Recommendations on Imaging in the Context of Alzheimer's Disease-Modifying Therapies from the CCNA Imaging Workgroup.

Background: Disease-modifying therapies (DMTs) for Alzheimer's disease (AD) are emerging following successful clinical trials of therapies targeting amyloid beta (Aβ) protofibrils or plaques. Determining patient eligibility and monitoring treatment efficacy and adverse events, such as Aβ-related imaging abnormalities, necessitates imaging with MRI and PET. The Canadian Consortium on Neurodegeneration in Aging (CCNA) Imaging Workgroup aimed to synthesize evidence and provide recommendations on implementing imaging protocols for AD DMTs in Canada.

Development of ectodermal and endodermal taste buds.

The sense of taste is mediated primarily by taste buds on the tongue. These multicellular sensory organs are induced, patterned and become innervated during embryogenesis such that a functional taste system is present at birth when animals begin to feed. While taste buds have been considered ectodermal appendages, this is only partly accurate as only fungiform taste buds in the anterior tongue arise from the ectoderm.

A large structural variant collection in Holstein cattle and associated database for variant discovery, characterization, and application.

Background: Structural variants (SVs) such as deletions, duplications, and insertions are known to contribute to phenotypic variation but remain challenging to identify and genotype. A more complete, accessible, and assessable collection of SVs will assist efforts to study SV function in cattle and to incorporate SV genotyping into animal evaluation.

Results: In this work we produced a large and deeply characterized collection of SVs in Holstein cattle using two popular SV callers (Manta and Smoove) and publicly available Illumina whole-genome sequence (WGS) read sets from 310 samples (290 male, 20 female, mean 20X coverage).

FASN negatively regulates p65 expression by reducing its stability via Thr phosphorylation and isomerization by Pin1.

FASN, the sole cytosolic enzyme responsible for de novo palmitate synthesis in mammalian cells, has been associated with poor prognosis in cancer and shown to cause drug and radiation resistance by upregulating DNA damage repair via suppression of p65 expression. Targeting FASN by repurposing proton pump inhibitors has generated impressive outcomes in triple-negative breast cancer patients. While p65 regulation of DNA damage repair was thought to be due to its suppression of poly(ADP-ribose) polymerase 1 gene transcription, the mechanism of FASN regulation of p65 expression was unknown.

Enhancement of protein immobilization on polydimethylsiloxane using a synergistic combination of polydopamine and micropattern surface modification.

Understanding protein interactions at biointerfaces is critical for the improved design of biomaterials and medical devices. Polydimethylsiloxane (PDMS) is used for numerous device applications, and surface modifications can enhance protein immobilization and the response to cells. A multifunctional approach combining topographical and biochemical modifications was applied to PDMS by fabricating 10-20 µm scale patterns onto PDMS surfaces and by coating with polydopamine (PDA).

Nonaqueous magnetization following adiabatic and selective pulses in brain: T1 and cross-relaxation dynamics.

Inversion pulses are commonly employed in MRI for -weighted contrast and relaxation measurements. In the brain, it is often assumed that adiabatic pulses saturate the nonaqueous magnetization. We investigated this assumption using solid-state NMR to monitor the nonaqueous signal directly following adiabatic inversion and compared this with signals following hard and soft inversion pulses.

Evaluation of aerosols in a simulated orthodontic debanding procedure.

Dental practitioners may be at risk for exposure to severe acute respiratory syndrome corona virus 2 when performing aerosol generating procedures. Though recent evidence suggests that coronavirus may be transmitted through aerosol generating procedures, it is unknown whether common procedures performed in dental clinics generate aerosol. The aim of this study was to simultaneously quantify airborne concentrations of the bacteriophage MS2 near the oral cavity of a dental mannequin and behind personal protective equipment (i.

High Sox2 expression predicts taste lineage competency of lingual progenitors in vitro.

Taste buds on the tongue contain taste receptor cells (TRCs) that detect sweet, sour, salty, umami and bitter stimuli. Like non-taste lingual epithelium, TRCs are renewed from basal keratinocytes, many of which express the transcription factor SOX2. Genetic lineage tracing has shown that SOX2+ lingual progenitors give rise to both taste and non-taste lingual epithelium in the posterior circumvallate taste papilla (CVP) of mice.

Endosomal vesicle fusion machinery is involved with the contractile vacuole in Dictyostelium discoideum.

Contractile vacuoles (CVs), enigmatic osmoregulatory organelles, share common characteristics, such as a requirement for RAB11 and high levels of V-ATPase. These commonalities suggest a conserved evolutionary origin for the CVs with implications for understanding of the last common ancestor of eukaryotes and eukaryotic diversification more broadly. A taxonomically broader sampling of CV-associated machinery is required to address this question further.

Comparative Genomics for Evolutionary Cell Biology Using AMOEBAE: Understanding the Golgi and Beyond.

Taking an evolutionary approach to cell biology can yield important new information about how the cell works and how it evolved to do so. This is true of the Golgi apparatus, as it is of all systems within the cell. Comparative genomics is one of the crucial first steps to this line of research, but comes with technical challenges that must be overcome for rigor and robustness.

The Cytidine Deaminase APOBEC3G Contributes to Cancer Mutagenesis and Clonal Evolution in Bladder Cancer.

Unlabelled: Mutagenic processes leave distinct signatures in cancer genomes. The mutational signatures attributed to APOBEC3 cytidine deaminases are pervasive in human cancers. However, data linking individual APOBEC3 proteins to cancer mutagenesis in vivo are limited.

Polydopamine modification of polydimethylsiloxane for multifunctional biomaterials: Immobilization and stability of albumin and fetuin-A on modified surfaces.

The surface of polydimethylsiloxane (PDMS) can be modified to immobilize proteins; however, most existing approaches are limited to complex reactions and achieving multifunctional modifications is challenging. This work applies a simple technique to modify PDMS using polydopamine (PDA) and investigates immobilization of multiple proteins. The surfaces were characterized in detail and stability was assessed, demonstrating that in a buffer solution, PDA modification was maintained without an effect on surface properties.

Therapeutic Activity of the Lansoprazole Metabolite 5-Hydroxy Lansoprazole Sulfide in Triple-Negative Breast Cancer by Inhibiting the Enoyl Reductase of Fatty Acid Synthase.

Fatty acid synthase (FASN), a sole cytosolic enzyme responsible for de-novo lipid synthesis, is overexpressed in cancer but not in normal non-lipogenic tissues. FASN has been targeted, albeit no such inhibitor has been approved. Proton pump inhibitors (PPIs), approved for digestive disorders, were found to inhibit FASN with anticancer activities in attempting to repurpose Food and Drug Administration-approved drugs.

Predictive Value of Acute Neuroplastic Response to rTMS in Treatment Outcome in Depression: A Concurrent TMS-fMRI Trial.

Objective: The study objective was to investigate the predictive value of functional connectivity changes induced by acute repetitive transcranial magnetic stimulation (rTMS) for clinical response in treatment-resistant depression.

Methods: Cross-sectional changes in functional connectivity induced by a single concurrent rTMS-fMRI session were assessed in 38 outpatients with treatment-resistant depression (26 of them female; mean age, 41.87 years) who subsequently underwent a 4-week course of rTMS.

Laser-stimulated fluorescence reveals unseen details in fossils from the Upper Jurassic Solnhofen Limestones.

Laser-stimulated fluorescence (LSF) has seen increased use in palaeontological investigations in recent years. The method uses the high flux of laser light of visible wavelengths to reveal details sometimes missed by traditional long-wave ultraviolet (UV) methods using a lamp. In this study, we compare the results of LSF with UV-A-generated fluorescence on a range of fossils from the Upper Jurassic Solnhofen Limestone Konservat-Lagerstätte of Bavaria, Germany.

The sense of taste: Development, regeneration, and dysfunction.

Gustation or the sense of taste is a primary sense, which functions as a gatekeeper for substances that enter the body. Animals, including humans, ingest foods that contain appetitive taste stimuli, including those that have sweet, moderately salty and umami (glutamate) components, and tend to avoid bitter-tasting items, as many bitter compounds are toxic. Taste is mediated by clusters of heterogeneous taste receptors cells (TRCs) organized as taste buds on the tongue, and these convey taste information from the oral cavity to higher order brain centers via the gustatory sensory neurons of the seventh and ninth cranial ganglia.

Pterosaurs evolved a muscular wing-body junction providing multifaceted flight performance benefits: Advanced aerodynamic smoothing, sophisticated wing root control, and wing force generation.

Pterosaurs were the first vertebrate flyers and lived for over 160 million years. However, aspects of their flight anatomy and flight performance remain unclear. Using laser-stimulated fluorescence, we observed direct soft tissue evidence of a wing root fairing in a pterosaur, a feature that smooths out the wing-body junction, reducing associated drag, as in modern aircraft and flying animals.

Racial and ethnic representation in primary research contributing to pelvic organ prolapse treatment guidelines.

Introduction And Hypothesis: To evaluate whether the studies contributing to the national treatment guidelines on pelvic organ prolapse adequately represent the racial and/or ethnic makeup of the American population.

Methods: This analysis examines the racial and ethnic makeup of all primary study cohorts contributing to the American College of Obstetricians and Gynecologists/American Urogynecologic Society Practice Bulletin No. 214 on pelvic organ prolapse.