Pattern and process: competition causes regular spacing of individuals within plant populations

1 We used simulated and experimental plant populations to analyse mortality-driven pattern formation under size-dependent competition. Larger plants had an advantage under size-asymmetric but not under symmetric competition. Initial patterns were random or clumped. 2 The simulations were individual-based and spatially explicit. Size-dependent competition was modelled with different rules to partition overlapping zones of influence. 3 The experiment used genotypes of Arabidopsis thaliana with different morphological plasticity and hence size-dependent competition. Compared with wild types, transgenic individuals over-expressed phytochrome A and had decreased plasticity because of disabled phytochrome-mediated shade avoidance. Therefore, competition among transgenics was more asymmetric compared with wild-types. 4 Density-dependent mortality under symmetric competition did not substantially change the initial spatial pattern. Conversely, simulations under asymmetric competition and experimental patterns of transgenic over-expressors showed patterns of survivors that deviated substantially from random mortality independent of initial patterns. 5 Small-scale initial patterns of wild types were regular rather than random or clumped. We hypothesize that this small-scale regularity may be explained by early shade avoidance of seedlings in their cotyledon stage. 6 Our experimental results support predictions from an individual-based simulation model and support the conclusion that regular spatial patterns of surviving individuals should be interpreted as evidence for strong, asymmetric competitive interactions and subsequent density-dependent mortality.

Multi-Environment Model Estimation for Motility Analysis of Caernorhabditis elegans

The nematode Caenorhabditis elegans is a well-known model organism used to investigate fundamental questions in biology. Motility assays of this small roundworm are designed to study the relationships between genes and behavior. Commonly, motility analysis is used to classify nematode movements and characterize them quantitatively. Over the past years, C. elegans' motility has been studied across a wide range of environments, including crawling on substrates, swimming in fluids, and locomoting through microfluidic substrates. However, each environment often requires customized image processing tools relying on heuristic parameter tuning. In the present study, we propose a novel Multi-Environment Model Estimation (MEME) framework for automated image segmentation that is versatile across various environments. The MEME platform is constructed around the concept of Mixture of Gaussian (MOG) models, where statistical models for both the background environment and the nematode appearance are explicitly learned and used to accurately segment a target nematode. Our method is designed to simplify the burden often imposed on users; here, only a single image which includes a nematode in its environment must be provided for model learning. In addition, our platform enables the extraction of nematode ‘skeletons’ for straightforward motility quantification. We test our algorithm on various locomotive environments and compare performances with an intensity-based thresholding method. Overall, MEME outperforms the threshold-based approach for the overwhelming majority of cases examined. Ultimately, MEME provides researchers with an attractive platform for C. elegans' segmentation and ‘skeletonizing’ across a wide range of motility assays.

Process and pattern in cichlid radiations - inferences for understanding unusually high rates of evolutionary diversification

The cichlid fish radiations in the African Great Lakes differ from all other known cases of rapid speciation in vertebrates by their spectacular trophic diversity and richness of sympatric species, comparable to the most rapid angiosperm radiations. I review factors that may have facilitated these radiations and compare these with insights from recent work on plant radiations. Work to date suggests that it was a coincidence of ecological opportunity, intrinsic ecological versatility and genomic flexibility, rapidly evolving behavioral mate choice and large amounts of standing genetic variation that permitted these spectacular fish radiations. I propose that spatially orthogonal gradients in the fit of phenotypes to the environment facilitate speciation because they allow colonization of alternative fitness peaks during clinal speciation despite local disruptive selection. Such gradients are manifold in lakes because of the interaction of water depth as an omnipresent third spatial dimension with other fitness-relevant variables. I introduce a conceptual model of adaptive radiation that integrates these elements and discuss its applicability to, and predictions for, plant radiations.

An improved simple rat model for global cerebral ischaemia by induced cardiac arrest

OBJECTIVES Cerebral hypoxic-ischaemic injury following cardiac arrest is a devastating disease affecting thousands of patients each year. There is a complex interaction between post-resuscitation injury after whole-body ischaemia-reperfusion and cerebral damage which cannot be explored in in vitro systems only; there is a need for animal models. In this study, we describe and evaluate the feasibility and efficiency of our simple rodent cardiac arrest model. METHODS Ten wistar rats were subjected to 9 and 10 minutes of cardiac arrest. Cardiac arrest was introduced with a mixture of the short-acting beta-blocking drug esmolol and potassium chloride. RESULTS All animals could be resuscitated within 1 minute, and survived until day 5.General health score and neurobehavioural testing indicated substantial impairment after cardiac arrest, without differences between groups. Histological examination of the hippocampus CA1 segment, the most vulnerable segment of the cerebrum, demonstrated extensive damage in the cresyl violet staining, as well as in the Fluoro-Jade B staining and in the Iba-1 staining, indicating recruitment of microglia after the hypoxic-ischaemic event. Again, there were no differences between the 9- and 10-minute cardiac arrest groups. DISCUSSION We were able to establish a simple and reproducible 9- and 10-minute rodent cardiac arrest models with a well-defined no-flow-time. Extensive damage can be found in the hippocampus CA1 segment. The lack of difference between 9- and 10-minute cardiac arrest time in the neuropsychological, the open field test and the histological evaluations is mainly due to the small sample size.

Untangling a Holocene pollen record with forest model simulations and independent climate data

Adaptation potential of forests to rapid climatic changes can be assessed from vegetation dynamics during past climatic changes as preserved in fossil pollen data. However, pollen data reflect the integrated effects of climate and biotic processes, such as establishment, survival, competition, and migration. To disentangle these processes, we compared an annually laminated late Würm and Holocene pollen record from the Central Swiss Plateau with simulations of a dynamic forest patch model. All input data used in the simulations were largely independent from pollen data; i.e. the presented analysis is non-circular. Temperature and precipitation scenarios were based on reconstructions from pollen-independent sources. The earliest arrival times of the species at the study site after the last glacial were inferred from pollen maps. We ran a series of simulations under different combinations of climate and immigration scenarios. In addition, the sensitivity of the simulated presence/absence of four major species to changes in the climate scenario was examined. The pattern of the pollen record could partly be explained by the used climate scenario, mostly by temperature. However, some features, in particular the absence of most species during the late Würm could only be simulated if the winter temperature anomalies of the used scenario were decreased considerably. Consequently, we had to assume in the simulations, that most species immigrated during or after the Younger Dryas (12 000 years BP), Abies and Fagus even later. Given the timing of tree species immigration, the vegetation was in equilibrium with climate during long periods, but responded with lags at the time-scale of centuries to millennia caused by a secondary succession after rapid climatic changes such as at the end of Younger Dryas, or immigration of dominant taxa. Climate influenced the tree taxa both directly and indirectly by changing inter-specific competition. We concluded, that also during the present fast climatic change, species migration might be an important process, particularly if geographic barriers, such as the Alps are in the migrational path.

Longitudinal extension of myelomalacia by intramedullary and subdural hemorrhage in a canine model of spinal cord injury

BACKGROUND CONTEXT In canine intervertebral disc (IVD) extrusion, a spontaneous animal model of spinal cord injury, hemorrhage is a consistent finding. In rodent models, hemorrhage might be involved in secondary tissue destruction by biochemical mechanisms. PURPOSE This study aimed to investigate a causal association between the extents of intramedullary, subdural and epidural hemorrhage and the severity of spinal cord damage following IVD extrusion in dogs. STUDY DESIGN/SETTING A retrospective study using histologic spinal cord sections from 83 dogs euthanized following IVD extrusion was carried out. METHODS The degree of hemorrhage (intramedullary, subdural, epidural), the degree of spinal cord damage in the epicenter (white and gray matter), and the longitudinal extent of myelomalacia were graded. Associations between the extent of hemorrhage and the degree of spinal cord damage were evaluated statistically. RESULTS Intramedullary and subdural hemorrhages were significantly associated with the degree of white (p<.001/ p=.004) and gray (both p<.001) matter damage, and with the longitudinal extension of myelomalacia (p<.001/p=.005). Intriguingly, accumulation of hemorrhagic cord debris inside or dorsal to a distended and ruptured central canal in segments distant to the epicenter of the lesion was observed exhibiting a wave-like pattern on longitudinal assessment. The occurrence of this debris accumulation was associated with high degrees of tissue destruction (all p<.001). CONCLUSIONS Tissue liquefaction and increased intramedullary pressure associated with hemorrhage are involved in the progression of spinal cord destruction in a canine model of spinal cord injury and ascending or descending myelomalacia. Functional and dynamic studies are needed to investigate this concept further.

Biochemical MRI predicts hip osteoarthritis in an experimental ovine femoroacetabular impingement model

BACKGROUND Cam-type femoroacetabular impingement (FAI) resulting from an abnormal nonspherical femoral head shape leads to chondrolabral damage and is considered a cause of early osteoarthritis. A previously developed experimental ovine FAI model induces a cam-type impingement that results in localized chondrolabral damage, replicating the patterns found in the human hip. Biochemical MRI modalities such as T2 and T2* may allow for evaluation of the cartilage biochemistry long before cartilage loss occurs and, for that reason, may be a worthwhile avenue of inquiry. QUESTIONS/PURPOSES We asked: (1) Does the histological grading of degenerated cartilage correlate with T2 or T2* values in this ovine FAI model? (2) How accurately can zones of degenerated cartilage be predicted with T2 or T2* MRI in this model? METHODS A cam-type FAI was induced in eight Swiss alpine sheep by performing a closing wedge intertrochanteric varus osteotomy. After ambulation of 10 to 14 weeks, the sheep were euthanized and a 3-T MRI of the hip was performed. T2 and T2* values were measured at six locations on the acetabulum and compared with the histological damage pattern using the Mankin score. This is an established histological scoring system to quantify cartilage degeneration. Both T2 and T2* values are determined by cartilage water content and its collagen fiber network. Of those, the T2* mapping is a more modern sequence with technical advantages (eg, shorter acquisition time). Correlation of the Mankin score and the T2 and T2* values, respectively, was evaluated using the Spearman's rank correlation coefficient. We used a hierarchical cluster analysis to calculate the positive and negative predictive values of T2 and T2* to predict advanced cartilage degeneration (Mankin ≥ 3). RESULTS We found a negative correlation between the Mankin score and both the T2 (p < 0.001, r = -0.79) and T2* values (p < 0.001, r = -0.90). For the T2 MRI technique, we found a positive predictive value of 100% (95% confidence interval [CI], 79%-100%) and a negative predictive value of 84% (95% CI, 67%-95%). For the T2* technique, we found a positive predictive value of 100% (95% CI, 79%-100%) and a negative predictive value of 94% (95% CI, 79%-99%). CONCLUSIONS T2 and T2* MRI modalities can reliably detect early cartilage degeneration in the experimental ovine FAI model. CLINICAL RELEVANCE T2 and T2* MRI modalities have the potential to allow for monitoring the natural course of osteoarthrosis noninvasively and to evaluate the results of surgical treatments targeted to joint preservation.

The use of electromyography interference pattern analysis to determine muscle force of the deep digital flexor muscle in healthy and laminitic horses

BACKGROUND: In equine laminitis, the deep digital flexor muscle (DDFM) appears to have increased muscle force, but evidence-based confirmation is lacking. OBJECTIVES: The purpose of this study was to test if the DDFM of laminitic equines has an increased muscle force detectable by needle electromyography interference pattern analysis (IPA). ANIMALS AND METHODS: The control group included six Royal Dutch Sport horses, three Shetland ponies and one Welsh pony [10 healthy, sound adults weighing 411 ± 217 kg (mean ± SD) and aged 10 ± 5 years]. The laminitic group included three Royal Dutch Sport horses, one Friesian, one Haflinger, one Icelandic horse, one Welsh pony, one miniature Appaloosa and six Shetland ponies (14 adults, weight 310 ± 178 kg, aged 13 ± 6 years) with acute/chronic laminitis. The electromyography IPA measurements included firing rate, turns/second (T), amplitude/turn (M) and M/T ratio. Statistical analysis used a general linear model with outcomes transformed to geometric means. RESULTS: The firing rate of the total laminitic group was higher than the total control group. This difference was smaller for the ponies compared to the horses; in the horses, the geometric mean difference of the laminitic group was 1.73 [geometric 95% confidence interval (CI) 1.29-2.32], and in the ponies this value was 1.09 (geometric 95% CI 0.82-1.45). CONCLUSION AND CLINICAL RELEVANCE: In human medicine, an increased firing rate is characteristic of increased muscle force. Thus, the increased firing rate of the DDFM in the context of laminitis suggests an elevated muscle force. However, this seems to be only a partial effect as in this study, the unchanged turns/second and amplitude/turn failed to prove the recruitment of larger motor units with larger amplitude motor unit potentials in laminitic equids.

Characterization of the Axial Jet Separator with a CO2/Helium Mixture: Toward GC-AMS Hyphenation

Development of interfaces for sample introduction from high pressures is important for real-time online hyphenation of chromatographic and other separation devices with mass spectrometry (MS) or accelerator mass spectrometry (AMS). Momentum separators can reduce unwanted low-density gases and introduce the analyte into the vacuum. In this work, the axial jet separator, a new momentum interface, is characterized by theory and empirical optimization. The mathematical model describes the different axial penetration of the components of a jetgas mixture and explains the empirical results for injections of CO2 in helium into MS and AMS instruments. We show that the performance of the new interface is sensitive to the nozzle size, showing good qualitative agreement with the mathematical model. Smaller nozzle sizes are more preferable due to their higher inflow capacity. The CO2 transmission efficiency of the interface into a MS instrument is ~14% (CO2/helium separation factor of 2.7). The interface receives and delivers flows of ~17.5 mL/min and ~0.9 mL/min, respectively. For the interfaced AMS instrument, the ionization and overall efficiencies are 0.7-3% and 0.1-0.4%, respectively, for CO2 amounts of 4-0.6 µg C, which is only slightly lower compared to conventional systems using intermediate trapping. The ionization efficiency depends on to the carbon mass flow in the injected pulse and is suppressed at high CO2 flows. Relative to a conventional jet separator, the transmission efficiency of the axial jet separator is lower, but its performance is less sensitive to misalignments.

In vivo TCR Signaling in CD4(+) T Cells Imprints a Cell-Intrinsic, Transient Low-Motility Pattern Independent of Chemokine Receptor Expression Levels, or Microtubular Network, Integrin, and Protein Kinase C Activity

Intravital imaging has revealed that T cells change their migratory behavior during physiological activation inside lymphoid tissue. Yet, it remains less well investigated how the intrinsic migratory capacity of activated T cells is regulated by chemokine receptor levels or other regulatory elements. Here, we used an adjuvant-driven inflammation model to examine how motility patterns corresponded with CCR7, CXCR4, and CXCR5 expression levels on ovalbumin-specific DO11.10 CD4(+) T cells in draining lymph nodes. We found that while CCR7 and CXCR4 surface levels remained essentially unaltered during the first 48-72 h after activation of CD4(+) T cells, their in vitro chemokinetic and directed migratory capacity to the respective ligands, CCL19, CCL21, and CXCL12, was substantially reduced during this time window. Activated T cells recovered from this temporary decrease in motility on day 6 post immunization, coinciding with increased migration to the CXCR5 ligand CXCL13. The transiently impaired CD4(+) T cell motility pattern correlated with increased LFA-1 expression and augmented phosphorylation of the microtubule regulator Stathmin on day 3 post immunization, yet neither microtubule destabilization nor integrin blocking could reverse TCR-imprinted unresponsiveness. Furthermore, protein kinase C (PKC) inhibition did not restore chemotactic activity, ruling out PKC-mediated receptor desensitization as mechanism for reduced migration in activated T cells. Thus, we identify a cell-intrinsic, chemokine receptor level-uncoupled decrease in motility in CD4(+) T cells shortly after activation, coinciding with clonal expansion. The transiently reduced ability to react to chemokinetic and chemotactic stimuli may contribute to the sequestering of activated CD4(+) T cells in reactive peripheral lymph nodes, allowing for integration of costimulatory signals required for full activation.

Tuberculosis in Cape Town: An age-structured transmission model.

BACKGROUND Tuberculosis (TB) is the leading cause of death in South Africa. The burden of disease varies by age, with peaks in TB notification rates in the HIV-negative population at ages 0-5, 20-24, and 45-49 years. There is little variation between age groups in the rates in the HIV-positive population. The drivers of this age pattern remain unknown. METHODS We developed an age-structured simulation model of Mycobacterium tuberculosis (Mtb) transmission in Cape Town, South Africa. We considered five states of TB progression: susceptible, infected (latent TB), active TB, treated TB, and treatment default. Latently infected individuals could be re-infected; a previous Mtb infection slowed progression to active disease. We further considered three states of HIV progression: HIV negative, HIV positive, on antiretroviral therapy. To parameterize the model, we analysed treatment outcomes from the Cape Town electronic TB register, social mixing patterns from a Cape Town community and used literature estimates for other parameters. To investigate the main drivers behind the age patterns, we conducted sensitivity analyses on all parameters related to the age structure. RESULTS The model replicated the age patterns in HIV-negative TB notification rates of Cape Town in 2009. Simulated TB notification rate in HIV-negative patients was 1000/100,000 person-years (pyrs) in children aged <5 years and decreased to 51/100,000 in children 5-15 years. The peak in early adulthood occurred at 25-29 years (463/100,000 pyrs). After a subsequent decline, simulated TB notification rates gradually increased from the age of 30 years. Sensitivity analyses showed that the dip after the early adult peak was due to the protective effect of latent TB and that retreatment TB was mainly responsible for the rise in TB notification rates from the age of 30 years. CONCLUSION The protective effect of a first latent infection on subsequent infections and the faster progression in previously treated patients are the key determinants of the age-structure of TB notification rates in Cape Town.

The Effects of Density, Spatial Pattern, and Competitive Symmetry on Size Variation in Simulated Plant Populations

Patterns of size inequality in crowded plant populations are often taken to be indicative of the degree of size asymmetry of competition, but recent research suggests that some of the patterns attributed to size‐asymmetric competition could be due to spatial structure. To investigate the theoretical relationships between plant density, spatial pattern, and competitive size asymmetry in determining size variation in crowded plant populations, we developed a spatially explicit, individual‐based plant competition model based on overlapping zones of influence. The zone of influence of each plant is modeled as a circle, growing in two dimensions, and is allometrically related to plant biomass. The area of the circle represents resources potentially available to the plant, and plants compete for resources in areas in which they overlap. The size asymmetry of competition is reflected in the rules for dividing up the overlapping areas. Theoretical plant populations were grown in random and in perfectly uniform spatial patterns at four densities under size‐asymmetric and size‐symmetric competition. Both spatial pattern and size asymmetry contributed to size variation, but their relative importance varied greatly over density and over time. Early in stand development, spatial pattern was more important than the symmetry of competition in determining the degree of size variation within the population, but after plants grew and competition intensified, the size asymmetry of competition became a much more important source of size variation. Size variability was slightly higher at higher densities when competition was symmetric and plants were distributed nonuniformly in space. In a uniform spatial pattern, size variation increased with density only when competition was size asymmetric. Our results suggest that when competition is size asymmetric and intense, it will be more important in generating size variation than is local variation in density. Our results and the available data are consistent with the hypothesis that high levels of size inequality commonly observed within crowded plant populations are largely due to size‐asymmetric competition, not to variation in local density.

Loss of Nogo-A-expressing neurons in a rat model of Parkinson's disease

The myelin-associated protein Nogo-A is among the most potent neurite growth inhibitors in the adult CNS. Recently, Nogo-A expression was demonstrated in a number of neuronal subpopulations of the adult and developing CNS but at present, little is known about the expression of Nogo-A in the nigrostriatal system, a brain structure severely affected in Parkinson's disease (PD). The present study sought to characterize the expression pattern of Nogo-A immunoreactive (ir) cells in the adult ventral mesencephalon of control rats and in the 6-hydroxydopamine (6-OHDA) rat model of PD. Immunohistochemical analyses of normal adult rat brain showed a distinct expression of Nogo-A in the ventral mesencephalon, with the highest level in the substantia nigra pars compacta (SNc) where it co-localized with dopaminergic neurons. Analyses conducted 1week and 1 month after unilateral striatal injections of 6-OHDA disclosed a severe loss of the number of Nogo-A-ir cells in the SNc. Notably, at 1week after treatment, more dopaminergic neurons expressing Nogo-A were affected by the 6-OHDA toxicity than Nogo-A-negative dopaminergic neurons. However, at later time points more of the surviving dopaminergic neurons expressed Nogo-A. In the striatum, both small and large Nogo-A-positive cells were detected. The large cells were identified as cholinergic interneurons. Our results suggest yet unidentified functions of Nogo-A in the CNS beyond the inhibition of axonal regeneration and plasticity, and may indicate a role for Nogo-A in PD.

A randomized trial of the effects of the noble gases helium and argon on neuroprotection in a rodent cardiac arrest model.

BACKGROUND The noble gas xenon is considered as a neuroprotective agent, but availability of the gas is limited. Studies on neuroprotection with the abundant noble gases helium and argon demonstrated mixed results, and data regarding neuroprotection after cardiac arrest are scant. We tested the hypothesis that administration of 50% helium or 50% argon for 24 h after resuscitation from cardiac arrest improves clinical and histological outcome in our 8 min rat cardiac arrest model. METHODS Forty animals had cardiac arrest induced with intravenous potassium/esmolol and were randomized to post-resuscitation ventilation with either helium/oxygen, argon/oxygen or air/oxygen for 24 h. Eight additional animals without cardiac arrest served as reference, these animals were not randomized and not included into the statistical analysis. Primary outcome was assessment of neuronal damage in histology of the region I of hippocampus proper (CA1) from those animals surviving until day 5. Secondary outcome was evaluation of neurobehavior by daily testing of a Neurodeficit Score (NDS), the Tape Removal Test (TRT), a simple vertical pole test (VPT) and the Open Field Test (OFT). Because of the non-parametric distribution of the data, the histological assessments were compared with the Kruskal-Wallis test. Treatment effect in repeated measured assessments was estimated with a linear regression with clustered robust standard errors (SE), where normality is less important. RESULTS Twenty-nine out of 40 rats survived until day 5 with significant initial deficits in neurobehavioral, but rapid improvement within all groups randomized to cardiac arrest. There were no statistical significant differences between groups neither in the histological nor in neurobehavioral assessment. CONCLUSIONS The replacement of air with either helium or argon in a 50:50 air/oxygen mixture for 24 h did not improve histological or clinical outcome in rats subjected to 8 min of cardiac arrest.

Respiratory rhythm generation: A modeling study of the respiratory central pattern generator and the phrenic motor neuron

The respiratory central pattern generator is a collection of medullary neurons that generates the rhythm of respiration. The respiratory central pattern generator feeds phrenic motor neurons, which, in turn, drive the main muscle of respiration, the diaphragm. The purpose of this thesis is to understand the neural control of respiration through mathematical models of the respiratory central pattern generator and phrenic motor neurons. ^ We first designed and validated a Hodgkin-Huxley type model that mimics the behavior of phrenic motor neurons under a wide range of electrical and pharmacological perturbations. This model was constrained physiological data from the literature. Next, we designed and validated a model of the respiratory central pattern generator by connecting four Hodgkin-Huxley type models of medullary respiratory neurons in a mutually inhibitory network. This network was in turn driven by a simple model of an endogenously bursting neuron, which acted as the pacemaker for the respiratory central pattern generator. Finally, the respiratory central pattern generator and phrenic motor neuron models were connected and their interactions studied. ^ Our study of the models has provided a number of insights into the behavior of the respiratory central pattern generator and phrenic motor neurons. These include the suggestion of a role for the T-type and N-type calcium channels during single spikes and repetitive firing in phrenic motor neurons, as well as a better understanding of network properties underlying respiratory rhythm generation. We also utilized an existing model of lung mechanics to study the interactions between the respiratory central pattern generator and ventilation. ^