T-helper 1 versus T-helper 2 lymphocyte immunodysregulation is the central factor in genesis of Burkitt lymphoma: hypothesis

<p>Abstract</p> <p>Background</p> <p>The HIV epidemic has challenged our previous understanding of endemic Burkitt's lymphoma. Despite the strong association of Burkitt's lymphoma and HIV infection in the Developed world, and against previous postulations that the cancer is due to immunosupression among African children, the HIV epidemic in the Malaria belt has not been associated with a corresponding increase in incidence of childhood Burkitt's lymphoma. Even outside the context of HIV infection, there is substantial evidence for a strong but skewed immune response towards a TH2 response in genesis of Burkitt lymphoma.</p> <p>Presentation of the hypothesis</p> <p>Rather than a global and/or profound immunosupression, the final common pathway in genesis of Burkitt's lymphoma is the dysregulation of the immune response towards a TH2 response dominated by B-lymphocytes, and the concomitant suppression of the TH1 cell-mediated immune surveillance, driven by various viral/parasitic/bacterial infections.</p> <p>Testing the hypothesis</p> <p>Case control studies comparing TH2 and TH1 immune responses in Burkitt lymphoma of different etiological types (sporadic, HIV-related, endemic and post-transplant) to demonstrate significant dominance of TH2 immune response in presence of poor CMI response as a common factor. Immunological profiling to evaluate differences between immune states that are associated (such as recurrent Malaria infection) and those that are not associated (such as severe protein-energy malnutrition) with Burkitt lymphoma. Prospective cohorts profiling chronology of immunological events leading to Burkitt lymphoma in children with EBV infection.</p> <p>Implications of the hypothesis</p> <p>The dysregulation of the immune response may be the missing link in our understanding of Burkitt lymphomagenesis. This will provide possibilities for determination of risk and for control of development of malignancy in individuals/populations exposed to the relevant infections.</p

Implications of Training in Incremental Theories of Intelligence for Undergraduate Statistics Students

This chapter documents the effects of training in incremental theories of intelligence on students in introductory statistics courses at a liberal arts university in the US. Incremental theories of intelligence examine the beliefs individuals hold of knowledge and how it is attained. An individual with an incremental theory of intelligence believes that intelligence can be developed. The research examined differences by gender in mastery of statistics and attitudes toward statistics for students who received growth mind-set training. A pre-test, post-test design utilised the Students’ Attitudes Toward Statistics© instrument and the Comprehensive Assessment of Outcomes in a first Statistics course. An ANCOVA revealed that females gained more than males on their value of statistics (F(1, 63) 9.40, MSE 3.79, p .003, η2 P 0.134) and decreased less for effort expended to learn statistics (F(1, 63) 4.41, MSE 4.07, p .040, η2 P 0.067). Females also gained mastery of statistical concepts at a greater rate (F(1, 63) 5.30, MSE 0.06, p .025, η2 P 0.080) indicating a possible path to alleviate the under-representation of females in STEM

Spatial Guilds in the Serengeti Food Web Revealed by a Bayesian Group Model

Food webs, networks of feeding relationships among organisms, provide fundamental insights into mechanisms that determine ecosystem stability and persistence. Despite long-standing interest in the compartmental structure of food webs, past network analyses of food webs have been constrained by a standard definition of compartments, or modules, that requires many links within compartments and few links between them. Empirical analyses have been further limited by low-resolution data for primary producers. In this paper, we present a Bayesian computational method for identifying group structure in food webs using a flexible definition of a group that can describe both functional roles and standard compartments. The Serengeti ecosystem provides an opportunity to examine structure in a newly compiled food web that includes species-level resolution among plants, allowing us to address whether groups in the food web correspond to tightly-connected compartments or functional groups, and whether network structure reflects spatial or trophic organization, or a combination of the two. We have compiled the major mammalian and plant components of the Serengeti food web from published literature, and we infer its group structure using our method. We find that network structure corresponds to spatially distinct plant groups coupled at higher trophic levels by groups of herbivores, which are in turn coupled by carnivore groups. Thus the group structure of the Serengeti web represents a mixture of trophic guild structure and spatial patterns, in contrast to the standard compartments typically identified in ecological networks. From data consisting only of nodes and links, the group structure that emerges supports recent ideas on spatial coupling and energy channels in ecosystems that have been proposed as important for persistence.Comment: 28 pages, 6 figures (+ 3 supporting), 2 tables (+ 4 supporting

New MR sequences in daily practice: susceptibility weighted imaging. A pictorial essay

Background Susceptibility-weighted imaging (SWI) is a relatively new magnetic resonance (MR) technique that exploits the magnetic susceptibility differences of various tissues, such as blood, iron and calcification, as a new source of contrast enhancement. This pictorial review is aimed at illustrating and discussing its main clinical applications. Methods SWI is based on high-resolution, threedimensional (3D), fully velocity-compensated gradientecho sequences using both magnitude and phase images. A phase mask obtained from the MR phase images is multiplied with magnitude images in order to increase the visualisation of the smaller veins and other sources of susceptibility effects, which are displayed at best after postprocessing of the 3D dataset with the minimal intensity projection (minIP) algorithm. Results SWI is very useful in detecting cerebral microbleeds in ageing and occult low-flow vascular malformations, in characterising brain tumours and degenerative diseases of the brain, and in recognizing calcifications in various pathological conditions. The phase images are especially useful in differentiating between paramagnetic susceptibility effects of blood and diamagnetic effects of calcium. SWI can also be used to evaluate changes in iron content in different neurodegenerative disorders. Conclusion SWI is useful in differentiating and characterising diverse brain disorders

Large introns in relation to alternative splicing and gene evolution: a case study of Drosophila bruno-3

Background: Alternative splicing (AS) of maturing mRNA can generate structurally and functionally distinct transcripts from the same gene. Recent bioinformatic analyses of available genome databases inferred a positive correlation between intron length and AS. To study the interplay between intron length and AS empirically and in more detail, we analyzed the diversity of alternatively spliced transcripts (ASTs) in the Drosophila RNA-binding Bruno-3 (Bru-3) gene. This gene was known to encode thirteen exons separated by introns of diverse sizes, ranging from 71 to 41,973 nucleotides in D. melanogaster. Although Bru-3's structure is expected to be conducive to AS, only two ASTs of this gene were previously described. Results: Cloning of RT-PCR products of the entire ORF from four species representing three diverged Drosophila lineages provided an evolutionary perspective, high sensitivity, and long-range contiguity of splice choices currently unattainable by high-throughput methods. Consequently, we identified three new exons, a new exon fragment and thirty-three previously unknown ASTs of Bru-3. All exon-skipping events in the gene were mapped to the exons surrounded by introns of at least 800 nucleotides, whereas exons split by introns of less than 250 nucleotides were always spliced contiguously in mRNA. Cases of exon loss and creation during Bru-3 evolution in Drosophila were also localized within large introns. Notably, we identified a true de novo exon gain: exon 8 was created along the lineage of the obscura group from intronic sequence between cryptic splice sites conserved among all Drosophila species surveyed. Exon 8 was included in mature mRNA by the species representing all the major branches of the obscura group. To our knowledge, the origin of exon 8 is the first documented case of exonization of intronic sequence outside vertebrates. Conclusion: We found that large introns can promote AS via exon-skipping and exon turnover during evolution likely due to frequent errors in their removal from maturing mRNA. Large introns could be a reservoir of genetic diversity, because they have a greater number of mutable sites than short introns. Taken together, gene structure can constrain and/or promote gene evolution

Relaxin: Review of Biology and Potential Role in Treating Heart Failure

Relaxin is a naturally occurring human peptide initially identified as a reproductive hormone. More recently, relaxin has been shown to play a key role in the maternal hemodynamic and renal adjustments that accommodate pregnancy. An understanding of these physiologic effects has led to the evaluation of relaxin as a pharmacologic agent for the treatment of patients with acute heart failure. Preliminary results have been encouraging. In addition, the other known biologic properties of relaxin, including anti-inflammatory effects, extracellular matrix remodeling effects, and angiogenic and anti-ischemic effects, all may play a role in potential benefits of relaxin therapy. Ongoing, large-scale clinical testing will provide additional insights into the potential role of relaxin in the treatment of heart failure

Neural Correlates of Threat Perception: Neural Equivalence of Conspecific and Heterospecific Mobbing Calls Is Learned

Songbird auditory areas (i.e., CMM and NCM) are preferentially activated to playback of conspecific vocalizations relative to heterospecific and arbitrary noise [1]–[2]. Here, we asked if the neural response to auditory stimulation is not simply preferential for conspecific vocalizations but also for the information conveyed by the vocalization. Black-capped chickadees use their chick-a-dee mobbing call to recruit conspecifics and other avian species to mob perched predators [3]. Mobbing calls produced in response to smaller, higher-threat predators contain more “D” notes compared to those produced in response to larger, lower-threat predators and thus convey the degree of threat of predators [4]. We specifically asked whether the neural response varies with the degree of threat conveyed by the mobbing calls of chickadees and whether the neural response is the same for actual predator calls that correspond to the degree of threat of the chickadee mobbing calls. Our results demonstrate that, as degree of threat increases in conspecific chickadee mobbing calls, there is a corresponding increase in immediate early gene (IEG) expression in telencephalic auditory areas. We also demonstrate that as the degree of threat increases for the heterospecific predator, there is a corresponding increase in IEG expression in the auditory areas. Furthermore, there was no significant difference in the amount IEG expression between conspecific mobbing calls or heterospecific predator calls that were the same degree of threat. In a second experiment, using hand-reared chickadees without predator experience, we found more IEG expression in response to mobbing calls than corresponding predator calls, indicating that degree of threat is learned. Our results demonstrate that degree of threat corresponds to neural activity in the auditory areas and that threat can be conveyed by different species signals and that these signals must be learned

The Influence of Personality Traits on Reported Adherence to Medication in Individuals with Chronic Disease: An Epidemiological Study in West Sweden

BACKGROUND: Limited research exists exploring the influence of personality on adherence behaviour. Since non-adherence is a major obstacle in treating prevalent chronic diseases the aim was to determine whether personality traits are related to reported adherence to medication in individuals with chronic disease. METHODOLOGY/PRINCIPAL FINDINGS: Individuals with chronic disease (n = 749) were identified in a random population sample of 5000 inhabitants aged 30-70 in two municipalities in West Sweden. Data on five personality traits, Neuroticism, Extraversion, Openness to experiences, Agreeableness, and Conscientiousness, and medication adherence behaviour was collected by questionnaires. Statistical analyses resulted in a negative relationship between Neuroticism and medication adherence (P < 0.001), while both Agreeableness (P < 0.001) and Conscientiousness (P < 0.001) were positively related to adherence. At high levels of Conscientiousness, low adherence was related to higher scores in Neuroticism. At high levels of Agreeableness, low adherence was related to low scores in Conscientiousness and high scores in Openness to experiences. CONCLUSIONS: This study demonstrated that multiple personality traits are of significant importance for adherence behaviour in individuals with chronic disease. The findings suggest that several personality traits may interact in influencing adherence behaviour. Personality traits could putatively be used to focus efforts to educate and support patients with high risk of low medical adherence