Circulating microRNA 122 in the methionine and choline‐deficient mouse model of non‐alcoholic steatohepatitis

Non‐alcoholic steatohepatitis (NASH) is a progressive form of non‐alcoholic fatty liver disease (NAFLD) and is a major cause of liver cirrhosis and hepatic failure. The methionine choline‐deficient diet (MCD) is a frequently used hepatotoxicity animal model of NASH that induces hepatic transaminase (ALT, AST) elevations and hepatobiliary histological changes similar to those observed in human NASH. Liver‐specific microRNA‐122 (miR‐122) has been shown as a key regulator of cholesterol and fatty acid metabolism in adult liver, and has recently been proposed as a sensitive and specific circulating biomarker of hepatic injury. The purpose of this study was to assess miR‐122 serum levels in mice receiving an MCD diet for 0, 3, 7, 14, 28 and 56 days and compare the performance vs. routine clinical chemistry when benchmarked against the histopathological liver findings. MiR‐122 levels were quantified in serum using RT‐qPCR. Both miR‐122 and ALT/AST levels were significantly elevated in serum at all timepoints. MiR‐122 levels increased on average by 40‐fold after 3 days of initiating the MCD diet, whereas ALT and AST changes were 4.8‐ and 3.3‐fold, respectively. In general, miR‐122 levels remained elevated across all time points, whereas the ALT/AST increases were less robust but correlated with the progressive severity of NASH as assessed by histopathology. In conclusion, serum levels of miR‐122 can potentially be used as a sensitive biomarker for the early detection of hepatotoxicity and can aid in monitoring the extent of NAFLD‐associated liver injury in mouse efficacy models. Copyright © 2013 John Wiley & Sons, Ltd.     

Molecular Investigation of Canine Parvovirus-2 (CPV-2) Outbreak in Nevis Island: Analysis of the Nearly Complete Genomes of CPV-2 Strains from the Caribbean Region

To date, there is a dearth of information on canine parvovirus-2 (CPV-2) from the Caribbean region. During August–October 2020, the veterinary clinic on the Caribbean island of Nevis reported 64 household dogs with CPV-2-like clinical signs (hemorrhagic/non-hemorrhagic diarrhea and vomiting), of which 27 animals died. Rectal swabs/fecal samples were obtained from 43 dogs. A total of 39 of the 43 dogs tested positive for CPV-2 antigen and/or DNA, while 4 samples, negative for CPV-2 antigen, were not available for PCR. Among the 21 untested dogs, 15 had CPV-2 positive littermates. Analysis of the complete VP2 sequences of 32 strains identified new CPV-2a (CPV-2a with Ser297Ala in VP2) as the predominant CPV-2 on Nevis Island. Two nonsynonymous mutations, one rare (Asp373Asn) and the other uncommon (Ala262Thr), were observed in a few VP2 sequences. It was intriguing that new CPV-2a was associated with an outbreak of gastroenteritis on Nevis while found at low frequencies in sporadic cases of diarrhea on the neighboring island of St. Kitts. The nearly complete CPV-2 genomes (4 CPV-2 strains from St. Kitts and Nevis (SKN)) were reported for the first time from the Caribbean region. Eleven substitutions were found among the SKN genomes, which included nine synonymous substitutions, five of which have been rarely reported, and the two nonsynonymous substitutions. Phylogenetically, the SKN CPV-2 sequences formed a distinct cluster, with CPV-2b/USA/1998 strains constituting the nearest cluster. Our findings suggested that new CPV-2a is endemic in the region, with the potential to cause severe outbreaks, warranting further studies across the Caribbean Islands. Analysis of the SKN CPV-2 genomes corroborated the hypothesis that recurrent parallel evolution and reversion might play important roles in the evolution of CPV-2.     

Artificial selection for structural color on butterfly wings and comparison with natural evolution

Brilliant animal colors often are produced from light interacting with intricate nano-morphologies present in biological materials such as butterfly wing scales. Surveys across widely divergent butterfly species have identified multiple mechanisms of structural color production; however, little is known about how these colors evolved. Here, we examine how closely related species and populations of Bicyclus butterflies have evolved violet structural color from brown-pigmented ancestors with UV structural color. We used artificial selection on a laboratory model butterfly, B. anynana, to evolve violet scales from UV brown scales and compared the mechanism of violet color production with that of two other Bicyclus species, Bicyclus sambulos and Bicyclus medontias, which have evolved violet/blue scales independently via natural selection. The UV reflectance peak of B. anynana brown scales shifted to violet over six generations of artificial selection (i.e., in less than 1 y) as the result of an increase in the thickness of the lower lamina in ground scales. Similar scale structures and the same mechanism for producing violet/blue structural colors were found in the other Bicyclus species. This work shows that populations harbor large amounts of standing genetic variation that can lead to rapid evolution of scales’ structural color via slight modifications to the scales’ physical dimensions.Organisms produce colors in two basic ways: by synthesizing pigments that selectively absorb light of certain spectral bands so that only light outside the absorption bands is backscattered (chemical color) or by developing nanomorphologies that enhance the reflection of light of certain wavelengths by interference (physical color or structural color). Structural colors play major roles in natural and sexual selection in many species (1) and have a broad range of applications in color display, paint, cosmetics, and textile industries (2). Structural color surveys across widely divergent species have revealed a large diversity of color-producing mechanisms (3–9). However, there has been a lack of systematic study and comparison of how different colors from closely related species or within populations of a single species evolve, even though these colors can vary dramatically. By examining how these species/populations evolve different colors, it is possible to identify the minimal amount of morphological change that results in significant color variation. Furthermore, this research may serve as an inspiration for future application of similar evolutionary principles to the design of photonic devices for color tuning, light trapping, or beam steering (2, 10–20). From an evolutionary biology point of view, we are curious to examine how structural colors respond to selection pressure and whether there is sufficient standing genetic variation in natural populations to allow the rapid evolution of novel colors. Here we focus on determining the morphological changes and the physical mechanisms that cause the evolution of violet structural color in populations of a single species and also across different species within a single genus of butterflies.We focus on the genus Bicyclus (Lepidoptera: Nymphalidae), composed of more than 80 species that predominantly exhibit brown color along with marginal eyespots. Some Bicyclus species, however, have independently evolved transverse bands of bright violet/blue structural color on the dorsal surface of the forewings (black asterisks in Fig. 1A) (21, 22). One species, Bicyclus anynana, has become a model species amenable to laboratory rearing, and multiple aspects of its marginal eyespots (size, relative width of the color rings, shape) have been altered by artificial selection (23–27). However, change of color (hue), either pigmentary or structural, via artificial selection has not been reported. B. anynana does not exhibit bright violet coloration on its wings and therefore provides an excellent opportunity for investigating whether there is genetic potential to produce violet color upon directed selection. We investigated this potential by performing an artificial selection experiment in B. anynana that targeted the color of the specific dorsal wing region that evolved violet/blue coloration in other members of the genus (Fig. 1 B–G).Open in a separate windowFig. 1.Structural color in Bicyclus butterflies and basic wing scale morphology. (A) A phylogenetic estimate of Bicyclus butterfly relationships (modified from ref. 41) illustrating the evolution of color in the genus. The black asterisks mark two clades that evolved violet/blue color independently, represented here by B. sambulos and B. medontias. (B–D) Dorsal wing images of B. sambulos, B. anynana (the region used for artificial selection is marked by white asterisk), and B. medontias. (E–G) Graphs of reflectance spectra of the blue/violet wing band showing reflectance peaks in the 400–450 nm range and in the brown-colored homologous region in B. anynana with a UV reflectance peak centered at 300 nm (colored arrows). (H) 3D illustration of the wing and scales in the selected wing area of B. anynana. (I) Magnified view of the ripped region in H showing how cover (c; brown) and ground (g; green) scales are attached to the wing membrane (m, pink) and alternate along rows. Scales on the other (ventral) side of the wing membrane are visible also. (J) Cross-sectional view of a single scale showing the trabeculae (T) connecting the lower lamina (LL) to the upper lamina that includes ridges (R), microribs (Mr), and crossribs (Cr). Windows (W) are the spaces between the ridges and crossribs. Cover and ground scales have the same basic morphology. [llustrations in H–J courtesy of Katerina Evangelou (Central Saint Martin’s College, London).]B. anynana, like other butterflies, has two types of scales, cover and ground, which alternate within a row with cover scales partially covering the ground scales and the point where both scales attach to the wing membrane (Fig. 1 H and I and Fig. S1) (28). Both cover and ground scales contain a lower lamina with a continuous smooth surface below a region composed of longitudinal ridges and crossribs, collectively referred to as the “upper lamina” and connected to the lower lamina via pillars called “trabeculae” (Fig. 1J and Fig. S1) (6). Previous studies on butterflies showed that structural color can be produced by interference with light reflected from the overlapping lamella that build the longitudinal ridges, from microribs protruding from the sides of the longitudinal ridges, or from the lower lamina, which can vary in thickness and patterning (Fig. 1J) (29, 30). However, it is not clear how the violet/blue color is produced in members of the two Bicyclus clades that separately evolved this color, whether B. anynana can be made to evolve the same violet/blue color via artificial selection, and whether it will generate the color in the same way as the other species. To answer these questions, we conducted detailed optical characterization and structural analysis of butterfly wing scales from three separate species and artificially evolved populations of Bicyclus to illustrate how color is generated and how it has evolved.     

IL-7 induces sCD127 release and mCD127 downregulation in human CD8+ T cells by distinct yet overlapping mechanisms,both of which are impaired in HIV infection

The IL-7 receptor specific α chain, CD127, can be expressed both as a membrane-associated (mCD127) and a soluble form (sCD127), however, the mechanisms involved in their regulation remain to be defined. We first demonstrated in primary human CD8⁺ T cells that IL-7-induced downregulation of mCD127 expression is dependent on JAK and PI3K signaling, whereas IL-7-induced sCD127 release is also mediated by STAT5. Following stimulation with IL-7, expression of alternatively spliced variants of the CD127 gene, sCD127 mRNA, is reduced, but to a lesser degree than the full-length gene. Evaluation of the role of proteases revealed that MMP-9 was involved in sCD127 release, without affecting the expression of mCD127, suggesting it does not induce direct shedding from the cell surface. Since defects in the IL-7/CD127 pathway occur in various diseases, including HIV, we evaluated CD8⁺ T cells derived from HAART-treated HIV-infected individuals and found that IL-7-induced (1) downregulation of mCD127, (2) release of sCD127, and (3) expression of the sCD127 mRNA were all impaired. Expression of mCD127 and sCD127 is, therefore, regulated by distinct, but overlapping, mechanisms and their impairment in HIV infection contributes to our understanding of the CD8⁺ T cell dysfunction that persists despite effective antiretroviral therapy.     

Occupational Therapy Interventions and Outcomes Measured in Residential Care: A Scoping Review

Abstract

Aims: This scoping review identified the interventions and outcome measures used by occupational therapists working with older adults in residential care facilities.

Methods: A five-step approach was used to retrieve and screen studies from five databases. Included studies described an occupational therapy intervention with older adults living in residential care facilities, were published in English, between 1990 and 2019 in a peer-reviewed publication. Data were mapped using domains of the Canadian Model of Occupational Performance and Engagement.

Results: Findings from 51 studies revealed that occupational therapists most commonly implemented occupations as the intervention with little focus on aspects of the environment. Outcomes predominantly measured person factors and less commonly occupational performance and engagement.

Conclusion: The exploration of the past foci of practice and measurement of therapeutic impact enables occupational therapists to consider how their practice can enhance future occupational performance and engagement of residential care facility residents.     

Coinfection of Fusobacterium nucleatum and Actinomyces israelii in Mastoiditis Diagnosed by Next-Generation DNA Sequencing

Some bacterial infections involve potentially complex mixtures of species that can now be distinguished using next-generation DNA sequencing. We present a case of mastoiditis where Gram stain, culture, and molecular diagnosis were nondiagnostic or discrepant. Next-generation sequencing implicated coinfection of Fusobacterium nucleatum and Actinomyces israelii, resolving these diagnostic discrepancies.