Chromosome Segregation Is Biased by Kinetochore Size

Chromosome missegregation during mitosis or meiosis is a hallmark of cancer and the main cause of prenatal death in humans. The gain or loss of specific chromosomes is thought to be random, with cell viability being essentially determined by selection. Several established pathways including centrosome amplification, sister-chromatid cohesion defects, or a compromised spindle assembly checkpoint can lead to chromosome missegregation. However, how specific intrinsic features of the kinetochore—the critical chromosomal interface with spindle microtubules—impact chromosome segregation remains poorly understood. Here we used the unique cytological attributes of female Indian muntjac, the mammal with the lowest known chromosome number (2n = 6), to characterize and track individual chromosomes with distinct kinetochore size throughout mitosis. We show that centromere and kinetochore functional layers scale proportionally with centromere size. Measurement of intra-kinetochore distances, serial-section electron microscopy, and RNAi against key kinetochore proteins confirmed a standard structural and functional organization of the Indian muntjac kinetochores and revealed that microtubule binding capacity scales with kinetochore size. Surprisingly, we found that chromosome segregation in this species is not random. Chromosomes with larger kinetochores bi-oriented more efficiently and showed a 2-fold bias to congress to the equator in a motor-independent manner. Despite robust correction mechanisms during unperturbed mitosis, chromosomes with larger kinetochores were also strongly biased to establish erroneous merotelic attachments and missegregate during anaphase. This bias was impervious to the experimental attenuation of polar ejection forces on chromosome arms by RNAi against the chromokinesin Kif4a. Thus, kinetochore size is an important determinant of chromosome segregation fidelity

Usulan Perancangan Tata Letak Penyimpanan Komponen Berdasarkan Kriteria Komoditi Komponen (Studi Kasus Di PT Triangle Motorindo Semarang)

Kurang lancarnya suplai komponen ke bagian produksi dapat menyebabkan menurunnya produktivitas dari bagian produksi. Untuk itu perlu dilakukan perancangan tata letak penyimpanan komponen yang lebih baik sehingga dapat mengurangi waktu mencari komponen, mengurangi jarak perjalanan operator dalam pengambilan dan pengiriman komponen, dan meningkatkan pemanfaatan kapasitas gudang. PT. Triangle Motorindo merupakan Perusahaan yang bergerak dalam USAha perakitan sepeda motor. Secara garis besar, Perusahaan dapat dibagi menjadi dua bagian yaitu bagian gudang dan bagian produksi dimana bagian gudang menjadi pendukung dari bagian produksi. Bagian gudang terdiri dari gudang sortir, gudang rangka, dan gudang mesin. Dalam mengalokasikan komponen yang disimpan, Perusahaan menggunakan kebijakan penyimpanan random/acak yang berakibat tidak standarnya waktu yang dibutuhkan untuk mencari komponen dan bertambahnya waktu perjalanan operator dalam menyuplai komponen. Penelitian ini memberikan alternatif perancangan tata letak penyimpanan komponen yang dilakukan dengan memperhatikan komponen itu sendiri, dalam hal ini disebut faktor komoditi yang terdiri atas popularity, similarity, characteristic, dan size. Selain berdasarkan komponen yang disimpan, perancangan tata letak penyimpanan ini juga memperhatikan kondisi ruangan yang tersedia. Hasil pengolahan data dan analisis yang dilakukan menunjukkan bahwa tata letak penyimpanan komponen yang terbaik adalah berdasarkan kriteria process similarity. Tata letak penyimpanan komponen berdasarkan kriteria process similarity ini merupakan tata letak penyimpanan komponen terbaik

Proanthocyanidins, from Ribes nigrum leaves, reduce endothelial adhesion molecules ICAM-1 and VCAM-1

BACKGROUND: The effects of proanthocyanidins (PACs), isolated from blackcurrant (Ribes nigrum L.) leaves, on neutrophil accumulation during inflammatory processes were investigated in vivo and in vitro. METHODS: In vivo studies were performed using carrageenin-induced pleurisy in rats pre-treated with PACs. Exudate volume and PMNs accumulation were measured. Leukocyte cell adhesion molecules (LFA-1, Mac-1 and VLA-4) mobilization in circulating granulocytes were analysed by flow cytometry and endothelial cell adhesion molecules (ICAM-1 and VCAM-1) were detected by immunohistochemistry on lung sections. In vitro studies were conducted on endothelial LT2 cells, stimulated with TNF-α, to evaluate ICAM-1, IL-8 and VEGF mRNA expression upon PACs treatment. Data sets were examined by one-way analysis of variance (ANOVA) followed by a Scheffe post-hoc test. RESULTS: Pretreatment of the animals with PACs (10, 30 and 60 mg/kg) inhibited dose-dependently carrageenin-induced pleurisy in rats by reducing pleural exudate formation and PMNs infliltration. Leukocyte cell adhesion molecules mobilization was not down-regulated on granulocytes by PACs. Immunohistochemistry on lung sections showed a decreased production of endothelial cell adhesion molecules. In vitro experiments demonstrated that PACs were able to significantly inhibit ICAM-1 but not IL-8 and VEGF(165 )mRNA expression. Moreover, VEGF(121 )mRNA expression was dose-dependently enhanced. CONCLUSION: This study provides evidence to support the anti-inflammatory activity of proanthocyanidins is related to an inhibition of leukocyte infiltration which can be explained at least in part by a down-regulation of endothelial adhesion molecules, ICAM-1 and VCAM-1 and that these compounds are capable of modulating TNF-α-induced VEGF transcription