV). FNA cytological features in this case of ACC-PCV differs from the two previously reported cases in that it showed prominent oncocytic and high grade features and absence of papillary pattern in the cytological smears. ACC-PCV is an uncommon tumour and knowledge of its varied FNA cytological features is important for the diagnosis of this neoplasm.

Matched MeSH terms: Cell Nucleus/pathology
Follicular adenoma with squamous metaplasia and cystic change: report of a case with fine needle aspiration cytological and histological features

Jayaram G, Jayalakshmi P

Malays J Pathol, 1999 Dec;21(2):101-4.
PMID: 11068414

Squamous metaplasia (SM) of thyroid follicular epithelium is known to occur in a variety of non-neoplastic lesions as well in thyroid neoplasms, notably papillary carcinoma (PC). In follicular thyroid tumors, on the other hand, SM is very rare. This case describes cytological and pathological findings in a follicular adenoma (FA) that presented as a cystic lesion with extensive SM. The fine needle aspiration (FNA) cytology sample in this case yielded only necrotic material from the cystic area and squamous cells, which being mostly of immature type, were not recognised as squamous in the cytological smears. The needle missed the solid (neoplastic) component of the lesion and on the whole the cytological picture was considered to be equivocal. FA can now be added to the spectrum of thyroid lesions that can show SM. Awareness of this will enable cytopathologists to consider non-papillary lesions in the differential diagnosis of thyroid nodules that yield squamous cells.

Matched MeSH terms: Cell Nucleus/pathology
Adrenal cytomegaly associated with diaphragmatic hernia: report of a case

Ong BB, Wong KT

Malays J Pathol, 1996 Dec;18(2):121-3.
PMID: 10879233

A rare case of a 22-week-old foetus with unilateral adrenal cytomegaly and left diaphragmatic hernia is reported. Typical cytomegalic cells were found focally in the left adrenal but the right adrenal was normal. There was no stigmata of the Beckwith-Wiedermann syndrome. The association of adrenal cytomegaly with various congenital malformations, the significance and possible pathogenesis of this condition is discussed.

Matched MeSH terms: Cell Nucleus/pathology
Nuclear morphometry and texture analysis on cytological smears of thyroid neoplasms: a study of 50 cases

Deka L, Gupta S, Gupta R, Gupta K, Kaur CJ, Singh S S

Malays J Pathol, 2017 Apr;39(1):33-37.
PMID: 28413203

BACKGROUND: Fine needle aspiration cytology (FNAC) is a reliable and reproducible diagnostic technique for thyroid lesions with certain limitations. Computed morphometric methods have been introduced with a view to improve the diagnostic yield of thyroid aspirates. However, a review of the existing literature revealed conflicting reports regarding morphometric parameters in thyroid neoplasms.
MATERIALS AND METHODS: This study included 50 cases of thyroid lesions (20 cases of colloid goitre, 15 of follicular adenoma, 5 of follicular carcinoma and 10 papillary carcinomas). Digital images of cytologic smears of these cases were captured using a dedicated photomicrography system and nuclear profiles traced manually. With self-designed image analysis software, nuclear morphometric measurements, including texture analysis, were performed. Discriminant analysis was performed including the morphometric parameters and percentage of correctly classified nuclei noted.
RESULTS: Nuclear morphometry parameters showed that papillary thyroid carcinoma had the highest perimeter, area, radius and elongation factor compared to other thyroid lesions. Discriminant analysis revealed that altogether 77.9% of cells could be correctly classified to their lesion category based on the nuclear morphometric and textural parameters. Of the neoplastic cases, 84.5% of cells of follicular neoplasms and 72.5% of papillary carcinoma were classified to the respective category.
CONCLUSION: Nuclear morphometry, including texture analysis, can assist in the cytologic diagnosis of thyroid lesions, considering the high degree of accuracy of classification. Further studies and methodological refinements can achieve higher accuracy.

Matched MeSH terms: Cell Nucleus/pathology
New wild Tetrahymena from Southeast Asia, China, and North America, including T. malaccensis, T. asiatica, T. nanneyi, T. caudata, and T. silvana n. spp

Simon EM, Meyer EB, Preparata RM

J. Protozool., 1985 Feb;32(1):183-9.
PMID: 3989748

Tetrahymena of the T. pyriformis complex collected from varied habitats in Malaysia, Thailand, and The People's Republic of China include strains of the micronucleate species T. americanis and T. canadensis and the amicronucleate T. pyriformis and T. elliotti. Two new breeding species are described-T. malaccensis from Malaysia and T. asiatica from China and Thailand. Two wild selfers from China and some of the amicronucleate strains from all three countries fall into isozymic groups similar to named micronucleate and amicronucleate species. The T. patula complex is represented by two groups of clones from Malaysia that fit the morphological description of T. vorax. They, however, have radically different isozymic electrophoretic patterns and both groups differ from those of previously described T. vorax. As their molecules indicate relationships to other "T. vorax" strains as distant as that between T. vorax and T. leucophrys, they are considered to be new species, T. caudata and T. silvana. A third new breeding species, T. nanneyi, was identified among strains previously collected in North America. Viable immature progeny were obtained from the new strains of the five breeding species. Maximum temperature tolerances were determined for the new strains of four of the breeding species.

Matched MeSH terms: Cell Nucleus/ultrastructure
Flavopiridol Inhibits TGF-β-Stimulated Biglycan Synthesis by Blocking Linker Region Phosphorylation and Nuclear Translocation of Smad2

Rostam MA, Shajimoon A, Kamato D, Mitra P, Piva TJ, Getachew R, et al.

J. Pharmacol. Exp. Ther., 2018 04;365(1):156-164.
PMID: 29438988 DOI: 10.1124/jpet.117.244483

Transforming growth factor-β (TGF-β) is a pleiotropic growth factor implicated in the development of atherosclerosis for its role in mediating glycosaminoglycan (GAG) chain hyperelongation on the proteoglycan biglycan, a phenomenon that increases the binding of atherogenic lipoproteins in the vessel wall. Phosphorylation of the transcription factor Smad has emerged as a critical step in the signaling pathways that control the synthesis of biglycan, both the core protein and the GAG chains. We have used flavopiridol, a well-known cyclin-dependent kinase inhibitor, to study the role of linker region phosphorylation in the TGF-β-stimulated synthesis of biglycan. We used radiosulfate incorporation and SDS-PAGE to assess proteoglycan synthesis, real-time polymerase chain reaction to assess gene expression, and chromatin immunoprecipitation to assess the binding of Smads to the promoter region of GAG Synthesizing genes. Flavopiridol blocked TGF-β-stimulated synthesis of mRNA for the GAG synthesizing enzymes, and chondroitin 4-sulfotransferase (C4ST-1), chondroitin sulfate synthase-1 (ChSy-1) and TGF-β-mediated proteoglycans synthesis as well as GAG hyperelongation. Flavopiridol blocked TGF-β-stimulated Smad2 phosphorylation at both the serine triplet and the isolated threonine residue in the linker region. The binding of Smad to the promoter region of the C4ST-1 and ChSy-1 genes was stimulated by TGF-β, and this response was blocked by flavopiridol, demonstrating that linker region phosphorylated Smad can pass to the nucleus and positively regulate transcription. These results demonstrate the validity of the kinases, which phosphorylate the Smad linker region as potential therapeutic target(s) for the development of an agent to prevent atherosclerosis.

Matched MeSH terms: Cell Nucleus/drug effects*; Cell Nucleus/metabolism*; Active Transport, Cell Nucleus/drug effects
Plasmodium hylobati: a malaria parasite of the gibbon

Collins WE, Contacos PG, Garnham PC, Warren M, Skinner JC

J Parasitol, 1972 Feb;58(1):123-8.
PMID: 4335047
Matched MeSH terms: Cell Nucleus
Bcp1 Is the Nuclear Chaperone of Rpl23 in Saccharomyces cerevisiae

Ting YH, Lu TJ, Johnson AW, Shie JT, Chen BR, Kumar S S, et al.

J Biol Chem, 2017 Jan 13;292(2):585-596.
PMID: 27913624 DOI: 10.1074/jbc.M116.747634

Eukaryotic ribosomes are composed of rRNAs and ribosomal proteins. Ribosomal proteins are translated in the cytoplasm and imported into the nucleus for assembly with the rRNAs. It has been shown that chaperones or karyopherins responsible for import can maintain the stability of ribosomal proteins by neutralizing unfavorable positive charges and thus facilitate their transports. Among 79 ribosomal proteins in yeast, only a few are identified with specific chaperones. Besides the classic role in maintaining protein stability, chaperones have additional roles in transport, chaperoning the assembly site, and dissociation of ribosomal proteins from karyopherins. Bcp1 has been shown to be necessary for the export of Mss4, a phosphatidylinositol 4-phosphate 5-kinase, and required for ribosome biogenesis. However, its specific function in ribosome biogenesis has not been described. Here, we show that Bcp1 dissociates Rpl23 from the karyopherins and associates with Rpl23 afterward. Loss of Bcp1 causes instability of Rpl23 and deficiency of 60S subunits. In summary, Bcp1 is a novel 60S biogenesis factor via chaperoning Rpl23 in the nucleus.

Matched MeSH terms: Cell Nucleus/genetics; Cell Nucleus/metabolism*

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