Effects of Disturbance and Conspecific Negative Density Dependence on Forest Composition and Diversity: A Simulation-Based Approach

Forests provide a wide range of services to humans and create critical habitat for countless species. Tree species composition and diversity, key attributes of forest health and identity, are influenced by both disturbance and conspecific negative density dependence (CNDD). These factors have been thoroughly researched in isolation, but much less is known about how they interact. We present results of a simulation model constructed to investigate the interactions of variable CNDD strengths and disturbance types. We found that while CNDD consistently increased diversity, the magnitude of this effect was heavily influenced by the disturbance regime. The difference between weak and strong CNDD was most pronounced with understory disturbance, and the greatest diversity overall was achieved when strong CNDD was paired with understory disturbance. Empirical studies of CNDD have yielded widely divergent results. Our study suggests a comprehensive understanding of forest ecosystems may require simultaneous consideration of both disturbance and CNDD

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways

UNLABELLED Patients with H3K27M-mutant diffuse midline glioma (DMG) have no proven effective therapies. ONC201 has recently demonstrated efficacy in these patients, but the mechanism behind this finding remains unknown. We assessed clinical outcomes, tumor sequencing, and tissue/cerebrospinal fluid (CSF) correlate samples from patients treated in two completed multisite clinical studies. Patients treated with ONC201 following initial radiation but prior to recurrence demonstrated a median overall survival of 21.7 months, whereas those treated after recurrence had a median overall survival of 9.3 months. Radiographic response was associated with increased expression of key tricarboxylic acid cycle-related genes in baseline tumor sequencing. ONC201 treatment increased 2-hydroxyglutarate levels in cultured H3K27M-DMG cells and patient CSF samples. This corresponded with increases in repressive H3K27me3 in vitro and in human tumors accompanied by epigenetic downregulation of cell cycle regulation and neuroglial differentiation genes. Overall, ONC201 demonstrates efficacy in H3K27M-DMG by disrupting integrated metabolic and epigenetic pathways and reversing pathognomonic H3K27me3 reduction. SIGNIFICANCE The clinical, radiographic, and molecular analyses included in this study demonstrate the efficacy of ONC201 in H3K27M-mutant DMG and support ONC201 as the first monotherapy to improve outcomes in H3K27M-mutant DMG beyond radiation. Mechanistically, ONC201 disrupts integrated metabolic and epigenetic pathways and reverses pathognomonic H3K27me3 reduction. This article is featured in Selected Articles from This Issue, p. 2293

Structure of a double ubiquitin-like domain in the talin head: a role in integrin activation

Talin is a 270-kDa protein that activates integrins and couples them to cytoskeletal actin. Talin contains an N-terminal FERM domain comprised of F1, F2 and F3 domains, but it is atypical in that F1 contains a large insert and is preceded by an extra domain F0. Although F3 contains the binding site for β-integrin tails, F0 and F1 are also required for activation of β1-integrins. Here, we report the solution structures of F0, F1 and of the F0F1 double domain. Both F0 and F1 have ubiquitin-like folds joined in a novel fixed orientation by an extensive charged interface. The F1 insert forms a loop with helical propensity, and basic residues predicted to reside on one surface of the helix are required for binding to acidic phospholipids and for talin-mediated activation of β1-integrins. This and the fact that basic residues on F2 and F3 are also essential for integrin activation suggest that extensive interactions between the talin FERM domain and acidic membrane phospholipids are required to orientate the FERM domain such that it can activate integrins

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Role of biomechanics in the understanding of normal, injured, and healing ligaments and tendons

Ligaments and tendons are soft connective tissues which serve essential roles for biomechanical function of the musculoskeletal system by stabilizing and guiding the motion of diarthrodial joints. Nevertheless, these tissues are frequently injured due to repetition and overuse as well as quick cutting motions that involve acceleration and deceleration. These injuries often upset this balance between mobility and stability of the joint which causes damage to other soft tissues manifested as pain and other morbidity, such as osteoarthritis

Silviculture in an uncertain world: utilizing multi-aged management systems to integrate disturbance†

Forest management faces an uncertain future with changing climates and disturbance regimes. Multi-aged forest management systems represent a promising approach for increasing resistance and resilience, thereby limiting major disruptions to timber production and other ecosystem services. Multi-aged stands inherently have greater resistance and resilience to disturbances because of the presence of several age classes and more potential pathways for post-disturbance management and recovery. The preponderance of research also indicates few differences in productivity between multi-aged and even-aged management strategies. These factors combined suggest that increased adoption of multi-aged management systems will lead to a reduction in long-term risks. We advocate a disturbance integration management strategy that encourages managers to emulate disturbance effects with management, anticipate disturbances in planning, integrate the management of residual stand structures into salvage operations and build variable treatment intervals or cutting cycles into management regimes

Conspecific negative density dependence in American beech

Abstract Background One of the most important drivers of forest biodiversity is conspecific negative density dependence (CNDD), a reduction in performance when conspecific densities are high. While the majority of CNDD research has focused on tropical forests, evidence is mounting that CNDD may also play an important role in temperate forests. To further explore the potential reach of this phenomenon, we investigated CNDD in American beech (Fagus grandifolia) in a mature mid-Atlantic forest. Methods We used bivariate point pattern analyses to examine spatial relationships between large beech trees and conspecific saplings, and we also contrasted these patterns with comparable patterns for heterospecifics. In addition, to address the possibility of dispersal limitation and the associated effects on spatial patterns, we analyzed seedling density as a function of adult conspecific abundance. Results We found that beech saplings were more repelled from large conspecifics than large heterospecifics, despite the fact that beech seedling density was positively correlated with beech basal area. However, saplings of other canopy tree species were also repelled from adult beech trees, suggesting a general suppressive effect. Nonetheless, the discrepancy between beech seedling and sapling densities beneath adult conspecifics suggests that beech seedling survival rates were reduced in vicinity of conspecific adults. Conclusions Regardless of the extent to which beech inhibits heterospecific trees, a negative effect on conspecific recruits may be critical for biodiversity maintenance. Without this conspecific suppression, a dense layer of shade-tolerant beech saplings could form beneath adult beech trees. If this were to occur, beech would have a substantial head-start following canopy disturbance, and this late-successional species could potentially dominate a stand in perpetuity, through repeated disturbance cycles

Effects of drought, disturbance, and biotic neighborhood on experimental tree seedling performance

Abstract Forest biodiversity is likely maintained by a complex suite of interacting drivers that vary in importance across both space and time. Contributing factors include disturbance, interannual variation in abiotic variables, and biotic neighborhood effects. To probe ongoing uncertainties and potential interactions, we investigated tree seedling performance in a temperate mid‐Atlantic forest ecosystem. We planted seedlings of five native tree species in mapped study plots, half of which were subjected to disturbance, and then monitored seedling survival, height growth, and foliar condition. The final year of data collection encompassed a drought, enabling comparison between intervals varying in water availability. Seedling performance was analyzed as a function of canopy cover and biotic neighborhood (conspecific and heterospecific abundance), including interactions, with separate generalized linear mixed models fit for each interval. All species exhibited: (a) pronounced declines in height growth during the drought year, (b) detrimental effects of adult conspecifics, and (c) beneficial effects of canopy openness. However, despite these consistencies, there was considerable variation across species in terms of the relevant predictors for each response variable in each interval. Our results suggest that drought may strengthen or reveal conspecific inhibition in some instances while weakening it or obscuring it in others, and that some forms of conspecific inhibition may manifest only under particular canopy conditions (although given the inconsistency of our findings, we are not convinced that conspecific inhibition is critical for diversity maintenance in our study system). Overall, our work reveals a complex forest ecosystem that appears simultaneously and interactively governed by biotic neighborhood structure (e.g., conspecific and/or heterospecific abundance), local habitat conditions (e.g., canopy cover), and interannual variability (e.g., drought)