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Motor cortex (M1) has been thought to form a continuous somatotopic homunculus extending down the precentral gyrus from foot to face representations1,2, despite evidence for concentric functional zones3 and maps of complex actions4. Here, using precision functional magnetic resonance imaging (fMRI) methods, we find that the classic homunculus is interrupted by regions with distinct connectivity, structure and function, alternating with effector-specific (foot, hand and mouth) areas. These inter-effector regions exhibit decreased cortical thickness and strong functional connectivity to each other, as well as to the cingulo-opercular network (CON), critical for action5 and physiological control6, arousal7, errors8 and pain9. This interdigitation of action control-linked and motor effector regions was verified in the three largest fMRI datasets. Macaque and pediatric (newborn, infant and child) precision fMRI suggested cross-species homologues and developmental precursors of the inter-effector system. A battery of motor and action fMRI tasks documented concentric effector somatotopies, separated by the CON-linked inter-effector regions. The inter-effectors lacked movement specificity and co-activated during action planning (coordination of hands and feet) and axial body movement (such as of the abdomen or eyebrows). These results, together with previous studies demonstrating stimulation-evoked complex actions4 and connectivity to internal organs10 such as the adrenal medulla, suggest that M1 is punctuated by a system for whole-body action planning, the somato-cognitive action network (SCAN). In M1, two parallel systems intertwine, forming an integrate-isolate pattern: effector-specific regions (foot, hand and mouth) for isolating fine motor control and the SCAN for integrating goals, physiology and body movement.

Fibroblast growth factor (FGF) 23 is a bone-derived hormone that promotes renal phosphate excretion. Serum FGF23 is increased in chronic kidney disease (CKD) and contributes to pathologic cardiac hypertrophy by activating FGF receptor (FGFR) 4 on cardiac myocytes, which might lead to the high cardiovascular mortality in CKD patients. Increases in serum FGF23 levels have also been observed following endurance exercise and in pregnancy, which are scenarios of physiologic cardiac hypertrophy as an adaptive response of the heart to increased demand. To determine whether FGF23/FGFR4 contributes to physiologic cardiac hypertrophy, we studied FGFR4 knockout mice (FGFR4−/−) during late pregnancy. In comparison to virgin littermates, pregnant wild-type and FGFR4−/− mice showed increases in serum FGF23 levels and heart weight; however, the elevation in myocyte area observed in pregnant wild-type mice was abrogated in pregnant FGFR4−/− mice. This outcome was supported by treatments of cultured cardiac myocytes with serum from fed Burmese pythons, another model of physiologic hypertrophy, where the co-treatment with an FGFR4-specific inhibitor abrogated the serum-induced increase in cell area. Interestingly, we found that in pregnant mice, the heart, and not the bone, shows elevated FGF23 expression, and that increases in serum FGF23 are not accompanied by changes in phosphate metabolism. Our study suggests that in physiologic cardiac hypertrophy, the heart produces FGF23 that contributes to hypertrophic growth of cardiac myocytes in a paracrine and FGFR4-dependent manner, and that the kidney does not respond to heart-derived FGF23.

Abstract Chronic pancreatitis is a debilitating disease affecting millions worldwide. These patients suffer from bouts of severe pain that are minimally relieved by pain medications and may necessitate major surgeries with high morbidity and mortality. Previously, we demonstrated that “chemical pancreatectomy,” a pancreatic intraductal infusion of dilute acetic acid solution, ablated the exocrine pancreas while preserving the endocrine pancreas. Notably, chemical pancreatectomy resolved chronic inflammation, alleviated allodynia in the cerulein pancreatitis model, and improved glucose homeostasis. Herein, we extensively tested the feasibility of a chemical pancreatectomy in NHPs and validated our previously published pilot study. We did serial computed tomography (CT) scans of the abdomen and pelvis, analyzed dorsal root ganglia, measured serum enzymes, and performed histological and ultrastructural assessments and pancreatic endocrine function assays. Based on serial CT scans, chemical pancreatectomy led to the loss of pancreatic volume. Immunohistochemistry and transmission electron microscopy demonstrated exocrine pancreatic ablation with endocrine islet preservation. Importantly, chemical pancreatectomy did not increase pro-nociceptive markers in harvested dorsal root ganglia. Also, chemical pancreatectomy improved insulin secretion to supranormal levels in vivo and in vitro. Thus, this study may provide a foundation for translating this procedure to patients with chronic pancreatitis or other conditions requiring a pancreatectomy.

Abstract Desmosomes have a central role in mediating extracellular adhesion between cells, but they also coordinate other biological processes such as proliferation, differentiation, apoptosis and migration. In particular, several lines of evidence have implicated desmosomal proteins in regulating the actin cytoskeleton and attachment to the extracellular matrix, indicating signaling crosstalk between cell–cell junctions and cell–matrix adhesions. In our study, we found that cells lacking the desmosomal cadherin Desmoglein-2 (Dsg2) displayed a significant increase in spreading area on both fibronectin and collagen, compared to control A431 cells. Intriguingly, this effect was observed in single spreading cells, indicating that Dsg2 can exert its effects on cell spreading independent of cell–cell adhesion. We hypothesized that Dsg2 may mediate cell–matrix adhesion via control of Rap1 GTPase, which is well known as a central regulator of cell spreading dynamics. We show that Rap1 activity is elevated in Dsg2 knockout cells, and that Dsg2 harnesses Rap1 and downstream TGFβ signaling to influence both cell spreading and focal adhesion protein phosphorylation. Further analysis implicated the Rap GEF PDZ-GEF2 in mediating Dsg2-dependent cell spreading. These data have identified a novel role for Dsg2 in controlling cell spreading, providing insight into the mechanisms via which cadherins exert non-canonical junction-independent effects.

We present the longest available dataset (by 15 years) of estuarine zooplankton abundance worldwide. Zooplankton have been monitored throughout the upper San Francisco Estuary from 1972 –present due to its status as a central hub of California water delivery and home to commercially important and endangered fishes. We integrated data from five monitoring programs, including over 300 locations, three size-classes of zooplankton targeted with different gears, over 80,000 samples, and over two billion sampled organisms. Over the duration of this dataset, species invasions have driven community turnover, periodic droughts have occurred, and important fishes have declined, likely due in part to reduced food supply from zooplankton. Data from the individual surveys have been used in prior studies on issues related to species invasions, flows, fish diets and population dynamics, zooplankton population dynamics, and community ecology. Our integrated dataset offers unparalleled spatio-temporal scope to address these and other fundamental ecological questions.

This narrative inquiry aimed to investigate whether the deliberate use of positive imagined interactions (IIs) could contribute to the enhancement of cross-cutting political conflict, and also tested the seventh theorem of II conflict linkage theory. Undergraduate student participants were assigned to one of three conditions: positive II, negative II, or control in a three-phase procedure. Participants engaged in an II and then reflected on their IIs through open-ended questions before having real cross-cutting conversations on a political topic of their choice with trained confederates. Participants then completed a questionnaire assessing the constructiveness or destructiveness of their interaction. Thematic analysis revealed that 40 out of the 45 total participants engaged in positive and constructive conflict with their conversation partners. Positive IIs facilitated perspective-taking, while negative IIs allowed individuals to mentally defend their beliefs. Although the results neither confirmed nor refuted Theorem 7 of II conflict linkage theory, they did provide support for Theorem 3, which suggests that negative intrusive IIs can manifest even when individuals attempt to have positive IIs. [ABSTRACT FROM AUTHOR]

For this piece, I visited Blue Cross-Blue Shield of Louisiana (BCBSLA) to get a feel for its public relations operation. In an on-site personal interview, corporate communications writer Robin Mayhall described the general operations of the company and walked me through the research, strategy, and tactics as practiced by BCBSLA. Though largely descriptive of the BCBSLA PR process, this work also demonstrates how public relations theory works its way into practice, though acknowledgement by practitioners of their use of theory is far more subtle than that which we see in academic writing. [ABSTRACT FROM AUTHOR]

The characterization of individual functional brain organization with Precision Functional Mapping has provided important insights in recent years in adults. However, little is known about the ontogeny of inter-individual differences in brain functional organization during human development. Precise characterization of systems organization during periods of high plasticity is likely to be essential for discoveries promoting lifelong health. Obtaining precision fMRI data during development has unique challenges that highlight the importance of establishing new methods to improve data acquisition, processing, and analysis. Here, we investigate two methods that can facilitate attaining this goal: multi-echo (ME) data acquisition and thermal noise removal with Noise Reduction with Distribution Corrected (NORDIC) principal component analysis. We applied these methods to precision fMRI data from adults, children, and newborn infants. In adults, both ME acquisitions and NORDIC increased temporal signal to noise ratio (tSNR) as well as the split-half reliability of functional connectivity matrices, with the combination helping more than either technique alone. The benefits of NORDIC denoising replicated in both our developmental samples. ME acquisitions revealed longer and more variable T2* relaxation times across the brain in infants relative to older children and adults, leading to major differences in the echo weighting for optimally combining ME data. This result suggests ME acquisitions may be a promising tool for optimizing developmental fMRI, albeit application in infants needs further investigation. The present work showcases methodological advances that improve Precision Functional Mapping in adults and developmental populations and, at the same time, highlights the need for further improvements in infant specific fMRI., Competing Interests: 8.Declaration of Competing Interests Damien A. Fair is a patent holder on the Framewise Integrated Real-Time Motion Monitoring (FIRMM) software. He is also a co-founder of Turing Medical Inc that licenses this software. The nature of this financial interest and the design of the study have been reviewed by two committees at the University of Minnesota. They have put in place a plan to help ensure that this research study is not affected by the financial interest. Steven M. Nelson consults for Turing Medical, which commercializes FIRMM. This interest has been reviewed and managed by the University of Minnesota in accordance with its Conflict of Interest policies. Author Nico U. F. Dosenbach is a co-founder of Turing Medical Inc, has financial interest, and may benefit financially if the company is successful in marketing FIRMM motion monitoring software products. NUFD may receive royalty income based on FIRMM technology developed at Washington University School of Medicine (WUSOM) and licensed to Turing Medical Inc. Timothy O. Laumann holds a patent for taskless mapping of brain activity licensed to Sora Neurosciences and a patent for optimizing targets for neuromodulation, implant localization, and ablation is pending. TOL is also a consultant for Turing Medical Inc. Abraham Z. Snyder is a consultant for Sora Neurosciences. These potential conflicts of interest have been reviewed and are managed by Washington University School of Medicine. The other authors declare no competing interests.

Heritability of regional subcortical brain volumes (rSBVs) describes the role of genetics in middle and inner brain development. rSBVs are highly heritable in adults but are not characterized well in adolescents. The Adolescent Brain Cognitive Development study (ABCD), taken over 22 US sites, provides data to characterize the heritability of subcortical structures in adolescence. In ABCD, site-specific effects co-occur with genetic effects which can bias heritability estimates. Existing methods adjusting for site effects require additional steps to adjust for site effects and can lead to inconsistent estimation. We propose a random-effect model-based method of moments approach that is a single step estimator and is a theoretically consistent estimator even when sites are imbalanced and performs well under simulations. We compare methods on rSBVs from ABCD. The proposed approach yielded heritability estimates similar to previous results derived from single-site studies. The cerebellum cortex and hippocampus were the most heritable regions (> 50% )., Competing Interests: Competing interests The authors declare no competing financial interests.

Functional MRI (fMRI) data are severely distorted by magnetic field (B0) inhomogeneities which currently must be corrected using separately acquired field map data. However, changes in the head position of a scanning participant across fMRI frames can cause changes in the B0 field, preventing accurate correction of geometric distortions. Additionally, field maps can be corrupted by movement during their acquisition, preventing distortion correction altogether. In this study, we use phase information from multi-echo (ME) fMRI data to dynamically sample distortion due to fluctuating B0 field inhomogeneity across frames by acquiring multiple echoes during a single EPI readout. Our distortion correction approach, MEDIC (Multi-Echo DIstortion Correction), accurately estimates B0 related distortions for each frame of multi-echo fMRI data. Here, we demonstrate that MEDIC's framewise distortion correction produces improved alignment to anatomy and decreases the impact of head motion on resting-state functional connectivity (RSFC) maps, in higher motion data, when compared to the prior gold standard approach (i.e., TOPUP). Enhanced framewise distortion correction with MEDIC, without the requirement for field map collection, furthers the advantage of multi-echo over single-echo fMRI., Competing Interests: Competing Interests A.N.V., D.A.F. and N.U.F.D. have a financial interest in Turing Medical Inc. and may benefit financially if the company is successful in marketing FIRMM motion monitoring software products. A.N.V., D.A.F. and N.U.F.D. may receive royalty income based on FIRMM technology developed at Washington University School of Medicine and Oregon Health and Sciences University and licensed to Turing Medical Inc. D.A.F. and N.U.F.D. are co-founders of Turing Medical Inc. These potential conflicts of interest have been reviewed and are managed by Washington University School of Medicine, Oregon Health and Sciences University and the University of Minnesota. A.N.V. is now an employee of Turing Medical Inc. The other authors declare no competing interests.

Functional neuroimaging is an essential tool for neuroscience research. Pre-processing pipelines produce standardized, minimally pre-processed data to support a range of potential analyses. However, post-processing is not similarly standardized. While several options for post-processing exist, they tend not to support output from disparate pre-processing pipelines, may have limited documentation, and may not follow BIDS best practices. Here we present XCP-D, which presents a solution to these issues. XCP-D is a collaborative effort between PennLINC at the University of Pennsylvania and the DCAN lab at the University at Minnesota. XCP-D uses an open development model on GitHub and incorporates continuous integration testing; it is distributed as a Docker container or Singularity image. XCP-D generates denoised BOLD images and functional derivatives from resting-state data in either NifTI or CIFTI files, following pre-processing with fMRIPrep, HCP, and ABCD-BIDS pipelines. Even prior to its official release, XCP-D has been downloaded >3,000 times from DockerHub. Together, XCP-D facilitates robust, scalable, and reproducible post-processing of fMRI data.

We propose a new type of reflective polarizer based on polarization-dependent coupling to surface plasmon polaritons (SPPs) from free space. This inexpensive polarizer is relatively narrowband but features an extinction ratio of up to 1000 with efficiency of up to 95% for the desired polarization (numbers from a calculation) and thus can be stacked to achieve extinction ratios of 10 6 or more. As a proof of concept, we experimentally realized a polarizer based on nanoporous aluminum oxide that operates around a wavelength of 10.6 μm, corresponding to the output of a CO 2 laser, using aluminum anodization, a low-cost electrochemical process.