The human gut microbiome represents an extended “second genome” harbouring about 1015 microbes containing >100 times the number of genes as the host. States of health and disease are largely mediated by host–microbial metabolic interplay, and the microbiome composition also underlies the differential responses to chemotherapeutic agents between people. Chemical information will be the key to tackle this complexity and discover specific gut microbiome metabolism for creating more personalised interventions. Additionally, rising antibiotic resistance and growing awareness of gut microbiome effects are creating a need for non-microbicidal therapeutic interventions. We classify chemical interventions for the gut microbiome into categories like molecular decoys, bacterial conjugation inhibitors, colonisation resistance-stimulating molecules, “prebiotics” to promote the growth of beneficial microbes, and inhibitors of specific gut microbial enzymes. Moreover, small molecule probes, including click chemistry probes, artificial substrates for assaying gut bacterial enzymes and receptor agonists/antagonists, which engage host receptors interacting with the microbiome, are some other promising developments in the expanding chemical toolkit for probing and modulating the gut microbiome. This review explicitly excludes “biologics” such as probiotics, bacteriophages, and CRISPR to concentrate on chemistry and chemical tools like chemoproteomics in the gut-microbiome context.

Objectives/Goals: Cerebral amyloid angiopathy (CAA) characterized by the accumulation of amyloid-beta in the cerebrovasculature, affects blood vessel integrity leading to brain hemorrhages and an accelerated cognitive decline in Alzheimer’s disease patients. In this study, we are conducting a genome-wide association study to identify genetic risk factors for CAA. Methods/Study Population: We genotyped 1253 additional AD cases using and curated existing genome-wide genotype data from 110 AD and 502 non-AD donors from the Mayo Clinic Brain Bank. We performed QC and imputation of all datasets. We conducted GWAS in AD only (N =  1,363), non-AD only, as well as the combined cohort (N = 1,865) by testing imputed variant dosages for association with square root transformed CAA using linear regression, adjusting for relevant covariates. To assess associations in the context of major CAA risk factors, we performed interaction analysis with APOEe4 presence and sex; and pursued stratified analyses. We collected peripheral gene expression measures using RNA isolated from 188 PAXgene tube samples of 95 donors collected across multiple time points. More than 1/3 of these participants have MRI measures collected. Results/Anticipated Results: Variants at the APOE locus were identified as the most significant in our study. In addition, several other variants with suggestive association were found under the main model adjusting for AD neuropathology (Braak and Thal). LINC-PINT splice variant remained associated with lower CAA scores in AD cases without the APOEe4 risk allele. To enhance the robustness of our findings, we are pursuing further expansion of our study cohort. In the periphery, we expect to identify expression changes associated with neuroimaging indicators of CAA and determine if variants and genes discovered via GWAS are implicated in these changes. Discussion/Significance of Impact: We expect this study will provide further insight into the genetic architecture underlying risk for CAA both in the context of significant AD pathology and without. Characterization of genetic variants and functional outcomes in the context of neuropathology may lead to new avenues of research aimed at identifying biomarkers and therapies to treat CAA

Corteva Agriscience recently registered a premix of tolpyralate and bromoxynil in the United States and Canada for weed control in cereal fields. Limited information exists on weed control efficacy and crop safety with this new herbicide premixture. Greenhouse trials were conducted for 2 yr to test the efficacy of tolpyralate and bromoxynil combinations on 14 broadleaf and four grass weeds and its safety to wheat and barley. Four combinations of tolpyralate and bromoxynil at a 1:10 ratio (3.75 + 37.5, 7.5+ 75, 11.25 + 112.5, and 15 + 150 g ai ha−1) as a tank mix and premix were tested. Stand-alone treatments of tolpyralate and bromoxynil were also included in this study. The lowest tested rate of tolpyralate (3.75 g ha−1) provided 10% to 98% control of broadleaf weeds and 27% to 77% control of grass weeds. Bromoxynil at the lowest tested rate (37.5 g ha−1) provided 16% to 80% control of broadleaf weeds and 0% to 30% control of grass weeds. Tank mixing these two herbicides at the same rates resulted in improved broadleaf (60% to 100%) and grass (45% to 94%) weed control. The minimum recommended field use rate of tolpyralate + bromoxynil (15 + 150 g ha−1) controlled all the broadleaf weeds by >95%. That combination also controlled green foxtail, barnyardgrass, and large crabgrass by >90%. An additive or synergistic effect between the two herbicides was observed against several broadleaf and grass weed species. Among all the tested weeds, a greater synergistic effect was observed when the herbicides were used on kochia, chickweed, wild mustard, corn poppy, barnyardgrass, green foxtail, and fall panicum. The premix of the two herbicides provided similar control of broadleaf weeds, but better control of grass weeds than the tank-mix combinations. The premix can be used safely on wheat and barley.

Wild species of rice possess tremendous genetic variations and harbour resistance genes for biotic stresses. Bacterial blight (BB), caused by Xanthomonas oryzae pv. oryzae (Xoo), is a major disease affecting rice production globally. The current study characterized 116 accessions from 17 species of Oryza for BB disease during three seasons viz., kharif 2020, rabi 2020–21, kharif 2021 using an isolate of Xanthomonas oryzae pv. oryzae (Xoo) strain IX-020. A total of 40 accessions including Oryza rufipogon, O. nivara, O. officinalis and O. australiensis showed consistence resistance to the bacterial blight disease across the seasons. These accessions were further subjected to molecular characterization using 11 Xa genes viz., Xa4, xa5, xa13, Xa21, Xa23, Xa27(t), Xa32(t), Xa33, Xa35(t), Xa38 and xa41 with gene-specific markers to ascertain the novelty. Some key resistance genes such as Xa4, Xa23, Xa27(t), Xa32(t), Xa33, Xa35(t) and xa41 were detected in multiple accessions, with O. rufipogon and O. eichingeri harbouring particularly complex combinations of these genes. Notably, several accessions viz., IC521672 (O. nivara), EC861665 (O. officinalis), EC861677 (O. latifolia), EC861711 (O. punctata) and EC861738 (O. eichingeri) did not show the presence of any known genes indicating the possibility of novel genetic loci conferring BB resistance in these wild species. These promising accessions identified in the study are potential novel sources for bacterial leaf blight resistance in rice and will be useful for the development of durable bacterial blight resistance rice cultivars.

Background: Pituicytoma is a rare, low grade tumour typically of the sellar region. Here we present a pituicytoma located in the third ventricle. Methods: 56 year old female presented with amenorrhea, hyperprolactinemia, and progressive bitemporal hemianopsia. MRI revealed a suprasellar mass located within the third ventricle and appearing separate from the pituitary. A supraciliary and translamina terminalis surgical approach to tumour resection was completed without complication. Post-operatively, she developed transient DI which resolved by post-opertaive day 3 and she was discharged hoem without any neurological deficits. Pathology revealed pituicytoma, WHO grade I. Results: Pituicytomas are rare tumours arising from neuroepithelial cells of the pituitary. The majority of cases are pure sellar or sellar with suprasellar extension, or at least have some connection to the pituitary. In many cases, imaging findings are synonymous to pituitary adenomas. We present a unique case in which the tumour was suprasellar but appeared separate from the pituitary. Surgical intervention is the most highly predictive factor of recurrence, as gross totoal reseciton can be curable. Conclusions: Here we present a unique location of pituictyoma. Due to the exceedingly rare nature of pituicytoma, unique presentations and management help to provide better understanding of the breadth of this disease presentation.

Background: Neurodegeneration with Brain Iron Accumulation (NBIA) is a heterogenous group of disorders with the common theme of iron accumulation in the basal ganglia. These disorders typically present in childhood with progressive neurodegeneration and neuropsychiatric symptoms. Caring for an individual with NBIAs is intensive, however it is unknown what factors impact caregiver well-being and quality of life. Methods: Common themes were obtained via literature review of quality of life surveys in children with neurological and chronic illnesses. Five domains were addressed: Diagnosis, Communication, Symptom Management, Clinical Experience and Resources/Support. The survey was approved by the Family Advisory Committee at the CHEO Research Institute and the CHEO REB. The survey was distributed via the Rare Connect Platform to Canadian caregivers. Results: Survey responses are being analyzed and will be presented at the CNSF. Within each domain, Likert scales will be analyzed. Domains will be ranked according to the caregiver responses. Conclusions: Results of this survey will assist in developing care management guidelines, resources for families and help with future advocacy for patients and families affected by NBIAs. The results will also help guide future NBIA Canada Family Conferences.

A 175 kDa antigen fraction with collagenase activity was isolated and purified from somatic extracts of adult Setaria cervi females using column chromatography involving consecutive steps of DEAE-Sepharose CL6B and Sephadex G-100. The optimum pH for 175 kDa collagenase was found to be pH 7.0. Sensitivities to a variety of inhibitors and activators indicated that the 175 kDa coIlagenolytic enzyme was metalloserine in nature. The enzyme hydrolysed a variety of protein substrates such as haemoglobin, casein, azocasein (general substrates) and collagen, FALGPA (furanoyl-acryloyl-leu-gly-pro-ala), the specific substrate of collagenase. The enzyme showed 57% inhibition by jird anti-somatic collagenase antibodies and reacted insignificantly with normal jird sera. Further analysis was undertaken on the immunoprophylactic potential of 175 kDa collagenase in inducing immunity against Brugia malayi (a human filarial parasite) in jirds (Meriones unguiculatus) in vitro and in situ. Immune sera of jirds raised against this antigen promoted partial adherence of peritoneal exudate cells to B. malayi microfilariae (mf) and infective larvae (L3) in vitro and induced partial cytotoxicity to the parasites within 48 h. The anti-S. cervi 175 kDa antigen serum was more effective in inducing cytotoxicity to B. malayi L3, than mf. In the microchambers implanted inside immune jirds, host cells could migrate and adhere to the mf and infective larvae thereby killing them partially within 48 h.

OBJECTIVES/GOALS: To identify novel panel of plasma protein biomarkers to improve prediction and diagnosis of Alzheimer’s disease (AD) for African Americans (AA), who are at greater risk of developing AD compared to non-Hispanic White individuals but are underrepresented in AD research. METHODS/STUDY POPULATION: Pre-existing plasma samples from 460 AA individuals with clinical diagnoses of AD, cognitively unimpaired (CU), mild cognitive impairment (MCI), or dementia with Lewy bodies (DLB) will undergo untargeted proteomics using the SomaScan assay, where modified single stranded DNA aptamers bind to protein targets which are quantified by DNA microarray. Protein expression levels will be compared between diagnostic groups to identify differentially expressed proteins. Additional clinical, genetic, and lifestyle factors will be compared with protein expression when available. Proteins of interest, identified by differential protein expression analysis results, will be included in receiver operating characteristic analyses to identify the optimal set of proteins for diagnostic classification. RESULTS/ANTICIPATED RESULTS: A pilot experiment utilizing plasma from 40 individuals identified multiple differentially expressed proteins (DEPs) between AD and non-AD groups. Eight proteins were nominated from the differential protein analysis into a receiver operating characteristic (ROC) analysis based on pvalue and previous implication in AD genome wide association studies. Proteins involved in microglial activation, neuronal adhesion, cell proliferation, and innate immunity were nominated. The ROC model achieved 100% classification accuracy of AD and CU groups using age, sex, and the eight nominated proteins. It is expected that there will be more significant associations when utilizing the full cohort of 460 AA and that DEPs between AD, CU, MCI, and DLB will be identified. DISCUSSION/SIGNIFICANCE: The nomination of a novel panel of plasma biomarkers developed from an AA cohort will directly serve the AA community by improving access to an early and accurate diagnosis of AD. Access to improved prediction and diagnosis will likely improve disease management, thus improving patient outcomes and decreasing burden on families and caregivers.

Chickpea is a cool season, photothermal-sensitive crop, that is adversely affected by high temperatures (>35°C) and whose flowering is promoted by long-day conditions (>12 h). This prevents horizontal crop spread under a variety of agro-climatic conditions and the development of insensitive genotypes that perform well in all seasons. Therefore, a study was conducted to identify genotypes that are mature early, insensitive to photoperiod, high temperature and tolerant to drought stress. A set of 74 genotypes was evaluated under rainfed conditions in Kharif 2021 (off-season) to select eight promising early-maturing genotypes with high-yielding capacity. Then further investigations were conducted in five different seasons Late Kharif 2021, rabi 2021, summer 2022, early Kharif 2022 and Kharif 2022 to identify the genotypes with photothermo-insensitivity among the selected eight genotypes. With the exception of rabi 2021, each of these seasons were distinct from the chickpea's typical growing season. Among these eight, the stable genotypes which are performed better in all the seasons, especially in summer were considered, such as IPC 06-11, MNK-1, JG-14 and ICE 15654-A as a photothermo-insensitive, were able to flower and set pods with higher seed yield and, resulting in early maturity in a temperature range of 41.4/9.3°C with photoperiods of 13.1/10.9 h to reach in all seasons throughout the year. The heritability was more than 60%. Hence, these genotypes can be used as donor aids in the development of early maturing, drought stress tolerant and photothermo-insensitive chickpea.

The present study was conducted to elucidate (1) the influence of kisspeptin (KP) on the in vitro development of preantral follicles (PFs) and (2) evolution of KP receptor gene (KISS1R) expression during ovarian follicular development in sheep. Kisspeptin was supplemented (0–100 µg/ml) in the culture medium of PFs for 6 days. The cumulus–oocyte complexes (COCs) from cultured PFs were subsequently matured to metaphase II (MII) for an additional 24 h. The proportions of PFs exhibiting growth, antrum formation, average increase in diameter, and maturation of oocytes to MII stage were the indicators of follicular development in vitro. The expression of the kisspeptin receptor gene at each development stages of in vivo developed (preantral, early antral, antral, large antral and COCs from Graafian follicles) and in vitro cultured PFs supplemented with KP was assessed using a real-time polymerase chain reaction. The best development in all the parameters under study was elicited with 10 µg/ml of KP. Supplementation of KP (10 µg/ml) in a medium containing other growth factors (insulin-like growth factor-I) and hormones (growth hormone, thyroxine, follicle-stimulating hormone) resulted in better PF development. The KISS1R gene was expressed in follicular cells and oocytes at all the development stages of both in vivo developed and in vitro cultured follicles. Higher KISS1R gene expression was supported by culture medium containing KP along with other hormones and growth factors. Accordingly, it is suggested that one of the mechanisms through which KP and other growth factors and hormones influence the ovarian follicular development in mammals is through the upregulation of expression of the KP receptor gene.

Soil moisture deficit is the major constraint for sesame crop production during its main rainfed and summer cultivation seasons. In summer cultivation, the crop frequently gets exposed to soil moisture deficit at various crop growth stages. Therefore, it is essential to identify the traits along with promising genotypes adapted to soil moisture deficit. A set of 35 sesame genotypes with checks was used to quantify the variation in morpho-physiological, yield, and quality traits under irrigated (WW) and deficit soil moisture stress (WS) conditions in the summer seasons of 2021 and 2022. The analysis of variance revealed the presence of high variability among the genotypes for various measured traits. The mean performance indicated that WS negatively affects the growth, development, yield and quality traits. Moreover, the correlation, path analysis and D2 analysis studies suggested that the traits, viz. leaf area (LA), total dry matter (TDM), canopy temperature (CT), number of branches per plant (NBP) and number of seeds per capsule (NSC) were significantly associated with seed yield under both the conditions. Quality traits like palmitic acid and oleic acid correlated positively with seed yield, particularly under WS. Furthermore, the genotypes with lower canopy temperatures were found to be better seed yielders under WS. In addition, mean performance and cluster analysis suggested that the genotypes: IC- 205776, JSCDT-112, JCSDT-26, IC-205610, and IC-204300, secured higher seed yield along with superior agronomical traits and net photosynthetic rate. These selected genotypes were most promising and could be used in future sesame crop improvement programmes.

The U.S. Department of Agriculture–Agricultural Research Service (USDA-ARS) has been a leader in weed science research covering topics ranging from the development and use of integrated weed management (IWM) tactics to basic mechanistic studies, including biotic resistance of desirable plant communities and herbicide resistance. ARS weed scientists have worked in agricultural and natural ecosystems, including agronomic and horticultural crops, pastures, forests, wild lands, aquatic habitats, wetlands, and riparian areas. Through strong partnerships with academia, state agencies, private industry, and numerous federal programs, ARS weed scientists have made contributions to discoveries in the newest fields of robotics and genetics, as well as the traditional and fundamental subjects of weed–crop competition and physiology and integration of weed control tactics and practices. Weed science at ARS is often overshadowed by other research topics; thus, few are aware of the long history of ARS weed science and its important contributions. This review is the result of a symposium held at the Weed Science Society of America’s 62nd Annual Meeting in 2022 that included 10 separate presentations in a virtual Weed Science Webinar Series. The overarching themes of management tactics (IWM, biological control, and automation), basic mechanisms (competition, invasive plant genetics, and herbicide resistance), and ecosystem impacts (invasive plant spread, climate change, conservation, and restoration) represent core ARS weed science research that is dynamic and efficacious and has been a significant component of the agency’s national and international efforts. This review highlights current studies and future directions that exemplify the science and collaborative relationships both within and outside ARS. Given the constraints of weeds and invasive plants on all aspects of food, feed, and fiber systems, there is an acknowledged need to face new challenges, including agriculture and natural resources sustainability, economic resilience and reliability, and societal health and well-being.

Background: The Epilepsy Monitoring Unit (EMU) plays a crucial role in a patient’s diagnosis and management for seizures and epilepsy. The duration of stay required to obtain adequate information is not clear, especially in the pediatric population. In this study, we examine whether a one to four day length of stay in the EMU is sufficient to obtain the necessary information. Methods: Retrospective review of 522 admissions (2014-2021). Included any patient admitted to CHEO’s EMU for any length of time. Results: The average admission was 1.75 days with 35.7% of patients requiring repeat EMU visits. Through a binary logistic regression, we show that a previous diagnosis of refractory seizures increases the chance of readmission to the EMU. However, a diagnosis of refractory seizures is also associated with a higher chance of achieving admission goals. While other factors including seizure type, weaning of meds, goals of admission, age, and gender have no influence on likelihood of readmission or achieving admission goals. Conclusions: This study indicates that having a short admission for EMU monitoring is sufficient to capture enough data to achieve admission goals in the pediatric population.

Bispyribac-sodium, a herbicide that inhibits acetolactate synthase (ALS), is frequently used in rice fields in India to control weeds, including the most common noxious weed, barnyardgrass. However, rice growers have recently reported reduced control of barnyardgrass with bispyribac-sodium. Hence, a large-scale survey was carried out to assess bispyribac-sodium resistance in Chhattisgarh and Kerala, two rice-growing states. Open-field pot experiments were conducted for 2 yr to confirm resistance to bispyribac-sodium. Of the 37 biotypes tested, 30% (11) survived the recommended label rate of bispyribac-sodium (25 g ai ha−1). The effective rate of bispyribac-sodium required to achieve 50% control (ED50) of putative resistant biotypes ranged from 18 to 41 g ha−1, whereas it was about 10 g ha−1 for susceptible biotypes. This suggests that putative biotypes were two to four times more resistant to bispyribac-sodium. At 6 d after herbicide application, an in vitro enzyme assay demonstrated higher ALS enzyme activity in putative resistant biotypes (66% to 75%) compared with susceptible biotypes (48% to 52%). This indicates the presence of an insensitive ALS enzyme in those biotypes and a target site mutation as a possible mechanism for resistance. Whole-plant bioassays also suggested that the resistance problem is more widespread in Chhattisgarh than in Kerala. This study confirmed the first case of evolved resistance in barnyardgrass to bispyribac-sodium in rice fields of India.

Long-term sequelae of severe acute respiratory coronavirus-2 (SARS-CoV-2) infection may include increased incidence of diabetes. Here we describe the temporal relationship between new type 2 diabetes and SARS-CoV-2 infection in a nationwide database. We found that while the proportion of newly diagnosed type 2 diabetes increased during the acute period of SARS-CoV-2 infection, the mean proportion of new diabetes cases in the 6 months post-infection was about 83% lower than the 6 months preinfection. These results underscore the need for further investigation to understand the timing of new diabetes after COVID-19, etiology, screening, and treatment strategies.