The Alternative Host with the Most: Understanding the Ecology of Xanthomonas hortorum pv. carotae on Noncarrot Crops in Central Oregon.

Bacterial blight of carrot, caused by Xanthomonas hortorum pv. carotae (Xhc), is an economically important disease in carrot (Daucus carota subsp. sativus) seed production. The objectives of this study were to determine if Xhc was present on noncarrot crops grown in central Oregon and, if detected, evaluate its ability to colonize alternative hosts. Surveys of three carrot seed fields and adjacent fields of rye (Secale cereale), alfalfa (Medicago sativa), parsley root (Petroselinum crispum var. tuberosum), and Kentucky bluegrass (Poa pratensis) demonstrated that Xhc was present on noncarrot crops. Greenhouse experiments were conducted to determine the ability of Xhc to colonize crops cultivated in the region. Carrot, alfalfa, curly parsley (Petroselinum crispum), Kentucky bluegrass, mint (Mentha × piperita), parsley root, roughstalk bluegrass (Poa trivialis), and wheat (Triticum aestivum) plants were spray-inoculated with Xhc and destructively sampled at 1, 7, 14, and 28 or 25 days post-inoculation. Xhc populations were quantified using viability quantitative PCR and dilution plating. A significant (P ≤ 0.03) effect of crop was observed at 1, 14, and 28 or 25 days in both experiments. While carrot hosted the most Xhc at the final timepoint, other crops supported epiphytic Xhc populations including wheat and both bluegrasses. Mint, parsley root, and alfalfa hosted the least Xhc. Bacterial blight symptoms were observed on carrots but not on noncarrot crops. This suggests that crops grown in central Oregon have the potential to be asymptomatically colonized by Xhc and may serve as reservoirs of the pathogen in carrot seed production systems.

First report of Spiroplasma citri associated with disease symptoms in field-grown hemp (Cannabis sativa L.) in the Pacific Northwest.

Hemp (Cannabis sativa L.) is grown for cannabinoid oil production in Oregon. During the 2021 and 2022 growing seasons, plants with leaf curling, puckering, chlorotic mosaic, fasciation, and vein clearing were observed in disease surveys of Oregon hemp fields (Fig. 1). Symptoms were present on 1-10% of 2-4-month-old plants in fields located in Benton, Clackamas, Deschutes, Jackson, Josephine, Lane, Linn, Marion, Morrow, and Polk counties between July and September. Leaf and stem samples were collected from 38 symptomatic plants. Symptoms resembled those caused by beet leafhopper-vectored (BLH, Circulifer tenellus Baker) curtovirus or phytoplasma infection. Therefore, total nucleic acids were extracted (Dellaporta et al. 1983) from leaf material, and PCR conducted on all 38 samples to detect curtovirus coat proteins (BCTV-1/2 primers; Rondon et al. 2016) and 16S rRNA of phytoplasmas (nested primers P1/P7 followed by FU/RU; Lorenz et al. 1995). No curtoviruses or phytoplasmas were detected in any samples. Spiroplasma citri is also transmitted by BLH, so PCR was conducted with primers targeting the putative P89 adhesin gene and spiralin gene of S. citri (Yokomi et al. 2008). For all samples, PCR using P89F/R primers resulted in a 707 bp amplicon, and a 675 bp amplicon with Spiralin-f/r primers. PCR products were purified with ExoSapIT (Applied Biosystems, Waltham, MA), and two representative samples (ScH1; ScH2) were Sanger sequenced (EuroFins, Lancaster, PA) in the forward and reverse direction. Pairwise aligned P89 sequences were found to be 99 to 100% (ScH1: 633/637 bp; ScH2: 654/654 bp) identical to S. citri accession KT377386. Aligned/span>spiralin sequences were found to be 99 to 100% (ScH1: 661/664 bp; ScH2: 647/647 bp) identical to S. citri accession CP013197 in the NCBI GenBank Database. All sequences were deposited into GenBank (accession no. OQ969983, OQ992766, OQ969984, OQ969986). Frozen leaf material from one sample was used to culture S. citri according to Lee and Davis (1984). Leaf tissue was surface sterilized for 60 s in 1% NaOCl in 70% ethanol, cut into pieces in LD8 broth, and incubated for 25 min at 25˚C. The solution was passed through a 0.45um filter and incubated for 14 days at 30°C with constant shaking (150 rpm). Then, cultures were centrifuged for 2 min at 12,000 rpm to pelletize, resuspended in 100µL sterile distilled water and passed through a 0.2um filter. From this culture, 2 µL of broth was used as template for both the P89F/R and Spiralin-f/r primer sets. Amplicons were purified and sequenced as above (accession nos. OQ969982, OQ969985). Leaf tissue from both representative samples (ScH1 and ScH2) were positive for S. citri using double antibody sandwich ELISA (Agdia, Inc., Elkhart, IN) following manufacturer instructions. These results from sequencing, culturing, and ELISA testing indicate the hemp samples were infected with S. citri. To our knowledge this is the first report of disease symptoms in hemp associated with S. citri in Oregon and the Pacific Northwest. Infection by S. citri can limit yield by reducing photosynthetic capability of the plant and distortion of plant growth. Other pathogens like curtoviruses and phytoplasmas have also been detected in hemp in Oregon and the U.S. (Hu 2021; Rivedal et al. 2022), and the addition of S. citri associated with disease symptoms indicates a need for BLH management research. This discovery has implications for arid regions with other S. citri hosts including cruciferous plants, carrots, and tree fruit crops, all of which were grown near the sampled hemp fields in this study.

Retinal electrophysiology in central nervous system disorders. A review of human and mouse studies.

The retina and brain share similar neurochemistry and neurodevelopmental origins, with the retina, often viewed as a "window to the brain." With retinal measures of structure and function becoming easier to obtain in clinical populations there is a growing interest in using retinal findings as potential biomarkers for disorders affecting the central nervous system. Functional retinal biomarkers, such as the electroretinogram, show promise in neurological disorders, despite having limitations imposed by the existence of overlapping genetic markers, clinical traits or the effects of medications that may reduce their specificity in some conditions. This narrative review summarizes the principal functional retinal findings in central nervous system disorders and related mouse models and provides a background to the main excitatory and inhibitory retinal neurotransmitters that have been implicated to explain the visual electrophysiological findings. These changes in retinal neurochemistry may contribute to our understanding of these conditions based on the findings of retinal electrophysiological tests such as the flash, pattern, multifocal electroretinograms, and electro-oculogram. It is likely that future applications of signal analysis and machine learning algorithms will offer new insights into the pathophysiology, classification, and progression of these clinical disorders including autism, attention deficit/hyperactivity disorder, bipolar disorder, schizophrenia, depression, Parkinson's, and Alzheimer's disease. New clinical applications of visual electrophysiology to this field may lead to earlier, more accurate diagnoses and better targeted therapeutic interventions benefiting individual patients and clinicians managing these individuals and their families.

Lifetime prevalence and knowledge of snakebite among graduates in Nigeria.

BACKGROUND: Given the lack of studies on snakebite envenoming knowledge in the general population, we examined the lifetime prevalence of snakebite and knowledge of snakebite and its prevention and first aid among recent Nigerian graduates in national service. METHODS: This questionnaire-based cross-sectional study involved 351 consenting national youth corps members at a rural orientation camp in Kano, Nigeria. RESULTS: Participants' mean age was 25.3±2.4 y. There were slightly more males (50.7%). Most attended universities (77.8%) and were mainly from the southwest (24.5%) and northeast (24.5%) geopolitical regions and the Yoruba tribe (24.7%). Their lifetime prevalence of snakebite was 4%. Their mean overall knowledge score was 6.8±3.1 out of 20. Only 0.9% had adequate knowledge. Gender (male; 7.2±3.1, t=2.83, p=0.0049), tribe (Yoruba; 7.5±2.9, F=2.968, p=0.0320), region (Southwest; 7.6±3.0, F=2.5289, p=0.0289) and nearly bitten by snake (7.8 ± 2.7, t=3.60, p=0.0004) were significantly associated with a higher mean knowledge score. CONCLUSIONS: Their lifetime prevalence of snakebites is significant, while knowledge of snakebite is very inadequate. However, the national service camp activities period provides an opportunity for educational intervention needed to raise their knowledge to optimal levels that will enable them serve as better snakebite prevention agents, as they will be working in rural communities where snakebite might be prevalent.

Optimizing Retinal Thermofusion in Retinal Detachment Repair: Achieving Instant Adhesion without Air Tamponade.

Purpose: Rhegmatogenous retinal detachment repair by intraoperative sealing of the tear without a tamponade agent should enable faster restoration of vision and resumption of normal activities. It avoids the need for further surgery in the case of silicone oil endotamponade. This study evaluated the retinal thermofusion (RTF) retinopexy method of subretinal space dehydration before photocoagulation to create an instantaneous intraoperative retina reattachment in a preclinical model. Design: Preclinical study. Participants: Twenty Dutch Belt, pigmented rabbits that underwent RTF repair after experimental retinal detachment. Methods: This ex vivo model quantified adhesion force between the retina and underlying retinal pigment epithelium and choroid after treatment of 1 retinal edge using postmortem porcine or human retina (6 × 12 mm). We compared (1) control, (2) laser photocoagulation alone, (3) dehydration alone, and (4) dehydration followed by photocoagulation (RTF). Optimized parameters for RTF were then applied in the in vivo rabbit model of retinal detachment. Animals were followed up for 14 days. Main Outcome Measures: For this ex vivo model, we measured adhesion force and related this to tissue temperature. For the in vivo study, we assessed retinal attachment using funduscopy and histologic analysis. Results: The ex vivo model showed that RTF repair produced significantly higher adhesion force than photocoagulation alone independent of dehydration method: warm (60° C) high airflow (50-70 ml/minute) or using laser wavelengths targeting water absorption peaks (1470 or 1940 nm) with coaxial low airflow (10-20 ml/minute). The latter approach produced a smaller footprint of dehydration. Application of RTF (1940-nm laser with coaxial airflow) in an in vivo retinal detachment model in rabbit eyes resulted in immediate retinal adhesion, achieving forces similar to those in the ex vivo experiments. Retinal thermofusion repair resulted in stable reattachment of the retina over the 2-week follow-up period. Conclusions: We showed that a short preliminary dehydrating laser treatment of a retinal tear margin before traditional laser photocoagulation creates an immediate intraoperative waterproof retinopexy adhesion independent of tamponade and a wound-healing response. This approach potentially will allow rapid postoperative recovery regardless of the tear location and improved vision.

Evaluation of Sulfur-Based Biostimulants for the Germination of Sclerotium cepivorum Sclerotia and Their Interaction with Soil.

White rot is an economically significant disease of Allium crops. The pathogen Sclerotium cepivorum produces long-lived sclerotia that germinate in response to sulfur-containing compounds released from Allium roots. Diallyl disulfide (DADS) was the primary organic sulfur compound detected in the rhizosphere soil of two garlic cultivars, "California Early and Late", growing in greenhouse conditions. DADS, dimethyl trisulfide (DMTS), dimethyl disulfide (DMDS), isopropyl disulfide (IPDS), dipropyl disulfide (DPDS), diethyl disulfide (DEDS), together with garlic oil, garlic juice, garlic powder, raw onion pieces, cabbage pieces, and Chinese cabbage pieces were investigated for their activities toward germinating dormant sclerotia. Results showed that DADS and other volatile sulfur compounds could stimulate sclerotial germination, and a dose-response was observed. In addition, garlic juice, powder, raw onion, and the two cabbages could stimulate sclerotial germination. Furthermore, the laboratory soil incubation experiments demonstrated the strong interaction of organic sulfur compounds with soil.

Beyond the Classroom: An Observational Study to Assess Student Pharmacists' Confidence and Perception of a High-Fidelity Manikin Chemotherapy Infusion Reaction Simulation.

Objective: To assess the impact of a high-fidelity manikin chemotherapy infusion simulation on student pharmacists' confidence in applying clinical knowledge and perception of oncology pharmacy practice. Methods: One cohort of third professional year student pharmacists completed a high-fidelity manikin simulation during the last week of their didactic training. The 10-minute manikin experience simulated an acute paclitaxel infusion reaction, requiring students to apply their knowledge on how to provide patient care during a chemotherapy-induced infusion reaction. A pre- and post-survey was administered to determine whether there was a change in students' confidence and perception. Results: Thirty-three student pharmacists (62%) completed the pre- and post-surveys and manikin simulation. A statistically significant improvement was seen in median confidence scores when comparing pre- and post-questions of all 10 survey items (P < 0.001). Students' perception of oncology pharmacy and the manikin simulation had mean of 4.4 on a 0- to 5-point Likert scale. Conclusion: The high-fidelity manikin experience improved student pharmacists' post-survey confidence of applying clinical skills. In addition, students' perception of oncology pharmacy improved and the use of a manikin simulation to support didactic learning was seen as an additional avenue for delivering didactic curriculum. This study explored the feasibility of introducing a manikin simulation into the oncology pharmacy curriculum and the benefit of providing hands-on application of clinical skills to support didactic concept-based learning.

Characterization of retinal function and structure in the MPTP murine model of Parkinson's disease.

In addition to well characterized motor symptoms, visual disturbances are increasingly recognized as an early manifestation in Parkinson's disease (PD). A better understanding of the mechanisms underlying these changes would facilitate the development of vision tests which can be used as preclinical biomarkers to support the development of novel therapeutics for PD. This study aims to characterize the retinal phenotype of a mouse model of dopaminergic dysfunction and to examine whether these changes are reversible with levodopa treatment. We use a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD to characterize the neurotoxic effects of MPTP on in vivo retinal function (electroretinography, ERG), retinal structure (optical coherence tomography, OCT) and retinal dopaminergic cell number (tyrosine hydroxylase immunohistochemistry, IHC) at two time points (21 and 45 days) post MPTP model induction. We also investigate the effect of levodopa (L-DOPA) as a proof-of-principle chronic intervention against MPTP-induced changes in the retina. We show that MPTP decreases dopaminergic amacrine cell number (9%, p < 0.05) and that a component of the ERG that involves these cells, in particular oscillatory potential (OP) peak timing, was significantly delayed at Day 45 (7-13%, p < 0.01). This functional deficit was paralleled by outer plexiform layer (OPL) thinning (p < 0.05). L-DOPA treatment ameliorated oscillatory potential deficits (7-13%, p < 0.001) in MPTP animals. Our data suggest that the MPTP toxin slows the timing of inner retinal feedback circuits related to retinal dopaminergic pathways which mirrors findings from humans with PD. It also indicates that the MPTP model causes structural thinning of the outer retinal layer on OCT imaging that is not ameliorated with L-DOPA treatment. Together, these non-invasive measures serve as effective biomarkers for PD diagnosis as well as for quantifying the effect of therapy.

Pepaxto: A New Peptide-Drug Conjugate for Heavily Pretreated Relapsed and Refractory Multiple Myeloma.

OBJECTIVE: The objective of this article was to review existing data of melflufen (Pepaxto) as an additional treatment option for heavily pretreated relapsed and refractory multiple myeloma. DATA SOURCES: A PubMed search was completed using the search terms melphalan flufenamide; melflufen; melflufen AND relapsed refractory multiple myeloma; melphalan flufenamide and relapsed refractory multiple myeloma between January 1, 2013, and October 18, 2021. Additional information was obtained from the National Institutes of Health Clinical Trial Registry, Federal Drug Administration (FDA) web updates, and Pepaxto prescribing information. STUDY SELECTION/DATA EXTRACTION: Clinical trials including melflufen in relapsed refractory multiple myeloma and trials related to safety and clinical pharmacology were included. DATA SYNTHESIS: The findings of this review show melflufen in combination with dexamethasone can be used as a treatment option for patients with relapsed and refractory multiple myeloma who have previously received greater than 4 previous lines of therapy, and documented resistance to a proteosome inhibitor, an anti-CD38 monoclonal antibody, and an immunomodulator. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Melflufen in combination with dexamethasone is a reasonable option for patients with relapsed and refractory multiple myeloma who have received at least 4 previous lines of therapy and considered ineligible for autologous stem cell transplant. Further clinical utilization in earlier lines of therapy is under review, pending the in-depth safety analysis by the FDA. CONCLUSIONS: The FDA approval of melflufen in combination with dexamethasone provides an additional therapy option for patients with heavily pretreated relapsed and refractory multiple myeloma.

Progressive impairments in executive function in the APP/PS1 model of Alzheimer's disease as measured by translatable touchscreen testing.

Executive function deficits in Alzheimer's disease (AD) occur early in disease progression and may be predictive of cognitive decline. However, no preclinical studies have identified deficits in rewarded executive function in the commonly used APPSwe/PS1∆E9 (APP/PS1) mouse model. To address this, we assessed 12-26 month old APP/PS1 mice on rewarded reversal and/or extinction tasks. 16-month-old, but not 13- or 26-month-old, APP/PS1 mice showed an attenuated rate of extinction. Reversal deficits were seen in 22-month-old, but not 13-month-old APP/PS1 animals. We then confirmed that impairments in reversal were unrelated to previously reported visual impairments in both AD mouse models and humans. Age, but not genotype, had a significant effect on markers of retinal health, indicating the deficits seen in APP/PS1 mice were directly related to cognition. This is the first characterisation of rewarded executive function in APP/PS1 mice, and has great potential to facilitate translation from preclinical models to the clinic.

Anterior cingulate and putamen neurons flexibly learn whether a hot dog is a sandwich.

Policy search lets you discover rules and adapt behavior. In this issue of Neuron, Cohen et al. (2021) demonstrate that the dynamics of neurons in primate anterior cingulate cortex and putamen indicate when a correct policy is discovered and confidence in executing decisions under that policy.

Retinal hyperspectral imaging in the 5xFAD mouse model of Alzheimer's disease.

Hyperspectral imaging of the retina has recently been posited as a potentially useful form of spectroscopy of amyloid-beta (Aß) protein in the eyes of those with Alzheimer's disease (AD). The concept of using the retina as a biomarker for AD is an attractive one, as current screening tools for AD are either expensive or inaccessible. Recent studies have investigated hyperspectral imaging in Aß models however these studies have been in younger mice. Here we characterised hyperspectral reflectance profile in 6 to 17 months old 5xFAD mice and compare this to Aß in isolated preparations. Hyperspectral imaging was conducted across two preparations of Aß using a custom built bench ophthalmoscope. In the in vitro condition, 1 mg of purified human Aß42 was solubilised and left to aggregate for 72 h. This soluble/insoluble Aß mixture was then imaged by suspending the solution at a pipette tip and compared against phosphate buffered saline (PBS) control (n = 10 ROIs / group). In the in vivo condition, a 5xFAD transgenic mouse model was used and retinae were imaged at the age of 6 (n = 9), 12 (n = 9) and 17 months (n = 8) with age matched wildtype littermates as control (n = 12, n = 13, n = 15 respectively). In the vitro condition, hyperspectral imaging of the solution showed greater reflectance compared with vehicle (p < 0.01), with the greatest differences occurring in the short visible spectrum (< 500 nm). In the in vivo preparation, 5xFAD showed greater hyperspectral reflectance at all ages (6, 12, 17 months, p < 0.01). These differences were noted most in the short wavelengths at younger ages, with an additional peak appearing at longer wavelengths (~ 550 nm) with advancing age. This study shows that the presence of Aß (soluble/insoluble mixture) can increase the hyperspectral reflectance profile in vitro as well as in vivo. Differences were evident in the short wavelength spectrum (< 500 nm) in vitro and were preserved when imaged through the ocular media in the in vivo conditions. With advancing age a second hump around ~ 550 nm became more apparent. Hyperspectral imaging of the retina does not require the use of contrast agents and is a potentially useful and non-invasive biomarker for AD.

Molecular and Alkaloid Characterization of Claviceps purpurea Sensu Lato From Grass Seed Production Areas of the U.S. Pacific Northwest.

Ergot, caused by Claviceps purpurea sensu lato, is an economically important seed replacement disease of Kentucky bluegrass (Poa pratensis) and perennial ryegrass (Lolium perenne) seed crops. C. purpurea sensu stricto is considered the primary Claviceps species responsible, but genetic diversity and cryptic species within C. purpurea sensu lato have previously been reported. Fifty-six C. purpurea sensu lato isolates collected from P. pratensis (n = 21) and L. perenne (n = 35) in Oregon and Washington between 2010 and 2014 were characterized via random amplified polymorphic DNA (RAPD), partial internal transcribed spacer (ITS), ß-tubulin and elongation factor-1α (EF-1α) sequences, conidial size, and ergot alkaloid chemotype. Based on RAPD analysis, seven isolates from P. pratensis and 33 isolates from L. perenne collected in Oregon corresponded to C. purpurea sensu stricto, and 13 isolates collected from P. pratensis in Washington and Oregon were identified as C. humidiphila. Partial ITS, ß-tubulin, and EF-1α sequences identified 10 isolates from P. pratensis as C. humidiphila, and seven isolates from P. pratensis and 33 isolates from L. perenne were identified as C. purpurea sensu stricto. Several isolates generated ambiguous RAPD bands or sequences that prevented identification. Ergot alkaloid chemotype profiling found that ergocornine and its epimer were predominant in sclerotia from P. pratensis, whereas ergotamine and its epimer were most abundant in sclerotia from L. perenne. This study confirms the presence of the C. purpurea sensu lato species complex in the U.S. Pacific Northwest and suggests that more research is needed to characterize and mitigate Claviceps spp. infection of grass seed crops in North America.

Morphometric Changes to Corneal Dendritic Cells in Individuals With Mild Cognitive Impairment.

PURPOSE: There has been increasing interest in identifying non-invasive, imaging biomarkers for neurodegenerative disorders of the central nervous system (CNS). The aim of this proof-of-concept study was to investigate whether corneal sensory nerve and dendritic cell (DC) parameters, captured using in vivo confocal microscopy (IVCM), are altered in individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD). METHODS: Fifteen participants were recruited from the Australian Imaging Biomarkers and Lifestyle (AIBL) study in Melbourne, VIC, Australia. The cohort consisted of cognitively normal (CN) individuals (n = 5), and those with MCI (n = 5) and AD (n = 5). Participants underwent a slit lamp examination of the anterior segment, followed by corneal imaging using laser-scanning in vivo confocal microscopy (IVCM) of the central and inferior whorl regions. Corneal DC density, field area, perimeter, circularity index, aspect ratio, and roundness were quantified using Image J. Quantitative data were derived for corneal nerve parameters, including nerve fiber length (CNFL), fiber density (CNFD), branch density (CNBD), and diameter. RESULTS: Corneal DC field area and perimeter were greater in individuals with MCI, relative to CN controls, in both the central and inferior whorl regions (p < 0.05 for all comparisons). In addition, corneal DCs in the whorl region of MCI eyes had lower circularity and roundness indices and a higher aspect ratio relative to CNs (p < 0.05 for all comparisons). DC density was similar across participant groups in both corneal regions. There was a trend toward lower quantitative parameters for corneal nerve architecture in the AD and MCI groups compared with CN participants, however, the inter-group differences did not reach statistical significance. Central corneal nerve diameters were similar between groups. CONCLUSION: This study is the first to report morphological differences in corneal DCs in humans with MCI. These differences were evident in both the central and mid-peripheral cornea, and in the absence of significant nerve abnormalities or a difference in DC density. These findings justify future large-scale studies to assess the utility of corneal IVCM and DC analysis for identifying early stage pathology in neurodegenerative disorders of the CNS.

Verticillium Wilt of Mint in the United States of America.

Verticillium wilt, caused by the fungus Verticillium dahliae, is the most important and destructive disease of mint (Mentha spp.) in the United States (U.S.). The disease was first observed in commercial mint fields in the Midwestern U.S. in the 1920s and, by the 1950s, was present in mint producing regions of the U.S. Pacific Northwest. Verticillium wilt continues to be a major limiting factor in commercial peppermint (Mentha x piperita) and Scotch spearmint (Mentha x gracilis) production, two of the most important sources of mint oil in the U.S. The perennial aspect of U.S. mint production, coupled with the soilborne, polyetic nature of V. dahliae, makes controlling Verticillium wilt in mint a challenge. Studies investigating the biology and genetics of the fungus, the molecular mechanisms of virulence and resistance, and the role of soil microbiota in modulating host-pathogen interactions are needed to improve our understanding of Verticillium wilt epidemiology and inform novel disease management strategies. This review will discuss the history and importance of Verticillium wilt in commercial U.S. mint production, as well as provide a format to highlight past and recent research advances in an effort to better understand and manage the disease.

Mesoscopic-scale functional networks in the primate amygdala.

The primate amygdala performs multiple functions that may be related to the anatomical heterogeneity of its nuclei. Individual neurons with stimulus- and task-specific responses are not clustered in any of the nuclei, suggesting that single-units may be too-fine grained to shed light on the mesoscale organization of the amygdala. We have extracted from local field potentials recorded simultaneously from multiple locations within the primate (Macaca mulatta) amygdala spatially defined and statistically separable responses to visual, tactile, and auditory stimuli. A generalized eigendecomposition-based method of source separation isolated coactivity patterns, or components, that in neurophysiological terms correspond to putative subnetworks. Some component spatial patterns mapped onto the anatomical organization of the amygdala, while other components reflected integration across nuclei. These components differentiated between visual, tactile, and auditory stimuli suggesting the presence of functionally distinct parallel subnetworks.

Retinal Functional and Structural Changes in the 5xFAD Mouse Model of Alzheimer's Disease.

Alzheimer's disease is characterized by the aberrant deposition of protein in the brain and is the leading cause of dementia worldwide. Increasingly, there have been reports of the presence of these protein hallmarks in the retina. In this study, we assayed the retina of 5xFAD mice, a transgenic model of amyloid deposition known to exhibit dementia-like symptoms with age. Using OCT, we found that the retinal nerve fiber layer was thinner in 5xFAD at 6, 12, and 17 months of age compared with wild-type littermates, but the inner plexiform layer was thicker at 6 months old. Retinal function showed reduced ganglion cell responses to light in 5xFAD at 6, 12, and 17 months of age. This functional loss was observed in the outer retina at 17 months of age but not in younger mice. We showed using immunohistochemistry and ELISA that soluble and insoluble amyloid was present in the retina and brain at all ages. In conclusion, we report that amyloid is present in brain and retina of 5xFAD mice and that the pattern of neuronal dysfunction occurs in the inner retina at the early ages and progresses to encompass the outer retina with age. This implies that the inner retina is more sensitive to amyloid changes in early disease and that the outer retina is also affected with disease progression.

Fostering global primary care research: a capacity-building approach.

The Alma Ata and Astana Declarations reaffirm the importance of high-quality primary healthcare (PHC), yet the capacity to undertake PHC research-a core element of high-quality PHC-in low-income and middle-income countries (LMIC) is limited. Our aim is to explore the current risks or barriers to primary care research capacity building, identify the ongoing tensions that need to be resolved and offer some solutions, focusing on emerging contexts. This paper arose from a workshop held at the 2019 North American Primary Care Research Group Annual Meeting addressing research capacity building in LMICs. Five case studies (three from Africa, one from South-East Asia and one from South America) illustrate tensions and solutions to strengthening PHC research around the world. Research must be conducted in local contexts and be responsive to the needs of patients, populations and practitioners in the community. The case studies exemplify that research capacity can be strengthened at the micro (practice), meso (institutional) and macro (national policy and international collaboration) levels. Clinicians may lack coverage to enable research time; however, practice-based research is precisely the most relevant for PHC. Increasing research capacity requires local skills, training, investment in infrastructure, and support of local academics and PHC service providers to select, host and manage locally needed research, as well as to disseminate findings to impact local practice and policy. Reliance on funding from high-income countries may limit projects of higher priority in LMIC, and 'brain drain' may reduce available research support; however, we provide recommendations on how to deal with these tensions.

Distribution of Xanthomonas hortorum pv. carotae Populations in Naturally Infested Carrot Seed Lots.

Bacterial blight of carrot (Daucus carota subsp. sativus), caused by the plant-pathogenic bacterium Xanthomonas hortorum pv. carotae, is a common seedborne disease of carrot wherever the crop is grown. Carrot seed lots were evaluated to determine the variability and distribution of populations of X. hortorum pv. carotae among individual carrot seeds. Twenty-four carrot seed lots harvested between 2014 and 2016 were subjected to a bulk seed wash dilution-plate assay to obtain mean X. hortorum pv. carotae levels. Mean infestation levels resulting from the bulk seed wash assays among the 24 seed lots ranged from 1.2 × 107 and 9.6 × 108 CFU/g seed and averaged 3.6 × 108 CFU/g seed. Individual seeds from the same 24 lots were also tested with a scaled-down wash assay of individual seeds. Among the 1,380 seeds that were individually assayed, 475 X. hortorum pv. carotae-positive seeds were detected (34.4%). Rates of X. hortorum pv. carotae detection on individual seed in seed lots ranged from 0% (not detected) to 97.9%, and the mean and median X. hortorum pv. carotae population on an individual seed was 8.3 × 104 and 6.3 × 101 CFU/seed, respectively. Among individual seeds, X. hortorum pv. carotae populations ranged from 2 (the limit of detection of the assay) to 3.6 × 107 CFU/seed. CFU data for 23 of the 24 seed lots were nonnormal and the Log-Logistic (3P) distribution best described populations of X. hortorum pv. carotae recovered from individual carrot seeds. The influence and impact of nonnormal distributions of X. hortorum pv. carotae in commercial carrot seed lots on seed health tests, seedborne transmission, and bacterial blight epidemiology requires further study.

Age-Specific Retinal and Cerebral Immunodetection of Amyloid-ß Plaques and Oligomers in a Rodent Model of Alzheimer's Disease.

BACKGROUND: Amyloid-ß soluble oligomers (Aßo) are believed to be the cause of the pathophysiology underlying Alzheimer's disease (AD) and are normally detected some two decades before clinical onset of the disease. Retinal pathology associated with AD pathogenesis has previously been reported, including ganglion cell loss, accumulation of Aß deposits in the retina, and reduction of nerve fiber layer thickness as well as abnormalities of the microvasculature. OBJECTIVE: This study's aim is to better understand the relationship between brain and retinal Aßo deposition and in particular to quantify levels of the toxic Aßo as a function of age in the retina of a rodent model of AD. METHODS: Retinas and brain tissue from 5×FAD mice were stained with Congo red, Thioflavin-T (Th-T), and Aß plaque-specific and Aßo-specific antibodies. RESULTS: We show that retinas displayed an age-dependent increase of Th-T-specific amyloid fibrils. Staining with anti-Aß antibody confirmed the presence of the Aß plaques in all 5×FAD retinas tested. In contrast, staining with anti-Aßo antibody showed an age-dependent decrease of retinal Aßo. Of note, Aßo was observed mainly in the retinal nuclear layers. Finally, we confirmed the localization of Aßo to neurons, typically accumulating in late endosomes, indicating possible impairment of the endocytic pathway. CONCLUSION: Our results demonstrate the presence of intraneuronal Aßo in the retina and its accumulation inversely correlated with retinal Aß plaque deposition, indicating an age-related conversion in this animal model. These results support the development of an early AD diagnostic test targeting Aßo in the eye.