Atlas of fetal metabolism during mid-to-late gestation and diabetic pregnancy.

Mounting evidence suggests metabolism instructs stem cell fate decisions. However, how fetal metabolism changes during development and how altered maternal metabolism shapes fetal metabolism remain unexplored. We present a descriptive atlas of in vivo fetal murine metabolism during mid-to-late gestation in normal and diabetic pregnancy. Using 13C-glucose and liquid chromatography-mass spectrometry (LC-MS), we profiled the metabolism of fetal brains, hearts, livers, and placentas harvested from pregnant dams between embryonic days (E)10.5 and 18.5. Our analysis revealed metabolic features specific to a hyperglycemic environment and signatures that may denote developmental transitions during euglycemic development. We observed sorbitol accumulation in fetal tissues and altered neurotransmitter levels in fetal brains isolated from hyperglycemic dams. Tracing 13C-glucose revealed disparate fetal nutrient sourcing depending on maternal glycemic states. Regardless of glycemic state, histidine-derived metabolites accumulated in late-stage fetal tissues. Our rich dataset presents a comprehensive overview of in vivo fetal tissue metabolism and alterations due to maternal hyperglycemia.

A parallel glycolysis provides a selective advantage through rapid growth acceleration.

Glycolysis is a universal metabolic process that breaks down glucose to produce adenosine triphosphate (ATP) and biomass precursors. The Entner-Doudoroff (ED) pathway is a glycolytic pathway that parallels textbook glycolysis but yields half as much ATP. Accordingly, in organisms that possess both glycolytic pathways (for example, Escherichia coli), its raison d'être remains a mystery. In this study, we found that the ED pathway provides a selective advantage during growth acceleration. Upon carbon and nitrogen upshifts, E. coli accelerates growth faster with than without the ED pathway. Concurrent isotope tracing reveals that the ED pathway flux increases faster than that of textbook glycolysis. We attribute the fast response time of the ED pathway to its strong thermodynamic driving force and streamlining of glucose import. Intermittent nutrient supply manifests the evolutionary advantage of the parallel glycolysis; thus, the dynamic nature of an ostensibly redundant pathway's role in promoting rapid adaptation constitutes a metabolic design principle.

EBV-positive mucocutaneous ulcer presenting as a nasopharyngeal tumor in an immune suppressed patient.

BACKGROUND: We describe an unusual presentation of EBV-associated mucocutaneous ulcer presenting as a large tumor of the nasopharynx in an immune suppressed child. This condition is newly characterized and has not been well-studied in the otolaryngology literature. CASE REPORT: Our patient is a 12-year-old female undergoing chemotherapy for T-cell acute lymphoblastic leukemia who presented with progressively severe headaches, nasal obstruction, facial pain/pressure, photophobia, fever and otalgia associated with neutropenia and refractory to empiric antibiotic therapy. Bedside nasal endoscopy and imaging revealed signs of acute sinusitis and a large nasopharyngeal mass suspicious for neoplasm. The mass was eccentric to the right and distending the right fossa of Rosenmuller. She underwent endoscopic sinus surgery and biopsy of her nasopharyngeal mass. Pathologic analysis of the nasopharyngeal mass revealed EBV-positive mucocutaneous ulcer. CONCLUSION: This is an unusual presentation of a rare entity. EBV-positive mucocutaneous ulcer warrants awareness among otolaryngologists and is not well-described in our literature.

Tag and Snag: A New Platform for Bioactive Natural Product Screening from Mixtures.

Natural products provide an unparalleled diversity of small molecules to fuel drug screening efforts, but deconvoluting the pharmacological activity of natural product mixtures to identify key bioactive compounds remains a vexing and labor-intensive process. Therefore, we have developed a new platform to probe the non-specific pharmacological potential of compounds present in common dietary supplements via shotgun derivatization with isotopically labeled propanoic acid, a live cell affinity assay, which was used to selectively recognize the population of compounds which bind tightly to HeLa cells in culture, and a computational LC-MS data analysis of isotopically labeled compounds from cell lysate. The data analysis showed that hundreds of compounds were successfully derivatized in each extract, and dozens of those compounds showed high affinity for HeLa cells. In total, over a thousand isotopically labeled compounds were screened for cell affinity across three separate experiments, resulting in the identification of several known bioactive compounds with specific protein targets and six previously unreported structures. The new natural products include three tulsinol compounds which were isolated from Ocimum tenuiflorum and three valeraninium alkaloids from Valeriana officinalis. The valeraninium alkaloids constitute a distinct new family of alkaloids from valerian, which may have previously undescribed bioactivity. These results collectively demonstrate the tag and snag workflow's viability as a drug discovery method.

Influence of design and material characteristics on 3D printed flow-cells for heat transfer-based analytical devices.

Redesigning 3D-printed flow cells is reported used for heat transfer based detection of biomolecules from a flow-through system to an addition-type measurement cell. The aim of this study is to assess the performance of this new measurement design and critically analyse the influence of material properties and 3D printing approach on thermal analysis. Particular attention is paid to reduce the time to stabilisation, the sample volume in order to make the technique suitable for clinical applications, and improving the sensitivity of the platform by decreasing the noise and interference of air bubbles. The three different approaches that were studied included a filament polylactic acid cell using only fused filament fabrication (FFF), a resin cell printed using stereolitography (SLA), and finally a design made of copper, which was manufactured by combining metal injection moulding (MIM) with fused filament fabrication (FFF). Computational fluid dynamic (CFD) modelling was undertaken using ANSYS Fluent V18.1 to provide insight into the flow of heat within the measurement cell, facilitating optimisation of the system and theoretical response speed.It was shown that the measurement cells using SLA had the lowest noise (~ 0.6%) and shortest measurement time (15 min), whereas measurement cells produced using other approaches had lower specificity or suffered from voiding issues. Finally, we assessed the potential of these new designs for detection of biomolecules and amoxicillin, a commonly used beta lactam antibiotic, to demonstrate the proof of concept. It can be concluded that the resin addition-type measurement cells produced with SLA are an interesting affordable alternative, which were able to detect amoxicillin with high sensitivity and have great promise for clinical applications due to the disposable nature of the measurement cells in addition to small sample volumes.

Correction: Szymanski et al. Recent Advances in Loop Heat Pipes with Flat Evaporator. Entropy 2021, 23, 1374.

The author of the original publication [...].

Middle turbinate resection is unlikely to cause empty nose syndrome in first year postoperatively.

PURPOSE: Empty nose syndrome (ENS) is characterized by nasal dryness, crusting, and paradoxical nasal obstruction most commonly after inferior turbinate resection. ENS has also been reported to occur after middle turbinate resection (MTR), and concern for causing ENS is a possible reason surgeons preserve the MT during endoscopic sinus surgery (ESS). The objective was to determine whether MTR during ESS led to ENS. MATERIALS AND METHODS: This was a prospective case series of 95 consecutive patients that underwent bilateral subtotal MTR during ESS with either Draf IIB or Draf III frontal sinusotomies, for chronic rhinosinusitis with or without nasal polyps, and frontal sinus inverted papillomas. Demographic data and postoperative Empty Nose Syndrome 6-item Questionnaire (ENS6Q) scores were obtained. Nasal crusting was also documented on last postoperative nasal endoscopy. RESULTS: Pathologies included chronic rhinosinusitis with nasal polyps (69), without nasal polyps (12), and inverted papillomas (14). Fifty-six patients underwent subtotal MTRs during ESS with Draf IIB, and 39 with Draf III. Mean follow-up was 19.4 months (range 12-49). Mean postoperative ENS6Q score was 2.1. Only 2.1% had ENS6Q scores ≥ 11, and 6.3% had nasal crusting at last follow-up. None of the patients with ENS6Q scores ≥ 11 had nasal crusting at last follow-up. There were no significant differences in outcomes between ages, genders, surgery types, or pathologies. CONCLUSIONS: Patients who underwent bilateral subtotal MTR during ESS were unlikely to develop ENS by at least 1 year postoperatively, based on patients rarely experiencing ENS6Q scores ≥ 11 or persistent nasal crusting.

Does insurance type influence overall survival in patients with laryngeal squamous cell carcinoma?

OBJECTIVE: Patients with head and neck cancer with Medicaid or no insurance present at a more advanced stage and have lower survival. This study is one of the first to examine the relationship between specific insurance types and overall survival for laryngeal squamous cell carcinoma patients. STUDY DESIGN: Retrospective chart review. SETTING: Henry Ford Cancer Institute. SUBJECTS AND METHODS: A retrospective database review was performed using the Henry Ford Virtual Data Warehouse Tumor Registry. Six hundred and fifty patients diagnosed with laryngeal squamous cell carcinoma were identified. Insurance groups analyzed were fee for service, health maintenance organization, Henry Ford Medical Group - a managed care type insurance, Medicare and Medicaid/uninsured. Cox proportional hazards and Kaplan-Meier curves were generated to analyze overall survival and display survival differences respectively. RESULTS: The uninsured group had the lowest median survival time of 29.8 months (95% CI: 20.3-44.8) and the highest HR of 1.85 (95% CI 1.16-2.93) as compared to the HMO group at p < 0.001. Patients with fee for service insurance had longer overall survival compared to the other insurance types. Patients with fee for service insurance also had a high proportion of patients with advanced stage disease, but a younger mean age. Henry Ford Medical Group had a higher mean age and no statistically significant difference in survival when compared to fee for service. (p = 0.999) After controlling for socioeconomic status, insurance type remains a significant predictor of overall survival. CONCLUSIONS: Fee for service had the highest overall survival of the different insurance types, but it was only statistically significant when compared to the Medicaid/uninsured group.

Recent Advances in Loop Heat Pipes with Flat Evaporator.

The focus of this review is to present the current advances in Loop Heat Pipes (LHP) with flat evaporators, which address the current challenges to the wide implementation of the technology. A recent advance in LHP is the design of flat-shaped evaporators, which is better suited to the geometry of discretely mounted electronics components (microprocessors) and therefore negate the need for an additional transfer surface (saddle) between component and evaporator. However, various challenges exist in the implementation of flat-evaporator, including (1) deformation of the evaporator due to high internal pressure and uneven stress distribution in the non-circular casing; (2) heat leak from evaporator heating zone and sidewall into the compensation chamber; (3) poor performance at start-up; (4) reverse flow through the wick; or (5) difficulties in sealing, and hence frequent leakage. This paper presents and reviews state-of-the-art LHP technologies; this includes an (a) review of novel manufacturing methods; (b) LHP evaporator designs; (c) working fluids; and (d) construction materials. The work presents solutions that are used to develop or improve the LHP construction, overall thermal performance, heat transfer distance, start-up time (especially at low heat loads), manufacturing cost, weight, possibilities of miniaturization and how they affect the solution on the above-presented problems and challenges in flat shape LHP development to take advantage in the passive cooling systems for electronic devices in multiple applications.

Postoperative pain with or without nasal splints after septoplasty and inferior turbinate reduction.

PURPOSE: To determine the effect of intranasal Doyle splints on postoperative pain following septoplasty and inferior turbinate reduction (ITR). Changes in Nasal Obstruction Symptom Evaluation (NOSE) scores were also evaluated. MATERIALS AND METHODS: A prospective cohort study conducted from January 2017 to January 2019. Patients were recruited if they experienced nasal obstruction due to septal deviation and inferior turbinate hypertrophy, and failed a one-month trial of intranasal corticosteroids. All patients underwent septoplasty with ITR, and either had Doyle splints or no splints placed. Patients were prescribed hydrocodone-acetaminophen 5-325 mg and asked to keep a daily log of pain medication use and visual analog scale (VAS) scores. Pain logs and NOSE scores were compared between patients who had splints versus patients who had no splints placed after septoplasty and ITR over the first postoperative week. NOSE scores were also collected at every postoperative visit (1 week, 1 month, and 6 months). RESULTS: Fifty-seven patients were enrolled (37 splints, 20 no-splints). The median postoperative pain VAS score was 3.0 (interquartile range [IQR] 2.0-5.0) for the splint group and 4.0 (IQR 2.0-5.0) for the no-splint group (P = 0.906). The median postoperative pain medication requirement in morphine equivalents at the first postoperative visit was 5.4 mg/day (IQR 2.0-13.3) for the splint group and 8.4 mg/day (IQR 1.8-15.3) for the no-splint group (P = 0.833). CONCLUSIONS: There were no statistically significant differences in postoperative pain VAS scores or pain medication use between the two groups. All patients experienced significant reductions in NOSE scores postoperatively.

Effects of excess thromboxane A2 on placental development and nutrient transporters in a Mus musculus model of fetal growth restriction.

Hypertensive disease of pregnancy (HDP) with placental insufficiency is the most common cause of fetal growth restriction (FGR) in the developed world. Despite the known negative consequences of HDP both to the mother and fetus, little is known about the longitudinal placental changes that occur as HDP progresses in pregnancy. This is because longitudinal sampling of human placentae during each gestation is impossible. Therefore, using a mouse model of thromboxane A2-analog infusion to mimic human HDP in the last trimester, we calculated placental efficiencies based on fetal and placental weights; quantified spongiotrophoblast and labyrinth thicknesses and vascular density within these layers; examined whether hypoxia signaling pathway involving vascular endothelial growth factor A (VEGFA) and its receptors (VEGFR1, VEGFR2) and matrix metalloproteinases (MMPs) contributed to vascular change; and examined nutrient transporter abundance including glucose transporters 1 and 3 (GLUT1, GLUT3), neutral amino acid transporters 1, 2, and 4 (SNAT1, SNAT2, and SNAT4), fatty acid transporters 2 and 4 (FATP2, FATP4), and fatty acid translocase (CD36) from embryonic day 15.5 to 19 in a 20-day C57Bl/6J mouse gestation. We conclude that early-to-mid gestation hypertensive placentae show compensatory mechanisms to preserve fetal growth by increasing placental efficiencies and maintaining abundance of important nutrient transporters. As placental vascular network diminishes over late hypertension, placental efficiency diminishes and fetal growth fails. Neither hypoxia signaling pathway nor MMPs mediated the vascular diminution in this model. Hypertensive placentae surprisingly exhibit a sex-differential expression of nutrient transporters in late gestation despite showing fetal growth failure in both sexes.

Sheldon spectrum and the plankton paradox: two sides of the same coin-a trait-based plankton size-spectrum model.

The Sheldon spectrum describes a remarkable regularity in aquatic ecosystems: the biomass density as a function of logarithmic body mass is approximately constant over many orders of magnitude. While size-spectrum models have explained this phenomenon for assemblages of multicellular organisms, this paper introduces a species-resolved size-spectrum model to explain the phenomenon in unicellular plankton. A Sheldon spectrum spanning the cell-size range of unicellular plankton necessarily consists of a large number of coexisting species covering a wide range of characteristic sizes. The coexistence of many phytoplankton species feeding on a small number of resources is known as the Paradox of the Plankton. Our model resolves the paradox by showing that coexistence is facilitated by the allometric scaling of four physiological rates. Two of the allometries have empirical support, the remaining two emerge from predator-prey interactions exactly when the abundances follow a Sheldon spectrum. Our plankton model is a scale-invariant trait-based size-spectrum model: it describes the abundance of phyto- and zooplankton cells as a function of both size and species trait (the maximal size before cell division). It incorporates growth due to resource consumption and predation on smaller cells, death due to predation, and a flexible cell division process. We give analytic solutions at steady state for both the within-species size distributions and the relative abundances across species.

Spatial point processes and moment dynamics in the life sciences: a parsimonious derivation and some extensions.

Mathematical models of dynamical systems in the life sciences typically assume that biological systems are spatially well mixed (the mean-field assumption). Even spatially explicit differential equation models typically make a local mean-field assumption. In effect, the assumption is that diffusive movement is strong enough to destroy spatial structure or that interactions between individuals are sufficiently long-range that the effects of spatial structure are weak. However, many important biophysical processes, such as chemical reactions of biomolecules within cells, disease transmission among humans, and dispersal of plants, have characteristic spatial scales that can generate strong spatial structure at the scale of individuals, with important effects on the behaviour of biological systems. This calls for mathematical methods that incorporate spatial structure. Here, we focus on one method, spatial-moment dynamics, which is based on the idea that important information about a spatial point process is held in its low-order spatial moments. The method goes beyond the dynamics of the first moment, i.e. the mean density or concentration of agents in space, in which no information about spatial structure is retained. By including the dynamics of at least the second moment, the method retains some information about spatial structure. Whereas mean-field models effectively use a closure assumption for the second moment, spatial-moment models use a closure assumption for the third (or a higher-order) moment. The aim of the paper was to provide a parsimonious and intuitive derivation of spatial-moment dynamic equations that is accessible to non-specialists. The derivation builds naturally from the first moment to the second, and we show how it can be extended to higher-order moments. Rather than tying the model to a specific biological example, we formulate a general model of movement, birth, and death of multiple types of interacting agents. This model can be applied to problems from a range of disciplines, some of which we discuss. The derivation is performed in a spatially non-homogeneous setting, to facilitate future investigations of biological scenarios, such as invasions, in which the spatial patterns are non-stationary over space.

Maternal transmission as a microbial symbiont sieve, and the absence of lactation in male mammals.

Gut microbiomes of mammals carry a complex symbiotic assemblage of microorganisms. Feeding newborn infants milk from the mammary gland allows vertical transmission of the parental milk microbiome to the offspring's gut microbiome. This has benefits, but also has hazards for the host population. Using mathematical models, we demonstrate that biparental vertical transmission enables deleterious microbial elements to invade host populations. In contrast, uniparental vertical transmission acts as a sieve, preventing these invasions. Moreover, we show that deleterious symbionts generate selection on host modifier genes that keep uniparental transmission in place. Since microbial transmission occurs during birth in placental mammals, subsequent transmission of the milk microbiome needs to be maternal to avoid the spread of deleterious elements. This paper therefore argues that viviparity and the hazards from biparental transmission of the milk microbiome, together generate selection against male lactation in placental mammals.

Difficulties in using land use pressure and soil quality indicators to predict water quality.

Intensive agriculture can impair river water quality. Soil quality monitoring has been used to measure the effect of land use intensification on water quality at a point and field scales but not at the catchment scale. Other farm scale land use pressures, like stocking rate and the value of land, which relate to land use intensity are now publicly available, nationally. We therefore tested whether point scale soil quality measures, together with newly available farm scale land use pressures (land valuation and stocking rate) and existing catchment and climatic characteristics could help predict the behaviour of water quality data across 192 catchments in New Zealand. We used a generalised additive model to make predictions of the change in nitrogen fractions (r2 = 0.65-0.71), phosphorus fractions (r2 = 0.51-0.70), clarity and turbidity (r2 = 0.42-0.46), and E. coli (r2 = 0.35) over 15 years. The state and trend of water quality was strongly related to a refined farm scale land use classification, and to catchment and climatic characteristics (e.g. slope, elevation, and rainfall). Relationships with point scale soil quality measures and the land use pressures were weak. The weak relationship with land use pressures may be caused by using a single snapshot in time (2022), which cannot account for lag times in water quality response but leaves room for additional temporal data to improve predictive power. The weak relationship to soil quality measures was probably caused by limited data points (n = 667 sites) that were unrepresentative of land use, and areas of catchment subject to processes like runoff or leaching. While national soil quality measures might be useful for evaluating environmental risk at the field or farm scale, without a large increase in sampling, they were not relevant at the catchment scale. Additional analyses should be performed to determine how many samples would be needed to detect a change using an environmentally focused soil test that can guide water quality management.

Nanoparticle Concentration in Surgical Plume During Tonsillectomy: A Comparison of Four Techniques.

OBJECTIVE: Surgical plume has known potential occupational health hazards. This study compares nanoparticle concentrations in surgical plumes generated between different pediatric tonsillectomy surgical techniques and assesses the efficacy of mitigation measures. METHODS: This is a cross-sectional study performed at a tertiary care academic center. Extracapsular or intracapsular tonsillectomy was performed in 60 patients using four techniques and in 10 additional patients using mitigation measures. Two nanoparticle counters were used to measure particulate concentrations: CPC™ and DiSCmini™. Tonsillectomy techniques included: (1) microdebrider (MD), (2) Bovie with manual suctioning by an assistant (B), (3) Bovie with built-in smoke evacuation system (BS), and (4) Coblator™ (CB). An additional Yankauer suction was used in the mitigation groups (BSY) and (CBY). Comparative analysis was performed using one-way ANOVA on ranks and pairwise comparisons between the groups. RESULTS: The mean concentrations (particles/cm3) and coefficient of variants for the DiSCmini particulate counter were MD: 5140 (1.6), B: 30700 (1.5), BS: 25001 (0.8), CB: 54814 (1.7), CBY: 2395 (1.3) and BSY: 11552 (1.0). Mean concentrations for the CPC particulate counter were MD: 1223 (1.4), B: 3405 (0.7), BS: 5002 (0.9), CB: 13273 (1.0), CBY: 1048 (1.2) and BSY: 3046 (0.6). The lowest mean concentrations were noted in cases using MD and the highest in cases using CB. However, after mitigation, CBY had the lowest overall levels. CONCLUSION: Tonsillectomy technique does impact the levels of nanoparticles emitted within the surgical plume, which may present an occupational hazard for operating room personnel. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2444-2448, 2024.

Intraoperative Parathyroid Hormone Monitoring In Normohormonal Primary Hyperparathyroidism: How Low Do You Go?

OBJECTIVE: The primary goal of this study was to determine in patients with normohormonal primary hyperparathyroidism (NHHPT) what percent reduction in post-excision intraoperative parathyroid hormone (IOPTH) from baseline would yield a rate of cure comparable to that in patients with classical primary hyperparathyroidism (PHPT). METHODS: This is a retrospective cohort study of patients who underwent parathyroidectomy between July 2013 and February 2020. Demographic data, preoperative, intraoperative, and postoperative metrics were collected. Patients with NHHPT were compared to those with classical PHPT. Subgroup analyses were performed. RESULTS: Of the 496 patients included in the study, 66 (13.3%) were of the normohormonal variant based on preoperative intact parathyroid hormone (PTH) levels and 28 (5.6%) based on baseline IOPTH levels. The cure rates in the two normohormonal groups were not significantly different from their classical counterparts (98.4% and 100.0% vs. 97.1%, p = 1.000). The median percent decline in post-excision IOPTH from baseline that achieved cure in the normohormonal groups were 82.6% and 80.4% compared to their respective controls at 87.3%, p = 0.011 and p = 0.001. Although the rate of multiglandular disease was higher in one of the normohormonal variant groups, this difference was due to a higher rate of double adenomas, not four-gland hyperplasia. CONCLUSION: Patients with NHHPT undergoing parathyroidectomy can expect cure rates similar to that in patients with classical PHPT. The results of this study indicate that achieving an 80% drop or more in IOPTH levels predicts a high likelihood of cure. This is true irrespective of whether the patient is deemed normohormonal based on preoperative or intraoperative testing. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2480-2484, 2024.

Robustness of mitochondrial biogenesis and respiration explain aerobic glycolysis.

A long-standing observation is that in fast-growing cells, respiration rate declines with increasing growth rate and is compensated by an increase in fermentation, despite respiration being more efficient than fermentation. This apparent preference for fermentation even in the presence of oxygen is known as aerobic glycolysis, and occurs in bacteria, yeast, and cancer cells. Considerable work has focused on understanding the potential benefits that might justify this seemingly wasteful metabolic strategy, but its mechanistic basis remains unclear. Here we show that aerobic glycolysis results from the saturation of mitochondrial respiration and the decoupling of mitochondrial biogenesis from the production of other cellular components. Respiration rate is insensitive to acute perturbations of cellular energetic demands or nutrient supplies, and is explained simply by the amount of mitochondria per cell. Mitochondria accumulate at a nearly constant rate across different growth conditions, resulting in mitochondrial amount being largely determined by cell division time. In contrast, glucose uptake rate is not saturated, and is accurately predicted by the abundances and affinities of glucose transporters. Combining these models of glucose uptake and respiration provides a quantitative, mechanistic explanation for aerobic glycolysis. The robustness of specific respiration rate and mitochondrial biogenesis, paired with the flexibility of other bioenergetic and biosynthetic fluxes, may play a broad role in shaping eukaryotic cell metabolism.

Toward an understanding of agonist binding to human Orexin-1 and Orexin-2 receptors with G-protein-coupled receptor modeling and site-directed mutagenesis.

The class A G-protein-coupled receptors (GPCRs) Orexin-1 (OX1) and Orexin-2 (OX2) are located predominantly in the brain and are linked to a range of different physiological functions, including the control of feeding, energy metabolism, modulation of neuro-endocrine function, and regulation of the sleep-wake cycle. The natural agonists for OX1 and OX2 are two neuropeptides, Orexin-A and Orexin-B, which have activity at both receptors. Site-directed mutagenesis (SDM) has been reported on both the receptors and the peptides and has provided important insight into key features responsible for agonist activity. However, the structural interpretation of how these data are linked together is still lacking. In this work, we produced and used SDM data, homology modeling followed by MD simulation, and ensemble-flexible docking to generate binding poses of the Orexin peptides in the OX receptors to rationalize the SDM data. We also developed a protein pairwise similarity comparing method (ProS) and a GPCR-likeness assessment score (GLAS) to explore the structural data generated within a molecular dynamics simulation and to help distinguish between different GPCR substates. The results demonstrate how these newly developed methods of structural assessment for GPCRs can be used to provide a working model of neuropeptide-Orexin receptor interaction.

On the growth of locally interacting plants: differential equations for the dynamics of spatial moments.

Ecologists are faced with the challenge of how to scale up from the activities of individual plants and animals to the macroscopic dynamics of populations and communities. It is especially difficult to do this in communities of plants where the fate of individuals depends on their immediate neighbors rather than an average over a larger region. This has meant that algorithmic, agent-based models are typically used to understand their dynamics, although certain macroscopic models have been developed for neighbor-dependent, birth death processes. Here we present a macroscopic model that, for the first time, incorporates explicit, gradual, neighbor-dependent plant growth, as a third fundamental process of plant communities. The model is derived from a stochastic, agent-based model, and describes the dynamics of the first and second spatial moments of a multispecies, spatially structured plant community with neighbor-dependent growth, births, and deaths. A simple example shows that strong neighborhood space-filling during tree growth in an even-aged stand of Scots pine is well captured by the spatial-moment model. The space-filling has a spatial signature consistent with that observed in several field studies of forests. Small neighborhoods of interaction, nonuniform spacing of trees, and asymmetric competition all contribute to the buildup of a wide range of tree sizes with some large dominant individuals and many smaller ones.