A robust approach to differentiate human monocyte-derived microglia from peripheral blood mononuclear cells

Microglia are implicated in most neurodegenerative diseases. Here, we present a robust and efficient protocol to differentiate monocyte-derived microglia-like cells (MDMi) from whole blood. The protocol consists of three parts. The first part will describe two methods for PBMC isolation. This will be followed by MDMi differentiation, and lastly, the characterization of MDMi by immunocytochemistry. MDMi can be used to investigate microglial-related responses in various age-related neurodegenerative diseases and can be applied to drug testing on a personalized basis. For complete details on the use and execution of this protocol, please refer to Quek et al

Defective myogenesis in the absence of the muscle-specific lysine methyltransferase SMYD1

AbstractThe SMYD (SET and MYND domain) family of lysine methyltransferases harbor a unique structure in which the methyltransferase (SET) domain is intervened by a zinc finger protein–protein interaction MYND domain. SMYD proteins methylate both histone and non-histone substrates and participate in diverse biological processes including transcriptional regulation, DNA repair, proliferation and apoptosis. Smyd1 is unique among the five family members in that it is specifically expressed in striated muscles. Smyd1 is critical for development of the right ventricle in mice. In zebrafish, Smyd1 is necessary for sarcomerogenesis in fast-twitch muscles. Smyd1 is expressed in the skeletal muscle lineage throughout myogenesis and in mature myofibers, shuttling from nucleus to cytosol during myoblast differentiation. Because of this expression pattern, we hypothesized that Smyd1 plays multiple roles at different stages of myogenesis. To determine the role of Smyd1 in mammalian myogenesis, we conditionally eliminated Smyd1 from the skeletal muscle lineage at the myoblast stage using Myf5cre. Deletion of Smyd1 impaired myoblast differentiation, resulted in fewer myofibers and decreased expression of muscle-specific genes. Muscular defects were temporally restricted to the second wave of myogenesis. Thus, in addition to the previously described functions for Smyd1 in heart development and skeletal muscle sarcomerogenesis, these results point to a novel role for Smyd1 in myoblast differentiation

A conceptual model for the integration of social and ecological information to understand human-wildlife interactions

There is growing recognition that interdisciplinary approaches that account for both ecological and social processes are necessary to successfully address human-wildlife interactions. However, such approaches are hindered by challenges in aligning data types, communicating across disciplines, and applying social science information to conservation actions. To meet these challenges, we propose a conceptual model that adopts a social-ecological systems approach and integrates social and ecological theory to identify the multiple, nested levels of influence on both human and animal behavior. By accounting for a diverse array of influences and feedback mechanisms between social and ecological systems, this model fulfills a need for approaches that treat social and ecological processes with equal depth and facilitates a comprehensive understanding of the drivers of human and animal behaviors that perpetuate human-wildlife interactions. We apply this conceptual model to our work on human-black bear conflicts in Colorado, USA to demonstrate its utility. Using this example, we identify key lessons and offer guidance to researchers and conservation practitioners for applying integrated approaches to other human-wildlife systems

Rapid changes in public perception toward a conservation initiative

Rapid, widespread changes in public perceptions and behaviors have the potential to influence conservation outcomes. However, few studies have documented whether and how such shifts occur throughout the span of a conservation initiative. We examined the 2020 ballot initiative to reintroduce wolves into Colorado, which passed with less support than prior surveys had estimated. We conducted a postelection survey of Colorado residents using the same methods as our preelection survey to compare responses between surveys and to official election results. Reported voting in favor of wolf reintroduction in the postelection survey decreased in comparison to voting intentions shared in the preelection survey, but not enough to reflect the actual vote. While bias from survey methods and/or sampling contributed to differences, we also found evidence that public perception changed. Specifically, beliefs about the potential for negative impacts of wolves increased, while beliefs about the potential for positive impacts of wolves decreased. Our findings highlight the need to conduct longitudinal monitoring of public perception given perceptions may be highly fluid as different entities attempt to sway voters. In addition, to better understand evolving perceptions, survey methods and sampling need to be improved

A pilot ASKAP survey for radio transients towards the Galactic Centre

We present the results of a radio transient and polarisation survey towards the Galactic Centre, conducted as part of the Australian Square Kilometre Array Pathfinder Variables and Slow Transients pilot survey. The survey region consisted of five fields covering $\sim265\,{\rm deg}^2$ ($350^\circ\lesssim l\lesssim10^\circ$, $\vert b\vert \lesssim 10^\circ$). Each field was observed for 12\,minutes, with between 7 and 9 repeats on cadences of between one day and four months. We detected eight highly variable sources and seven highly circularly-polarised sources (14 unique sources in total). Seven of these sources are known pulsars including the rotating radio transient PSR~J1739--2521 and the eclipsing pulsar PSR~J1723--2837. One of them is a low mass X-ray binary, 4U 1758--25. Three of them are coincident with optical or infrared sources and are likely to be stars. The remaining three may be related to the class of Galactic Centre Radio Transients (including a highly likely one, VAST~J173608.2--321634, that has been reported previously), although this class is not yet understood. In the coming years, we expect to detect $\sim$40 bursts from this kind of source with the proposed four-year VAST survey if the distribution of the source is isotropic over the Galactic fields.Comment: 17 pages, 13 figures, Accepted for publication in MNRA

A search for radio afterglows from gamma-ray bursts with the Australian Square Kilometre Array Pathfinder

We present a search for radio afterglows from long gamma-ray bursts using the Australian Square Kilometre Array Pathfinder (ASKAP). Our search used the Rapid ASKAP Continuum Survey, covering the entire celestial sphere south of declination $+41^\circ$, and three epochs of the Variables and Slow Transients Pilot Survey (Phase 1), covering $\sim 5,000$ square degrees per epoch. The observations we used from these surveys spanned a nine-month period from 2019 April 21 to 2020 January 11. We crossmatched radio sources found in these surveys with 779 well-localised (to $\leq 15''$) long gamma-ray bursts occurring after 2004 and determined whether the associations were more likely afterglow- or host-related through the analysis of optical images. In our search, we detected one radio afterglow candidate associated with GRB 171205A, a local low-luminosity gamma-ray burst with a supernova counterpart SN 2017iuk, in an ASKAP observation 511 days post-burst. We confirmed this detection with further observations of the radio afterglow using the Australia Telescope Compact Array at 859 days and 884 days post-burst. Combining this data with archival data from early-time radio observations, we showed the evolution of the radio spectral energy distribution alone could reveal clear signatures of a wind-like circumburst medium for the burst. Finally, we derived semi-analytical estimates for the microphysical shock parameters of the burst: electron power-law index $p = 2.84$, normalised wind-density parameter $A_* = 3$, fractional energy in electrons $\epsilon_{e} = 0.3$, and fractional energy in magnetic fields $\epsilon_{B} = 0.0002$.Comment: 18 pages, 7 figures; accepted for publication in MNRA

Patient-centred innovation for multimorbidity care : mixed-methods, randomized trial and qualitative study of the patients’ experience

Background Patient-centred interventions to help patients with multimorbidity have had mixed results. Aim To assess the effectiveness of a provider-created, patient-centred, multi-provider case conference with follow-up, and understand underwhal circumstances it worked. and did not work Design and setting Mixed-methods design with a pragmatic randomised trial and qualitative study. involving nine urban primary care sites in Ontario, Canada. Method Patients aged 18-80 years with >= 3 chronic conditions were referred to the Telemedicine IMPACT Plus intervention; a nurse and patient planned a multi provider case conference during which a care plan could be created. The patients were randomised into an intervention or control group. Two subgroup analyses and a fidelity assessment were conducted, with the primary outcomes at 4 months being self-management and self-efficacy. Secondary outcomes were mental and physical health status, quality of life, and health behaviours. A thematic analysis explored the patients' experiences of the intervention. Results A total of 86 patients in the intervention group and 77 in the control group showed no differences, except that the intervention improved mental health status in the subgroup with an annual income of >= C$50 000 [beta-coefficient 11.003, P= 0.006]. More providers and follow-up hours were associated with poorer outcomes. Five themes were identified in the qualitative study: valuing the team, patients feeling supported. receiving a follow-up plan, being offered new and helpful additions to their treatment regimen, and experiencing positive outcomes. Conclusion Overall, the intervention showed improvements only for patients who had an annual income of >= C$50 000, implying a need to address the Wsis of intervention components not covered by existing health policies. Findings suggest a need to optimise learn composition by revising the number and type of providers according to patient preferences and to enhance the hours of nurse follow-up to better support the patient in carrying out the case conference's recommendations

Retrospective and prospective assessments of gambling-related behaviors across the female menstrual cycle

Background and aims: Despite increases in female gambling, little research investigates female-specific factors affecting gambling behavior (GB). Although research suggests that some addictive behaviors may fluctuate across menstrual cycle phase (MCP), gambling requires further investigation. In two studies, we examined associations between MCP and three risky GBs: time spent gambling, money spent gambling, and the probability of consuming alcohol while gambling. Associations between MCP and negative affect were also examined in Study 2. We predicted that, consistent with self-medication theory, increases in negative affect (Study 2) and risky GBs (Studies 1 and 2) would occur premenstrually/menstrually relative to other phases. Methods: Data were obtained from 33 female gamblers using a retrospective timeline followback procedure (Study 1) and from 20 female gamblers using a prospective 32-day, daily diary method (Study 2). In Study 2, salivary progesterone levels verified self-reported MCP validity. Results: Findings revealed significant, but somewhat inconsistent, MCP effects on GBs across studies. The self-medication hypothesis was partially supported. Increases relative to another MCP(s) were found for alcohol consumption while gambling premenstrually, time spent gambling menstrually/premenstrually, money spent gambling menstrually, and negative affect premenstrually. Unexpectedly, findings more consistently indicated that GBs increased during ovulation, suggestive of enhanced reward sensitivity. Progesterone assays validated self-reported MCP (Study 2). Discussion and conclusions: The results suggest a role of ovarian hormones on negative affect and GBs in females. This research could lead to the identification of female-specific factors affecting gambling and the development of more effective interventions for females with, or at risk for, problematic gambling