Differences In Growth Dynamics Research Articles

Cell population growth kinetics in the presence of stochastic heterogeneity of cell phenotype

Recent studies at individual cell resolution have revealed phenotypic heterogeneity in nominally clonal tumor cell populations. The heterogeneity affects cell growth behaviors, which can result in departure from the idealized uniform exponential growth of the cell population. Here we measured the stochastic time courses of growth of an ensemble of populations of HL60 leukemia cells in cultures, starting with distinct initial cell numbers to capture a departure from the uniform exponential growth model for the initial growth (“take-off”). Despite being derived from the same cell clone, we observed significant variations in the early growth patterns of individual cultures with statistically significant differences in growth dynamics, which could be explained by the presence of inter-converting subpopulations with different growth rates, and which could last for many generations. Based on the hypothesis of existence of multiple subpopulations, we developed a branching process model that was consistent with the experimental observations.

Progression Dynamics of Early versus Later Stage Atrophic Lesions in Nonneovascular Age-Related Macular Degeneration Using Quantitative OCT Biomarker Segmentation

To investigate the progression of geographic atrophy (GA) secondary to non-neovascular age-related macular degeneration (AMD) in early and later stage lesions using AI-based precision tools. Retrospective analysis of an observational cohort study. Seventy-four eyes of forty-nine patients with at least one complete retinal pigment epithelial and outer retinal atrophy (cRORA) lesion secondary to AMD were included. Patients were divided between recently developed cRORA and lesions with advanced disease status. Patients were prospectively imaged by spectral domain optical coherence tomography (SD-OCT) volume scans. The study period encompassed 18 months with scheduled visits every 6 months. Growth rates of recently to cRORA converted lesions were compared with lesions in an advanced disease status using mixed effect models. The progression of retinal pigment epithelial loss (RPEL) was considered the primary endpoint. Secondary endpoints consisted of external limiting membrane disruption (ELMD) and ellipsoid zone loss (EZL). These pathognomonic imaging biomarkers were quantified using validated deep learning algorithms. Further the EZ/RPE-Loss ratio was analysed in both study cohorts. Mean [95%CI] square root progression of recently converted lesions was 79.676[-77.140 - 236.493], 68.219[-101.210 - 237.648) and 84.825[-124.816 - 294.467] mm/half year for RPEL, ELML and EZL respectively. Mean square root progression of advanced lesions was 131.737[-22.574 - 286.047], 129.964[-36.666 - 296.594] and 116.837[-90.556 - 324.301] mm/half year for RPEL, ELML and EZL respectively. RPEL (p=0.038) and ELMD (p=0.026) progression showed significant differences between the two study cohorts. Further recent converters had significantly (p<0.001) higher EZ/RPE-Loss ratios in all time points compared to patients in an advanced disease status (1.716 [1.135 - 2.296] versus 1.153 [0.576 - 1.729]). Early cRORA lesions have a slower growth rate in comparison to atrophic lesions in advanced disease stages. Differences in growth dynamics may play a crucial role in understanding the pathophysiology of non-neovascular AMD and for the interpretation of clinical trials in GA. Individual disease monitoring using AI-based quantification paves the way towards optimized GA management.

Growing faster, longer or both? Modelling plastic response of Juniperus communis growth phenology to climate change

AbstractAimPlant growth and phenology respond plastically to changing climatic conditions in both space and time. Species‐specific levels of growth plasticity determine biogeographical patterns and the adaptive capacity of species to climate change. However, a direct assessment of spatial and temporal variability in radial growth dynamics is complicated, because long records of cambial phenology do not exist.LocationSixteen sites across European distribution margins of Juniperus communis L. (the Mediterranean, the Arctic, the Alps and the Urals).Time period1940–2016.Major taxa studiedJuniperus communis.MethodsWe applied the Vaganov–Shashkin process‐based model of wood formation to estimate trends in growing season duration and growth kinetics since 1940. We assumed that J. communis would exhibit spatially and temporally variable growth patterns reflecting local climatic conditions.ResultsOur simulations indicate regional differences in growth dynamics and plastic responses to climate warming. The mean growing season duration is the longest at Mediterranean sites and, recently, there has been a significant trend towards its extension of up to 0.44 days/year. However, this stimulating effect of a longer growing season is counteracted by declining summer growth rates caused by amplified drought stress. Consequently, overall trends in simulated ring widths are marginal in the Mediterranean. In contrast, durations of growing seasons in the Arctic show lower and mostly non‐significant trends. However, spring and summer growth rates follow increasing temperatures, leading to a growth increase of up to 0.32 %/year.Main conclusionsThis study highlights the plasticity in growth phenology of widely distributed shrubs to climate warming: an earlier onset of cambial activity that offsets the negative effects of summer droughts in the Mediterranean and, conversely, an intensification of growth rates during the short growing seasons in the Arctic. Such plastic growth responsiveness allows woody plants to adapt to the local pace of climate change.

P–332 Endometrium thickness is increased in gonadotropin stimulated IVF compared to unstimulated cycles, but this increase does not have a positive effect on pregnancy rate

Abstract Study question Is endometrial growth and endometrial thickness different in controlled ovarian stimulation (COS)-IVF compared to unstimulated cycles and does this have an effect on pregnancy rates? Summary answer Endometrial growth dynamic is different and endometrium is thicker in COS-IVF but this does not have a positive effect on pregnancy and live birth rates. What is known already Endometrial growth and endometrial thickness are a function of duration and concentration of estradiol (E2) stimulation. Endometrial thickness &amp;lt;8mm is related with lower pregnancy rates in IVF treatments. It is commonly assumed that an increase of endometrial thickness by increasing estrogen stimulation could have a positive effect on pregnancy rate. However, such a relationship has never been systematically analysed. Natural Cycle IVF (NC-IVF) is an ideal model to analyse the effect of high dose gonadotropin stimulation on several parameters such as thickness of endometrium and pregnancy rate. Study design, size, duration Retrospective single center, University based study including 235 COS-IVF and 616 NC-IVF cycles from 2015 to 2019. Polyfollicular COS-IVF cycles were only analysed until 09 2017 as embryo selection was introduced in Switzerland afterwards. Limiting the analysis to cycles without embryo selection enabled us to compare embryos derived from cIVF and NC-IVF. 1550 endometrial and 1068 E2 measurements were included in the analysis. Participants/materials, setting, methods Mean female age at the time when the cycles were performed was in NC-IVF 35.8±3.9y and in COS-IVF 34.9±4.2y (maximum 42y). Each woman performed on average 1.96±1.45 IVF cycles. Endometrial thickness and E2 serum concentrations were evaluated daily between day –4 and –2 (0=day of aspiration). Pregnancy and live birth rate were evaluated per transferred embryo. Statistically, student test and a repeated measure model and a logistic regression model both adjusted for age were used. Main results and the role of chance Endometrial thickness was different in COS-IVF and NC-IVF. At each time point endometrial thickness was found to be higher in COS-IVF compared to NC-IVF (p &amp;lt; 0.001 on days –4,–3, and –2). On day –2, the day when ovulation was triggered, mean endometrial thickness was 9.75 ±2.05mm in COS-IVF and 8.12 ±1.66mm in NC-IVF. Endometrial growth dynamic was also different in COS-IVF and NC-IVF. Endometrial thickness increased significantly faster in NC-IVF cycles (0.58mm/day [0.43,0.73]) than in cIVF cycles (0.22mm/day [–0.12, 0.55], Pval= 0.034). The increase of endometrial thickness per day was less pronounced if E2 concentrations were high (–0.19 [–0.34, 0.05]). Therefore it can be assumed that the observed differences in growth dynamics in both treatments are caused by differences in E2. Increased endometrial thickness in COS-IVF was not associated with higher success rate. There was no significant effect of endometrium thickness on pregnancy (Pval=0.318) and Live birth rate (Pval=0.461). Limitations, reasons for caution Pregnancy and live birth rates might be affected by more than just endometrial thickness. The study was only based on the thickness of the endometrium but not on its ultrasound pattern. Wider implications of the findings: Postponing the aspiration to allow endometrium to further proliferate has only a limited effect in COS-IVF. Increasing gonadotropin stimulation dosage just to increase endometrial thickness is not a feasible strategy to improve pregnancy rate. The need to apply high dosages of estrogen supplementation in thawing cycles need to be questioned. Trial registration number “not applicable”

Biological Effects of a Low-Frequency Electromagnetic Field on Yeast Cells of the Genus Saccharomyces Cerevisiae

Abstract Background: Although the scientific community is extensively concerned with the effects of the EMF, the unambiguous explanation of its effects on living structures is still lacking. Goals: The goal of the study was to evaluate the effect of a low-frequency (LF) electromagnetic field (EMF) on the growth and multiplication of the yeast Saccharomyces cerevisiae. Methods: Yeast cells were exposed to a frequency of 900 Hz and a magnetic flux density of 2.3 mT. The duration of each experiment was 8 hours, in the beginning of the measurement the value of frequency, rms (root mean square) value of electric current (2 A), and magnetic flux density were fixed set on the exposure device. A paired experiment was performed, a sample exposed to EMF, and a sample shielded from the field. Subsequently, samples were taken every two hours, the number of cells was recorded, and then the concentration of the yeast cells was evaluated at time points. The time points reflected the exposure time of the samples exposed to EMF. Results: The results indicate that LF EMF at given parameters has an inhibitory effect on the growth and multiplication of yeast cells. Conclusion: Exposure to EMF can cause the differences in growth dynamics between cells exposed to the field and the unexposed ones.

Clinical and immunological characteristics of sarcomas patients with clonogenic tumors

Tumorigenesis is related to the generation of heterogeneous tumor cell population, which is the result of genetic and epigenetic alterations followed by clonal selections and subsequent expansion. In basic studies genetic, histological and morphological diversity of different clones within a patient's neoplasm and specifics of their interrelation with patient's immune system are investigated mostly on the models of tumors of epithelial origin. Mesenchymal tumors such as soft tissue and bone-derived sarcomas (STBS) have been poorly studied in this regard. The molecular genetic methods used to examine intratumoral heterogeneity do not currently provide insight into which portion of the identified subclones are able to grow autonomously. Limiting dilution cloning demonstrates the existence of self-regulating tumor cells in the population and can serve as an independent prognostic predictor of poor prognosis.Intratumoral heterogeneity results not only in differences in growth dynamics, gene expression, and phenotypic markers, but also in the resistance to treatment, especially immunotherapy, thus causing tumor eluding immune escape. The changes that accompany this process can be affected by the cellular immune system, resulting in an imbalance between populations. The variations in the population composition of immune system cells are now widely debated as a predictor of response to immunotherapy, which is of obvious interest for sarcomas, where the effectiveness of chemotherapy is low and the prognosis is unfavorable, especially in case of metastatic disease development. The search for new predictive markers of disease prognosis and treatment efficacy is an important task, to which this study is focused. Our results demonstrate that clonogenic tumor characteristics such as clonogenic potential is independent predictor of unfavorable prognosis in cases of cancer and correlate with the clinical characteristics of the tumor such as overall survival (OS) and progression free survival (PFS). It was found that patients with clonogenic sarcomas had a lower content of activated cytotoxic T-lymphocytes (CTL) with the CD3+CD8+HLA-DR+ phenotype and an increased number of natural NK killers (p < 0.05) compared to nonclonogenic tumors. In addition, according to our data, a high neutrophil to lymphocyte ratio (NLR), a low value of major T-lymphocyte populations, and a higher number of natural killer cells (NK) in the blood can be negative prognostic factors for the immunotherapy of this disease.

A Simple Label-Free Method Reveals Bacterial Growth Dynamics and Antibiotic Action in Real-Time

Background: Understanding the response of bacteria to environmental stress is hampered by the relative insensitivity of methods to detect growth. This means studies of antibiotic resistance and other physiological methods often exceed 24 hours. Methods: We developed a scattered light and detection system (SLIC) to address this challenge, establishing the LoD (LoD), and the time to growth detection of small inocula. We compared the light-scattering of bacteria grown in different nutrient conditions and the growth dynamics of two closely related organisms. Scattering data was modelled using Gompertz and Broken Stick equations. Bacteria were also exposed to meropenem, gentamicin, and cefoxitin at various concentrations and light-scattering was captured in real-time. Findings: We established the LoD for SLIC to be between 10-100 cfu mL-1 in a volume of 1-2mL. Quantitative measurements of the different nutrient effects on bacteria were obtained in less than four hours and it was possible to rapidly distinguish differences in growth dynamics of Klebsiella pneumoniae strains with and without the BlaKPC gene. There was a dose-dependent difference in the speed of action of each antibiotic tested at supra-MIC concentrations. The lethal effect of gentamicin, lytic effect of meropenem, and the slow bactericidal effect of cefoxitin were demonstrated in real-time. Significantly, strains that were sensitive to antibiotics could be identified in seconds. Interpretation: This research demonstrates the critical importance of improving the sensitivity of bacterial detection. The ability to rapidly assess susceptibility and to capture a wealth of data on bacterial growth dynamics is presented. The rapid bactericidal effect at supra-MIC concentrations is an important finding that needs to be incorporated into pharmacokinetic and pharmacodynamic models. Importantly, enhanced sensitivity of bacterial detection opens the possibility of susceptibility results being reportable clinically in a few minutes. Funding Information: Scottish Enterprise, NESTA Longitude Prize, and the University of St Andrews Declaration of Interests: None to declare.

Systems biology analysis of the Clostridioides difficile core-genome contextualizes microenvironmental evolutionary pressures leading to genotypic and phenotypic divergence

Hospital acquired Clostridioides (Clostridium) difficile infection is exacerbated by the continued evolution of C. difficile strains, a phenomenon studied by multiple laboratories using stock cultures specific to each laboratory. Intralaboratory evolution of strains contributes to interlaboratory variation in experimental results adding to the challenges of scientific rigor and reproducibility. To explore how microevolution of C. difficile within laboratories influences the metabolic capacity of an organism, three different laboratory stock isolates of the C. difficile 630 reference strain were whole-genome sequenced and profiled in over 180 nutrient environments using phenotypic microarrays. The results identified differences in growth dynamics for 32 carbon sources including trehalose, fructose, and mannose. An updated genome-scale model for C. difficile 630 was constructed and used to contextualize the 28 unique mutations observed between the stock cultures. The integration of phenotypic screens with model predictions identified pathways enabling catabolism of ethanolamine, salicin, arbutin, and N-acetyl-galactosamine that differentiated individual C. difficile 630 laboratory isolates. The reconstruction was used as a framework to analyze the core-genome of 415 publicly available C. difficile genomes and identify areas of metabolism prone to evolution within the species. Genes encoding enzymes and transporters involved in starch metabolism and iron acquisition were more variable while C. difficile distinct metabolic functions like Stickland fermentation were more consistent. A substitution in the trehalose PTS system was identified with potential implications in strain virulence. Thus, pairing genome-scale models with large-scale physiological and genomic data enables a mechanistic framework for studying the evolution of pathogens within microenvironments and will lead to predictive modeling to combat pathogen emergence.

Experimental immunization of mice with a recombinant bovine enterovirus vaccine expressing BVDV E0 protein elicits a long-lasting serologic response

BackgroundBovine viral diarrhea virus (BVDV) is a cause of substantial economic loss to the cattle industry worldwide, and there are currently no effective treatment or preventive measures. Bovine enterovirus (BEV) has a broad host range with low virulence and is a good candidate as a viral vaccine vector. In this study, we explored new insertion sites for the expression of exogenous genes in BEV, and developed a recombinant infectious cDNA clone for BEV BJ101 strain expressing BVDV E0 protein.MethodsA recognition site for the viral proteinase 3Cpro was inserted in the GpBSK-BEV plasmid at the 2C/3A junction by overlapping PCR. Subsequently, the optimized full-length BVDV E0 gene was inserted to obtain the recombinant infectious plasmid GpBSK-BEV-E0. The rescued recombinant virus was obtained by transfection with linearized plasmid. Expression of BVDV E0 in the recombinant virus was confirmed by PCR, western blotting, and immunofluorescence analysis, and the genetic stability was tested in MDBK cells over 10 passages. We further tested the ability of the recombinant virus to induce an antibody response in mice infected with BVDV and immunized them with the recombinant virus and parental strain.ResultsThe rescued recombinant virus rBEV-E0 was identified and confirmed by western blot and indirect immunofluorescence. The sequencing results showed that the recombinant virus remained stable for 10 passages without genetic changes. There was also no significant difference in growth dynamics and plaque morphology between the recombinant virus and parental virus. Mice infected with both recombinant and parental viruses produced antibodies against BEV VP1, while the recombinant virus also induced antibodies against BVDV E0.ConclusionA new insertion site in the BEV vector can be used for the prevention and control of both BEV and BVDV, providing a useful tool for future research on the development of viral vector vaccines.

Secular Changes in the Morphotype of the Modern Human (Based on Anthropometric Data from a Retrospective Survey of Moscow Youth)

Trends in body size in young men and women in the early 21st century were analyzed based on the results of anthropometric examination of more than 6300 undergraduate students of various departments of Moscow State University that were obtained in 2000–2018. The retrospective analysis was conducted by comparing data of total body dimensions collected based on a sample of Moscow youth examined in different years since the 1920s. The observations of 17–18-year-old young men and women demonstrated an increase in height during the last 80 years until the beginning of the 21st century in Moscow. This parameter was noted to be relatively stable in both sexes since the beginning of 2000s until present. Against the background of the secular increase in body weight, which continues at present, some sex differences in growth dynamics of this index were observed. From the microevolutionary prospect, the noted tendencies could be explained as a result of changing lifestyle in modern human populations. Along with secular changes in body size, both sexes were observed to have concomitant changes of head and face dimensions, which were probably related to debrachycephalization (decrease in cephalic index) and a tendency toward leptoprosopia (increase in facial index). The observed patterns of secular (cross-generational) changes in morphological characteristic of modern youth can reflect socio-economic processes occurring in society and could be of great importance for fundamental studies in biology and sociology as well as for preventive medicine.

Loblolly pine outperforms slash pine in the southeastern United States – A long-term experimental comparison study

Loblolly pine (Pinus taeda L.) and slash pine (Pinus elliottii Engelm.) are the two most important commercial timber species in the southeastern U.S. A long-term experimental comparison study, in which loblolly and slash pine plots were paired for combinations of planting density (741, 2224, 3706 trees ha−1) and cultural intensity (operational versus intensive), was established in the lower Coastal Plain to investigate species differences in growth dynamics. Using age 2–21-year inventory plot data and destructive biomass/nutrient sampling data, species comparisons were conducted comprehensively, and the reasons of the species differences and management implications were discussed. When compared to slash pine, loblolly pine had higher stand basal area carrying capacity and maximum stand density index, lower fusiform rust infection rate and less wind damage, leading to its lower mortality. With no species difference in average DBH, loblolly pine consistently had greater average height and live crown length and higher level of tree size inequality. Loblolly pine had lower foliar biomass and lower foliar density, and higher crown length/width ratios due primarily to its longer crowns, suggesting perhaps a slightly greater shade tolerance or less dense canopy. As a result, loblolly pine outperformed slash pine in terms of stand basal area, total volume, aboveground biomass and carbon accumulation. Loblolly pine consistently accumulated more potassium, and this species difference increased with increasing stand age; while slash pine had slightly higher nitrogen and phosphorus contents before age 12. Species differences in mortality patterns and in nutrient accumulations in aboveground biomass emphasized the need to develop species-specific management strategies including different thinning and fertilization regimes.

The Role of Sexual Dimorphism and Tissue Selection in Ecotoxicological Studies Using the Riparian Spider Tetragnatha elongata.

Tetragnathid spiders (Tetragnatha spp.) found in riparian habitats have recently been used as bioindicators of sediment contamination and insect-mediated contaminant flux. We investigated whether sexual dimorphism (size and behavior) influenced the female:male ratio in composite samples, stable isotope ratios (carbon [δ13C], nitrogen [δ15N]), and Hg concentrations in the southern United States. Additionally, we explored whether biomass for contaminant analysis could be preserved by using the legs of tetragnathids as a surrogate for whole-body δ13C and δ15N signatures. We found that female tetragnathids were significantly larger than male spiders and represented a larger proportion of spiders collected at all sites. However, despite the difference in size between sexes, no differences in growth dynamics, isotopic signatures (δ13C and δ15N), or mercury concentrations were observed. It was determined that the leg of a tetragnathid can accurately represent the stable isotope signature of an entire spider.

Temporal niche differentiation among species changes with habitat productivity and light conditions

AbstractAimNiche differentiation along the temporal axis has often been suggested as a potential mechanism of species coexistence. Species may co‐occur by shifting timing of growth, or by changing their growth rate to avoid competition for resources, namely light. However, due to the lack of data on growth phenology of a large set of species, we do not know how common each phenomenon is and whether the phenology of coexisting species shows a non‐random distribution, which would be indicative of either niche differentiation or resource competition.LocationCzech Republic.MethodsWe recorded growth phenological data of 381 perennial herbaceous species in plant collections in the Botanical Garden of Charles University in Prague, allowing frequent recordings on a large number of species that grow in conditions close to their natural habitats. We used the measurements to derive the day of peak growth and two types of growth rates. We then used co‐occurrence data of these species from the Czech National Phytosociological Database and examined whether co‐occurring species show non‐random patterns of these parameters in 11 individual habitats, which were identified by the European Nature Information System.ResultsWe found large differences among habitat types, partly due to differences in habitat productivity, indicated by the mean height and summed cover of all species in the habitats. Unexpectedly, we did not find temporal niche differentiation in woodlands, indicating the day of peak growth of species was essentially random. Growth rates in forests were strongly over‐dispersed. This pattern contrasted with grasslands where the distribution of all parameters showed synchronization, which is likely because plants need to succeed in asymmetric competition for light.ConclusionThese data provide the first quantitative assessment of differences in growth dynamics across communities and show one of the first unequivocal demonstrations of trait overdispersion in plant communities.

A Comparison of Growth on Mercuric Chloride for Three Lemnaceae Species Reveals Differences in Growth Dynamics That Effect Their Suitability for Use in Either Monitoring or Remediating Ecosystems Contaminated With Mercury

Mercury (Hg) is a toxic heavy metal that can alter the ecological balance when it contaminates aquatic ecosystems. Previously, researchers have used various Lemnaceae species either to monitor and/or remove heavy metals from freshwater systems. As Hg contamination is a pressing issue for aquatic systems worldwide, we assessed its impact on the growth of three commonly species of Lemnaceae- Lemna gibba 6745, Lemna minor 6580 and Spirodela polyrhiza 5543. We exposed plants to different concentrations of mercuric chloride (HgCl2) and monitored their growth, including relative growth rate, frond number (FN), and fresh weight (FW). These data were coupled with measurements of starch content, levels of photosynthetic pigment and the activities of antioxidant substances. The growth of all three lines showed significant negative correlations with Hg concentrations, and starch content, photosynthetic pigment, soluble protein and antioxidant enzymes levels were all clearly affected. Our results indicate that the L. gibba line used in this study was the most suitable of the three for biomonitoring of water contaminated with Hg. Accumulation of Hg was highest in the S. polyrhiza line with a bioconcentration factor over 1,000, making this line the most suitable of the three tested for use in an Hg bioremediation system.

(Invited) Experimental Synthesis of 2D Borophene

The recent experimental discovery of borophene, the metallic 2-dimensional allotrope of boron, has sparked tremendous interest in further exploration of this unique material. The initial synthesis of borophene was accomplished on Ag substrates and serves as a quintessential example of predictive modeling to experimental realization. In this talk, we expand the phase-space of borophene synthesis to Au. Borophene synthesis was accomplished by evaporating elemental boron onto a Au(111) substrate. The synthesized borophene retains its metallic character on Au as verified with scanning tunneling spectroscopy. Most fascinating is the difference in growth dynamics on the Au(111) substrate where the reconstructed surface presents a unique energy landscape for borophene nucleation and growth. We find that the initial low-coverage growth of borophene modifies the herringbone reconstruction into a “trigonal” network, where the 2D boron islands are uniformly templated across the surface. Increasing coverage results in the increasing size of the templated borophene islands until they coalesce into larger sheets. The observed growth dynamics are supported by the computational modeling of boron nucleation on Au.

A comparison of growth patterns between non‐indigenous Halophila nipponica and the native sympatric Zostera marina on the southern coast of the Korean peninsula

AbstractThe growth dynamics of two co‐occurring seagrass species, Zostera marina and Halophila nipponica, were examined on the southern coast of the Korean peninsula. Zostera marina is a native dominant seagrass species in Korean coastal waters, whereas H. nipponica is a non‐native tropical and subtropical species that has extended its distributional range to the temperate coastal areas of Korea. To examine the differences in the growth dynamics of H. nipponica and Z. marina, their morphology, density, productivity and biomass, as well as local environmental conditions, were monitored monthly from January 2008 to July 2009. Underwater irradiance at the study site was the highest in April 2009 and the lowest in January 2008. Water temperature ranged from 10.4°C in January 2009 to 24.8°C in September 2008. Significant differences in growth dynamics were observed between the species, due to the effect of water temperature at the study site. Density and areal productivity were the highest in April 2008 and June 2008, respectively, for Z. marina but the highest in July 2008 for H. nipponica. Leaf size, shoot height and shoot weight were the highest in July 2008 for Z. marina but the highest in August 2008 or September 2008 for H. nipponica. The productivity of both species was strongly correlated with water temperature at the study site. However, the productivity of these species was not strongly correlated with underwater irradiance or the nutrient availability of either the water column or sediment pore water. Zostera marina exhibited the ecological characteristics of a temperate seagrass, whereas H. nipponica retained the features of a subtropical/tropical seagrass, even after adapting to the temperate coastal waters of Korea.

Abstract P1-01-08: The evolution of breast cancer circulating tumor cells mediating brain metastasis

Abstract Multiple studies concur that CTCs - the “seeds” of fatal metastasis - intravasate into the bloodstream throughout the early stages of cancer promoting generation of micro-metastatic reservoirs, some of which ultimately evolve to metastatic tumors. However, while it may take decades for CTCs to progress from cells in circulation to clinically detectable metastases, once detected, the tumor usually grows at an exponential rate. This difference in growth dynamics at two ends of the metastatic spectrum should also be reflected in the behavior of CTCs shed from these organ sites. Having a focus towards breast cancer brain-colonizing CTCs and their properties, we hypothesized that a gradual evolution of dormant CTCs into mitotically active CTCs with brain-metastatic potency is central to the progression of primary breast cancer to brain metastasis. We isolated CD44+/CD24- (stem-like) and Pan-Cytokeratin+ (epithelial) breast cancer CTCs from peripheral blood of two groups of breast cancer patients – five with brain metastases (BCBM) (MRI-detectable) and five without brain metastases (No BCBM). CTCs were isolated by multi-parametric flow cytometry and the expression of CTC-specific antigen was confirmed by immuno-cytochemistry and DEPArrayTM platform. Intra-cellular flow cytometry showed that No BCBM patients had 3-fold higher mitotically dormant (Ki67-) CTCs compared to BCBM patients. Whole genome expression arrays demonstrated low generalized transcriptional activity in CTCs suggestive of mitotic/metabolic dormancy. Comparison of CTC transcriptomes with ER+/PR+, HER2+ and triple negative breast cancers identified a unique CTC gene signature valid not only across the three molecular subtypes but also independent of the molecular subtype patients were initially diagnosed as. Pathway analyses predicted increased activation of pluripotency-related pathways along with decreased protein translational machinery and proliferative pathways in CTCs. Further, to dissect mechanisms of metastatic reactivation in the brain microenvironment, we compared the CTC transcriptome in BCBM vs No BCBM patients and identified a 126 gene signature potentiated in BCBM CTCs. Subsequent pathway analyses revealed upregulation of known CTC pathways like Notch along with novel hematopoietic and immune evasion networks. Cellular and functional annotations of cell migration and chemotaxis were significantly activated in BCBM along with pro-inflammatory (TNF, IL1β, NF-kB), immunomodulatory chemokines (CXCL8, CXCR4, CD86) and mitogenic growth factors (PDGF-BB). Lastly, lack of cell surface expression of Urokinase Plasminogen Activator Receptor (uPAR) and integrin beta-1 (int-β1) were used to identify CTCs in a state of metastatic dormancy. Whole genome sequencing showed significantly higher incidence of genomic mutations in proliferating CTCs compared to their dormant counterparts. We provide first time evidence of signaling pathways keenly implicated in breast cancer CTC biology based on comprehensive analyses of CTC transcriptomes. We discovered the existence of CTCs in a state of metabolic/mitotic dormancy and identified genomic instability as a switch for CTCs to revert to their proliferative phenotype. Citation Format: Boral D, Vishnoi M, Liu HN, Yin W, Hong DS, Scamardo AT, Marchetti D. The evolution of breast cancer circulating tumor cells mediating brain metastasis [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-01-08.

Time-lapse imaging reveals differences in growth dynamics of embryos after in vitro maturation compared with conventional stimulation

To study the impact of invitro maturation (IVM) on embryonal development with the use of time-lapse imaging. Retrospective case-control study. University hospital. In total, 294 embryos were cultured after intracytoplasmic sperm injection treatment of three groups: patients with polycystic ovary syndrome (PCOS) and IVM (n = 105; group 1 [G1]), patients after conventional stimulation without PCOS (n = 115; G2) and with PCOS (n = 74; G3). In total, 171 embryos were finally analyzed (57 G1, 65 G2, and 49 G3). Data of 23 PCOS patients (30 IVM cycles) from January 2012 to July 2015 were matched according to age and number of oocytes to patients after conventional stimulation without PCOS (n = 30; 30 cycles) and with PCOS (n = 16; 19 cycles). Markers of embryo development were analyzed at different time points. Pregnancy rates (PRs) and live birth rates (LBRs) were recorded. Morphokinetic differences in embryo development after IVM compared with conventional stimulation with or without PCOS. The rate of good-quality embryos was significantly lower in G1. Embryo development in G1 was significantly accelerated to the time of appearance of two pronuclei but slowed down by the time of reaching 6-cell stage and remained slower compared with embryos of G2 and G3. PRs as well as LBRs did not differ significantly among the study groups. Although growth dynamics of embryos from G1 differ from G2 and G3 and the rate of good-quality embryos was lower in IVM embryos, PRs and LBRs did not differ significantly.

Manufacturing and economic development: The actuality of Kaldor's first and second laws

The objective of this paper is to evaluate the role of the manufacturing sector in the development process based on two laws of Kaldor. The first law states that the higher the growth of the manufacturing output, the more significant is the growth rate of the economy's product as a whole. The second law, known as the Kaldor–Verdoorn law, establishes a deterministic relation between the growth of manufacturing productivity and manufacturing output growth. This paper begins showing stylized facts of the production and exports of manufactured goods to show that these remain related to the income level of countries in recent years. Thereafter, a theoretical reflection on the importance of manufacturing in the process of economic development is performed, associating it to the manufacturing exports and to the exchange rate regime. Then, the paper performs a Kaldorian model systematization to assess the importance of manufacturing and its exports on the economic development. Econometric tests are performed based on a dynamic panel data for a sample of 63 middle and high-income countries, excluding major exporters of fuels for the period between 1990 and 2011, to analyze whether there is any difference in growth dynamics between these two groups. Estimates attest the occurrence of the two Kaldor laws, demonstrating that output growth in the manufacturing sector is essential to increasing economic growth and productivity, particularly in middle-income economies. The results also confirm that manufacturing exports are relevant to the development process and that the exchange rate contributes to this process in middle-income countries.

Nonlinear tree growth dynamics predict resilience to disturbance

Following a disturbance, why does one tree survive while another dies? Physiological mechanisms may explain varying responses to disturbance between different tree species, but fewer studies have investigated conspecific variation in resilience to forest disturbance. We propose that a dynamic signal found in trees may provide clues to their post‐disturbance fate. Specifically, linear versus nonlinear growth dynamics of a tree may be an indicator of its likelihood to survive a disturbance. Here, we investigate stands of red oak (Quercus rubra L.) that experienced disturbances in the form of drought and insect attack. Earlier work indicated that oaks dying during these disturbances had faster growth rates in their first years of life, but there was no obvious difference in canopy status, size, age, or microsite habitat between trees that survived and those that died. To investigate potential differences in growth dynamics between these trees, we quantified radial growth of individual trees and used two forecasting models to classify tree growth dynamics as linear or nonlinear. Trees were classified as healthy, declining, or dying based on crown cover, and dynamic patterns of growth were related to these health classifications. Contrary to expectations, we found healthy Q. rubra were significantly more likely to exhibit nonlinear growth dynamics relative to declining and dying trees. The drivers of this effect remain unclear, but nonlinear growth dynamics in healthy trees may represent an enhanced ability to benefit from resource pulses, in turn promoting greater resilience. Our work suggests that forecasting models offer a means of predicting tree survival during forest disturbances and thus represent an increasingly valuable tool as forest disturbances increase in frequency and severity.