Subcellular NAD pools are interconnected and buffered by mitochondrial NAD.

The coenzyme NAD is consumed by signalling enzymes, including poly-ADP-ribosyltransferases (PARPs) and sirtuins. Ageing is associated with a decrease in cellular NAD levels, but how cells cope with persistently decreased NAD concentrations is unclear. Here, we show that subcellular NAD pools are interconnected, with mitochondria acting as a rheostat to maintain NAD levels upon excessive consumption.

Effect of In Vitro Low-Impulse Laser Irradiation on Morphofunctional Properties of Human Platelets.

We studied morphofunctional features of human platelets exposed in vitro to low-pulse laser radiation (LPLR) with different wavelengths. Platelet-rich plasma (PRP) was irradiated at wavelengths of 635, 488, and 355 nm. LPLR with λ=635 nm and 1 W power after 10 min caused degranulation of many platelets, formation of small platelet conglomerates, and accelerated platelet adhesion on glass.

The interplay between peptides and RNA is critical for protoribosome compartmentalization and stability.

The ribosome, owing to its exceptional conservation, harbours a remarkable molecular fossil known as the protoribosome. It surrounds the peptidyl transferase center (PTC), responsible for peptide bond formation. While previous studies have demonstrated the PTC activity in RNA alone, our investigation reveals the intricate roles of the ribosomal protein fragments (rPeptides) within the ribosomal core.

Computational Modeling of Extrasynaptic NMDA Receptors: Insights into Dendritic Signal Amplification Mechanisms.

Dendritic structures play a pivotal role in the computational processes occurring within neurons. Signal propagation along dendrites relies on both passive conduction and active processes related to voltage-dependent ion channels. Among these channels, extrasynaptic N-methyl-D-aspartate channels (exNMDA) emerge as a significant contributor.

Metabolic Dysregulation and Its Role in Postoperative Pain among Knee Osteoarthritis Patients.

Unlabelled: Knee osteoarthritis (KOA) is characterized by low-grade inflammation, loss of articular cartilage, subchondral bone remodeling, synovitis, osteophyte formation, and pain. Strong, continuous pain may indicate the need for joint replacement in patients with end-stage OA, although postoperative pain (POP) of at least a two-month duration persists in 10-40% of patients with OA.

Study Purpose: The inflammation observed in joint tissues is linked to pain caused by the production of proinflammatory cytokines.

Unique Method for Facile Postsynthetic Modification of Nonisocyanate Polyurethanes.

Nonisocyanate polyurethanes (NIPUs) are broadly investigated as a potential replacement for conventional polyurethanes (PUs) to eliminate the use of toxic isocyanates and reduce occupational hazards. One of the most popular approaches to NIPU synthesis is the polyaddition of cyclic bis(carbonate)s and diamines to form poly(hydroxyurethane)s (PHUs). However, such PHUs are highly hydrophilic due to the presence of two hydroxyl groups per repeat unit, and the resulting moisture absorption significantly degrades their thermomechanical performance and physical stability upon exposure to humidity, thus limiting their utility.

Human arm endpoint-impedance in rhythmic human-robot interaction exhibits cyclic variations.

Estimating the human endpoint-impedance interacting with a physical environment provides insights into goal-directed human movements during physical interactions. This work examined the endpoint-impedance of the upper limb during a hybrid ball-bouncing task with simulated haptic feedback while participants manipulated an admittance-controlled robot. Two experiments implemented a force-perturbation method to estimate the endpoint parameters of 31 participants.

The Modified Fels and Abbreviated Modified Fels Knee Skeletal-Maturity Systems in the Prediction of Leg-Length Discrepancy.

Background: The Modified Fels (mFels) and Abbreviated Modified Fels (abFels) knee systems have been recently developed as options for grading skeletal maturity without the need for a separate hand radiograph. We sought to determine the interobserver reliability of these systems and to compare their prediction accuracy with that of the Greulich and Pyle (G-P) atlas in a cohort managed with epiphysiodesis for leg-length discrepancy (LLD).

Methods: Three reviewers scored 20 knee radiographs using the mFels system, which includes 5 qualitative and 2 quantitative measures as well as a quantitative output.

Ipsilateral Healthy-segment Response to Leg Length Discrepancy.

Background: Few studies address frequency or magnitude of healthy lower-extremity segment response to ipsilateral companion segment shortening. We sought to document and quantify this occurrence in a variety of pediatric etiologies.

Methods: We reviewed the medical record and radiographs of patients undergoing epiphysiodesis to manage leg length discrepancy.

Presenilins and mitochondria-an intriguing link: mini-review.

This review uncovers the intricate relationship between presenilins, calcium, and mitochondria in the context of Alzheimer's disease (AD), with a particular focus on the involvement of presenilin mutations in mitochondrial dysfunction. So far, it is unclear whether the impairment of mitochondrial function arises primarily from damage inflicted by -amyloid upon mitochondria or from the disruption of calcium homeostasis due to presenilins dysfunctions. The roles of presenilins in mitophagy, autophagy, mitochondrial dynamics, and many other functions, non--secretase related, also require close attention in future research.

Morphofunctional Properties of Spindle-Shaped Platelets.

Morphofunctional properties of spindle-shaped platelets under normal and pathological conditions were studied by the method based on vital staining. In donor blood and plasma isolated by centrifugation at 300g, no spindle-shaped platelets were detected; after centrifugation at 3000g, spindle-shaped platelets were detected in a small amount in 20% samples. During plasma storage at 20-22°C, spindle-shaped platelets appeared after 1-2 days, after 3 days their number increased to 30% and higher.

Color-Coding Method Reveals Enhancement of Stereotypic Locomotion by Phenazepam in Rat Open Field Test.

One of the most important tasks in neuroscience is the search for theoretical foundations for the development of methods for diagnosing and treating neurological pathology, and for assessing the effect of pharmacological drugs on the nervous system. Specific behavioral changes associated with exposure to systemic influences have been invisible to the human eye for a long time. A similar pattern of changes is characteristic of phenazepam, a drug with a wide range of effects on the brain.

Differential Role of Active Compounds in Mitophagy and Related Neurodegenerative Diseases.

Neurodegenerative diseases, such as Alzheimer's disease or Parkinson's disease, significantly reduce the quality of life of patients and eventually result in complete maladjustment. Disruption of the synapses leads to a deterioration in the communication of nerve cells and decreased plasticity, which is associated with a loss of cognitive functions and neurodegeneration. Maintaining proper synaptic activity depends on the qualitative composition of mitochondria, because synaptic processes require sufficient energy supply and fine calcium regulation.

Early Selection of the Amino Acid Alphabet Was Adaptively Shaped by Biophysical Constraints of Foldability.

Whereas modern proteins rely on a quasi-universal repertoire of 20 canonical amino acids (AAs), numerous lines of evidence suggest that ancient proteins relied on a limited alphabet of 10 "early" AAs and that the 10 "late" AAs were products of biosynthetic pathways. However, many nonproteinogenic AAs were also prebiotically available, which begs two fundamental questions: Why do we have the current modern amino acid alphabet and would proteins be able to fold into globular structures as well if different amino acids comprised the genetic code? Here, we experimentally evaluate the solubility and secondary structure propensities of several prebiotically relevant amino acids in the context of synthetic combinatorial 25-mer peptide libraries. The most prebiotically abundant linear aliphatic and basic residues were incorporated along with or in place of other early amino acids to explore these alternative sequence spaces.

Comparison of "Human" and Artificial Intelligence Hand-and-Wrist Skeletal Age Estimation in an Epiphysiodesis Cohort.

Background: We previously demonstrated that the White-Menelaus arithmetic formula combined with skeletal age as estimated with the Greulich and Pyle (GP) atlas was the most accurate method for predicting leg lengths and residual leg-length discrepancy (LLD) at maturity in a cohort of patients treated with epiphysiodesis. We sought to determine if an online artificial intelligence (AI)-based hand-and-wrist skeletal age system provided consistent readings and to evaluate how these readings influenced the prediction of the outcome of epiphysiodesis in this cohort.

Methods: JPEG images of perioperative hand radiographs for 76 subjects were independently submitted by 2 authors to an AI skeletal age web site (http://physis.

Regulation of Human Platelet Adhesion with Ascorbic Acid.

Morphofunctional characteristics of human platelets in the presence of 0.1-5 mM ascorbic acid were studied. The platelet ability to form lamellae and the preservation of granules in platelets in suspension and during adhesion were evaluated.

NAD precursors cycle between host tissues and the gut microbiome.

Nicotinamide adenine dinucleotide (NAD) is an essential redox cofactor in mammals and microbes. Here we use isotope tracing to investigate the precursors supporting NAD synthesis in the gut microbiome of mice. We find that dietary NAD precursors are absorbed in the proximal part of the gastrointestinal tract and not available to microbes in the distal gut.

Growth-Stimulating Effect of Platelet Preparations Obtained by Different Methods on Human Fibroblast Culture.

We studied the growth-stimulating effect of platelet-based preparations obtained by different methods on cultured human fibroblasts M-22. Platelet lysates prepared from platelet-rich plasma, platelet-poor plasma, concentrated suspension of platelets washed from plasma, and platelet-rich plasma activated with calcium chloride (ActPRP) were used. The volume of the platelet preparations was 10-500 μl per 10 cells.

Synthesis of Mixed Dinucleotides by Mechanochemistry.

We report the synthesis of vitamin B1, B2, and B3 derived nucleotides and dinucleotides generated either through mechanochemical or solution phase chemistry. Under the explored conditions, adenosine and thiamine proved to be particularly amenable to milling conditions. Following optimization of the chemistry related to the formation pyrophosphate bonds, mixed dinucleotides of adenine and thiamine (vitamin B1), riboflavin (vitamin B2), nicotinamide riboside and 3-carboxamide 4-pyridone riboside (both vitamin B3 derivatives) were generated in good yields.

In Vitro Evolution Reveals Noncationic Protein-RNA Interaction Mediated by Metal Ions.

RNA-peptide/protein interactions have been of utmost importance to life since its earliest forms, reaching even before the last universal common ancestor (LUCA). However, the ancient molecular mechanisms behind this key biological interaction remain enigmatic because extant RNA-protein interactions rely heavily on positively charged and aromatic amino acids that were absent (or heavily under-represented) in the early pre-LUCA evolutionary period. Here, an RNA-binding variant of the ribosomal uL11 C-terminal domain was selected from an approximately 1010 library of partially randomized sequences, all composed of ten prebiotically plausible canonical amino acids.

Peptides before and during the nucleotide world: an origins story emphasizing cooperation between proteins and nucleic acids.

Recent developments in Origins of Life research have focused on substantiating the narrative of an abiotic emergence of nucleic acids from organic molecules of low molecular weight, a paradigm that typically sidelines the roles of peptides. Nevertheless, the simple synthesis of amino acids, the facile nature of their activation and condensation, their ability to recognize metals and cofactors and their remarkable capacity to self-assemble make peptides (and their analogues) favourable candidates for one of the earliest functional polymers. In this mini-review, we explore the ramifications of this hypothesis.