Land-use diversity within an agricultural landscape promotes termite nutrient cycling services in a southern African savanna

CITATION: LeClare, S. K. et al. 2020. Land-use diversity within an agricultural landscape promotes termite nutrient cycling services in a southern African savanna. Global Ecology and Conservation, 21. doi:10.1016/j.gecco.2019.e00885The original publication is available at https://www.sciencedirect.com/journal/global-ecology-and-conservationSoil macrofauna provide key supporting ecosystem services by transporting nutrients against physical and chemical gradients. In the semi-arid savannas of southern Africa, termites are the dominant macrofauna whose foraging activities increase nutrient availability, soil aeration and water infiltration. With increasing land-use conversion, savanna landscapes are becoming surrounded by a matrix of agricultural landscapes. We tested how compositional and configurational landscape heterogeneity influenced the presence of soil sheetings, a termite foraging activity, within savanna habitat patches embedded in a heterogeneous agricultural landscape in north-east Eswatini. We found that landscape heterogeneity most strongly influenced termite foraging activity at smaller spatial scales (1- to 2-km surrounding the savanna patch). Within this spatial scale, high compositional heterogeneity, which was indicative of diverse habitat patches, promoted termite foraging activity, yet high configurational heterogeneity, indicative of a fragmented landscape, reduced termite foraging activity. At larger landscape scales (5-km), the heterogeneity of the landscape no longer influenced termite foraging activity, yet low to moderate proportions of sugarcane surrounding savanna patches promoted termite foraging activity within those patches. Our results provide novel insights in how the structure of the landscape affects termite foraging activity, demonstrating that diverse, intact landscapes are a critical buffer in maintaining positive nutrient cycling services within an agricultural landscape.https://www.sciencedirect.com/science/article/pii/S2351989419304408Publishers versio

Using Wearable Technology to Quantify Physical Activity Recovery: Secondary Report From the AFTER (App-Facilitated Tele-Rehabilitation) Program for COVID-19 Survivors Randomized Study

Background: Knowledge on physical activity recovery after COVID-19 survival is limited. The AFTER (App-Facilitated Tele-Rehabilitation) program for COVID-19 survivors randomized participants, following hospital discharge, to either education and unstructured physical activity or a telerehabilitation program. Step count data were collected as a secondary outcome, and we found no significant differences in total step count trajectories between groups at 6 weeks. Further step count data were not analyzed. Objective: The purpose of this analysis was to examine step count trajectories and correlates among all participants (combined into a single group) across the 12-week study period. Methods: Linear mixed models with random effects were used to model daily steps over the number of study days. Models with 0, 1, and 2 inflection points were considered, and the final model was selected based on the highest log-likelihood value. Results: Participants included 44 adults (41 with available Fitbit [Fitbit LLC] data). Initially, step counts increased by an average of 930 (95% CI 547-1312; PPPP Conclusions: Participants showed a marked improvement in daily step counts during the first 3 weeks of the study, followed by more gradual improvement in the remaining 9 weeks. Physical activity data and step count recovery trajectories may be considered surrogates for physiological recovery, although further research is needed to examine this relationship

Methadone Initiation in the Emergency Department for Opioid Use Disorder

Introduction: Overdose deaths from high-potency synthetic opioids, including fentanyl and its analogs, continue to rise along with emergency department (ED) visits for complications of opioid use disorder (OUD). Fentanyl accumulates in adipose tissue; although rare, this increases the risk of precipitated withdrawal in patients upon buprenorphine initiation. Many EDs have implemented medication for opioid use disorder (MOUD) programs using buprenorphine. However, few offer methadone, a proven therapy without the risk of precipitated withdrawal associated with buprenorphine initiation. We describe the addition of an ED-initiated methadone treatment pathway and compared its 72-hour follow-up outpatient treatment engagement rates to our existing ED-initiated buprenorphine MOUD program. Methods: We expanded our ED MOUD program with a methadone treatment pathway. From February 20–September 19, 2023, we screened 20,504 ED arrivals; 5.1% had signs of OUD. We enrolled 61 patients: 28 in the methadone; and 33 in the buprenorphine pathways. For patients who screened positive for opioid use, shared decision-making was employed to determine whether buprenorphine or methadone therapy was more appropriate. Patients in the methadone pathway received their first dose of up to 30 milligrams (mg) of methadone in the ED. Two additional methadone doses of up to 40 mg were dispensed at the time of the ED visit and held in the department, allowing patients to return each day for observed dosing until intake at an opioid treatment program (OTP). We compared 72-hour rates of outpatient follow-up treatment engagement at the OTP (for those on methadone) or at the addiction treatment center (ATC) (for those on buprenorphine) for the two treatment pathways. Results: Of the 28 patients enrolled in the methadone pathway, 12 (43%) successfully engaged in follow-up treatment at the OTP. Of the 33 patients enrolled in the buprenorphine pathway, 15 (45%) successfully engaged in follow-up treatment at the ATC (relative risk 1.06; 95% confidence interval 0.60–1.87). Conclusion: Methadone initiation in the ED to treat patients with OUD resulted in similar 72-hour follow-up outpatient treatment engagement rates compared to ED-buprenorphine initiation, providing another viable option for MOUD

Progressive Motor Neuron Pathology and the Role of Astrocytes in a Human Stem Cell Model of VCP-Related ALS.

Motor neurons (MNs) and astrocytes (ACs) are implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), but their interaction and the sequence of molecular events leading to MN death remain unresolved. Here, we optimized directed differentiation of induced pluripotent stem cells (iPSCs) into highly enriched (> 85%) functional populations of spinal cord MNs and ACs. We identify significantly increased cytoplasmic TDP-43 and ER stress as primary pathogenic events in patient-specific valosin-containing protein (VCP)-mutant MNs, with secondary mitochondrial dysfunction and oxidative stress. Cumulatively, these cellular stresses result in synaptic pathology and cell death in VCP-mutant MNs. We additionally identify a cell-autonomous VCP-mutant AC survival phenotype, which is not attributable to the same molecular pathology occurring in VCP-mutant MNs. Finally, through iterative co-culture experiments, we uncover non-cell-autonomous effects of VCP-mutant ACs on both control and mutant MNs. This work elucidates molecular events and cellular interplay that could guide future therapeutic strategies in ALS

A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome

Superoxide Dismutase 1 and tgSOD1G93A Mouse Spinal Cord Seed Fibrils, Suggesting a Propagative Cell Death Mechanism in Amyotrophic Lateral Sclerosis

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that specifically affects motor neurons and leads to a progressive and ultimately fatal loss of function, resulting in death typically within 3 to 5 years of diagnosis. The disease starts with a focal centre of weakness, such as one limb, and appears to spread to other parts of the body. Mutations in superoxide dismutase 1 (SOD1) are known to cause disease and it is generally accepted they lead to pathology not by loss of enzymatic activity but by gain of some unknown toxic function(s). Although different mutations lead to varying tendencies of SOD1 to aggregate, we suggest abnormal proteins share a common misfolding pathway that leads to the formation of amyloid fibrils.Methodology/Principal Findings: Here we demonstrate that misfolding of superoxide dismutase 1 leads to the formation of amyloid fibrils associated with seeding activity, which can accelerate the formation of new fibrils in an autocatalytic cascade. The time limiting event is nucleation to form a stable protein "seed" before a rapid linear polymerisation results in amyloid fibrils analogous to other protein misfolding disorders. This phenomenon was not confined to fibrils of recombinant protein as here we show, for the first time, that spinal cord homogenates obtained from a transgenic mouse model that overexpresses mutant human superoxide dismutase 1 (the TgSOD1(G93A) mouse) also contain amyloid seeds that accelerate the formation of new fibrils in both wildtype and mutant SOD1 protein in vitro.Conclusions/Significance: These findings provide new insights into ALS disease mechanism and in particular a mechanism that could account for the spread of pathology throughout the nervous system. This model of disease spread, which has analogies to other protein misfolding disorders such as prion disease, also suggests it may be possible to design assays for therapeutics that can inhibit fibril propagation and hence, possibly, disease progression