5,748 research outputs found

    Too Broke to Hire an Attorney - How to Conduct Basic Legal Research in a Law Library

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    This article targets as its audience pro se patrons - individuals who cannot afford counsel and need to conduct their own legal research. The poor and disenfranchised have historically had difficulty getting equal access to justice. The cause is often the fact that they cannot afford legal representation. This could lead to exclusion from the legal process. A solution might be self-representation, which presents its own difficulties, as the pro se litigant will likely need to access resources in a law library

    HTLV-1 Tax-1 interacts with SNX27 to regulate cellular localization of the HTLV-1 receptor molecule, GLUT1

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    An estimated 10–20 million people worldwide are infected with human T cell leukemia virus type 1 (HTLV-1), with endemic areas of infection in Japan, Australia, the Caribbean, and Africa. HTLV-1 is the causative agent of adult T cell leukemia (ATL) and HTLV-1 associated myopathy/tropic spastic paraparesis (HAM/TSP). HTLV-1 expresses several regulatory and accessory genes that function at different stages of the virus life cycle. The regulatory gene Tax-1 is required for efficient virus replication, as it drives transcription of viral gene products, and has also been demonstrated to play a key role in the pathogenesis of the virus. Several studies have identified a PDZ binding motif (PBM) at the carboxyl terminus of Tax-1 and demonstrated the importance of this domain for HTLV-1 induced cellular transformation. Using a mass spectrometry-based proteomics approach we identified sorting nexin 27 (SNX27) as a novel interacting partner of Tax-1. Further, we demonstrated that their interaction is mediated by the Tax-1 PBM and SNX27 PDZ domains. SNX27 has been shown to promote the plasma membrane localization of glucose transport 1 (GLUT1), one of the receptor molecules of the HTLV-1 virus, and the receptor molecule required for HTLV-1 fusion and entry. We postulated that Tax-1 alters GLUT1 localization via its interaction with SNX27. We demonstrate that over expression of Tax-1 in cells causes a reduction of GLUT1 on the plasma membrane. Furthermore, we show that knockdown of SNX27 results in increased virion release and decreased HTLV-1 infectivity. Collectively, we demonstrate the first known mechanism by which HTLV-1 regulates a receptor molecule post-infection.</div

    De Novo Occurrence of a Variant in ARL3 and Apparent Autosomal Dominant Transmission of Retinitis Pigmentosa.

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    BackgroundRetinitis pigmentosa is a phenotype with diverse genetic causes. Due to this genetic heterogeneity, genome-wide identification and analysis of protein-altering DNA variants by exome sequencing is a powerful tool for novel variant and disease gene discovery. In this study, exome sequencing analysis was used to search for potentially causal DNA variants in a two-generation pedigree with apparent dominant retinitis pigmentosa.MethodsVariant identification and analysis of three affected members (mother and two affected offspring) was performed via exome sequencing. Parental samples of the index case were used to establish inheritance. Follow-up testing of 94 additional retinitis pigmentosa pedigrees was performed via retrospective analysis or Sanger sequencing.Results and conclusionsA total of 136 high quality coding variants in 123 genes were identified which are consistent with autosomal dominant disease. Of these, one of the strongest genetic and functional candidates is a c.269A&gt;G (p.Tyr90Cys) variant in ARL3. Follow-up testing established that this variant occurred de novo in the index case. No additional putative causal variants in ARL3 were identified in the follow-up cohort, suggesting that if ARL3 variants can cause adRP it is an extremely rare phenomenon

    Mitochondrial Energetics of Benthic and Pelagic Antarctic Teleosts

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    Antarctic fauna are highly adapted to the frigid waters of the Southern Ocean. This study describes the in vitro temperature sensitivity of oxygen consumption rates measured in liver mitochondria from the pelagic notothenioid Pleuragramma antarcticum between 5 and 35 C. Oxygen fluxes were measured after the addition of millimolar levels of pyruvate, malate, succinate and glutamate (state II, LEAK) and saturating levels of ADP [state III, oxidative phosphorylation (OXPHOS)]. State III respiration significantly decreased above 18.7 C. A comparison of the oxidative capacities among P. antarcticum and other notothenioids showed significant differences in state III respiration, where benthic species exhibited about 50 % lower rates than P. antarcticum . In addition, state III respiration rates normalized per milligram of mitochondrial protein of P. antarcticum were up to eight times higher than state III rates reported in the literature for other notothenioids. The comparatively high respiration rates measured in this study may be explained by our approach, which engaged both complexes I and II under conditions of oxidative phosphorylation. State III rates of independently activated complexes I and II were found to range from 42 to 100 % of rates obtained when both complexes were activated simultaneously in the same species. The remarkable tolerance of P. antarcticum OXPHOS toward warmer temperatures was unexpected for an Antarctic stenotherm and may indicate that thermal sensitivity of their mitochondria is not the driving force behind their stenothermy

    Mitochondrial Energetics of Benthic and Pelagic Antarctic Teleosts

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    Antarctic fauna are highly adapted to the frigid waters of the Southern Ocean. This study describes the in vitro temperature sensitivity of oxygen consumption rates measured in liver mitochondria from the pelagic notothenioid Pleuragramma antarcticum between 5 and 35 C. Oxygen fluxes were measured after the addition of millimolar levels of pyruvate, malate, succinate and glutamate (state II, LEAK) and saturating levels of ADP [state III, oxidative phosphorylation (OXPHOS)]. State III respiration significantly decreased above 18.7 C. A comparison of the oxidative capacities among P. antarcticum and other notothenioids showed significant differences in state III respiration, where benthic species exhibited about 50 % lower rates than P. antarcticum . In addition, state III respiration rates normalized per milligram of mitochondrial protein of P. antarcticum were up to eight times higher than state III rates reported in the literature for other notothenioids. The comparatively high respiration rates measured in this study may be explained by our approach, which engaged both complexes I and II under conditions of oxidative phosphorylation. State III rates of independently activated complexes I and II were found to range from 42 to 100 % of rates obtained when both complexes were activated simultaneously in the same species. The remarkable tolerance of P. antarcticum OXPHOS toward warmer temperatures was unexpected for an Antarctic stenotherm and may indicate that thermal sensitivity of their mitochondria is not the driving force behind their stenothermy

    Updated Lessons in Conducting Basics Legal Research by Pro Se Litigants Who Cannot Afford an Attorney

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    The first generation of this article was written and published by The Scholar in 2006.1 Because the trend to accessing legal materials is geared more and more toward the Internet, the tour of the book world that was the focus of the original article requires expansion to include those sources available on the World Wide Web.2 Thus, this article contains most of the content in the original article, and then is supplemented by discussions of content currently available from online legal resources

    Primary stroke in a woman with sickle cell anemia responsive to hydroxyurea therapy.

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    The most common cause of stroke in children with sickle cell anemia is infarction due to ischemia. In adults, however, stroke is most commonly hemorrhagic in nature. Other causes of stroke in patients with sickle cell disease are very rare. In this short communication, we describe a woman with sickle cell anemia responsive to hydroxyurea (HU) therapy who had primary stroke due to paradoxical embolization caused by a large atrial septal defect. Successful management of the stroke included surgical closure of the defect with trans-esophageal echocardiographic guidance. To the best of our knowledge, this is the first patient with sickle cell anemia and stroke due to congenital heart disease who did not require open heart surgery for successful management

    Design, Testing and Evaluation of Mobile Corn Mill for Village-Level Operation in the Philippines

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    The efficiency and availability of corn mills operating in the Philippines play a vital role in achieving food self-sufficiency in the entire country.   Majority of operational corn mills are situated along the highway where three-phase electrical line is available. Current design of operational corn mills still utilizes emery stone for its degermination process, two-steel rollers for its milling process and oscillating sifter that all require huge amount of power. The purpose of this research was to develop a technically viable and financially feasible new type of mobile corn mill that can be used in the countryside particularly in the remote areas. The developed corn mill system is comprised of the degerminator, rotary mill, rotary grader and equipped with a pre-cleaner (destoner and winnower), two elevators and a suction blower.  It is powered by 60 HP, 4-cylinder diesel engine.   Performance test results revealed that the developed mobile corn mill has an input capacity of 940 - 1,100  kg/h with product recovery of 66-71 % and degerminator efficiency of 82-88 %.  Cost of milling is estimated at Php0.86 per kg output.  The estimated cost of the developed corn mill is Php850,000 per unit (US$1=Php50).  The developed corn mill technology can be used by farmer cooperatives and local entrepreneurs that will engage in custom-milling business and the processing of corn for food and animal feeds

    RIPK3 restricts viral pathogenesis via cell death-independent neuroinflammation

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    Receptor-interacting protein kinase-3 (RIPK3) is an activator of necroptotic cell death, but recent work has implicated additional roles for RIPK3 in inflammatory signaling independent of cell death. However, while necroptosis has been shown to contribute to antiviral immunity, death-independent roles for RIPK3 in host defense have not been demonstrated. Using a mouse model of West Nile virus (WNV) encephalitis, we show that RIPK3 restricts WNV pathogenesis independently of cell death. Ripk3(-/-) mice exhibited enhanced mortality compared to wild-type (WT) controls, while mice lacking the necroptotic effector MLKL, or both MLKL and caspase-8, were unaffected. The enhanced susceptibility of Ripk3(-/-) mice arose from suppressed neuronal chemokine expression and decreased central nervous system (CNS) recruitment of T lymphocytes and inflammatory myeloid cells, while peripheral immunity remained intact. These data identify pleiotropic functions for RIPK3 in the restriction of viral pathogenesis and implicate RIPK3 as a key coordinator of immune responses within the CNS
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