U.S. cereal rye winter cover crop growth database.

Winter cover crop performance metrics (i.e., vegetative biomass quantity and quality) affect ecosystem services provisions, but they vary widely due to differences in agronomic practices, soil properties, and climate. Cereal rye (Secale cereale) is the most common winter cover crop in the United States due to its winter hardiness, low seed cost, and high biomass production. We compiled data on cereal rye winter cover crop performance metrics, agronomic practices, and soil properties across the eastern half of the United States. The dataset includes a total of 5,695 cereal rye biomass observations across 208 site-years between 2001-2022 and encompasses a wide range of agronomic, soils, and climate conditions. Cereal rye biomass values had a mean of 3,428 kg ha-1, a median of 2,458 kg ha-1, and a standard deviation of 3,163 kg ha-1. The data can be used for empirical analyses, to calibrate, validate, and evaluate process-based models, and to develop decision support tools for management and policy decisions.

Nitrous oxide emissions are driven by environmental conditions rather than nitrogen application methods in a perennial hayfield.

Agricultural best management practices (BMPs) intended to solve one environmental challenge may have unintended climate impacts. For example, manure injection is often promoted for its potential to reduce runoff and nitrogen (N) loss as NH3 , but the practice has been shown to increase N2 O, a powerful greenhouse gas, compared to surface application. Urease inhibitor application with N fertilizer is another BMP that can enhance N retention by reducing NH3 emissions, but its impact on N2 O emissions is mixed. Thus, we measured N2 O, CO2 , soil mineral N availability, soil moisture, soil temperature, and yield in a 2-year perennial hayfield trial with four fertilization treatments (manure injection, manure broadcast, synthetic urea, and control) applied with or without a urease inhibitor in Alburgh, VT. We used linear models to examine treatment effects on daily and cumulative N2 O emissions and a boosted regression tree (BRT) model to identify the most important drivers of daily N2 O fluxes in our trial. While fertilization type had a significant impact on N2 O fluxes (p < 0.05), our treatments explained an unexpectedly small amount of the variation in emissions (R2  = 0.042), and urease inhibitor had no effect. Instead, soil moisture was the most important predictor of daily N2 O fluxes (39.7% relative influence in BRT model), followed by CO2 fluxes, soil inorganic N, and soil temperature. Soil moisture and temperature interacted to produce the largest daily N2 O fluxes when both were relatively high, suggesting that injecting manure during dry periods or during wet but cool periods could reduce its climate impacts.

Extended Sentinel Monitoring of Helicoverpa zea Resistance to Cry and Vip3Aa Toxins in Bt Sweet Corn: Assessing Changes in Phenotypic and Allele Frequencies of Resistance.

Transgenic corn and cotton that produce Cry and Vip3Aa toxins derived from Bacillus thuringiensis (Bt) are widely planted in the United States to control lepidopteran pests. The sustainability of these Bt crops is threatened because the corn earworm/bollworm, Helicoverpa zea (Boddie), is evolving a resistance to these toxins. Using Bt sweet corn as a sentinel plant to monitor the evolution of resistance, collaborators established 146 trials in twenty-five states and five Canadian provinces during 2020-2022. The study evaluated overall changes in the phenotypic frequency of resistance (the ratio of larval densities in Bt ears relative to densities in non-Bt ears) in H. zea populations and the range of resistance allele frequencies for Cry1Ab and Vip3Aa. The results revealed a widespread resistance to Cry1Ab, Cry2Ab2, and Cry1A.105 Cry toxins, with higher numbers of larvae surviving in Bt ears than in non-Bt ears at many trial locations. Depending on assumptions about the inheritance of resistance, allele frequencies for Cry1Ab ranged from 0.465 (dominant resistance) to 0.995 (recessive resistance). Although Vip3Aa provided high control efficacy against H. zea, the results show a notable increase in ear damage and a number of surviving older larvae, particularly at southern locations. Assuming recessive resistance, the estimated resistance allele frequencies for Vip3Aa ranged from 0.115 in the Gulf states to 0.032 at more northern locations. These findings indicate that better resistance management practices are urgently needed to sustain efficacy the of corn and cotton that produce Vip3Aa.

A newly discovered PD-L1 B-cell epitope peptide vaccine (PDL1-Vaxx) exhibits potent immune responses and effective anti-tumor immunity in multiple syngeneic mice models and (synergizes) in combination with a dual HER-2 B-cell vaccine (B-Vaxx).

Blockade of checkpoint receptors with monoclonal antibodies against CTLA-4, PD-1 and PD-L1 has shown great clinical success in several cancer subtypes, yielding unprecedented responses albeit a significant number of patients develop resistance and remain refractory. Both PD-1/PD-L1 and HER-2 signaling pathway inhibitors have limited efficacy and exhibits significant toxicities that limit their use. Ongoing clinical studies support the need for rationale combination of immuno-oncology agents to make a significant impact in the lives of cancer patients. We introduce the development of a novel chimeric PD-L1 B-cell peptide epitope vaccine (amino acid 130-147) linked to a "promiscuous" T cell measles virus fusion (MVF) peptide (MVF-PD-L1(130); PDL1-Vaxx) or linked to tetanus toxoid (TT3) TT3-PD-L1 (130) via a linker (GPSL). These vaccine constructs are highly immunogenic and antigenic in several syngeneic animal models. The PD-L1 vaccines elicited high titers of polyclonal antibodies that inhibit tumor growth in multiple syngeneic cancer models, eliciting antibodies of different subtypes IgG1, IgG2a, IgG2b and IgG3, induced PD-1/PD-L1 blockade, decreased proliferation, induced apoptosis and caused ADCC of tumor cells. The PDL1-Vaxx induces similar inhibition of tumor growth versus the standard anti-mouse PD-L1 antibody in both syngeneic BALB/c and C57BL/6J mouse models. The combination of PDL1-Vaxx with HER-2 vaccine B-Vaxx demonstrated synergistic tumor inhibition in D2F2/E2 carcinoma cell line. The anti-PDL1-Vaxx block PD-1/PD-L1 interaction and significantly prolonged anti-tumor responses in multiple syngeneic tumor models. The combination of HER-2 vaccine (B-Vaxx) with either PDL1-Vaxx or PD1-Vaxx demonstrated synergistic tumor inhibition. PDL1-Vaxx is a promising novel safe checkpoint inhibitor vaccine.

Humoral and cellular immune responses to recombinant herpes zoster vaccine in patients with chronic lymphocytic leukemia and monoclonal B cell lymphocytosis.

Monoclonal B-cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL) are clonal B-cell disorders associated with an increased risk of infections and impaired vaccination responses. We investigated the immunogenicity of recombinant zoster vaccine (RZV) in these patients. Individuals with MBL/untreated CLL and Bruton tyrosine kinase inhibitor (BTKi)-treated CLL patients were given two doses of RZV separated by 2 months. Responses assessed at 3 and 12 months from the first dose of RZV by an anti-glycoprotein E ELISA antibody assay and by dual-color Interferon-γ and Interleukin-2FLUOROSPOT assays were compared to historic controls matched by age and sex. About 62 patients (37 MBL/untreated CLL and 25 BTKi-treated CLL) were enrolled with a median age of 68 years at vaccination. An antibody response at 3 months was seen in 45% of participants, which was significantly lower compared to historic controls (63%, p = .03). The antibody response did not significantly differ between MBL/untreated CLL and BTKi-treated CLL (51% vs. 36%, respectively, p = .23). The CD4+ T-cell response to vaccination was significantly lower in study participants compared to controls (54% vs. 96%, p < .001), mainly due to lower responses among BTKi-treated patients compared to untreated MBL/CLL (32% vs. 73%, p = .008). Overall, only 29% of participants achieved combined antibody and cellular responses to RZV. Among participants with response assessment at 12 months (n = 47), 24% had antibody titers below the response threshold. Hypogammaglobulinemia and BTKi therapy were associated with reduced T-cell responses in a univariate analysis. Strategies to improve vaccine response to RZV among MBL/CLL patients are needed.

Omega-3 Fatty Acid Fortification of Flax Through Nutri-Priming.

Omega-3 (n-3) fatty acids (FA) play an essential role in human physiology and health. As a result, a variety of n-3 FA-fortified functional foods have become commercially available for human consumption. These fortified functional foods are created through various processes; however, nutri-priming, a potentially promising fortification approach, has not been utilized to develop plant-based n-3 fortified foods. We sought to determine whether nutri-priming is a viable option to enrich seeds and sprouts with n-3 FA. Additionally, we assessed whether n-3 FA nutri-priming would inhibit germination of the primed seeds. To address these goals, we nutri-primed brown flax in three priming solutions, control [0% fish oil (FO)], 10% FO and a 20% FO solution, and determined the FA content and profile of seeds and sprouts and germination percentage of primed seeds. n-3 FA nutri-priming with FO altered the FA profile in seeds and sprouts, with increases in the absolute content of 20:5 n-3, 22:6 n-3, 22:5 n3, 18:4 n-3, and 20:4 n-6. However, n-3 FA nutri-priming did not increase the absolute content of 18:2 n-6, 18:3 n-3, total saturated FA, total monounsaturated FA, total polyunsaturated FA, total n-6 FA, or total n-3 FA. Our results also showed that n-3 nutri-priming decreased the germination percentage of primed seeds, with 10 and 20% FO priming solution reducing germination by 4.3 and 6.2%, respectively. Collectively, n-3 nutri-priming modified the n-3 FA profile in flax; however, the process does not increase the total n-3 FA content and inhibits germination of primed seeds. Further research utilizing different seed types, oil types, and oil concentrations needs to be conducted to fully determine if n-3 nutri-priming is a commercially viable approach for n-3 fortification of seeds and sprouts.

Benefits and tradeoffs of reduced tillage and manure application methods in a Zea mays silage system.

A critical question is whether there are agricultural management practices that can attain the multiple management goals of increasing yields, preventing nutrient losses, and suppressing greenhouse gas (GHG) emissions. No-till and manure application methods, such as manure injection, can enhance nutrient retention, but both may also enhance emissions of nitrous oxide (N2 O), a powerful GHG. We assessed differences in soil N2 O and carbon dioxide (CO2 ) emissions, nitrate and ammonium retention, and crop yield and protein content under combinations of vertical-till, no-till, manure injection, and manure broadcast without incorporation in a corn (Zea mays L.) silage system. During the growing seasons of 2015-2017, GHG emissions and soil mineral nitrogen (N) were measured every other week or more frequently after management events. Crop yield and protein content were measured annually at harvest. No-till reduced CO2 emissions but had no impact on N2 O emissions relative to vertical-till. Manure injection increased N2 O and CO2 emissions, with the magnitude of this effect being greatest for 1 mo post-application. Manure injection also increased soil ammonium and nitrate but did not increase yield or crop quality relative to broadcast application. Similarly, tillage did not affect crop yield or protein content. Despite the tradeoffs between mineral N retention and elevated GHG emissions, manure injection in no-till systems benefits farmers by reducing soil carbon losses as CO2 , retaining mineral N, and maintaining crop yields and quality.

Potent Tetrahydroquinolone Eliminates Apicomplexan Parasites.

Apicomplexan infections cause substantial morbidity and mortality, worldwide. New, improved therapies are needed. Herein, we create a next generation anti-apicomplexan lead compound, JAG21, a tetrahydroquinolone, with increased sp3-character to improve parasite selectivity. Relative to other cytochrome b inhibitors, JAG21 has improved solubility and ADMET properties, without need for pro-drug. JAG21 significantly reduces Toxoplasma gondii tachyzoites and encysted bradyzoites in vitro, and in primary and established chronic murine infections. Moreover, JAG21 treatment leads to 100% survival. Further, JAG21 is efficacious against drug-resistant Plasmodium falciparum in vitro. Causal prophylaxis and radical cure are achieved after P. berghei sporozoite infection with oral administration of a single dose (2.5 mg/kg) or 3 days treatment at reduced dose (0.625 mg/kg/day), eliminating parasitemia, and leading to 100% survival. Enzymatic, binding, and co-crystallography/pharmacophore studies demonstrate selectivity for apicomplexan relative to mammalian enzymes. JAG21 has significant promise as a pre-clinical candidate for prevention, treatment, and cure of toxoplasmosis and malaria.

Longitudinal Cerebrospinal Fluid Biomarker Changes in Preclinical Alzheimer Disease During Middle Age.

IMPORTANCE: Individuals in the presymptomatic stage of Alzheimer disease (AD) are increasingly being targeted for AD secondary prevention trials. How early during the normal life span underlying AD pathologies begin to develop, their patterns of change over time, and their relationship with future cognitive decline remain to be determined. OBJECTIVE: To characterize the within-person trajectories of cerebrospinal fluid (CSF) biomarkers of AD over time and their association with changes in brain amyloid deposition and cognitive decline in cognitively normal middle-aged individuals. DESIGN, SETTING, AND PARTICIPANTS: As part of a cohort study, cognitively normal (Clinical Dementia Rating [CDR] of 0) middle-aged research volunteers (n = 169) enrolled in the Adult Children Study at Washington University, St Louis, Missouri, had undergone serial CSF collection and longitudinal clinical assessment (mean, 6 years; range, 0.91-11.3 years) at 3-year intervals at the time of analysis, between January 2003 and November 2013. A subset (n = 74) had also undergone longitudinal amyloid positron emission tomographic imaging with Pittsburgh compound B (PiB) in the same period. Serial CSF samples were analyzed for ß-amyloid 40 (Aß40), Aß42, total tau, tau phosphorylated at threonine 181 (P-tau181), visinin-like protein 1 (VILIP-1), and chitinase-3-like protein 1 (YKL-40). Within-person measures were plotted according to age and AD risk defined by APOE genotype (ε4 carriers vs noncarriers). Linear mixed models were used to compare estimated biomarker slopes among middle-age bins at baseline (early, 45-54 years; mid, 55-64 years; late, 65-74 years) and between risk groups. Within-person changes in CSF biomarkers were also compared with changes in cortical PiB binding and progression to a CDR higher than 0 at follow-up. MAIN OUTCOMES AND MEASURES: Changes in Aß40, Aß42, total tau, P-tau181, VILIP-1, and YKL-40 and, in a subset of participants, changes in cortical PiB binding. RESULTS: While there were no consistent longitudinal patterns in Aß40 (P = .001-.97), longitudinal reductions in Aß42 were observed in some individuals as early as early middle age (P ≤ .05) and low Aß42 levels were associated with the development of cortical PiB-positive amyloid plaques (area under receiver operating characteristic curve = 0.9352; 95% CI, 0.8895-0.9808), especially in mid middle age (P < .001). Markers of neuronal injury (total tau, P-tau181, and VILIP-1) dramatically increased in some individuals in mid and late middle age (P ≤ .02), whereas the neuroinflammation marker YKL-40 increased consistently throughout middle age (P ≤ .003). These patterns were more apparent in at-risk ε4 carriers (Aß42 in an allele dose-dependent manner) and appeared to be associated with future cognitive deficits as determined by CDR. CONCLUSIONS AND RELEVANCE: Longitudinal CSF biomarker patterns consistent with AD are first detectable during early middle age and are associated with later amyloid positivity and cognitive decline. Such measures may be useful for targeting middle-aged, asymptomatic individuals for therapeutic trials designed to prevent cognitive decline.