Sistem Informasi SMPK Santo Yusuf di Madiun

SMPK Santo yusuf nerupakan salah satu lembaga pendidikan dasar yang berada di kota Hadiun. Sekarang ini SMPK Santo Yusuf mempunyai kurang lebih 30 orang guru (guru yayasan guru DPK dan guru honor dan 5 orang pegawai. Dengan jumlah guru dan pegawai sebanyak itu, SMPK Santo Yusuf dapat.melayani kurang lebih 460 orang siswa. Dalam nangka meningkatkan kualitas pelayanan, maka perlu dirancang dan dibuat suatu program aplikasi sistem informasi. Karena SMPK Santo yusuf terbagi atas bagian- bagian yang terpisah, maka program aplikasi sistem informasi tersebut perlu sedikit dimodlfikasi menjadi program apl ikasi sistem i nformasi yang terintegrasi yang ,memung- kinkan komunikasi antar bagian, Sistem informasi SMPK St, yusuf yang dirancang dan diimplementasikan dalam bentuk program apl ikasi, terdtri atas empat bagian utama, yaitu bagian kesiswaan, bagian kepegawaian, bagian guru dan bagian keuangan. Bagian kesiswaan meliputi pendataan siswa, kurikulum, pendataan kelas, pendataan jenis evaluasi, penilaian, absen6i, mutasi masuk, mutasi keluar, pendataan siswa keluar, kenaikan kelas, kelulusan, perumusan nilai raport, perumusan nilai STTB, mengolah nilai raport, mengolah nilai STTB dan laporan-laporan. Bagian kepegawaian meliputi pendataan pegawai, kepangkatan, absensi, pegawai keluar, tanggungan, pendataan kondit, pendataan pangkat dan jabatan suatu golongan dan laporan-laporan. Bagian guru meliputl pendataan guru, kepangkatan guru yayasan, kepangkatan guru DpK, absensi guru, presensi gunu honor, mutasi nasuk dan mutasi keluar guru DpK, pendataan guru keluar, pendataan jam kosong gupu, pendataan guru mengajar, pendataan kondit, pendataan angka kredit, pengaturan jadwal mengajar serta laporan-laporan Bagian keuangan mel iputi penerimaan uang sekolah, pendataan gaji pokok berdasarkan golongan, pendataan tunjangan lain-lain, penggajian guru dan pegawai, pendataan account yayasan, pendataan account SMPK Santo yusuf, pendataan penerimaan dan pengel uaran kas harian, pendataan rencana anggaran dan laporan-laporan. Sistem operasi yang dipakal untuk program aplikasi tugas akhir adalah novell netware. perangkat lunak yang dipakai untuk membuat program aplikasi tugas akhir adalah paket perangkat lunak FOXPRO untuk DOS versi 2.6 dan paket perangkat lunak FOXGRAPH versi 1.0. Program aplikasi sistem informasi ini sudah diujicobakan di SMPK Santo yusuf dan berhasil dengan baik (dalam arti sekarang ini sudah dalam keadaan ON RU

The nuclear receptor LXRα controls the functional specialization of splenic macrophages.

Macrophages are professional phagocytic cells that orchestrate innate immune responses and have considerable phenotypic diversity at different anatomical locations. However, the mechanisms that control the heterogeneity of tissue macrophages are not well characterized. Here we found that the nuclear receptor LXRα was essential for the differentiation of macrophages in the marginal zone (MZ) of the spleen. LXR-deficient mice were defective in the generation of MZ and metallophilic macrophages, which resulted in abnormal responses to blood-borne antigens. Myeloid-specific expression of LXRα or adoptive transfer of wild-type monocytes restored the MZ microenvironment in LXRα-deficient mice. Our results demonstrate that signaling via LXRα in myeloid cells is crucial for the generation of splenic MZ macrophages and identify an unprecedented role for a nuclear receptor in the generation of specialized macrophage subsets

Domain III function of Mu transposase analysed by directed placement of subunits within the transpososome

Assembly of the functional tetrameric form of Mu transposase (MuA protein) at the two att ends of Mu depends on interaction of MuA with multiple att and enhancer sites on supercoiled DNA, and is stimulated by MuB protein. The N-terminal domain I of MuA harbours distinct regions for interaction with the att ends and enhancer; the C-terminal domain III contains separate regions essential for tetramer assembly and interaction with MuB protein (IIIα and IIIβ, respectively). Although the central domain II (the 'DDE' domain) of MuA harbours the known catalytic DDE residues, a 26 amino acid peptide within IIIα also has a non-specific DNA binding and nuclease activity which has been implicated in catalysis. One model proposes that active sites for Mu transposition are assembled by sharing structural/catalytic residues between domains II and III present on separate MuA monomers within the MuA tetramer. We have used substrates with altered att sites and mixtures of MuA proteins with either wild-type or altered att DNA binding specificities, to create tetrameric arrangements wherein specific MuA subunits are nonfunctional in II, IIIα or IIIβ domains. From the ability of these oriented tetramers to carry out DNA cleavage and strand transfer we conclude that domain IIIα or IIIβ function is not unique to a specific subunit within the tetramer, indicative of a structural rather than a catalytic function for domain III in Mu transposition

Громадянське виховання підлітків у контексті педагогічної спадщини А. Б. Рєзніка

У статті висвітлено основні положення педагогічної спадщини видатного педагога Кіровоградщини А. Б. Рєзніка в царині громадянського виховання. Доведено, що теоретичні положення, педагогічні висновки, методичні поради, які він розробив, набувають особливої актуальності у наш час і їх застосування у виховній практиці, сприятиме вибору активної життєвої позиції та свідомому формуванню громадянського світогляду молоді

LXR Nuclear receptors are transcriptional regulators of dendritic cell chemotaxis

The liver X receptors (LXRs) are ligand-activated nuclear receptors with established roles in the maintenance of lipid homeostasis in multiple tissues. LXRs exert additional biological functions as negative regulators of inflammation, particularly in macrophages. However, the transcriptional responses controlled by LXRs in other myeloid cells, such as dendritic cells (DCs), are still poorly understood. Here we used gain- and loss-of-function models to characterize the impact of LXR deficiency on DC activation programs. Our results identified an LXR-dependent pathway that is important for DC chemotaxis. LXR-deficient mature DCs are defective in stimulus-induced migration in vitro and in vivo. Mechanistically, we show that LXRs facilitate DC chemotactic signaling by regulating the expression of CD38, an ectoenzyme important for leukocyte trafficking. Pharmacological or genetic inactivation of CD38 activity abolished the LXR-dependent induction of DC chemotaxis. Using the low-density lipoprotein receptor-deficient (LDLR−/−) LDLR−/− mouse model of atherosclerosis, we also demonstrated that hematopoietic CD38 expression is important for the accumulation of lipid-laden myeloid cells in lesions, suggesting that CD38 is a key factor in leukocyte migration during atherogenesis. Collectively, our results demonstrate that LXRs are required for the efficient emigration of DCs in response to chemotactic signals during inflammation

Short-term prognosis of polypharmacy in elderly patients treated in emergency departments: results from the EDEN project

Background: Polypharmacy is a growing phenomenon among elderly individuals. However, there is little information about the frequency of polypharmacy among the elderly population treated in emergency departments (EDs) and its prognostic effect. This study aims to determine the prevalence and short-term prognostic effect of polypharmacy in elderly patients treated in EDs. Methods: A retrospective analysis of the Emergency Department Elderly in Needs (EDEN) project's cohort was performed. This registry included all elderly patients who attended 52 Spanish EDs for any condition. Mild and severe polypharmacy was defined as the use of 5-9 drugs and >10 drugs, respectively. The assessed outcomes were ED revisits, hospital readmissions, and mortality 30 days after discharge. Crude and adjusted logistic regression analyses, including the patient's comorbidities, were performed. Results: A total of 25,557 patients were evaluated [mean age: 78 (IQR: 71-84) years]; 10,534 (41.2%) and 5678 (22.2%) patients presented with mild and severe polypharmacy, respectively. In the adjusted analysis, mild polypharmacy and severe polypharmacy were associated with an increase in ED revisits [odds ratio (OR) 1.13 (95% confidence interval (CI): 1.04-1.23) and 1.38 (95% CI: 1.24-1.51)] and hospital readmissions [OR 1.18 (95% CI: 1.04-1.35) and 1.36 (95% CI: 1.16-1.60)], respectively, compared to non-polypharmacy. Mild and severe polypharmacy were not associated with increased 30-day mortality [OR 1.05 (95% CI: 0.89-2.26) and OR 0.89 (95% CI: 0.72-1.12)], respectively. Conclusion: Polypharmacy was common among the elderly treated in EDs and associated with increased risks of ED revisits and hospital readmissions 10 drugs. In these patients comorbidities were associated with an increase in the number of drugs. In the patients with severe polypharmacy (>10 drugs), diuretics were the most frequently drugs prescribed, followed by antihypertensives and statins. The results obtained indicate that polypharmacy is a frequent phenomenon among the elderly population treated in Emergency departments, being antihypertensives the most frequently used drugs in this population. Those patients who takes >10 drugs have a higher risk of new visits to the emergency room and hospital readmissions in short term period

The impact of zeolite pore structure on the catalytic behavior of CuZnAl/zeolite hybrid catalysts for the direct DME synthesis

[EN] In this work, the influence of the pore structure of 10-ring zeolites used as the methanol dehydration func-tion in CuZnAl(CZA)/zeolite hybrid catalysts was studied for the direct dimethyl ether (DME) synthesis. Tothis purpose, six different 10-ring H-zeolites (ZSM-5, FER, IM-5, TNU-9, MCM-22, ITQ-2) with alike bulkSi/Al ratios (in the 9 14 range) were employed. Additionally, the effect of crystallite size (for ZSM-5) andselective surface dealumination by treatment with oxalic acid (for MCM-22) was also investigated. Whilethe initial activity of the zeolites for methanol dehydration was driven by the concentration of strongBrønsted acid sites, the extent of decay was dictated by the pore structure, which determined the amountand nature of the formed carbon species. When evaluated for direct DME synthesis under methanolsynthesis-controlled conditions, all CZA/zeolite hybrid catalysts (prepared by grinding, CZA:zeolite massratio of 2:1) experienced a decline of CO conversion (and DME yield) with time-on-stream (TOS) due toa gradual loss of the methanol synthesis activity of the Cu-based component. Interestingly, the stabilitywith TOS was the lowest for the hybrid catalysts comprising zeolites with large external surface areas(Sext) such as ITQ-2 and MCM-22. Moreover, for zeolites with similar Sext, the deactivation extent of thehybrid catalysts increased with the concentration of surface Al species (from XPS) in the zeolite. Thus,the delaminated ITQ-2 zeolite (Si/Alsurf= 10.6, Sext= 324 m2/g) produced the less stable hybrid while thatcomprising zeolite TNU-9 (Si/Alsurf= 17.9, Sext= 12 m2/g) displayed the highest stability during the syngas-to-DME experiments. These results suggest that the deterioration of the methanol synthesis activity ofthe CZA catalyst in the hybrid catalysts prepared by grinding is produced by detrimental interactionsbetween zeolitic Al species and Cu sites at the surface-contact between zeolite and CZA particleFinancial support by the Comision Interministerial de Ciencia y Tecnologia (CICYT) of Spain through the Project CTQ2010-17988/PPQ is gratefully acknowledged. A. Garcia-Trenco thanks the Ministerio de Economia y Competitividad (former Ministerio de Ciencia e Innovacion) of Spain for a predoctoral (FPI) scholarship.García Trenco, A.; Valencia Valencia, S.; Martinez Feliu, A. (2013). The impact of zeolite pore structure on the catalytic behavior of CuZnAl/zeolite hybrid catalysts for the direct DME synthesis. Applied Catalysis A General. 468:102-111. doi:10.1016/j.apcata.2013.08.038S10211146

Silicon particles as trojan horses for potential cancer therapy

[EN] Background: Porous silicon particles (PSiPs) have been used extensively as drug delivery systems, loaded with chemical species for disease treatment. It is well known from silicon producers that silicon is characterized by a low reduction potential, which in the case of PSiPs promotes explosive oxidation reactions with energy yields exceeding that of trinitrotoluene (TNT). The functionalization of the silica layer with sugars prevents its solubilization, while further functionalization with an appropriate antibody enables increased bioaccumulation inside selected cells. Results: We present here an immunotherapy approach for potential cancer treatment. Our platform comprises the use of engineered silicon particles conjugated with a selective antibody. The conceptual advantage of our system is that after reaction, the particles are degraded into soluble and excretable biocomponents. Conclusions: In our study, we demonstrate in particular, specific targeting and destruction of cancer cells in vitro. The fact that the LD50 value of PSiPs-HER-2 for tumor cells was 15-fold lower than the LD50 value for control cells demonstrates very high in vitro specificity. This is the first important step on a long road towards the design and development of novel chemotherapeutic agents against cancer in general, and breast cancer in particular.The authors acknowledge financial support from the following projects FIS2009-07812, MAT2012-35040, PROMETEO/2010/043, CTQ2011-23167, CrossSERS, FP7 MC-IEF 329131, and HSFP (project RGP0052/2012) and Medcom Tech SA. Xiang Yu acknowledges support by the Chinese government (CSC, Nr. 2010691036).Fenollosa Esteve, R.; Garcia-Rico, E.; Alvarez, S.; Alvarez, R.; Yu, X.; Rodriguez, I.; Carregal-Romero, S.... (2014). Silicon particles as trojan horses for potential cancer therapy. Journal of Nanobiotechnology. 12:1-10. https://doi.org/10.1186/s12951-014-0035-7S11012Prasad PN: Introduction to Nanomedicine and Nanobioengineering. Wiley, New York, 2012.Randall CL, Leong TG, Bassik N, Gracias DH: 3D lithographically fabricated nanoliter containers for drug delivery. Adv Drug Del Rev. 2007, 59: 1547-1561. 10.1016/j.addr.2007.08.024.Reibetanz U, Chen MHA, Mutukumaraswamy S, Liaw ZY, Oh BHL, Venkatraman S, Donath E, Neu BR: Colloidal DNA carriers for direct localization in cell compartments by pH sensoring. Biogeosciences. 2010, 11: 1779-1784.Tasciotti E, Liu X, Bhavane R, Plant K, Leonard AD, Price BK, Cheng MM-C, Decuzzi P, Tour JM, Robertson F, Ferrari M: Mesoporous silicon particles as a multistage delivery system for imaging and therapeutic applications. Nat Nano. 2008, 3: 151-157. 10.1038/nnano.2008.34.Park J-H, Gu L, von Maltzahn G, Ruoslahti E, Bhatia SN, Sailor MJ: Biodegradable luminescent porous silicon nanoparticles for in vivo applications. Nat Mater. 2009, 8: 331-336. 10.1038/nmat2398.Hong C, Lee J, Son M, Hong SS, Lee C: In-vivo cancer cell destruction using porous silicon nanoparticles. Anti-Cancer Drugs. 2011, 22: 971-977. 910.1097/CAD.1090b1013e32834b32859cCanham LT: Device Comprising Resorbable Silicon for Boron Capture Neutron Therapy. UK Patent Nr. 0302283.7. Book Device Comprising Resorbable Silicon for Boron Capture Neutron Therapy. UK Patent Nr. 0302283.7 (Editor ed.^eds.). 2003, UK Patent Nr. 0302283.7, CityXiao L, Gu L, Howell SB, Sailor MJ: Porous silicon nanoparticle photosensitizers for singlet oxygen and their phototoxicity against cancer cells. ACS Nano. 2011, 5: 3651-3659. 10.1021/nn1035262.Gil PR, Parak WJ: Composite nanoparticles take Aim at cancer. ACS Nano. 2008, 2: 2200-2205. 10.1021/nn800716j.Gomella LG: Is interstitial hyperthermia a safe and efficacious adjunct to radiotherapy for localized prostate cancer?. Nat Clin Pract Urol. 2004, 1: 72-73. 10.1038/ncpuro0041.Maier-Hauff K, Ulrich F, Nestler D, Niehoff H, Wust P, Thiesen B, Orawa H, Budach V, Jordan A: Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme. J Neuro-Oncol. 2011, 103: 317-324. 10.1007/s11060-010-0389-0.Lal S, Clare SE, Halas NJ: Nanoshell-enabled photothermal cancer therapy: Impending clinical impact. Acc Chem Res. 2008, 41: 1842-1851. 10.1021/ar800150g.Lee C, Kim H, Hong C, Kim M, Hong SS, Lee DH, Lee WI: Porous silicon as an agent for cancer thermotherapy based on near-infrared light irradiation. J Mater Chem. 2008, 18: 4790-4795. 10.1039/b808500e.Osminkina LA, Gongalsky MB, Motuzuk AV, Timoshenko VY, Kudryavtsev AA: Silicon nanocrystals as photo- and sono-sensitizers for biomedical applications. Appl Phys B. 2011, 105: 665-668. 10.1007/s00340-011-4562-8.Jain PK, Huang X, El-Sayed IH, El-Sayed MA: Noble metals on the nanoscale: optical and photothermal properties and some applications in imaging, sensing, biology, and medicine. Acc Chem Res. 2008, 41: 1578-1586. 10.1021/ar7002804.Serda RE, Godin B, Blanco E, Chiappini C, Ferrari M: Multi-stage delivery nano-particle systems for therapeutic applications. Biochim Biophys Acta. 1810, 2011: 317-329.Xu R, Huang Y, Mai J, Zhang G, Guo X, Xia X, Koay EJ, Qin G, Erm DR, Li Q, Liu X, Ferrari M, Shen H: Multistage vectored siRNA targeting ataxia-telangiectasia mutated for breast cancer therapy. Small. 2013, 9: 1799-1808. 10.1002/smll.201201510.Park JS, Kinsella JM, Jandial DD, Howell SB, Sailor MJ: Cisplatin-loaded porous Si microparticles capped by electroless deposition of platinum. Small. 2011, 7: 2061-2069. 10.1002/smll.201100438.Xue M, Zhong X, Shaposhnik Z, Qu Y, Tamanoi F, Duan X, Zink JI: pH-operated mechanized porous silicon nanoparticles. J Am Chem Soc. 2011, 133: 8798-8801. 10.1021/ja201252e.Canham LT: Bioactive silicon structure fabrication through nanoetching techniques. Adv Mater. 1995, 7: 1033-1037. 10.1002/adma.19950071215.Popplewell JF, King SJ, Day JP, Ackrill P, Fifield LK, Cresswell RG, Di Tada ML, Liu K: Kinetics of uptake and elimination of silicic acid by a human subject: a novel application of 32Si and accelerator mass spectrometry. J Inorganic Biochem. 1998, 69: 177-180. 10.1016/S0162-0134(97)10016-2.Shabir Q, Pokale A, Loni A, Johnson DR, Canham LT, Fenollosa R, Tymczenko M, Rodr guez I, Meseguer F, Cros A, Cantarero A: Medically biodegradable hydrogenated amorphous silicon microspheres. Silicon. 2011, 3: 173-176. 10.1007/s12633-011-9097-4.Chen Y, Wan Y, Wang Y, Zhang H, Jiao Z: Anticancer efficacy enhancement and attenuation of side effects of doxorubicin with titanium dioxide nanoparticles. Int J Nanomed. 2011, 6: 2321-2326.Mackowiak SA, Schmidt A, Weiss V, Argyo C, von Schirnding C, Bein T, Bräuchle C: Targeted drug delivery in cancer cells with Red-light photoactivated mesoporous silica nanoparticles. Nano Lett. 2013, 13: 2576-2583. 10.1021/nl400681f.Li Z, Barnes JC, Bosoy A, Stoddart JF, Zink JI: Mesoporous silica nanoparticles in biomedical applications. Chem Soc Rev. 2012, 41: 2590-2605. 10.1039/c1cs15246g.O Mara WC, Herring B, Hunt P: Handbook of Semiconductor Silicon Technology. Noyes Publication, New Jersey, 1990.Mikulec FV, Kirtland JD, Sailor MJ: Explosive nanocrystalline porous silicon and its Use in atomic emission spectroscopy. Adv Mater. 2002, 14: 38-41. 10.1002/1521-4095(20020104)14:13.0.CO;2-Z.Clement D, Diener J, Gross E, Kunzner N, Timoshenko VY, Kovalev D: Highly explosive nanosilicon-based composite materials. Phys Stat Sol A. 2005, 202: 1357-1359. 10.1002/pssa.200461102.Canham LT: Silicon quantum wire array fabrication by electrochemical and chemical dissolution of wafers. Appl Phys Lett. 1990, 57: 1046-1049. 10.1063/1.103561.Canham LT: Properties of Porous Silicon. INSPEC, United Kindom, 1997.Heinrich JL, Curtis CL, Credo GM, Sailor MJ, Kavanagh KL: Luminescent colloidal silicon suspensions from porous silicon. Science. 1992, 255: 66-68. 10.1126/science.255.5040.66.Littau KA, Szajowski PJ, Muller AJ, Kortan AR, Brus LE: A luminescent silicon nanocrystal colloid via a high-temperature aerosol reaction. J Phys Chem. 1993, 97: 1224-1230. 10.1021/j100108a019.Menz WJ, Shekar S, Brownbridge GPE, Mosbach S, Kōrmer R, Peukert W, Kraft M: Synthesis of silicon nanoparticles with a narrow size distribution: a theoretical study. J Aerosol Sci. 2012, 44: 46-61. 10.1016/j.jaerosci.2011.10.005.Swihart MT, Girshick SL: Thermochemistry and kinetics of silicon hydride cluster formation during thermal decomposition of silane. J Phys Chem B. 1998, 103: 64-76. 10.1021/jp983358e.Fenollosa R, Ramiro-Manzano F, Tymczenko M, Meseguer F: Porous silicon microspheres: synthesis, characterization and application to photonic microcavities. J Mater Chem. 2010, 20: 5210-5214. 10.1039/c0jm00079e.Ramiro-Manzano F, Fenollosa R, Xifré-Pérez E, Garín M, Meseguer F: Porous silicon microcavities based photonic barcodes. Adv Mater. 2011, 23: 3022-3025. 10.1002/adma.201100986.Kastl L, Sasse D, Wulf V, Hartmann R, Mircheski J, Ranke C, Carregal-Romero S, Martínez-López JA, Fernández-Chacón R, Parak WJ, Elsasser HP, Rivera-Gil P: Multiple internalization pathways of polyelectrolyte multilayer capsules into mammalian cells. ACS Nano. 2013, 7: 6605-6618. 10.1021/nn306032k.Schweiger C, Hartmann R, Zhang F, Parak W, Kissel T, Rivera_Gil P: Quantification of the internalization patterns of superparamagnetic iron oxide nanoparticles with opposite charge. J Nanobiotech. 2012, 10: 28-10.1186/1477-3155-10-28.Sanles-Sobrido M, Exner W, Rodr guez-Lorenzo L, Rodríguez-Gonzílez B, Correa-Duarte MA, Álvarez-Puebla RA, Liz-Marzán LM: Design of SERS-encoded, submicron, hollow particles through confined growth of encapsulated metal nanoparticles. J Am Chem Soc. 2009, 131: 2699-2705. 10.1021/ja8088444.Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J: Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011, 365: 1273-1283. 10.1056/NEJMoa0910383.Agus DB, Gordon MS, Taylor C, Natale RB, Karlan B, Mendelson DS, Press MF, Allison DE, Sliwkowski MX, Lieberman G, Kelsey SM, Fyfe G: Phase I clinical study of pertuzumab, a novel HER dimerization inhibitor, in patients with advanced cancer. J Clin Oncol. 2005, 23: 2534-2543. 10.1200/JCO.2005.03.184.Colombo M, Mazzucchelli S, Montenegro JM, Galbiati E, Corsi F, Parak WJ, Prosperi D: Protein oriented ligation on nanoparticles exploiting O6-alkylguanine-DNA transferase (SNAP) genetically encoded fusion. Small. 2012, 8: 1492-1497. 10.1002/smll.201102284.Franklin MC, Carey KD, Vajdos FF, Leahy DJ, de Vos AM, Sliwkowski MX: Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell. 2004, 5: 317-328. 10.1016/S1535-6108(04)00083-2.Paris L, Cecchetti S, Spadaro F, Abalsamo L, Lugini L, Pisanu ME, Lorio E, Natali PG, Ramoni C, Podo F: Inhibition of phosphatidylcholine-specific phospholipase C downregulates HER2 overexpression on plasma membrane of breast cancer cells. Breast Cancer Res. 2010, 12: R27-10.1186/bcr2575.Fenollosa R, Meseguer F, Tymczenko M: Silicon colloids: from microcavities to photonic sponges. Adv Mater. 2008, 20: 95-98. 10.1002/adma.200701589.Jasinski JM, Gates SM: Silicon chemical vapor deposition one step at a time: fundamental studies of silicon hydride chemistry. Acc Chem Res. 1991, 24: 9-15. 10.1021/ar00001a002.Xiao Q, Liu Y, Qiu Y, Zhou G, Mao C, Li Z, Yao Z-J, Jiang S: Potent antitumor mimetics of annonaceous acetogenins embedded with an aromatic moiety in the left hydrocarbon chain part. J Med Chem. 2010, 54: 525-533. 10.1021/jm101053k.Allman SA, Jensen HH, Vijayakrishnan B, Garnett JA, Leon E, Liu Y, Anthony DC, Sibson NR, Feizi T, Matthews S, Davis BG: Potent fluoro-oligosaccharide probes of adhesion in toxoplasmosis. ChemBioChem. 2009, 10: 2522-2529. 10.1002/cbic.200900425.Chambers DJ, Evans GR, Fairbanks AJ: Elimination reactions of glycosyl selenoxides. Tetrahedron. 2004, 60: 8411-8419. 10.1016/j.tet.2004.07.005.Tomabechi Y, Suzuki R, Haneda K, Inazu T: Chemo-enzymatic synthesis of glycosylated insulin using a GlcNAc tag. Bioorg Med Chem. 2010, 18: 1259-1264. 10.1016/j.bmc.2009.12.031.Pastoriza-Santos I, Gomez D, Perez-Juste J, Liz-Marzan LM, Mulvaney P: Optical properties of metal nanoparticle coated silica spheres: a simple effective medium approach. Phys Chem Chem Phys. 2004, 6: 5056-5060. 10.1039/b405157b

The Histone H3K79 Methyltransferase Dot1L Is Essential for Mammalian Development and Heterochromatin Structure

Dot1 is an evolutionarily conserved histone methyltransferase specific for lysine 79 of histone H3 (H3K79). In Saccharomyces cerevisiae, Dot1-mediated H3K79 methylation is associated with telomere silencing, meiotic checkpoint control, and DNA damage response. The biological function of H3K79 methylation in mammals, however, remains poorly understood. Using gene targeting, we generated mice deficient for Dot1L, the murine Dot1 homologue. Dot1L-deficient embryos show multiple developmental abnormalities, including growth impairment, angiogenesis defects in the yolk sac, and cardiac dilation, and die between 9.5 and 10.5 days post coitum. To gain insights into the cellular function of Dot1L, we derived embryonic stem (ES) cells from Dot1L mutant blastocysts. Dot1L-deficient ES cells show global loss of H3K79 methylation as well as reduced levels of heterochromatic marks (H3K9 di-methylation and H4K20 tri-methylation) at centromeres and telomeres. These changes are accompanied by aneuploidy, telomere elongation, and proliferation defects. Taken together, these results indicate that Dot1L and H3K79 methylation play important roles in heterochromatin formation and in embryonic development

Left-Right Function of dmrt2 Genes Is Not Conserved between Zebrafish and Mouse

Background: Members of the Dmrt family, generally associated with sex determination, were shown to be involved in several other functions during embryonic development. Dmrt2 has been studied in the context of zebrafish development where, due to a duplication event, two paralog genes dmrt2a and dmrt2b are present. Both zebrafish dmrt2a/terra and dmrt2b are important to regulate left-right patterning in the lateral plate mesoderm. In addition, dmrt2a/terra is necessary for symmetric somite formation while dmrt2b regulates somite differentiation impacting on slow muscle development. One dmrt2 gene is also expressed in the mouse embryo, where it is necessary for somite differentiation but with an impact on axial skeleton development. However, nothing was known about its role during left-right patterning in the lateral plate mesoderm or in the symmetric synchronization of somite formation. Methodology/Principal Findings: Using a dmrt2 mutant mouse line, we show that this gene is not involved in symmetric somite formation and does not regulate the laterality pathway that controls left-right asymmetric organ positioning. We reveal that dmrt2a/terra is present in the zebrafish laterality organ, the Kupffer’s vesicle, while its homologue is excluded from the mouse equivalent structure, the node. On the basis of evolutionary sub-functionalization and neo-functionalization theories we discuss this absence of functional conservation. Conclusions/Significance: Our results show that the role of dmrt2 gene is not conserved during zebrafish and mous