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"Cobb, Allan B"
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Small Caves and Sacred Geography: A Case Study from the Prehispanic Maya Site of Maax Na, Belize
Contemporary research on prehispanic Maya landscapes has focused on caves as core features of the cultural geography. Investigations within a number of large caves have suggested that they served as the loci for important rituals, legitimized inhabitants’ claims to their territory, and helped establish the authority of a site’s ruling elite. The ubiquity and centrality of caves in the Maya worldview raises questions about what happened in regions where large caves did not naturally form. Recent investigations at the site of Maax Na in northern Belize suggest that small caves, despite their diminutive size, still functioned to establish legitimacy and uphold power. The results serve to demonstrate the pervasive power of key ideological concepts in shaping the cultural landscape and indicate the need to take these into account in documenting landmarks at Maya sites, as even the less imposing ones may have been important to their inhabitants.
Journal Article
Brain Responses to Noxious Stimuli in Patients With Chronic Pain
Functional neuroimaging is a valuable tool for understanding how patients with chronic pain respond to painful stimuli. However, past studies have reported heterogenous results, highlighting opportunities for a quantitative meta-analysis to integrate existing data and delineate consistent associations across studies.
To identify differential brain responses to noxious stimuli in patients with chronic pain using functional magnetic resonance imaging (fMRI) while adhering to current best practices for neuroimaging meta-analyses.
All fMRI experiments published from January 1, 1990, to May 28, 2019, were identified in a literature search of PubMed/MEDLINE, EMBASE, Web of Science, Cochrane Library, PsycINFO, and SCOPUS.
Experiments comparing brain responses to noxious stimuli in fMRI between patients and controls were selected if they reported whole-brain results, included at least 10 patients and 10 healthy control participants, and used adequate statistical thresholding (voxel-height P < .001 or cluster-corrected P < .05). Two independent reviewers evaluated titles and abstracts returned by the search. In total, 3682 abstracts were screened, and 1129 full-text articles were evaluated.
Thirty-seven experiments from 29 articles met inclusion criteria for meta-analysis. Coordinates reporting significant activation differences between patients with chronic pain and healthy controls were extracted. These data were meta-analyzed using activation likelihood estimation. Data were analyzed from December 2019 to February 2020.
A whole-brain meta-analysis evaluated whether reported differences in brain activation in response to noxious stimuli between patients and healthy controls were spatially convergent. Follow-up analyses examined the directionality of any differences. Finally, an exploratory (nonpreregistered) region-of-interest analysis examined differences within the pain network.
The 37 experiments from 29 unique articles included a total of 511 patients and 433 controls (944 participants). Whole-brain meta-analyses did not reveal significant differences between patients and controls in brain responses to noxious stimuli at the preregistered statistical threshold. However, exploratory analyses restricted to the pain network revealed aberrant activity in patients.
In this systematic review and meta-analysis, preregistered, whole-brain analyses did not reveal aberrant fMRI activity in patients with chronic pain. Exploratory analyses suggested that subtle, spatially diffuse differences may exist within the pain network. Future work on chronic pain biomarkers may benefit from focus on this core set of pain-responsive areas.
Journal Article
Large-Scale Screening for Targeted Knockouts in the Caenorhabditis elegans Genome
The nematode Caenorhabditis elegans is a powerful model system to study contemporary biological problems. This system would be even more useful if we had mutations in all the genes of this multicellular metazoan. The combined efforts of the C. elegans Deletion Mutant Consortium and individuals within the worm community are moving us ever closer to this goal. At present, of the 20,377 protein-coding genes in this organism, 6764 genes with associated molecular lesions are either deletions or null mutations (WormBase WS220). Our three laboratories have contributed the majority of mutated genes, 6841 mutations in 6013 genes. The principal method we used to detect deletion mutations in the nematode utilizes polymerase chain reaction (PCR). More recently, we have used array comparative genome hybridization (aCGH) to detect deletions across the entire coding part of the genome and massively parallel short-read sequencing to identify nonsense, splicing, and missense defects in open reading frames. As deletion strains can be frozen and then thawed when needed, these strains will be an enduring community resource. Our combined molecular screening strategies have improved the overall throughput of our gene-knockout facilities and have broadened the types of mutations that we and others can identify. These multiple strategies should enable us to eventually identify a mutation in every gene in this multicellular organism. This knowledge will usher in a new age of metazoan genetics in which the contribution to any biological process can be assessed for all genes.
Journal Article
A globally synthesised and flagged bee occurrence dataset and cleaning workflow
Species occurrence data are foundational for research, conservation, and science communication, but the limited availability and accessibility of reliable data represents a major obstacle, particularly for insects, which face mounting pressures. We present
BeeBDC
, a new
R
package, and a global bee occurrence dataset to address this issue. We combined >18.3 million bee occurrence records from multiple public repositories (GBIF, SCAN, iDigBio, USGS, ALA) and smaller datasets, then standardised, flagged, deduplicated, and cleaned the data using the reproducible
BeeBDC R
-workflow. Specifically, we harmonised species names (following established global taxonomy), country names, and collection dates and, we added record-level flags for a series of potential quality issues. These data are provided in two formats, “cleaned” and “flagged-but-uncleaned”. The
BeeBDC
package with online documentation provides end users the ability to modify filtering parameters to address their research questions. By publishing reproducible
R
workflows and globally cleaned datasets, we can increase the accessibility and reliability of downstream analyses. This workflow can be implemented for other taxa to support research and conservation.
Journal Article
NPRL3: Direct Effects on Human Phenotypic Variability, mTOR Signaling, Subcellular mTOR Localization, Cortical Lamination, and Seizure Susceptibility
Abstract Nitrogen Permease Regulator Like 3 (NPRL3) variants are associated with malformations of cortical development (MCD) and epilepsy. We report a large (n=133) founder NPRL3 (c.349delG, p.Glu117LysFS) pedigree dating to 1727, with heterogeneous epilepsy and MCD phenotypes. Whole exome analysis in individuals with and without seizures in this cohort did not identify a genetic modifier to explain the variability in seizure phenotype. Then as a strategy to investigate the developmental effects of NPRL3 loss in human brain, we show that CRISPR/Cas9 Nprl3 knockout (KO) in Neuro2a cells (N2aC) in vitro causes mechanistic target of rapamycin (mTOR) pathway hyperactivation, cell soma enlargement, and excessive cellular aggregation. Amino acid starvation caused mTOR inhibition and cytoplasmic mTOR localization in wildtype cells, whereas following Nprl3 KO, mTOR remained inappropriately localized on the lysosome and activated, evidenced by persistent ribosomal S6 and 4E-BP1 phosphorylation, demonstrating that Nprl3 loss decouples mTOR activation from metabolic state. Nprl3 KO by in utero electroporation in fetal (E14) mouse cortex resulted in mTOR-dependent cortical dyslamination with ectopic neurons in subcortical white matter. EEG recordings of these mice showed hyperexcitability in the electroporated hemisphere. NPRL3 variants are linked to a highly variable clinical phenotype likely as a consequence of mTOR-dependent effects on cell structure, cortical development, and network organization. Competing Interest Statement The authors have declared no competing interest. Footnotes * Conflict of Interest: The authors have declared that no conflict of interest exists.
Paper
Convergent neural representations of acute nociceptive pain in healthy volunteers: A large-scale fMRI meta-analysis
Characterizing a reliable, pain-related neural signature is critical for translational applications. Many prior fMRI studies have examined acute pain-related brain activation in healthy participants. However, synthesizing these data to identify convergent patterns of activation can be challenging due to the heterogeneity of experimental designs and samples. To address this challenge, we conducted a comprehensive meta-analysis of fMRI studies of stimulus-induced pain in healthy participants. Following pre-registration, two independent reviewers evaluated 4,927 abstracts returned from a search of 8 databases, with 222 fMRI experiments meeting inclusion criteria. We analyzed these experiments using Activation Likelihood Estimation with rigorous type I error control (voxel height p < 0.001, cluster p < 0.05 FWE-corrected) and found a convergent, largely bilateral pattern of pain-related activation in the secondary somatosensory cortex, insula, midcingulate cortex, and thalamus. Notably, these regions were consistently recruited regardless of stimulation technique, location of induction, and participant sex. These findings suggest a highly-conserved core set of pain-related brain areas, encouraging applications as a biomarker for novel therapeutics targeting acute pain. Footnotes * https://github.com/PennBBL/Xu_PainHealthy
Paper
The Cambridge Handbook of the Learning Sciences
Learning sciences is an interdisciplinary field that studies teaching and learning. The sciences of learning include cognitive science, educational psychology, computer science, anthropology, sociology, neuroscience, and other fields. The Cambridge Handbook of the Learning Sciences, first published in 2006, shows how educators can use the learning sciences to design more effective learning environments - including school classrooms and also informal settings such as science centers or after-school clubs, on-line distance learning, and computer-based tutoring software. The chapters in this handbook each describe exciting new classroom environments, based on the latest science about how children learn. CHLS is a true handbook in that readers can use it to design the schools of the future - schools that will prepare graduates to participate in a global society that is increasingly based on knowledge and innovation.
eBook
A globally synthesised and flagged bee occurrence dataset and cleaning workflow
Species occurrence data are foundational for research, conservation, and science communication, but the limited availability and accessibility of reliable data represents a major obstacle, particularly for insects, which face mounting pressures. We present BeeBDC, a new R package, and a global bee occurrence dataset to address this issue. We combined >18.3 million bee occurrence records from multiple public repositories (GBIF, SCAN, iDigBio, USGS, ALA) and smaller datasets, then standardised, flagged, deduplicated, and cleaned the data using the reproducible BeeBDC R-workflow. Specifically, we harmonised species names (following established global taxonomy), country names, and collection dates and we added record-level flags for a series of potential quality issues. These data are provided in two formats, “cleaned” and “flagged-but-uncleaned”. The BeeBDC package with online documentation provides end users the ability to modify filtering parameters to address their research questions. By publishing reproducible R workflows and globally cleaned datasets, we can increase the accessibility and reliability of downstream analyses. This workflow can be implemented for other taxa to support research and conservation.
Paper
Preclassic Cave Utilization near Cobanerita, San Benito, Peten
Uso de cuevas cerca de Cobanerita, San Benito, Petén en el período preclásico. Durante mayo y agosto de 1997 un grupo multidisciplinario de especialistas investigó cinco cuevas ubicadas a 15 kilómetros de la carretera Flores—Sayaxché. Cuatro de ellas fueron exploradas y documentadas cartográficamente. El artículo analiza los hallazgos arqueológicos encontrados en la \"Cueva de las Pinturas\". Esta cueva destaca por sus pinturas jeroglíficas polícromas que ya habían sido documentados anteriormente por otros investigadores. Además se encontraron roca escarpada labrada, restos de muros y de un sacbé ancho, diferentes estratos artificiales de barro rojo, diversos objetos de cerámica y piedra (entre ellos fragmentos de manos y metates), maíz carbonizado e instrumentos de obsidiana y huesos utilizados para sacrificios. Todos estos hallazgos indican un uso ritual de la cueva. Hasta la fecha no se ha terminado una datación exacta del material orgánico. Excavaciones explorativas y el análisis de la cerámica indican una ocupación humana y el uso de la cueva a partir de la época preclásica mediana y tardía. Sin embargo, numerosas destrucciones resultado del saqueo y vandalismo han limitado las posibilidades del análisis arqueológico. Präklassische Höhlennutzung nahe Cobanerita, San Benito, Peten. Im Mai und August 1997 untersuchte ein multidisziplinäres Expertenteam fünf, etwa 15 km westlich der Straße Flores—Sayaxche gelegene Höhlen, von denen vier exploriert und kartographiert werden konnten. Der Artikel beschreibt die Funde in der \"Cueva de las Pinturas\", deren Wandmalereien mit polychromen Hieroglyphen bereits vorher von Wissenschaftlern dokumentiert worden waren. Daneben belegen Skulptierungen des Höhlengesteins, Mauern, Überreste eines breiten Zeremonialweges (sacbe), künstlich eingezogene Bodenschichten aus rotem Ton, zahlreiche Keramik- und Steinobjektfunde (darunter Fragmente von manos und metates) sowie karbonisierter Mais und Opferinstrumente (Klingen aus Obsidian sowie ein Stück einer Knochennadel) die rituelle Nutzung der Höhle. Zwar steht die zeitliche Bestimmung des organischen Fundmaterials noch aus, doch konnte durch Testgrabungen und Keramikanalyse die Natzung dieser Höhle durch den Menschen in die mittlere und späte Präklassik datiert werden. Der archäologische Befund wurde allerdings durch zahlreiche Zerstörungen infolge von Plünderung und Vandalismus beeinträchtigt.
Journal Article