Distinct Growth Patterns Research Articles

Economic activity and patterns of infant growth in a high altitude district of Peru.

Changing economic activities bring significant cultural, epidemiological, and nutritional transitions. Infancy represents a critical period when rapid growth and metabolic programming occur, making infants particularly vulnerable to long-lasting biological changes due to such transitions. This paper examines the relationship between residence in distinct economic production zones (urban, herding, and dairy) and early growth in a highland district of Peru. The length, weight, body mass index, and triceps skinfold of 93 infants (55 boys and 38 girls, aged 2 to 24 months) from 3 economic zones were measured at two time points 6 months apart. Z-scores were calculated based on the WHO Growth Reference for children under 5 years of age. Comparisons were made to the reference group and between economic zones to examine the impacts of different economic activities on infant growth. Female infants had significantly higher height-for-age z-scores (HAZ) than males (P < 0.05). Across zones, dairying infants had the highest HAZ scores and the lowest prevalence of stunting. There was a significant association between zone and HAZ at baseline. While these associations were attenuated in measurements, taken 6 months later, longitudinal growth monitoring revealed differential patterns of weight gain and adiposity deposition across the zones with herding infants showing consistent high adiposity and urban infants gaining both weight and adiposity between rounds. Changes in economic activity are bringing about nutritional and epidemiological transitions in the Nuñoa district. Economic activity is a key factor influencing early growth with distinct longitudinal growth patterns in each economic zone.

Solute mixing regulates heterogeneity of mineral precipitation in porous media

AbstractSynchrotron X‐ray microtomography was used to track the spatiotemporal evolution of mineral precipitation and the consequent alteration of the pore structure. Column experiments were conducted by injecting CaCl2 and NaHCO3 solutions into granular porous media either as a premixed supersaturated solution (external mixing) or as separate solutions that mixed within the specimen (internal mixing). The two mixing modes produced distinct mineral growth patterns. While internal mixing promoted transverse heterogeneity with precipitation at the mixing zone, external mixing favored relatively homogeneous precipitation along the flow direction. The impact of precipitation on pore water flow and permeability was assessed via 3‐D flow simulations, which indicated anisotropic permeability evolution for both mixing modes. Under both mixing modes, precipitation decreased the median pore size and increased the skewness of the pore size distribution. Such similar pore‐scale evolution patterns suggest that the clogging of individual pores depends primarily on local supersaturation state and pore geometry.

Abstract 2834: Metastatic colorectal cancer: characterization of distinct histological growth patterns which demonstrate different response to current treatment regimes

Abstract Colorectal cancer (CRC) is the third most common cancer in North America, and the third leading cause of cancer-related death. About 50% of patients will be diagnosed with CRC liver metastasis (CRCLM) during the course of their disease. We have identified two major histological growth patterns (HGP) in CRCLM resected from patients. In the desmoplastic HGP (DHGP), the tumor cells are enclosed within a desmoplastic stromal ring, physically separating them from the normal liver tissue. In the replacement HGP (RHGP), the tumor cells replace normal hepatocytes without disrupting adjacent cells or structures within the liver parenchyma. We have recently shown that patients with RHGP lesions who received neoadjuvant bevacizumab plus chemotherapy had a worse pathological response and five-year overall survival. Our group has also shown that RHGP CRCLM is resistant to anti-angiogenic therapy due to it promoting vessel co-option as a means of tumor vascularization, rather than VEGF-dependent angiogenesis as seen in DHGP. However, the molecular mechanisms that drive the CRCLM HGPs remain unknown. This project aims to shed light on the biological processes that underlie the diversity of HGPs, with an emphasis on the key genes and pathways that support the RHGP. To test this, we have: Aim 1) performed RNAseq on chemonaïve RHGP and DHGP CRCLM lesions to identify pathways that are significantly upregulated in the RHGP. We have validated these genes via real-time PCR (RT-PCR), and a subset by immunohistochemistry (IHC). Aim 2) To further refine the RHGP gene signature and to examine the effects of cell-cell interactions on hepatocyte and tumor cell gene expression, individual cells have been isolated from distinct regions within RHGP CRCLM tissues using laser capture microdissection (LCM), followed by single-cell transcriptomics analyses. Our preliminary data have identified three major pathways with differentially expressed genes: i. cell motility, ii. cell junctions, and iii. ECM-receptor interactions, which are upregulated in RHGP relative to the DHGP and normal liver. A panel of RHGP-specific genes has been identified and validated via RT-PCR. We selected a subset of these genes and are performing IHC to further validate and locate their expression. We have also performed LCM and are in the process of performing transcriptomics analyses – the data will be presented. We expect to gain some insight into the mechanisms responsible for driving and/or maintaining the RHGP lesions. In the longer term, this work will result in identification of targets in the HGPs that will help stratify patients in terms of treatment. It would appear that we have fewer treatment options for the RHGP patients and it would be important to utilize the data to develop new treatment strategies for those patients. These new therapies would lead to further clinical trials. Citation Format: Vincent Palmieri, Anthoula Lazaris, Hussam Alamri, Abdellatif Amri, Nisreen Ibrahim, Pablo Zoroquiain, Peter Vermeulen, Peter Metrakos. Metastatic colorectal cancer: characterization of distinct histological growth patterns which demonstrate different response to current treatment regimes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2834. doi:10.1158/1538-7445.AM2017-2834

Pseudomonas syringae pv. tomato DC3000 growth in multiple gene knockouts predicts interactions among hormonal, biotic and abiotic stress responses

Among other environmental factors, phytopathogens have key roles in limiting global crop production. While an in-depth understanding of plant-pathogen interactions is therefore necessary to develop sustainable crop protection strategies, the genetic basis of plant-pathogen interactions is poorly understood. In this study, we tested the growth and resistance of an important phytopathogen, Pseudomonas syringae pv tomato DC3000 (Pst DC3000), in 80 gene knockouts, identified previously through genome-wide association mapping of global Arabidopsis thaliana populations. Amongst these, most of the genes are previously known to regulate multiple functions in plants including cellular mechanisms, growth, reproduction, hormonal signaling, and tolerance to both biotic and abiotic stresses (extreme temperature, drought, salinity, pollutants, and nutrient stresses, etc.). The Pst DC3000 demonstrated two distinct growth patterns in all gene knockouts, showing maximum growth after 4 or 7 days of inoculation (DOI). Mostly, the wild-type (Col-0) demonstrated higher phytopathogen growth than almost all gene knockouts after 4 or 7 DOI. The differential abundance of Pst DC3000 in the multiple gene knockouts reveals a number of new genes important for plant defense. Meanwhile, our results and a review of previous literature suggest interaction of plant defense with plant growth, reproduction, hormonal and abiotic stress tolerance. Thus in future studies, a mechanistic understanding of the genetic, ecological and physiological basis of plant-pathogen interactions, and pleiotropic interactions may prove instrumental in developing sustainable plant protection practices.

Post-term growth and cognitive development at 5 years of age in preterm children: Evidence from a prospective population-based cohort.

While the effects of growth from birth to expected term on the subsequent development of preterm children has attracted plentiful attention, less is known about the effects of post-term growth. We aimed to delineate distinct patterns of post-term growth and to determine their association with the cognitive development of preterm children. Data from a prospective population-based cohort of 3,850 surviving infants born at less than 35 weeks of gestational age were used. Growth was assessed as the Body Mass Index (BMI) Z-scores at 3, 9, 18, 24, 36, 48, and 60 months. Cognitive development at five years of age was evaluated by the Global School Adaptation score (GSA). Latent class analysis was implemented to identify distinct growth patterns and logistic regressions based on propensity matching were used to evaluate the relationship between identified growth trajectories and cognitive development. Four patterns of post-term growth were identified: a normal group with a Z-score consistently around zero during childhood (n = 2,469; 64%); a group with an early rapid rise in the BMI Z-score, but only up to 2 years of age (n = 195; 5%); a group with a slow yet steady rise in the BMI Z-score during childhood (n = 510; 13%); and a group with a negative Z-score growth until 3 years of age (n = 676; 18%). The group with a slow yet steady rise in the BMI Z-score was significantly associated with low GSA scores. Our findings indicate heterogeneous post-term growth of preterm children, with potential for association with their cognitive development.

Economic Growth and Financial Statement Verification

ABSTRACTWe use a proprietary data set of financial statements collected by banks to examine whether economic growth is related to the use of financial statement verification in debt financing. Exploiting the distinct economic growth and contraction patterns of the construction industry over the years 2002–2011, our estimates reveal that banks reduced their collection of unqualified audited financial statements from construction firms at nearly twice the rate of firms in other industries during the housing boom period before 2008. This reduction was most severe in the regions that experienced the most significant construction growth. These trends reversed during the subsequent housing crisis in 2008–2011 when construction activity contracted. Moreover, using bank‐ and firm‐level data, we find a strong negative (positive) relation between audited financial statements during the growth period, and subsequent loan losses (construction firm survival) during the contraction period. Collectively, our results reveal that macroeconomic fluctuations produce temporal shifts in the overall level of financial statement verification and temporal shifts in verification are related to bank loan portfolio quality and borrower performance.

Lymphomatoid papulosis - making sense of the alphabet soup: a proposal to simplify terminology.

Clinically, lymphomatoid papulosis (LYP) is characterized by recurrent papulonodular lesions. Unlike this stereotypical clinical presentation, the histological spectrum of LYP is very wide, comprising distinct growth patterns, variably sized neoplastic cells, and different immunophenotypes. The revised 2016 WHO classification includes the histological LYP types A to E as well as another type characterized by a specific chromosomal alteration. In addition, new LYP types are going to be proposed, based not only on histological but also on clinical and genetic features. The ensuing expansion of the alphabetical list of histological types will add to the complexity of the terminology of LYP, thereby potentially increasing the risk of complicating rather than facilitating the diagnostic approach to the disease. Moreover, there may be overlap between individual disease types. This development raises the question as to how to simplify the terminology of LYP while still respecting its histological complexity. Herein, we advocate a practical approach to the terminology of LYP based on descriptive terms rather than the designation of LYP types by alphabetical characters. Our proposal aims to contribute to a pragmatic and user-friendly approach, thus not only facilitating the diagnostic process but also the communication between clinicians and pathologists.

Dinamika populasi wereng punggung putih, sogatella furcifera Stål (Hemiptera: Delphacidae) di jawa tengah

A field study was conducted at paddy fields in Petarukan and Pekalongan regencies of Central Java province during wet season crop 1989/90 and 1990/91 to elucidate population dynamic of whitebacked planthopper, Sogatella furcifera Stål. Seven and three observation fields were set up in 1989/90 and the 1990/91, respectively. Cisadane rice cultivar was transplanted following the usual farmer’s parctices except that no pesticide was applied. The population of the whitebacked planthopper and the brown planthopper, (Nilaparvata lugens Stål) were sampled by using an insect suction catcher, a farmcop. Identification of generation was based on thermal constant required by the whitebacked planthopper to complete one generation and mean population density was calculated by graphical method. Two distinct seasonal population growth patterns were identified. The population with short population growth pattern completed four generations in one crop season in which their population density increased consecutively in two generations since immigrant generation, and thereafter decreased. The population with long population growth completed five generations in one crop season in which their population density increased consecutively in three generations, and thereafter decreased. The density of brachiptera adults determined 90% of the total population density. The proportion of brachiptera adults were not correlated with large nymphal density in both vegetative and generative stages of rice. The proportion of brachiptera adults showed significant negative linear regression with population density of the brown planthopper. Therefore, interspesific competition determined the proportion of wingform and population dynamics of the whitebacked planthopper.

Growth characteristics and endocrine abnormalities in 22q11.2 deletion syndrome.

22q11.2 deletion syndrome (22q11.2DS) has a wide range of clinical features including endocrine abnormalities. We aimed to characterize growth patterns, hypoparathyroidism, and thyroid dysfunction of individuals with 22q11.2DS. Anthropometric and laboratory measurements were obtained from the charts of 48 individuals (males=28, 8.0±6.8 visits/participant) followed at a national 22q11.2DS clinic between 2009 and 2016. Age at diagnosis was 4.3±4.9 years and age at last evaluation 11.2±7.2 years. Median height-SDS was negative at all ages. Height-SDS at last visit was correlated to the midparental height-SDS (r=0.52 P=0.002). Yet, participants did not reach their target height, with a difference of 1.06±1.07 SD (P <0.0001). Height-SDS at last visit of participants with a heart defect was lower compared to participants with a normal heart (-1.5±1.4 vs. -0.6±0.8, P=0.036), with lower height-SDS in the subgroup of participants with severe heart defects (-2.1±1.6, P=0.009). Mean IGF1-SDS was low (-0.99±1.68) but was not correlated with height-SDS. Thirteen patients (27%) had hypoparathyroidism: 10 presented during infancy and 3 during adolescence. Five patients (10.4%, female=4) had thyroid abnormalities. In conclusions, individuals with 22q11.2 DS have a distinct growth pattern consisting of growth restriction at all ages, resulting in final adult height in the low-normal range. Hypoparathyroidism is common and may present during the neonatal period as well as later in life. Thyroid abnormalities may present during childhood, adolescence, or adulthood.

Latent sprawl patterns and the spatial distribution of businesses in a southern European city

The relocation of businesses beyond the consolidated city is an important aspect of recent urbanization trends. With economic restructuring driven by suburbanization and counter-urbanization, Southern European metropolitan areas experienced distinct growth patterns compared with north-western Europe. The present study assesses the impact of recent changes in the spatial distribution of businesses on land-use structure, sprawl trends and land consumption in a Mediterranean urban region (Athens, Greece) with the aim to identify economic drivers of sprawl and to inform urban containment strategies. Businesses showed two distinct localization patterns: manufacture, publishing and transport companies, construction and hotels were concentrated in urban municipalities; real estate, finance, high-tech, telecommunication, mining and energy enterprises settled preferentially in suburban municipalities. Dispersed urban expansion mainly reflects the spatial relocation of economic activities with high returns on capital to cheaper land. High-tech enterprises and finance/real estate businesses dominated the economic structure of municipalities with sprawled settlements. Policies securing economic development and a land-saving spatial structure are increasingly required to work towards integrated measures promoting semi-compact metropolitan poles and containing deregulated urban expansion.

Vessel co-option is common in human lung metastases and mediates resistance to anti-angiogenic therapy in preclinical lung metastasis models.

Anti‐angiogenic therapies have shown limited efficacy in the clinical management of metastatic disease, including lung metastases. Moreover, the mechanisms via which tumours resist anti‐angiogenic therapies are poorly understood. Importantly, rather than utilizing angiogenesis, some metastases may instead incorporate pre‐existing vessels from surrounding tissue (vessel co‐option). As anti‐angiogenic therapies were designed to target only new blood vessel growth, vessel co‐option has been proposed as a mechanism that could drive resistance to anti‐angiogenic therapy. However, vessel co‐option has not been extensively studied in lung metastases, and its potential to mediate resistance to anti‐angiogenic therapy in lung metastases is not established. Here, we examined the mechanism of tumour vascularization in 164 human lung metastasis specimens (composed of breast, colorectal and renal cancer lung metastasis cases). We identified four distinct histopathological growth patterns (HGPs) of lung metastasis (alveolar, interstitial, perivascular cuffing, and pushing), each of which vascularized via a different mechanism. In the alveolar HGP, cancer cells invaded the alveolar air spaces, facilitating the co‐option of alveolar capillaries. In the interstitial HGP, cancer cells invaded the alveolar walls to co‐opt alveolar capillaries. In the perivascular cuffing HGP, cancer cells grew by co‐opting larger vessels of the lung. Only in the pushing HGP did the tumours vascularize by angiogenesis. Importantly, vessel co‐option occurred with high frequency, being present in >80% of the cases examined. Moreover, we provide evidence that vessel co‐option mediates resistance to the anti‐angiogenic drug sunitinib in preclinical lung metastasis models. Assuming that our interpretation of the data is correct, we conclude that vessel co‐option in lung metastases occurs through at least three distinct mechanisms, that vessel co‐option occurs frequently in lung metastases, and that vessel co‐option could mediate resistance to anti‐angiogenic therapy in lung metastases. Novel therapies designed to target both angiogenesis and vessel co‐option are therefore warranted. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Promotion of first internode elongation in perennial paddy weeds Sagittaria trifolia and Sagittaria pygmaea tubers by oxygen depletion and carbon dioxide

The semiaquatic plants, S agittaria trifolia and S agittaria pygmaea, are perennial and troublesome weeds of rice paddy fields. These species mainly reproduce vegetatively via tubers, which sprout after the rice paddy fields are irrigated. Sprouting finally leads to the emergence of the shoots from the water in the paddy fields. In both species, the first internode elongates around the time of emergence and this lifts the shoot meristems in the soil, aiding in the establishment of the young plants. Therefore, elongation of the internode is a factor that determines the weed damage to rice caused by these species. In this study, the first internode elongation of both species was characterized. During emergence, S . trifolia and S . pygmaea showed distinct growth patterns. In S . trifolia, the internodes elongated before the emergence of the shoots from the water; whereas, in S . pygmaea, the internodes started to elongate only after emergence. We examined environmental prerequisites for internode elongation, and found that the internode elongation of S . trifolia was induced by submergence and was independent of the soil cover, while that of S . pygmaea required both submergence and covering. Next, we determined which gaseous factors were responsible for internode elongation. Treatment with ethylene, which enhances growth of several other aquatic and semiaquatic plants, did not stimulate internode elongation in either species under an anaerobic condition. Our results suggested that the gaseous factor stimulating internode elongation in S . trifolia and S . pygmaea may be oxygen depletion and carbon dioxide, respectively.

A Study of the Growth Patterns of Breast Carcinoma Using 3D Reconstruction: A Pilot Study.

Lumpectomy with microscopically clear margins is a safe and effective approach for surgical management of breast carcinoma. Margins are positive for tumor in 18-50% of lumpectomies, as it is not possible to accurately determine the shape or microscopic borders of a tumor preoperatively or intraoperatively. We examined the 3D microanatomy and growth patterns of common breast carcinoma subtypes to provide guidance for lumpectomy surgery. Prospective consent was obtained for the use of excess tissue from patients undergoing lumpectomy or mastectomy for breast carcinoma. Tissue blocks from nine breast carcinomas were serially sectioned. Hematoxylin and eosin-stained slides at 100 μm intervals were scanned using a Nanozoomer (Hamamatsu, Japan) microscopic-resolution scanner. Three-dimensional reconstructions of tumors were created from scanned images using Reconstruct, open-access software. Breast carcinoma subtypes demonstrated characteristic growth patterns within breast tissue, which may have implications for lumpectomy surgery. Invasive ductal carcinomas showed a spherical shape, with a spiculated surface representing tumor cells infiltrating into surrounding parenchyma. Ductal carcinoma in situ appeared to spread along the duct system, creating dilated, tortuous, tumor-filled ducts. The invasive lobular carcinomas examined had a haphazard, linear, infiltrative growth pattern, different from the shape seen in ductal carcinomas. Our preliminary work suggests that invasive ductal and invasive lobular carcinomas appear to have distinct growth patterns in three dimensions and ductal carcinoma in situ appears to grow in a linear fashion along the duct network. The microanatomy studies described have the potential to guide refinements in breast lumpectomy technique.

The development of self-regulation across early childhood.

The development of early childhood self-regulation is often considered an early life marker for later life successes. Yet little longitudinal research has evaluated whether there are different trajectories of self-regulation development across children. This study investigates the development of behavioral self-regulation between the ages of 3 and 7 years, with a direct focus on possible heterogeneity in the developmental trajectories, and a set of potential indicators that distinguish unique behavioral self-regulation trajectories. Across 3 diverse samples, 1,386 children were assessed on behavioral self-regulation from preschool through first grade. Results indicated that majority of children develop self-regulation rapidly during early childhood, and that children follow 3 distinct developmental patterns of growth. These 3 trajectories were distinguishable based on timing of rapid gains, as well as child gender, early language skills, and maternal education levels. Findings highlight early developmental differences in how self-regulation unfolds, with implications for offering individualized support across children. (PsycINFO Database Record

In vitro assays for determining the metastatic potential of melanoma cell lines with characterized in vivo invasiveness.

The metastatic potential of cancer cells is an elusive property that is indicative of the later stages of cancer progression. The ability to distinguish between poorly and highly metastatic cells is invaluable for understanding the basic biology of cancer and to develop more treatments. In this paper, we exploit a A375 melanoma cell line series (A375P, A375MA1, A375MA2) that vary in metastatic potential, to demonstrate an in vitro screening assay using polydimethylsiloxane (PDMS) microbubble well arrays that can distinguish these cell lines by their growth characteristics in including morphology, migratory potential, and clonogenic potential. These cell lines cannot be distinguished by their growth characteristics when cultured on standard tissue culture plastic or planar PDMS. Results show that the more metastatic cell lines (A375MA1, A375MA2) have a higher proliferative potential and a distinctive radial spreading growth pattern out of the microbubble well. The A375MA2 cell line also has a higher tendency to form multicellular spheroids. The ability to successfully correlate the metastatic potential of cancer cells with their growth characteristics is essential first step toward developing a high-throughput screening assay to identify aggressive tumor cells in primary samples. The capability to culture and recover aggressive cells from microbubble wells will enable identification of candidate metastatic biomarkers which has immense clinical significance.

The sellar and suprasellar region: A “hideaway” of rare lesions. Clinical aspects, imaging findings, surgical outcome and comparative analysis

ObjectiveApart from the “common” lesions (e.g. pituitary adenomas, Rathke’s cleft cysts, meningiomas and craniopharyngiomas), there is a plethora of rare tumors or tumor-mimicking lesions in the sellar and suprasellar region (SSR). Due to a lack of characteristic imaging features, there is a dilemma in distinguishing these rare lesions from the more “common” ones preoperatively. Consequently, both diagnosis and definition of surgical goals, as well as further treatment strategies continue to be challenging for all attending physicians.To replenish the scarce data on this issue, we analysed all patients with infrequent non-adenomatous pathologies in the SSR treated in our clinic, providing a database for further studies. MethodsA retrospective study was performed including 223 patients who were operated on lesions within the SSR at the Department of Neurosurgery, Hannover Medical School, between 2006 and 2014.The patients’ charts were analysed with regard to the results of pre-/postoperative endocrinological and neuroophthalmological examinations. Preoperative T2WI were analysed with special focus on distinct growth patterns within four quadrants constituting the (supra-)sellar region. In this way, a comparative analysis between the diverse lesions regarding their clinical features, resectability and the final outcome was possible. ResultsAfter exclusion of cases with “common” lesions, a collective of 20 patients with rare lesions within the SSR was obtained. The histopathological diagnosis revealed xanthogranulomas (n=6), metastatic tumors (n=5), colloid/epidermal cysts (n=3), pilocytic astrocytomas (n=2), and one case each of gangliocytoma, lymphocytic hypophysitis or concomitant germ cell tumor/rhabdomyosarcoma. In comparison to non-infiltrative lesions, those of infiltrative nature caused more frequently diplopia and deterioration of visual acuity (4 cases; p<0,05) that were less prone to improve postoperatively. Regarding growth pattern, metastatic tumors demonstrated main growth within the third quadrant with destructive remodelling of the dorsum sellae (p<0,05). While patients harbouring large lesions (>20mm) showed a significantly worse outcome regarding hormonal deficits (p=0,0313), the overall prognosis was heavily linked to the histopathological diagnosis. ConclusionThe correlation of the subtle radiological findings demonstrated with the specific clinical features may facilitate the differential diagnosis of rare lesions of the SSR and aid in establishing an interdisciplinary diagnostic and therapeutic procedure for these lesions.

Credit Cycles and Financial Statement Verification

We use a proprietary dataset of financial statements collected by banks to examine whether economic growth is related to the use of financial statement verification in debt financing. Exploiting the distinct economic growth and contraction patterns of the construction industry over the years 2002 to 2011, our estimates reveal that banks reduced their collection of unqualified audited financial statements from construction firms at nearly twice the rate of firms in other industries during the housing boom period before 2008. This reduction was most severe in the regions that experienced the most significant construction growth. These trends reversed during the sub-sequent housing crisis in 2008 to 2011 when construction activity contracted. Moreover, using bank- and firm-level data we find a strong negative (positive) relation between audited financial statements during the growth period and subsequent loan losses (construction firm survival) during the contraction period. Collectively, our results reveal that macroeconomic fluctuations pro-duce temporal shifts in the overall level of financial statement verification and that temporal shifts in verification are related to bank loan portfolio quality and borrower performance.

Metastatic ocular melanoma to the liver exhibits infiltrative and nodular growth patterns

We examined liver specimens from 15 patients with uveal melanoma (UM) who had died of their disseminated disease. We found 2 distinct growth patterns of UM metastasis: infiltrative (n = 12) and nodular (n = 3). In the infiltrative pattern, individual UM cells with a CD133+ cancer stem cell-like phenotype were present and formed aggregates of stage I <50-μm-diameter micrometastases in the sinusoidal spaces. These micrometastases appeared to expand, destroy adjacent hepatocytes, and form stage II 51- to 500-μm-diameter and then stage III >500μm-diameter metastases, which were encapsulated by collagenized fibrous septae. In the nodular growth pattern, CD133+ melanoma cells aggregated adjacent to portal venules and subsequently appeared to grow and efface the adjacent hepatocytes to form stage II 51- to 500-μm-diameter nodules that surrounded the portal venule. These avascular nodules appeared to further expand to form stage III >500-μm-diameter nodules that exhibited vascularization with minimal fibrosis. The tumor stem cell-like phenotype seen in individual UM cells was lost as the tumors progressed. There were CD56+ natural killer cells in sinusoidal spaces and CD3+ lymphocytes in periportal areas. The nodular growth pattern showed UM cells expressing MMP9 and VEGF. UM cells in both above-described growth patterns exhibited variable BAP1 expression. We propose that changes in the liver microenvironment are related to metastatic UM growth. We hypothesize that these changes include immune regulation within the sinusoidal space for the infiltrative pattern and changes in the VEGF/PEDF ratio for the nodular pattern.

Investigation of availability of a high throughput screening method for predicting butanol solvent -producing ability of Clostridium beijerinckii.

BackgroundCurrently, efficient screening methods for selection of desired bacterial phenotypes from large populations are not easy feasible or readily available due to the complicated physiological and metabolic networks of solventogenic clostridia. In this study, to contribute to the improvement of methods for predicting the butanol-producing ability of Clostridium beijerinckii based on starch substrate, we further investigate a simple, visualization screening method for selecting target strains from mutant library of Clostridium beijerinckii NCIMB 8052 by using trypan blue dye as an indicator in solid starch via statistical survey and validation of fermentation experiment with controlling pH.ResultsTo verify an effective, efficient phenotypic screening method for isolating high butanol-producing mutants, the revalidation process was conducted based on Trypan Blue was used for visualization, and starch was used as the bacterial metabolic substrate. The availability of the screening system was further evaluated based on the relationship between characteristics of mutant strains and their α-amylase activities. Mutant clones were analyzed in detail based on their distinctive growth patterns and rate of fermentation of soluble starch to form butanol and were compared by statistical method. Significant correlations were identified between colony morphology and changes in butanol concentrations. The screening method was validated via statistical analysis for characterizing phenotypic parameters. The fermentation experiment of mutant strains with controlling pH value also demonstrated a positive correlation between increased α-amylase activity and increased solvent production by Clostridium beijerinckii was observed, and therefore indicated that the trypan blue dyeing method can be used as a fast method to screen target mutant strain for better solvent producers from, for instance, a mutant library.ConclusionsThe suitability of the novel screening procedure was validated, opening up a new indicator of approach to select mutant solventogenic clostridia with improved fermentation of starch to increase butanol concentrations. The applicability can easily be broadened to a wide range of interesting microbes such as cellulolytic or acetogenic microorganisms, which produce biofuels from feedstock rich in starch.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-016-0776-6) contains supplementary material, which is available to authorized users.

Composite growth model applied to human oral and pharyngeal structures and identifying the contribution of growth types

The growth patterns of different anatomic structures in the human body vary in terms of growth amount over time, growth rate and growth periods. The oral and pharyngeal structures, also known as vocal tract structures, are housed in the craniofacial complex where the cranium/brain follows a distinct neural growth pattern, and the face follows a distinct somatic or skeletal growth pattern. Thus, it is reasonable to expect the oral and pharyngeal structures to follow a combined or mixed growth pattern. Existing parametric growth models are limited in that they are mainly focused on modeling one particular type of growth pattern. In this paper, we propose a novel composite growth model using neural and somatic baseline curves to fit the combined growth pattern of select vocal tract structures. The method can also determine the overall percent contribution of each of the growth types.