Search

Exogenous β-glucanase (BGase) in barley-based feed has been shown to reduce digesta viscosity in chickens, and thereby improve performance. Less well studied is the potential for BGase to convert barley β-glucan into low molecular weight carbohydrates, which might influence digestive tract function and enteric disease. Coccidiosis-vaccinated broiler chickens were fed graded levels of hulless barley (HB) and BGase to determine their effects on β-glucan depolymerization and digestive tract characteristics. Broilers were fed high β-glucan HB (0%, 30% and 60% replacing wheat) and BGase (0%, 0.01% and 0.1%) in a 3 × 3 factorial arrangement. A total of 5,346 broilers were raised in litter floor pens and vaccinated for coccidiosis on d 5. Each treatment was assigned to 1 pen in each of 9 rooms. The significance level was set at P ≤ 0.05. At both 11 and 33 d of broiler ages, peak molecular weight of β-glucan in ileal digesta decreased with increasing BGase for 30% and 60% HB. The maximum molecular weight for the smallest 10% β-glucan molecules (MW-10%) decreased with BGase at both ages for 30% and 60% HB; for birds fed 0% HB, only 0.1% BGase decreased MW-10%. The 0.1% BGase increased caecal short chain fatty acids (SCFA) compared to the 0.01% BGase at d 11 only for the 60% HB. Ileal pH increased with increasing HB and BGase at d 11 and 33. Caecal pH was lower for 0.1% BGase than 0% BGase for 60% HB at d 11. Relative mRNA expression of interleukin 6 (IL-6) and IL-8 in the ileum increased with 0.1% BGase at d 11 and 33, respectively, whereas expression of ileal mucin 2 (MUC2) decreased with 0.1% BGase at d 33. In the caeca, interactions between HB and BGase were significant for monocarboxylate transporter 1 (MCT1) and mucin 5AC (MUC5AC) on d 11, but no treatment effects were found at d 33. In conclusion, BGase depolymerized high molecular weight β-glucan in HB in a dose-dependent manner. Hulless barley and BGase did not increase SCFA concentrations (except for 60% HB with 0.1% BGase at d 11) and caused minor effects on digestive tract histomorphological measurements and relative mRNA gene expression.

The accumulation and propagation of hyperphosphorylated tau (p-Tau) is a neuropathological hallmark occurring with neurodegeneration of Alzheimer’s disease (AD). Extracellular vesicles, exosomes, have been shown to initiate tau propagation in the brain. Notably, exosomes from human-induced pluripotent stem cell (iPSC) neurons expressing the AD familial A246E mutant form of presenilin 1 (mPS1) are capable of inducing tau deposits in the mouse brain after in vivo injection. To gain insights into the exosome proteome cargo that participates in propagating tau pathology, this study conducted proteomic analysis of exosomes produced by human iPSC neurons expressing A246E mPS1. Significantly, mPS1 altered the profile of exosome cargo proteins to result in (1) proteins present only in mPS1 exosomes and not in controls, (2) the absence of proteins in the mPS1 exosomes which were present only in controls, and (3) shared proteins which were upregulated or downregulated in the mPS1 exosomes compared to controls. These results show that mPS1 dysregulates the proteome cargo of exosomes to result in the acquisition of proteins involved in the extracellular matrix and protease functions, deletion of proteins involved in RNA and protein translation systems along with proteasome and related functions, combined with the upregulation and downregulation of shared proteins, including the upregulation of amyloid precursor protein. Notably, mPS1 neuron-derived exosomes displayed altered profiles of protein phosphatases and kinases involved in regulating the status of p-tau. The dysregulation of exosome cargo proteins by mPS1 may be associated with the ability of mPS1 neuron-derived exosomes to propagate tau pathology.

Calmodulin (CaM) regulates the activity of a Ca(2+) channel known as the cardiac ryanodine receptor (RyR2), which facilitates the release of Ca(2+) from the sarcoplasmic reticulum during excitation–contraction coupling in cardiomyocytes. Mutations that disrupt this CaM-dependent channel inactivation result in cardiac arrhythmias. RyR2 contains three different CaM binding sites: CaMBD1 (residues 1940–1965), CaMBD2 (residues 3580–3611), and CaMBD3 (residues 4246–4275). Here, we report a crystal structure of Ca(2+)-bound CaM bound to RyR2 CaMBD3. The structure reveals Ca(2+) bound to the four EF-hands of CaM as well as a fifth Ca(2+) bound to CaM in the interdomain linker region involving Asp81 and Glu85. The CaM mutant E85A abolishes the binding of the fifth Ca(2+) and weakens the binding of CaMBD3 to Ca(2+)-bound CaM. Thus, the binding of the fifth Ca(2+) is important for stabilizing the complex in solution and is not a crystalline artifact. The CaMBD3 peptide in the complex adopts an α-helix (between Phe4246 and Val4271) that interacts with both lobes of CaM. Hydrophobic residues in the CaMBD3 helix (Leu4255 and Leu4259) form intermolecular contacts with the CaM N-lobe, and the CaMBD3 mutations (L4255A and L4259A) each weaken the binding of CaM to RyR2. Aromatic residues on the opposite side of the CaMBD3 helix (Phe4246 and Tyr4250) interact with the CaM C-lobe, but the mutants (F4246A and Y4250A) have no detectable effect on CaM binding in solution. We suggest that the binding of CaM to CaMBD3 and the binding of a fifth Ca(2+) to CaM may contribute to the regulation of RyR2 channel function.

The combination of oats such as water-soluble oat extract (SOE) and probiotic microorganisms can add nutritional value to the food and benefits to the consumer’s health. The SOE contains soluble fiber, whose major soluble fraction is composed of β-glucan contains soluble antioxidants such as ferulic acid, avenanthramides and other phenolic acids. The purpose of this study was to develop a fermented dairy beverage containing SOE, evaluating the viability of the probiotic culture, the fatty acid profile, phenolic compounds content and sensory characteristics during the storage. It was verified that Lactobacillus casei remained viable during the 21 days of storage (count above 7 Log CFU.mL(−1)) and that the addition of SOE does not affect the viability of probiotic bacteria. The levels of bioactive compounds soluble in aqueous medium, increased between the beginning of the experiment and the end, being influenced by the addition of SOE. Seven fatty acids were found in all formulations with a prevalence of C16:0 followed by C18:1. The addition of SOE in the formulation contributes to a significant increase in linoleic acid (C18:2n6). The sensory evaluation of the fermented oat dairy beverage with L. casei (BAC) was positive: the product was highly appreciated by consumers, with acceptance rate of 84.4%. The combination of SOE, with L. casei in the production of novel probiotic fermented dairy beverage, was technologically feasible, improving the functional properties of the product and offering health benefits to the consumer. More studies should be made to evaluate the composition and functional properties of SOE.

Cyanobacteriochromes (CBCRs) are cyanobacterial photoreceptors that exhibit photochromism between two states: a thermally stable dark-adapted state and a metastable light-adapted state with bound linear tetrapyrrole (bilin) chromophores possessing 15Z and 15E configurations, respectively. The photodynamics of canonical red/green CBCRs have been extensively studied; however, the time scales of their excited-state lifetimes and subsequent ground-state evolution rates widely differ and, at present, remain difficult to predict. Here, we compare the photodynamics of two closely related red/green CBCRs that have substantial sequence identity (∼68%) and similar chromophore environments: AnPixJg2 from Anabaena sp. PCC 7120 and NpR6012g4 from Nostoc punctiforme. Using broadband transient absorption spectroscopy on the primary (125 fs to 7 ns) and secondary (7 ns to 10 ms) time scales together with global analysis modeling, our studies revealed that AnPixJg2 and NpR6012g4 have comparable quantum yields for initiating the forward (15ZPr → 15EPg) and reverse (15EPg → 15ZPr) reactions, which proceed through monotonic and nonmonotonic mechanisms, respectively. In addition to small discrepancies in the kinetics, the secondary reverse dynamics resolved unique features for each domain: intermediate shunts in NpR6012g4 and a Meta-Gf intermediate red-shifted from the 15ZPr photoproduct in AnPixJg2. Overall, this study supports the conclusion that sequence similarity is a useful criterion for predicting pathways of the light-induced evolution and quantum yield of generating primary intermediate Φp within subfamilies of CBCRs, but more studies are still needed to develop a comprehensive molecular level understanding of these processes.

The present study evaluated the anti-inflammatory effect of nanoencapsulated curcuminoid preparations of poly(vinyl pyrrolidone) (Nano-cur) and free curcuminoids (Cur) in an experimental model of croton oil-induced cutaneous inflammation. Male Swiss mice, weighing 25-30 g, received oral treatment by gavage 1 h before CO application or topical treatment immediately after CO application (200 μg diluted in 70% acetone) with a single dose of Cur and Nano-cur. After 6 h, the animals were anesthetized and euthanized. The ears were sectioned into disks (6.0 mm diameter) and used to determine edema, myeloperoxidase (MPO) activity, and oxidative stress. Photoacoustic spectroscopy (PAS) was used to evaluate the percutaneous penetration of Cur and Nano-cur. Topical treatment with both preparations had a similar inhibitory effect on the development of edema, MPO activity, and the oxidative response. The PAS technique showed that the percutaneous permeation of both topically applied preparations was similar. Oral Nano-cur administration exerted a higher anti-inflammatory effect than Cur. Topical Cur and Nano-cur application at the same dose similarly inhibited the inflammatory and oxidative responses. Oral Nano-cur administration inhibited such responses at doses that were eight times lower than Cur, suggesting the better bioavailability of Nano-cur compared with Cur.Graphical abstract.

Classic homocystinuria is due to deficiency of cystathionine beta-synthase (CBS), a pyridoxine-dependent enzyme that, depending on the molecular variants, may be co-factor responsive. Elevated methionine is often used as the primary analyte to detect CBS deficiency (CBSD) on newborn screening (NBS), but is limited by increased detection of other biochemical disorders with less clear clinical significance such as methionine aminotransferase (MAT) I/III heterozygotes. Our state has implemented a two-tier NBS algorithm for CBSD that successfully reduced the number of MATI/III heterozygotes, yet effectively detected a mild, co-factor responsive form of CBSD. After initial diagnosis, newborns with CBSD often undergo a pyridoxine challenge with high-dose pyridoxine to determine responsiveness. Here we describe our NBS-identified patient with a mild form of pyridoxine responsive CBSD who developed respiratory failure and rhabdomyolysis consistent with pyridoxine toxicity during a pyridoxine challenge. This case highlights the need for weight-based dosing and duration recommendations for pyridoxine challenge in neonates.

Background Lipid metabolism is altered in Alzheimer's disease (AD); however, the relationship between AD risk factors (age, APOEɛ4, and gender) and lipid metabolism is not well defined. Objective We investigated whether altered lipid metabolism associated with increased age, gender, and APOE status may contribute to the development of AD by examining these risk factors in healthy controls and also clinically diagnosed AD individuals. Methods We performed plasma lipidomic profiling (582 lipid species) of the Australian Imaging, Biomarkers and Lifestyle flagship study of aging cohort (AIBL) using liquid chromatography-mass spectrometry. Linear regression and interaction analysis were used to explore the relationship between risk factors and plasma lipid species. Results We observed strong associations between plasma lipid species with gender and increasing age in cognitively normal individuals. However, APOEɛ4 was relatively weakly associated with plasma lipid species. Interaction analysis identified differential associations of sphingolipids and polyunsaturated fatty acid esterified lipid species with AD based on age and gender, respectively. These data indicate that the risk associated with age, gender, and APOEɛ4 may, in part, be mediated by changes in lipid metabolism. Conclusion This study extends our existing knowledge of the relationship between the lipidome and AD and highlights the complexity of the relationships between lipid metabolism and AD at different ages and between men and women. This has important implications for how we assess AD risk and also for potential therapeutic strategies involving modulation of lipid metabolic pathways.

Anethole (AN) is a natural compound that has attracted great scientific interest because of its numerous biological activities, including anti-inflammatory effects. However, these effects were obtained with high doses of AN, which may be one limitation of its therapeutic use. This study evaluated the effects of a low-dose AN and ibuprofen (IB) combination on inflammatory parameters in Freund’s complete adjuvant-induced arthritis (AIA) and arthritis-induced hepatic metabolic changes. Holtzman rats were used and divided into groups: normal, AIA (control), arthritics treated with IB, arthritics treated with AN, and arthritics treated with AN + IB. The volume of the paws, the appearance of secondary lesions, and the number of synovial leukocytes were evaluated. Gluconeogenesis and ureagenesis from alanine were determined in the rat liver in isolated perfusion. The AN + IB (62.5 + 8.75 mg/kg) treatment exerted an inhibitory effect on inflammatory parameters and partially prevented hepatic metabolic changes that was similar to the effect of high-dose IB (35 mg/kg) and AN (250 mg/kg) treatment. This effect of the treatments on hepatic metabolism can be, partly at least, explained by the preservation of both the alanine aminotransferase (ALT) activity and the cytosolic NADH/NAD+ redox potential in the liver. Taken together, the data obtained provided evidence that the AN + IB combination at lower doses than AN and IB treatment alone had beneficial inhibitory potential for the treatment of AIA and attenuated metabolic changes in the liver.

College students transition from the parental home environment to the college environment. This study examined the transitioning role of parent/child relationships and religiosity in Christian coll...

Tumor cells rely on glycolysis to meet their elevated demand for energy. Thereby they produce significant amounts of lactate and protons, which are exported via monocarboxylate transporters (MCTs), supporting the formation of an acidic microenvironment. The present study demonstrates that carbonic anhydrase IX (CAIX), one of the major acid/base regulators in cancer cells, forms a protein complex with MCT1 and MCT4 in tissue samples from human breast cancer patients, but not healthy breast tissue. Formation of this transport metabolon requires binding of CAIX to the Ig1 domain of the MCT1/4 chaperon CD147 and is required for CAIX-mediated facilitation of MCT1/4 activity. Application of an antibody, directed against the CD147-Ig1 domain, displaces CAIX from the transporter and suppresses CAIX-mediated facilitation of proton-coupled lactate transport. In cancer cells, this “metabolon disruption” results in a decrease in lactate transport, reduced glycolysis and ultimately reduced cell proliferation. Taken together, the study shows that carbonic anhydrases form transport metabolons with acid/base transporters in human tumor tissue and that these interactions can be exploited to interfere with tumor metabolism and proliferation.

Background: Worldwide, coffee is one of the most popular beverages consumed. Several studies have suggested a protective role of coffee, including reduced risk of Alzheimer’s disease (AD). However, there is limited longitudinal data from cohorts of older adults reporting associations of coffee intake with cognitive decline, in distinct domains, and investigating the neuropathological mechanisms underpinning any such associations.Methods: The aim of the current study was to investigate the relationship between self-reported habitual coffee intake, and cognitive decline assessed using a comprehensive neuropsychological battery in 227 cognitively normal older adults from the Australian Imaging, Biomarkers, and Lifestyle (AIBL) study, over 126 months. In a subset of individuals, we also investigated the relationship between habitual coffee intake and cerebral Aβ-amyloid accumulation (n = 60) and brain volumes (n = 51) over 126 months.Results: Higher baseline coffee consumption was associated with slower cognitive decline in executive function, attention, and the AIBL Preclinical AD Cognitive Composite (PACC; shown reliably to measure the first signs of cognitive decline in at-risk cognitively normal populations), and lower likelihood of transitioning to mild cognitive impairment or AD status, over 126 months. Higher baseline coffee consumption was also associated with slower Aβ-amyloid accumulation over 126 months, and lower risk of progressing to “moderate,” “high,” or “very high” Aβ-amyloid burden status over the same time-period. There were no associations between coffee intake and atrophy in total gray matter, white matter, or hippocampal volume.Discussion: Our results further support the hypothesis that coffee intake may be a protective factor against AD, with increased coffee consumption potentially reducing cognitive decline by slowing cerebral Aβ-amyloid accumulation, and thus attenuating the associated neurotoxicity from Aβ-amyloid-mediated oxidative stress and inflammatory processes. Further investigation is required to evaluate whether coffee intake could be incorporated as a modifiable lifestyle factor aimed at delaying AD onset.

Our objective was to evaluate the effects of application rate (AR) of sodium lignosulfonate and propionic acid on the in vitro fermentation measures of high moisture alfalfa hay. Treatments (TRT) were sodium lignosulfonate (NaL) and Propionic Acid (PRP), which were applied at four AR: 0 (CON), 0.25, 0.5 and 1% (w/w fresh basis) to 20% bloom alfalfa hay (second cut) at 68.5% DM and packed into mini bales (10.3×10.8×13cm; 346 kg fresh/m3). The treated bales were stored for 33 days in open-top insulation boxes in a room kept at 22°C, after which they were dried, ground to 1 mm and incubated in vitro for 48hr with ruminal fluid from two ruminally cannulated Holstein cows in lactation. Gas kinetics were recorded using the Ankom RF Gas Production System. Data were analyzed as a randomized complete block design (5 blocks) with a 2 (TRT) x 4 (AR) factorial arrangement, and differences were declared at P ≤ 0.05. Both TRT increased apparent in vitro DM digestibility (DMD) at all AR relative to CON (54.3 vs 50.1 ± 1.20%, respectively). PRP increased asymptotic maximal (188.4) and rate of gas production (9.46) compared to NaL (179.7 ± 4.82 ml/g of incubated DM and 8.72 ± 0.45%/h, respectively). Total VFA were higher for PRP (117.5) vs NaL (114.8), and for both TRT at 1% relative to CON (118.9 vs. 113.8 ± 1.68mM). Acetate (A) was increased by both TRT at 1% (~73.5) and propionate (P) was increased by PRP at 1% (26.1) relative to CON (69.9 ± 1.10 and 24.2 ± 0.29mM, respectively), but the A:P ratio was higher for NaL at 1% (3.02) vs. CON (2.89 ± 0.04). In conclusion, NaL and PRP at 1% improved the rumen in vitro fermentation measures of high moisture alfalfa hay but PRP did so to a greater extent.

Postsynaptic density protein-95 (PSD95) contributes to the postsynaptic architecture of neuronal synapses and plays an important role in controlling synaptic plasticity. The N-terminal domain of PSD95 (residues 1–71, called PSD95-NT) interacts with target proteins (calmodulin, α-actinin-1 and CDKL5), which regulate the Ca2+-dependent degradation of glutamate receptors. We report complete backbone NMR chemical shift assignments of PSD95-NT (BMRB No. 50752).

Chemical synaptic transmission represents the most sophisticated dynamic process and is highly regulated with optimized neurotransmitter balance. Imbalanced transmitters can lead to transmission impairments, for example, intracellular zinc accumulation is a hallmark of degenerating neurons. However, the underlying mechanisms remain elusive. Postsynaptic density protein‐95 (PSD‐95) is a primary postsynaptic membrane‐associated protein and the major scaffolding component in the excitatory postsynaptic densities, which performs substantial functions in synaptic development and maturation. Its membrane association induced by palmitoylation contributes largely to its regulatory functions at postsynaptic sites. Unlike other structural domains in PSD‐95, the N‐terminal region (PSD‐95NT) is flexible and interacts with various targets, which modulates its palmitoylation of two cysteines (C3/C5) and glutamate receptor distributions in postsynaptic densities. PSD‐95NT contains a putative zinc‐binding motif (C2H2) with undiscovered functions. This study is the first effort to investigate the interaction between Zn(2+) and PSD‐95NT. The NMR titration of (15)N‐labeled PSD‐95NT by ZnCl(2) was performed and demonstrated Zn(2+) binds to PSD‐95NT with a binding affinity (K (d)) in the micromolar range. The zinc binding was confirmed by fluorescence and mutagenesis assays, indicating two cysteines and two histidines (H24, H28) are critical residues for the binding. These results suggested the concentration‐dependent zinc binding is likely to influence PSD‐95 palmitoylation since the binding site overlaps the palmitoylation sites, which was verified by the mimic PSD‐95 palmitoyl modification and intact cell palmitoylation assays. This study reveals zinc as a novel modulator for PSD‐95 postsynaptic membrane association by chelating its N‐terminal region, indicative of its importance in postsynaptic signaling.

A novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. While the world is striving for a treatment modality against SARS-CoV-2, our understanding about the virus entry mechanisms may help to design entry inhibitors, which may help to limit the virus spreading. Owing to the importance of cellular ACE2 and heparan sulfate in SARS-CoV-2 entry, we aimed to evaluate the efficacy of cationic G1 and G2 peptides in virus entry inhibition. In silico binding affinity studies revealed possible binding sites of G1 and G2 peptides on HS and ACE2, which are required for the spike–HS and spike–ACE2 interactions. Prophylactic treatment of G1 and G2 peptide was also proved to decrease the cell surface HS, an essential virus entry receptor. With these two mechanisms we confirm the possible use of cationic peptides to inhibit the entry of SARS-CoV-2.

Naegleria fowleri causes the usually fatal disease primary amebic meningoencephalitis (PAM), typically in people who have been swimming in warm, untreated freshwater. Recently, some cases in the United States were associated with exposure to treated drinking water. In 2013, a case of PAM was reported for the first time in association with the exposure to water from a US treated drinking water system colonized with culturable N. fowleri. This system and another were found to have multiple areas with undetectable disinfectant residual levels. In response, the water distribution systems were temporarily converted from chloramine disinfection to chlorine to inactivate N. fowleri and reduced biofilm in the distribution systems. Once >1.0 mg/L free chlorine residual was attained in all systems for 60 days, water testing was performed; N. fowleri was not detected in water samples after the chlorine conversion. This investigation highlights the importance of maintaining adequate residual disinfectant levels in drinking water distribution systems. Water distribution system managers should be knowledgeable about the ecology of their systems, understand potential water quality changes when water temperatures increase, and work to eliminate areas in which biofilm growth may be problematic and affect water quality.

Neonicotinoids are the most widely used insecticides worldwide and are typically deployed as seed treatments (hereafter NST) in many grain and oilseed crops, including soybeans. However, there is a surprising dearth of information regarding NST effectiveness in increasing soybean seed yield, and most published data suggest weak, or inconsistent yield benefit. The US is the key soybean-producing nation worldwide and this work includes soybean yield data from 194 randomized and replicated field studies conducted specifically to evaluate the effect of NSTs on soybean seed yield at sites within 14 states from 2006 through 2017. Here we show that across the principal soybean-growing region of the country, there are negligible and management-specific yield benefits attributed to NSTs. Across the entire region, the maximum observed yield benefits due to fungicide (FST = fungicide seed treatment) + neonicotinoid use (FST + NST) reached 0.13 Mg/ha. Across the entire region, combinations of management practices affected the effectiveness of FST + NST to increase yield but benefits were minimal ranging between 0.01 to 0.22 Mg/ha. Despite widespread use, this practice appears to have little benefit for most of soybean producers; across the entire region, a partial economic analysis further showed inconsistent evidence of a break-even cost of FST or FST + NST. These results demonstrate that the current widespread prophylactic use of NST in the key soybean-producing areas of the US should be re-evaluated by producers and regulators alike.

T-cell-dependent bispecific antibodies (TDBs) are promising cancer immunotherapies that recruit patients’ T cells to kill cancer cells. There are many TDBs in clinical trials, demonstrating their widely recognized therapeutic potential. However, their complex, multi-step mechanism of action (MoA), which includes bispecific antigen binding, T-cell activation, and target-cell killing, presents unique challenges for biological characterization and potency assay selection. Here, we describe the development of a single reporter-gene potency assay for a TDB (TDB1) that is MoA reflective and sensitive to binding of both antigens. Our reporter-gene assay measures T-cell activation using Jurkat cells engineered to express luciferase under the control of an NFkB response element. The potencies of select samples were measured both by this assay and by a flow-cytometry-based cell-killing assay using human lymphocytes as effector cells. Correlating the two sets of potency results clearly establishes our reporter-gene assay as MoA reflective. Furthermore, correlating potencies for the same panel of samples against binding data measured by binding assays for each individual arm demonstrates that the reporter-gene potency assay reflects dual-antigen binding and can detect changes in affinity for either arm. This work demonstrates that one reporter-gene assay can be used to measure the potency of TDB1 while capturing key aspects of its MoA, thus serving as a useful case study of selection and justification of reporter-gene potency assays for TDBs. Furthermore, our strategy of correlating reporter-gene potency, target-cell killing, and antigen binding for each individual arm serves as a useful example of a thorough, holistic approach to biological characterization for TDBs that can be applied to other bispecific molecules.

The Marathon platinum group element (PGE)–Cu deposit is hosted by the Two Duck Lake Gabbro of the Mesoproterozoic Coldwell Complex, Canada, and comprises three zones of mineralization, which have different textural, mineralogical and geochemical characteristics. The Footwall Zone occurs at the base of the Two Duck Lake Gabbro, at the contact with the Archean country rocks. The Main Zone occurs within the Two Duck Lake Gabbro, above the Footwall Zone. The W Horizon is an extraordinarily PGE-enriched zone that is characterized by very low Cu/Pd values, less pyrrhotite, and appreciably more bornite than the Footwall and Main zones. It occurs above Main Zone-equivalent mineralization in the southern half of the Two Duck Lake intrusion. Silicate mineral textures and chemistry reveal that the Marathon deposit formed in a dynamic magma conduit system with a complex magma evolution history. The deposit developed into three zones as a result of the multiple pulses of compositionally different magmas. Plagioclase commonly shows resorption surfaces with overgrowths and the anorthite content and concentrations of trace elements such as Fe, Sr, Ba, and rare earth elements in plagioclase change significantly across these surfaces. In rocks that contain sulfide minerals, plagioclase crystals have been partly resorbed and the resorbed rims are Ca-enriched and intergrown with sulfide mineral inclusions. These rims contain higher base-metal and sulfur contents and are light rare earth element-enriched compared with the primary plagioclase. These characteristics indicate input of a separate sulfide-enriched melt with a different composition compared with that from which the primary plagioclase crystallized. Additional evidence for the involvement of slightly different magmas during evolution of the three mineralized zones is derived from variations in pyroxene chemistry (e.g. higher Fe, lower Mg, V, and Sc) between the Footwall Zone and the other two zones and the absence of inverted pigeonite from the W Horizon. The PGE enrichment occurred at depth prior to intrusion and late-stage PGE-rich sulfide-bearing magmas intruded and formed the W Horizon. Therefore, the W Horizon is a zone of mineralization that formed late in the evolution of the Two Duck Lake Gabbro.

The amino acid asparagine is considered the rate limiting precursor in the formation of acrylamide in cereal-based baked foods. However, there are no data on the quantity of this precursor in Canadian wheat. Wholemeal and white flour samples obtained from 30 Canadian hard red spring wheat grown in the Prairie provinces were analysed for asparagine content by liquid chromatography. The asparagine content varied from 302 to 965 and 116 to 336 μg g−1 for wholemeal and white flour, respectively. Therefore, wheat grown in Canada has similar asparagine levels to wheat grown in other parts of the world. Analysis of variance suggested that asparagine content is significantly affected by genotype (p

Brown marmorated stink bug (Halyomorpha halys Stål) is an invasive agricultural pest that causes severe damage to many crops. To determine potential associations between H. halys feeding damage, Fusarium infection, and mycotoxin contamination in field corn, a field survey was conducted in eight counties in Virginia. Results indicated an association between H. halys feeding damage and fumonisin contamination. Subsequent field experiments in Delaware, Maryland, and Virginia examined the ability of H. halys to increase Fusarium verticillioides (Sacc.) Nirenberg infection and fumonisin concentrations in corn. At the milk stage, H. halys (0 or 4 adults) and Fusarium (with or without F. verticillioides inoculum) treatments were applied to bagged ears in a two by two factorial randomized complete block design with 12 replicates. H. halys treatments increased levels of feeding damage (P < 0.0001) and Fusarium infection (P = 0.0380). Interaction between H. halys and Fusarium treatments influenced severity of infection (P = 0.0018) and fumonisin concentrations (P = 0.0360). Results suggest H. halys has the ability to increase both Fusarium infection and fumonisin concentrations in field corn. Further studies are needed to understand mechanisms by which H. halys increases fumonisin and to develop management strategies to mitigate impacts of H. halys on field corn in the region.

In recent years, AIM has established molecular beam epitaxy growth of mercury cadmium telluride (MCT) on GaAs substrates for the cost-effective production of standard infrared (IR)-detectors in the mid-wave infrared (MWIR) spectral range. The most recent progress in development is to apply this technology to the fabrication of 3rd generation IR-modules. The growth of MCT multi-layers with high homogeneity in layer thickness and composition, coupled with a low defect density, is the basis of high performance multi-color IR-detectors. Applying this technology to 3rd generation IR-modules, AIM is developing short-wave/mid-wave (SW/MW) and mid-wave/mid-wave (MW/MW) infrared bispectral MCT detectors with 320 × 256 pixels and a 30 μm pitch. The sensitivity of two different IR wavelengths in one detector greatly enhances the ability to gather information from a scene, which is a significant additional benefit for IR systems. In particular, the combination of the SWIR/MWIR or MWIR/MWIR spectral bands promote an enhanced target discrimination and identification by increasing the identification range, by enabling the target acquisition in front of strongly structured backgrounds, or of targets with low thermal signature. Results will be presented on AIM’s SW/MW, as well as MW/MW bispectral MCT IR detectors. The detectors demonstrate very low color cross-talk, low defect densities, thermal resolution of about 20 mK, and high quantum efficiencies.

Chronic activation of the renin‐angiotensin‐aldosterone system (RAAS) promotes and perpetuates the syndromes of congestive heart failure, systemic hypertension, and chronic kidney disease. Excessive circulating and tissue angiotensin II (AngII) and aldosterone levels lead to a pro‐fibrotic, ‐inflammatory, and ‐hypertrophic milieu that causes remodeling and dysfunction in cardiovascular and renal tissues. Understanding of the role of the RAAS in this abnormal pathologic remodeling has grown over the past few decades and numerous medical therapies aimed at suppressing the RAAS have been developed. Despite this, morbidity from these diseases remains high. Continued investigation into the complexities of the RAAS should help clinicians modulate (suppress or enhance) components of this system and improve quality of life and survival. This review focuses on updates in our understanding of the RAAS and the pathophysiology of AngII and aldosterone excess, reviewing what is known about its suppression in cardiovascular and renal diseases, especially in the cat and dog.

Introduction Neuronal p3-Alcβ peptides are generated from the precursor protein Alcadein β (Alcβ) through cleavage by α- and γ-secretases of the amyloid β (Aβ) protein precursor (APP). To reveal whether p3-Alcβ is involved in Alzheimer's disease (AD) contributes for the development of novel therapy and/or drug targets. Methods We developed new sandwich enzyme-linked immunosorbent assay (sELISA) systems to quantitate levels of p3-Alcβ in the cerebrospinal fluid (CSF). Results In monkeys, CSF p3-Alcβ decreases with age, and the aging is also accompanied by decreased brain expression of Alcβ. In humans, CSF p3-Alcβ levels decrease to a greater extent in those with AD than in age-matched controls. Subjects carrying presenilin gene mutations show a significantly lower CSF p3-Alcβ level. A cell study with an inverse modulator of γ-secretase remarkably reduces the generation of p3-Alcβ37 while increasing the production of Aβ42. Discussion Aging decreases the generation of p3-Alcβ, and further significant decrease of p3-Alcβ caused by aberrant γ-secretase activity may accelerate pathogenesis in AD.

Oat has procured its acclaim as a health promoting food partially due to its positive effect on glucose control. It has been demonstrated that oat β-glucan can interfere with postprandial glucose response. A large majority of this action is attributed to the increase in viscosity due to the β-glucan content in oat foods. While it is known that an increase in viscosity due to higher molecular weight of β-glucan can improve its glycemic effects, it is not known if an increase in viscosity attained by processing variables can further enhance the positive effect of oat on glucose control. In the current study we have examined the effect of kilning, tempering, microwaving, cooking, soaking and flaking on oat β-glucan viscosity. An acute randomized crossover clinical trial was also conducted to test oatmeal products containing low, medium and high β-glucan viscosity for their effect on postprandial glycemic response. Results from the processing experiments demonstrate that kilned samples, when tempered to 25% moisture and microwaved for 2 minutes, can produce much higher final viscosity compared to other samples with similar β-glucan content, molecular weight and solubility. However, results from the clinical trial show that the increase in the viscosity of the oat β-glucan attained through processing in this study did not have any effect on postprandial glucose control.

Exposures to phthalates, parabens, and other phenols are often correlated due to their ubiquitous use in personal care products and plastics. Examining these compounds as a complex mixture may clarify inconsistent relationships between individual chemicals and childhood adiposity. Using data from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a longitudinal cohort of children in Salinas Valley, California (n = 309), we examined biomarkers of 11 phthalate metabolites and 9 phenols, including several parabens and bisphenol A, measured in maternal urine at two time points during pregnancy. We measured child height and weight at age five to calculate the body mass index (BMI) z-scores and overweight/obesity status. The association between prenatal urinary concentrations of biomarkers with the childhood BMI z-score and overweight/obesity status was analyzed using single-pollutant models and two mixture methods: Bayesian hierarchical modeling (BMH) and Bayesian kernel machine regression (BKMR). Urinary concentrations of monoethyl phthalate, monocarboxy-isononly phthalate (metabolites of diethyl phthalate and di-isodecyl phthalate, respectively), and propylparaben were consistently associated with an increased BMI z-score and overweight/obesity status across all modeling approaches. Higher prenatal exposures to the cumulative biomarker mixture also trended with greater childhood adiposity. These results, robust across two methods that control for co-pollutant confounding, suggest that prenatal exposure to certain phthalates and parabens may increase the risk for obesity in early childhood.

African Americans have higher incidence of, and mortality from, many health-related problems than European Americans. They also have a 15 to 20-fold higher prevalence of severe vitamin D deficiency. Here we summarize evidence that: (i) this health disparity is partly due to insufficient vitamin D production, caused by melanin in the skin blocking the UVB solar radiation necessary for its synthesis; (ii) the vitamin D insufficiency is exacerbated at high latitudes because of the combination of dark skin color with lower UVB radiation levels; and (iii) the health of individuals with dark skin can be markedly improved by correcting deficiency and achieving an optimal vitamin D status, as could be obtained by supplementation and/or fortification. Moderate-to-strong evidence exists that high 25-hydroxyvitamin D levels and/or vitamin D supplementation reduces risk for many adverse health outcomes including all-cause mortality rate, adverse pregnancy and birth outcomes, cancer, diabetes mellitus, Alzheimer’s disease and dementia, multiple sclerosis, acute respiratory tract infections, COVID-19, asthma exacerbations, rickets, and osteomalacia. We suggest that people with low vitamin D status, which would include most people with dark skin living at high latitudes, along with their health care provider, consider taking vitamin D3 supplements to raise serum 25-hydroxyvitamin D levels to 30 ng/mL (75 nmol/L) or possibly higher.

Type II toxin-antitoxin systems contain a toxin protein, which mediates diverse interactions within the bacterial cell when it is not bound by its cognate antitoxin protein. These toxins provide a rich source of evolutionarily-conserved tertiary folds that mediate diverse catalytic reactions. These properties make toxins of interest in biotechnology applications, and studies of the catalytic mechanisms continue to provide surprises. In the current work, our studies on a YoeB family toxin from Agrobacterium tumefaciens have revealed a conserved ribosome-independent non-specific nuclease activity. We have quantified the RNA and DNA cleavage activity, revealing they have essentially equivalent dose-dependence while differing in requirements for divalent cations and pH sensitivity. The DNA cleavage activity is as a nickase for any topology of double-stranded DNA, as well as cleaving single-stranded DNA. AtYoeB is able to bind to double-stranded DNA with mid-micromolar affinity. Comparison of the ribosome-dependent and -independent reactions demonstrates an approximate tenfold efficiency imparted by the ribosome. This demonstrates YoeB toxins can act as non-specific nucleases, cleaving both RNA and DNA, in the absence of being bound within the ribosome.