Broad Changes Research Articles

Food security and knowledge politics in rural Oaxaca

This study uses an embodied political ecology framework to evaluate the structural, discursive, and visceral effects of government food assistance policy in an agrarian community in southern Mexico. During the administration of President Enrique Peña Nieto (2012-2018), the government’s efforts to resolve the growing double-burden of under- and over-nutrition included the expansion of food assistance programs alongside cash transfers conditioned on health and nutritional education. A parastatal company sourced and distributed foodstuffs to community and school kitchens, where mothers prepared them into meals. This research explores how women participating in government food assistance in the agricultural community of Santa Inés del Monte, Oaxaca, evaluated the foods they received and conceptualized broader changes in their food system and community health. Qualitative research methods, including interviews, focus groups and a community survey of 87 households, were conducted in the community in 2015, 2017 and 2018. Through attention to visceral experience, this study demonstrates how sensations of taste, embodied knowledge, nutrition discourses, gendered development programs, and structural marginalization combined to produce an outcome in which mothers accepted and prepared foods in the community kitchens that did not meet their standards of food quality. However, this study also finds that participating mothers and other residents continue to conceive of direct food production—especially organic production of local heirloom crop and animal varieties—as the best way to access good nutrition. These findings suggest the need for attention to knowledge politics in the design and evaluation of culturally appropriate food security policy.

Impact of anesthetist licensing examination on quality of education in Ethiopia: a qualitative study of faculty and student perceptions

BackgroundEthiopia drastically increased the anesthesia workforce density by training ‘associate clinician anesthetists’ as a task-shifting and sharing strategy. However, there were growing concerns about educational quality and patient safety. Accordingly, the Ministry of Health introduced the anesthetist national licensing examination (NLE) to assure the quality of education. However, empirical evidence is scarce to support or refute the overall impact of NLEs, which are relatively costly for low- and middle-income settings. Therefore, this study aimed to explore the impact of introducing NLE on anesthetists’ education in Ethiopia.MethodsWe conducted a qualitative study using a constructivist grounded theory approach. Data were prospectively collected from ten anesthetist teaching institutions. Fifteen in-depth interviews were conducted with instructors and academic leaders, and six focus groups were held with students and recently tested anesthetists. Additional data were gathered by analyzing relevant documents, including versions of curricula, academic committee minutes, program quality review reports, and faculty appraisal reports. Interviews and group discussions were audiotaped, transcribed verbatim and analyzed using Atlas.ti 9 software.ResultsBoth faculty and students demonstrated positive attitudes toward the NLE. Student motivation, faculty performance, and curriculum strengthening were the three primary changes that emerged, resulting in three subsequent spin-offs on assessment, learning, and quality management practices. Academic leaders’ dedication to evaluating examination data and turning these into action led to changes that improved education quality. Increased accountability, engagement, and collaboration were the predominant factors facilitating change.ConclusionOur study indicates that the Ethiopian NLE has prompted anesthesia teaching institutions to improve their teaching, learning, and assessment practices. However, more work is required to improve exam acceptability among stakeholders and drive broader changes.

Linking muscle mechanics to the metabolic cost of human hopping.

Many models have been developed to predict metabolic energy expenditure based on biomechanical proxies of muscle function. However, current models may only perform well for select forms of locomotion, not only because the models are rarely rigorously tested across subtle and broad changes in locomotor task but also because previous research has not adequately characterised different forms of locomotion to account for the potential variability in muscle function and thus metabolic energy expenditure. To help to address the latter point, the present study imposed frequency and height constraints to hopping and quantified gross metabolic power as well as the activation requirements of medial gastrocnemius (MG), lateral gastrocnemius (GL), soleus (SOL), tibialis anterior (TA), vastus lateralis (VL), rectus femoris (RF) and biceps femoris (BF), and the work requirements of GL, SOL and VL. Gross metabolic power increased with a decrease in hop frequency and increase in hop height. There was no hop frequency or hop height effect on the mean electromyography (EMG) data of ankle musculature; however, the mean EMG of VL and RF increased with a decrease in hop frequency and that of BF increased with an increase in hop height. With a reduction in hop frequency, GL, SOL and VL fascicle shortening, fascicle shortening velocity and fascicle to MTU shortening ratio increased, whereas with an increase in hop height, only SOL fascicle shortening velocity increased. Therefore, within the constraints that we imposed, decreases in hop frequency and increases in hop height resulted in increases in metabolic power that could be explained by increases in the activation requirements of knee musculature and/or increases in the work requirements of both knee and ankle musculature.

Defining the Human Condition in Stoic Philosophy: A Case Study on the characterization of Emperor Marcus Aurelius

This paper investigates, from a psycho-sociological perspective, notions of self-reflection and the human condition in the Greco-Roman world during the ancient period, focusing on the social constructionism of personal characterisation. In this context, Marcus Aurelius, one of Rome's most remarkable philosopher-emperors, was considered an exemplary, wise, and moral leader during a tumultuous period marked by wars, epidemics, and betrayals. The positive image of Marcus Aurelius has endured in history due to the efforts of recording and transmission of this depiction in ancient sources, which emphasised the enrichment of imperial power with attention to the philosophical form. Both within the Stoic doctrine and from the perspective of symbolic interactionism, the human condition is perceived as a result of social construction and subjective interpretations, in which the individual has the power to shape their own experience and create their reality. Qualitative research methods associated with symbolic interactionism emphasise individual experience and understanding of the world, being helpful in explaining broad social changes and the agency of participants. This perspective provides a broad framework for analysing interactions that shape social architecture through which the image of Marcus Aurelius is propagated.

Endothelial-specific loss of IKKβ disrupts pulmonary endothelial angiogenesis and impairs postnatal lung growth.

Pulmonary angiogenesis drives alveolarization, but the transcriptional regulators directing pulmonary angiogenesis remain poorly defined. Global, pharmacological inhibition of nuclear factor-kappa B (NF-κB) impairs pulmonary angiogenesis and alveolarization. However, establishing a definitive role for NF-κB in pulmonary vascular development has been hindered by embryonic lethality induced by constitutive deletion of NF-κB family members. We created a mouse model allowing inducible deletion of the NF-κB activator, IKKβ, in endothelial cells (ECs) and assessed the effect on lung structure, endothelial angiogenic function, and the lung transcriptome. Embryonic deletion of IKKβ permitted lung vascular development but resulted in a disorganized vascular plexus, while postnatal deletion significantly decreased radial alveolar counts, vascular density, and proliferation of both endothelial and nonendothelial lung cells. Loss of IKKβ impaired survival, proliferation, migration, and angiogenesis in primary lung ECs in vitro, in association with decreased expression of VEGFR2 and activation of downstream effectors. Loss of endothelial IKKβ in vivo induced broad changes in the lung transcriptome with downregulation of genes related to mitotic cell cycle, extracellular matrix (ECM)-receptor interaction, and vascular development, and the upregulation of genes related to inflammation. Computational deconvolution suggested that loss of endothelial IKKβ decreased general capillary, aerocyte capillary, and alveolar type I cell abundance. Taken together, these data definitively establish an essential role for endogenous endothelial IKKβ signaling during alveolarization. A deeper understanding of the mechanisms directing this developmental, physiological activation of IKKβ in the lung vasculature may provide novel targets for the development of strategies to enhance beneficial proangiogenic signaling in lung development and disease.NEW & NOTEWORTHY This study highlights the cell-specific complexity of nuclear factor kappa B signaling in the developing lung by demonstrating that inducible loss of IKKβ in endothelial cells impairs alveolarization, disrupts EC angiogenic function, and broadly represses genes important for vascular development.

Hype or hope? What consumer motives tell us about the prospects for plant and animal-based dairy products in six European countries

The expanding market in plant-based dairy products (PBDPs) is challenging traditional markets for animal-based dairy products (ABDPs). Using an extended ordered probit model, the drivers and barriers of PBDP consumption were investigated across six European countries for indicators of broader changes in consumption. Results revealed country-specific consumer core groups with a pronounced willingness to extend PBDP consumption, e.g. among individuals already following largely plant-based diets in Denmark or France. However, price or product characteristics, such as taste or variety, constituted country-specific barriers to PBDP consumption. Furthermore, consumers’ willingness to obtain information about the sustainability of PBDPs seemed to provide the basis for a general and profound trend towards their consumption across the six European countries studied.

School Leaders’ Perspectives Implementing Whole School Restorative Practices Across Grade Levels: A Case Study of a School-Based Pilot Project

Whole school restorative practice (WSRP) calls for creating supportive, equitable schools, requiring broad systems change. This case study explores the journeys of three schools piloting WSRP in one Midwestern district and examines how school leaders designed and implemented within their school contexts. Schools were purposefully selected from within a three-year pilot project; data sources included annual interviews and focus groups with school leaders, and annual school reports. Each school developed a leadership team comprised of administrators and other staff who were knowledgeable of and committed to restorative justice principles. While grounded in common restorative principles, language, and approaches as part of their district’s pilot project, school WSRP leaders simultaneously developed contextually-specific practices, including tailoring to learners’ developmental stages. Overall, this study highlights the influential role of school leaders in navigating complexities that arise when working from a worldview that values human relationality and interconnection. Impact Statement In this case study, school leaders’ design and implementation of whole-school restorative practices (WSRP) reflected school-level contexts, including students’ developmental stages, in alignment with restorative principles and values. Overall, this study highlights the influential role of school leaders in navigating whole-school change toward a worldview that values human relationality and interconnection. This study may inform how school psychologists, who often play a critical role in leading systems change initiatives in schools, can leverage their skills, knowledge, and experiences as part of WSRP leadership and implementation efforts.

Body-Plan Reorganization in a Sponge Correlates with Microbiome Change.

Mounting evidence suggests that animals and their associated bacteria interact via intricate molecular mechanisms, and it is hypothesized that disturbances to the microbiome influence animal development. Here, we show that the loss of a key photosymbiont (i.e., bleaching) upon shading correlates with a stark body-plan reorganization in the common aquarium cyanosponge Lendenfeldia chondrodes. The morphological changes observed in shaded sponges include the development of a thread-like morphology that contrasts with the flattened, foliose morphology of control specimens. The microanatomy of shaded sponges markedly differed from that of control sponges, with shaded specimens lacking a well-developed cortex and choanosome. Also, the palisade of polyvacuolar gland-like cells typical in control specimens was absent in shaded sponges. The morphological changes observed in shaded specimens are coupled with broad transcriptomic changes and include the modulation of signaling pathways involved in animal morphogenesis and immune response, such as the Wnt, transforming growth factor β (TGF-β), and TLR-ILR pathways. This study provides a genetic, physiological, and morphological assessment of the effect of microbiome changes on sponge postembryonic development and homeostasis. The correlated response of the sponge host to the collapse of the population of symbiotic cyanobacteria provides evidence for a coupling between the sponge transcriptomic state and the state of its microbiome. This coupling suggests that the ability of animals to interact with their microbiomes and respond to microbiome perturbations has deep evolutionary origins in this group.

Safety and early biologic effects of phase 1 PERIO-01 trial of pressure-enabled drug delivery (PEDD) of TLR9 agonist SD-101 and immune checkpoint inhibition (ICI) in uveal melanoma metastatic to the liver (MUM).

2521 Background: Delivery barriers due to intratumoral pressure and immunosuppression related to myeloid-derived suppressor cells (MDSC) in liver tumors have created challenges for immunotherapy. TLR9 agonists seem to improve response to ICI. PERIO-01 is a first-in-man trial of PEDD of SD-101 using hepatic arterial infusion (HAI) with ICI in MUM. Methods: PERIO-01 is an open-label phase 1 trial of SD-101 given by HAI in MUM (NCT04935229). The study consists of dose-escalation cohorts of SD-101 alone (Cohort A), with nivolumab (Cohort B), or nivolumab + ipilimumab (Cohort C). SD-101 is delivered over 2 cycles, with 3 weekly doses per cycle. Blood, liver metastasis (LM) and normal liver biopsies are collected for correlative studies. Results: At data cutoff, 33 patients were enrolled, 30 of whom received at least one dose of SD-101, 13 in Cohort A (2, 4, and 8 mg), 15 patients in Cohort B (2 mg and 4 mg) and 2 patients in Cohort C (2 mg). The median age was 63 years of equal gender. Only 3 patients were treatment-naïve and 2 were HLA-A*-02:01+ who received prior tebentafusp. Nine subjects had 4-7 LM and 4 had > 10. The median index LM size was 4.7 cm. Only one patient experienced a grade ≥3 adverse event (AE) related to SD-101, which was increased liver enzymes. All AEs related to cytokine release syndrome have been low-grade with the most common being fever (9), chills (5), and dizziness (4). Treatment resulted in high liver drug levels (median at 2 mg = 1540 ng/g and 8 mg = 2325 ng/g, p = 0.035), with only transient exposure in the periphery ( < 4 hours) and a maximum peak serum level of 554 mg/ml 30 minutes post-infusion. Increases in serum IL-18 and IFNγ were noted, with highest levels at 8 mg. Expansion of natural killer cells were detected in 9 of 10 patients from flow cytometry data peripherally. Monocytic MDSC levels were decreased in 5 of 5 patients on immunofluorescence, and NanoString analysis revealed decreases in ARG-1 and IDO-1 gene levels up to 100 days from initial treatment. Broad immunostimulatory gene expression changes were noted in tumor and normal liver following SD-101, including increases in IFNB1 and IL-9. Using the available samples from 13 patients, 7 of 10 had decrease in ctDNA, with complete clearance in 3, along with circulating tumor cell decreases in 6 of 13. In cohort B at 2 mg, 5 of 6 with available response data have stable disease with a median duration of disease control of 12 weeks (range = 7.5-24) at data cutoff. Conclusions: HAI of SD-101 has been well tolerated and associated with encouraging immunologic activity. Evidence of biologic effects at the lower doses of SD-101 with nivolumab is encouraging and enrollment with escalation continues in Cohorts B and C. Clinical trial information: NCT04935229 .

A non-canonical function of Arabidopsis ERECTA proteins and a role of the SWI3B subunit of the SWI/SNF chromatin remodeling complex in gibberellin signaling.

The Arabidopsis ERECTA family (ERf) of leucine-rich repeat receptor-like kinases (LRR-RLKs) comprising ERECTA (ER), ERECTA-LIKE 1 (ERL1), and ERECTA-LIKE 2 (ERL2) controls epidermal patterning, inflorescence architecture, and stomata development and patterning. These proteins are reported to be plasma membrane associated. Here we show that the er/erl1/erl2 mutant exhibits impaired gibberellin (GA) biosynthesis and perception alongside broad transcriptional changes. The ERf kinase domains were found to localize to the nucleus where they interact with the SWI3B subunit of the SWI/SNF chromatin remodeling complex (CRCs). The er/erl1/erl2 mutant exhibits reduced SWI3B protein level and affected nucleosomal chromatin structure. Similar to swi3c and brm plants with inactivated subunits of SWI/SNF CRCs, it also does not accumulate DELLA RGA and GAI proteins. The ER kinase phosphorylates SWI3B in vitro, and the inactivation of all ERf proteins leads to the decreased phosphorylation of SWI3B protein in vivo. The identified correlation between DELLA overaccumulation and SWI3B proteasomal degradation, and the physical interaction of SWI3B with DELLA proteins indicate an important role of SWI3B-containing SWI/SNF CRCs in gibberellin signaling. Co-localization of ER and SWI3B on GID1 (GIBBERELLIN INSENSITIVE DWARF 1) DELLA target gene promoter regions and abolished SWI3B binding to GID1 promoters in er/erl1/erl2 plants supports the conclusion that ERf-SWI/SNF CRC interaction is important for transcriptional control of GA receptors. Thus, the involvement of ERf proteins in the transcriptional control of gene expression, and observed similar features for human HER2 (epidermal growth family receptor member), indicate an exciting target for further studies of evolutionarily conserved non-canonical functions of eukaryotic membrane receptors.

The geography of breakthrough invention in the United States over the 20th century

The geography of breakthrough invention in the U.S. – defined as the spatial distribution of the production of patents that are both novel and impactful – underwent three broad changes during the 20th century. At the start of the century, breakthrough invention was concentrated in populous metropolitan areas with high levels of local knowledge variety. By the 1930s, breakthroughs were created less frequently across the entire country and so their invention had a less distinct geography. The substantial creation of breakthroughs resumed in the 1960s, and while their invention was once again concentrated in major metropolitan areas with high knowledge variety, they frequently involved long-distance collaboration. In this article, I document these changes and propose a theory to interpret why they occurred. The theory emphasizes how changes in inventors' institutional and communication technology environments influence the geographical locations that are advantageous for breakthrough invention. In support of the model, I find that the disruptiveness of the regime of technological change, the knowledge intensity of breakthroughs, the distance-based frictions incurred by collaboration technologies, and the distance-based frictions incurred by knowledge-sourcing technologies help to predict the spatial distribution of breakthrough invention. To conclude the article, I discuss lessons that the 20th century's geography of breakthrough innovation provide for anticipating the geography of innovation in the 21st century, including in the years beyond COVID-19.

Distributing task-related neural activity across a cortical network through task-independent connections

Task-related neural activity is widespread across populations of neurons during goal-directed behaviors. However, little is known about the synaptic reorganization and circuit mechanisms that lead to broad activity changes. Here we trained a subset of neurons in a spiking network with strong synaptic interactions to reproduce the activity of neurons in the motor cortex during a decision-making task. Task-related activity, resembling the neural data, emerged across the network, even in the untrained neurons. Analysis of trained networks showed that strong untrained synapses, which were independent of the task and determined the dynamical state of the network, mediated the spread of task-related activity. Optogenetic perturbations suggest that the motor cortex is strongly-coupled, supporting the applicability of the mechanism to cortical networks. Our results reveal a cortical mechanism that facilitates distributed representations of task-variables by spreading the activity from a subset of plastic neurons to the entire network through task-independent strong synapses.

Using mechanistic insights to predict the climate‐induced expansion of a key aquatic predator

AbstractAmeliorating the impacts of climate change on communities requires understanding the mechanisms of change and applying them to predict future responses. One way to prioritize efforts is to identify biotic multipliers, which are species that are sensitive to climate change and disproportionately alter communities. We first evaluate the mechanisms underlying the occupancy dynamics of marbled salamanders, a key predator in temporary ponds in the eastern United States We use long‐term data to evaluate four mechanistic hypotheses proposed to explain occupancy patterns, including autumn flooding, overwintering predation, freezing, and winterkill from oxygen depletion. Results suggest that winterkill and fall flooding best explain marbled salamander occupancy patterns. A field introduction experiment supports the importance of winterkill via hypoxia rather than freezing in determining overwinter survival and rejects dispersal limitation as a mechanism preventing establishment. We build climate‐based correlative models that describe salamander occupancy across ponds and years at two latitudinally divergent sites, a southern and middle site, with and without field‐collected habitat characteristics. Correlative models with climate and habitat variation described occupancy patterns better than climate‐only models for each site, but poorly predicted occupancy patterns at the site not used for model development. We next built hybrid mechanistic metapopulation occupancy models that incorporated flooding and winterkill mechanisms. Although hybrid models did not describe observed site‐specific occupancy dynamics better than correlative models, they better predicted the other site's dynamics, revealing a performance trade‐off between model types. Under future climate scenarios, models predict an increased occupancy of marbled salamanders, especially at the middle site, and expansion at a northern site beyond the northern range boundary. Evidence for the climate sensitivity of marbled salamanders combined with their disproportionate ecological impacts suggests that they might act as biotic multipliers of climate change in temporary ponds. More generally, we predict that top aquatic vertebrate predators will expand into temperate‐boreal lakes as climate change reduces winterkill worldwide. Predaceous species with life histories sensitive to winter temperatures provide good candidates for identifying additional biotic multipliers. Building models that include biological mechanisms for key species such as biotic multipliers could better predict broad changes in communities and design effective conservation actions.

The scientific system in the Global South in an emerging multipolar world

ABSTRACT The article analyses the changes and trends in the scientific systems of countries and regions in the Global South shifting the focus away from the BRICS countries. The research is underpinned by the critical scholarship on the globalisation, internationalisation and regionalisation of science and higher education. The empirical analysis is positioned within the broader changes in the international system characterised by multipolarity. The article first aims to map and identify trends, processes and discourses characterising science in the Global South. Second, it aims to investigate and analyse challenges, changes and developments in the scientific system of countries and regions in the Global South by focusing on publications and regional/international collaborations. While knowledge-based theories and discourses are informing science development and changes in countries in the Global South in line with global trends, this is not only done to sustain and increase economic competitiveness. Countries are seeking to reposition themselves in a changing international system by increasing their scientific and technological sovereignty through strategic publications and regional collaborations.

Small extracellular vesicles derived from four dimensional-culture of mesenchymal stem cells induce alternatively activated macrophages by upregulating IGFBP2/EGFR to attenuate inflammation in the spinal cord injury of rats.

Effectively reducing the inflammatory response after spinal cord injury (SCI) is a challenging clinical problem and the subject of active investigation. This study employed a porous scaffold-based three dimensional long-term culture technique to obtain human umbilical cord mesenchymal stem cell (hUC-MSC)-derived Small Extracellular Vesicles (sEVs) (three dimensional culture over time, the "4D-sEVs"). Moreover, the vesicle size, number, and inner protein concentrations of the MSC 4D-sEVs contained altered protein profiles compared with those derived from 2D culture conditions. A proteomics analysis suggested broad changes, especially significant upregulation of Epidermal Growth Factors Receptor (EGFR) and Insulin-like Growth Factor Binding Protein 2 (IGFBP2) in 4D-sEVs compared with 2D-sEVs. The endocytosis of 4D-sEVs allowed for the binding of EGFR and IGFBP2, leading to downstream STAT3 phosphorylation and IL-10 secretion and effective induction of macrophages/microglia polarization from the pro-inflammatory M1 to anti-inflammatory M2 phenotype, both in vitro and in the injured areas of rats with compressive/contusive SCI. The reduction in neuroinflammation after 4D-sEVs delivery to the injury site epicenter led to significant neuroprotection, as evidenced by the number of surviving spinal neurons. Therefore, applying this novel 4D culture-derived Small Extracellular Vesicles could effectively curb the inflammatory response and increase tissue repair after SCI.

Impact of Cofacilitated, Collaborative, Recovery-Oriented Practice Training on Clinical Mental Health Workforce Competencies.

The authors aimed to evaluate the impact of a staff development training program informed by the collaborative recovery model (CRM) on staff outcomes in the largest implementation of CRM undertaken by a public clinical mental health service. Implementation spanned community, rehabilitation, inpatient, and crisis programs for children and youths, adults, and older persons in metropolitan Melbourne, 2017-2018. The CRM staff development program was cofacilitated and coproduced by trainers with clinical and lived experience of recovery (including caregivers) and delivered to the mental health workforce (N=729, including medical, nursing, allied health, lived experience, and leadership staff). The 3-day training program was supplemented by booster training and coaching in team-based reflective practice. Pre- and posttraining measures assessed changes in self-reported CRM-related knowledge, attitudes, skills, and confidence and in the perceived importance of CRM implementation. Staff definitions of recovery were analyzed to understand changes in language related to collaborative recovery. The staff development program significantly (p<0.001) improved self-rated knowledge, attitudes, and skills in applying CRM. At booster training, improvements in attitudes and self-confidence in implementing CRM were maintained. Ratings of the importance of CRM and confidence in the organization's implementation did not change. Definitions of recovery illustrated development of shared language throughout the large mental health program. The cofacilitated CRM staff development program achieved significant changes in staff knowledge, attitudes, skills, and confidence and changes in language related to recovery. These results suggest that implementing collaborative, recovery-oriented practice in a large public mental health program is feasible and can result in broad and sustainable change.

Modelling host-Trypanosoma brucei gambiense interactions in vitro using human induced pluripotent stem cell-derived cortical brain organoids

Background: Sleeping sickness is caused by the extracellular parasite Trypanosoma brucei and is associated with neuroinflammation and neuropsychiatric disorders, including disruption of sleep/wake patterns, and is now recognised as a circadian disorder. Sleeping sickness is traditionally studied using murine models of infection due to the lack of alternative in vitro systems that fully recapitulate the cellular diversity and functionality of the human brain. The aim of this study is to develop a much-needed in vitro system that reduces and replaces live animals for the study of infections in the central nervous system, using sleeping sickness as a model infection. Methods: We developed a co-culture system using induced pluripotent stem cell (iPSC)-derived cortical human brain organoids and the human pathogen T. b. gambiense to model host-pathogen interactions in vitro. Upon co-culture, we analysed the transcriptional responses of the brain organoids to T. b. gambiense over two time points. Results: We detected broad transcriptional changes in brain organoids exposed to T. b. gambiense, mainly associated with innate immune responses, chemotaxis, and blood vessel differentiation compared to untreated organoids. Conclusions: Our co-culture system provides novel, more ethical avenues to study host-pathogen interactions in the brain as alternative models to experimental infections in mice. Future work is required to increase the complexity of the organoids (e.g., addition of microglia and vasculature). We envision that the adoption of organoid systems will be beneficial to researchers studying mechanisms of brain infection by protozoan parasites. Furthermore, organoid systems have the potential to be used to study other parasites that affect the brain, including neurocysticercosis, significantly reducing the number of animals undergoing moderate and/or severe protocols associated with the study of neuroinflammation and brain infections.

Carbonate diagenesis: A celebration of the work of John Anthony Dawson (Tony) Dickson

Carbonate diagenesis: A celebration of the work of John Anthony Dawson (Tony) Dickson

Lumbar endplate microfracture injury induces Modic-like changes, intervertebral disc degeneration and spinal cord sensitization – an in vivo rat model

BACKGROUND CONTEXTEndplate (EP) injury plays critical roles in painful IVD degeneration since Modic changes (MCs) are highly associated with pain. Models of EP microfracture that progress to painful conditions are needed to better understand pathophysiological mechanisms and screen therapeutics. PURPOSEEstablish in vivo rat lumbar EP microfracture model and assess crosstalk between IVD, vertebra and spinal cord. STUDY DESIGN/SETTINGIn vivo rat EP microfracture injury model with characterization of IVD degeneration, vertebral remodeling, spinal cord substance P (SubP), and pain-related behaviors. METHODSEP-injury was induced in 5 month-old male Sprague-Dawley rats L4–5 and L5–6 IVDs by puncturing through the cephalad vertebral body and EP into the NP of the IVDs followed by intradiscal injections of TNFα (n=7) or PBS (n=6), compared with Sham (surgery without EP-injury, n=6). The EP-injury model was assessed for IVD height, histological degeneration, pain-like behaviors (hindpaw von Frey and forepaw grip test), lumbar spine MRI and μCT, and spinal cord SubP. RESULTSSurgically-induced EP microfracture with PBS and TNFα injection induced IVD degeneration with decreased IVD height and MRI T2 signal, vertebral remodeling, and secondary damage to cartilage EP adjacent to the injury. Both EP injury groups showed MC-like changes around defects with hypointensity on T1-weighted and hyperintensity on T2-weighted MRI, suggestive of MC type 1. EP injuries caused significantly decreased paw withdrawal threshold, reduced axial grip, and increased spinal cord SubP, suggesting axial spinal discomfort and mechanical hypersensitivity and with spinal cord sensitization. CONCLUSIONSSurgically-induced EP microfracture can cause crosstalk between IVD, vertebra, and spinal cord with chronic pain-like conditions. CLINICAL SIGNIFICANCEThis rat EP microfracture model was validated to induce broad spinal degenerative changes that may be useful to improve understanding of MC-like changes and for therapeutic screening.

“Even I am a Part of Nature”: Unraveling the Human/Nature Binary to Enable Systems Change

ABSTRACT While contemporary ecocidal cultures are premised on a human/nature binary that treats humans as separate from, superior to, and entitled to mastery over nature, this study explores a range of commonly existing imaginaries that unravel the binary and could enable broad systems change. We introduce a deceptively simple freewrite methodology around the foundational concept “nature” to decipher such unravelings in Western/ized settings. Applying this methodology in the United States, Australia, and New Zealand, we exhibit how freewrites can improvisationally reveal and engage productive tensions (dialectics) that trouble the binary, support reflexive ecologically centered becoming, and, in some cases, provide ways to eschew the binary altogether. The present study operates from the stubbornly optimistic perspective that our species’ capacity to collectively, even quickly embrace ecocentric meaning systems that trigger massive change should be widely acknowledged and actively encouraged.