Protected biofactors and antioxidants reduce the negative consequences of virus and cold challenge by modulating immunometabolism via changes in the interleukin-6 receptor signaling cascade in the liver.

Protected biofactors and antioxidants (PBA), and protected biofactors and antioxidants with protected organic acids and essential oils (PBA+POAEO) have been shown to have benefits in stressed or challenged birds. Here, we describe the immunometabolic changes observed in the liver of Ross 308 broilers during feed supplementation and brief physiological stress. These studied additives contain protected essential oils, organic acids, and vitamins which may have protective effects on the liver. Thus, we aimed to determine the signaling changes induced by these supplements and the resultant immunometabolic effects in the liver. All birds received a 2X dose of live bronchitis vaccine at d 0 and a 48-h cold challenge by reducing the temperature from 30 to 32°C, to 20 to 23°C on d 3 to 5. Control birds were fed a standard diet without supplementation. Liver samples were collected to evaluate the effects of these treatments on cytokine gene expression and protein phosphorylation via kinome peptide array. ANOVA was used for statistical analysis of the gene expression data (significance at a p-value of 0.05), and PIIKA2 was used for statistical evaluation and comparative analysis of the kinome peptide array data. At d 15, the kinome peptide array analysis and gene expression data showed stimulation of the interleukin 6 receptor (IL-6R) signal transduction for host protection via heightened immune response while inducing immune modulation and reducing inflammation in both supplement treated groups. Significant changes were observed via IL-6R signaling in the metabolic profiles of both groups compared to control and no significant differences when compared to each other. In the liver, these 2 feed additives induced immunometabolic changes predominantly via the IL-6 receptor family signaling cascade. Differences between the 2 treated groups were predominantly in the metabolic pathways, centered around the mTOR pathway and the proteins AMPK, mTOR and S6K, with a more anabolic phenotype following the addition of essential oils.

Lessons From Leading During a Pandemic: An Exploratory Study of Public Health Leadership Insights on Training, Preparation, and Experiences From the Field During COVID-19.

CONTEXT: The public health workforce encountered challenges during the COVID-19 pandemic that exposed areas for improvement in preparation for future public health threats. Key among these is well-trained public health leaders equipped with an array of crisis leadership skills. OBJECTIVES: To examine the training background, assess the perceived preparedness, and garner recommendations for training of the future public health workforce from public health leaders who navigated the COVID-19 pandemic. DESIGN: This exploratory research gleaned information by utilizing an online questionnaire and interviews to provide lessons learned regarding improvements needed for public health leader preparedness. SETTING: Three California public health departments representing urban, suburban, and rural populations. PARTICIPANTS: Thirty public health leaders who were directly involved in public health work for ≥3 years in a leadership/management role and involved in COVID-19-related work for at least 6 months participated. RESULTS: Questionnaire findings revealed gaps in crisis leadership, communication, and collaboration training. Interview results supported and expanded upon the quantitative findings, including the value of various competencies and recommendations to improve the preparedness of future public health leaders. CONCLUSIONS: The findings suggested that although many of the skills needed are competencies for accredited public health training programs, effective leadership during public health emergencies may require additional training beyond what is generally provided. Recommendations include integrating study findings into public health training programs to address competency gaps, leveraging results to enhance leadership skills, and promoting collaboration between public health departments and academic institutions to develop evidence-informed crisis leadership training. These findings inform strategies to ensure the preparedness of the public health workforce for future crises.

Comparison of recovery of sheep, goats, and calves from reversible electrical head-only and head-to-body stunning for halal meat production.

AIMS: To compare the recovery of lambs, goats, and calves from head-only (HO) or high-frequency head-to-body stunning and evaluate the complementary use of behaviour and electroencephalography (EEG) to assess return to consciousness after electrical stunning in these species. METHODS: Six-month-old lambs, adult goats and calves (< 7 days old) were subjected to reversible head-only stunning (50 Hz, 1 A, 2 seconds) or reversible high-frequency head-to-body stunning (RHTB: HO followed by 2,000 Hz, 2 A, 4-second stun to body). Following stunning, behavioural recovery was assessed in 21 lambs, 22 goats, and 20 calves. Latencies to first perform behaviours (end of convulsions, head lift, attempt to right, successful righting, attempt to stand, successful standing) after stunning were scored from video recordings. Recovery of electrical brain activity indicative of consciousness was assessed using EEG in a separate cohort of minimally-anaesthetised lambs, goats and calves (n = 20 per species). EEG traces collected before and after stunning were classified as normal, epileptiform, isoelectric, or transitional activity. Following stunning, the duration of epileptiform and isoelectric activity combined (states of brain activity incompatible with conscious awareness) was calculated, as was latency to return of normal (pre-stun) EEG. RESULTS: The RHTB stun was reversible in all three species, although one sheep failed to recover and was euthanised. Both methods caused tonic and clonic convulsions in all species. Behavioural recovery of sheep and calves was similar for both methods while goats took longer to recover from RHTB than HO stunning. There was no evidence of differences between methods in the duration of EEG incompatible with consciousness or the latency to recovery of normal EEG. CONCLUSIONS: Head-to-body stunning as applied here produced a reversible electrical stun in lambs, adult goats and young calves, although the benefits in terms of meat quality and operator safety are uncertain. Goats took longer to recover behaviourally from head-to-body stunning, possibly due to disrupted motor function, but there was no indication that post-stun unconsciousness lasted longer than following head-only stunning in any species. The normal behaviour for the animals' developmental age should be considered when deciding on behavioural indicators of recovery. The minimal anaesthesia model provided excellent quality EEG data that was valuable for interpretation of the behavioural responses. CLINICAL RELEVANCE: For the purposes of pre-slaughter stunning of sheep, goats and young calves, recovery appears comparable between the two methods, with all but 1/63 animals in the behaviour study recovering normal function.

Prediction of potentially toxic elements in water resources using MLP-NN, RBF-NN, and ANFIS: a comprehensive review.

Water resources are constantly threatened by pollution of potentially toxic elements (PTEs). In efforts to monitor and mitigate PTEs pollution in water resources, machine learning (ML) algorithms have been utilized to predict them. However, review studies have not paid attention to the suitability of input variables utilized for PTE prediction. Therefore, the present review analyzed studies that employed three ML algorithms: MLP-NN (multilayer perceptron neural network), RBF-NN (radial basis function neural network), and ANFIS (adaptive neuro-fuzzy inference system) to predict PTEs in water. A total of 139 models were analyzed to ascertain the input variables utilized, the suitability of the input variables, the trends of the ML model applications, and the comparison of their performances. The present study identified seven groups of input variables commonly used to predict PTEs in water. Group 1 comprised of physical parameters (P), chemical parameters (C), and metals (M). Group 2 contains only P and C; Group 3 contains only P and M; Group 4 contains only C and M; Group 5 contains only P; Group 6 contains only C; and Group 7 contains only M. Studies that employed the three algorithms proved that Groups 1, 2, 3, 5, and 7 parameters are suitable input variables for forecasting PTEs in water. The parameters of Groups 4 and 6 also proved to be suitable for the MLP-NN algorithm. However, their suitability with respect to the RBF-NN and ANFIS algorithms could not be ascertained. The most commonly predicted PTEs using the MLP-NN algorithm were Fe, Zn, and As. For the RBF-NN algorithm, they were NO3, Zn, and Pb, and for the ANFIS, they were NO3, Fe, and Mn. Based on correlation and determination coefficients (R, R2), the overall order of performance of the three ML algorithms was ANFIS > RBF-NN > MLP-NN, even though MLP-NN was the most commonly used algorithm.

Human mutations in high-confidence Tourette disorder genes affect sensorimotor behavior, reward learning, and striatal dopamine in mice.

Tourette disorder (TD) is poorly understood, despite affecting 1/160 children. A lack of animal models possessing construct, face, and predictive validity hinders progress in the field. We used CRISPR/Cas9 genome editing to generate mice with mutations orthologous to human de novo variants in two high-confidence Tourette genes, CELSR3 and WWC1. Mice with human mutations in Celsr3 and Wwc1 exhibit cognitive and/or sensorimotor behavioral phenotypes consistent with TD. Sensorimotor gating deficits, as measured by acoustic prepulse inhibition, occur in both male and female Celsr3 TD models. Wwc1 mice show reduced prepulse inhibition only in females. Repetitive motor behaviors, common to Celsr3 mice and more pronounced in females, include vertical rearing and grooming. Sensorimotor gating deficits and rearing are attenuated by aripiprazole, a partial agonist at dopamine type II receptors. Unsupervised machine learning reveals numerous changes to spontaneous motor behavior and less predictable patterns of movement. Continuous fixed-ratio reinforcement shows that Celsr3 TD mice have enhanced motor responding and reward learning. Electrically evoked striatal dopamine release, tested in one model, is greater. Brain development is otherwise grossly normal without signs of striatal interneuron loss. Altogether, mice expressing human mutations in high-confidence TD genes exhibit face and predictive validity. Reduced prepulse inhibition and repetitive motor behaviors are core behavioral phenotypes and are responsive to aripiprazole. Enhanced reward learning and motor responding occur alongside greater evoked dopamine release. Phenotypes can also vary by sex and show stronger affection in females, an unexpected finding considering males are more frequently affected in TD.

Pictorial essay: improving diagnostic effectiveness of colorectal cancer at CT.

As the routine use for CT increases, there is an opportunity to increase the detection rate of unsuspected and asymptomatic colorectal cancers. This pictorial essay provides abundant examples of the typical morphologic appearances of colorectal cancer in the unprepared colorectum. Many examples of lesions that were missed in clinical practice are illustrated with lessons on how to avoid these errors. Atypical appearances of colorectal cancer are also illustrated. The overall aim is to increase the detection rate of colorectal cancer at routine CT.

More about making profits or providing safe drinking water? A state-of-the-art review on sachet water contamination in Nigeria.

Public health concerns on surface and groundwater contamination worldwide have increased. Sachet water contamination has also raised serious concerns across many developing countries. While previous studies attempted to address this issue, this review takes a different approach by utilizing a comprehensive analysis of physicochemical parameters, heavy metals, and microbial loads tested in sachet water across Nigeria's six geopolitical zones, within the period of 2020-2023. In this review study, over 50 articles were carefully analyzed. Collected data unveiled regional variations in the quality of sachet water across Nigeria. Noteworthy concerns revolve around levels of pH, total hardness, magnesium, calcium, nickel, iron, lead, mercury, arsenic, and cadmium. Fecal contamination was also identified as a significant issue, with the prevalence of several pathogens like Escherichia coli, Salmonella typhi, Enterobacter cloacae, Staphylococcus aureus, and Enterococcus faecalis. The manufacturing, delivery, storage, and final sale of sachet water, as well as poor environmental hygiene, were identified as potential contamination sources. The intake of contaminated sachet water exposes the citizens to waterborne and carcinogenic diseases. While the sachet water industry keeps growing and making profits, it is apparent that improvement calls made by previous studies, regarding the quality of water produced, have not been paid serious attention.

Inhalable porous particles as dual micro-nano carriers demonstrating efficient lung drug delivery for treatment of tuberculosis.

Inhalation therapy treating severe infectious disease is among the more complex and emerging topics in controlled drug release. Micron-sized carriers are needed to deposit drugs into the lower airways, while nano-sized carriers are of preference for cell targeting. Here, we present a novel and versatile strategy using micron-sized spherical particles with an excellent aerodynamic profile that dissolve in the lung fluid to ultimately generate nanoparticles enabling to enhance both extra- and intra-cellular drug delivery (i.e., dual micro-nano inhalation strategy). The spherical particles are synthesised through the condensation of nano-sized amorphous silicon dioxide resulting in high surface area, disordered mesoporous silica particles (MSPs) with monodispersed size of 2.43 µm. Clofazimine (CLZ), a drug shown to be effective against multidrug-resistant tuberculosis, was encapsulated in the MSPs obtaining a dry powder formulation with high respirable fraction (F.P.F. <5 µm of 50%) without the need of additional excipients. DSC, XRPD, and Nitrogen adsorption-desorption indicate that the drug was fully amorphous when confined in the nano-sized pores (9-10 nm) of the MSPs (shelf-life of 20 months at 4 °C). Once deposited in the lung, the CLZ-MSPs exhibited a dual action. Firstly, the nanoconfinement within the MSPs enabled a drastic dissolution enhancement of CLZ in simulated lung fluid (i.e., 16-fold higher than the free drug), increasing mycobacterial killing than CLZ alone (p = 0.0262) and reaching concentrations above the minimum bactericidal concentration (MBC) against biofilms of M. tuberculosis (i.e., targeting extracellular bacteria). The released CLZ permeated but was highly retained in a Calu-3 respiratory epithelium model, suggesting a high local drug concentration within the lung tissue minimizing risk for systemic side effects. Secondly, the micron-sized drug carriers spontaneously dissolve in simulated lung fluid into nano-sized drug carriers (shown by Nano-FTIR), delivering high CLZ cargo inside macrophages and drastically decreasing the mycobacterial burden inside macrophages (i.e., targeting intracellular bacteria). Safety studies showed neither measurable toxicity on macrophages nor Calu-3 cells, nor impaired epithelial integrity. The dissolved MSPs also did not show haemolytic effect on human erythrocytes. In a nutshell, this study presents a low-cost, stable and non-invasive dried powder formulation based on a dual micro-nano carrier to efficiently deliver drug to the lungs overcoming technological and practical challenges for global healthcare.

Nano-FTIR spectroscopy of surface confluent polydopamine films - What is the role of deposition time and substrate material?

Polydopamine (PDA) is a widely used anchoring layer for multiple purposes. While simple to prepare, PDA is characterized by high chemical and topological diversity, which can limit its versatility. Unraveling the formation mechanism and physicochemical properties of continuous confluent layer and adherent nanoparticles on the nanoscale is crucial to further extend the prospective applications of PDA. Utilizing nano-FTIR spectroscopy, we investigate layers of PDA on three different substrates (silicon/silicon dioxide, nitrogen-doped titanium oxide, and gold substrates) at varying times of deposition (ToD). We observed a good correlation between the nano-FTIR and macroscopic FTIR spectra that reflected the changes in the relative abundance of PDA and polymerization intermediates as ToD increased. To gain analytical power, we utilized the principal component analysis (PCA) and extracted additional information from the resulting loadings spectral curves and data distribution in the score plots. We revealed a higher variability of the spectra of ultrathin surface confluent layers compared to the adherent nanoparticles. While the spectra of nanoparticles showed no apparent dependency on either ToD or the substrate material, the spectra of layers were highly affected by the increasing ToD and exhibited a rise in the absorption of PDA. Concomitantly, the spectra of layers grouped according to the substrate material at the lowest ToD point to the fact that the substrate material affects the PDA's initial physicochemical structure. The observed separation gradually diminished with the increasing ToD as the PDA physicochemical structure became less influenced by the substrate material.

A review of the status, challenges, trends, and prospects of groundwater quality assessment in Nigeria: an evidence-based meta-analysis approach.

With the imminent industrial growth and population increase, Nigeria will continue to experience significant shifts in the quality of water, with a rise in emerging contaminants. This will increase the irregularity and complexity of the water quality information. Therefore, using the PRISMA meta-analysis approach, this review systematically identified the commonly used water quality assessment techniques in Nigeria, the drawback in the application of these techniques as well as the gaps in the area of water quality assessment and monitoring from 2003 to 2023. Recommendations were also made based on the evaluation of a new research direction; through the review of the effectiveness of advanced techniques for monitoring water quality in Nigeria. Sixty-eight published articles were chosen for the meta-analysis while the VOSviewer program was used to perform bibliographic coupling and visualization. The review revealed that the application of machine learning in water quality prediction has not been well explored in Nigeria. This is attributed to limited data availability and poor funding by the government. It was found that southwestern Nigeria has a greater amount of research on groundwater quality monitoring and evaluation than other regions. The variability was explained by variations in the underlying geology, aquifer features; variability in anthropogenic activities, and level of literacy among various geopolitical zones. Further studies should focus on the application of soft-computing and integrated biomonitoring techniques for effective prediction and monitoring of emerging contaminants for improved water quality. Effective collaboration between environmental stakeholders and government agencies is recommended for effective water resource sustainability.

Trace element pollution tracking in the complex multi-aquifer groundwater system of Al-Hassa oasis (Saudi Arabia) using spatial, chemometric and index-based techniques.

In a global context, trace element pollution assessment in complex multi-aquifer groundwater systems is important, considering the growing concerns about water resource quality and sustainability worldwide. This research addresses multiple objectives by integrating spatial, chemometric, and indexical study approaches, for assessing trace element pollution in the multi-aquifer groundwater system of the Al-Hassa Oasis, Saudi Arabia. Groundwater sampling and analysis followed standard methods. For this purpose, the research employed internationally recognized protocols for groundwater sampling and analysis, including standardized techniques outlined by regulatory bodies such as the United States Environmental Protection Agency (USEPA) and the World Health Organization (WHO). Average values revealed that Cr (0.041) and Fe (2.312) concentrations surpassed the recommended limits for drinking water quality, posing serious threats to groundwater usability by humans. The trace elemental concentrations were ranked as: Li < Mn < Co < As < Mo < Zn < Al < Ba < Se < V < Ni < Cr < Cu < B < Fe < Sr. Various metal(loid) pollution indices, including degree of contamination, heavy metal evaluation index, heavy metal pollution index, and modified heavy metal index, indicated low levels of groundwater pollution. Similarly, low values of water pollution index and weighted arithmetic water quality index were observed for all groundwater points, signifying excellent groundwater quality for drinking and domestic purposes. Spatial distribution analysis showed diverse groundwater quality across the study area, with the eastern and western parts displaying a less desirable quality, while the northern has the best, making water users in the former more vulnerable to potential pollution effects. Thus, the zonation maps hinted the necessity for groundwater quality enhancement from the western to the northern parts. Chemometric analysis identified both human activities and geogenic factors as contributors to groundwater pollution, with human activities found to have more significant impacts. This research provides the scientific basis and insights for protecting the groundwater system and ensuring efficient water management.

ISCEV and IPS guideline for the full-field stimulus test (FST).

The full-field stimulus test (FST) is a psychophysical technique designed for the measurement of visual function in low vision. The method involves the use of a ganzfeld stimulator, as used in routine full-field electroretinography, to deliver full-field flashes of light. This guideline was developed jointly by the International Society for Clinical Electrophysiology of Vision (ISCEV) and Imaging and Perimetry Society (IPS) in order to provide technical information, promote consistency of testing and reporting, and encourage convergence of methods for FST. It is intended to aid practitioners and guide the formulation of FST protocols, with a view to future standardisation.

Human mutations in high-confidence Tourette disorder genes affect sensorimotor behavior, reward learning, and striatal dopamine in mice.

Tourette disorder (TD) is poorly understood, despite affecting 1/160 children. A lack of animal models possessing construct, face, and predictive validity hinders progress in the field. We used CRISPR/Cas9 genome editing to generate mice with mutations orthologous to human de novo variants in two high-confidence Tourette genes, CELSR3 and WWC1 . Mice with human mutations in Celsr3 and Wwc1 exhibit cognitive and/or sensorimotor behavioral phenotypes consistent with TD. Sensorimotor gating deficits, as measured by acoustic prepulse inhibition, occur in both male and female Celsr3 TD models. Wwc1 mice show reduced prepulse inhibition only in females. Repetitive motor behaviors, common to Celsr3 mice and more pronounced in females, include vertical rearing and grooming. Sensorimotor gating deficits and rearing are attenuated by aripiprazole, a partial agonist at dopamine type II receptors. Unsupervised machine learning reveals numerous changes to spontaneous motor behavior and less predictable patterns of movement. Continuous fixed-ratio reinforcement shows Celsr3 TD mice have enhanced motor responding and reward learning. Electrically evoked striatal dopamine release, tested in one model, is greater. Brain development is otherwise grossly normal without signs of striatal interneuron loss. Altogether, mice expressing human mutations in high-confidence TD genes exhibit face and predictive validity. Reduced prepulse inhibition and repetitive motor behaviors are core behavioral phenotypes and are responsive to aripiprazole. Enhanced reward learning and motor responding occurs alongside greater evoked dopamine release. Phenotypes can also vary by sex and show stronger affection in females, an unexpected finding considering males are more frequently affected in TD. Significance Statement: We generated mouse models that express mutations in high-confidence genes linked to Tourette disorder (TD). These models show sensorimotor and cognitive behavioral phenotypes resembling TD-like behaviors. Sensorimotor gating deficits and repetitive motor behaviors are attenuated by drugs that act on dopamine. Reward learning and striatal dopamine is enhanced. Brain development is grossly normal, including cortical layering and patterning of major axon tracts. Further, no signs of striatal interneuron loss are detected. Interestingly, behavioral phenotypes in affected females can be more pronounced than in males, despite male sex bias in the diagnosis of TD. These novel mouse models with construct, face, and predictive validity provide a new resource to study neural substrates that cause tics and related behavioral phenotypes in TD.

Academic clinician frontline-worker wellbeing and resilience during the COVID-19 pandemic experience: Were there gender differences?

Prior research suggests COVID-19 has amplified stress on Academic Clinician Frontline-Workers (ACFW). The aim of this paper is: (1) to better understand the experiences of ACFW during the COVID-19 pandemic including their mental-emotional wellbeing, academic productivity, clinical experiences, and (2) to examine any gender differences. A cross-sectional survey was administered to University of Minnesota/M Health Fairview systems' faculty February-June 2021. Of the 291 respondents, 156 were clinicians, with 91 (58 %) identifying as Frontline-Workers (ACFW). Faculty wellbeing was assessed using validated measures in addition to measures of productivity and sociodemographics. For example, ACFW reported a higher Work-Family Conflict (WFC) scores compared to non-ACFW (26.5 vs. 24.1, p = 0.057) but did not report higher Family-Work Conflict (FWC) scores (17.7 vs. 16.3, p = 0.302). Gender sub-analyses, revealed that women ACFW compared to men ACFW reported higher WFC scores (27.7 vs. 24.1, p = 0.021) and FWC (19.3 vs. 14.3, p = 0.004). Academically, ACFW reported submitting fewer grants and anticipated delays in promotion and tenure due to the COVID-19 (p = 0.035). Results suggest COVID-19 has exacerbated ACFW stress and gender inequities. Reports of anticipated delay in promotion for ACFW may pose a challenge for the long-term academic success of ACFW, especially women ACFW. In addition, women may experience higher FWC and WFC as compared to men. Schools of academic medicine should consider re-evaluating promotion/tenure processes and creating resources to support women ACFW as well as ACFW caregivers.

Understanding the connections between climate change, air pollution, and human health in Africa: Insights from a literature review.

Climate change and air pollution are two interconnected global challenges that have profound impacts on human health. In Africa, a continent known for its rich biodiversity and diverse ecosystems, the adverse effects of climate change and air pollution are particularly concerning. This review study examines the implications of air pollution and climate change for human health and well-being in Africa. It explores the intersection of these two factors and their impact on various health outcomes, including cardiovascular disease, respiratory disorders, mental health, and vulnerable populations such as children and the elderly. The study highlights the disproportionate effects of air pollution on vulnerable groups and emphasizes the need for targeted interventions and policies to protect their health. Furthermore, it discusses the role of climate change in exacerbating air pollution and the potential long-term consequences for public health in Africa. The review also addresses the importance of considering temperature and precipitation changes as modifiers of the health effects of air pollution. By synthesizing existing research, this study aims to shed light on complex relationships and highlight the key findings, knowledge gaps, and potential solutions for mitigating the impacts of climate change and air pollution on human health in the region. The insights gained from this review can inform evidence-based policies and interventions to mitigate the adverse effects on human health and promote sustainable development in Africa.

Binding affinity predictions with hybrid quantum-classical convolutional neural networks.

Central in drug design is the identification of biomolecules that uniquely and robustly bind to a target protein, while minimizing their interactions with others. Accordingly, precise binding affinity prediction, enabling the accurate selection of suitable candidates from an extensive pool of potential compounds, can greatly reduce the expenses associated to practical experimental protocols. In this respect, recent advances revealed that deep learning methods show superior performance compared to other traditional computational methods, especially with the advent of large datasets. These methods, however, are complex and very time-intensive, thus representing an important clear bottleneck for their development and practical application. In this context, the emerging realm of quantum machine learning holds promise for enhancing numerous classical machine learning algorithms. In this work, we take one step forward and present a hybrid quantum-classical convolutional neural network, which is able to reduce by 20% the complexity of the classical counterpart while still maintaining optimal performance in the predictions. Additionally, this results in a significant cost and time savings of up to 40% in the training stage, which means a substantial speed-up of the drug design process.

Backbone Conformational Equilibrium in Mismatched DNA Correlates with Enzyme Activity.

T:G mismatches in mammals arise primarily from the deamination of methylated CpG sites or the incorporation of improper nucleotides. The process by which repair enzymes such as thymine DNA glycosylase (TDG) identify a canonical DNA base in the incorrect pairing context remains a mystery. However, the abundant contacts of the repair enzymes with the DNA backbone suggest a role for protein-phosphate interaction in the recognition and repair processes, where conformational properties may facilitate the proper interactions. We have previously used 31P NMR to investigate the energetics of DNA backbone BI-BII interconversion and the effect of a mismatch or lesion compared to canonical DNA and found stepwise differences in ΔG of 1-2 kcal/mol greater than equivalent steps in unmodified DNA. We have currently compared our results to substrate dependence for TDG, MBD4, M. HhaI, and CEBPß, testing for correlations to sequence and base-pair dependence. We found strong correlations of our DNA phosphate backbone equilibrium (Keq) to different enzyme kinetics or binding parameters of these varied enzymes, suggesting that the backbone equilibrium may play an important role in mismatch recognition and/or conformational rearrangement and energetics during nucleotide flipping or other aspects of enzyme interrogation of the DNA substrate.

Effect of feeding Yucca schidigera extract and a live yeast on the rumen microbiome and performance of dairy cows fed a diet excess in rumen degradable nitrogen.

Nitrogen (N) loss from livestock agriculture via ammonia and nitrous oxide can reduce feed efficiency, production and negatively affect the environment. One option to reduce N loss is to add dietary supplements such as Yucca schidigera extract which has ammonia-binding properties and contains antimicrobial steroidal saponins, or Saccharomyces cerevisiae yeast, which can stabilise rumen pH and promote fibre degradation, increasing microbial growth and demand for degradable N. To determine the effect of Yucca schidigera extract when fed alone or in combination with a live yeast on the performance, rumen metabolism, microbiome and N balance, six rumen cannulated dairy cows were fed a mixed ration (C), mixed ration with Y. schidigera extract (De-Odorase®, Alltech®; 5 g/cow/day; D), or mixed ration with Y. schidigera extract (5 g/day) and Saccharomyces cerevisiae (Yea-Sacc®, Alltech®, 1 g/cow per day; DY), in a 3 × 3 Latin rectangle design study with three periods of 49-day duration. Digesta samples were collected via the ruminal cannula during the final week of each period and separated into liquid (LPD) and solid (SPD) phases for microbiome analysis using 16S rRNA amplicon sequencing. DM intake was 0.8 kg/d lower (P < 0.05) in cows fed DY than C or D, with milk protein concentration 1.7 g/kg higher in C than D or DY. There was a beta diversity (Bray Curtis) clustering of the LPD in cows fed D or DY compared to C (P < 0.05), driven by an increase in Prevotella ruminicola-related operational taxonomic units (OTUs), and a decrease in P. brevis and P. bryantii OTUs. A methanogen OTU, Methanobrevibacter olleyae, was decreased in cows fed D or DY and an unclassified species of Gammaproteobacteria was increased in DY (LDA > 2.0, P < 0.05) compared to C. Rumen pH, ammonia and total VFA concentration were not affected by treatment (P > 0.05) but the concentration of propionate and iso-butyrate were lower at 1700 and 2000 h in cows fed DY compared to C (P < 0.05). Measurements of N balance were unaffected by supplementation with D or DY, and there was no effect of treatment on slurry pH. In conclusion, supplementing with an extract of Yucca schidigera either alone or in combination with a live yeast had only a small effect on performance, with Yucca schidigera altering species associated with carbohydrate and protein metabolism, and reduced Methanobrevibacter olleyae which is involved in methanogenesis.

Groundwater pollution and risk assessment using indexed-based models: a case study of Igbo-Etiti area, eastern Nigeria.

Water is one of the most abundant resources on earth not evenly distributed. Due to the high shortage of water sources in Igbo-Etiti and intensive agricultural practices in the area, assessment of groundwater pollution and its potential risk to contamination is imperative, as its remediation when contaminated is extremely challenging. Vertical electrical sounding (VES) and physicochemical analysis were carried out in twenty (20) locations and five groundwater samples, respectively, with the aim to evaluate the groundwater pollution indices and the ecological and human health risk associated with its pollution. The VES results delineated five geologic layers and ten characteristic curve types. The fourth layer with the aid of the VES results constrained by the borehole lithologic information on the water bearing geologic unit was delineated as the major exploitable aquifer layer. Results of groundwater vulnerability to pollution classified the area into low (15%), moderate (60%), and high (20%) vulnerability. Physicochemical analysis results on the studied groundwater revealed acidic (pH 4.6) to alkaline (pH 7.2) groundwater conditions. Pollution index of groundwater results delineated a moderate to very high pollution index, with cadmium and arsenic consistently identified as the heavy metals contaminating the groundwater. Ecological risk assessment revealed a moderate to very high integrated potential ecological risk, while human health risk results delineated a target hazard index greater than one in all the studied groundwater samples. This study will serve as a guide to the residents and society in sustainable development decision-making that will preserve the quality of the study area groundwater.