Allometric trajectories of body and head morphology in three sympatric Arctic charr (Salvelinus alpinus (L.)) morphs

A study of body and head development in three sympatric reproductively isolated Arctic charr (Salvelinus alpinus (L.)) morphs from a subarctic lake (Skogsfjordvatn, northern Norway) revealed allometric trajectories that resulted in morphological differences. The three morphs were ecologically assigned to a littoral omnivore, a profundal benthivore and a profundal piscivore, and this was confirmed by genetic analyses (microsatellites). Principal component analysis was used to identify the variables responsible for most of the morphological variation of the body and head shape. The littoral omnivore and the profundal piscivore morph had convergent allometric trajectories for the most important head shape variables, developing bigger mouths and relatively smaller eyes with increasing head size. The two profundal morphs shared common trajectories for the variables explaining most of the body and head shape variation, namely head size relative to body size, placement of the dorsal and pelvic fins, eye size and mouth size. In contrast, the littoral omnivore and the profundal benthivore morphs were not on common allometric trajectories for any of the examined variables. The findings suggest that different selective pressures could have been working on traits related to their trophic niche such as habitat and diet utilization of the three morphs, with the two profundal morphs experiencing almost identical environmental conditions

Heparan Sulfate Binding Can Contribute to the Neurovirulence of Neuroadapted and Nonneuroadapted Sindbis Viruses

Cell culture-adapted laboratory strains of Sindbis virus (SB) exhibit efficient initial attachment to cell surface heparan sulfate (HS) receptors. In contrast, non-cell-adapted strains, such as the SB consensus sequence virus TR339, interact weakly with HS and cell surfaces. Regardless of their HS binding phenotype, most SB strains do not cause fatal disease in adult mice, whether inoculated subcutaneously (s.c.) or intracranially (i.c.). However, laboratory strains of SB can be rendered neurovirulent for adult mice by introduction of a glutamine (Gln)-to-histidine (His) mutation at position 55 of the E2 envelope glycoprotein. In the current work, we have determined that E2 His 55-containing viruses require a second-site mutation (Glu to Lys) at E2 position 70 that confers efficient HS binding in order to exhibit virulence for adult mice and that virulence is correlated with very high infectivity for many cell types. Furthermore, introduction of E2 Lys 70 or certain other HS-binding mutations alone also increased morbidity and/or mortality over that of TR339 for older mice inoculated i.c. However, all viruses containing single HS-binding mutations were attenuated in s.c. inoculated suckling mice in comparison with TR339. These results suggest that HS binding may attenuate viral disease that is dependent on high-titer viremia; however, efficient cell attachment through HS binding can increase virulence, presumably through enhancing the replication of SB within specific host tissues such as the brain

Wandering behaviour prevents inter and intra oceanic speciation in a coastal pelagic fish

Small pelagic fishes have the ability to disperse over long distances and may present complex evolutionary histories. Here, Old World Anchovies (OWA) were used as a model system to understand genetic patterns and connectivity of fish between the Atlantic and Pacific basins. We surveyed 16 locations worldwide using mtDNA and 8 microsatellite loci for genetic parameters, and mtDNA (cyt b; 16S) and nuclear (RAG1; RAG2) regions for dating major lineage-splitting events within Engraulidae family. The OWA genetic divergences (0-0.4%) are compatible with intra-specific divergence, showing evidence of both ancient and contemporary admixture between the Pacific and Atlantic populations, enhanced by high asymmetrical migration from the Pacific to the Atlantic. The estimated divergence between Atlantic and Pacific anchovies (0.67 [0.53-0.80] Ma) matches a severe drop of sea temperature during the Gunz glacial stage of the Pleistocene. Our results support an alternative evolutionary scenario for the OWA, suggesting a coastal migration along south Asia, Middle East and eastern Africa continental platforms, followed by the colonization of the Atlantic via the Cape of the Good Hope.Portuguese Foundation for Science & Technology (FCT) [SFRH/BD/36600/2007]; FCT [UID/MAR/04292/2013, SFRH/BPD/65830/2009]; FCT strategic plan [UID/Multi/04326/2013]info:eu-repo/semantics/publishedVersio

A mixed methods approach to evaluating community drug distributor performance in the control of neglected tropical diseases

BACKGROUND: Trusted literate, or semi-literate, community drug distributors (CDDs) are the primary implementers in integrated preventive chemotherapy (IPC) programmes for Neglected Tropical Disease (NTD) control. The CDDs are responsible for safely distributing drugs and for galvanising communities to repeatedly, often over many years, receive annual treatment, create and update treatment registers, monitor for side-effects and compile treatment coverage reports. These individuals are 'volunteers' for the programmes and do not receive remuneration for their annual work commitment. METHODS: A mixed methods approach, which included pictorial diaries to prospectively record CDD use of time, structured interviews and focus group discussions, was used to triangulate data on how 58 CDDs allocated their time towards their routine family activities and to NTD Programme activities in Uganda. The opportunity costs of CDD time were valued, performance assessed by determining the relationship between time and programme coverage, and CDD motivation for participating in the programme was explored. RESULTS: Key findings showed approximately 2.5 working weeks (range 0.6-11.4 working weeks) were spent on NTD Programme activities per year. The amount of time on NTD control activities significantly increased between the one and three deliveries that were required within an IPC campaign. CDD time spent on NTD Programme activities significantly reduced time available for subsistence and income generating engagements. As CDDs took more time to complete NTD Programme activities, their treatment performance, in terms of validated coverage, significantly decreased. Motivation for the programme was reported as low and CDDs felt undervalued. CONCLUSIONS: CDDs contribute a considerable amount of opportunity cost to the overall economic cost of the NTD Programme in Uganda due to the commitment of their time. Nevertheless, programme coverage of at least 75 %, as required by the World Health Organisation, is not being achieved and vulnerable individuals may not have access to treatment as a consequence of sub-optimal performance by the CDDs due to workload and programmatic factors

Individual and Contextual Factors Associated with Low Childhood Immunisation Coverage in Sub-Saharan Africa: A Multilevel Analysis

Background: In 2010, more than six million children in sub-Saharan Africa did not receive the full series of three doses of the diphtheria-tetanus-pertussis vaccine by one year of age. An evidence-based approach to addressing this burden of un-immunised children requires accurate knowledge of the underlying factors. We therefore developed and tested a model of childhood immunisation that includes individual, community and country-level characteristics. Method and Findings: We conducted multilevel logistic regression analysis of Demographic and Health Survey data for 27,094 children aged 12–23 months, nested within 8,546 communities from 24 countries in sub-Saharan Africa. According to the intra-country and intra-community correlation coefficient implied by the estimated intercept component variance, 21% and 32% of the variance in unimmunised children were attributable to country- and community-level factors respectively. Children born to mothers (OR 1.35, 95%CI 1.18 to 1.53) and fathers (OR 1.13, 95%CI 1.12 to 1.40) with no formal education were more likely to be unimmunised than those born to parents with secondary or higher education. Children from the poorest households were 36% more likely to be unimmunised than counterparts from the richest households. Maternal access to media significantly reduced the odds of children being unimmunised (OR 0.94, 95%CI 0.94 to 0.99). Mothers with health seeking behaviours were less likely to have unimmunised children (OR 0.56, 95%CI 0.54 to 0.58). However, children from urban areas (OR 1.12, 95% CI 1.01 to 1.23), communities with high illiteracy rates (OR 1.13, 95% CI 1.05 to 1.23), and countries with high fertility rates (OR 4.43, 95% CI 1.04 to 18.92) were more likely to be unimmunised. Conclusion: We found that individual and contextual factors were associated with childhood immunisation, suggesting that public health programmes designed to improve coverage of childhood immunisation should address people, and the communities and societies in which they live

Scenario-based requirements elicitation for user-centric explainable AI

Explainable Artificial Intelligence (XAI) develops technical explanation methods and enable interpretability for human stakeholders on why Artificial Intelligence (AI) and machine learning (ML) models provide certain predictions. However, the trust of those stakeholders into AI models and explanations is still an issue, especially domain experts, who are knowledgeable about their domain but not AI inner workings. Social and user-centric XAI research states it is essential to understand the stakeholder’s requirements to provide explanations tailored to their needs, and enhance their trust in working with AI models. Scenario-based design and requirements elicitation can help bridge the gap between social and operational aspects of a stakeholder early before the adoption of information systems and identify its real problem and practices generating user requirements. Nevertheless, it is still rarely explored the adoption of scenarios in XAI, especially in the domain of fraud detection to supporting experts who are about to work with AI models. We demonstrate the usage of scenario-based requirements elicitation for XAI in a fraud detection context, and develop scenarios derived with experts in banking fraud. We discuss how those scenarios can be adopted to identify user or expert requirements for appropriate explanations in his daily operations and to make decisions on reviewing fraudulent cases in banking. The generalizability of the scenarios for further adoption is validated through a systematic literature review in domains of XAI and visual analytics for fraud detection

FIB-SEM imaging of carbon nanotubes in mouse lung tissue

Ultrastructural characterisation is important for understanding carbon nanotube (CNT) toxicity and how the CNTs interact with cells and tissues. The standard method for this involves using transmission electron microscopy (TEM). However, in particular, the sample preparation, using a microtome to cut thin sample sections for TEM, can be challenging for investigation of regions with agglomerations of large and stiff CNTs because the CNTs cut with difficulty. As a consequence, the sectioning diamond knife may be damaged and the uncut CNTs are left protruding from the embedded block surface excluding them from TEM analysis. To provide an alternative to ultramicrotomy and subsequent TEM imaging, we studied focused ion beam scanning electron microscopy (FIB-SEM) of CNTs in the lungs of mice, and we evaluated the applicability of the method compared to TEM. FIB-SEM can provide serial section volume imaging not easily obtained with TEM, but it is time-consuming to locate CNTs in the tissue. We demonstrate that protruding CNTs after ultramicrotomy can be used to locate the region of interest, and we present FIB-SEM images of CNTs in lung tissue. FIB-SEM imaging was applied to lung tissue from mice which had been intratracheally instilled with two different multiwalled CNTs; one being short and thin, and the other longer and thicker. FIB-SEM was found to be most suitable for detection of the large CNTs (Ø ca. 70 nm), and to be well suited for studying CNT agglomerates in biological samples which is challenging using standard TEM techniques. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00216-013-7566-x) contains supplementary material, which is available to authorized users

Destructive arthritis in a patient with chikungunya virus infection with persistent specific IgM antibodies

<p>Abstract</p> <p>Background</p> <p>Chikungunya fever is an emerging arboviral disease characterized by an algo-eruptive syndrome, inflammatory polyarthralgias, or tenosynovitis that can last for months to years. Up to now, the pathophysiology of the chronic stage is poorly understood.</p> <p>Case presentation</p> <p>We report the first case of CHIKV infection with chronic associated rheumatism in a patient who developed progressive erosive arthritis with expression of inflammatory mediators and persistence of specific IgM antibodies over 24 months following infection.</p> <p>Conclusions</p> <p>Understanding the specific features of chikungunya virus as well as how the virus interacts with its host are essential for the prevention, treatment or cure of chikungunya disease.</p

Sonic diaspora, vibrations and rhythm: thinking through the sounding of the Jamaican dancehall session

The propagation of vibrations may provide a better way of understanding diasporic spread than the conventional focus on the circulation of products (Hall 1980, Appadurai 1986, 1996, Gilroy 1993a, Brah 1996). Jamaican sound systems operate as a broadcast medium and a source of CDs, DVDs and other commercial products (Henriques 2007a). But the dancehall sound system session also propagates a broad spectrum of frequencies diffused through a range of media and activities - described as “sounding” (following Small’s 1998 concept of “musicking”). These include the material vibrations of the signature low-pitched auditory frequencies of Reggae as a bass culture (Johnson 1980), at the loudness of “sonic dominance” (Henriques 2003). Secondly a session propagates the corporeal vibrations of rituals, dance routines and bass-line “riddims” (Veal 2007). Thirdly it propagates the ethereal vibrations (Henriques 2007b), “vibes” or atmosphere of the sexually charged popular subculture by which the crowd (audience) appreciate each dancehall session as part of the Dancehall scene (Cooper 2004). The paper concludes that thinking though vibrating frequencies makes it easier to appreciate how audiences with no direct or inherited connection with a particular music genre can be energetically infected and affected - to form a sonic diaspora

Modifying Ligand-Induced and Constitutive Signaling of the Human 5-HT4 Receptor

G protein–coupled receptors (GPCRs) signal through a limited number of G-protein pathways and play crucial roles in many biological processes. Studies of their in vivo functions have been hampered by the molecular and functional diversity of GPCRs and the paucity of ligands with specific signaling effects. To better compare the effects of activating different G-protein signaling pathways through ligand-induced or constitutive signaling, we developed a new series of RASSLs (receptors activated solely by synthetic ligands) that activate different G-protein signaling pathways. These RASSLs are based on the human 5-HT4b receptor, a GPCR with high constitutive Gs signaling and strong ligand-induced G-protein activation of the Gs and Gs/q pathways. The first receptor in this series, 5-HT4-D100A or Rs1 (RASSL serotonin 1), is not activated by its endogenous agonist, serotonin, but is selectively activated by the small synthetic molecules GR113808, GR125487, and RO110-0235. All agonists potently induced Gs signaling, but only a few (e.g., zacopride) also induced signaling via the Gq pathway. Zacopride-induced Gq signaling was enhanced by replacing the C-terminus of Rs1 with the C-terminus of the human 5-HT2C receptor. Additional point mutations (D66A and D66N) blocked constitutive Gs signaling and lowered ligand-induced Gq signaling. Replacing the third intracellular loop of Rs1 with that of human 5-HT1A conferred ligand-mediated Gi signaling. This Gi-coupled RASSL, Rs1.3, exhibited no measurable signaling to the Gs or Gq pathway. These findings show that the signaling repertoire of Rs1 can be expanded and controlled by receptor engineering and drug selection