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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.

Sensory processing disorder (SPD) is a neurodevelopmental condition characterized by impaired sensory discrimination and responsivity. Although the causes and neural correlates of SPD remain poorly understood, prenatal influences should be considered, as the prenatal environment is strongly implicated in the progression of neurodevelopmental disorders. One factor hypothesized to promote SPD is perinatal Western‐style diet (WSD) exposure. This study explored the effects of perinatal WSD exposure on the proposed neural correlates of SPD in Japanese macaques. Functional connectivity between sensory and emotional processing areas was assessed at 4 months of age using resting‐state functional magnetic resonance imaging (rs‐fMRI). A machine learning model successfully predicted perinatal diet group based on functional connectivity strengths, indicating that differences in sensory connectivity exist between diet groups. Intra‐somatomotor, visual‐auditory, somatomotor‐auditory, somatomotor‐visual, and intra‐visual network connections demonstrated the greatest differences between groups, with primary motor cortex connectivity being the most impacted. Connections to the amygdala were not major contributors to accurate model performance, but amygdala connectivity, especially to the somatomotor network, may still be a weak driver of model performance. These findings suggest that a proposed predictor of SPD, perinatal WSD exposure, impacts the functional connectivity of sensory processing areas relevant in SPD during early infancy. Perinatal Western‐style diet exposure was associated with altered functional connectivity in sensory and emotional processing areas in 4‐month‐old macaques.

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.

Chronic kidney disease (CKD) is associated with various pathologic changes, including elevations in serum phosphate levels (hyperphosphatemia), vascular calcification, and skeletal muscle atrophy. Elevated phosphate can damage vascular smooth muscle cells and cause vascular calcification. Here, we determined whether high phosphate can also affect skeletal muscle cells and whether hyperphosphatemia, in the context of CKD or by itself, is associated with skeletal muscle atrophy. As models of hyperphosphatemia with CKD, we studied mice receiving an adenine-rich diet for 14 weeks and mice with deletion of Collagen 4a3 (Col4a3−/−). As models of hyperphosphatemia without CKD, we analyzed mice receiving a high-phosphate diet for three and six months as well as a genetic model for klotho deficiency (kl/kl). We found that adenine, Col4a3−/−, and kl/kl mice have reduced skeletal muscle mass and function and develop atrophy. Mice on a high-phosphate diet for six months also had lower skeletal muscle mass and function but no significant signs of atrophy, indicating less severe damage compared with the other three models. To determine the potential direct actions of phosphate on skeletal muscle, we cultured primary mouse myotubes in high phosphate concentrations, and we detected the induction of atrophy. We conclude that in experimental mouse models, hyperphosphatemia is sufficient to induce skeletal muscle atrophy and that, among various other factors, elevated phosphate levels might contribute to skeletal muscle injury in CKD.

By prohibiting fishing, marine protected areas （MPAs） provide a refuge for harvested species. Humans are often perceived as predators by prey and therefore respond fearfully to humans. Thus, fish responses to humans inside and outside of an MPA can provide insights into their perception of humans as a predatory threat. Previous studies have found differences in the distance that har- vested species of fish initiate flight （flight initiation distance--FID） from humans inside and outside an MPA, but less is known about unharvested species. We focused on whether the lined bristle- tooth Ctenochaetus striatus, an unharvested surgeonfish, can discriminate between a snorkeler and a snorkeler with a spear gun inside and outside of a no-take MPA in Mo＇orea, French Polynesia. Additionally, we incorporated starting distance （the distance between the person and prey at the start of an experimental approach）, a variable that has been found to be important in as- sessing prey escape decisions in terrestrial species, but that has not been extensively studied in aquatic systems. Lined bristletooth FID was significantly greater in the presence of a spear gun and varied depending on if the spear gun encounter was inside or outside of the MPA. These results imply a degree of sophistication of fish antipredator behavior, generate questions as to how a non- targeted species of fish could acquire fear of humans, and demonstrate that behavioral surveys can provide insights about antipredator behavior.

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.

Efficient management of medical supplies is crucial for ensuring quality patient care and controlling costs within healthcare facilities. It was identified that a comprehensive approach to establishing par levels for medical supplies and implementing a systematic process for monitoring expiration dates was needed after disposal of copious quantities of expired supplies. Supply management prevents the use of expired medical supplies, which could compromise patient safety and regulatory compliance. Ambulatory care clinics span three clinic locations and house an excess of fifty clinic rooms. The potential of ten different disease sites, both medical and surgical, practicing out of these clinical areas happens daily. Some clinics do planned procedures including scopes and internal exams, while others accommodate postoperative surgical issues. Due to the variety of clinics sharing space, the rooms were often overstocked with supplies leading to expired and wasted items. Multiple workflows were attempted for the supply management. A schedule of twice weekly checks with a two-person sign-off on clinic rooms was first attempted. This process quickly became cumbersome, and staff became noncompliant. The next step was to invest in locked supply carts to house all the medical supplies. Evaluation of the project demonstrated the same problems existed within the carts after moving supplies from the rooms to the carts. In response, a team of medical assistants (MAs) and RNs assembled to discuss ideas on management of the supplies and producing a system of checking the carts and preventing overstocking. The team consisted of majority MAs with an RN resource. They developed a workflow in which the carts were checked once a month, and supplies expiring by the end of the month were placed in a separate bag for first use. Supply Carts are currently checked once per month and recorded in a central location. Each cart has a team member assigned, and compliance is measured by our weekly regulatory checks on random carts. The maintenance of carts has been established and has shown improvement in supply expenses, staff satisfaction, survey readiness, and of most importance, patient safety. Through this committee's development, we have removed the risk of using expired items on patients and drastically reduced wasted medical supplies.

Motor cortex (M1) has been thought to form a continuous somatotopic homunculus extending down the precentral gyrus from foot to face representations 1 , 2 , despite evidence for concentric functional zones 3 and maps of complex actions 4 . 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 action 5 and physiological control 6 , arousal 7 , errors 8 and pain 9 . 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 actions 4 and connectivity to internal organs 10 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. Functional MRI studies across ages show that the classic homunculus of the motor cortex in humans is in fact discontinuous, alternating with action control-linked regions termed the somato-cognitive action network.

Cybersecurity is an important aspect of all businesses as well as the public sector. As information technology becomes more interconnected with our everyday lives, it opens more opportunities for network vulnerabilities and therefore more breach opportunities. Previous work within the State of Indiana has produced a cybersecurity scorecard but leaves those using the scorecard with no way to improve their scores. This research is conducted to help Indiana counties improve their cybersecurity practices with a limited budget. As well, this research and implementation guide will be accessible in a way that any employee at the county level, despite their cybersecurity knowledge, will have a solid foundation on where to begin to improve their score. The goal of this study is to develop a framework that identifies the weaknesses in an Indiana county's response to the Cybersecurity Scorecard and provides resources to improve their scores. The framework should identify the specific issues and give definitions or resources for the counties to use to improve their score.