1,307 research outputs found
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Arbitration in English law and society before the Act of 1698
The practice of arbitration in seventeenth-century England has not been the subject of close study. Whilst it is recognised that arbitration was a frequent and favoured means to resolve disputes during this period, previous historians of law and social relations have focused their interests elsewhere. For this reason, little has been done to account for the passing of the Arbitration Act of 1698, the first statute on arbitration to be enacted in England. The statute authorised the common law courts to imprison individuals for contempt of court if they did not comply with an arbitration, thereby instituting a procedure that is dissonant with the conciliatory or ‘neighbourly’ view of arbitration espoused by historians. The aim, then, of this dissertation is two-fold. First, it seeks to examine the structure and practice of arbitration in seventeenth-century England to provide an introduction to the topic that is long overdue. This will offer the opportunity to question some of the prevailing assumptions about the process, and it will be argued that arbitration was often far more coercive and law-related than previous scholars have indicated. Second, the dissertation seeks to explain why the Arbitration Act of 1698 was made. By analysing the development of the enforcement procedure on which the statute was based and the circumstances surrounding its drafting and enactment, it will be argued that the making of the Arbitration Act was in fact a two-stage process, the stages of which were largely unconnected to one another. Whereas the enforcement procedure the statute authorised first arose to ensure the specific performance of an award, the decision made as a result of an arbitration, the statute itself was passed to address political and commercial exigencies of the 1690s.F.W. Maitland Memorial Fund Studentshi
Lithium alters expression of RNAs in a type-specific manner in differentiated human neuroblastoma neuronal cultures, including specific genes involved in Alzheimer's disease.
Lithium (Li) is a medication long-used to treat bipolar disorder. It is currently under investigation for multiple nervous system disorders, including Alzheimer's disease (AD). While perturbation of RNA levels by Li has been previously reported, its effects on the whole transcriptome has been given little attention. We, therefore, sought to determine comprehensive effects of Li treatment on RNA levels. We cultured and differentiated human neuroblastoma (SK-N-SH) cells to neuronal cells with all-trans retinoic acid (ATRA). We exposed cultures for one week to lithium chloride or distilled water, extracted total RNA, depleted ribosomal RNA and performed whole-transcriptome RT-sequencing. We analyzed results by RNA length and type. We further analyzed expression and protein interaction networks between selected Li-altered protein-coding RNAs and common AD-associated gene products. Lithium changed expression of RNAs in both non-specific (inverse to sequence length) and specific (according to RNA type) fashions. The non-coding small nucleolar RNAs (snoRNAs) were subject to the greatest length-adjusted Li influence. When RNA length effects were taken into account, microRNAs as a group were significantly less likely to have had levels altered by Li treatment. Notably, several Li-influenced protein-coding RNAs were co-expressed or produced proteins that interacted with several common AD-associated genes and proteins. Lithium's modification of RNA levels depends on both RNA length and type. Li activity on snoRNA levels may pertain to bipolar disorders while Li modification of protein coding RNAs may be relevant to AD
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Shakespeare's Satire of the Literary and Theatrical Milieu, 1593-1603
The purpose of this study is to investigate the evidence of Shakespeare's satire in certain plays written during the years 1593-1603. The study examines only the satire which deals with other writers and actors and events that are connected in some way with the theater
In Situ Studies of the Primary Immune Response to (4-Hydroxy-3-Nitrophenyl)Acetyl. V. Affinity Maturation Develops in Two Stages of Clonal Selection
To examine the role of germinal centers (GCs) in the generation and selection of high affinity antibody-forming cells (AFCs), we have analyzed the average affinity of (4-hydroxy-3-nitrophenyl)acetyl (NP)-specific AFCs and serum antibodies both during and after the GC phase of the immune response. In addition, the genetics of NP-binding AFCs were followed to monitor the generation and selection of high affinity AFCs at the clonal level. NP-binding AFCs gradually accumulate in bone marrow (BM) after immunization and BM becomes the predominant locale of specific AFCs in the late primary response. Although the average affinity of NP-specific BM AFCs rapidly increased while GCs were present (GC phase), the affinity of both BM AFCs and serum antibodies continued to increase even after GCs waned (post-GC phase). Affinity maturation in the post-GC phase was also reflected in a shift in the distribution of somatic mutations as well as in the CDR3 sequences of BM AFC antibody heavy chain genes. Disruption of GCs by injection of antibody specific for CD154 (CD40 ligand) decreased the average affinity of subsequent BM AFCs, suggesting that GCs generate the precursors of high affinity BM AFCs; inhibition of CD154-dependent cellular interactions after the GC reaction was complete had no effect on high affinity BM AFCs. Interestingly, limited affinity maturation in the BM AFC compartment still occurs during the late primary response even after treatment with anti-CD154 antibody. Thus, GCs are necessary for the generation of high affinity AFC precursors but are not the only sites for the affinity-driven clonal selection responsible for the maturation of humoral immune responses
Identification and utilization of arbitrary correlations in models of recombination signal sequences
BACKGROUND: A significant challenge in bioinformatics is to develop methods for detecting and modeling patterns in variable DNA sequence sites, such as protein-binding sites in regulatory DNA. Current approaches sometimes perform poorly when positions in the site do not independently affect protein binding. We developed a statistical technique for modeling the correlation structure in variable DNA sequence sites. The method places no restrictions on the number of correlated positions or on their spatial relationship within the site. No prior empirical evidence for the correlation structure is necessary. RESULTS: We applied our method to the recombination signal sequences (RSS) that direct assembly of B-cell and T-cell antigen-receptor genes via V(D)J recombination. The technique is based on model selection by cross-validation and produces models that allow computation of an information score for any signal-length sequence. We also modeled RSS using order zero and order one Markov chains. The scores from all models are highly correlated with measured recombination efficiencies, but the models arising from our technique are better than the Markov models at discriminating RSS from non-RSS. CONCLUSIONS: Our model-development procedure produces models that estimate well the recombinogenic potential of RSS and are better at RSS recognition than the order zero and order one Markov models. Our models are, therefore, valuable for studying the regulation of both physiologic and aberrant V(D)J recombination. The approach could be equally powerful for the study of promoter and enhancer elements, splice sites, and other DNA regulatory sites that are highly variable at the level of individual nucleotide positions
Very Low Affinity B Cells Form Germinal Centers, Become Memory B Cells, and Participate in Secondary Immune Responses When Higher Affinity Competition Is Reduced
To understand the relationship between the affinity of the B cell antigen receptor (BCR) and the immune response to antigen, two lines of immunoglobulin H chain transgenic (Tg) mice were created. H50Gμa and T1(V23)μa mice express μ H chain transgenes that associate with the λ1 L chains to bind the (4-hydroxy-3-nitrophenyl)acetyl hapten with association constants (Kas) of only 1.2 × 105 M−1 and 3 × 104 M−1, respectively. Both lines mounted substantial antibody-forming cell (AFC) and germinal center (GC) responses. H50Gμa Tg mice also generated memory B cells. T1(V23)μa B cells formed AFC and GCs, but were largely replaced in late GCs by antigen-specific cells that express endogenous BCRs. Thus, B lymphocytes carrying BCRs with affinities previously thought to be irrelevant in specific immune responses are in fact capable of complete T cell–dependent immune responses when relieved of substantial competition from other B cells. The failure to observe such B cells normally in late primary responses and in memory B cell populations is the result of competition, rather than an intrinsic inability of low affinity B cells
Circadian polymorphisms associated with affective disorders
<p>Abstract</p> <p>Background</p> <p>Clinical symptoms of affective disorders, their response to light treatment, and sensitivity to other circadian interventions indicate that the circadian system has a role in mood disorders. Possibly the mechanisms involve circadian seasonal and photoperiodic mechanisms. Since genetic susceptibilities contribute a strong component to affective disorders, we explored whether circadian gene polymorphisms were associated with affective disorders in four complementary studies.</p> <p>Methods</p> <p>Four groups of subjects were recruited from several sources: 1) bipolar proband-parent trios or sib-pair-parent nuclear families, 2) unrelated bipolar participants who had completed the BALM morningness-eveningness questionnaire, 3) sib pairs from the GenRed Project having at least one sib with early-onset recurrent unipolar depression, and 4) a sleep clinic patient group who frequently suffered from depression. Working mainly with the SNPlex assay system, from 2 to 198 polymorphisms in genes related to circadian function were genotyped in the participant groups. Associations with affective disorders were examined with TDT statistics for within-family comparisons. Quantitative trait associations were examined within the unrelated samples.</p> <p>Results</p> <p>In <it>NR1D1</it>, rs2314339 was associated with bipolar disorder (P = 0.0005). Among the unrelated bipolar participants, 3 SNPs in <it>PER3 </it>and <it>CSNK1E </it>were associated with the BALM score. A <it>PPARGC1B </it>coding SNP, rs7732671, was associated with affective disorder with nominal significance in bipolar family groups and independently in unipolar sib pairs. In <it>TEF</it>, rs738499 was associated with unipolar depression; in a replication study, rs738499 was also associated with the QIDS-SR depression scale in the sleep clinic patient sample.</p> <p>Conclusion</p> <p>Along with anti-manic effects of lithium and the antidepressant effects of bright light, these findings suggest that perturbations of the circadian gene network at several levels may influence mood disorders, perhaps ultimately through regulation of MAOA and its modulation of dopamine transmission. Twenty-three associations of circadian polymorphisms with affective symptoms met nominal significance criteria (P < 0.05), whereas 15 would be expected by chance, indicating that many represented false discoveries (Type II errors). Some evidence of replication has been gathered, but more studies are needed to ascertain if circadian gene polymorphisms contribute to susceptibility to affective disorders.</p
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