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Simple Summary: Grapevine red blotch virus (GRBV, species Grablovirus vitis, genus Grablovirus, family Geminiviridae) is the first virus of grapevine to be transmitted by a treehopper vector, Spissistilus festinus, the three-cornered alfalfa hopper. Hypotheses for GRBV transmission have been by analogy with other viruses in the family Geminiviridae. In this study, we investigated novel attributes of GRBV transmission by S. festinus and determined the potential for vertical transmission and the differences in horizontal transmission by male and female S. festinus in a greenhouse. We found a lack of transovarial transmission, meaning females did not pass GRBV along to their offspring, and we found that males are overall greater contributors to GRBV spread than females. Moreover, we documented that S. festinus primarily spread GRBV in a walking and jumping dispersal pattern.. These results suggest a need for future studies in vineyard ecosystems to understand the sex-associated transmission of GRBV. Grapevine red blotch is an emerging disease that threatens vineyard productions in North America. Grapevine red blotch virus (GRBV, species Grablovirus vitis, genus Grablovirus, family Geminiviridae), the causal agent of red blotch disease, is transmitted by Spissistilus festinus (Hemiptera: Membracidae) in a circulative, non-propagative mode. To gain new insight into GRBV-S. festinus interactions, we delved into vertical transmission and documented a lack of transovarial transmission. In addition, we investigated S. festinus sex differences in the horizontal transmission of GRBV by creating small arenas with 30 detached trifoliates of common snap bean, an experimental host of GRBV, and a preferred feeding host of S. festinus. Tracking the movement of viruliferous males, females, or a combination of the two sexes over two weeks in replicated experiments demonstrated that male S. festinus dispersed more than females with specimens of both sexes predominantly grouping together on trifoliates spatially surrounding the trifoliate onto which they were released. These behaviors resulted in a greater rate of GRBV transmission by S. festinus males (17%, 20 of 120) than females (4%, 5 of 120) or mixed-sex cohorts (9%, 17 of 180). In arenas with aviruliferous S. festinus and one (single) or four (hotspot) GRBV-infected trifoliates out of 30 total trifoliates, a higher GRBV transmission rate by males was confirmed in both single infection (50%, 30 of 60) and hotspot infection (83%, 50 of 60) arenas than by females in single infection (35%, 21 of 60) and hotspot infection (67%, 40 of 60) arenas. These findings highlighted sex-associated differences in the transmission of GRBV by S. festinus and a positive correlation between the initial virus prevalence and the rate of transmission. Finally, the secondary spread of GRBV resulted primarily from S. festinus dispersal by walking or jumping. Together, these unique GRBV transmission features support the need to characterize dispersal behaviors of S. festinus in vineyard ecosystems. [ABSTRACT FROM AUTHOR]

Transcutaneous spinal cord stimulation (tSCS) is becoming a promising neuromodulation technique to promote motor recovery in various neurological conditions, including stroke. As this intervention moves forward into clinical practice, it is important to understand how the elicited neurophysiological measures are related to the functional and neuromuscular deficits of the population of interest in order to personalize tSCS interventions and assess its effectiveness. Specifically, neurophysiological measurements of spinal cord excitability can be achieved by recording with EMG spinal motor evoked responses (sMERs) in muscles after applying single pulses of tSCS to the spinal cord. The objective of this study was to investigate potential correlations between baseline spinal cord excitability, as measured by resting motor threshold (RMT) and peak-to-peak (P2P) amplitude of the sMERs, and various factors including demographic characteristics, severity of spasticity, muscle strength, and gait speed in individuals post-stroke. Additionally, the study sought to explore disparities in excitability between the paretic and non-paretic sides. Fifteen participants with chronic stroke underwent sMER assessments. We observed a strong positive correlation between RMT and body weight, indicating weight as a potential confounding variable when comparing RMTs from sMERs between individuals. Furthermore, paretic muscles exhibited lower RMTs and higher P2P amplitudes compared to non-paretic muscles. The results demonstrate that sMERs hold promise in uncovering disparities in spinal excitability in stroke participants. Furthermore, careful interpretation and analysis of sMERs is advised, particularly as higher RMTs were associated with higher body weight and could impact the clinical feasibility of tSCS for some participants. These results should be considered in future tSCS protocols that aim to develop more personalized interventions across different neurological populations and optimize sMERs' utility as an outcome measure. [ABSTRACT FROM AUTHOR]

Reduced propulsion of the paretic leg contributes to impaired walking in people poststroke. The goal of this study was to determine whether phasic electrical stimulation to the paretic gastrocnemius muscle combined with resistance applied to the nonparetic leg during swing phase while walking would enhance muscle activation of the paretic gastrocnemius and propulsive force of the paretic leg. Fifteen individuals who had a stroke visited the lab once to complete two experimental sessions (i.e., crossover design; session order randomized). Each session consisted of 1) treadmill walking with either "motor stimulation and swing resistance" or "swing resistance only" (10-min walking: 1-min baseline, 7-min adaptation to intervention, and 2-min postadaptation) and 2) instrumented treadmill walking before and after treadmill walking. Participants showed enhanced muscle activation of the paretic gastrocnemius (P = 0.03) and improved anteroposterior ground reaction force of the paretic leg (P = 0.01) immediately after the treadmill walking with "motor stimulation and swing resistance," whereas no improvements after the walking with "swing resistance only." Those enhanced gastrocnemius muscle activation (P = 0.02) and improved ground reaction force (P = 0.03) were retained until the late postadaptation period and 10 min after treadmill walking, respectively. Walking with "motor stimulation and swing resistance" may enhance forced use of the paretic leg and improve propulsive force of the paretic leg. Applying phasic electrical stimulation to the paretic gastrocnemius muscle and swing resistance to the nonparetic leg during walking can be used as a novel intervention strategy to improve motor control of the paretic leg and walking in people poststroke. NEW & NOTEWORTHY: Applying targeted motor stimulation to the paretic calf muscle and swing resistance to the nonparetic leg during walking induced significant enhancement in muscle activation of the paretic gastrocnemius and anterior-posterior ground reaction force of the paretic leg, whereas no enhancements were observed after walking with swing resistance only. Furthermore, the enhanced gastrocnemius muscle activation and ground reaction force of the paretic leg were partially retained at the late postadaptation period and 10 min after treadmill walking. [ABSTRACT FROM AUTHOR]

Hemodialysis is a life-sustaining treatment for persons with kidney failure. However, those on hemodialysis still face a poor quality of life and a short life expectancy. High-quality research evidence from large randomized controlled trials is needed to identify interventions that improve the experiences, outcomes, and health care of persons receiving hemodialysis. With the support of the Canadian Institutes of Health Research and its Strategy for Patient-Oriented Research, the Innovative Clinical Trials in Hemodialysis Centers initiative brought together Canadian and international kidney researchers, patients, health care providers, and health administrators to participate in a workshop held in Toronto, Canada, on June 2 and 3, 2018. The workshop served to increase knowledge and awareness about the conduct of innovative, pragmatic, cluster-randomized registry trials embedded into routine hemodialysis care and provided an opportunity to discuss and build support for new trial ideas. The workshop content included structured presentations, facilitated group discussions, and expert panel feedback. Partnerships and promising trial ideas borne out of the workshop will continue to be developed to support the implementation of future large-scale trials.

Charge noise is a major limitation to achieving high-fidelity quantum gate performance with semiconductor qubits. Here the authors report the results of charge noise spectroscopy for electron spin qubits in silicon quantum dots, spanning nearly twelve decades in frequency.

Abstract Evolution can involve periods of rapid divergent adaptation and expansion in the range of diversity, but evolution can also be relatively conservative over certain timescales due to functional, genetic‐developmental, and ecological constraints. One way in which evolution may be conservative is in terms of allometry, the scaling relationship between the traits of organisms and body size. Here, we investigate patterns of allometric conservatism in the evolution of bird beaks with beak size and body size data for a representative sample of over 5000 extant bird species within a phylogenetic framework. We identify clades in which the allometric relationship between beak size and body size has remained relatively conserved across species over millions to tens of millions of years. We find that allometric conservatism is nonetheless punctuated by occasional shifts in the slopes and intercepts of allometric relationships. A steady accumulation of such shifts through time has given rise to the tremendous diversity of beak size relative to body size across birds today. Our findings are consistent with the Simpsonian vision of macroevolution, with evolutionary conservatism being the rule but with occasional shifts to new adaptive zones.

A universal taxonomy of viruses is essential for a comprehensive view of the virus world and for communicating the complicated evolutionary relationships among viruses. However, there are major differences in the conceptualisation and approaches to virus classification and nomenclature among virologists, clinicians, agronomists, and other interested parties. Here, we provide recommendations to guide the construction of a coherent and comprehensive virus taxonomy, based on expert scientific consensus. Firstly, assignments of viruses should be congruent with the best attainable reconstruction of their evolutionary histories, i.e., taxa should be monophyletic. This fundamental principle for classification of viruses is currently included in the International Committee on Taxonomy of Viruses (ICTV) code only for the rank of species. Secondly, phenotypic and ecological properties of viruses may inform, but not override, evolutionary relatedness in the placement of ranks. Thirdly, alternative classifications that consider phenotypic attributes, such as being vector-borne (e.g., “arboviruses”), infecting a certain type of host (e.g., “mycoviruses,” “bacteriophages”) or displaying specific pathogenicity (e.g., “human immunodeficiency viruses”), may serve important clinical and regulatory purposes but often create polyphyletic categories that do not reflect evolutionary relationships. Nevertheless, such classifications ought to be maintained if they serve the needs of specific communities or play a practical clinical or regulatory role. However, they should not be considered or called taxonomies. Finally, while an evolution-based framework enables viruses discovered by metagenomics to be incorporated into the ICTV taxonomy, there are essential requirements for quality control of the sequence data used for these assignments. Combined, these four principles will enable future development and expansion of virus taxonomy as the true evolutionary diversity of viruses becomes apparent. Transforming an existing phenotypic classification of viruses into one based on evolutionary relationships that can accommodate the vast number of viruses characterized in metagenomics and environmental studies is an ongoing challenge. This Consensus View explains how such a taxonomy can be expanded to encapsulate viral diversity and to recognize independent biological origins of different virus groups.

Abstract Background Leucine rich repeat kinase 2 (LRRK2) and SNCA are genetically linked to late-onset Parkinson’s disease (PD). Aggregated α-synuclein pathologically defines PD. Recent studies identified elevated LRRK2 expression in pro-inflammatory CD16+ monocytes in idiopathic PD, as well as increased phosphorylation of the LRRK2 kinase substrate Rab10 in monocytes in some LRRK2 mutation carriers. Brain-engrafting pro-inflammatory monocytes have been implicated in dopaminergic neurodegeneration in PD models. Here we examine how α-synuclein and LRRK2 interact in monocytes and subsequent neuroinflammatory responses. Methods Human and mouse monocytes were differentiated to distinct transcriptional states resembling macrophages, dendritic cells, or microglia, and exposed to well-characterized human or mouse α-synuclein fibrils. LRRK2 expression and LRRK2-dependent Rab10 phosphorylation were measured with monoclonal antibodies, and myeloid cell responses to α-synuclein fibrils in R1441C-Lrrk2 knock-in mice or G2019S-Lrrk2 BAC mice were evaluated by flow cytometry. Chemotaxis assays were performed with monocyte-derived macrophages stimulated with α-synuclein fibrils and microglia in Boyden chambers. Results α-synuclein fibrils robustly stimulate LRRK2 and Rab10 phosphorylation in human and mouse macrophages and dendritic-like cells. In these cells, α-synuclein fibrils stimulate LRRK2 through JAK-STAT activation and intrinsic LRRK2 kinase activity in a feed-forward pathway that upregulates phosphorylated Rab10. In contrast, LRRK2 expression and Rab10 phosphorylation are both suppressed in microglia-like cells that are otherwise highly responsive to α-synuclein fibrils. Corroborating these results, LRRK2 expression in the brain parenchyma occurs in pro-inflammatory monocytes infiltrating from the periphery, distinct from brain-resident microglia. Mice expressing pathogenic LRRK2 mutations G2019S or R1441C have increased numbers of infiltrating pro-inflammatory monocytes in acute response to α-synuclein fibrils. In primary cultured macrophages, LRRK2 kinase inhibition dampens α-synuclein fibril and microglia-stimulated chemotaxis. Conclusions Pathologic α-synuclein activates LRRK2 expression and kinase activity in monocytes and induces their recruitment to the brain. These results predict that LRRK2 kinase inhibition may attenuate damaging pro-inflammatory monocyte responses in the brain.

Abstract Electrochemical random‐access memory (ECRAM) is a recently developed and highly promising analog resistive memory element for in‐memory computing. One longstanding challenge of ECRAM is attaining retention time beyond a few hours. This short retention has precluded ECRAM from being considered for inference classification in deep neural networks, which is likely the largest opportunity for in‐memory computing. In this work, an ECRAM cell with orders of magnitude longer retention than previously achieved is developed, and which is anticipated to exceed ten years at 85 °C. This study hypothesizes that the origin of this exceptional retention is phase separation, which enables the formation of multiple effectively equilibrium resistance states. This work highlights the promises and opportunities to use phase separation to yield ECRAM cells with exceptionally long, and potentially permanent, retention times.

Background and objectivesWe investigated the rate, stage, and prognosis of thyroid cancer in patients after solid-organ transplantations, and compared this to the general population.MethodsWe performed a retrospective review of patients who developed thyroid cancer after a solid-organ transplantation between January 1988 and December 2013 at a high volume transplant center. Standardized Incidence Ratio's (SIR) were calculated. Additionally, a systematic review of the literature was performed.ResultsA total of 10,428 patients underwent solid organ transplantation. Eleven patients (11.4 per 100,000 person-years) developed thyroid cancer: six men and five women with a mean age at diagnosis of thyroid cancer of 58 years. Ten patients underwent surgery and had stage I thyroid cancer. One patient had recurrent disease after a mean follow-up time of 78 months. The SIR varied between 0.75 and 2.3. Seventeen studies were included in the systematic review with a SIR ranging from 2.5 to 35.ConclusionRate of thyroid cancer is not significantly higher in patients who underwent solid organ transplantation compared to general population. Stage at presentation and prognosis also appear to be similar to that of the general population. Post-transplant screening for thyroid cancer remains debatable; however, when thyroid cancer is discovered, treatment should be similar to that of non-transplant patients. J. Surg. Oncol. 2017;115:105-108. © 2017 Wiley Periodicals, Inc.