Metal-promoted self-assembly of collagen mimetic peptides into biofunctional scaffolds for stem cell delivery with the aim of tissue regeneration

Collagen is a strong, sturdy, but malleable, protein found abundantly in the extracellular matrix. Consequently, it has become an invaluable biomaterial for use in regenerative medicine. However, natural collagen poses difficulties when it comes to customization and structural control, as well as the risk of infectious prions from animal sources. Our approach utilizes shorter, synthetic collagen mimetic peptide sequences. These peptides retain the incredible triple helical stability of natural collagen but can be modified with versatile metal-binding ligands. In the presence of an appropriate metal ion, the peptides self-assemble into diverse, three-dimensional morphologies. The peptide NCoH, functionalized with N-terminal NTA and C-terminal dihistidine, self-assembles into ruffled spheres called microflorettes that can be selectively functionalized internally and / or externally with biomolecules containing a His tag. A novel fluorophore, Rho-(Gly)3-(His)6, was synthesized to enable high-quality visualization of NCoH microflorette interactions with cells. Fluorescent confocal microscopy confirmed that NCoH microflorettes sequester HeLa and human mesenchymal stem cells. Moreover, these microflorettes were shown to bind to human epidermal growth factor. The peptide NCoH alone holds great possibilities for use in biomedicine, but such possibilities could be expanded ever more by mixing NCoH with other collagen mimetic peptides. Self-assembly of mixtures of NCoH with the cross-linked peptide HBN in the presence of various divalent metal ions resulted in integrated mesh / florette systems. Joint metal-promoted self-assembly of NCoH mixed with its analogs HisCol and / or IdaCol results in an array of highly intricate morphologies, including and especially novel, spiraled “horned” bundles with well-ordered periodicity that form within minutes and under neutral conditions. Moreover, such assemblies can be carried out on a glass surface, producing structures with a high degree of order on both the micro- and nanoscales that could potentially be exploited for future biochemical applications. The vast array of structures that can be produced through metal-promoted self-assembly of collagen mimetic peptides holds great potential for the development of highly customizable tissue engineering therapies

Glutaric acidemia type 1: Treatment and outcome of 168 patients over three decades

Glutaric acidemia type 1 (GA1) is a disorder of cerebral organic acid metabolism resulting from biallelic mutations of GCDH. Without treatment, GA1 causes striatal degeneration in \u3e 80% of affected children before two years of age. We analyzed clinical, biochemical, and developmental outcomes for 168 genotypically diverse GA1 patients managed at a single center over 31 years, here separated into three treatment cohorts: children in Cohort I (n = 60; DOB 2006-2019) were identified by newborn screening (NBS) and treated prospectively using a standardized protocol that included a lysine-free, arginine-enriched metabolic formula, enteral l-carnitine (100 mg/kg*day), and emergency intravenous (IV) infusions of dextrose, saline, and l-carnitine during illnesses; children in Cohort II (n = 57; DOB 1989-2018) were identified by NBS and treated with natural protein restriction (1.0-1.3 g/kg*day) and emergency IV infusions; children in Cohort III (n = 51; DOB 1973-2016) did not receive NBS or special diet. The incidence of striatal degeneration in Cohorts I, II, and III was 7%, 47%, and 90%, respectively (p \u3c .0001). No neurologic injuries occurred after 19 months of age. Among uninjured children followed prospectively from birth (Cohort I), measures of growth, nutritional sufficiency, motor development, and cognitive function were normal. Adherence to metabolic formula and l-carnitine supplementation in Cohort I declined to 12% and 32%, respectively, by age 7 years. Cessation of strict dietary therapy altered plasma amino acid and carnitine concentrations but resulted in no serious adverse outcomes. In conclusion, neonatal diagnosis of GA1 coupled to management with lysine-free, arginine-enriched metabolic formula and emergency IV infusions during the first two years of life is safe and effective, preventing more than 90% of striatal injuries while supporting normal growth and psychomotor development. The need for dietary interventions and emergency IV therapies beyond early childhood is uncertain

Branched-chain alpha-ketoacid dehydrogenase deficiency (maple syrup urine disease): Treatment, biomarkers, and outcomes

Over the past three decades, we studied 184 individuals with 174 different molecular variants of branched-chain alpha-ketoacid dehydrogenase activity, and here delineate essential clinical and biochemical aspects of the maple syrup urine disease (MSUD) phenotype. We collected data about treatment, survival, hospitalization, metabolic control, and liver transplantation from patients with classic (i.e., severe; n = 176), intermediate (n = 6) and intermittent (n = 2) forms of MSUD. A total of 13,589 amino acid profiles were used to analyze leucine tolerance, amino acid homeostasis, estimated cerebral amino acid uptake, quantitative responses to anabolic therapy, and metabolic control after liver transplantation. Standard instruments were used to measure neuropsychiatric outcomes. Despite advances in clinical care, classic MSUD remains a morbid and potentially fatal disorder. Stringent dietary therapy maintains metabolic variables within acceptable limits but is challenging to implement, fails to restore appropriate concentration relationships among circulating amino acids, and does not fully prevent cognitive and psychiatric disabilities. Liver transplantation eliminates the need for a prescription diet and safeguards patients from life-threatening metabolic crises, but is associated with predictable morbidities and does not reverse pre-existing neurological sequelae. There is a critical unmet need for safe and effective disease-modifying therapies for MSUD which can be implemented early in life. The biochemistry and physiology of MSUD and its response to liver transplantation afford key insights into the design of new therapies based on gene replacement or editing

Linear filtering and mathematical morphology on an image: A bridge

International audienceIn this paper, we propose to show that a particular fuzzy extension of mathematical morphology coincides with a non-additive extension of linear filtering based on convolution kernels thus bridging the two approaches

Attention-based Adversarial Appearance Learning of Augmented Pedestrians

Synthetic data became already an essential component of machine learning-based perception in the field of autonomous driving. Yet it still cannot replace real data completely due to the sim2real domain shift. In this work, we propose a method that leverages the advantages of the augmentation process and adversarial training to synthesize realistic data for the pedestrian recognition task. Our approach utilizes an attention mechanism driven by an adversarial loss to learn domain discrepancies and improve sim2real adaptation. Our experiments confirm that the proposed adaptation method is robust to such discrepancies and reveals both visual realism and semantic consistency. Furthermore, we evaluate our data generation pipeline on the task of pedestrian recognition and demonstrate that generated data resemble properties of the real domain

The Impact of Community-Based Dental Education on Students

Community-based dental education (CBDE) shifts a substantial portion of dental clinical education from dental school clinics to mainly public health settings. For dental students to learn effectively in community settings they need preparatory education in cultural awareness, communication skills, and the social and behavioral sciences. The effective integration of CBDE into a dental curriculum requires reflective components, evaluation, and highly organized community-based experiences. This chapter reviews organizational principles and specific strategies to ensure that CBDE is conducted in a fashion that enables student learning and community oral health service. CBDE has substantial potential for affecting the values and behaviors of dental students relative to health care access for underserved populations and for attracting diverse students to dental education. CBDE also provides dentistry with an opportunity to guide dental faculty and student values and orientation towards public service, engagement, ethics, and the health of the public

Comparing client and staff reports on tobacco-related knowledge, attitudes, beliefs and services provided in substance use treatment

INTRODUCTION Smoking is highly prevalent in substance use disorder (SUD) programs, but few studies have explored the tobacco-related attitudes of staff and clients in the same program. The aim of this study was to compare staff and client reports on 10 tobacco-related items and associate them with tobacco measures implemented in the programs. METHODS A cross-sectional survey was conducted in 18 residential SUD programs from 2019 to 2020. Overall, 534 clients and 183 clinical staff self-reported their tobacco use, knowledge, attitudes, beliefs, and practices/services regarding smoking cessation. Ten comparable items were asked of both clients and staff. Differences in their responses were tested using bivariate analyses. We examine the association between selected tobacco-related items on making a quit attempt and planning to quit in the next 30 days. RESULTS In all, 63.7% of clients were current cigarette users versus 22.9% of staff. About half of clinicians (49.4%) said they had the skills to help patients quit smoking, while only 34.0% of clients thought their clinicians had these skills (p=0.003). About 28.4% of staff reported encouraging their patients to use nicotine replacement treatment (NRT), and 23.4% of patients said they had been encouraged to use these products. Client reports of planning a quit attempt were positively correlated with whether both staff and clients reported that the use of higher percentage of smokers planned a quit attempt. Tobacco-related training among staff, and communication about tobacco use with clients, should be improved to make tobacco services more visible and accessible in SUD treatment

Inflight Resources Recycling and Pollution Mitigation Impacts Through the WolfSat-1 CubeSat Mission

Mission: A CubeSat to Monitor Enzyme Activity of Ideonella Sakaiensis in the Microgravity Environmen

Pantothenamides Are Potent, On-Target Inhibitors of Plasmodium falciparum Growth When Serum Pantetheinase Is Inactivated

Growth of the virulent human malaria parasite Plasmodium falciparum is dependent on an extracellular supply of pantothenate (vitamin B(5)) and is susceptible to inhibition by pantothenate analogues that hinder pantothenate utilization. In this study, on the hunt for pantothenate analogues with increased potency relative to those reported previously, we screened a series of pantothenamides (amide analogues of pantothenate) against P. falciparum and show for the first time that analogues of this type possess antiplasmodial activity. Although the active pantothenamides in this series exhibit only modest potency under standard in vitro culture conditions, we show that the potency of pantothenamides is selectively enhanced when the parasite culture medium is pre-incubated at 37°C for a prolonged period. We present evidence that this finding is linked to the presence in Albumax II (a serum-substitute routinely used for in vitro cultivation of P. falciparum) of pantetheinase activity: the activity of an enzyme that hydrolyzes the pantothenate metabolite pantetheine, for which pantothenamides also serve as substrates. Pantetheinase activity, and thereby pantothenamide degradation, is reduced following incubation of Albumax II-containing culture medium for a prolonged period at 37°C, revealing the true, sub-micromolar potency of pantothenamides. Importantly we show that the potent antiplasmodial effect of pantothenamides is attenuated with pantothenate, consistent with the compounds inhibiting parasite proliferation specifically by inhibiting pantothenate and/or CoA utilization. Additionally, we show that the pantothenamides interact with P. falciparum pantothenate kinase, the first enzyme involved in converting pantothenate to coenzyme A. This is the first demonstration of on-target antiplasmodial pantothenate analogues with sub-micromolar potency, and highlights the potential of pantetheinase-resistant pantothenamides as antimalarial agents.Aspects of this work were supported by grants from the South African Malaria Initiative (SAMI) to ES and KJS and the American Lebanese Syrian Associated Charities (ALSAC), St. Jude Children’s Research Hospital, to REL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Chemical Composition of Second Rotation Populus Hybrid NE-388

The influence of management strategy and rotation on specific gravity and chemical content (extractive, holocellulose, alpha-cellulose, and Klason lignin) values for second rotation 4-year-old Populus Hybrid NE-388 wood and bark specimens were investigated. Specific gravity values for wood were lowest for fertilization and fertilization/irrigation strategies and for bark were highest for fertilization and fertilization/irrigation strategies compared to control and irrigation strategies. Management strategies had little effect on the holocellulose and alpha-cellulose values for the second rotation. Management strategy and rotation had significant effects on extractive and Klason lignin contents for bark and the extractive content for wood. Second rotation average specific gravity values for wood were similar to or higher than first rotation values and average Klason lignin content values for bark were higher than first rotation values