Harmonisasi Pasal 21 Undang-undang Hak Tanggungan dengan Pasal 56 dan Pasal 59 Undang-undang Kepailitan dan Penundaan Kewajiban Pembayaran Utang Terkait Kreditor Separatis Pemegang Hak Tanggungan yang Melekat pada Benda Jaminan

Penelitian ini dilatar belakangi adanya disharmonisasi norma hukum antara Pasal 21 Undang-Undang Hak Tanggungan dengan Pasal 56 dan Pasal 59 Undang-Undang Kepailitan dan PKPU, maka skripsi ini berjudul “Harmonisasi Pasal 21 Undang-Undang Hak Tanggungan Dengan Pasal 56 Dan Pasal 59 Undang-Undang Kepailitan dan PKPU Terkait Kreditor Separatis Pemegang Hak Tanggungan Yang Melekat Pada Benda Jaminan”, dengan 2 (dua) Pokok permasalahan yaitu: (1) Bagaimana Kewenangan Kreditor Pemegang Hak Tanggungan Benda Jaminan Akibat Ketidakharmonisan antara Pasal 21 Undang-undang Hak Tanggungan dengan Pasal 56 dan Pasal 59 Undang-undang Kepailitan dan PKPU? (2) Apakah Perjanjian Utang dengan Hak Tanggungan dapat Memberikan Kepastian Hukum bagi Kreditor Separatis ketika Debitor Pailit?. Penulisan skripsi ini menggunakan metode penelitian hukum normatif. Pendekatan Penelitian dengan pendekatan Perundang-undangan dan pendekatan konseptual. Cara pengumpulan data secara studi pustaka yaitu dengan cara meneliti bahan pustaka atau data sekunder serta mempelajari sumber-sumber atau bahan tertulis yang dijadikan bahan dalam penulisan skripsi ini misalnya buku-buku ilmiah, peraturan Perundang-undangan, jurnal hukum dari internet, dan lain-lain yang memiliki kaitan dengan skripsi ini. Dari hasil penelitian diketahui bahwa (1) Akibat Ketidakharmonisan Antara Pasal 21 Undang-undang Hak Tanggungan dengan Pasal 56 dan Pasal 59 Undang-Undang Kepailitan dan PKPU kewenangan kreditor separatis menjadi disfungsi kewenangan karena terjadi benturan norma hukum yang terdapat dalam pasal-pasal di kedua undang-undang tersebut, tetapi bukan konflik undang-undang. Ketentuan {asa; 56 dan Pasal 59 Undang-undang Kepailitan dan PKPU melemahkan kreditor separatis untuk mengeksekusi sendiri objek hak tanggungan, tetapi kedudukan kreditor pemegang hak tanggungan tetap diutamakan untuk mendapatkan haknya atas objek Hak Tanggunagn sebagai pelunasan piutang sebagaimana pasal 21 Undang-undang Hak Tanggungan. (2) Kepastian Hukum Perjanjian Utang dengan Objek Hak Tanggungan Bagi Kreditor Separatis Ketika Debitor Pailit dapat memberikan kepastian hukum, namun dengan Hak Tanggungan pun Undang-Undang tidak memberikan kepastian pelunasan piutang Kreditor Separatis akan terpenuhi seluruhnya. Adanya ketentuan Pasal 56 dan Pasal 59 Undang-Undang Kepailitan dan PKPU yang sekarang menjadikan proses eksekusi sendiri dapat dibatalkan oleh hukum jika proses eksekusi objek hak tanggungan dilakukan atas title eksekutorial padahal prosedur kepailitan memerlukan biaya dan waktu yang lebih panjang dan tidak terpenuhinya asas lex certa

Soluble curcumin ameliorates motility, adhesiveness and abrogate parthanatos in cadmium-exposed retinal pigment epithelial cells

Cadmium (Cd) is a nonessential transition metal and one of the most toxic environmental pollutants. Industrial, agricultural and urban activities are the main sources of Cd environmental contamination. Multiple deleterious effects of Cd exposure were reported for different cell types and living organisms in a great number of research papers. Cd bioaccumulation hazard is mediated by the relatively long half-life of this metal in an organism. For example, in mammals its half-life lasts for about 10–30 years. Cd exposure affects many tissues. However, some of them, including the central nervous system and sensory organs, are most susceptible to its toxicity. The harmful effects of Cd could be linked to oxidative stress generation and consequently intracellular signalling disruption. Since Cd induces redox imbalance the antioxidants could be a prospective tool to ameliorate Cd cytotoxicity. In present work, we have studied the protective efficacy of soluble curcumin on Cd-caused retinal pigment epithelium (RPE) cells viability, reactive oxygen species production, adhesive and extracellular matrix proteins expression, cell migration and parthanatos level. Low dose (5 µM) of soluble curcumin ameliorated all aforementioned indices of Cd-induced cytotoxicity. Curcumin has restored the RPE cells motility as well as fibronectin and E-cadherin expression. Therefore, the modulation of RPE adhesiveness could be regarded as a cytoprotective effect of curcumin. Furthermore, Cd-caused poly(ADP-ribose) polymerase-1 (PARP-1) suppression and cleaved PARP-1 upregulation were ameliorated by curcumin exposure. Therefore, the protective effect of soluble curcumin could be related, at least partially, to the modulation of PARP activity and inhibition of parthanatos flux. The observed results have demonstrated that low doses of soluble curcumin are a promising tool to protect RPE cells against Cd-caused retinal injury

Local industrial pollution induces astrocyte cytoskeleton rearrangement in the dice snake brain: GFAP as a biomarker

The present study was designed to evaluate the responsiveness of modulation of glial fibrillary acidic protein (GFAP) content and its fragmentation in the snake brain as a biomarker of local industrial pollution of aquatic ecosystems. Despite GFAP being a well known cytoskeleton marker of astrocytes’ reactivity in the brain of vertebrates, its expression in the snake brain remains insufficiently described. The GFAP expression and its fragmentation were detected using the immunoblot method in the snake brain. ROS level was determined with dichlorofluorescein diacetate fluorescence. The content of the glial fibrillary acidic protein (GFAP) of filament (cytoskeleton) and soluble (cytosol) fractions in the brain of dice snake Natrix tessellata from three ecosystems with different rates of industrial pollution were studied (two polluted and one clean control site). Characteristic increase in GFAP fragmentation was noted for the snakes from both the researched polluted sites. Significant increase in the content of the GFAP cleaved polypeptide fragments induced by industrial pollution exposure was confirmed in the snakes’ brains. Meaningful GFAP fragmentation was determined in snake brain astrocytes as an increase in cleaved fragments of 47–35 kDa molecular weight for both soluble and cytoskeletal GFAP fractions. We found significant abnormality in the ratio of the GFAP soluble fraction to the cytoskeletal one in contaminant-exposed dice snakes. It should testify to significant metabolic disturbance in nerve cells of the dice snakes. Furthermore, growth of reactive oxygen species level as the main cause of oxidative stress was determined in brains of the snakes exposed to environmental toxicity. Thus, astrocyte cytoskeleton disorders are associated with pollutant-induced redox imbalance in the snake brain. Despite the limited data on glial cell biology in the reptilian brain, the observed results prove that snake astrocytes can respond to the environmental toxicity using typical astroglial response. The presented results evidence that monitoring of molecular characteristics of glial cytoskeleton in dice snakes could be used as reliable biomarker of neurotoxicity and adverse effects of industrial pollution. Further studies are required to elucidate the role of astrocyte cytoskeleton in the response against neurotoxic contaminants

Development of transgenic rats producing human β-amyloid precursor protein as a model for Alzheimer's disease: Transgene and endogenous APP genes are regulated tissue-specifically

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease (AD) is a devastating neurodegenerative disorder that affects a large and growing number of elderly individuals. In addition to idiopathic disease, AD is also associated with autosomal dominant inheritance, which causes a familial form of AD (FAD). Some instances of FAD have been linked to mutations in the β-amyloid protein precursor (APP). Although there are numerous mouse AD models available, few rat AD models, which have several advantages over mice, have been generated.</p> <p>Results</p> <p>Fischer 344 rats expressing human APP driven by the ubiquitin-C promoter were generated via lentiviral vector infection of Fischer 344 zygotes. We generated two separate APP-transgenic rat lines, APP21 and APP31. Serum levels of human amyloid-beta (Aβ)₄₀were 298 pg/ml for hemizygous and 486 pg/ml for homozygous APP21 animals. Serum Aβ₄₂levels in APP21 homozygous rats were 135 pg/ml. Immunohistochemistry in brain showed that the human APP transgene was expressed in neurons, but not in glial cells. These findings were consistent with independent examination of enhanced green fluorescent protein (eGFP) in the brains of eGFP-transgenic rats. APP21 and APP31 rats expressed 7.5- and 3-times more APP mRNA, respectively, than did wild-type rats. Northern blots showed that the human APP transgene, driven by the ubiquitin-C promoter, is expressed significantly more in brain, kidney and lung compared to heart and liver. A similar expression pattern was also seen for the endogenous rat APP. The unexpected similarity in the tissue-specific expression patterns of endogenous rat APP and transgenic human APP mRNAs suggests regulatory elements within the cDNA sequence of APP.</p> <p>Conclusion</p> <p>This manuscript describes the generation of APP-transgenic inbred Fischer 344 rats. These are the first human AD model rat lines generated by lentiviral infection. The APP21 rat line expresses high levels of human APP and could be a useful model for AD. Tissue-specific expression in the two transgenic rat lines and in wild-type rats contradicts our current understanding of APP gene regulation. Determination of the elements that are responsible for tissue-specific expression of APP may enable new treatment options for AD.</p

Blood pro-resolving mediators are linked with synovial pathology and are predictive of DMARD responsiveness in rheumatoid arthritis.

Biomarkers are needed for predicting the effectiveness of disease modifying antirheumatic drugs (DMARDs). Here, using functional lipid mediator profiling and deeply phenotyped patients with early rheumatoid arthritis (RA), we observe that peripheral blood  specialized pro-resolving mediator (SPM) concentrations are linked with both DMARD responsiveness and disease pathotype. Machine learning analysis demonstrates that baseline plasma concentrations of resolvin D4, 10S, 17S-dihydroxy-docosapentaenoic acid, 15R-Lipoxin (LX)A4 and n-3 docosapentaenoic-derived Maresin 1 are predictive of DMARD responsiveness at 6 months. Assessment of circulating SPM concentrations 6-months after treatment initiation establishes that differences between responders and non-responders are maintained, with a decrease in SPM concentrations in patients resistant to DMARD therapy. These findings elucidate the potential utility of  plasma SPM concentrations as biomarkers of DMARD responsiveness in RA

Laser-Assisted In Vitro Fertilization Facilitates Fertilization of Vitrified-Warmed C57BL/6 Mouse Oocytes with Fresh and Frozen-Thawed Spermatozoa, Producing Live Pups

The utility of cryopreserved mouse gametes for reproduction of transgenic mice depends on development of assisted reproductive technologies, including vitrification of unfertilized mouse oocytes. Due to hardening of the zona pellucida, spermatozoa are often unable to penetrate vitrified-warmed (V-W) oocytes. Laser-assisted in vitro fertilization (LAIVF) facilitates fertilization by allowing easier penetration of spermatozoa through a perforation in the zona. We investigated the efficiency of V-W C57BL/6NTac oocytes drilled by the XYClone laser, compared to fresh oocytes. By using DAP213 for cryoprotection, 83% (1,470/1,762) of vitrified oocytes were recovered after warming and 78% were viable. Four groups were evaluated for two-cell embryo and live offspring efficiency: 1) LAIVF using V-W oocytes, 2) LAIVF using fresh oocytes, 3) conventional IVF using V-W oocytes and 4) conventional IVF using fresh oocytes. First, the groups were tested using fresh C57BL/6NTac spermatozoa (74% motile, 15 million/ml). LAIVF markedly improved the two-cell embryo efficiency using both V-W (76%, 229/298) and fresh oocytes (69%, 135/197), compared to conventional IVF (7%, 12/182; 6%, 14/235, respectively). Then, frozen-thawed C57BL/6NTac spermatozoa (35% motile, 15 million/ml) were used and LAIVF was again found to enhance fertilization efficiency, with two-cell embryo rates of 87% (298/343) using V-W oocytes (P<0.05, compared to fresh spermatozoa), and 73% (195/266) using fresh oocytes. Conventional IVF with frozen-thawed spermatozoa using V-W (6%, 10/168) and fresh (5%, 15/323) oocytes produced few two-cell embryos. Although live offspring efficiency following embryo transfer was greater with conventional IVF (35%, 18/51; LAIVF: 6%, 50/784), advantage was seen with LAIVF in live offspring obtained from total oocytes (5%, 50/1,010; conventional IVF: 2%, 18/908). Our results demonstrated that zona-drilled V-W mouse oocytes can be used for IVF procedures using both fresh and frozen-thawed spermatozoa, producing live pups. The ability to cryopreserve mouse gametes for LAIVF may facilitate management of large-scale transgenic mouse production facilities.National Institutes of Health (U.S.) (NIH National Research Service Award (T32-RR070036))National Institutes of Health (U.S.) (NIH National Cancer Institute Program Project (P01CA10451)

The performance of deterministic and stochastic interest rate risk measures : Another Question of Dimensions?

The efficiency of traditional and stochastic interest rate risk measures is compared under one-, two-, and three-factor no-arbitrage Gauss-Markov term structure models, and for different immunization periods. The empirical analysis, run on the German Treasury bond market from January 2000 to December 2010, suggests that: i) Stochastic interest rate risk measures provide better portfolio immunization than the Fisher-Weil duration; and ii) The superiority of the stochastic risk measures is more evident for multi-factor models and for longer investment horizons. These findings are supported by a first-order stochastic dominance analysis, and are robust against yield curve estimation errors.info:eu-repo/semantics/publishedVersio