Assessing Artificial Intelligence (AI) Implementation for Assisting Gene Linking (at the National Library of Medicine).

Objectives: The National Library of Medicine (NLM) currently indexes close to a million articles each year pertaining to more than 5300 medicine and life sciences journals. Of these, a significant number of articles contain critical information about the structure, genetics, and function of genes and proteins in normal and disease states. These articles are identified by the NLM curators, and a manual link is created between these articles and the corresponding gene records at the NCBI Gene database.

NCBI RefSeq: reference sequence standards through 25 years of curation and annotation.

Reference sequences and annotations serve as the foundation for many lines of research today, from organism and sequence identification to providing a core description of the genes, transcripts and proteins found in an organism's genome. Interpretation of data including transcriptomics, proteomics, sequence variation and comparative analyses based on reference gene annotations informs our understanding of gene function and possible disease mechanisms, leading to new biomedical discoveries. The Reference Sequence (RefSeq) resource created at the National Center for Biotechnology Information (NCBI) leverages both automatic processes and expert curation to create a robust set of reference sequences of genomic, transcript and protein data spanning the tree of life.

The effects of buprenorphine and morphine during pregnancy: Impact of exposure length on maternal brain, behavior, and offspring neurodevelopment.

The escalating incidence of opioid-related issues among pregnant women in the United States underscores the critical necessity to understand the effects of opioid use and Medication for Opioid Use Disorders (MOUDs) during pregnancy. This research employed a translational rodent model to examine the impact of gestational exposure to buprenorphine (BUP) or morphine on maternal behaviors and offspring well-being. Female rats received BUP or morphine before conception, representing established use, with exposure continuing until postnatal day 2 or discontinued on gestational day 19 to mimic treatment cessation before birth.

Volumetric dried blood spots for determination of phosphatidylethanol: Validation of a liquid chromatography tandem masspectrometry method and clinical application.

Phosphatidylethanol (PEth) measurement in whole blood samples is established as a specific alcohol biomarker with clinical and forensic applications. Establishment of dried blood spots (DBSs) as a specimen for PEth determination offers several advantages and was the focus of this work. A liquid chromatography tandem mass spectrometry method using a 96-well format for sample preparation was developed and validated.

Product labeling accuracy and contamination analysis of commercially available cannabidiol product samples.

Commercially available cannabidiol (CBD) products are increasingly being used for medicinal purposes, including for the treatment of various neurological conditions, but there are growing concerns around adherence to quality control measures that protect consumers. This study was conducted to assess the purity and label accuracy of commercially available CBD products. Commercially available CBD products were chosen from the open stream of commerce in the United States based on formulations as a tincture, gummy, vape, or topical product.

Big dynorphin is a neuroprotector scaffold against amyloid β-peptide aggregation and cell toxicity.

Amyloid β-peptide (Aβ) misfolding into β-sheet structures triggers neurotoxicity inducing Alzheimer's disease (AD). Molecules able to reduce or to impair Aβ aggregation are highly relevant as possible AD treatments since they should protect against Aβ neurotoxicity. We have studied the effects of the interaction of dynorphins, a family of opioid neuropeptides, with Aβ the most abundant species of Aβ.

Heavy metal and phthalate contamination and labeling integrity in a large sample of US commercially available cannabidiol (CBD) products.

Background: The demand and availability of commercially available cannabidiol (CBD) products has grown substantially, which is of particular interest among medically vulnerable people. Because the cannabis plant is recognized as a bioaccumulator, which is highly effective at absorbing and retaining contaminants (e.g.

A joint NCBI and EMBL-EBI transcript set for clinical genomics and research.

Comprehensive genome annotation is essential to understand the impact of clinically relevant variants. However, the absence of a standard for clinical reporting and browser display complicates the process of consistent interpretation and reporting. To address these challenges, Ensembl/GENCODE and RefSeq launched a joint initiative, the Matched Annotation from NCBI and EMBL-EBI (MANE) collaboration, to converge on human gene and transcript annotation and to jointly define a high-value set of transcripts and corresponding proteins.

RefSeq Functional Elements as experimentally assayed nongenic reference standards and functional interactions in human and mouse.

Eukaryotic genomes contain many nongenic elements that function in gene regulation, chromosome organization, recombination, repair, or replication, and mutation of those elements can affect genome function and cause disease. Although numerous epigenomic studies provide high coverage of gene regulatory regions, those data are not usually exposed in traditional genome annotation and can be difficult to access and interpret without field-specific expertise. The National Center for Biotechnology Information (NCBI) therefore provides RefSeq Functional Elements (RefSeqFEs), which represent experimentally validated human and mouse nongenic elements derived from the literature.

Opioid use during pregnancy can impair maternal behavior and the Maternal Brain Network: A literature review.

Opioid Use Disorder (OUD) is a global epidemic also affecting women of reproductive age. A standard form of pharmacological treatment for OUD is Opioid Maintenance Therapy (OMT) and buprenorphine has emerged as the preferred treatment for pregnant women with OUD relative to methadone. However, the consequences of BUP exposure on the developing Maternal Brain Network and mother-infant dyad are not well understood.

A nutty idea: Exploring a novel method using a hazelnut cocoa spread to temporarily increase maternal care behavior within a rat litter.

Maternal care plays a crucial role for infant development. In humans, skin-to-skin care is often used for preterm infants to reduce acute stress and improve long-term developmental outcome. Here we propose a new translational approach to study the effects of acute increases in maternal care on offspring development in rodents.

ATP Impedes the Inhibitory Effect of Hsp90 on Aβ Fibrillation.

Heat shock protein 90 (Hsp90) is a molecular chaperone that assists protein folding in an Adenosine triphosphate (ATP)-dependent way. Hsp90 has been reported to interact with Alzheimeŕs disease associated amyloid-β (Aβ) peptides and to suppress toxic oligomer- and fibril formation. However, the mechanism remains largely unclear.

Metal ion coordination delays amyloid-β peptide self-assembly by forming an aggregation-inert complex.

A detailed understanding of the molecular pathways for amyloid-β (Aβ) peptide aggregation from monomers into amyloid fibrils, a hallmark of Alzheimer's disease, is crucial for the development of diagnostic and therapeutic strategies. We investigate the molecular details of peptide fibrillization by perturbing this process through addition of differently charged metal ions. Here, we used a monovalent probe, the silver ion, that, similarly to divalent metal ions, binds to monomeric Aβ peptide and efficiently modulates Aβ fibrillization.

Studies on citrullinated LL-37: detection in human airways, antibacterial effects and biophysical properties.

Arginine residues of the antimicrobial peptide LL-37 can be citrullinated by peptidyl arginine deiminases, which reduce the positive charge of the peptide. Notably, citrullinated LL-37 has not yet been detected in human samples. In addition, functional and biophysical properties of citrullinated LL-37 are not fully explored.

Mercury and Alzheimer's Disease: Hg(II) Ions Display Specific Binding to the Amyloid-β Peptide and Hinder Its Fibrillization.

Brains and blood of Alzheimer's disease (AD) patients have shown elevated mercury concentrations, but potential involvement of mercury exposure in AD pathogenesis has not been studied at the molecular level. The pathological hallmark of AD brains is deposition of amyloid plaques, consisting mainly of amyloid-β (Aβ) peptides aggregated into amyloid fibrils. Aβ peptide fibrillization is known to be modulated by metal ions such as Cu(II) and Zn(II).

Gestational buprenorphine exposure: Effects on pregnancy, development, neonatal opioid withdrawal syndrome, and behavior in a translational rodent model.

Background: The opioid crisis has led to an increased number of pregnant opioid-dependent women receiving opioid-maintenance therapy (e.g. buprenorphine, BUP), but little is known about the consequences of gestational BUP exposure on pregnancy outcomes, maternal care, or offspring development.

Metal binding to the amyloid-β peptides in the presence of biomembranes: potential mechanisms of cell toxicity.

The amyloid-β (Aβ) peptides are key molecules in Alzheimer's disease (AD) pathology. They interact with cellular membranes, and can bind metal ions outside the membrane. Certain oligomeric Aβ aggregates are known to induce membrane perturbations and the structure of these oligomers-and their membrane-perturbing effects-can be modulated by metal ion binding.

Pro-Inflammatory S100A9 Protein Aggregation Promoted by NCAM1 Peptide Constructs.

Amyloid cascade and neuroinflammation are hallmarks of neurodegenerative diseases, and pro-inflammatory S100A9 protein is central to both of them. Here, we have shown that NCAM1 peptide constructs carrying polycationic sequences derived from Aβ peptide (KKLVFF) and PrP protein (KKRPKP) significantly promote the S100A9 amyloid self-assembly in a concentration-dependent manner by making transient interactions with individual S100A9 molecules, perturbing its native structure and acting as catalysts. Since the individual molecule misfolding is a rate-limiting step in S100A9 amyloid aggregation, the effects of the NCAM1 construct on the native S100A9 are so critical for its amyloid self-assembly.

Copper ions induce dityrosine-linked dimers in human but not in murine islet amyloid polypeptide (IAPP/amylin).

Dysregulation and aggregation of the peptide hormone IAPP (islet amyloid polypeptide, a.k.a.

Nondegenerate Parametric Resonance in Large Ensembles of Coupled Micromechanical Cantilevers with Varying Natural Frequencies.

We investigate the collective dynamics and nondegenerate parametric resonance (NPR) of coplanar, interdigitated arrays of microcantilevers distinguished by their cantilevers having linearly expanding lengths and thus varying natural frequencies. Within a certain excitation frequency range, the resonators begin oscillating via NPR across the entire array consisting of 200 single-crystal silicon cantilevers. Tunable coupling generated from fringing electrostatic fields provides a mechanism to vary the scope of the NPR.

Absolute Deflection Measurements in a Micro- and Nano-Electromechanical Fabry-Perot Interferometry System.

Fabry-Perot laser interferometry is a common laboratory technique used to interrogate resonant micro- and nano-electromechanical systems (MEMS/NEMS). This method uses the substrate beneath a vibrating MEMS/NEMS device as a static reference mirror, encoding relative device motion in the reflected laser power. In this work, we present a general approach for calibrating these optical systems based on measurements of large-amplitude motion that exceeds one half of the laser wavelength.

Co-aggregation of pro-inflammatory S100A9 with α-synuclein in Parkinson's disease: ex vivo and in vitro studies.

Background: Chronic neuroinflammation is a hallmark of Parkinson's disease (PD) pathophysiology, associated with increased levels of pro-inflammatory factors in PD brain tissues. The pro-inflammatory mediator and highly amyloidogenic protein S100A9 is involved in the amyloid-neuroinflammatory cascade in Alzheimer's disease. This is the first report on the co-aggregation of α-synuclein (α-syn) and S100A9 both in vitro and ex vivo in PD brain.

The Neuronal Tau Protein Blocks in Vitro Fibrillation of the Amyloid-β (Aβ) Peptide at the Oligomeric Stage.

In Alzheimer's disease, amyloid-β (Aβ) plaques and tau neurofibrillary tangles are the two pathological hallmarks. The co-occurrence and combined reciprocal pathological effects of Aβ and tau protein aggregation have been observed in animal models of the disease. However, the molecular mechanism of their interaction remain unknown.

Amyloid-β Peptide Interactions with Amphiphilic Surfactants: Electrostatic and Hydrophobic Effects.

The amphiphilic nature of the amyloid-β (Aβ) peptide associated with Alzheimer's disease facilitates various interactions with biomolecules such as lipids and proteins, with effects on both structure and toxicity of the peptide. Here, we investigate these peptide-amphiphile interactions by experimental and computational studies of Aβ(1-40) in the presence of surfactants with varying physicochemical properties. Our findings indicate that electrostatic peptide-surfactant interactions are required for coclustering and structure induction in the peptide and that the strength of the interaction depends on the surfactant net charge.

Actuation of higher harmonics in large arrays of micromechanical cantilevers for expanded resonant peak separation.

A large array of elastically coupled micro cantilevers of variable length is studied experimentally and numerically. Full-scale finite element modal analysis is implemented to determine the spectral behavior of the array and to extract a global coupling matrix. A compact reduced order model is used for numerical investigation of the array's dynamic response.