The molecular basis of color vision in colorful fish: Four Long Wave-Sensitive (LWS) opsins in guppies (Poecilia reticulata) are defined by amino acid substitutions at key functional sites

<p>Abstract</p> <p>Background</p> <p>Comparisons of functionally important changes at the molecular level in model systems have identified key adaptations driving isolation and speciation. In cichlids, for example, long wavelength-sensitive (LWS) opsins appear to play a role in mate choice and male color variation within and among species. To test the hypothesis that the evolution of elaborate coloration in male guppies (<it>Poecilia reticulata</it>) is also associated with opsin gene diversity, we sequenced long wavelength-sensitive (LWS) opsin genes in six species of the family Poeciliidae.</p> <p>Results</p> <p>Sequences of four LWS opsin genes were amplified from the guppy genome and from mRNA isolated from adult guppy eyes. Variation in expression was quantified using qPCR. Three of the four genes encode opsins predicted to be most sensitive to different wavelengths of light because they vary at key amino acid positions. This family of LWS opsin genes was produced by a diversity of duplication events. One, an intronless gene, was produced prior to the divergence of families Fundulidae and Poeciliidae. Between-gene PCR and DNA sequencing show that two of the guppy LWS opsins are linked in an inverted orientation. This inverted tandem duplication event occurred near the base of the poeciliid tree in the common ancestor of <it>Poecilia </it>and <it>Xiphophorus</it>. The fourth sequence has been uncovered only in the genus <it>Poecilia</it>. In the guppies surveyed here, this sequence is a hybrid, with the 5' end most similar to one of the tandem duplicates and the 3' end identical to the other.</p> <p>Conclusion</p> <p>Enhanced wavelength discrimination, a possible consequence of opsin gene duplication and divergence, might have been an evolutionary prerequisite for color-based sexual selection and have led to the extraordinary coloration now observed in male guppies and in many other poeciliids.</p

Voting power measurement: a story of misreinvention

In this account of the history of voting-power measurement, we confine ourselves to the concept of a priori voting power. We show how the concept was re-invented several times and how the circumstances in which it was reinvented led to conceptual confusion as to the true meaning of what is being measured. In particular, power-as-influence was conflated with value in the sense of transferable utility cooperative game theory (power as share in constant total payoff). Influence was treated, improperly, as though it were transferable utility, and hence an additive and distributive quantity. We provide examples of the resulting misunderstanding and mis-directed criticism

Uncovering treatment burden as a key concept for stroke care: a systematic review of qualitative research

&lt;b&gt;Background&lt;/b&gt; Patients with chronic disease may experience complicated management plans requiring significant personal investment. This has been termed ‘treatment burden’ and has been associated with unfavourable outcomes. The aim of this systematic review is to examine the qualitative literature on treatment burden in stroke from the patient perspective.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods and findings&lt;/b&gt; The search strategy centred on: stroke, treatment burden, patient experience, and qualitative methods. We searched: Scopus, CINAHL, Embase, Medline, and PsycINFO. We tracked references, footnotes, and citations. Restrictions included: English language, date of publication January 2000 until February 2013. Two reviewers independently carried out the following: paper screening, data extraction, and data analysis. Data were analysed using framework synthesis, as informed by Normalization Process Theory. Sixty-nine papers were included. Treatment burden includes: (1) making sense of stroke management and planning care, (2) interacting with others, (3) enacting management strategies, and (4) reflecting on management. Health care is fragmented, with poor communication between patient and health care providers. Patients report inadequate information provision. Inpatient care is unsatisfactory, with a perceived lack of empathy from professionals and a shortage of stimulating activities on the ward. Discharge services are poorly coordinated, and accessing health and social care in the community is difficult. The study has potential limitations because it was restricted to studies published in English only and data from low-income countries were scarce.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; Stroke management is extremely demanding for patients, and treatment burden is influenced by micro and macro organisation of health services. Knowledge deficits mean patients are ill equipped to organise their care and develop coping strategies, making adherence less likely. There is a need to transform the approach to care provision so that services are configured to prioritise patient needs rather than those of health care systems

Toward a theory‐based specification of non‐pharmacological treatments in aging and dementia: Focused reviews and methodological recommendations

INTRODUCTION: Non-pharmacological treatments (NPTs) have the potential to improve meaningful outcomes for older people at risk of, or living with dementia, but research often lacks methodological rigor and continues to produce mixed results. METHODS: In the current position paper, experts in NPT research have specified treatment targets, aims, and ingredients using an umbrella framework, the Rehabilitation Treatment Specification System. RESULTS: Experts provided a snapshot and an authoritative summary of the evidence for different NPTs based on the best synthesis efforts, identified main gaps in knowledge and relevant barriers, and provided directions for future research. Experts in trial methodology provide best practice principles and recommendations for those working in this area, underscoring the importance of prespecified protocols. DISCUSSION: We conclude that the evidence strongly supports various NPTs in relation to their primary targets, and discuss opportunities and challenges associated with a unifying theoretical framework to guide future efforts in this area

In Vitro Evolution of Allergy Vaccine Candidates, with Maintained Structure, but Reduced B Cell and T Cell Activation Capacity

Allergy and asthma to cat (Felis domesticus) affects about 10% of the population in affluent countries. Immediate allergic symptoms are primarily mediated via IgE antibodies binding to B cell epitopes, whereas late phase inflammatory reactions are mediated via activated T cell recognition of allergen-specific T cell epitopes. Allergen-specific immunotherapy relieves symptoms and is the only treatment inducing a long-lasting protection by induction of protective immune responses. The aim of this study was to produce an allergy vaccine designed with the combined features of attenuated T cell activation, reduced anaphylactic properties, retained molecular integrity and induction of efficient IgE blocking IgG antibodies for safer and efficacious treatment of patients with allergy and asthma to cat. The template gene coding for rFel d 1 was used to introduce random mutations, which was subsequently expressed in large phage libraries. Despite accumulated mutations by up to 7 rounds of iterative error-prone PCR and biopanning, surface topology and structure was essentially maintained using IgE-antibodies from cat allergic patients for phage enrichment. Four candidates were isolated, displaying similar or lower IgE binding, reduced anaphylactic activity as measured by their capacity to induce basophil degranulation and, importantly, a significantly lower T cell reactivity in lymphoproliferative assays compared to the original rFel d 1. In addition, all mutants showed ability to induce blocking antibodies in immunized mice.The approach presented here provides a straightforward procedure to generate a novel type of allergy vaccines for safer and efficacious treatment of allergic patients

Molecular Dynamics Simulations Suggest that Electrostatic Funnel Directs Binding of Tamiflu to Influenza N1 Neuraminidases

Oseltamivir (Tamiflu) is currently the frontline antiviral drug employed to fight the flu virus in infected individuals by inhibiting neuraminidase, a flu protein responsible for the release of newly synthesized virions. However, oseltamivir resistance has become a critical problem due to rapid mutation of the flu virus. Unfortunately, how mutations actually confer drug resistance is not well understood. In this study, we employ molecular dynamics (MD) and steered molecular dynamics (SMD) simulations, as well as graphics processing unit (GPU)-accelerated electrostatic mapping, to uncover the mechanism behind point mutation induced oseltamivir-resistance in both H5N1 “avian” and H1N1pdm “swine” flu N1-subtype neuraminidases. The simulations reveal an electrostatic binding funnel that plays a key role in directing oseltamivir into and out of its binding site on N1 neuraminidase. The binding pathway for oseltamivir suggests how mutations disrupt drug binding and how new drugs may circumvent the resistance mechanisms

Effect of a mixed reality-based intervention on arm, hand, and finger function on chronic stroke

[EN] Background: Virtual and mixed reality systems have been suggested to promote motor recovery after stroke. Basing on the existing evidence on motor learning, we have developed a portable and low-cost mixed reality tabletop system that transforms a conventional table in a virtual environment for upper limb rehabilitation. The system allows intensive and customized training of a wide range of arm, hand, and finger movements and enables interaction with tangible objects, while providing audiovisual feedback of the participants' performance in gamified tasks. This study evaluates the clinical effectiveness and the acceptance of an experimental intervention with the system in chronic stroke survivors. Methods: Thirty individuals with stroke were included in a reversal (A-B-A) study. Phase A consisted of 30 sessions of conventional physical therapy. Phase B consisted of 30 training sessions with the experimental system. Both interventions involved flexion and extension of the elbow, wrist, and fingers, and grasping of different objects. Sessions were 45-min long and were administered three to five days a week. The body structures (Modified Ashworth Scale), functions (Motricity Index, Fugl-Meyer Assessment Scale), activities (Manual Function Test, Wolf Motor Function Test, Box and Blocks Test, Nine Hole Peg Test), and participation (Motor Activity Log) were assessed before and after each phase. Acceptance of the system was also assessed after phase B (System Usability Scale, Intrinsic Motivation Inventory). Results: Significant improvement was detected after the intervention with the system in the activity, both in arm function measured by the Wolf Motor Function Test (p < 0.01) and finger dexterity measured by the Box and Blocks Test (p < 0.01) and the Nine Hole Peg Test (p < 0.01); and participation (p < 0.01), which was maintained to the end of the study. The experimental system was reported as highly usable, enjoyable, and motivating. Conclusions: Our results support the clinical effectiveness of mixed reality interventions that satisfy the motor learning principles for upper limb rehabilitation in chronic stroke survivors. This characteristic, together with the low cost of the system, its portability, and its acceptance could promote the integration of these systems in the clinical practice as an alternative to more expensive systems, such as robotic instruments.The authors wish to thank the staff and patients of the Servicio de Neurorrehabilitación y Daño Cerebral de los Hospitales NISA for their involvement in the study. The authors also wish to thank the staff of LabHuman for their support in this project, especially Francisco Toledo and José Roda for their assistance. 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Functional significance of the hemadsorption activity of influenza virus neuraminidase and its alteration in pandemic viruses

Human influenza viruses derive their genes from avian viruses. The neuraminidase (NA) of the avian viruses has, in addition to the catalytic site, a separate sialic acid binding site (hemadsorption site) that is not present in human viruses. The biological significance of the NA hemadsorption activity in avian influenza viruses remained elusive. A sequence database analysis revealed that the NAs of the majority of human H2N2 viruses isolated during the influenza pandemic of 1957 differ from their putative avian precursor by amino acid substitutions in the hemadsorption site. We found that the NA of a representative pandemic virus A/Singapore/1/57 (H2N2) lacks hemadsorption activity and that a single reversion to the avian-virus-like sequence (N367S) restores hemadsorption. Using this hemadsorption-positive NA, we generated three NA variants with substitutions S370L, N400S and W403R that have been found in the hemadsorption site of human H2N2 viruses. Each substitution abolished hemadsorption activity. Although, there was no correlation between hemadsorption activity of the NA variants and their enzymatic activity with respect to monovalent substrates, all four hemadsorption-negative NAs desialylated macromolecular substrates significantly slower than did the hemadsorption-positive counterpart. The NA of the 1918 pandemic virus A/Brevig Mission/1/18 (H1N1) also differed from avian N1 NAs by reduced hemadsorption activity and less efficient hydrolysis of macromolecular substrates. Our data indicate that the hemadsorption site serves to enhance the catalytic efficiency of NA and they suggest that, in addition to changes in the receptor-binding specificity of the hemagglutinin, alterations of the NA are needed for the emergence of pandemic influenza viruses

Long Distance Movements and Disjunct Spatial Use of Harbor Seals (Phoca vitulina) in the Inland Waters of the Pacific Northwest

BACKGROUND: Worldwide, adult harbor seals (Phoca vitulina) typically limit their movements and activity to <50 km from their primary haul-out site. As a result, the ecological impact of harbor seals is viewed as limited to relatively small spatial scales. Harbor seals in the Pacific Northwest are believed to remain <30 km from their primary haul-out site, one of several contributing factors to the current stock designation. However, movement patterns within the region are not well understood because previous studies have used radio-telemetry, which has range limitations. Our objective was to use satellite-telemetry to determine the regional spatial scale of movements. METHODOLOGY/PRINCIPAL FINDINGS: Satellite tags were deployed on 20 adult seals (n=16 males and 4 females) from two rocky reefs and a mudflat-bay during April-May 2007. Standard filtering algorithms were used to remove outliers, resulting in an average (± SD) of 693 (± 377) locations per seal over 110 (± 32) days. A particle filter was implemented to interpolate locations temporally and decrease erroneous locations on land. Minimum over-water distances were calculated between filtered locations and each seal's capture site to show movement of seals over time relative to their capture site, and we estimated utilization distributions from kernel density analysis to reflect spatial use. Eight males moved >100 km from their capture site at least once, two of which traveled round trip to and from the Pacific coast, a total distance >400 km. Disjunct spatial use patterns observed provide new insight into general harbor seal behavior. CONCLUSIONS/SIGNIFICANCE: Long-distance movements and disjunct spatial use of adult harbor seals have not been reported for the study region and are rare worldwide in such a large proportion of tagged individuals. Thus, the ecological influence of individual seals may reach farther than previously assumed