bluuebunny/crossref_metadata_2025_split huggingface dataset:
How does it feel to be on psilocybin? Dose-response relationships of subjective experiences in humans
Authors: Hirschfeld Tim , Schmidt Timo Torsten 
Published: June 2020

AbstractPsilocybin is the active component of magic mushrooms and is well known for its psychoactive properties. Different questionnaires have been developed to systematically quantify altered states of consciousness induced by psychoactive drugs. The aim of this study was to obtain the dose-response relationships of the subjective experiences induced by psilocybin in healthy study participants. For this purpose, we applied a linear meta-regression approach on questionnaire ratings after oral administration of psilocybin in a controlled setting. Data was obtained from The Altered States Database, which contains psychometric data extracted from peer-reviewed articles published in MEDLINE-listed journals that used standardized and validated questionnaires. Our meta-analysis included data of the Altered States of Consciousness Rating Scale, the Mystical Experience Questionnaire (MEQ30), and the Hallucinogen Rating Scale (HRS). We used the Robust Variance Estimation Framework to obtain linear dose-response relationship estimates for each dimension of the given questionnaires. Ratings on most dimensions and subscales of the included questionnaires correlated positively with dose. Since subjective experiences are not only determined by dose, but also by individual differences and environmental factors, our results do not necessarily generalize to recreational use, as our analyses are based on data from controlled laboratory experiments. The paper at hand could serve as a general literature citation for the use of psilocybin in experimental and clinical research, especially for the comparison of expected and observed subjective drug experiences.
Understanding the role of apolipoproteinA-I in atherosclerosis. Post-translational modifications synergize dysfunction?
Authors: Ludovico Ivo Díaz , Gisonno Romina A. , Gonzalez Marina C. , Garda Horacio A. , Ramella Nahuel A. , Tricerri M. Alejandra 
Published: June 2020

AbstractBackgroundThe identification of dysfunctional human apolipoprotein A-I (apoA-I) in atherosclerotic plaques suggests that protein structure and function may be hampered under a chronic pro inflammatory scenario. Moreover, the fact that natural mutants of this protein elicit severe cardiovascular diseases (CVD) strongly indicates that the native folding could shift due to the mutation, yielding a structure more prone to misfold or misfunction. To understand the events that determine the failure of apoA-I structural flexibility to fulfill its protective role, we took advantage of the study of a natural variant with a deletion of the residue lysine 107 (K107del) associated with atherosclerosis.MethodsBiophysical approaches, such as electrophoresis, fluorescence and spectroscopy were used to characterize proteins structure and function, either in the native conformation or under oxidation or intramolecular crosslinking.ResultsK107del structure was more flexible than the protein with the native sequence (Wt) but interactions with artificial membranes were preserved. Instead, structural restrictions by intramolecular crosslinking impaired the Wt and K107del lipid solubilization function. In addition, controlled oxidation decreased the yield of the native dimer conformation for both variants.ConclusionsWe conclude that even though mutations may alter protein structure and spatial arrangement, the highly flexible conformation compensates the mild shift from the native folding. Instead, post translational apoA-I modifications (probably chronic and progressive) are required to raise a protein conformation with significant loss of function and increased aggregation tendency.General SignificanceThe results learnt from this variant strength a close association between amyloidosis and atherosclerosis.Graphical abstractHighlights-Oxidation is clue to induce protein misfolding-Natural mutation does not seem critical as a sole reason to determine pathogenicity-Atherosclerosis and amyloidosis are closely related-Intramolecular crosslinking restrains protein flexibility and function
Combining small-molecule bioconjugation and hydrogen-deuterium exchange mass spectrometry (HDX-MS) to expose allostery: the case of human cytochrome P450 3A4
Authors: Ducharme Julie , Thibodeaux Christopher J. , Auclair Karine 
Published: June 2020

AbstractWe report herein a novel approach to study allostery which combines the use of carefully selected bioconjugates and hydrogen-deuterium exchange mass spectrometry (HDX-MS). The utility of our method is demonstrated using human cytochrome P450 3A4 (CYP3A4). CYP3A4 is arguably the most important drug-metabolizing enzyme, and as such, is involved in numerous drug interactions. Diverse allosteric ligand effects have been reported for this enzyme, yet the structural mechanism of these phenomena remain poorly understood. We have described different CYP3A4-effector bioconjugates, some of which mimic the allosteric effect of positive effectors on CYP3A4, while others show activity enhancement even though the label does not occupy the allosteric pocket (agonistic), or do not show activation while still blocking the allosteric site (antagonistic). These bioonjugates were studied here by HDX-MS, which enabled us to better define the position of the allosteric site, and to identify important regions involved in CYP3A4 activation.
Michigan ZoomIN: validating crowd-sourcing to identify mammals from camera surveys
Authors: Gadsden Gabriel I. , Malhotra Rumaan , Schell Justin , Carey Tiffany , Harris Nyeema C. 
Published: June 2020

ABSTRACTCamera trap studies have become a popular medium to assess many ecological phenomena including population dynamics, patterns of biodiversity, and monitoring of endangered species. In conjunction with the benefit to scientists, camera traps present an unprecedented opportunity to involve the public in scientific research via image classifications. However, this engagement strategy comes with a myriad of complications. Volunteers vary in their familiarity with wildlife, and thus, the accuracy of user-derived classifications may be biased by the commonness or popularity of species and user-experience. From an extensive multi-site camera trap study across Michigan U.S.A, images were compiled and identified through a public science platform calledMichigan ZoomIN. We aggregated responses from 15 independent users per image using multiple consensus methods to assess accuracy by comparing to species identification completed by wildlife experts. We also evaluated how different factors including consensus algorithms, study area, wildlife species, user support, and camera type influenced the accuracy of user-derived classifications. Overall accuracy of user-derived classification was 97%; although, several canid (e.g.,Canis lupus, Vulpes vulpes) and mustelid (e.g.,Neovison vison) species were repeatedly difficult to identify by users and had lower accuracy. When validating user-derived classification, we found that study area, consensus method, and user support best explained accuracy. To continue to overcome stigma associated with data from untrained participants, we demonstrated their value by showing the accuracy from volunteers was comparable to experts when classifying North American mammals. Our hierarchical workflow that integrated multiple consensus methods lead to more image classifications without extensive training and even when the expertise of the volunteer was unknown. Ultimately, adopting such an approach can harness broader participation, expedite future camera trap data synthesis, and improve allocation of resources by scholars to enhance performance of public participants and increase accuracy of user-derived data.
Temporal refuges differ between anthropogenic and natural top down pressures in a subordinate carnivore
Authors: Malhotra Rumaan , Lima Samantha , Harris Nyeema C. 
Published: June 2020

ABSTRACTApex predators structure communities through consumptive and non-consumptive pathways. In the carnivore guild, this can result in a within-guild cascade through the suppression of mesocarnivores. As the top-down influences of apex predators wane due to human-driven declines, landscape level anthropogenic pressures are rising. Human impacts can be analogous to apex predators in that humans can drive increased mortality in both prey species and carnivores, and impact communities through indirect fear effects and food subsidies. Here, we evaluate whether anthropogenic top-down pressures can structure communities in a similar manner as apex predators in shaping the interactions of mesocarnivores. Specifically, we expect anthropogenic forces to induce comparable effects as occurrence of apex predators in driving spatiotemporal partitioning between two mesocarnivores. Using multiple camera-trap surveys, we compared the temporal response of a small carnivore, the raccoon (Procyon lotor), to the larger coyote (Canis latrans)at four sites across Michigan that represented opposing gradients of pressure from humans and apex predators. Contrary to our expectations, we found that raccoons shifted their activity pattern in response to coyotes at sites with higher anthropogenic pressures and exhibited no temporal response at sites with apex predators. Temporal shifts were characterized by raccoons being more diurnal in areas of high coyote activity. We conclude that despite superficial similarities, anthropogenic forces do not replace the function of native apex predators in structuring the mesocarnivore guild. As such, an intact and functioning native predator guild remains necessary to preserve spatiotemporal community structure, in natural and disturbed systems alike.
Harmonization of L1CAM Expression Facilitates Axon Outgrowth and Guidance of a Motor Neuron
Authors: Sherry Tessa , Nicholas Hannah R. , Pocock Roger 
Published: June 2020

ABSTRACTBrain development requires precise regulation of axon outgrowth, guidance and termination by multiple signaling and adhesion molecules. How the expression of these neurodevelopmental regulators is transcriptionally controlled is poorly understood. TheCaenorhabditis elegansSMD motor neurons terminate axon outgrowth upon sexual maturity and partially retract their axons during early adulthood. Here we show that C-Terminal Binding Protein-1 (CTBP-1), a transcriptional corepressor, is required for correct SMD axonal development. Loss of CTBP-1 causes multiple defects in SMD axon development: premature outgrowth, defective guidance, delayed termination and absence of retraction. CTBP-1 controls SMD axon development by repressing the expression of SAX-7 – a L1 cell adhesion molecule (L1CAM). CTBP-1-regulated repression is crucial as deregulated SAX-7/L1CAM causes aberrant SMD axons. We found that axonal defects caused by SAX-7/L1CAM misexpression are dependent on a distinct L1CAM, called LAD-2, which itself plays a parallel role in SMD axon guidance. Our results reveal that harmonization of L1CAM expression controls the development and maturation of a single neuron.
Defining Relictual Biodiversity: Conservation Units in Speckled Dace (Cyprinidae:Rhinichthys osculus) of the Greater Death Valley Ecosystem
Authors: Mussmann Steven M. , Douglas Marlis R. , Oakey David D. , Douglas Michael E. 
Published: June 2020

AbstractThe tips in the tree of life serve as foci for conservation and management, yet clear delimitations are masked by inherent variance at the species-population interface. Analyses using thousands of nuclear loci can potentially sort inconsistencies, yet standard categories applied to this parsing are themselves potentially conflicting and/or subjective [e.g., DPS (distinct population segments); DUs (Diagnosable Units-Canada); MUs (management units); SSP (subspecies); Evolutionarily Significant Units (ESUs)]. One potential solution for consistent categorization is to create a comparative framework by accumulating statistical results from independent studies and evaluating congruence among data sets. Our study illustrates this approach in speckled dace (Cyprinidae:Rhinichthys osculus) endemic to two basins (Owens and Amargosa) in the Death Valley ecosystem (DVE). These fish persist in the Mojave Desert as isolated Pleistocene-relicts and are of conservation concern, but lack formal taxonomic descriptions/designations. Double-digest RAD (ddRAD) methods identified 14,355 SNP loci across 10 populations (N=140). Species delimitation analyses [multispecies coalescent (MSC) and unsupervised machine learning (UML)] delineated four putative ESUs.FSToutlier loci (N=106) were juxtaposed to uncover the potential for localized adaptations. We detected one hybrid population that resulted from upstream reconnection of habitat following contemporary pluvial periods, whereas remaining populations represent relics of ancient tectonism within geographically-isolated springs and groundwater-fed streams. Our study offers three salient conclusions: A blueprint for a multi-faceted delimitation of conservation units; a proposed mechanism by which criteria for intraspecific biodiversity can be potentially standardized; and a strong argument for the proactive management of critically-endangered DVE fishes.
Neuroprotective effects of motherhood on brain function in late-life: a resting state fMRI study
Authors: Orchard Edwina R , Ward Phillip GD , Chopra Sidhant , Storey Elsdon , Egan Gary F , Jamadar Sharna D 
Published: June 2020

AbstractThe maternal brain undergoes structural and functional plasticity during pregnancy and the postpartum period. Little is known about functional plasticity outside caregiving-specific contexts, and whether changes persist across the lifespan. Structural neuroimaging studies suggest that parenthood may confer a protective effect against the ageing process, however it is unknown whether parenthood is associated with functional brain differences in late-life. We examined the relationship between resting state functional connectivity and number of children parented in 220 healthy older females (73.82±3.53years) and 252 healthy older males (73.95±3.50years). We compared patterns of resting state functional connectivity with three different models of age-related functional change to assess whether these effects may be functionally neuroprotective for the ageing human parental brain. No relationship between functional connectivity and number of children was obtained for males. For females, we found widespread decreasing functional connectivity with increasing number of children parented, with increased segregation between networks, decreased connectivity between hemispheres, and decreased connectivity between anterior and posterior regions. The patterns of functional connectivity related to the number of children an older woman has parented were in the opposite direction to those usually associated with age-related cognitive decline, suggesting that motherhood may be beneficial for brain function in late-life.
Single Cell-type Integrative Network Modeling Identified Novel Microglial-specific Targets for the Phagosome in Alzheimer’s disease
Authors: Patel Kruti Rajan , Zhu Kuixi , Henrion Marc Y.R. , Beckmann Noam D. , Moein Sara , Alamprese Melissa L. , Allen Mariet , Wang Xue , Chan Gail , Pertel Thomas , Nejad Parham , Reddy Joseph S. , Carrasquillo Minerva M. , Bennett David A , Ertekin-Taner Nilüfer , De Jager Philip L. , Schadt Eric E. , Bradshaw Elizabeth M. , Chang Rui 
Published: June 2020

SummaryLate-Onset Alzheimer’s Disease (LOAD) results from a complex pathological process influenced by genetic variation, aging and environment factors. Genetic susceptibility factors indicate that myeloid cells such as microglia play a significant role in the onset of LOAD. Here, we developed a computational systems biology approach to construct probabilistic causal and predictive network models of genetic regulatory programs of microglial cells under LOAD diagnosis by integrating two independent brain transcriptome and genome-wide genotype datasets from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP) and Mayo Clinic (MAYO) studies in the AMP-AD consortium. From this network model, we identified and replicated novel microglial-specific master regulators predicted to modulate network states associated with LOAD. We experimentally validated three microglial master regulators (FCER1G,HCKandLAPTM5) in primary human microglia-like cells (MDMi) by demonstrating the molecular impact these master regulators have on modulating downstream genomic targets identified by our top-down/bottom-up method and the causal relations among the three key drivers. These master regulators are involved in phagocytosis, a process associated with LOAD. Thus, we propose three new master regulator (key driver) genes that emerged from our network analyses as robust candidates for further evaluation in LOAD therapeutic development efforts.
Beyond olfactory cortex – severity of post-traumatic olfactory loss is associated with response to odors in frontal-parietal-insular networks
Authors: Pellegrino Robert , Farruggia Michael C. , Small Dana M. , Veldhuizen Maria G. 
Published: June 2020

Olfactory impairment after trauma is associated with changes in olfactory cortex, including decreased gray matter density and decreased response to odors. Much less is known about the role of other cortical areas in olfactory impairment. We used fMRI in a sample of 63 participants, consisting of 25 with post-traumatic functional anosmia, 16 with post-traumatic hyposmia, and 22 healthy controls with normosmia to investigate whole brain response to odors. Similar neural responses were observed across the groups to odor versus odorless stimuli in the primary olfactory areas in piriform cortex, whereas response in the frontal operculum and anterior insula (fO/al) increased with olfactory function (normosmia > hyposmia > functional anosmia). Unexpectedly, a negative association was observed between response and olfactory function in the mediodorsal thalamus (mdT), ventromedial prefrontal cortex (vmPFC) and posterior cingulate cortex (pCC). Finally, connectivity within a network consisting of vmPFC, fO, and pCC could be used to successfully classify participants as having functional anosmia or normosmia. We conclude that, at the neural level, olfactory impairment due to head trauma is best characterized by heightened responses and differential connectivity in higher-order areas beyond olfactory cortex.Significance StatementOlfactory impairment affects a quarter of the population, with subjective complaints usually confirmed with psychophysical measurements. Here, we demonstrate that the degree of olfactory impairment can also be categorized using neural responses to odors. Remarkably, regions with neural responses that were predictive usually showed an increase in response to odors with degree of impairment, rather than a reduction, as might be expected. Further, predictive cortical regions were not isolated to canonical olfactory areas.
Prevalence of anticipatory nausea and vomiting in children undergoing cytotoxic chemotherapy for malignant disease - the SiCK2 (Sickness prior to Chemotherapy in Kids) study
Authors: Phillips Bob , ffrench-Devitt Patric , Wellings Lucy 
Published: June 2020

AbstractIntroductionAnticipatory nausea and vomiting (ANV) is thought to be a conditioned response to nausea and vomiting experienced in previous chemotherapy cycles, and has a significant negative impact on quality of life for children having treatment for cancer. The prevalence of this aversive experience with current antiemetics remains uncertain.MethodsSelf-report questionnaires completed by patients and parents across seven sites in the UK. Nausea and vomiting symptoms 24 hours prior to commencing chemotherapy were assessed with the Pediatric Nausea Assessment Tool (PeNAT). Data were also collected on the patients’ age, sex, oncological diagnosis, and previous experience of chemotherapy induced nausea and vomiting. Correlation between demographic data, chemotherapy information and prior reported experience of chemotherapy related nausea and vomiting was under-taken using multiple ordinal regression.Results191 episodes of anticipatory nausea and vomiting status were returned. 34% of patients described severe or very severe anticipatory nausea and/or vomiting. The severity of anticipatory nausea and vomiting was predicted two factors related to prior chemotherapy: control of anticipatory (OR 0.23 95%CI 0.09 to 0.53) and acute/delayed (OR 0.37, 95% CI 0.16 to 0.83) nausea and vomiting, and one current factor, the administration of antiemetic medication prior to arrival at the hospital (OR 3.0, 95%CI 1.3 to 6.8).ConclusionsThis study re-enforces, disappointingly, the continued high prevalence of anticipatory nau-sea and vomiting in children about to receive chemotherapy. There is clearly a need to improve interventions for this rarely discussed aversive experience of childhood cancer. Its high prevalence suggests trials of interventions should be possible to power effectively, and develop interventions that are both acceptable and deliverable.
Modeling the Transmission of Respiratory Infectious Diseases in Mass Transportation Systems
Authors: Buhat Christian Alvin H. , Lutero Destiny SM. , Olave Yancee H. , Torres Monica C. , Rabajante Jomar F. 
Published: June 2020

AbstractMass transportation is one of the areas that are badly hit by respiratory infectious disease outbreaks due to moderate to high exposure risk to pathogens brought about by the interaction among commuters. Here, we formulate agent-based models that simulate the spread of a respiratory infectious disease in a train wagon in the Manila Light Rail Transit System, and in a 49-seater public utility bus. We consider preventive measures such as implementation of social distancing, and limitation of interaction or movement among the commuters to investigate how these measures will inhibit disease transmission. We also consider the effect of protective gears and practices, crowd density, and prevalence of disease in the community on the possible number of newly-infected individuals. Our simulations show that (i) individuals must have protection with more than 90% effectiveness to inhibit transmission of the disease; (ii) social or physical distancing by more than 1m distance reduces the risk of being infected; (iii) minimizing movement or interaction with other passengers reduces the risk of transmission by 50%; (iv) passenger capacity should be less than 10-50% of the maximum seating capacity to reduce the number of infections depending on the level of imposed social distancing and passenger interaction; (v) vehicles with greater number of occupied seating capacity generate higher number of infections but vehicles with smaller dimensions have faster disease transmissions; and (vi) ideal set-up for a 24-seater train wagon (49-seater bus) is to allow a maximum of 12 (24) passengers, with little to no interaction among passengers, with social distancing of more than 1m distance apart, and each person has a protection with 90% effectiveness as much as possible. These results can aid policy makers in determining optimal strategies to minimize infections while maintaining transportation services during pandemics or disease outbreaks.