Mycobacteriophage-antibiotic therapy promotes enhanced clearance of drug-resistant Mycobacterium abscessus.

Infection by multidrug-resistant Mycobacterium abscessus is increasingly prevalent in cystic fibrosis (CF) patients, leaving clinicians with few therapeutic options. A compassionate study showed the clinical improvement of a CF patient with a disseminated M. abscessus (GD01) infection, following injection of a phage cocktail, including phage Muddy. Broadening the use of phage therapy in patients as a potential antibacterial alternative necessitates the development of biological models to improve the reliability and successful prediction of phage therapy in the clinic. Herein, we demonstrate that Muddy very efficiently lyses GD01 in vitro, an effect substantially increased with standard drugs. Remarkably, this cooperative activity was retained in an M. abscessus model of infection in CFTR-depleted zebrafish, associated with a striking increase in larval survival and reduction in pathological signs. The activity of Muddy was lost in macrophage-ablated larvae, suggesting that successful phage therapy relies on functional innate immunity. CFTR-depleted zebrafish represent a practical model to rapidly assess phage treatment efficacy against M. abscessus isolates, allowing the identification of drug combinations accompanying phage therapy and treatment prediction in patients. This article has an associated First Person interview with the first author of the paper

African mountain thistles: generic delimitation problems analyzed with NGS

Póster presentado en el III Simposio Anual de Botánica Española celebrado en el Institut Botànic de Barcelona, 25-26 de noviembre de 202

ManneqKit Cards:A Kinesthetic Empathic Design Tool Communicating Depression Experiences

While depression is a mood disorder with significant societal impact, the experiences of people living with depression are yet not easy to access. HCI’s tenet to understand users, particularly addressed by the empathic design approach, has prioritized verbal communication of such experiences. We introduce ManneqKit, a kinesthetic empathic design tool consisting of 15 cards with bodily postures and vignettes leveraging the nonverbal aspects of depression experiences. We report ManneqKit’s co-design with 10 therapists, its piloting with 4 therapists and 10 non-therapists, and evaluation through design workshops with 9 interaction designers. Findings indicate cards’ ability to elicit non-therapists’ increased empathy, and richer emotional depictions when compared to text-based description of depression symptoms. We discuss the value of these findings for interaction design in supporting richer understanding of vulnerable users experiencing depression, for more sensitive conceptual designs in the ideation stage, and more nuanced ethical values underpinning the overall design process

Increasing phylogenetic stochasticity at high elevations on summits across a remote North American wilderness

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/1/ajb21328-sup-0002-AppendixS2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/2/ajb21328-sup-0003-AppendixS3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/3/ajb21328-sup-0004-AppendixS4.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/4/ajb21328.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/5/ajb21328-sup-0009-AppendixS9.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/6/ajb21328-sup-0005-AppendixS5.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/7/ajb21328-sup-0007-AppendixS7.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/8/ajb21328-sup-0006-AppendixS6.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/9/ajb21328-sup-0008-AppendixS8.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/10/ajb21328_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150529/11/ajb21328-sup-0001-AppendixS1.pd

The impact of Southern Ocean topographic barriers on the ocean circulation and the overlying atmosphere

Southern Ocean bathymetry constrains the path of the Antarctic Circumpolar Current (ACC), but the bathymetric influence on the coupled ocean–atmosphere system is poorly understood. Here, we investigate this impact by respectively flattening large topographic barriers around the Kerguelen Plateau, Campbell Plateau, Mid-Atlantic Ridge, and Drake Passage in four simulations in a coupled climate model. The barriers impact both the wind and buoyancy forcing of the ACC transport, which increases by between 4% and 14% when barriers are removed individually and by 56% when all barriers are removed simultaneously. The removal of Kerguelen Plateau bathymetry increases convection south of the plateau and the removal of Drake Passage bathymetry reduces convection upstream in the Ross Sea. When the barriers are removed, zonal flattening of the currents leads to sea surface temperature (SST) anomalies that strongly correlate to precipitation anomalies, with correlation coefficients ranging between r = 0.92 and r = 0.97 in the four experiments. The SST anomalies correlate to the surface winds too in some locations. However, they also generate circumpolar waves of sea level pressure (SLP) anomalies, which induce remote wind speed changes that are unconnected to the underlying SST field. The meridional variability in the wind stress curl contours over the Mid-Atlantic Ridge, the Kerguelen Plateau, and the Campbell Plateau disappears when these barriers are removed, confirming the impact of bathymetry on surface winds. However, bathymetry-induced wind changes are too small to affect the overall wave-3 asymmetry in the Southern Hemisphere westerlies. Removal of Southern Hemisphere orography is also inconsequential to the wave-3 pattern

Pitch perception and production in congenital amusia: evidence from Cantonese speakers

This study investigated pitch perception and production in speech and music in individuals with congenital amusia (a disorder of musical pitch processing) who are native speakers of Cantonese, a tone language with a highly complex tonal system. Sixteen Cantonese-speaking congenital amusics and 16 controls performed a set of lexical tone perception, production, singing, and psychophysical pitch threshold tasks. Their tone production accuracy and singing proficiency were subsequently judged by independent listeners, and subjected to acoustic analyses. Relative to controls, amusics showed impaired discrimination of lexical tones in both speech and non-speech conditions. They also received lower ratings for singing proficiency, producing larger pitch interval deviations and making more pitch interval errors compared to controls. Demonstrating higher pitch direction identification thresholds than controls for both speech syllables and piano tones, amusics nevertheless produced native lexical tones with comparable pitch heights/contours and intelligibility as controls. Significant correlations were found between pitch threshold and lexical tone perception, music perception and production, but not between lexical tone perception and production for amusics. These findings provide further evidence that congenital amusia is domain-general language-independent pitch-processing deficit that is associated with severely impaired music perception and production, mildly impaired speech perception, and largely intact speech production

Trackly:A Customisable and Pictorial Self-Tracking App to Support Agency in Multiple Sclerosis Self-Care

Self-tracking is an important part of self-care. However, predefined self-tracking approaches can impede people's agency in managing their health. We investigated a customisable and pictorial self-tracking approach in multiple sclerosis self-management by implementing and conducting a field study of Trackly: a prototype app that supports people in defining and colouring pictorial trackers, such as body shapes. We found that participants utilised the elements of Trackly designed to support agentive behaviour: they defined personally meaningful tracking parameters in their own words, and particularly valued being able to flexibly colour in and make sense of their pictorial trackers. Having been able to support their individual self-care intentions with Trackly, participants reported a spectrum of interrelated experiences of agency, including a sense of ownership, identity, self-awareness, mindfulness, and control. Our findings demonstrate the importance of supporting people's individual needs and creative capacities to foster mindful and personally meaningful engagement with health and wellbeing data

Colloquium: Mechanical formalisms for tissue dynamics

The understanding of morphogenesis in living organisms has been renewed by tremendous progressin experimental techniques that provide access to cell-scale, quantitative information both on theshapes of cells within tissues and on the genes being expressed. This information suggests that ourunderstanding of the respective contributions of gene expression and mechanics, and of their crucialentanglement, will soon leap forward. Biomechanics increasingly benefits from models, which assistthe design and interpretation of experiments, point out the main ingredients and assumptions, andultimately lead to predictions. The newly accessible local information thus calls for a reflectionon how to select suitable classes of mechanical models. We review both mechanical ingredientssuggested by the current knowledge of tissue behaviour, and modelling methods that can helpgenerate a rheological diagram or a constitutive equation. We distinguish cell scale ("intra-cell")and tissue scale ("inter-cell") contributions. We recall the mathematical framework developpedfor continuum materials and explain how to transform a constitutive equation into a set of partialdifferential equations amenable to numerical resolution. We show that when plastic behaviour isrelevant, the dissipation function formalism appears appropriate to generate constitutive equations;its variational nature facilitates numerical implementation, and we discuss adaptations needed in thecase of large deformations. The present article gathers theoretical methods that can readily enhancethe significance of the data to be extracted from recent or future high throughput biomechanicalexperiments.Comment: 33 pages, 20 figures. This version (26 Sept. 2015) contains a few corrections to the published version, all in Appendix D.2 devoted to large deformation

Repeatedly Northwards and Upwards: Southern African Grasslands Fuel the Colonization of the African Sky Islands in Helichrysum (Compositae)

The Afromontane and Afroalpine areas constitute some of the main biodiversity hotspots of Africa. They are particularly rich in plant endemics, but the biogeographic origins and evolutionary processes leading to this outstanding diversity are poorly understood. We performed phylogenomic and biogeographic analyses of one of the most species-rich plant genera in these mountains, Helichrysum (Compositae-Gnaphalieae). Most previous studies have focused on Afroalpine elements of Eurasian origin, and the southern African origin of Helichrysum provides an interesting counterexample. We obtained a comprehensive nuclear dataset from 304 species (≈50% of the genus) using target-enrichment with the Compositae1061 probe set. Summary-coalescent and concatenation approaches combined with paralog recovery yielded congruent, well-resolved phylogenies. Ancestral range estimations revealed that Helichrysum originated in arid southern Africa, whereas the southern African grasslands were the source of most lineages that dispersed within and outside Africa. Colonization of the tropical Afromontane and Afroalpine areas occurred repeatedly throughout the Miocene-Pliocene. This timing coincides with mountain uplift and the onset of glacial cycles, which together may have facilitated both speciation and intermountain gene flow, contributing to the evolution of the Afroalpine flora.This work received financial support from the Spanish Ministry of Science, Innovation and Universities (PID2019-105583GB-C22/AEI/10.13039/501100011033) and the Catalan government (“Ajuts a grups consolidats” 2021SGR00315 and FI grant to C.B.-G. 2022FI_B 00150). The Ph.D. thesis was carried out under the Ph.D. program “Plant Biology and Biotechnology” of the Autonomous University of Barcelona (UAB). Additional support was provided by the Czech Science Foundation GAČR project no. 20-10878S to R.S. and F.K. and long-term research development project (RVO 67985939) of the Czech Academy of Sciences. Additional funds were obtained from the Norwegian Programme for Development, Research and Higher Education (NUFU; project AFROALP-II, no 2007/1058) and the Research Council of Norway (project SpeciationClock, no 274607) to C.B.Abstract 1. Introduction 2. Materials and Methods 2.1. Taxon Sampling 2.2. DNA Extraction, Library Preparation, Target Capture, and Sequencing 2.3. Molecular Data Processing and Phylogenetic Analyses 2.4. Divergence Time Estimation 2.5. Ancestral Range Estimation 3. Results 3.1. Alignment Processing and Filtering 3.2. Phylogenetic Analyses 3.3. Divergence Time and Ancestral Range Estimation 3.4. Number, Type, and Directionality Estimation of Biogeographical Events 4. Discussion 4.1. Utility of Target-Enrichment Strategies in Reconstructing the Radiation of Helichrysum 4.2. The Early History of Helichrysum and Colonization of Madagascar 4.3. Repeatedly Northwards 4.4. Repeatedly Upwards 5. Conclusions Supplementary Materials Author Contributions Funding Data Availability Statement Acknowledgments Conflicts of Interest Reference