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OBJECTIVE: The purpose of this article is to provide an overview of the growth of chiropractic education globally and a chronological list of current training programs. Another purpose is to provide exemplars of enduring programs and offer suggestions for how chiropractic practitioners may celebrate education on Chiropractic Day, which is September 18. DISCUSSION: Chiropractic education has transformed considerably over the past 125 years, and there are now 52 programs globally. We consider the 5 longest-existing chiropractic programs and propose hypotheses for what may have contributed to their durability. In addition, we offer ideas and opportunities for how chiropractic practitioners may focus on chiropractic education when celebrating the founding of the profession. CONCLUSION: Since its inception, chiropractic education has expanded around the world and continues to develop. Recognized accreditation agencies and testing organizations are ensuring that standards of education are established and maintained internationally. With innovation, international collaboration, and a commitment to continuous professional development, the future of chiropractic education is bright. We urge chiropractic practitioners from all over the world to celebrate these accomplishments on Chiropractic Day.

Theories that explain the power of legislative leaders have been developed for the U.S. Congress and lower chambers of state legislatures, but they have not been tested for state senates, even though senate leaders can be quite influential. Following Mooney (2013a), I develop a new numerical index score measuring the formal power of the top chamber-elected leader of each state senate from 1995 through 2010. I then use the data to test various hypotheses explaining variation in the power of legislative leaders. The results uncover partial evidence for conditional party government theory, but only for senates that elect their own president. When the lieutenant governor serves as senate president, senators do not perceive their top chamber-elected leader as an officer able to best carry out their ideological, electoral, or policy objectives. This underscores crucial differences between senate chambers that elect their own presidents and those that do not.

The oxygen-evolving complex (OEC) located in photosystem II (PSII) of green plants is one of the best-known examples of a manganese-containing enzyme in nature, but it is also used in a range of other biological processes. OEC models incorporate two multi-dentate nitrogen-containing ligands coordinated to a bis-μ-oxo Mn(III,IV) core. Open-chain ligands were the initial scaffold used for biomimetic studies, but their macrocyclic counterparts have proven to be particularly appropriate due to their enhanced stability. Dimer and monomer complexes with such ligands have shown to be useful for a wide range of applications, which will be reviewed herein. The purpose of this review is to state with some clarity the different spectroscopic and structural characteristics of the Mn complexes formed with tetraaza macrocyclic ligands both in solution and solid-state that allow the reader to successfully identified the species involved when dealing with similar complexes of Mn.

The gut plays a critical role in maintaining human health by facilitating the absorption of nutrients, regulating metabolism, and interacting with the immune system and gut microbiota. The co-culture of two human colorectal cancer cell lines, Caco-2 and HT29, on Transwell is commonly used as anin vitrogut mimic in studies of intestine absorption pharmacokinetic, gut mechanics, and gut-microbes interplay given the similar morphology, expression of transporters and enzymes, and barrier function. However, to sufficiently evaluate the translatability of insights from such a system to human physiological contexts, a detailed survey of cell type heterogeneity in the system and a holistic comparison with human physiology needs to be conducted rather than by the presence of a few well-studied proteins. Single-cell RNA sequencing provides high-resolution expression profiles of cells in the co-culture, enabling the heterogeneity to be characterized and the similarity to human epithelial cells to be evaluated. 16019 genes transcriptional profile in 13784 cells were acquired and compared to human epithelial cells (GSE185224). We identified the intestinal stem cell, transit amplifying, enterocyte, goblet cell, and enteroendocrine-like cells together with differentiating HT29 cells in the system based on the expression of canonical markers in healthy adult human epithelial cells. The epithelium-like co-culture was fetal intestine-like, with less variety of gene expression compared to the human gut. Transporters for major types of substance (lipid, amino acid, ion, water, etc.) were found transcribed in the majority of the enterocytes-like cells in the system. However, some of the well-studied transporters were absent. Toll-like receptors were not highly expressed in the sample, yet the treatment of LPS still caused a mild change in TEER and gene expression, possibly by the interaction with CD14. Overall, the Caco-2/HT29 co-culture is a cost-effective epithelium model for drug permeability testing or mechanical simulation, but its discrepancy with the real epithelium phenotype-wise is not negligible. As a result, its response to biological factors might not provide transferrable knowledge to the study of human gut physiology, especially the innate immune aspect.

SUMMARY Air-to-ground coupled seismic arrivals, resulting from infrasound interacting with the ground surface, can be identified on seismometers co-located with microbarometers. Dense networks of co-located sensors provide detailed spatial information about the infrasonic wavefield, allowing investigation of infrasonic propagation and an assessment of the variability in air-to-ground coupling mechanisms. Signals generated by an explosion at Camp Minden, Louisiana, United States, on 2012 October 16 were recorded across the eastern United States on the USArray Transportable Array. 233 infrasound signals were identified at distances of up to 1566 km from the source, with 105 of these sites, at distances of up to 1147 km from the source, recording above-noise air-to-ground coupled seismic arrivals in the 2–4 Hz passband (chosen to maximise seismic arrival signal-to-noise ratios). The spatially dense infrasound recordings allowed a unique investigation of the azimuthal variation in infrasound amplitudes, showing that stratospheric arrival amplitudes increased by a factor greater than 4 between the edge and centre of the stratospheric propagation duct. Air-to-ground coupling coefficients, calculated as the ratios of temporally coincident peak-to-trough seismic and infrasound time-domain amplitudes, span over two orders of magnitude ([9.0 × 10−8, 5.0 × 10−5] ms−1 Pa−1). Sites exhibiting high coupling coefficients are predominantly located on alluvial sediments that support the generation of air-to-ground coupled Rayleigh waves, resulting in poor coherence between the seismic and infrasonic waveforms. In contrast, sites exhibiting low coupling coefficients are predominantly located on chemically weathered bedrock and only support direct coupling, leading to high coherence between air-to-ground coupled seismic and infrasonic recordings. The Camp Minden explosion observations, and a consideration of expected seismic noise and air-to-ground coupled arrival amplitudes, suggest that co-located pairs of seismometers and microbarometers are likely to record signals from small (tens of tons) explosions at distances of over 1000 km under favourable propagation conditions. Co-located deployments may therefore provide a cost-effective method for augmenting current state-of-the-art infrasound array networks, by providing a higher spatial density of recordings; this may assist in correctly associating recorded signals with, and estimating the location of, source events.

The process of proplatelet formation (PPF) requires coordinated interaction between megakaryocytes (MKs) and the extracellular matrix (ECM), followed by a dynamic reorganization of the actin and microtubule cytoskeleton. Localized fluxes of intracellular calcium ions (Ca2+) facilitate MK-ECM interaction and PPF. Glutamate-gated N-methyl-D-aspartate receptor (NMDAR) is highly permeable to Ca2+. NMDAR antagonists inhibit MK maturation ex vivo; however, there are no in vivo data. Using the Cre-loxP system, we generated a platelet lineage–specific knockout mouse model of reduced NMDAR function in MKs and platelets (Pf4-Grin1−/− mice). Effects of NMDAR deletion were examined using well-established assays of platelet function and production in vivo and ex vivo. We found that Pf4-Grin1−/− mice had defects in megakaryopoiesis, thrombopoiesis, and platelet function, which manifested as reduced platelet counts, lower rates of platelet production in the immune model of thrombocytopenia, and prolonged tail bleeding time. Platelet activation was impaired to a range of agonists associated with reduced Ca2+ responses, including metabotropic like, and defective platelet spreading. MKs showed reduced colony and proplatelet formation. Impaired reorganization of intracellular F-actin and α-tubulin was identified as the main cause of reduced platelet function and production. Pf4-Grin1−/− MKs also had lower levels of transcripts encoding crucial ECM elements and enzymes, suggesting NMDAR signaling is involved in ECM remodeling. In summary, we provide the first genetic evidence that NMDAR plays an active role in platelet function and production. NMDAR regulates PPF through a mechanism that involves MK-ECM interaction and cytoskeletal reorganization. Our results suggest that NMDAR helps guide PPF in vivo.

On 7 July 2011, a series of accidental explosions occurred in the town of Abadan, Turkmenistan. The explosions were observed at local distances (11 and 23 km) at the International Monitoring System (IMS) seismic array, GEYT, and at the Central Asian Cross-border Network (CAREMON), seismic station, ASHT. A total of 30 individual seismic events could be identified. IMS infrasound arrays also observed these explosions at longer ranges, for example, from 1374 km (I31KZ, Kazakhstan) to 4307 km (I48TN, Tunisia). These local and long-range observations allow us to compare yields estimated from the seismic data, 0.05–45 tonnes (trinitrotoluene [TNT] equivalent; using P-wave and Rg amplitude relationships) to those estimated from the infrasound data, 4–90 tonnes (using the dominant period). Given the long propagation distances to the closest IMS infrasound arrays, the signal durations are long and individual events in the series cannot be identified in the infrasound signals. Comparison of the seismic and infrasonic yield estimates suggests that the infrasonic dominant periods are likely associated with the largest explosions in the series. In addition to the seismic arrivals observed locally, air-to-ground coupled waves exhibiting downward first motions consistent with an initial positive blast overpressure are also observed at both GEYT and ASHT. The peak-to-peak amplitude of the air-to-ground coupled waves increases with increasing yield, whereas the period of these signals is yield independent. These amplitude observations suggest that air-to-ground coupled arrivals could be better exploited within event analyses and provide a further constraint upon yield. Fully exploiting these events of opportunity, that have multiphenomenology observations, will help to further improve our understanding of how energy from near-surface explosions partitions into the ground and atmosphere and, therefore, improve our understanding of future events.

Background The TREM2 R47H variant is one of the strongest genetic risk factors for late-onset Alzheimer’s Disease (AD). Unfortunately, many current Trem2R47H mouse models are associated with cryptic mRNA splicing of the mutant allele that produces a confounding reduction in protein product. To overcome this issue, we developed the Trem2R47H NSS (Normal Splice Site) mouse model in which the Trem2 allele is expressed at a similar level to the wild-type Trem2 allele without evidence of cryptic splicing products. Methods Trem2R47H NSS mice were treated with the demyelinating agent cuprizone, or crossed with the 5xFAD mouse model of amyloidosis, to explore the impact of the TREM2 R47H variant on inflammatory responses to demyelination, plaque development, and the brain’s response to plaques. Results Trem2R47H NSS mice display an appropriate inflammatory response to cuprizone challenge, and do not recapitulate the null allele in terms of impeded inflammatory responses to demyelination. Utilizing the 5xFAD mouse model, we report age- and disease-dependent changes in Trem2R47H NSS mice in response to development of AD-like pathology. At an early (4-month-old) disease stage, hemizygous 5xFAD/homozygous Trem2R47H NSS (5xFAD/Trem2R47H NSS) mice have reduced size and number of microglia that display impaired interaction with plaques compared to microglia in age-matched 5xFAD hemizygous controls. This is associated with a suppressed inflammatory response but increased dystrophic neurites and axonal damage as measured by plasma neurofilament light chain (NfL) level. Homozygosity for Trem2R47H NSS suppressed LTP deficits and loss of presynaptic puncta caused by the 5xFAD transgene array in 4-month-old mice. At a more advanced (12-month-old) disease stage 5xFAD/Trem2R47H NSS mice no longer display impaired plaque-microglia interaction or suppressed inflammatory gene expression, although NfL levels remain elevated, and a unique interferon-related gene expression signature is seen. Twelve-month old Trem2R47H NSS mice also display LTP deficits and postsynaptic loss. Conclusions The Trem2R47H NSS mouse is a valuable model that can be used to investigate age-dependent effects of the AD-risk R47H mutation on TREM2 and microglial function including its effects on plaque development, microglial-plaque interaction, production of a unique interferon signature and associated tissue damage.

Elision is the least well investigated of the processes collectively known as ‘linking phenomena’ in French phonology. Data from a corpus of late 20th-century interviews show that 39% of new CV onsets created by forward resyllabification are due to elision (considerably more than those due to liaison or enchaînement of fixed consonants) and a further 9% to sites created by intrusive fillers (notably euh and hein), a source hitherto overlooked. Yet elision is not categorical. We document instances of minor but stable variability alongside tokens of non-elision of que and its compound forms. Non-elision is characteristic of fluent, relaxed speech and seems to be spreading. We argue that it is not motivated by phonology but by register and discourse factors in continuous speech.

A question relevant to nicotine addiction is how nicotine and other nicotinic receptor membrane-permeant ligands, such as the anti-smoking drug varenicline (Chantix), distribute in brain. Ligands, like varenicline, with high pKaand high affinity for α4β2-type nicotinic receptors (α4β2Rs) are trapped in intracellular acidic vesicles containing α4β2Rsin vitro. Nicotine, with lower pKaand α4β2R affinity, is not trapped. Here, we extend our results by imaging nicotinic PET ligandsin vivoin male and female mouse brain and identifying the trapping brain organellein vitroas Golgi satellites (GSats). Two PET18F-labeled imaging ligands were chosen: [18F]2-FA85380 (2-FA) with varenicline-like pKaand affinity and [18F]Nifene with nicotine-like pKaand affinity. [18F]2-FA PET-imaging kinetics were very slow consistent with 2-FA trapping in α4β2R-containing GSats. In contrast, [18F]Nifene kinetics were rapid, consistent with its binding to α4β2Rs but no trapping. Specific [18F]2-FA and [18F]Nifene signals were eliminated in β2 subunit knock-out (KO) mice or by acute nicotine (AN) injections demonstrating binding to sites on β2-containing receptors. Chloroquine (CQ), which dissipates GSat pH gradients, reduced [18F]2-FA distributions while having little effect on [18F]Nifene distributionsin vivoconsistent with only [18F]2-FA trapping in GSats. These results are further supported byin vitrofindings where dissipation of GSat pH gradients blocks 2-FA trapping in GSats without affecting Nifene. By combiningin vitroandin vivoimaging, we mapped both the brain-wide and subcellular distributions of weak-base nicotinic receptor ligands. We conclude that ligands, such as varenicline, are trapped in neurons in α4β2R-containing GSats, which results in very slow release long after nicotine is gone after smoking.SIGNIFICANCE STATEMENTMechanisms of nicotine addiction remain poorly understood. An earlier study usingin vitromethods found that the anti-smoking nicotinic ligand, varenicline (Chantix) was trapped in α4β2R-containing acidic vesicles. Using a fluorescent-labeled high-affinity nicotinic ligand, this study provided evidence that these intracellular acidic vesicles were α4β2R-containing Golgi satellites (GSats).In vivoPET imaging with F-18-labeled nicotinic ligands provided additional evidence that differences in PET ligand trapping in acidic vesicles were the cause of differences in PET ligand kinetics and subcellular distributions. These findings combiningin vitroandin vivoimaging revealed new mechanistic insights into the kinetics of weak base PET imaging ligands and the subcellular mechanisms underlying nicotine addiction.

A key challenge in developing diagnosis and treatments for Alzheimer's disease (AD) is to detect abnormal network activity at as early a stage as possible. To date, behavioral and neurophysiological investigations in AD model mice have yet to conduct a longitudinal assessment of cellular pathology, memory deficits, and neurophysiological correlates of neuronal activity. We therefore examined the temporal relationships between pathology, neuronal activities and spatial representation of environments, as well as object location memory deficits across multiple stages of development in the 5xFAD mice model and compared these results to those observed in wild-type mice. We performed longitudinal in vivo calcium imaging with miniscope on hippocampal CA1 neurons in behaving mice. We find that 5xFAD mice show amyloid plaque accumulation, depressed neuronal calcium activity during immobile states, and degenerate and unreliable hippocampal neuron spatial tuning to environmental location at early stages by 4months of age while their object location memory (OLM) is comparable to WT mice. By 8months of age, 5xFAD mice show deficits of OLM, which are accompanied by progressive degradation of spatial encoding and, eventually, impaired CA1 neural tuning to object-location pairings. Furthermore, depressed neuronal activity and unreliable spatial encoding at early stage are correlated with impaired performance in OLM at 8-month-old. Our results indicate the close connection between impaired hippocampal tuning to object-location and the presence of OLM deficits. The results also highlight that depressed baseline firing rates in hippocampal neurons during immobile states and unreliable spatial representation precede object memory deficits and predict memory deficits at older age, suggesting potential early opportunities for AD detecting.

Item does not contain fulltext BACKGROUND AND PURPOSE: Superagers are defined as older adults with episodic memory performance similar or superior to that in middle-aged adults. This study aimed to investigate the key differences in discriminative networks and their main nodes between superagers and cognitively average elderly controls. In addition, we sought to explore differences in sensitivity in detecting these functional activities across the networks at 3T and 7T MR imaging fields. MATERIALS AND METHODS: Fifty-five subjects 80 years of age or older were screened using a detailed neuropsychological protocol, and 31 participants, comprising 14 superagers and 17 cognitively average elderly controls, were included for analysis. Participants underwent resting-state-fMRI at 3T and 7T MR imaging. A prediction classification algorithm using a penalized regression model on the measurements of the network was used to calculate the probabilities of a healthy older adult being a superager. Additionally, ORs quantified the influence of each node across preselected networks. RESULTS: The key networks that differentiated superagers and elderly controls were the default mode, salience, and language networks. The most discriminative nodes (ORs > 1) in superagers encompassed areas in the precuneus posterior cingulate cortex, prefrontal cortex, temporoparietal junction, temporal pole, extrastriate superior cortex, and insula. The prediction classification model for being a superager showed better performance using the 7T compared with 3T resting-state-fMRI data set. CONCLUSIONS: Our findings suggest that the functional connectivity in the default mode, salience, and language networks can provide potential imaging biomarkers for predicting superagers. The 7T field holds promise for the most appropriate study setting to accurately detect the functional connectivity patterns in superagers. 01 april 2023