Methodology, theoretical framework and scholarly significance: An overview of International best practices in legal research

Communicating the results of painstaking legal research efforts is arguably as important as conducting the research itself. Established international publication outlets apply diverse submission guidelines for prospective authors. One common currency, however, is that getting a research paper from conception to publication, as a journal article, book chapter, or forum paper, requires an author to demonstrate a potential contribution to knowledge in the field. This requires a systematic research approach that unpacks contemporary issues in an analytical manner; a clear and concise presentation of ideas with focus on effectiveness; adoption of tested theoretical frameworks to underpin new ideas; and a careful proofreading of manuscript to ensure that a prospective publication meets the expected standards of good quality contribution to theory, practice or policy. This article discusses the indispensable standards and important guidelines that authors should weigh before writing papers for publication, most especially for internationally recognized journals. The authors draw on their experiences as Editorial Board members of national and international journals to unpack key theoretical, methodological and practical issues that legal researchers should consider when developing legal research papers.Keywords: Legal Research, Methodology, Theory, Pedagogy, Legal Training, Scholarshi

Identitag, a relational database for SAGE tag identification and interspecies comparison of SAGE libraries

BACKGROUND: Serial Analysis of Gene Expression (SAGE) is a method of large-scale gene expression analysis that has the potential to generate the full list of mRNAs present within a cell population at a given time and their frequency. An essential step in SAGE library analysis is the unambiguous assignment of each 14 bp tag to the transcript from which it was derived. This process, called tag-to-gene mapping, represents a step that has to be improved in the analysis of SAGE libraries. Indeed, the existing web sites providing correspondence between tags and transcripts do not concern all species for which numerous EST and cDNA have already been sequenced. RESULTS: This is the reason why we designed and implemented a freely available tool called Identitag for tag identification that can be used in any species for which transcript sequences are available. Identitag is based on a relational database structure in order to allow rapid and easy storage and updating of data and, most importantly, in order to be able to precisely define identification parameters. This structure can be seen like three interconnected modules : the first one stores virtual tags extracted from a given list of transcript sequences, the second stores experimental tags observed in SAGE experiments, and the third allows the annotation of the transcript sequences used for virtual tag extraction. It therefore connects an observed tag to a virtual tag and to the sequence it comes from, and then to its functional annotation when available. Databases made from different species can be connected according to orthology relationship thus allowing the comparison of SAGE libraries between species. We successfully used Identitag to identify tags from our chicken SAGE libraries and for chicken to human SAGE tags interspecies comparison. Identitag sources are freely available on web site. CONCLUSIONS: Identitag is a flexible and powerful tool for tag identification in any single species and for interspecies comparison of SAGE libraries. It opens the way to comparative transcriptomic analysis, an emerging branch of biology

Circadian Timing of Food Intake Contributes to Weight Gain

Studies of body weight regulation have focused almost entirely on caloric intake and energy expenditure. However, a number of recent studies in animals linking energy regulation and the circadian clock at the molecular, physiological, and behavioral levels raise the possibility that the timing of food intake itself may play a significant role in weight gain. The present study focused on the role of the circadian phase of food consumption in weight gain. We provide evidence that nocturnal mice fed a high‐fat diet only during the 12‐h light phase gain significantly more weight than mice fed only during the 12‐h dark phase. A better understanding of the role of the circadian system for weight gain could have important implications for developing new therapeutic strategies for combating the obesity epidemic facing the human population today

Large, binge-type meals of high fat diet change feeding behaviour and entrain food anticipatory activity in mice

Copyright © 2014. Published by Elsevier Ltd.Peer reviewedPublisher PD

Population genetic analysis of Plasmodium knowlesi reveals differential selection and exchange events between Borneo and Peninsular sub-populations

Funding: A.T. was funded by a Newton Institutional Links Grant (British Council, no. 261868591). S.C. was funded by BloomsburySET and Medical Research Council UK grants (MR/M01360X/1, MR/R025576/1, MR/R020973/1, and MR/X005895/1). T.G.C. was funded by the Medical Research Council UK (Grant nos. MR/M01360X/1, MR/N010469/1, MR/R025576/1, MR/R020973/1, and MR/X005895/1).The zoonotic Plasmodium knowlesi parasite is a growing public health concern in Southeast Asia, especially in Malaysia, where elimination of P. falciparum and P. vivax malaria has been the focus of control efforts. Understanding of the genetic diversity of P. knowlesi parasites can provide insights into its evolution, population structure, diagnostics, transmission dynamics, and the emergence of drug resistance. Previous work has revealed that P. knowlesi fall into three main sub-populations distinguished by a combination of geographical location and macaque host (Macaca fascicularis and M. nemestrina). It has been shown that Malaysian Borneo groups display profound heterogeneity with long regions of high or low divergence resulting in mosaic patterns between sub-populations, with some evidence of chromosomal-segment exchanges. However, the genetic structure of non-Borneo sub-populations is less clear. By gathering one of the largest collections of P. knowlesi whole-genome sequencing data, we studied structural genomic changes across sub-populations, with the analysis revealing differences in Borneo clusters linked to mosquito-related stages of the parasite cycle, in contrast to differences in host-related stages for the Peninsular group. Our work identifies new genetic exchange events, including introgressions between Malaysian Peninsular and M. nemestrina-associated clusters on various chromosomes, including in parasite invasion genes (DBPβ, NBPXα and NBPXβ), and important proteins expressed in the vertebrate parasite stages. Recombination events appear to have occurred between the Peninsular and M. fascicularis-associated groups, including in the DBPβ and DBPγ invasion associated genes. Overall, our work finds that genetic exchange events have occurred among the recognised contemporary groups of P. knowlesi parasites during their evolutionary history, leading to apparent mosaicism between these sub-populations. These findings generate new hypotheses relevant to parasite evolutionary biology and P. knowlesi epidemiology, which can inform malaria control approaches to containing the impact of zoonotic malaria on human communities.Publisher PDFPeer reviewe

Petrophysical Characterization and Reservoir Simulator for Methane Gas Production from Gulf of Mexico Hydrates

Gas hydrates are crystalline, ice-like compounds of gas and water molecules that are formed under certain thermodynamic conditions. Hydrate deposits occur naturally within ocean sediments just below the sea floor at temperatures and pressures existing below about 500 meters water depth. Gas hydrate is also stable in conjunction with the permafrost in the Arctic. Most marine gas hydrate is formed of microbially generated gas. It binds huge amounts of methane into the sediments. Estimates of the amounts of methane sequestered in gas hydrates worldwide are speculative and range from about 100,000 to 270,000,000 trillion cubic feet (modified from Kvenvolden, 1993). Gas hydrate is one of the fossil fuel resources that is yet untapped, but may play a major role in meeting the energy challenge of this century. In this project novel techniques were developed to form and dissociate methane hydrates in porous media, to measure acoustic properties and CT properties during hydrate dissociation in the presence of a porous medium. Hydrate depressurization experiments in cores were simulated with the use of TOUGHFx/HYDRATE simulator. Input/output software was developed to simulate variable pressure boundary condition and improve the ease of use of the simulator. A series of simulations needed to be run to mimic the variable pressure condition at the production well. The experiments can be matched qualitatively by the hydrate simulator. The temperature of the core falls during hydrate dissociation; the temperature drop is higher if the fluid withdrawal rate is higher. The pressure and temperature gradients are small within the core. The sodium iodide concentration affects the dissociation pressure and rate. This procedure and data will be useful in designing future hydrate studies

Artificial feeding synchronizes behavioral, hormonal, metabolic and neural parameters in mother‐deprived neonatal rabbit pups

Nursing in the rabbit is under circadian control, and pups have a daily anticipatory behavioral arousal synchronized to this unique event, but it is not known which signal is the main entraining cue. In the present study, we hypothesized that food is the main entraining signal. Using mother‐deprived pups, we tested the effects of artificial feeding on the synchronization of locomotor behavior, plasma glucose, corticosterone, c‐Fos (FOS) and PERIOD1 (PER1) rhythms in suprachiasmatic, supraoptic, paraventricular and tuberomammillary nuclei. At postnatal day 1, an intragastric tube was placed by gastrostomy. The next day and for the rest of the experiment, pups were fed with a milk formula through the cannula at either 02:00 h or 10:00 h [feeding time = zeitgeber time (ZT)0]. At postnatal days 5–7, pups exhibited behavioral arousal, with a significant increase in locomotor behavior 60 min before feeding. Glucose levels increased after feeding, peaking at ZT4–ZT12 and then declining. Corticosterone levels were highest around the time of feeding, and then decreased to trough concentrations at ZT12–ZT16, increasing again in anticipation of the next feeding bout. In the brain, the suprachiasmatic nucleus had a rhythm of FOS and PER1 that was not significantly affected by the feeding schedule. Conversely, the supraoptic, paraventricular and tuberomammillary nuclei had rhythms of both FOS and PER1 induced by the time of scheduled feeding. We conclude that the nursing rabbit pup is a natural model of food entrainment, as food, in this case milk formula, is a strong synchronizing signal for behavioral, hormonal, metabolic and neural parameters. Nursing in the rabbit is under circadian control, and pups have a daily anticipatory behavioral arousal synchronized to this unique event, but it is not known which signal is the main entraining cue. In the present study, we hypothesized that food is the main entraining signal.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/88087/1/j.1460-9568.2011.07898.x.pd

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Temperature Regulates Transcription in the Zebrafish Circadian Clock

It has been well-documented that temperature influences key aspects of the circadian clock. Temperature cycles entrain the clock, while the period length of the circadian cycle is adjusted so that it remains relatively constant over a wide range of temperatures (temperature compensation). In vertebrates, the molecular basis of these properties is poorly understood. Here, using the zebrafish as an ectothermic model, we demonstrate first that in the absence of light, exposure of embryos and primary cell lines to temperature cycles entrains circadian rhythms of clock gene expression. Temperature steps drive changes in the basal expression of certain clock genes in a gene-specific manner, a mechanism potentially contributing to entrainment. In the case of the per4 gene, while E-box promoter elements mediate circadian clock regulation, they do not direct the temperature-driven changes in transcription. Second, by studying E-box-regulated transcription as a reporter of the core clock mechanism, we reveal that the zebrafish clock is temperature-compensated. In addition, temperature strongly influences the amplitude of circadian transcriptional rhythms during and following entrainment by light–dark cycles, a property that could confer temperature compensation. Finally, we show temperature-dependent changes in the expression levels, phosphorylation, and function of the clock protein, CLK. This suggests a mechanism that could account for changes in the amplitude of the E-box-directed rhythm. Together, our results imply that several key transcriptional regulatory elements at the core of the zebrafish clock respond to temperature

The circadian clock, metabolism and obesity

In the last decades, obesity has been on the rise becoming a burden for health care systems. The reasons behind this rise are most likely caused by lifestyle rather than by an increase in gene mutations, because manifestations of genetic alterations would take longer than just a few decades. Lifestyle has a great impact on the circadian system and therefore on the body internal organization of physiological and biochemical processes, regulating various aspects of behavior and metabolism. In the following, I will discuss recent studies delineating relationships between metabolic processes and the circadian system, how metabolites and nutrients regulate the circadian clock and how nuclear receptors can act as metabolic sensors and clock regulators. Finally, I will discuss how clock modulation and feeding patterns influence the development of obesity