The use of animals as models of human physiology is, and has been for many years, an indispensable tool for understanding the mechanisms of human disease. In Parkinson’s disease, various mouse models form the cornerstone of these investigations. Early models were developed to reflect the traditional histological features and motor symptoms of Parkinson’s disease. However, it is important that models accurately encompass important facets of the disease to allow for comprehensive mechanistic understanding and translational significance. Circadian rhythm and sleep issues are tightly correlated to Parkinson’s disease, and often arise prior to the presentation of typical motor deficits. It is essential that models used to understand Parkinson’s disease reflect these dysfunctions in circadian rhythms and sleep, both to facilitate investigations into mechanistic interplay between sleep and disease, and to assist in the development of circadian rhythm-facing therapeutic treatments. This review describes the extent to which various genetically- and neurotoxically-induced murine models of Parkinson’s reflect the sleep and circadian abnormalities of Parkinson’s disease observed in the clinic.
While the use of medical and recreational cannabis is rapidly expanding under state jurisdiction, the convolution of federal regulations is obstructing research progress to the detriment of healthcare equity and the protection of vulnerable populations, such as the underaged. U.S. Senate bill S.253 is designed to accelerate the development of trusted preclinical and clinical principles based on scientific data to guide physicians in their daily practice, inform lawmakers, and thereby protect public health. This goes together with a reinforcement of the legal protection that practitioners have acquired over years of litigation with the federal government when working with their patients. S.253 supports open communication between physicians and their patients when discussing cannabis as a treatment option. The bill passed the U.S. Senate on March 24, 2022. Funding This work was supported by intramural funding (NYIT College of Osteopathic Medicine) to the corresponding author, Dr. Joerg R. Leheste.
Background Social and behavioral aspects of our lives significantly impact our health, yet minimal social determinants of health (SDOH) data elements are collected in the healthcare system. Methods In this proof-of-concept study we developed a repeatable SDOH enrichment and integration process to incorporate dynamically evolving SDOH domain concepts from consumers into clinical data. This process included SDOH mapping, linking compiled consumer data to patient records in Electronic Health Records, data quality analysis and preprocessing, and storage. Results Consumer compilers data coverage ranged from ~90 to ~54% and the percentage match rate between compilers was between ~21 and 64%. Our preliminary analysis showed that apart from demographic factors, several SDOH factors like home-ownership, marital-status, presence of children, number of members per household, economic stability and education were significantly different between the COVID-19 positive and negative patient groups while estimated family-income and home market-value were not. Conclusion Our preliminary analysis shows commercial consumer data can be a viable source of SDOH factor at an individual-level for clinical data thus providing a path for clinicians to improve patient treatment and care.
We name and describe a new iguanodontian dinosaur from the Early Cretaceous Kirkwood Formation, Eastern Cape Province, South Africa. This dinosaur is one of only two ornithopod dinosaurs known from the Cretaceous of southern Africa, and is unique in being represented primarily by hatchling to young juvenile individuals as demonstrated by bone histological analysis. All of the juvenile material of this new taxon comes from a single , laterally-restricted bonebed and specimens were primarily recovered as partial to complete single elements, although rare articulated materials and one partial skeleton were found. Sedimentology of the bonebed suggests that this horizon heralds a change in environment upsection to a drier and more seasonal climate. This accumulation of bones is interpreted as seasonal mortality from a nesting site or nesting grounds and may be linked to this environmental shift. K E Y W O R D S dinosaur, Early Cretaceous, Iguanodontian, morphology, ornithopod, South Africa
The ascomycete fungus Ophidiomyces ophiodiicola (Oo) is the causative agent of ophidiomycosis (Snake Fungal Disease), which has been detected globally. However, surveillance efforts in the central U.S., specifically Texas, have been minimal. The threatened and rare Brazos water snake (Nerodia harteri harteri) is one of the most range restricted snakes in the U.S. and is sympatric with two wide-ranging congeners, Nerodiaerythrogaster transversa and Nerodiarhombifer, in north central Texas; thus, providing an opportunity to test comparative host–pathogen associations in this system. To accomplish this, we surveyed a portion of the Brazos river drainage (~ 400 river km) over 29 months and tested 150 Nerodia individuals for the presence of Oo via quantitative PCR and recorded any potential signs of Oo infection. We found Oo was distributed across the entire range of N. h. harteri, Oo prevalence was 46% overall, and there was a significant association between Oo occurrence and signs of infection in our sample. Models indicated adults had a higher probability of Oo infection than juveniles and subadults, and adult N. h. harteri had a higher probability of infection than adult N. rhombifer but not higher than adult N. e. transversa. High Oo prevalence estimates (94.4%) in adult N. h. harteri has implications for their conservation and management owing to their patchy distribution, comparatively low genetic diversity, and threats from anthropogenic habitat modification.
This research work is devoted to the experimental investigation of both rheological and mechanical properties of self-compacting concrete (SCC) produced with waste galvanized copper wire fiber and rice husk ash (RHA). In the study, three different volume fractions of 0.5 p to 0.75 percent, 1 percent of scrap copper wire fiber as reinforcing material, and 2 percent RHA as cement replacement were used. To evaluate the fresh characteristics of SCC, the slump flow, J-ring, and V-funnel experiments were conducted for this investigation. Compressive strength, splitting tensile strength, and flexural strength of the concrete were conducted to assess the hardened properties. The test was carried out to compare each characteristic of plain SCC with this modified SCC mixture, containing RHA as pozzolanic materials and copper fiber as reinforcing material. Incorporating copper fiber in the SCC leads to a drop in fresh properties compared to plain SCC but remains within an acceptable range. On the other hand, the inclusion of 2% RHA makes the SCC more viscous. Although adding 2% RHA and 1% copper wire in SCC provide the highest strength, this mix has an unacceptable passing ability. The SCC mix prepared with 2% RHA and 0.75% copper fiber is suggested to be optimum in terms of the overall performance. According to this study, adding metallic fiber reinforcement like copper wire and mineral admixture like RHA can improve the mechanical properties of SCC up to a certain level.
Reptiles, the only ectothermic amniotes, employ a wide variety of physiological adaptations to adjust to their environments but remain vastly understudied in the field of immunology and ecoimmunology in comparison to other vertebrate taxa. To address this knowledge gap, we assessed the current state of research on reptilian innate immunology by conducting an extensive literature search of peer-reviewed articles published across the four orders of Reptilia (Crocodilia, Testudines, Squamata, Rhynchocephalia). Using our compiled dataset, we investigated common techniques, characterization of immune components, differences in findings and type of research among the four orders, and immune responses to ecological and life-history variables. We found that there are differences in the types of questions asked and approaches used for each of these reptilian orders. The different conceptual frameworks applied to each group has led to a lack of a unified understanding of reptilian immunological strategies, which, in turn, have resulted in large conceptual gaps in the field of ecoimmunology as a whole. To apply ecoimmunological concepts and techniques most effectively to reptiles, we must combine traditional immunological studies with ecoimmunological studies to continue to identify, characterize, and describe the reptilian immune components and responses. This review highlights the advances and gaps that remain to help identify targeted and cohesive approaches for future research in reptilian ecoimmunological studies.
From a library of compounds, 11 hit antibacterial agents have been identified as potent anti-Gram-positive bacterial agents. These pyrazole derivatives are active against two groups of pathogens, staphylococci and enterococci, with minimum inhibitory concentration (MIC) values as low as 0.78 μg/mL. These potent compounds showed bactericidal action, and some were effective at inhibiting and eradicating Staphylococcus aureus and Enterococcus faecalis biofilms. Real-time biofilm inhibition by the potent compounds was studied, by using Bioscreen C. These lead compounds were also very potent against S. aureus persisters as compared to controls, gentamycin and vancomycin. In multiple passage studies, bacteria developed little resistance to these compounds (no more than 2 × MIC). The plausible mode of action of the lead compounds is the permeabilization of the cell membrane determined by flow cytometry and protein leakage assays. With the detailed antimicrobial studies, both in planktonic and biofilm contexts, some of these potent compounds have the potential for further antimicrobial drug development. View Full-Text
The mitochondrial genomes (mitogenomes) of bilaterian animals are highly conserved structures that usually consist of a single circular chromosome. However, several species of parasitic lice (Insecta: Phthiraptera) possess fragmented mitogenomes, where the mitochondrial genes are present on separate, circular chromosomes. Nevertheless, the extent, causes, and consequences of this structural variation remain poorly understood. Here, we combined new and existing data to better understand the evolution of mitogenome fragmentation in major groups of parasitic lice. We found strong evidence that fragmented mitogenomes evolved many times within parasitic lice and that the level of fragmentation is highly variable, including examples of heteroplasmic arrangements. We also found a significant association between mitochondrial fragmentation and signatures of relaxed selection. Mitochondrial fragmentation was also associated with changes to a lower AT%, possibly due to differences in mutation biases. Together, our results provide a significant advance in understanding the process of mitogenome fragmentation and provide an important perspective on mitochondrial evolution in eukaryotes. Multiple independent origins of fragmented mitochondrial genome evolution in parasitic lice provide insights into eukaryotic mitochondrial evolution.
Diabetic peripheral neuropathy (DPN) is a medical condition that is progressively becoming more prevalent. The underlying cause of DPN is still unknown, although there have been several hypothesized mechanisms. There are current pharmaceutical treatments used to manage the pain, but their efficacy is largely unsatisfactory and are often associated with serious adverse effects. This review will explore the evidence of a new potential target for treating DPN, the ligands for nicotinic acetylcholine receptors (nAChRs), specifically α4ꞵ2 agonists and α9α10 antagonists.
Background The gut microbiome may play a role in the pathogenesis of neuropsychiatric diseases including major depressive disorder (MDD). Bile acids (BAs) are steroid acids that are synthesized in the liver from cholesterol and further processed by gut-bacterial enzymes, thus requiring both human and gut microbiome enzymatic processes in their metabolism. BAs participate in a range of important host functions such as lipid transport and metabolism, cellular signaling and regulation of energy homeostasis. BAs have recently been implicated in the pathophysiology of Alzheimer's and several other neuropsychiatric diseases, but the biochemical underpinnings of these gut microbiome-linked metabolites in the pathophysiology of depression and anxiety remains largely unknown. Method Using targeted metabolomics, we profiled primary and secondary BAs in the baseline serum samples of 208 untreated outpatients with MDD. We assessed the relationship of BA concentrations and the severity of depressive and anxiety symptoms as defined by the 17-item Hamilton Depression Rating Scale (HRSD 17 ) and the 14-item Hamilton Anxiety Rating Scale (HRSA-Total), respectively. We also evaluated whether the baseline metabolic profile of BA informs about treatment outcomes. Results The concentration of the primary BA chenodeoxycholic acid (CDCA) was significantly lower at baseline in both severely depressed (log 2 fold difference (LFD) = −0.48; p = 0.021) and highly anxious (LFD = −0.43; p = 0.021) participants compared to participants with less severe symptoms. The gut bacteria-derived secondary BAs produced from CDCA such as lithocholic acid (LCA) and several of its metabolites, and their ratios to primary BAs, were significantly higher in the more anxious participants (LFD's range = [0.23, 1.36]; p 's range = [6.85E-6, 1.86E-2]). The interaction analysis of HRSD 17 and HRSA-Total suggested that the BA concentration differences were more strongly correlated to the symptoms of anxiety than depression. Significant differences in baseline CDCA (LFD = −0.87, p = 0.0009), isoLCA (LFD = −1.08, p = 0.016) and several BA ratios (LFD's range [0.46, 1.66], p 's range [0.0003, 0.049]) differentiated treatment failures from remitters. Conclusion In patients with MDD, BA profiles representing changes in gut microbiome compositions are associated with higher levels of anxiety and increased probability of first-line treatment failure. If confirmed, these findings suggest the possibility of developing gut microbiome-directed therapies for MDD characterized by gut dysbiosis.
Nutritional changes immediately after insemination cause increased embryonic mortality, but the mechanisms controlling this are not well known. Our objective was to evaluate the impact of nutritional change on estrus expression, steroid concentrations, peripheral and uterine luminal fluid metabolites, and embryo quality in beef heifers. Heifers (n = 139) were assigned to one of two pre-artificial insemination (AI) dietary treatments: LOW (≤ 90% NEm) or HIGH (≥ 139% NEm). Heifers were on treatment for 33 to 36 days before AI (d0) when half of the heifers in each treatment were randomly reassigned to generate four treatments; HIGH-HIGH, HIGH-LOW, LOW-HIGH, and LOW-LOW. Heifers remained on treatments until embryo collection (6-8). Negative energy balance was achieved among LOW heifers as demonstrated by body weight loss and increased NEFA concentrations (P < 0.05). Pre-AI treatment influenced expression of estrus (P = 0.05; HIGH 80.4± 4.0% vs. LOW 69.4 ± 4.2%). Estradiol concentrations and interval to estrus were not affected by treatment (P > 0.55); however, progesterone concentrations were reduced among LOW compared to HIGH (3.57 ± 0.27, 4.64 ± 0.26 ng/mL, respectively; P = 0.004), and heifers maintained on the HIGH pre-AI diet had consistently greater concentrations of progesterone from d 0 to d 8 (P = 0.014). Pre-AI treatment influenced embryo stage (P = 0.05; HIGH 3.61 ± 0.32 vs. LOW 2.72 ± 0.30). Post-AI treatment affected embryo grade (P = 0.02; HIGH 1.78 ± 0.23 vs. LOW 2.64 ± 0.27). In summary, pre-AI nutrient restriction caused decreased expression of estrus, reduced progesterone concentrations after AI, and negatively impacted embryo development, while post-AI restriction hindered embryo quality.
High-throughput phenotyping (HTP) allows automation of fast and precise acquisition and analysis of digital images for the detection of key traits in real time. HTP improves characterization of the growth and development of plants in controlled environments in a nondestructive fashion. Marchantia polymorpha has emerged as a very attractive model for studying the evolution of the physiological, cellular, molecular, and developmental adaptations that enabled plants to conquer their terrestrial environments. The availability of the M. polymorpha genome in combination with a full set of functional genomic tools including genetic transformation, homologous recombination, and genome editing has allowed the inspection of its genome through forward and reverse genetics approaches. The increasing number of mutants has made it possible to perform informative genome-wide analyses to study the phenotypic consequences of gene inactivation. Here we present an HTP protocol for M. polymorpha that will aid current efforts to quantify numerous morphological parameters that can potentially reveal genotype-to-phenotype relationships and relevant connections between individual traits.
High-throughput phenotyping enables the temporal detection of subtle changes in plant plasticity and adaptation to different conditions, such as nitrogen deficiency, in an accurate, nondestructive, and unbiased way. Here, we describe a protocol to assess the contribution of nitrogen addition or deprival using an image-based system to analyze plant phenotype. Thousands of images can be captured throughout the life cycle of Arabidopsis, and those images can be used to quantify parameters such as plant growth (area, caliper length, diameter, etc.), in planta chlorophyll fluorescence, and in planta relative water content.
The purpose of this paper is to develop gather data on the rheological and mechanical properties of self-compacting concrete (SCC) containing varying percentages of waste glass aggregate (WGA). In this current experiment, the coarse aggregate was substituted by adding WGA, with replacement percentages of 0%, 10%, 20%, and 30% by weight being investigated. The rheological properties of SCC were performed to explore the consequence of WGA using various methods, including the J-ring, slump flow, L-box, and V-funnel. In contrast, the compressive, flexural, modulus of elasticity, and stress-strain responses of hardened concrete were assessed in this study. The results of the fresh concrete tests revealed that the substitution of an optimal level of waste glass in SCC provides adequate implementation in flowability, passing ability, and viscosity behaviors. Besides, hardened characteristics were shown to have a steady decrease in strength with increasing WGA content in the concrete mixtures.
Behavior disorders in early childhood are a major public health concern. A large percentage of young children spend their day in childcare settings, making early childhood educators a relevant population to target for behavior management interventions and training. Conscious Discipline® (CD®) is an evidence-based program targeting social emotional learning that involves helping teachers modify classroom environment and teacher strategies to address children’s disruptive behavior. Although CD® has been widely disseminated across the country, very few studies have examined the implementation of the intervention, particularly within early childhood education settings. The current study utilized the promoting action on research implementation in health services framework (i-PARIHS) to assess both facilitators and barriers related to successful implementation among a large cohort of pre-Kindergarten teachers (N = 269). Qualitative methods were utilized to assess teachers’ perceived impact of CD®; implementation of structures, rituals, and routines; and both facilitators and barriers to implementation. Results revealed both facilitators and barriers across domains of the innovation; recipients; and local, organizational, and external contexts. Theoretical and practical implications are discussed.
Uncertainty is high in the ovarian cancer context; yet, limited research has focused on how uncertainty is experienced and managed by patients/survivors. This study, thus, examined sources and management of uncertainty among ovarian cancer patients/survivors. It analyzed qualitative interview data from 28 patients/survivors and found that possibility of disease recurrence, limited social buffer, and exposure to death contributed to uncertainties in women about finances, health, and relationships. Depending on how uncertainties were appraised, women managed these by adapting, regulating social interaction, or maintaining a sense of control. Also, survivor guilt was identified as a component of ovarian cancer survivorship.
The flat-headed snake, Tantilla gracilis Baird and Girard is a small reptile belonging to the family Colubridae. Feces from a single T. gracilis from McCurtain County, Oklahoma, USA, was collected and examined for coccidia; it was found to be passing a new species of Caryospora. Oöcysts of Caryospora sargentae n. sp. are spheroidal to typically subspheroidal with a moderately-pitted bi-layered wall, measure (L × W) 20.7 × 19.2 µm, and have a length/width (L/W) ratio of 1.1; a micropyle and oöcyst residuum were absent but one to several small, irregular to spheroidal masses of non-refractile debris within the oocyst was present as well as a polar granule attached to the inner oöcyst wall. Sporocysts are ovoidal and measure 15.0 × 11.0 µm, L/W 1.4; a nipple-like Stieda body is present as well as a distinct rounded sub-Stieda body. The sporocyst residuum is composed of a large, dense, irregular mass of various sized granules located between and often obscuring the sporozoites. This is the third coccidian described from the flat-headed snake. In addition, we include some data on the endogenous development of the coccidian.
Institution pages aggregate content on ResearchGate related to an institution. The members listed on this page have self-identified as being affiliated with this institution. Publications listed on this page were identified by our algorithms as relating to this institution. This page was not created or approved by the institution. If you represent an institution and have questions about these pages or wish to report inaccurate content, you can contact us here.