122 research outputs found
Kebijakan Reformulasi Ancaman Pidana Mati Tindak Pidana Korupsi dalam Peraturan Perundang-undangan
Corruption in Indonesia systematically in all sectors of public life, has threatened the efforts of sustainable development and the achievement of social welfare in Indonesia. Society demanded that the death sentence meted out to the criminals, so that corruption can be prevented and eradicated systematically. However, until now there has been no single criminals sentenced to death. This happens because of the legal weaknesses in the formulation death sentence for corruption. Some disadvantages juridical include: the death penalty only for offenses threatened enrich themselves / others / corporate corruption, death penalty only for corruption perpetrated under certain circumstances, the law does not formulate terms / limitations repetition acts criminal (recidive) for corruption, crime repeated terms and repetition period in terms of providing capital punishment for repeat offenses (recidive) for corruption. Reformulation of capital punishment for corruption should be threatened by the principal alternative to other types of criminal offense-specific corruption offenses considered very disgraceful and extremely harmful and damaging the wider society (nation / state). In addition, given the threat of the death penalty is a last resort in combating corruption should also formulated an alternative capital punishment or other forms of death penalty mitigation
Kebijakan Reformasi Maqâshid Al-Syarîah dan Kontribusinya dalam Formulasi Alternatif Keringanan Pidana Penjara
Criminal law is often built on the paradigm of giving suffering to perpetrators of crime. This paradigm is no longer in accordance with the concept of modern punishment which focuses on efforts to foster criminals so that they would no longer repeat their actions. The changes in the paradigm of punishment, to some extent, have been accommodated by Article 73 of the Criminal Code Bill which contains alternative provisions/criminal sanctions.in jail. With this provision, a prisoner with one year or under punishment is able to repay his sentence as long as there are certain emergency conditions leading to a precarious situation/worry to him if he has to undergo consecutive penalties. This study tries to examine the new provision, using a normative juridical approach from the perspective of Islamic law. This study concludes that the paradigmatic change in punishment as shown in article 73 of the Criminal Code Bill has conformity with the perspective of maqâshid al-syarî'ah which put forward the 5 (five) main objectives in the law, namely maintaining and nurturing religion (al-dîn), soul (al-nafs), descent (al-nasl), wealth (al-mâl), and mind (al-aql)
HIV-1 Nef Employs Two Distinct Mechanisms to Modulate Lck Subcellular Localization and TCR Induced Actin Remodeling
The Nef protein acts as critical factor during HIV pathogenesis by increasing HIV replication in vivo via the modulation of host cell vesicle transport and signal transduction processes. Recent studies suggested that Nef alters formation and function of immunological synapses (IS), thereby modulating exogenous T-cell receptor (TCR) stimulation to balance between partial T cell activation required for HIV-1 spread and prevention of activation induced cell death. Alterations of IS function by Nef include interference with cell spreading and actin polymerization upon TCR engagement, a pronounced intracellular accumulation of the Src kinase Lck and its reduced IS recruitment. Here we use a combination of Nef mutagenesis and pharmacological inhibition to analyze the relative contribution of these effects to Nef mediated alterations of IS organization and function on TCR stimulatory surfaces. Inhibition of actin polymerization and IS recruitment of Lck were governed by identical Nef determinants and correlated well with Nef's association with Pak2 kinase activity. In contrast, Nef mediated Lck endosomal accumulation was separable from these effects, occurred independently of Pak2, required integrity of the microtubule rather than the actin filament system and thus represents a distinct Nef activity. Finally, reduction of TCR signal transmission by Nef was linked to altered actin remodeling and Lck IS recruitment but did not require endosomal Lck rerouting. Thus, Nef affects IS function via multiple independent mechanisms to optimize virus replication in the infected host
Ubiquitin-specific protease 5 is required for the efficient repair of DNA double-strand breaks
During the DNA damage response (DDR), ubiquitination plays an important role in the recruitment and regulation of repair proteins. However, little is known about elimination of the ubiquitination signal after repair is completed. Here we show that the ubiquitin-specific protease 5 (USP5), a deubiquitinating enzyme, is involved in the elimination of the ubiquitin signal from damaged sites and is required for efficient DNA double-strand break (DSB) repair. Depletion of USP5 sensitizes cells to DNA damaging agents, produces DSBs, causes delayed disappearance of γH2AX foci after Bleocin treatment, and influences DSB repair efficiency in the homologous recombination pathway but not in the non-homologous end joining pathway. USP5 co-localizes to DSBs induced by laser micro-irradiation in a RAD18-dependent manner. Importantly, polyubiquitin chains at sites of DNA damage remained for longer periods in USP5-depleted cells. Our results show that disassembly of polyubiquitin chains by USP5 at sites of damage is important for efficient DSB repair. © 2014 Nakajima et al
Natural Killer Cell Signal Integration Balances Synapse Symmetry and Migration
Imaging immune surveillance by natural killer (NK) cells has revealed that integration of activating and inhibitory signals determines whether or not NK cells stop to kill the target cell or retain a migratory configuration
Nck adapter proteins: functional versatility in T cells
Nck is a ubiquitously expressed adapter protein that is almost exclusively built of one SH2 domain and three SH3 domains. The two isoproteins of Nck are functionally redundant in many aspects and differ in only few amino acids that are mostly located in the linker regions between the interaction modules. Nck proteins connect receptor and non-receptor tyrosine kinases to the machinery of actin reorganisation. Thereby, Nck regulates activation-dependent processes during cell polarisation and migration and plays a crucial role in the signal transduction of a variety of receptors including for instance PDGF-, HGF-, VEGF- and Ephrin receptors. In most cases, the SH2 domain mediates binding to the phosphorylated receptor or associated phosphoproteins, while SH3 domain interactions lead to the formation of larger protein complexes. In T lymphocytes, Nck plays a pivotal role in the T cell receptor (TCR)-induced reorganisation of the actin cytoskeleton and the formation of the immunological synapse. However, in this context, two different mechanisms and adapter complexes are discussed. In the first scenario, dependent on an activation-induced conformational change in the CD3ε subunits, a direct binding of Nck to components of the TCR/CD3 complex was shown. In the second scenario, Nck is recruited to the TCR complex via phosphorylated Slp76, another central constituent of the membrane proximal activation complex. Over the past years, a large number of putative Nck interactors have been identified in different cellular systems that point to diverse additional functions of the adapter protein, e.g. in the control of gene expression and proliferation
Myosin IIA Modulates T Cell Receptor Transport and CasL Phosphorylation during Early Immunological Synapse Formation
Activation of T cell receptor (TCR) by antigens occurs in concert with an elaborate multi-scale spatial reorganization of proteins at the immunological synapse, the junction between a T cell and an antigen-presenting cell (APC). The directed movement of molecules, which intrinsically requires physical forces, is known to modulate biochemical signaling. It remains unclear, however, if mechanical forces exert any direct influence on the signaling cascades. We use T cells from AND transgenic mice expressing TCRs specific to the moth cytochrome c 88–103 peptide, and replace the APC with a synthetic supported lipid membrane. Through a series of high spatiotemporal molecular tracking studies in live T cells, we demonstrate that the molecular motor, non-muscle myosin IIA, transiently drives TCR transport during the first one to two minutes of immunological synapse formation. Myosin inhibition reduces calcium influx and colocalization of active ZAP-70 (zeta-chain associated protein kinase 70) with TCR, revealing an influence on signaling activity. More tellingly, its inhibition also significantly reduces phosphorylation of the mechanosensing protein CasL (Crk-associated substrate the lymphocyte type), raising the possibility of a direct mechanical mechanism of signal modulation involving CasL
Assessing the potential for sea-based macroalgae cultivation and its application for nutrient removal in the Baltic Sea
Marine eutrophication is a pervasive and growing threat to global sustainability. Macroalgal cultivation is a promising circular economy solution to achieve nutrient reduction and food security. However, the location of production hotspots is not well known. In this paper the production potential of macroalgae of high commercial value was predicted across the Baltic Sea region. In addition, the nutrient limitation within and adjacent to macroalgal farms was investigated to suggest optimal site-specific configuration of farms. The production potential of Saccharina latissima was largely driven by salinity and the highest production yields are expected in the westernmost Baltic Sea areas where salinity is >23. The direct and interactive effects of light availability, temperature, salinity and nutrient concentrations regulated the predicted changes in the production of Ulva intestinalis and Fucus vesiculosus. The western and southern Baltic Sea exhibited the highest farming potential for these species, with promising areas also in the eastern Baltic Sea. Macroalgal farming did not induce significant nutrient limitation. The expected spatial propagation of nutrient limitation caused by macroalgal farming was less than 100–250 m. Higher propagation distances were found in areas of low nutrient and low water exchange (e.g. offshore areas in the Baltic Proper) and smaller distances in areas of high nutrient and high water exchange (e.g. western Baltic Sea and Gulf of Riga). The generated maps provide the most sought-after input to support blue growth initiatives that foster the sustainable development of macroalgal cultivation and reduction of in situ nutrient loads in the Baltic Sea.</p
Development of a multiplex fluorescence immunological assay for the simultaneous detection of antibodies against Cooperia oncophora, Dictyocaulus viviparus and Fasciola hepatica in cattle
Paediatric schistosomiasis:What we know and what we need to know
Schistosomiasis affects over 200 million people worldwide, most of whom are children. Research and control strategies directed at preschool-aged children (PSAC), i.e., ≤5 years old, have lagged behind those in older children and adults. With the recent WHO revision of the schistosomiasis treatment guidelines to include PSAC, and the recognition of gaps in our current knowledge on the disease and its treatment in this age group, there is now a concerted effort to address these shortcomings. Global and national schistosome control strategies are yet to include PSAC in treatment schedules. Maximum impact of schistosome treatment programmes will be realised through effective treatment of PSAC. In this review, we (i) discuss the current knowledge on the dynamics and consequences of paediatric schistosomiasis and (ii) identify knowledge and policy gaps relevant to these areas and to the successful control of schistosome infection and disease in this age group. Herein, we highlight risk factors, immune mechanisms, pathology, and optimal timing for screening, diagnosis, and treatment of paediatric schistosomiasis. We also discuss the tools required for treating schistosomiasis in PSAC and strategies for accessing them for treatment
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