ADVERSE EFFECTS OF PRENATAL EXPOSURE TO ATRAZINE DURING A CRITICAL PERIOD OF MAMMARY GLAND GROWTH

EPA Science Inventory

Prenatal exposure to 100 mg/kg atrazine (ATR) was previously shown to delay mammary gland (MG) development in the female offspring of Long Evans (LE) rats. To determine if the fetal MG was most sensitive to ATR effects during specific periods of development, timed-pregnant dams ...

Incidence of delayed hair re-growth, pruritus, and urinary retention after epidural anaesthesia in dogs.

PubMed

Kalchofner Guerrero, K S; Guerrero, T G; Schweizer-Kölliker, M; Ringer, S K; Hässig, M; Bettschart-Wolfensberger, R

2014-04-16

Delayed hair re-growth, pruritus and urinary retention are known complications after epidural anaesthesia in dogs. The aim of this study was to prospectively evaluate the effect of epidurally administered drugs on the occurrence of these complications in dogs. Ninety dogs were included in this study. Eighty client-owned dogs undergoing surgery were randomly assigned to one of three epidural treatment groups: either morphine and bupivacaine (MB), bupivacaine (B), or saline solution 0.9% (S) was administered epidurally to these patients. Ten dogs were only clipped in the lumbosacral area (C). Follow-up started 4 weeks after clipping and was performed every 4-5 weeks in cases of delayed hair re-growth or pruritus. Hair re-growth in the lumbosacral area was observed and compared to hair re-growth in the surgical field and the fentanyl patch area. Cytological analysis and a trichogram were performed if hair re-growth was delayed after 6 months. Time interval to first urination postoperatively was recorded (n = 80). Hair re-growth was delayed in 11 dogs (12.2%; B: n = 7, S: n = 2, MB: n = 1, C: n = 1) with no differences between groups. Pruritus was evident in two dogs (2.2%; MB: n = 1, S: n = 1). After 6 months, hair had started to re-grow in all but one dog (B). After 10 months the coat of this dog had re-grown. Time to first urination did not differ between groups. No direct correlation between the particular drugs injected epidurally and delayed hair re-growth, pruritus and urinary retention could be shown. Dog owners should be informed that hair re-growth after epidural anaesthesia could be markedly delayed.

Multirate state and parameter estimation in an antibiotic fermentation with delayed measurements.

PubMed

Gudi, R D; Shah, S L; Gray, M R

1994-12-01

This article discusses issues related to estimation and monitoring of fermentation processes that exhibit endogenous metabolism and time-varying maintenance activity. Such culture-related activities hamper the use of traditional, software sensor-based algorithms, such as the extended kalman filter (EKF). In the approach presented here, the individual effects of the endogenous decay and the true maintenance processes have been lumped to represent a modified maintenance coefficient, m(c). Model equations that relate measurable process outputs, such as the carbon dioxide evolution rate (CER) and biomass, to the observable process parameters (such as net specific growth rate and the modified maintenance coefficient) are proposed. These model equations are used in an estimator that can formally accommodate delayed, infrequent measurements of the culture states (such as the biomass) as well as frequent, culture-related secondary measurements (such as the CER). The resulting multirate software sensor-based estimation strategy is used to monitor biomass profiles as well as profiles of critical fermentation parameters, such as the specific growth for a fed-batch fermentation of Streptomyces clavuligerus.

Ectopic Expression of Capsicum-Specific Cell Wall Protein Capsicum annuum Senescence-Delaying 1 (CaSD1) Delays Senescence and Induces Trichome Formation in Nicotiana benthamiana

PubMed Central

Seo, Eunyoung; Yeom, Seon-In; Jo, SungHwan; Jeong, Heejin; Kang, Byoung-Cheorl; Choi, Doil

2012-01-01

Secreted proteins are known to have multiple roles in plant development, metabolism, and stress response. In a previous study to understand the roles of secreted proteins, Capsicum annuum secreted proteins (CaS) were isolated by yeast secretion trap. Among the secreted proteins, we further characterized Capsicum annuum senescence-delaying 1 (CaSD1), a gene encoding a novel secreted protein that is present only in the genus Capsicum. The deduced CaSD1 contains multiple repeats of the amino acid sequence KPPIHNHKPTDYDRS. Interestingly, the number of repeats varied among cultivars and species in the Capsicum genus. CaSD1 is constitutively expressed in roots, and Agrobacterium-mediated transient overexpression of CaSD1 in Nicotiana benthamiana leaves resulted in delayed senescence with a dramatically increased number of trichomes and enlarged epidermal cells. Furthermore, senescence- and cell division-related genes were differentially regulated by CaSD1-overexpressing plants. These observations imply that the pepper-specific cell wall protein CaSD1 plays roles in plant growth and development by regulating cell division and differentiation. PMID:22441673

Effect of time between x-irradiation and chemotherapy on the growth of three solid mouse tumors. V. Bleomycin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Twentyman, P.R.; Kallman, R.F.; Brown, J.M.

1979-09-01

Experiments have been carried out to determine the effect of different time intervals between the administration of x-radiation (1200 rad) and bleomycin (20 mg/kg) on the growth delay produced in three mouse tumors. The tumors used were the EMT6 tumor in BALB/c mice and the KHT and RIF-1 sarcomas in C3H mice. All tumors were grown intramuscularly in the gastrocnemius muscle and treatment was carried out at a mean tumor weight of 450 mg. Time to reach 2X (for KHT) or 4X (for EMT6 and RIF-1) treatment volume was used as the endpoint of response. The drug was administered bymore » the intraperitoneal route either 24, 6, or 2 hr before radiation, immediately before the start of radiation, or 3, 6, or 24 hr after radiation. All irradiations were carried out in unanesthetized mice. For a single administration at this dose level, bleomycin alone did not produce a significant growth delay in any of the tumors. In the RIF-1 tumor, growth delays following combination treatments were equal to the addition of the single agent growth delays. In two experiments with EMT6, contrary results were obtained, one producing longer delays following combination treatments than predicted and the other producing shorter delays. This is apparently due to the variability in the growth delay after treatment with radiation alone for this tumor. For the KHT tumor, only small differences from the addition of single agent delays were seen.« less

Persistent G. lamblia impairs growth in a murine malnutrition model

PubMed Central

Bartelt, Luther A.; Roche, James; Kolling, Glynis; Bolick, David; Noronha, Francisco; Naylor, Caitlin; Hoffman, Paul; Warren, Cirle; Singer, Steven; Guerrant, Richard

2013-01-01

Giardia lamblia infections are nearly universal among children in low-income countries and are syndemic with the triumvirate of malnutrition, diarrhea, and developmental growth delays. Amidst the morass of early childhood enteropathogen exposures in these populations, G. lamblia–specific associations with persistent diarrhea, cognitive deficits, stunting, and nutrient deficiencies have demonstrated conflicting results, placing endemic pediatric giardiasis in a state of equipoise. Many infections in endemic settings appear to be asymptomatic/subclinical, further contributing to uncertainty regarding a causal link between G. lamblia infection and developmental delay. We used G. lamblia H3 cyst infection in a weaned mouse model of malnutrition to demonstrate that persistent giardiasis leads to epithelial cell apoptosis and crypt hyperplasia. Infection was associated with a Th2-biased inflammatory response and impaired growth. Malnutrition accentuated the severity of these growth decrements. Faltering malnourished mice exhibited impaired compensatory responses following infection and demonstrated an absence of crypt hyperplasia and subsequently blunted villus architecture. Concomitantly, severe malnutrition prevented increases in B220+ cells in the lamina propria as well as mucosal Il4 and Il5 mRNA in response to infection. These findings add insight into the potential role of G. lamblia as a “stunting” pathogen and suggest that, similarly, malnourished children may be at increased risk of G. lamblia–potentiated growth decrements. PMID:23728173

Persistent G. lamblia impairs growth in a murine malnutrition model.

PubMed

Bartelt, Luther A; Roche, James; Kolling, Glynis; Bolick, David; Noronha, Francisco; Naylor, Caitlin; Hoffman, Paul; Warren, Cirle; Singer, Steven; Guerrant, Richard

2013-06-01

Giardia lamblia infections are nearly universal among children in low-income countries and are syndemic with the triumvirate of malnutrition, diarrhea, and developmental growth delays. Amidst the morass of early childhood enteropathogen exposures in these populations, G. lamblia–specific associations with persistent diarrhea, cognitive deficits, stunting, and nutrient deficiencies have demonstrated conflicting results, placing endemic pediatric giardiasis in a state of equipoise. Many infections in endemic settings appear to be asymptomatic/ subclinical, further contributing to uncertainty regarding a causal link between G. lamblia infection and developmental delay. We used G. lamblia H3 cyst infection in a weaned mouse model of malnutrition to demonstrate that persistent giardiasis leads to epithelial cell apoptosis and crypt hyperplasia. Infection was associated with a Th2-biased inflammatory response and impaired growth. Malnutrition accentuated the severity of these growth decrements. Faltering malnourished mice exhibited impaired compensatory responses following infection and demonstrated an absence of crypt hyperplasia and subsequently blunted villus architecture. Concomitantly, severe malnutrition prevented increases in B220+ cells in the lamina propria as well as mucosal Il4 and Il5 mRNA in response to infection. These findings add insight into the potential role of G. lamblia as a "stunting" pathogen and suggest that, similarly, malnourished children may be at increased risk of G. lamblia– potentiated growth decrements.

How long can fisheries management delay action in response to ecosystem and climate change?

PubMed

Brown, Christopher J; Fulton, Elizabeth A; Possingham, Hugh P; Richardson, Anthony J

2012-01-01

Sustainable management of fisheries is often compromised by management delaying implementation of regulations that reduce harvest, in order to maintain higher catches in the short-term. Decreases or increases in fish population growth rate driven by environmental change, including ecosystem and climate change, affect the harvest that can be taken sustainably. If not acted on rapidly, environmental change could result in unsustainable fishing or missed opportunity for higher catches. Using simulation models of harvested fish populations influenced by environmental change, we explore how long fisheries managers can afford to wait before changing harvest regulations in response to changes in population growth. If environmental change causes population declines, delays greater than five years increase the probability of population collapse. Species with fast and highly variable population growth rates are more susceptible to collapse under delays and should be a priority for revised management where delays occur. Generally, the long-term cost of delay, in terms of lost fishing opportunity, exceeds the short-term benefits of overfishing. Lowering harvest limits and monitoring for environmental change can alleviate the impact of delays; however, these measures may be more costly than reducing delays. We recommend that management systems that allow rapid responses to population growth changes be enacted for fisheries management to adapt to ecosystem and climate change.

Delayed Cell Cycle Progression and Apoptosis Induced by Hemicellulase-Treated Agaricus blazei

PubMed Central

Kasai, Hirotake

2007-01-01

We examined the effects of hemicellulase-treated Agaricus blazei (AB fraction H, ABH) on growth of several tumor cell lines. ABH inhibited the proliferation of some cell lines without cytotoxic effects. It markedly prolonged the S phase of the cell cycle. ABH also induced mitochondria-mediated apoptosis in different cell lines. However, it had no impact on the growth of other cell lines. ABH induced strong activation of p38 mitogen-activated protein kinase (MAPK) in the cells in which it evoked apoptosis. On the other hand, ABH showed only a weak p38 activation effect in those cell lines in which it delayed cell cycle progression with little induction of apoptosis. However, p38 MAPK-specific inhibitor inhibited both ABH-induced effects, and ABH also caused apoptosis in the latter cells under conditions of high p38 MAPK activity induced by combined treatment with TNF-α. These results indicate that the responsiveness of p38 MAPK to ABH, which differs between cell lines, determines subsequent cellular responses on cell growth. PMID:17342245

The role of the Arabidopsis FUSCA3 transcription factor during inhibition of seed germination at high temperature.

PubMed

Chiu, Rex S; Nahal, Hardeep; Provart, Nicholas J; Gazzarrini, Sonia

2012-01-27

Imbibed seeds integrate environmental and endogenous signals to break dormancy and initiate growth under optimal conditions. Seed maturation plays an important role in determining the survival of germinating seeds, for example one of the roles of dormancy is to stagger germination to prevent mass growth under suboptimal conditions. The B3-domain transcription factor FUSCA3 (FUS3) is a master regulator of seed development and an important node in hormonal interaction networks in Arabidopsis thaliana. Its function has been mainly characterized during embryonic development, where FUS3 is highly expressed to promote seed maturation and dormancy by regulating ABA/GA levels. In this study, we present evidence for a role of FUS3 in delaying seed germination at supraoptimal temperatures that would be lethal for the developing seedlings. During seed imbibition at supraoptimal temperature, the FUS3 promoter is reactivated and induces de novo synthesis of FUS3 mRNA, followed by FUS3 protein accumulation. Genetic analysis shows that FUS3 contributes to the delay of seed germination at high temperature. Unlike WT, seeds overexpressing FUS3 (ML1:FUS3-GFP) during imbibition are hypersensitive to high temperature and do not germinate, however, they can fully germinate after recovery at control temperature reaching 90% seedling survival. ML1:FUS3-GFP hypersensitivity to high temperature can be partly recovered in the presence of fluridone, an inhibitor of ABA biosynthesis, suggesting this hypersensitivity is due in part to higher ABA level in this mutant. Transcriptomic analysis shows that WT seeds imbibed at supraoptimal temperature activate seed-specific genes and ABA biosynthetic and signaling genes, while inhibiting genes that promote germination and growth, such as GA biosynthetic and signaling genes. In this study, we have uncovered a novel function for the master regulator of seed maturation, FUS3, in delaying germination at supraoptimal temperature. Physiologically, this is important since delaying germination has a protective role at high temperature. Transcriptomic analysis of seeds imbibed at supraoptimal temperature reveal that a complex program is in place, which involves not only the regulation of heat and dehydration response genes to adjust cellular functions, but also the activation of seed-specific programs and the inhibition of germination-promoting programs to delay germination. © 2011 Chiu et al; licensee BioMed Central Ltd.

The role of the Arabidopsis FUSCA3 transcription factor during inhibition of seed germination at high temperature

PubMed Central

2012-01-01

Background Imbibed seeds integrate environmental and endogenous signals to break dormancy and initiate growth under optimal conditions. Seed maturation plays an important role in determining the survival of germinating seeds, for example one of the roles of dormancy is to stagger germination to prevent mass growth under suboptimal conditions. The B3-domain transcription factor FUSCA3 (FUS3) is a master regulator of seed development and an important node in hormonal interaction networks in Arabidopsis thaliana. Its function has been mainly characterized during embryonic development, where FUS3 is highly expressed to promote seed maturation and dormancy by regulating ABA/GA levels. Results In this study, we present evidence for a role of FUS3 in delaying seed germination at supraoptimal temperatures that would be lethal for the developing seedlings. During seed imbibition at supraoptimal temperature, the FUS3 promoter is reactivated and induces de novo synthesis of FUS3 mRNA, followed by FUS3 protein accumulation. Genetic analysis shows that FUS3 contributes to the delay of seed germination at high temperature. Unlike WT, seeds overexpressing FUS3 (ML1:FUS3-GFP) during imbibition are hypersensitive to high temperature and do not germinate, however, they can fully germinate after recovery at control temperature reaching 90% seedling survival. ML1:FUS3-GFP hypersensitivity to high temperature can be partly recovered in the presence of fluridone, an inhibitor of ABA biosynthesis, suggesting this hypersensitivity is due in part to higher ABA level in this mutant. Transcriptomic analysis shows that WT seeds imbibed at supraoptimal temperature activate seed-specific genes and ABA biosynthetic and signaling genes, while inhibiting genes that promote germination and growth, such as GA biosynthetic and signaling genes. Conclusion In this study, we have uncovered a novel function for the master regulator of seed maturation, FUS3, in delaying germination at supraoptimal temperature. Physiologically, this is important since delaying germination has a protective role at high temperature. Transcriptomic analysis of seeds imbibed at supraoptimal temperature reveal that a complex program is in place, which involves not only the regulation of heat and dehydration response genes to adjust cellular functions, but also the activation of seed-specific programs and the inhibition of germination-promoting programs to delay germination. PMID:22279962

Diagnosis and management of Silver-Russell syndrome: first international consensus statement.

PubMed

Wakeling, Emma L; Brioude, Frédéric; Lokulo-Sodipe, Oluwakemi; O'Connell, Susan M; Salem, Jennifer; Bliek, Jet; Canton, Ana P M; Chrzanowska, Krystyna H; Davies, Justin H; Dias, Renuka P; Dubern, Béatrice; Elbracht, Miriam; Giabicani, Eloise; Grimberg, Adda; Grønskov, Karen; Hokken-Koelega, Anita C S; Jorge, Alexander A; Kagami, Masayo; Linglart, Agnes; Maghnie, Mohamad; Mohnike, Klaus; Monk, David; Moore, Gudrun E; Murray, Philip G; Ogata, Tsutomu; Petit, Isabelle Oliver; Russo, Silvia; Said, Edith; Toumba, Meropi; Tümer, Zeynep; Binder, Gerhard; Eggermann, Thomas; Harbison, Madeleine D; Temple, I Karen; Mackay, Deborah J G; Netchine, Irène

2017-02-01

This Consensus Statement summarizes recommendations for clinical diagnosis, investigation and management of patients with Silver-Russell syndrome (SRS), an imprinting disorder that causes prenatal and postnatal growth retardation. Considerable overlap exists between the care of individuals born small for gestational age and those with SRS. However, many specific management issues exist and evidence from controlled trials remains limited. SRS is primarily a clinical diagnosis; however, molecular testing enables confirmation of the clinical diagnosis and defines the subtype. A 'normal' result from a molecular test does not exclude the diagnosis of SRS. The management of children with SRS requires an experienced, multidisciplinary approach. Specific issues include growth failure, severe feeding difficulties, gastrointestinal problems, hypoglycaemia, body asymmetry, scoliosis, motor and speech delay and psychosocial challenges. An early emphasis on adequate nutritional status is important, with awareness that rapid postnatal weight gain might lead to subsequent increased risk of metabolic disorders. The benefits of treating patients with SRS with growth hormone include improved body composition, motor development and appetite, reduced risk of hypoglycaemia and increased height. Clinicians should be aware of possible premature adrenarche, fairly early and rapid central puberty and insulin resistance. Treatment with gonadotropin-releasing hormone analogues can delay progression of central puberty and preserve adult height potential. Long-term follow up is essential to determine the natural history and optimal management in adulthood.

Constitutional growth delay pattern of growth in velo-cardio-facial syndrome: longitudinal follow up and final height of two cases.

PubMed

Turan, Serap; Ozdemir, Nihal; Güran, Tülay; Akalın, Figen; Akçay, Teoman; Ayabakan, Canan; Yılmaz, Yüksel; Bereket, Abdullah

2008-01-01

We report two patients with velo-cardio-facial syndrome (VCFS) who were admitted to our pediatric endocrinology clinic because of short stature and followed longitudinally until attainment of final height. Both patients followed a growth pattern consistent with constitutional delay of puberty with normal and near normal final height. Case 2 also had partial growth hormone (GH) deficiency and severe short stature (height SDS -3.4 SDS), but showed spontaneous catch-up and ended up with a final height of -2 SDS. These cases suggest that short stature in children with VCFS is due to a pattern of growth similar to that observed in constitutional delay of growth and puberty.

Risk Factors and Relationship Between Intestinal Parasites and the Growth Retardation and Psychomotor Development Delays of Children in Şanlıurfa, Turkey.

PubMed

Yentur Doni, Nebiye; Yildiz Zeyrek, Fadile; Simsek, Zeynep; Gurses, Gulcan; Sahin, İbrahim

2015-12-01

The objective of this study was to determine the risk factors for and relationship among parasitic infections, growth retardation, and psychomotor developmental delays in children aged 6 years and below. This case-control study was performed in Şanlıurfa in southeastern Turkey between October and December 2007. Data were collected using a structured questionnaire, anthropometry, Ankara Development Screening Inventory, and laboratory analysis of stool specimens. The most common parasite was Giardia intestinalis (42.53%) followed by Enterobius vermicularis (27.58%), Ascaris lumbricoides (18.39%), Hymenolepis nana (5.75%), Trichuris trichiura (3.45%), Escherichia coli (1.15%), and Blastocystis spp. (1.15%). Fifty-eight percent of all children were infected with intestinal parasites; 55.2% had only one parasite, whereas 44.8% had multiple parasites. The children infected with G. intestinalis and other intestinal parasites had significantly higher levels of growth retardation and psychomotor development delay than non-infected children. Children with parasitic infections had growth delay up to 2.9 times, general development delay up to 1.9 times, language-cognitive development delay up to 2.2 times, and fine motor development delay up to 2.9 times higher than children without any parasitic infections. However, no significant relationship among intestinal parasites, gross motor development, social-self skills, and development delay was identified. The education level of parents, poor economic situation, number of households, not washing hands, playing with soil, family history of parasitic infection were the significant risk factors for intestinal parasites. Our study indicates that the presence of either malnutrition or intestinal parasites may put a child in a high-risk group for developmental delays and growth retardation. Therefore, public health interventions can embrace nationwide deworming in children.

Gompertzian stochastic model with delay effect to cervical cancer growth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mazlan, Mazma Syahidatul Ayuni binti; Rosli, Norhayati binti; Bahar, Arifah

2015-02-03

In this paper, a Gompertzian stochastic model with time delay is introduced to describe the cervical cancer growth. The parameters values of the mathematical model are estimated via Levenberg-Marquardt optimization method of non-linear least squares. We apply Milstein scheme for solving the stochastic model numerically. The efficiency of mathematical model is measured by comparing the simulated result and the clinical data of cervical cancer growth. Low values of Mean-Square Error (MSE) of Gompertzian stochastic model with delay effect indicate good fits.

Duration of lack of money for basic needs and growth delay in the Quebec Longitudinal Study of Child Development birth cohort.

PubMed

Ehounoux, N Z; Zunzunegui, M-V; Séguin, L; Nikiema, B; Gauvin, L

2009-01-01

To examine the relationship between duration of lack of money for basic needs and growth delay in a birth cohort. Mothers of children (n = 1929) from the Quebec Longitudinal Study of Child Development (QLSCD) participating when the children were ages 2(1/2) and 4 years were interviewed at home and data were extracted from birth records. Children's height at 4 years old was transformed into an age- and sex-adjusted z-score. A z-score under the 10th percentile of the Centers for Disease Control and Prevention population growth curve was equated with growth delay. Lack of money for basic needs (paying for rent, electricity and/or heating, clothing, medications or other needs) when the children were ages 2(1/2) and 4 years was reported by the mother. Only 2.5% of children experienced two episodes of lack of money for basic needs. Logistic regression analyses showed that, after adjusting for confounding variables, the probability of growth delay at 4 years among children whose families experienced two episodes of lack of money was higher than for their peers who had not lacked money (OR 3.43; 95% CI 1.54 to 7.66). Experiencing lack of money only at 2(1/2) years showed higher but not significant odds of growth delay at 4 years (OR 1.51; 95% CI 0.84 to 2.72), whereas the likelihood of growth delay was similar for children who experienced lack of money only at 4 years and for their counterparts who never lacked money (OR 0.74; 95% CI 0.26 to 2.11). In an industrialised country toddlers whose families experienced persistent lack of money for basic needs are more likely to have growth delay even after controlling for neonatal conditions and their mothers' characteristics.

ROLES OF EPIDERMAL GROWTH FACTOR (EGF) AND TRANSFORMING GROWTH FACTOR-ALPHA (TGF-A) IN MEDIATION OF DIOXIN (TCDD)-INDUCED DELAYS IN DEVELOPMENT OF THE MOUSE MAMMARY GLAND

EPA Science Inventory

Roles of Epidermal Growth Factor (EGF) and Transforming Growth Factor-alpha (TGF-a) in Mediation of Dioxin (TCDD)-Induced Delays in Development of the Mouse Mammary Gland.
Suzanne E. Fenton, Barbara Abbott, Lamont Bryant, and Angela Buckalew. U.S. EPA, NHEERL, Reproductive Tox...

Catalyst–substrate interaction and growth delay in vapor–liquid–solid nanowire growth

NASA Astrophysics Data System (ADS)

Kolíbal, Miroslav; Pejchal, Tomáš; Musálek, Tomáš; Šikola, Tomáš

2018-05-01

Understanding of the initial stage of nanowire growth on a bulk substrate is crucial for the rational design of nanowire building blocks in future electronic and optoelectronic devices. Here, we provide in situ scanning electron microscopy and Auger microscopy analysis of the initial stage of Au-catalyzed Ge nanowire growth on different substrates. Real-time microscopy imaging and elementally resolved spectroscopy clearly show that the catalyst dissolves the underlying substrate if held above a certain temperature. If the substrate dissolution is blocked (or in the case of heteroepitaxy) the catalyst needs to be filled with nanowire material from the external supply, which significantly increases the initial growth delay. The experiments presented here reveal the important role of the substrate in metal-catalyzed nanowire growth and pave the way for different growth delay mitigation strategies.

Catalyst-substrate interaction and growth delay in vapor-liquid-solid nanowire growth.

PubMed

Kolíbal, Miroslav; Pejchal, Tomáš; Musálek, Tomáš; Šikola, Tomáš

2018-05-18

Understanding of the initial stage of nanowire growth on a bulk substrate is crucial for the rational design of nanowire building blocks in future electronic and optoelectronic devices. Here, we provide in situ scanning electron microscopy and Auger microscopy analysis of the initial stage of Au-catalyzed Ge nanowire growth on different substrates. Real-time microscopy imaging and elementally resolved spectroscopy clearly show that the catalyst dissolves the underlying substrate if held above a certain temperature. If the substrate dissolution is blocked (or in the case of heteroepitaxy) the catalyst needs to be filled with nanowire material from the external supply, which significantly increases the initial growth delay. The experiments presented here reveal the important role of the substrate in metal-catalyzed nanowire growth and pave the way for different growth delay mitigation strategies.

Constitutional Growth Delay Pattern of Growth in Velo−Cardio−Facial Syndrome: Longitudinal follow up and final height of two cases

PubMed Central

Özdemir, Nihal; Güran, Tülay; Akalın, Figen; Akçay, Teoman; Ayabakan, Canan; Yılmaz, Yüksel; Bereket, Abdullah

2008-01-01

We report two patients with velo−cardio−facial syndrome (VCFS) who were admitted to our pediatric endocrinology clinic because of short stature and followed longitudinally until attainment of final height. Both patients followed a growth pattern consistent with constitutional delay of puberty with normal and near normal final height. Case 2 also had partial growth hormone (GH) deficiency and severe short stature (height SDS −3.4 SDS), but showed spontaneous catch−up and ended up with a final height of −2 SDS. These cases suggest that short stature in children with VCFS is due to a pattern of growth similar to that observed in constitutional delay of growth and puberty. Conflict of interest:None declared. PMID:21318064

Effects of Phytoplankton Growth Phase on Delayed Settling Behavior of Marine Snow Aggregates at Sharp Density Transitions

NASA Astrophysics Data System (ADS)

Proctor, K. W.; Montgomery, Q. W.; Prairie, J. C.

2016-02-01

Marine snow aggregates play a fundamental role in the marine carbon cycle. Since marine snow aggregates are larger and thus sink faster than individual phytoplankton, aggregates often dominate carbon flux. Previous studies have shown that marine snow aggregates will significantly decrease their settling velocity when passing through sharp density transitions within the ocean, a phenomenon defined as delayed settling. Given the importance of aggregate settling to carbon export, these small-scale changes in aggregate settling dynamics may have significant impacts on the efficiency of the biological pump. However, there is still a lack of knowledge about how different physical properties of aggregates can affect this delayed settling. In this study, we investigated the effect of phytoplankton growth phase on delayed settling behavior. Using phytoplankton cultures stopped at four different growth phases, we formed marine snow aggregates in the laboratory in rotating cylindrical tanks. We then observed individual aggregates as they settled through a stratified tank. We will present data which illustrates that aggregates experience greatly reduced settling rates when passing through sharp density gradients and that the growth phase of the phytoplankton used to form these aggregates has a significant effect on this delayed settling behavior. A thorough understanding of the impact of phytoplankton growth phase on the delayed settling behavior of marine snow will offer insight into the way phytoplankton growth phase may influence the efficiency of the biological pump, carbon flux, and the carbon cycle as a whole.

Anti-Tumor Effect of the Alphavirus-based Virus-like Particle Vector Expressing Prostate-Specific Antigen in a HLA-DR Transgenic Mouse Model of Prostate Cancer

PubMed Central

Riabov, V.; Tretyakova, I.; Alexander, R. B.; Pushko, P.; Klyushnenkova, E. N.

2015-01-01

The goal of this study was to determine if an alphavirus-based vaccine encoding human Prostate-Specific Antigen (PSA) could generate an effective anti-tumor immune response in a stringent mouse model of prostate cancer. DR2bxPSA F1 male mice expressing human PSA and HLA-DRB1*1501 transgenes were vaccinated with virus-like particle vector encoding PSA (VLPV-PSA) followed by the challenge with Transgenic Adenocarcinoma of Mouse Prostate cells engineered to express PSA (TRAMP-PSA). PSA-specific cellular and humoral immune responses were measured before and after tumor challenge. PSA and CD8 reactivity in the tumors was detected by immunohistochemistry. Tumor growth was compared in vaccinated and control groups. We found that VLPV-PSA could infect mouse dendritic cells in vitro and induce a robust PSA-specific immune response in vivo. A substantial proportion of splenic CD8+ T cells (19.6±7.4%) produced IFNγ in response to the immunodominant peptide PSA65–73. In the blood of vaccinated mice, 18.4±4.1% of CD8+ T cells were PSA-specific as determined by the staining with H-2Db/PSA65–73 dextramers. VLPV-PSA vaccination also strongly stimulated production of IgG2a/b anti-PSA antibodies. Tumors in vaccinated mice showed low levels of PSA expression and significant CD8 T cell infiltration. Tumor growth in VLPV-PSA vaccinated mice was significantly delayed at early time points (p=0.002, Gehan-Breslow test). Our data suggest that TC-83-based VLPV-PSA vaccine can efficiently overcome immune tolerance to PSA, mediate rapid clearance of PSA-expressing tumor cells and delay tumor growth. The VLPV-PSA vaccine will undergo further testing for the immunotherapy of prostate cancer. PMID:26319744

Growth Coordination During Drosophila melanogaster Imaginal Disc Regeneration Is Mediated by Signaling Through the Relaxin Receptor Lgr3 in the Prothoracic Gland.

PubMed

Jaszczak, Jacob S; Wolpe, Jacob B; Bhandari, Rajan; Jaszczak, Rebecca G; Halme, Adrian

2016-10-01

Damage to Drosophila melanogaster imaginal discs activates a regeneration checkpoint that (1) extends larval development and (2) coordinates the regeneration of the damaged disc with the growth of undamaged discs. These two systemic responses to damage are both mediated by Dilp8, a member of the insulin/insulin-like growth factor/relaxin family of peptide hormones, which is released by regenerating imaginal discs. Growth coordination between regenerating and undamaged imaginal discs is dependent on Dilp8 activation of nitric oxide synthase (NOS) in the prothoracic gland (PG), which slows the growth of undamaged discs by limiting ecdysone synthesis. Here we demonstrate that the Drosophila relaxin receptor homolog Lgr3, a leucine-rich repeat-containing G-protein-coupled receptor, is required for Dilp8-dependent growth coordination and developmental delay during the regeneration checkpoint. Lgr3 regulates these responses to damage via distinct mechanisms in different tissues. Using tissue-specific RNA-interference disruption of Lgr3 expression, we show that Lgr3 functions in the PG upstream of NOS, and is necessary for NOS activation and growth coordination during the regeneration checkpoint. When Lgr3 is depleted from neurons, imaginal disc damage no longer produces either developmental delay or growth inhibition. To reconcile these discrete tissue requirements for Lgr3 during regenerative growth coordination, we demonstrate that Lgr3 activity in both the CNS and PG is necessary for NOS activation in the PG following damage. Together, these results identify new roles for a relaxin receptor in mediating damage signaling to regulate growth and developmental timing. Copyright © 2016 by the Genetics Society of America.

CO2 induced seawater acidification impacts sea urchin larval development I: elevated metabolic rates decrease scope for growth and induce developmental delay.

PubMed

Stumpp, M; Wren, J; Melzner, F; Thorndyke, M C; Dupont, S T

2011-11-01

Anthropogenic CO(2) emissions are acidifying the world's oceans. A growing body of evidence is showing that ocean acidification impacts growth and developmental rates of marine invertebrates. Here we test the impact of elevated seawater pCO(2) (129 Pa, 1271 μatm) on early development, larval metabolic and feeding rates in a marine model organism, the sea urchin Strongylocentrotus purpuratus. Growth and development was assessed by measuring total body length, body rod length, postoral rod length and posterolateral rod length. Comparing these parameters between treatments suggests that larvae suffer from a developmental delay (by ca. 8%) rather than from the previously postulated reductions in size at comparable developmental stages. Further, we found maximum increases in respiration rates of +100% under elevated pCO(2), while body length corrected feeding rates did not differ between larvae from both treatments. Calculating scope for growth illustrates that larvae raised under high pCO(2) spent an average of 39 to 45% of the available energy for somatic growth, while control larvae could allocate between 78 and 80% of the available energy into growth processes. Our results highlight the importance of defining a standard frame of reference when comparing a given parameter between treatments, as observed differences can be easily due to comparison of different larval ages with their specific set of biological characters. Copyright © 2011 Elsevier Inc. All rights reserved.

Osterix/Sp7 limits cranial bone initiation sites and is required for formation of sutures

PubMed Central

Kague, Erika; Roy, Paula; Asselin, Garrett; Hu, Gui; Stanley, Alexandra; Albertson, Craig; Simonet, Jacqueline; Fisher, Shannon

2017-01-01

During growth, individual skull bones overlap at sutures, where osteoblast differentiation and bone deposition occur. Mutations causing skull malformations have revealed some required genes, but many aspects of suture regulation remain poorly understood. We describe a zebrafish mutation in osterix/sp7, which causes a generalized delay in osteoblast maturation. While most of the skeleton is patterned normally, mutants have specific defects in the anterior skull and upper jaw, and the top of the skull comprises a random mosaic of bones derived from individual initiation sites. Osteoblasts at the edges of the bones are highly proliferative and fail to differentiate, consistent with global changes in gene expression. We propose that signals from the bone itself are required for orderly recruitment of precursor cells and growth along the edges. The delay in bone maturation caused by loss of Sp7 leads to unregulated bone formation, revealing a new mechanism for patterning the skull and sutures. PMID:26992365

The effects of bilingual growth on toddlers’ executive function

PubMed Central

Crivello, Cristina; Kuzyk, Olivia; Rodrigues, Monyka; Friend, Margaret; Zesiger, Pascal; Poulin-Dubois, Diane

2015-01-01

The mastery of two languages provides bilingual speakers with cognitive benefits over monolinguals, particularly on cognitive flexibility and selective attention. However, extant research is limited to comparisons between monolinguals and bilinguals at a single point in time. This study investigated whether growth in bilingual proficiency, as shown by an increased number of translation equivalents (TEs) over a 7-month period, improves executive function. We hypothesized that bilingual toddlers with a larger increase of TEs would have more practice in switching across lexical systems, boosting executive function abilities. Expressive vocabulary and TEs were assessed at 24 and 31 months of age. A battery of tasks, including conflict, delay, and working memory tasks, was administered at 31 months. As expected, we observed a task-specific advantage in inhibitory control in bilinguals. More important, within the bilingual group, larger increases in the number of TEs predicted better performance on conflict tasks but not on delay tasks. This unique longitudinal design confirms the relation between executive function and early bilingualism. PMID:26402219

Health of children adopted from Ethiopia.

PubMed

Miller, Laurie C; Tseng, Beverly; Tirella, Linda G; Chan, Wilma; Feig, Emily

2008-09-01

Since 2000, American families have adopted 1,700 children from Ethiopia. Little is known about the health and development of these children. Retrospective chart review of the arrival health status of all 50 (26F:24M) children from Ethiopia/Eritrea seen in the International Adoption Clinic. Prior to adoption, most children resided with relatives; 36% were >18 months old prior to entry into care. More than 50% were true orphans, often due to HIV. Arrival age ranged from 3 months to 15 years (mean +/- SD 4 years +/- 43.8 months). At arrival, growth z scores were near-average (weight -.59, height -.64, head circumference -.09); significantly better than adopted children Guatemala, China, or Russia seen in our clinic. However, some Ethiopian children were significantly growth delayed (WAZ < or =-2, 8%, HAZ 12%, HCZ 18%). Age at adoption did not relate to growth delays. Medical issues on arrival included intestinal parasites (53%, [14% with > or =3 types]), skin infections (45%), dental caries (25%), elevated liver transaminases (20%), latent tuberculosis (18%), and hepatitis B (2%). Age-appropriate vaccines had been administered in 15-77% of children (depending on specific vaccine). Behavior problems were uncommon. Gross/fine motor and cognitive skills were approximately 86% of expected for age. Age correlated inversely with developmental scores for cognition (r = -.49, P = .003). Five children had age reassignments. Ethiopian/Eritean adoptees differ from other groups of internationally adopted children: they reside for relatively long periods of time with relatives prior to institutionalization, often have uncertain ages, exhibit few behavioral problems at arrival, have better growth, and may have less severe developmental delays. Whether these differences at arrival predict better outcomes for the Ethiopian/Eritrean children is unknown.

Induction of Metamorphosis Causes Differences in Sex-Specific Allocation Patterns in Axolotls (Ambystoma mexicanum) that Have Different Growth Histories.

PubMed

Clarkson, Pamela M; Beachy, Christopher K

2015-12-01

We tested the hypothesis that salamanders growing at different rates would have allocation patterns that differ among male and female metamorphic and larval salamanders. We raised individual axolotls, Ambystoma mexicanum , on four food regimes: constant high growth (throughout the experiment), constant low growth (restricted throughout the experiment), high growth switched to low growth (ad libitum switched after 140 d to restricted), and low growth switched to high growth (restricted switched after 140 d to ad libitum). Because axolotls are obligate paedomorphs, we exposed half of the salamanders to thyroid hormone to induce metamorphosis. We assayed growth and dissected and weighed gonads and fat bodies. Salamanders that were switched from restricted to ad libitum food regime delayed metamorphosis. In all treatment groups, females had larger gonads than males and males had larger fat bodies than females. The association between storage and reproduction differed between larvae and metamorphs and depended on sex.

Polyploidization delay in rat hepatocytes under liver growth inhibition by hypokinesia

NASA Technical Reports Server (NTRS)

Faktor, V. M.; Malyutin, V. F.; Li, S. Y.; Brodskiy, V. Y.

1981-01-01

A study of young rats, weighing 55 to 59 g, after being for 10 days in conditions of limited mobility, shows a retardation of body growth as well as that of liver growth. The decrease in the rate of growth is accompanied by a reduction of cell proliferation and by delay polyploidization of hepatocytes in the liver of experimental rats. The materials, methods, and results of research are discussed.

Constitutional Delay Influences the Auxological Response to Growth Hormone Treatment in Children with Short Stature and Growth Hormone Sufficiency

PubMed Central

Gunn, Katherine C.; Cutfield, Wayne S.; Hofman, Paul L.; Jefferies, Craig A.; Albert, Benjamin B.; Gunn, Alistair J.

2014-01-01

In a retrospective, population based cohort study, we examined whether constitutional delay was associated with the growth response to growth hormone (GH) in children with short stature and normal GH responses. 70 patients were treated with 21 GH iu/m2/week from 1975 to 2013 throughout New Zealand. Demographic and auxological data were prospectively collected and standard deviation scores (SDS) were calculated for height (HtSDS), yearly growth velocity (GV-SDS), body mass index (BMI-SDS) and predicted adult height (PAH-SDS) at time of the last available bone age. In the first year, GH was associated with marked increase in HtSDS (+0.46 (0.19, 0.76), p < 0.001) and GV-SDS (from −1.9 (−3.6, −0.7) to +2.7 (0.45, 4.2), p < 0.001). The increase in HtSDS but not in GV-SDS was greatest with younger patients and greater bone age delay, with no effect of sex, BMI-SDS or baseline HtSDS. PAH-SDS increased with treatment (+0.94 (0.18, 1.5)); increased PAH-SDS was associated with less bone age delay and greater initial increase in HtSDS. This study shows that greater bone age delay was associated with greater initial improvement in height but less improvement in predicted adult heights, suggesting that children with very delayed bone ages may show accelerated maturation during GH treatment. PMID:25317732

Constitutional delay influences the auxological response to growth hormone treatment in children with short stature and growth hormone sufficiency.

PubMed

Gunn, Katherine C; Cutfield, Wayne S; Hofman, Paul L; Jefferies, Craig A; Albert, Benjamin B; Gunn, Alistair J

2014-08-14

In a retrospective, population based cohort study, we examined whether constitutional delay was associated with the growth response to growth hormone (GH) in children with short stature and normal GH responses. 70 patients were treated with 21 GH iu/m2/week from 1975 to 2013 throughout New Zealand. Demographic and auxological data were prospectively collected and standard deviation scores (SDS) were calculated for height (HtSDS), yearly growth velocity (GV-SDS), body mass index (BMI-SDS) and predicted adult height (PAH-SDS) at time of the last available bone age. In the first year, GH was associated with marked increase in HtSDS (+0.46 (0.19, 0.76), p < 0.001) and GV-SDS (from -1.9 (-3.6, -0.7) to +2.7 (0.45, 4.2), p < 0.001). The increase in HtSDS but not in GV-SDS was greatest with younger patients and greater bone age delay, with no effect of sex, BMI-SDS or baseline HtSDS. PAH-SDS increased with treatment (+0.94 (0.18, 1.5)); increased PAH-SDS was associated with less bone age delay and greater initial increase in HtSDS. This study shows that greater bone age delay was associated with greater initial improvement in height but less improvement in predicted adult heights, suggesting that children with very delayed bone ages may show accelerated maturation during GH treatment.

Could head circumference be used to screen for autism in young males with developmental delay?

PubMed

Gray, Kylie M; Taffe, John; Sweeney, Deborah J; Forster, Sheridan; Tonge, Bruce J

2012-04-01

Research has suggested an abnormal acceleration in head circumference growth in children with autism within the first 12 months of life. This study aimed to examine head circumference at birth and head circumference growth rates in young children with autism and developmental delay, and young children with developmental delay without autism. This study assessed head circumference at birth and rate of change in head circumference in young children with autism (n=86) and children with developmental delay without autism (n=40). For both groups of children, head circumference at birth and head circumference growth were compared with Centers for Disease Control normative data. No differences were found between the group of children with autism and developmental delay compared with the group with developmental delay only. However, when the sample was compared with a range of selected Centers for Disease Control normative medians, the children with autism were found to have significantly smaller head circumferences at birth and significantly larger head circumference at 18.5 months of age. These results are discussed in relation to the potential of accelerated head circumference growth as an early marker for autism. This study failed to find a difference in the head circumferences of children with autism and developmental delay and children with developmental delay only, thus suggesting that head circumference measurement has limited value as an early marker for autism. © 2011 The Authors. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Early life exposure to PCB126 results in delayed mortality and growth impairment in the zebrafish larvae.

PubMed

Di Paolo, Carolina; Groh, Ksenia J; Zennegg, Markus; Vermeirssen, Etiënne L M; Murk, Albertinka J; Eggen, Rik I L; Hollert, Henner; Werner, Inge; Schirmer, Kristin

2015-12-01

The occurrence of chronic or delayed toxicity resulting from the exposure to sublethal chemical concentrations is an increasing concern in environmental risk assessment. The Fish Embryo Toxicity (FET) test with zebrafish provides a reliable prediction of acute toxicity in adult fish, but it cannot yet be applied to predict the occurrence of chronic or delayed toxicity. Identification of sublethal FET endpoints that can assist in predicting the occurrence of chronic or delayed toxicity would be advantageous. The present study characterized the occurrence of delayed toxicity in zebrafish larvae following early exposure to PCB126, previously described to cause delayed effects in the common sole. The first aim was to investigate the occurrence and temporal profiles of delayed toxicity during zebrafish larval development and compare them to those previously described for sole to evaluate the suitability of zebrafish as a model fish species for delayed toxicity assessment. The second aim was to examine the correlation between the sublethal endpoints assessed during embryonal and early larval development and the delayed effects observed during later larval development. After exposure to PCB126 (3-3000ng/L) until 5 days post fertilization (dpf), larvae were reared in clean water until 14 or 28 dpf. Mortality and sublethal morphological and behavioural endpoints were recorded daily, and growth was assessed at 28 dpf. Early life exposure to PCB126 caused delayed mortality (300 ng/L and 3000 ng/L) as well as growth impairment and delayed development (100 ng/L) during the clean water period. Effects on swim bladder inflation and cartilaginous tissues within 5 dpf were the most promising for predicting delayed mortality and sublethal effects, such as decreased standard length, delayed metamorphosis, reduced inflation of swim bladder and column malformations. The EC50 value for swim bladder inflation at 5 dpf (169 ng/L) was similar to the LC50 value at 8 dpf (188 and 202 ng/L in two experiments). Interestingly, the patterns of delayed mortality and delayed effects on growth and development were similar between sole and zebrafish. This indicates the comparability of critical developmental stages across divergent fish species such as a cold water marine flatfish and a tropical freshwater cyprinid. Additionally, sublethal effects in early embryo-larval stages were found promising for predicting delayed lethal and sublethal effects of PCB126. Therefore, the proposed method with zebrafish is expected to provide valuable information on delayed mortality and delayed sublethal effects of chemicals and environmental samples that may be extrapolated to other species. Copyright © 2015 Elsevier B.V. All rights reserved.

Evidence for a Transketolase-Mediated Metabolic Checkpoint Governing Biotrophic Growth in Rice Cells by the Blast Fungus Magnaporthe oryzae

PubMed Central

Fernandez, Jessie; Marroquin-Guzman, Margarita; Wilson, Richard A.

2014-01-01

The blast fungus Magnaporthe oryzae threatens global food security through the widespread destruction of cultivated rice. Foliar infection requires a specialized cell called an appressorium that generates turgor to force a thin penetration hypha through the rice cuticle and into the underlying epidermal cells, where the fungus grows for the first days of infection as a symptomless biotroph. Understanding what controls biotrophic growth could open new avenues for developing sustainable blast intervention programs. Here, using molecular genetics and live-cell imaging, we dismantled M. oryzae glucose-metabolizing pathways to reveal that the transketolase enzyme, encoded by TKL1, plays an essential role in facilitating host colonization during rice blast disease. In the absence of transketolase, Δtkl1 mutant strains formed functional appressoria that penetrated rice cuticles successfully and developed invasive hyphae (IH) in rice cells from primary hyphae. However, Δtkl1 could not undertake sustained biotrophic growth or cell-to-cell movement. Transcript data and observations using fluorescently labeled histone H1:RFP fusion proteins indicated Δtkl1 mutant strains were alive in host cells but were delayed in mitosis. Mitotic delay could be reversed and IH growth restored by the addition of exogenous ATP, a metabolite depleted in Δtkl1 mutant strains. We show that ATP might act via the TOR signaling pathway, and TOR is likely a downstream target of activation for TKL1. TKL1 is also involved in controlling the migration of appressorial nuclei into primary hyphae in host cells. When taken together, our results indicate transketolase has a novel role in mediating - via ATP and TOR signaling - an in planta-specific metabolic checkpoint that controls nuclear migration from appressoria into primary hyphae, prevents mitotic delay in early IH and promotes biotrophic growth. This work thus provides new information about the metabolic strategies employed by M. oryzae to enable rice cell colonization. PMID:25188286

Effect of time between x-irradiation and chemotherapy on the growth of three solid mouse tumors. III. Cis-diamminedichloroplatinum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Twentyman, P.R.; Kallman, R.F.; Brown, J.M.

1979-08-01

Experiments have been carried out to determine the effect of different time intervals between the administration of x-irradiation (1200 rad) and cis-diamminedichloroplatinum (cis-DDP) (7 mg/kg) on the growth delay produced in three mouse tumors. The tumors used were the EMT6 tumor in BALB/c mice and the KHT and RIF-1 sarcomas in C3H mice. All tumors were grown intramuscularly in the gastrocnemius muscle and treatment was carried out at a mean tumor weight of 450 mg. Time to reach 2X (for KHT) or 4X (for EMT6 and RIF-1) treatment volume was used as the endpoint of response. The drug was administeredmore » by the intraperitoneal route either 24, 6, or 2 h before radiation, immediately before the start of radiation, or 3, 6, or 24 h after radiation. All irradiations were carried out in unanesthetized mice. The growth delays due to the drug alone were 2, 10, and 2 days for the EMT6, RIF-1, and KHT tumors, respectively. In the RIF-1 and KHT tumors, the combined modality groups tend to show longer growth delays than predicted by the addition of the growth delays for the single agents. For the EMT6 tumor, however, the trend is in the opposite direction. There is no particular timing between irradiation and drug administration which appears to produce consistently longer or shorter growth delays from system to system.« less

Effect of time between x-irradiation and chemotherapy on the growth of three solid mouse tumors. IV. Actinomycin-d

DOE Office of Scientific and Technical Information (OSTI.GOV)

Twentyman, P.R.; Kallman, R.F.; Brown, J.M.

1979-09-01

Experiments have been carried out to determine the effect of different intervals between the administration of x-radiation (1200 rad) and actinomycin-D (200 ..mu..g/kg) on the growth delay produced in three mouse tumors. The tumors used were the EMT6 tumor in BALB/c mice and the KHT and RIF-1 sarcomas in C3H mice. All tumors were grown intramuscularly in the gastrocnemius muscle, and treatment was carried out at a mean tumor weight of 450 mg. Time to reach 2 x (for KHT) or 4 x (for EMT6 and RIF-1) treatment volume was used as the endpoint of response. The drug was administeredmore » intraperitoneally either 24, 6, or 2 hr before radiation, immediately before the start of radiation, or 3, 6, or 24 hr after radiation. All irradiations were carried out in unanesthetized mice. For a single administration at this dose level (close to the maximum tolerated dose) actinomycin-D did not produce a significant delay in the growth of any of the tumors. For the RIF-1 and KHT tumors, the growth delays produced by drug/radiation combinations generally were not significantly greater than that produced by irradiation alone. For the EMT6 tumor, great variability in the growth delays of combined modality groups seen, with mean growth delays significantly longer than predicted by the radiation alone data. No consistent dependence on timing between irradiation and drug administration was seen.« less

Relations of Growth in Effortful Control to Family Income, Cumulative Risk, and Adjustment in Preschool-age Children

PubMed Central

Lengua, Liliana J.; Moran, Lyndsey; Zalewski, Maureen; Ruberry, Erika; Kiff, Cara; Thompson, Stephanie

2014-01-01

The study examined growth in effortful control (executive control, delay ability) in relation to income, cumulative risk (aggregate of demographic and psychosocial risk factors), and adjustment in 306 preschool-age children (50% girls, 50% boys) from families representing a range of income (29% at- or near-poverty; 28% lower-income; 25% middle-income; 18% upper-income), with 4 assessments starting at 36–40 mos. Income was directly related to levels of executive control and delay ability. Cumulative risk accounted for the effects of income on delay ability but not executive control. Higher initial executive control and slope of executive control and delay ability predicted academic readiness, whereas levels, but not growth, of executive control and delay ability predicted social competence and adjustment problems. Low income is a marker for lower effortful control, which demonstrates additive or mediating effects in the relation of income to children’s preschool adjustment. PMID:25253079

A variant microcephalic osteodysplastic slender-bone disorder with growth hormone deficiency and a pigmentary retinopathy.

PubMed

Maclean, K; Ambler, G; Flaherty, M; Kozlowski, K; Adès, L C

2002-10-01

We present the case of a 3-year-old boy with post-natal growth failure, microcephaly, developmental delay, facial dysmorphism, an evolving pigmentary retinopathy, pituitary hypoplasia, micropenis, and growth hormone (GH) deficiency. He has a microcephalic osteodysplastic slender-bone disorder with disharmonic delayed osseous maturation, most closely resembling patients with microcephalic osteodysplastic primordial dwarfism type II (MOPD II). Intrauterine growth retardation, a universal finding in the MOPD II, was absent in our patient.

Nicotine-induced retardation of chondrogenesis through down-regulation of IGF-1 signaling pathway to inhibit matrix synthesis of growth plate chondrocytes in fetal rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deng, Yu; Cao, Hong; Cu, Fenglong

Previous studies have confirmed that maternal tobacco smoking causes intrauterine growth retardation (IUGR) and skeletal growth retardation. Among a multitude of chemicals associated with cigarette smoking, nicotine is one of the leading candidates for causing low birth weights. However, the possible mechanism of delayed chondrogenesis by prenatal nicotine exposure remains unclear. We investigated the effects of nicotine on fetal growth plate chondrocytes in vivo and in vitro. Rats were given 2.0 mg/kg·d of nicotine subcutaneously from gestational days 11 to 20. Prenatal nicotine exposure increased the levels of fetal blood corticosterone and resulted in fetal skeletal growth retardation. Moreover, nicotinemore » exposure induced the inhibition of matrix synthesis and down-regulation of insulin-like growth factor 1 (IGF-1) signaling in fetal growth plates. The effects of nicotine on growth plates were studied in vitro by exposing fetal growth plate chondrocytes to 0, 1, 10, or 100 μM of nicotine for 10 days. Nicotine inhibited matrix synthesis and down-regulated IGF-1 signaling in chondrocytes in a concentration-dependent manner. These results suggest that prenatal nicotine exposure induces delayed chondrogenesis and that the mechanism may involve the down-regulation of IGF-1 signaling and the inhibition of matrix synthesis by growth plate chondrocytes. The present study aids in the characterization of delayed chondrogenesis caused by prenatal nicotine exposure, which might suggest a candidate mechanism for intrauterine origins of osteoporosis and osteoarthritis. - Highlights: ► Prenatal nicotine-exposure could induce delayed chondrogenesis in fetal rats. ► Nicotine inhibits matrix synthesis of fetal growth plate chondrocytes. ► Nicotine inhibits IGF-1 signaling pathway in fetal growth plate chondrocytes.« less

Mechanics of the Delayed Fracture of Viscoelastic Bodies with Cracks: Theory and Experiment (Review)

NASA Astrophysics Data System (ADS)

Kaminsky, A. A.

2014-09-01

Theoretical and experimental studies on the deformation and delayed fracture of viscoelastic bodies due to slow subcritical crack growth are reviewed. The focus of this review is on studies of subcritical growth of cracks with well-developed fracture process zones, the conditions that lead to their critical development, and all stages of slow crack growth from initiation to the onset of catastrophic growth. Models, criteria, and methods used to study the delayed fracture of viscoelastic bodies with through and internal cracks are analyzed. Experimental studies of the fracture process zones in polymers using physical and mechanical methods as well as theoretical studies of these zones using fracture mesomechanics models that take into account the structural and rheological features of polymers are reviewed. Particular attention is given to crack growth in anisotropic media, the effect of the aging of viscoelastic materials on their delayed fracture, safe external loads that do not cause cracks to propagate, the mechanism of multiple-flaw fracture of viscoelastic bodies with several cracks and, especially, processes causing cracks to coalesce into a main crack, which may result in a break of the body. Methods and results of solving two- and three-dimensional problems of the mechanics of delayed fracture of aging and non-aging viscoelastic bodies with cracks under constant and variable external loads, wedging, and biaxial loads are given

Delayed flood recession in central Yangtze floodplains can cause significant food shortages for wintering geese: results of inundation experiment.

PubMed

Guan, Lei; Wen, Li; Feng, Duoduo; Zhang, Hong; Lei, Guangchun

2014-12-01

Carex meadows are critical habitat for wintering geese in the floodplains of the middle and lower reaches of Yangtze River, China. These meadows follow a growth cycle closely tied to the seasonal hydrological fluctuation: as water levels recede in the fall, exposed mudflats provide habitat for Carex spp. growth. The seasonal growth of Carex overlaps the arrival of wintering geese and provides an important food source for the migrants. Recent alterations to the Yangtze's hydrology, however, have disrupted the synchronous relationship between water levels, Carex growth and wintering geese at Dongting Lake. In October 2012, we carried out an outdoor mesocosm experiment to investigate potential impacts of delayed water recession on the germination and growth of Carex heterolepis, the dominant Carex species at Dongting Lake, to understand how changes in hydrology might impact wintering goose habitat. Results showed that the delayed flood recession exerted significant impact on the first growth cycle of Carex growth. Prolonged inundation significantly lowered the intrinsic growth rate (P = 0.03) and maximum growth rates (P = 0.02). It also took significantly longer time to reach the peak growth rate (P = 0.04 and 0.05 for number of shoot and biomass, respectively). As a result, biomass accumulation was reduced by 45, 62 and 90 % for 10-day, 20-day and 30-day inundation treatments, respectively. These results indicate a severe risk of food shortage for wintering geese when water recession delayed. This potential risk should be taken into consideration when operating any hydrological control structures that alter the flood regimes in Dongting Lake.

Earlier growing seasons and changes in migration timing influence carbon uptake and plant production in Arctic coastal wetlands

NASA Astrophysics Data System (ADS)

Leffler, A. J.; Beard, K. H.; Kelsey, K.; Choi, R. T.; Welker, J. M.

2015-12-01

The wetlands of the Yukon-Kuskokwim Delta in western Alaska are important breeding areas for geese and are experiencing rapid climate change, specifically earlier onset of the growing season. Consequently, geese arrive 'later' in the growing season than in the past, potentially setting up a phenological mismatch with consequences for their nutrition, plant growth, and C and N processes in the ecosystem. We examined the interactive effects between the start of the growing season and Black Brant arrival time on these processes in a manipulative experiment. Advancing the growing season had a modest influence on CO2 exchange and plant growth. An early growing season shifted the rate of net ecosystem exchange (NEE) by 1-1.5 µmol m-2 s-1 toward a carbon (C) source. This change was driven by an increase in the rate of ecosystem respiration (ER). The advanced growing season nearly doubled the rate of leaf elongation in the early summer and this difference persisted as taller vegetation later in the year; belowground biomass was not affected. Timing of grazing had greater influence on CO2 exchange and plant growth. Grazing early in the season shifted the system to a carbon source by ca. 2 μmol m-2 s-1 while delaying grazing enhanced the carbon sink by 1 μmol m-2 s-1. Here, the influence was not through ER, but through reducing and enhancing standing leaf area, respectively. Early grazing also reduced season-long root production by over 50% while delayed grazing enhanced root production by 30%. Although delaying grazing enhanced C uptake and promoted plant growth in this ecosystem, leaf tissue in delayed-grazing plots had C:N of 16.7 compared to 14.2 in the typical-grazing plots, potentially reducing the digestibility of goose forage and slowing rates of decomposition. Biotic forcing in arctic tundra can thus be major drivers of ecosystem function and need to be considered as tundra system respond to changing conditions.

Temporally controlled release of multiple growth factors from a self-assembling peptide hydrogel

NASA Astrophysics Data System (ADS)

Bruggeman, Kiara F.; Rodriguez, Alexandra L.; Parish, Clare L.; Williams, Richard J.; Nisbet, David R.

2016-09-01

Protein growth factors have demonstrated great potential for tissue repair, but their inherent instability and large size prevents meaningful presentation to biologically protected nervous tissue. Here, we create a nanofibrous network from a self-assembling peptide (SAP) hydrogel to carry and stabilize the growth factors. We significantly reduced growth factor degradation to increase their lifespan by over 40 times. To control the temporal release profile we covalently attached polysaccharide chitosan molecules to the growth factor to increase its interactions with the hydrogel nanofibers and achieved a 4 h delay, demonstrating the potential of this method to provide temporally controlled growth factor delivery. We also describe release rate based analysis to examine the growth factor delivery in more detail than standard cumulative release profiles allow and show that the chitosan attachment method provided a more consistent release profile with a 60% reduction in fluctuations. To prove the potential of this system as a complex growth factor delivery platform we demonstrate for the first time temporally distinct release of multiple growth factors from a single tissue specific SAP hydrogel: a significant goal in regenerative medicine.

Testosterone treatment and arginine-induced growth hormone stimulation in male delayed puberty: effects on serum calcium, phosphate and vitamin D metabolites.

PubMed

Hyldstrup, L; Christiansen, C; Nielsen, M D; Transbøl, I

1984-06-01

Hormonal changes after arginine-induced growth hormone stimulation and subsequent testosterone treatment were examined in 5 patients classified as having male delayed puberty. All the patients responded well to growth hormone stimulation and a significant negative correlation was found between the delay in height age and the maximal growth hormone response, r = 0.80, P less than 0.05. The testosterone treatment did not alter this pattern. Changes in PTH, 25OHD, 24.25(OH)2D, and 1.25(OH)2D were examined at 24 h after the infusion. The results showed significant reductions in PTH (P less than 0.05) and 24.25 (OH)2D (P less than 0.05) and a possible increase in 1.25(OH)2D, whereas 25OHD remained unchanged. These results may support the conception of growth hormone as a common denominator of growth and bone metabolism.

Role of Diet Modulation and AMPK in Ovarian Cancer Progression and Outcome

DTIC Science & Technology

2014-10-01

preventive agent in not only preventing or delaying ovarian cancer growth but also cancers. It can be the ‘ aspirin ’ for cancers...preventive agent in not only preventing or delaying ovarian cancer growth but also cancers. It can be the ‘ aspirin ’ for cancers

Determinants of relative skeletal maturity in South African children.

PubMed

Hawley, Nicola L; Rousham, Emily K; Johnson, William; Norris, Shane A; Pettifor, John M; Cameron, Noël

2012-01-01

The variation of skeletal maturity about chronological age is a sensitive indicator of population health. Age appropriate or advanced skeletal maturity is a reflection of adequate environmental and social conditions, whereas delayed maturation suggests inadequate conditions for optimal development. There remains a paucity of data, however, to indicate which specific biological and environmental factors are associated with advancement or delay in skeletal maturity. The present study utilises longitudinal data from the South African Birth to Twenty (Bt20) study to indentify predictors of relative skeletal maturity (RSM) in early adolescence. A total of 244 black South African children (n=131 male) were included in this analysis. Skeletal maturity at age 9/10 years was assessed using the Tanner and Whitehouse III RUS technique. Longitudinal data on growth, socio-economic position and pubertal development were entered into sex-specific multivariable general linear regression models with relative skeletal maturity (skeletal age-chronological age) as the outcome. At 9/10 years of age males showed an average of 0.66 years delay in skeletal maturation relative to chronological age. Females showed an average of 1.00 year delay relative to chronological age. In males, being taller at 2 years (p<0.01) and heavier at 2 years (p<0.01) predicted less delay in RSM at age 9/10 years, independent of current size and body composition. In females, both height at 2 years and conditional weight at 2 years predicted less delay in RSM at 9/10 years (p<0.05) but this effect was mediated by current body composition. Having greater lean mass at 9/10 years was associated with less delayed RSM in females (p<0.01) as was pubertal status at the time of skeletal maturity assessment (p<0.01). This study identifies several predictors of skeletal maturation at 9/10 years, indicating a role for early life exposures in determining the rate of skeletal maturation during childhood independently of current stature. Copyright © 2011 Elsevier Inc. All rights reserved.

Stability and Hopf bifurcation for a regulated logistic growth model with discrete and distributed delays

NASA Astrophysics Data System (ADS)

Fang, Shengle; Jiang, Minghui

2009-12-01

In this paper, we investigate the stability and Hopf bifurcation of a new regulated logistic growth with discrete and distributed delays. By choosing the discrete delay τ as a bifurcation parameter, we prove that the system is locally asymptotically stable in a range of the delay and Hopf bifurcation occurs as τ crosses a critical value. Furthermore, explicit algorithm for determining the direction of the Hopf bifurcation and the stability of the bifurcating periodic solutions is derived by normal form theorem and center manifold argument. Finally, an illustrative example is also given to support the theoretical results.

A new balancing act: The many roles of melatonin and serotonin in plant growth and development

PubMed Central

Erland, Lauren A E; Murch, Susan J; Reiter, Russel J; Saxena, Praveen K

2015-01-01

Melatonin and serotonin are indoleamines first identified as neurotransmitters in vertebrates; they have now been found to be ubiquitously present across all forms of life. Both melatonin and serotonin were discovered in plants several years after their discovery in mammals, but their presence has now been confirmed in almost all plant families. The mechanisms of action of melatonin and serotonin are still poorly defined. Melatonin and serotonin possess important roles in plant growth and development, including functions in chronoregulation and modulation of reproductive development, control of root and shoot organogenesis, maintenance of plant tissues, delay of senescence, and responses to biotic and abiotic stresses. This review focuses on the roles of melatonin and serotonin as a novel class of plant growth regulators. Their roles in reproductive and vegetative plant growth will be examined including an overview of current hypotheses and knowledge regarding their mechanisms of action in specific responses. PMID:26418957

Scaling-up vaccine production: implementation aspects of a biomass growth observer and controller.

PubMed

Soons, Zita I T A; van den IJssel, Jan; van der Pol, Leo A; van Straten, Gerrit; van Boxtel, Anton J B

2009-04-01

This study considers two aspects of the implementation of a biomass growth observer and specific growth rate controller in scale-up from small- to pilot-scale bioreactors towards a feasible bulk production process for whole-cell vaccine against whooping cough. The first is the calculation of the oxygen uptake rate, the starting point for online monitoring and control of biomass growth, taking into account the dynamics in the gas-phase. Mixing effects and delays are caused by amongst others the headspace and tubing to the analyzer. These gas phase dynamics are modelled using knowledge of the system in order to reconstruct oxygen consumption. The second aspect is to evaluate performance of the monitoring and control system with the required modifications of the oxygen consumption calculation on pilot-scale. In pilot-scale fed-batch cultivation good monitoring and control performance is obtained enabling a doubled concentration of bulk vaccine compared to standard batch production.

A new balancing act: The many roles of melatonin and serotonin in plant growth and development.

PubMed

Erland, Lauren A E; Murch, Susan J; Reiter, Russel J; Saxena, Praveen K

2015-01-01

Melatonin and serotonin are indoleamines first identified as neurotransmitters in vertebrates; they have now been found to be ubiquitously present across all forms of life. Both melatonin and serotonin were discovered in plants several years after their discovery in mammals, but their presence has now been confirmed in almost all plant families. The mechanisms of action of melatonin and serotonin are still poorly defined. Melatonin and serotonin possess important roles in plant growth and development, including functions in chronoregulation and modulation of reproductive development, control of root and shoot organogenesis, maintenance of plant tissues, delay of senescence, and responses to biotic and abiotic stresses. This review focuses on the roles of melatonin and serotonin as a novel class of plant growth regulators. Their roles in reproductive and vegetative plant growth will be examined including an overview of current hypotheses and knowledge regarding their mechanisms of action in specific responses.

ssrA (tmRNA) Plays a Role in Salmonella enterica Serovar Typhimurium Pathogenesis

PubMed Central

Julio, Steven M.; Heithoff, Douglas M.; Mahan, Michael J.

2000-01-01

Escherichia coli ssrA encodes a small stable RNA molecule, tmRNA, that has many diverse functions, including tagging abnormal proteins for degradation, supporting phage growth, and modulating the activity of DNA binding proteins. Here we show that ssrA plays a role in Salmonella enterica serovar Typhimurium pathogenesis and in the expression of several genes known to be induced during infection. Moreover, the phage-like attachment site, attL, encoded within ssrA, serves as the site of integration of a region of Salmonella-specific sequence; adjacent to the 5′ end of ssrA is another region of Salmonella-specific sequence with extensive homology to predicted proteins encoded within the unlinked Salmonella pathogenicity island SPI4. S. enterica serovar Typhimurium ssrA mutants fail to support the growth of phage P22 and are delayed in their ability to form viable phage particles following induction of a phage P22 lysogen. These data indicate that ssrA plays a role in the pathogenesis of Salmonella, serves as an attachment site for Salmonella-specific sequences, and is required for the growth of phage P22. PMID:10692360

Specificity redirection by CAR with human VEGFR-1 affinity endows T lymphocytes with tumor-killing ability and anti-angiogenic potency.

PubMed

Wang, W; Ma, Y; Li, J; Shi, H-S; Wang, L-Q; Guo, F-C; Zhang, J; Li, D; Mo, B-H; Wen, F; Liu, T; Liu, Y-T; Wang, Y-S; Wei, Y-Q

2013-10-01

Immunotherapy that is based on adoptive transfer of T lymphocytes, which are genetically modified to express chimeric antigen receptors (CARs) that recognize tumor-associated antigens, has been demonstrated to be an efficient cancer therapy. Vascular endothelial growth factor receptor-1 (VEGFR-1), a vital molecule involved in tumor growth and angiogenesis, has not been targeted by CAR-modified T lymphocytes. In this study, we generated CAR-modified T lymphocytes with human VEGFR-1 specificity (V-1 CAR) by electroporation. V-1 CAR-modified T lymphocytes were demonstrated to elicit lytic cytotoxicity to target cells in a VEGFR-1-dependent manner. The adoptive transfer of V-1 CAR T lymphocytes delayed tumor growth and formation and inhibited pulmonary metastasis in xenograft models and such efficacies were enhanced by cotransfer of T lymphocytes that expressed interleukin-15 (IL-15). Moreover, V-1 CAR-modified T lymphocytes lysed primary endothelial cells and impaired tube formation, in vitro. These data demonstrated the antitumor and anti-angiogenesis ability of V-1 CAR-modified T lymphocytes. Our study provides the rationale for the clinical translation of CAR-modified T lymphocytes with VEGFR-1 specificity.

Effects of Ion Irradiation on Seedlings Growth Monitored by Ultraweak Delayed Luminescence

PubMed Central

Abe, Tomoko; Cirrone, Giuseppe A. P.; Cuttone, Giacomo; Gulino, Marisa; Musumeci, Francesco; Romano, Francesco; Ryuto, Hiromichi; Scordino, Agata

2016-01-01

The optical technique based on the measurement of delayed luminescence emitted from the biological samples has demonstrated its ability to provide valid and predictive information on the functional status of various biological systems. We want to extend this technique to study the effect of ionizing radiation on biological systems. In particular we are interested in the action of ion beams, used for therapeutic purposes or to increase the biological diversity. In general, the assessment of the damage that radiation produces both in the target objects and in the surrounding tissues, requires considerable time because is based on biochemical analysis or on the examination of the evolution of the irradiated systems. The delayed luminescence technique could help to simplify this investigation. We have so started our studies performing irradiations of some relatively simple vegetable models. In this paper we report results obtained from mung bean (Vigna radiata) seeds submitted to a 12C ion beam at the energy of 62 MeV/nucleon. The dry seeds were irradiated at doses from 50 to 7000 Gy. The photoinduced delayed luminescence of each seed before and after ion irradiation was measured. The growth of seedlings after irradiation was compared with that of untreated seeds. A growth reduction on increasing the dose was registered. The results show strong correlations between the ion irradiation dose, seeds growth and delayed luminescence intensity. In particular, the delayed luminescence intensity is correlated by a logistic function to the seedlings elongation and, after performing a suitable measurement campaign based on blind tests, it could become a tool able to predict the growth of seeds after ion irradiation. Moreover these results demonstrate that measurements of delayed luminescence could be used as a fast and non-invasive technique to check the effects of ion beams on relatively simple biological systems. PMID:27936220

The model of root graviresponse with retarded arguments

NASA Astrophysics Data System (ADS)

Kondrachuk, Alexander

The graviperception mechanism (GPM) of the roots of higher plants localized in the cap region of a root and supposedly related to statoliths sedimentation produces the signals in response to the change of the root axis orientation relative to the gravity vector G. Meanwhile, the regions (Distal Elongation Zone -DEZ and Central Elongation Zone-CEZ), where the signals initiate the changes of the growth rates of the upper and lower flanks of the root, are located at the significant distances from the cap (thousands microns for some plants). It causes the time delays between the relocation of statoliths in statocytes and the change of the growth rates in elongation zones. It is suggested that the signal targeting the CEZ modulates the initially uniform lateral distribution of some specific substances (S) in the cap region. Then already nonhomogeneous lateral distribution of S is transferred to the CEZ to initiate the change of the growth rates of the opposite flanks. It results in the bending of the root in the line of G and thus in the change of the GPM signal in the cap region. In the present model the kinetics of a root apex bending (angle A) in response to the time (t)-dependent change of the G orientation is described by the integro-differential equation in A(t). The main peculiarity of this model is the presence of retarded (time-delayed) arguments t-TCEZ and t-TDEZ . In this case the solutions of this equation depend on the preceding kinetics of A(t) during the time delays TCEZ and TDEZ . It is suggested that the signals activating the CEZ and DEZ are of different nature. The work is focused on two problems concerning the modeling of the effects of time-delay(s) on the root bending. The first problem supposes the existence of one zone (CEZ) and one time-delay TCEZ . This equation was studied and solved using analytical and numerical methods. We analyzed the model as to whether it can be used to describe the kinetics of root graviresponse in the case of different orientations of the root apex relative to the G vector during the time interval equal to TCEZ (TCEZ > TDEZ ) that precedes the beginning of gravistimultion. Also we explored the conditions of the overshooting (the vertical) and non-overshooting regimes of gravistimulated root bending. Good correlation between the results of the modeling and known experimental data (Barlow et al, 1993, Stochkus, 1994, Mullen, 1998) was found. This allowed us to estimate and analyze the parameters of the model. The second problem supposed the existence of two zones of growth (CEZ and DEZ) and two corresponding time-delays. The effects of the second time-delay connected with the presence of the DEZ on the behavior of the model equation of the root graviresponse kinetics were analyzed and discussed.

The mRNA cap-binding protein Cbc1 is required for high and timely expression of genes by promoting the accumulation of gene-specific activators at promoters.

PubMed

Li, Tianlu; De Clercq, Nikki; Medina, Daniel A; Garre, Elena; Sunnerhagen, Per; Pérez-Ortín, José E; Alepuz, Paula

2016-02-01

The highly conserved Saccharomyces cerevisiae cap-binding protein Cbc1/Sto1 binds mRNA co-transcriptionally and acts as a key coordinator of mRNA fate. Recently, Cbc1 has also been implicated in transcription elongation and pre-initiation complex (PIC) formation. Previously, we described Cbc1 to be required for cell growth under osmotic stress and to mediate osmostress-induced translation reprogramming. Here, we observe delayed global transcription kinetics in cbc1Δ during osmotic stress that correlates with delayed recruitment of TBP and RNA polymerase II to osmo-induced promoters. Interestingly, we detect an interaction between Cbc1 and the MAPK Hog1, which controls most gene expression changes during osmostress, and observe that deletion of CBC1 delays the accumulation of the activator complex Hot1-Hog1 at osmostress promoters. Additionally, CBC1 deletion specifically reduces transcription rates of highly transcribed genes under non-stress conditions, such as ribosomal protein (RP) genes, while having low impact on transcription of weakly expressed genes. For RP genes, we show that recruitment of the specific activator Rap1, and subsequently TBP, to promoters is Cbc1-dependent. Altogether, our results indicate that binding of Cbc1 to the capped mRNAs is necessary for the accumulation of specific activators as well as PIC components at the promoters of genes whose expression requires high and rapid transcription. Copyright © 2016 Elsevier B.V. All rights reserved.

Elite athletes and pubertal delay.

PubMed

Kapczuk, Karina

2017-10-01

Intensive physical training and participation in competitive sports during childhood and early adolescence may affect athletes' pubertal development. On the other hand, pubertal timing, early or late, may impact on an athlete selection for a particular sport. Genetic predisposition, training load, nutritional status and psychological stress determine athletes' pubertal timing. Athletes that practice esthetic sports, especially gymnasts, are predisposed to a delay in pubertal development. The growing evidence indicates that energy deficiency, not a systemic training per se, plays a crucial role in the pathogenesis of functional hypothalamic hypogonadism in female athletes. Metabolic and psychologic stress activate hypothalamic-pituitary-adrenal axis and suppress hypothalamic-pituitary-ovarian axis. Female athletes who do not begin secondary sexual development by the age of 14 or menstruation by the age of 16 warrant a comprehensive evaluation and a targeted treatment. Somatic growth and sexual maturation of elite female athletes are largely sport-specific since each sport favors a particular somatotype and requires a specific training. Chronic negative energy balance resulting from a systemic physical training and inadequate energy intake may delay pubertal development in elite athletes. Youth athletes, especially those engaged in competitive sports that emphasize prepubertal or lean appearance, are at risk of developing relative energy deficiency in sport associated with disordered eating or eating disorders. Management strategies should address the complex conditions underlying functional hypothalamic hypogonadism.

Inhibition of androgen receptor by decoy molecules delays progression to castration-recurrent prostate cancer.

PubMed

Myung, Jae-Kyung; Wang, Gang; Chiu, Helen H L; Wang, Jun; Mawji, Nasrin R; Sadar, Marianne D

2017-01-01

Androgen receptor (AR) is a member of the steroid receptor family and a therapeutic target for all stages of prostate cancer. AR is activated by ligand binding within its C-terminus ligand-binding domain (LBD). Here we show that overexpression of the AR NTD to generate decoy molecules inhibited both the growth and progression of prostate cancer in castrated hosts. Specifically, it was shown that lentivirus delivery of decoys delayed hormonal progression in castrated hosts as indicated by increased doubling time of tumor volume, prolonged time to achieve pre-castrate levels of serum prostate-specific antigen (PSA) and PSA nadir. These clinical parameters are indicative of delayed hormonal progression and improved therapeutic response and prognosis. Decoys reduced the expression of androgen-regulated genes that correlated with reduced in situ interaction of the AR with androgen response elements. Decoys did not reduce levels of AR protein or prevent nuclear localization of the AR. Nor did decoys interact directly with the AR. Thus decoys did not inhibit AR transactivation by a dominant negative mechanism. This work provides evidence that the AR NTD plays an important role in the hormonal progression of prostate cancer and supports the development of AR antagonists that target the AR NTD.

Inhibition of androgen receptor by decoy molecules delays progression to castration-recurrent prostate cancer

PubMed Central

Myung, Jae-Kyung; Wang, Gang; Chiu, Helen H. L.; Wang, Jun; Mawji, Nasrin R.; Sadar, Marianne D.

2017-01-01

Androgen receptor (AR) is a member of the steroid receptor family and a therapeutic target for all stages of prostate cancer. AR is activated by ligand binding within its C-terminus ligand-binding domain (LBD). Here we show that overexpression of the AR NTD to generate decoy molecules inhibited both the growth and progression of prostate cancer in castrated hosts. Specifically, it was shown that lentivirus delivery of decoys delayed hormonal progression in castrated hosts as indicated by increased doubling time of tumor volume, prolonged time to achieve pre-castrate levels of serum prostate-specific antigen (PSA) and PSA nadir. These clinical parameters are indicative of delayed hormonal progression and improved therapeutic response and prognosis. Decoys reduced the expression of androgen-regulated genes that correlated with reduced in situ interaction of the AR with androgen response elements. Decoys did not reduce levels of AR protein or prevent nuclear localization of the AR. Nor did decoys interact directly with the AR. Thus decoys did not inhibit AR transactivation by a dominant negative mechanism. This work provides evidence that the AR NTD plays an important role in the hormonal progression of prostate cancer and supports the development of AR antagonists that target the AR NTD. PMID:28306720

Measuring functional developmental delay in infants and young children: prevalence rates from the NHIS-D.

PubMed

Simpson, Gloria A; Colpe, Lisa; Greenspan, Stanley

2003-01-01

In order to measure the prevalence of developmental delay among US infants and children, two types of questions were asked of parents in the 1994-95 National Health Interview Survey on Disability (NHIS-D). To measure functional delay (FD), questions from the Functional Developmental Growth Chart (FDQ), which measures specific age-appropriate tasks, were used. General delay (GD) was defined using the general type of questions about developmental delay that had been used in previous surveys. Using a nationally representative sample of 15 291 infants and children aged 4-59 months from the NHIS-D, analyses revealed that, according to these questions, approximately 3.3% had FD and 3.4% of the children had GD. However, only one-third of the children were identified by both sets of questions. Thus, two-thirds of the children identified as having FD were not recognised by their parents as having a delay. Conversely, many parents responded to the GD questions indicating that their child had a delay, but failed to indicate that their child had a functional problem. In addition, only 17% of the children with FD and 31% of those with GD were receiving special services. Multivariable logistic regression analyses found that children with both FD and GD were more likely to be male and to be living in families with incomes below 200% of the poverty level. The findings suggest that the general types of developmental delay questions used in national surveys may not identify children with functional delays. As parents failed to identify these children, it is possible that many of these children may be slipping through paediatric surveillance. Further research to evaluate the use of these measures in population surveys is recommended.

Vaccination with OVA-bound nanoparticles encapsulating IL-7 inhibits the growth of OVA-expressing E.G7 tumor cells in vivo.

PubMed

Toyota, Hiroko; Yanase, Noriko; Yoshimoto, Takayuki; Harada, Mitsunori; Kato, Yasuki; Mizuguchi, Junichiro

2015-01-01

Immunotherapy has gained special attention due to its specific effects on tumor cells and systemic action to block metastasis. We recently demonstrated that ovalbumin (OVA) conjugated to the surface of nanoparticles (NPs) (OVA‑NPs) can manipulate humoral immune responses. In the present study, we aimed to ascertain whether vaccination with OVA-NPs entrapping IL-7 (OVA-NPs-IL-7) are able to induce antitumor immune responses in vivo. Pretreatment with a subcutaneous inoculation of OVA-NPs delayed the growth of thymic lymphoma cells expressing a model tumor antigen OVA (E.G7-OVA), and OVA-NPs-IL-7 substantially blocked the growth of E.G7-OVA tumor cells, although NPs-IL-7 alone had a meager effect, as assessed by the mean tumor size and the percentage of tumor-free mice. However, pretreatment with OVA-NPs-IL-7 failed to reduce the growth of parental thymic tumor cells, suggesting that the antitumor effect was antigen-specific. A tetramer assay revealed that vaccination with OVA-NPs-IL-7 tended to enhance the proportion of cytotoxic T cells (CTLs) specific for OVA. When the tumor-free mice inoculated with OVA-NPs-IL-7 plus EG.7 cells were rechallenged with E.G7-OVA cells, they demonstrated reduced growth compared with that in the control mice. Thus, a single subcutaneous injection of OVA-NPs-IL-7 into mice induced tumor-specific and also memory-like immune responses, resulting in regression of tumor cells. Antigens on NPs entrapping IL-7 would be a promising carrier to develop and enhance immune responses, including humoral and cellular immunity as well as a method of drug delivery to a specific target of interest.

Androgen therapy for delayed male puberty.

PubMed

Ambler, Geoffrey R

2009-06-01

Delayed puberty in men is a commonly presenting problem to paediatricians and an understanding of the available evidence on cause, treatments and outcomes is important to guide practice. Understanding of the regulation of the onset of puberty is gradually unfolding, although the genetic factors that dictate the timing of puberty in individuals and families remain poorly elucidated. Mutations and polymorphisms in candidate genes are being actively studied and it is likely that there is significant overlap between traditional diagnostic categories. Also, environmental endocrine disruptors may interact with the genetic regulation of puberty. Delayed puberty may not always be a benign condition, with increased risks of failing to achieve target height, adverse psychological and educational consequences, delayed sexual and psychosocial integration into society and effects on skeletal proportions and bone mass reported. Appropriate evaluation and follow-up is needed to guide clinical practice, particularly to distinguish constitutional delay in growth and puberty from that associated with other medical disease or permanent disorders. In milder cases of delayed puberty, treatment is often not required; however, considerable evidence exists for the efficacy and safety of short courses of low-dose testosterone therapy for appropriately selected individuals. This treatment is associated with high levels of patient satisfaction. There is not yet sufficient evidence for the routine use of other therapies (e.g. growth hormone, aromatase inhibitors) for constitutional delay in growth and puberty and better characterization of cause may lead to more targeted individual therapy.

Mechanism of growth delay induced in Escherichia coli by near ultraviolet radiation.

PubMed Central

Ramabhadran, T V; Jagger, J

1976-01-01

Continuously growing cultures of E. coli B/r were irradiated with a fluence of broad-band near-ultraviolet radiation (315-405 nm) sufficient to cause extensive growth delay and complete cessation of net RNA synthesis. Chloramphenicol treatment was found to stimulate resumption of RNA synthesis, similar to that observed with chloramphenicol treatment after amino-acid starvation. E. coli strains in which amino-acid starvation does not result in cessation of RNA synthesis ("relaxed" or rel- strains) show no cessation of growth and only a slight effect on the rate of growth or of RNA synthesis. These findings show that such near-UV fluences do not inactivate the RNA synthetic machinery but affect the regulation of RNA synthesis, in a manner similat to that produced by amino-acid starvation. Such regulation is believed to be mediated through alterations in concentration of guanosine tetraphosphate (ppGpp), and our estimations of ppGpp after near-UV irradiation are consistent with such an interpretation. These data, combined with earlier published data, strongly suggest that the mechanism of near-UV-induced growth delay in E. coli involves partial inactivation of certain tRNA species, which is interpreted by the cell in a manner similar to that of amino-acid starvation, causing a rise in ppGpp levels, a shut-off of net RNA synthesis, and the induction of a growth delay. Images PMID:1108019

Effects of nisin on growth of bacteria attached to meat.

PubMed Central

Chung, K T; Dickson, J S; Crouse, J D

1989-01-01

Nisin had an inhibitory effect on gram-positive bacteria (Listeria monocytogenes, Staphylococcus aureus, and Streptococcus lactis) but did not have an inhibitory effect on gram-negative bacteria (Serratia marcescens, Salmonella typhimurium, and Pseudomonas aeruginosa) attached to meat. Nisin delayed bacterial growth on meats which were artificially inoculated with L. monocytogenes or Staphylococcus aureus for at least 1 day at room temperature. If the incubation temperature was 5 degrees C, growth of L. monocytogenes was delayed for more than 2 weeks, and growth of Staphylococcus aureus did not occur. We also found that the extractable activity of nisin decreased rapidly when the meats were incubated at ambient temperatures and that this decrease was inversely related to the observed inhibitory effect. These findings disclosed that nisin delays the growth of some gram-positive bacteria attached to meat. However, nisin alone may not be sufficient to prevent meat spoilage because of the presence of gram-negative and other nisin-resistant gram-positive bacteria. PMID:2764559

Brain-region–specific alterations of the trajectories of neuronal volume growth throughout the lifespan in autism

PubMed Central

2014-01-01

Several morphometric studies have revealed smaller than normal neurons in the neocortex of autistic subjects. To test the hypothesis that abnormal neuronal growth is a marker of an autism-associated global encephalopathy, neuronal volumes were estimated in 16 brain regions, including various subcortical structures, Ammon’s horn, archicortex, cerebellum, and brainstem in 14 brains from individuals with autism 4 to 60 years of age and 14 age-matched control brains. This stereological study showed a significantly smaller volume of neuronal soma in 14 of 16 regions in the 4- to 8-year-old autistic brains than in the controls. Arbitrary classification revealed a very severe neuronal volume deficit in 14.3% of significantly altered structures, severe in 50%, moderate in 21.4%, and mild in 14.3% structures. This pattern suggests desynchronized neuronal growth in the interacting neuronal networks involved in the autistic phenotype. The comparative study of the autistic and control subject brains revealed that the number of structures with a significant volume deficit decreased from 14 in the 4- to 8-year-old autistic subjects to 4 in the 36- to 60-year-old. Neuronal volumes in 75% of the structures examined in the older adults with autism are comparable to neuronal volume in age-matched controls. This pattern suggests defects of neuronal growth in early childhood and delayed up-regulation of neuronal growth during adolescence and adulthood reducing neuron soma volume deficit in majority of examined regions. However, significant correction of neuron size but limited clinical improvements suggests that delayed correction does not restore functional deficits. PMID:24612906

Hormones and Human and Nonhuman Primate Growth.

PubMed

Bernstein, Robin Miriam

2017-01-01

The aim of this paper was to review information pertaining to the hormonal regulation of nonhuman primate growth, with specific focus on the growth hormone (GH)-insulin-like growth factor (IGF) axis and adrenal androgens. Hormones of the GH-IGF axis are consistently associated with measures of growth - linear, weight, or both - during the growth period; in adulthood, concentrations of IGF-I, IGF-binding protein-3, and GH-binding protein are not associated with any measures of size. Comparing patterns of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) may be especially relevant for understanding whether the childhood stage of growth and development is unique to humans and perhaps other apes. Genetic, hormonal, and morphological data on adrenarche in other nonhuman primate species suggest that this endocrine transition is delayed in humans, chimpanzees, and possibly gorillas, while present very early in postnatal life in macaques. This suggests that although perhaps permitted by an extension of the pre-adolescent growth period, childhood builds upon existing developmental substrates rather than having been inserted de novo into an ancestral growth trajectory. Hormones can provide insight regarding the evolution of the human growth trajectory. © 2017 S. Karger AG, Basel.

The attitudes of family physicians toward a child with delayed growth and development.

PubMed

Aker, Servet; Şahin, Mustafa Kürşat; Kınalı, Ömer; Şimşek Karadağ, Elif; Korkmaz, Tuğba

2017-09-01

Aim The purpose of this study was to assess the attitude of family physicians toward a child with delayed growth and development. Primary healthcare professionals play a key role in monitoring growth and development, the best indicator of the child's health status. If delayed growth and development can be detected early, then it is usually possible to restore functioning. This descriptive study was performed in Samsun, Turkey, in May and June 2015. In total, 325 family physicians were included. The study consisted of two parts. In the first session of the research, the story of an 18-month-old child with delayed growth and development was presented using visual materials. An interview between the child's mother and a member of primary healthcare staff was then enacted by two of the authors using role-playing. Subsequently, participants were given the opportunity to ask the mother and member of primary healthcare staff questions about the case. During the sessions, two observers observed the participants, took notes and compared these after the presentation. In the second part of the study, the participants were asked to complete a questionnaire consisting of three open-ended questions. Findings When asking questions of the mother, family physicians generally used accusatory and judgmental language. One of the questions most commonly put to the mother was 'Do you think you are a good mother?' Family physicians were keen to provide instruction for the patient and relatives. Family physicians to a large extent thought that the problem of a child with delayed growth and development can be resolved through education. Family physicians' manner of establishing relations with the patient and relatives is inappropriate. We therefore think that they should receive on-going in-service training on the subject.

Patterns of physical growth and dental development in Jordanian children and adolescents with thalassemia major.

PubMed

Hattab, Faiez N

2013-03-01

Dental development and physical growth are of particular interest in pediatric dentistry and orthodontics. This study evaluated these variables in patients with thalassemia major (TM). Physical growth was assessed in 54 patients (31 males and 23 females) aged 5.5 to 18.3 years and dental development was analyzed using panoramic radiographs from 39 of the 54 patients. The Demirjian system was used to characterize dental development of the seven left mandibular permanent teeth. Chronologic age (CA) and dental age (DA) were compared using the paired t-test, and the correlation between CA and extent of delay in dental development (DA minus CA) was assessed using Pearson's correlation coefficients. Growth retardation (< 10th percentile for height and weight) was present in 75.9% of TM patients. Height less than the third percentile was noted in 41.9% (13/31) of males and 34.8% (8/23) of females. Mean (SD) body mass index was 16.5 ± 2.2 kg/m(2). The extent of growth retardation increased with advancing age. Patient radiographs revealed a delay in dental development in 31 of 39 (79.5%) of participants (mean delay, 1.12 years in males and 0.81 years in females; range, 0.1 to 2.7 years). The mean difference between CA and DA was 0.97 years (P < 0.001). CA was significant correlated with extent of dental developmental delay (r = 0.64, P < 0.01). The results show that, among children and adolescents with TM, the proportions of those who had short stature, were underweight, and had a low growth rate increased with age. In addition, participants had significant delays in dental development.

Subcutaneous fat accumulation in early infancy is more strongly associated with motor development and delay than muscle growth.

PubMed

Kanazawa, H; Kawai, M; Niwa, F; Hasegawa, T; Iwanaga, K; Ohata, K; Tamaki, A; Heike, T

2014-06-01

Physical growth in neurologically healthy preterm infants affects motor development. This study investigated the separate relationships between muscle and fat in infancy and later motor development and physical growth. Muscle thickness and subcutaneous fat thickness of the anterior thigh were measured using ultrasound images obtained from neurologically healthy preterm infants at birth, 3, 6, 12 and 18 months' corrected age. We also obtained the Pediatric Evaluation of Disability Inventory and Alberta Infant Motor Scale scores at 18 months' corrected age to assess motor ability and motor delay. Thirty preterm infants completed the study protocol. There was a significant positive correlation between motor ability and increments in subcutaneous fat thickness during the first 3 and 6 months' corrected age (r = 0.48 and 0.40, p < 0.05, respectively), but not between motor ability and muscle thickness growth in any of the periods. A secondary, logistic regression analysis showed that increments in subcutaneous fat thickness during the first 3 months were a protective factor for motor delay. Subcutaneous fat accumulation in early infancy is more strongly associated with motor development and delay than muscle growth. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Cytotoxic effects of cylindrospermopsin in mitotic and non-mitotic Vicia faba cells.

PubMed

Garda, Tamás; Riba, Milán; Vasas, Gábor; Beyer, Dániel; M-Hamvas, Márta; Hajdu, Gréta; Tándor, Ildikó; Máthé, Csaba

2015-02-01

Cylindrospermopsin (CYN) is a cyanobacterial toxin known as a eukaryotic protein synthesis inhibitor. We aimed to study its effects on growth, stress responses and mitosis of a eukaryotic model, Vicia faba (broad bean). Growth responses depended on exposure time (3 or 6d), cyanotoxin concentration, culture conditions (dark or continuous light) and V. faba cultivar ("Standard" or "ARC Egypt Cross"). At 6d of exposure, CYN had a transient stimulatory effect on root system growth, roots being possibly capable of detoxification. The toxin induced nucleus fragmentation, blebbing and chromosomal breaks indicating double stranded DNA breaks and programmed cell death. Root necrotic tissue was observed at 0.1-20 μg mL(-1) CYN that probably impeded toxin uptake into vascular tissue. Growth and cell death processes observed were general stress responses. In lateral root tip meristems, lower CYN concentrations (0.01-0.1 μg mL(-1)) induced the stimulation of mitosis and distinct mitotic phases, irrespective of culture conditions or the cultivar used. Higher cyanotoxin concentrations inhibited mitosis. Short-term exposure of hydroxylurea-synchronized roots to 5 μg mL(-1) CYN induced delay of mitosis that might have been related to a delay of de novo protein synthesis. CYN induced the formation of double, split and asymmetric preprophase bands (PPBs), in parallel with the alteration of cell division planes, related to the interference of cyanotoxin with protein synthesis, thus it was a plant- and CYN specific alteration. Copyright © 2014 Elsevier Ltd. All rights reserved.

Growth hormone deficiency: an unusual presentation of floating harbor syndrome.

PubMed

Galli-Tsinopoulou, Assimina; Kyrgios, Ioannis; Emmanouilidou, Eleftheria; Maggana, Ioanna; Kotanidou, Eleni; Kokka, Paraskevi; Stylianou, Charilaos

2011-01-01

Floating-Harbor Syndrome (FHS) is a very rare condition of unknown etiology characterized by short stature, delayed bone age, characteristic facial features, delayed language skills and usually normal motor development. This syndrome has only once been associated with growth hormone deficiency and precocious puberty in the same patient. We describe a 5 4/12 year-old girl with the typical features of FHS in whom growth hormone deficiency was diagnosed and two years later central precocious puberty was noted. The patient showed a good response to human recombinant growth hormone as well as gonadotropin releasing hormone analogue treatment.

[Effects of light intensity on Quercus liaotungensis seed germination and seedling growth].

PubMed

Yan, Xing-fu; Wang, Jian-li; Zhou, Li-biao

2011-07-01

This paper studied the effects of different shading (55.4%, 18.9%, 5.5%, 2.2%, 0.5% , and 0.3% natural sunlight) on the seed germination and seedling growth of Quercus liaotungensis. The seed germination rate and germination index were the highest (72.5% and 0.22, respectively) at 55.4% natural sunlight, declined with decreasing light intensity, and were the lowest (42.5% and 0.11, respectively) at 0.3% natural sunlight. Strong light had definite delaying effect on the germination. The index of germination vigor increased with decreasing light intensity, being the maximum at 0.5% natural sunlight. The delay of seed germination under strong light could be the selective tradeoff on varied seed fates. Strong light benefited the basal stem diameter and root system growth and dry mass accumulation of Q. liaotunensis seedling, but resulted in the minimum seedlings height (6.06 cm). Greater morphological plasticity was observed for the seedlings under different shading, which lent support to the higher adaptability of the seedlings to light environment. For example, the specific leaf area, specific shoot length, specific root length, and chlorophyll b and total chlorophyll contents were the maximum at 0.5% natural sunlight, being 142.57 cm2 x g(-1), 156.86 cm x g(-1), 271.87 cm x g(-1), 0.07 g x cm(-2), and 0.24 g x cm(-2), respectively, and the minimum at 55.4% natural sunlight, being 44.89 cm2 x g(-1), 52.84 cm x g(-1), 101.98 cm x g(-1), 0.04 g x cm(-2), and 0.15 g x cm(-2), respectively. The variation of the root/shoot ratio of Q. liaotungensis seedlings under different shading could be the effects of the combination of light intensity and water availability.

Inhibition of cancer cell growth by exposure to a specific time-varying electromagnetic field involves T-type calcium channels.

PubMed

Buckner, Carly A; Buckner, Alison L; Koren, Stan A; Persinger, Michael A; Lafrenie, Robert M

2015-01-01

Electromagnetic field (EMF) exposures affect many biological systems. The reproducibility of these effects is related to the intensity, duration, frequency, and pattern of the EMF. We have shown that exposure to a specific time-varying EMF can inhibit the growth of malignant cells. Thomas-EMF is a low-intensity, frequency-modulated (25-6 Hz) EMF pattern. Daily, 1 h, exposures to Thomas-EMF inhibited the growth of malignant cell lines including B16-BL6, MDA-MB-231, MCF-7, and HeLa cells but did not affect the growth of non-malignant cells. Thomas-EMF also inhibited B16-BL6 cell proliferation in vivo. B16-BL6 cells implanted in syngeneic C57b mice and exposed daily to Thomas-EMF produced smaller tumours than in sham-treated controls. In vitro studies showed that exposure of malignant cells to Thomas-EMF for > 15 min promoted Ca(2+) influx which could be blocked by inhibitors of voltage-gated T-type Ca(2+) channels. Blocking Ca(2+) uptake also blocked Thomas-EMF-dependent inhibition of cell proliferation. Exposure to Thomas-EMF delayed cell cycle progression and altered cyclin expression consistent with the decrease in cell proliferation. Non-malignant cells did not show any EMF-dependent changes in Ca(2+) influx or cell growth. These data confirm that exposure to a specific EMF pattern can affect cellular processes and that exposure to Thomas-EMF may provide a potential anti-cancer therapy.

Inhibition of Cancer Cell Growth by Exposure to a Specific Time-Varying Electromagnetic Field Involves T-Type Calcium Channels

PubMed Central

Buckner, Carly A.; Buckner, Alison L.; Koren, Stan A.; Persinger, Michael A.; Lafrenie, Robert M.

2015-01-01

Electromagnetic field (EMF) exposures affect many biological systems. The reproducibility of these effects is related to the intensity, duration, frequency, and pattern of the EMF. We have shown that exposure to a specific time-varying EMF can inhibit the growth of malignant cells. Thomas-EMF is a low-intensity, frequency-modulated (25-6 Hz) EMF pattern. Daily, 1 h, exposures to Thomas-EMF inhibited the growth of malignant cell lines including B16-BL6, MDA-MB-231, MCF-7, and HeLa cells but did not affect the growth of non-malignant cells. Thomas-EMF also inhibited B16-BL6 cell proliferation in vivo. B16-BL6 cells implanted in syngeneic C57b mice and exposed daily to Thomas-EMF produced smaller tumours than in sham-treated controls. In vitro studies showed that exposure of malignant cells to Thomas-EMF for > 15 min promoted Ca2+ influx which could be blocked by inhibitors of voltage-gated T-type Ca2+ channels. Blocking Ca2+ uptake also blocked Thomas-EMF-dependent inhibition of cell proliferation. Exposure to Thomas-EMF delayed cell cycle progression and altered cyclin expression consistent with the decrease in cell proliferation. Non-malignant cells did not show any EMF-dependent changes in Ca2+ influx or cell growth. These data confirm that exposure to a specific EMF pattern can affect cellular processes and that exposure to Thomas-EMF may provide a potential anti-cancer therapy. PMID:25875081

Topical naltrexone accelerates full-thickness wound closure in type 1 diabetic rats by stimulating angiogenesis.

PubMed

McLaughlin, Patricia J; Immonen, Jessica A; Zagon, Ian S

2013-07-01

Delays in wound healing often result in infection, chronic ulceration, and possible amputation of extremities. Impaired wound healing is a major complication of the 23 million people in the USA with diabetes, and financial and medical burdens are demanding new treatments for wound healing. Previous studies have demonstrated that topical application of the opioid antagonist naltrexone (NTX) dissolved in moisturizing cream reverses delays in wound closure in rats with streptozotocin-induced type 1 diabetes. A target of NTX's action is DNA synthesis and cell proliferation. In this study, granulation tissue was evaluated to ascertain the specific cellular targets that were impaired in diabetic wounds, as well as those that were enhanced following NTX application. Mast cell number as well as the number of new blood vessels immunoreactive to fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), and alpha smooth muscle actin (α-SMA) antibodies were recorded at 3, 5, 8, 10, 15, and 20 days following creation of full-thickness dorsal cutaneous wounds in normal and type 1 diabetic rats. Diabetic rats displayed delays in wound closure as well as a reduction in the number of mast cells responding to the injury, and delays in the spatial and temporal expression of FGF-2, VEGF, and α-SMA in capillaries. Topical NTX accelerated the rate of wound closure and stimulated expression of angiogenic factors within granulation tissue of diabetic rats relative to control animals receiving saline in moisturizing cream. These data support observations that a novel biological pathway is impaired under diabetic conditions and can be modulated by topical NTX to enhance proliferative events in wound healing.

Aloe vera oral administration accelerates acute radiation-delayed wound healing by stimulating transforming growth factor-β and fibroblast growth factor production.

PubMed

Atiba, Ayman; Nishimura, Mayumi; Kakinuma, Shizuko; Hiraoka, Takeshi; Goryo, Masanobu; Shimada, Yoshiya; Ueno, Hiroshi; Uzuka, Yuji

2011-06-01

Delayed wound healing is a significant clinical problem in patients who have had previous irradiation. This study investigated the effectiveness of Aloe vera (Av) on acute radiation-delayed wound healing. The effect of Av was studied in radiation-exposed rats compared with radiation-only and control rats. Skin wounds were excised on the back of rats after 3 days of local radiation. Wound size was measured on days 0, 3, 6, 9, and 12 after wounding. Wound tissues were examined histologically and the expressions of transforming growth factor β-1 (TGF-β-1) and basic fibroblast growth factor (bFGF) were examined by immunohistochemistry and reverse-transcription polymerase chain reaction. Wound contraction was accelerated significantly by Av on days 6 and 12 after wounding. Furthermore, the inflammatory cell infiltration, fibroblast proliferation, collagen deposition, angiogenesis, and the expression levels of TGF-β-1 and bFGF were significantly higher in the radiation plus Av group compared with the radiation-only group. These data showed the potential application of Av to improve the acute radiation-delayed wound healing by increasing TGF-β-1 and bFGF production. Copyright © 2011 Elsevier Inc. All rights reserved.

Delayed growth in two German shepherd dog littermates with normal serum concentrations of growth hormone, thyroxine, and cortisol.

PubMed

Randolph, J F; Miller, C L; Cummings, J F; Lothrop, C D

1990-01-01

Four German Shepherd Dogs from a litter of 10 were evaluated because of postnatal onset of proportionate growth stunting that clinically resembled well-documented hypopituitary dwarfism in that breed. Although 2 pups had histologic evidence of hypopituitarism, the remaining 2 pups had normal serum growth hormone concentration and adrenocorticotropin secretory capability, and normal adrenal function test and thyroid function study results. Furthermore, the initially stunted German Shepherd Dogs grew at a steady rate until at 1 year, body weight and shoulder height approximated normal measurements. Seemingly, delayed growth in these pups may represent one end of a clinical spectrum associated with hypopituitarism in German Shepherd Dogs.

A Two-Layer Gene Circuit for Decoupling Cell Growth from Metabolite Production.

PubMed

Lo, Tat-Ming; Chng, Si Hui; Teo, Wei Suong; Cho, Han-Saem; Chang, Matthew Wook

2016-08-01

We present a synthetic gene circuit for decoupling cell growth from metabolite production through autonomous regulation of enzymatic pathways by integrated modules that sense nutrient and substrate. The two-layer circuit allows Escherichia coli to selectively utilize target substrates in a mixed pool; channel metabolic resources to growth by delaying enzymatic conversion until nutrient depletion; and activate, terminate, and re-activate conversion upon substrate availability. We developed two versions of controller, both of which have glucose nutrient sensors but differ in their substrate-sensing modules. One controller is specific for hydroxycinnamic acid and the other for oleic acid. Our hydroxycinnamic acid controller lowered metabolic stress 2-fold and increased the growth rate 2-fold and productivity 5-fold, whereas our oleic acid controller lowered metabolic stress 2-fold and increased the growth rate 1.3-fold and productivity 2.4-fold. These results demonstrate the potential for engineering strategies that decouple growth and production to make bio-based production more economical and sustainable. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Radiotherapy-Induced Anti-Tumor Immunity Contributes to the Therapeutic Efficacy of Irradiation and Can Be Augmented by CTLA-4 Blockade in a Mouse Model

PubMed Central

Yoshimoto, Yuya; Suzuki, Yoshiyuki; Mimura, Kousaku; Ando, Ken; Oike, Takahiro; Sato, Hiro; Okonogi, Noriyuki; Maruyama, Takanori; Izawa, Shinichiro; Noda, Shin-ei; Fujii, Hideki; Kono, Koji; Nakano, Takashi

2014-01-01

Purpose There is growing evidence that tumor-specific immune responses play an important role in anti-cancer therapy, including radiotherapy. Using mouse tumor models we demonstrate that irradiation-induced anti-tumor immunity is essential for the therapeutic efficacy of irradiation and can be augmented by modulation of cytotoxic T lymphocyte (CTL) activity. Methods and Materials C57BL/6 mice, syngeneic EL4 lymphoma cells, and Lewis lung carcinoma (LL/C) cells were used. Cells were injected into the right femurs of mice. Ten days after inoculation, tumors were treated with 30 Gy of local X-ray irradiation and their growth was subsequently measured. The effect of irradiation on tumor growth delay (TGD) was defined as the time (in days) for tumors to grow to 500 mm3 in the treated group minus that of the untreated group. Cytokine production and serum antibodies were measured by ELISA and flow cytometry. Results In the EL4 tumor model, tumors were locally controlled by X-ray irradiation and re-introduced EL4 cells were completely rejected. Mouse EL4-specific systemic immunity was confirmed by splenocyte cytokine production and detection of tumor-specific IgG1 antibodies. In the LL/C tumor model, X-ray irradiation also significantly delayed tumor growth (TGD: 15.4 days) and prolonged median survival time (MST) to 59 days (versus 28 days in the non-irradiated group). CD8(+) cell depletion using an anti-CD8 antibody significantly decreased the therapeutic efficacy of irradiation (TGD, 8.7 days; MST, 49 days). Next, we examined whether T cell modulation affected the efficacy of radiotherapy. An anti-CTLA-4 antibody significantly increased the anti-tumor activity of radiotherapy (TGD was prolonged from 13.1 to 19.5 days), while anti-FR4 and anti-GITR antibodies did not affect efficacy. Conclusions Our results indicate that tumor-specific immune responses play an important role in the therapeutic efficacy of irradiation. Immunomodulation, including CTLA-4 blockade, may be a promising treatment in combination with radiotherapy. PMID:24686897

Radiotherapy-induced anti-tumor immunity contributes to the therapeutic efficacy of irradiation and can be augmented by CTLA-4 blockade in a mouse model.

PubMed

Yoshimoto, Yuya; Suzuki, Yoshiyuki; Mimura, Kousaku; Ando, Ken; Oike, Takahiro; Sato, Hiro; Okonogi, Noriyuki; Maruyama, Takanori; Izawa, Shinichiro; Noda, Shin-ei; Fujii, Hideki; Kono, Koji; Nakano, Takashi

2014-01-01

There is growing evidence that tumor-specific immune responses play an important role in anti-cancer therapy, including radiotherapy. Using mouse tumor models we demonstrate that irradiation-induced anti-tumor immunity is essential for the therapeutic efficacy of irradiation and can be augmented by modulation of cytotoxic T lymphocyte (CTL) activity. C57BL/6 mice, syngeneic EL4 lymphoma cells, and Lewis lung carcinoma (LL/C) cells were used. Cells were injected into the right femurs of mice. Ten days after inoculation, tumors were treated with 30 Gy of local X-ray irradiation and their growth was subsequently measured. The effect of irradiation on tumor growth delay (TGD) was defined as the time (in days) for tumors to grow to 500 mm3 in the treated group minus that of the untreated group. Cytokine production and serum antibodies were measured by ELISA and flow cytometry. In the EL4 tumor model, tumors were locally controlled by X-ray irradiation and re-introduced EL4 cells were completely rejected. Mouse EL4-specific systemic immunity was confirmed by splenocyte cytokine production and detection of tumor-specific IgG1 antibodies. In the LL/C tumor model, X-ray irradiation also significantly delayed tumor growth (TGD: 15.4 days) and prolonged median survival time (MST) to 59 days (versus 28 days in the non-irradiated group). CD8(+) cell depletion using an anti-CD8 antibody significantly decreased the therapeutic efficacy of irradiation (TGD, 8.7 days; MST, 49 days). Next, we examined whether T cell modulation affected the efficacy of radiotherapy. An anti-CTLA-4 antibody significantly increased the anti-tumor activity of radiotherapy (TGD was prolonged from 13.1 to 19.5 days), while anti-FR4 and anti-GITR antibodies did not affect efficacy. Our results indicate that tumor-specific immune responses play an important role in the therapeutic efficacy of irradiation. Immunomodulation, including CTLA-4 blockade, may be a promising treatment in combination with radiotherapy.

Delayed growth

MedlinePlus

Growth - slow (child 0 - 5 years); Weight gain - slow (child 0 - 5 years); Slow rate of growth; Retarded growth and development; ... A child should have regular, well-baby check-ups with a health care provider. These checkups are usually scheduled ...

Modelling the Effect of Fruit Growth on Surface Conductance to Water Vapour Diffusion

PubMed Central

GIBERT, CAROLINE; LESCOURRET, FRANÇOISE; GÉNARD, MICHEL; VERCAMBRE, GILLES; PÉREZ PASTOR, ALEJANDRO

2005-01-01

• Background and Aims A model of fruit surface conductance to water vapour diffusion driven by fruit growth is proposed. It computes the total fruit conductance by integrating each of its components: stomata, cuticle and cracks. • Methods The stomatal conductance is computed from the stomatal density per fruit and the specific stomatal conductance. The cuticular component is equal to the proportion of cuticle per fruit multiplied by its specific conductance. Cracks are assumed to be generated when pulp expansion rate exceeds cuticle expansion rate. A constant percentage of cracks is assumed to heal each day. The proportion of cracks to total fruit surface area multiplied by the specific crack conductance accounts for the crack component. The model was applied to peach fruit (Prunus persica) and its parameters were estimated from field experiments with various crop load and irrigation regimes. • Key Results The predictions were in good agreement with the experimental measurements and for the different conditions (irrigation and crop load). Total fruit surface conductance decreased during early growth as stomatal density, and hence the contribution of the stomatal conductance, decreased from 80 to 20 % with fruit expansion. Cracks were generated for fruits exhibiting high growth rates during late growth and the crack component could account for up to 60 % of the total conductance during the rapid fruit growth. The cuticular contribution was slightly variable (around 20 %). Sensitivity analysis revealed that simulated conductance was highly affected by stomatal parameters during the early period of growth and by both crack and stomatal parameters during the late period. Large fruit growth rate leads to earlier and greater increase of conductance due to higher crack occurrence. Conversely, low fruit growth rate accounts for a delayed and lower increase of conductance. • Conclusions By predicting crack occurrence during fruit growth, this model could be helpful in managing cropping practices for integrated plant protection. PMID:15655107

[Characteristics of growth and development in children from families at social risk].

PubMed

Stojadinović, A

2001-01-01

Body height and weight are important indicators of children's health status. There are many evidences that children from disadvantaged families have lower height and weight than children of the same age from families without social risk. The aim of this study was to investigate characteristics of growth and development of children from economically disadvantaged families. The study was partly retrospective and partly prospective. The retrospective study included 509 children from disadvantaged families hospitalized at the Institute of Child and Adolescent Health Care in Novi Sad, during a five-year period. The prospective study included 90 children from disadvantaged families (experimental group) and 132 children from families without social risk (control group) hospitalized at the Institute during a six month period. Height/length, weight, head circumference, and psychomotor/intellectual development have been examined. In the retrospective study results were compared with theoretically expected values, whereas the prospective study results of experimental and control group were compared. In the retrospective study that included only children from disadvantaged families, 136 (26.7%) children had height/length, 173 (34%) had weight, and 86 (16.9%) children had head circumference below 10th percentile. Delay in psychomotor/intellectual development was established in 177 (34.8%) children. Children from families with social risk have significantly more often height/length, weight, head circumference and developmental delay than theoretically expected. In the prospective study 40 (44.4%) children from experimental group had height/length, 29 (32.2%) had weight, 20 (22.2%) children had head circumference below 10th percentile, and 17 (26.2%) had delay in psychomotor/intellectual development. Children from disadvantaged families (experimental group) significantly more often had delay in growth and development comparing with children from families without social risk (control group). Children from disadvantaged families significantly more often exhibit delay in growth and development, comparing with children of the same age from families without social risk. Therefore, pediatricians should consider social risk factors whenever treating children with growth or developmental delay.

Skeletal muscle characterization of Japanese quail line selectively bred for lower body weight as an avian model of delayed muscle growth with hypoplasia.

PubMed

Choi, Young Min; Suh, Yeunsu; Shin, Sangsu; Lee, Kichoon

2014-01-01

This study was designed to extensively characterize the skeletal muscle development in the low weight (LW) quail selected from random bred control (RBC) Japanese quail in order to provide a new avian model of impaired and delayed growth in physically normal animals. The LW line had smaller embryo and body weights than the RBC line in all age groups (P<0.05). During 3 to 42 d post-hatch, the LW line exhibited approximately 60% smaller weight of pectoralis major muscle (PM), mainly resulting from lower fiber numbers compared to the RBC line (P<0.05). During early post-hatch period when myotubes are still actively forming, the LW line showed impaired PM growth with prolonged expression of Pax7 and lower expression levels of MyoD, Myf-5, and myogenin (P<0.05), likely leading to impairment of myogenic differentiation and consequently, reduced muscle fiber formation. Additionally, the LW line had delayed transition of neonatal to adult myosin heavy chain isoform, suggesting delayed muscle maturation. This is further supported by the finding that the LW line continued to grow unlike the RBC line; difference in the percentages of PMW to body weights between both quail lines diminished with increasing age from 42 to 75 d post-hatch. This delayed muscle growth in the LW line is accompanied by higher levels of myogenin expression at 42 d (P<0.05), higher percentage of centered nuclei at 42 d (P<0.01), and greater rate of increase in fiber size between 42 and 75 d post-hatch (P<0.001) compared to the RBC line. Analysis of physiological, morphological, and developmental parameters during muscle development of the LW quail line provided a well-characterized avian model for future identification of the responsible genes and for studying mechanisms of hypoplasia and delayed muscle growth.

The epigenetic agents suberoylanilide hydroxamic acid and 5‑AZA‑2' deoxycytidine decrease cell proliferation, induce cell death and delay the growth of MiaPaCa2 pancreatic cancer cells in vivo.

PubMed

Susanto, Johana M; Colvin, Emily K; Pinese, Mark; Chang, David K; Pajic, Marina; Mawson, Amanda; Caldon, C Elizabeth; Musgrove, Elizabeth A; Henshall, Susan M; Sutherland, Robert L; Biankin, Andrew V; Scarlett, Christopher J

2015-05-01

Despite incremental advances in the diagnosis and treatment for pancreatic cancer (PC), the 5‑year survival rate remains <5%. Novel therapies to increase survival and quality of life for PC patients are desperately needed. Epigenetic thera-peutic agents such as histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors (DNMTi) have demonstrated therapeutic benefits in human cancer. We assessed the efficacy of these epigenetic therapeutic agents as potential therapies for PC using in vitro and in vivo models. Treatment with HDACi [suberoylanilide hydroxamic acid (SAHA)] and DNMTi [5‑AZA‑2' deoxycytidine (5‑AZA‑dc)] decreased cell proliferation in MiaPaCa2 cells, and SAHA treatment, with or without 5‑AZA‑dc, resulted in higher cell death and lower DNA synthesis compared to 5‑AZA‑dc alone and controls (DMSO). Further, combination treatment with SAHA and 5‑AZA‑dc significantly increased expression of p21WAF1, leading to G1 arrest. Treatment with epigenetic agents delayed tumour growth in vivo, but did not decrease growth of established pancreatic tumours. In conclusion, these data demonstrate a potential role for epigenetic modifier drugs for the management of PC, specifically in the chemoprevention of PC, in combination with other chemotherapeutic agents.

Effects of spectral composition, photoperiod and light intensity on the gonadal development of Atlantic salmon Salmo salar in recirculating aquaculture systems (RAS)

NASA Astrophysics Data System (ADS)

Qiu, Denggao; Xu, Shihong; Song, Changbin; Chi, Liang; Li, Xian; Sun, Guoxiang; Liu, Baoliang; Liu, Ying

2015-01-01

Artificial lighting regimes have been successfully used to inhibit sexual maturity of Atlantic salmon in confinement. However, when these operations are applied in commercial recirculating aquaculture systems (RAS) using standard lighting technology, sexual maturation is not suppressed. In this study, an L9 (33) orthogonal design was used to determine the effects of three factors (spectral composition, photoperiod, and light intensity) on the gonadal development of Atlantic salmon in RAS. We demonstrated that the photoperiod at the tested levels had a much greater effect on the gonadosomatic index and female Fulton condition factor than spectral composition and light intensity. The photoperiod had a significant effect on the secretion of sex steroids and melatonin ( P<0.05), and a short photoperiod delayed sex steroid and melatonin level increases. The three test factors had no significant effects on the survival rate, specific growth rate, relative weight gain, and male Fulton condition factor ( P>0.05). The optimum lighting levels in female and male Atlantic salmon were LD 8:16, 455 nm (or 625 nm), 8.60 W/m2; and LD 8:16, 8.60 W/m2, 455 nm respectively. These conditions not only delayed gonadal development, but also had no negative effects on Atlantic salmon growth in RAS. These results demonstrate that a combination of spectral composition, photoperiod and light intensity is effective at delaying the gonadal development of both male and female salmon in RAS.

Sleep Problems and Early Developmental Delay: Implications for Early Intervention Programs

ERIC Educational Resources Information Center

Bonuck, Karen; Grant, Roy

2012-01-01

Sleep disorders negatively impact behavior, cognition, and growth--the same areas targeted by early intervention. Conversely, developmental delays and disabilities may themselves precipitate sleep disorders. Young children with developmental delays experience sleep disorders at a higher rate than do typically developing children; the most common…

In vitro 3D regeneration-like growth of human patient brain tissue.

PubMed

Tang-Schomer, M D; Wu, W B; Kaplan, D L; Bookland, M J

2018-05-01

In vitro culture of primary neurons is widely adapted with embryonic but not mature brain tissue. Here, we extended a previously developed bioengineered three-dimensional (3D) embryonic brain tissue model to resected normal patient brain tissue in an attempt to regenerate human neurons in vitro. Single cells and small sized (diameter < 100 μm) spheroids from dissociated brain tissue were seeded into 3D silk fibroin-based scaffolds, with or without collagen or Matrigel, and compared with two-dimensional cultures and scaffold-free suspension cultures. Changes of cell phenotypes (neuronal, astroglial, neural progenitor, and neuroepithelial) were quantified with flow cytometry and analyzed with a new method of statistical analysis specifically designed for percentage comparison. Compared with a complete lack of viable cells in conventional neuronal cell culture condition, supplements of vascular endothelial growth factor-containing pro-endothelial cell condition led to regenerative growth of neurons and astroglial cells from "normal" human brain tissue of epilepsy surgical patients. This process involved delayed expansion of Nestin+ neural progenitor cells, emergence of TUJ1+ immature neurons, and Vimentin+ neuroepithelium-like cell sheet formation in prolonged cultures (14 weeks). Micro-tissue spheroids, but not single cells, supported the brain tissue growth, suggesting importance of preserving native cell-cell interactions. The presence of 3D scaffold, but not hydrogel, allowed for Vimentin+ cell expansion, indicating a different growth mechanism than pluripotent cell-based brain organoid formation. The slow and delayed process implied an origin of quiescent neural precursors in the neocortex tissue. Further optimization of the 3D tissue model with primary human brain cells could provide personalized brain disease models. Copyright © 2018 John Wiley & Sons, Ltd.

Defective postnatal endochondral bone development by chondrocyte-specific targeted expression of parathyroid hormone type 2 receptor.

PubMed

Panda, Dibyendu Kumar; Goltzman, David; Karaplis, Andrew C

2012-12-15

The human parathyroid hormone type 2 receptor (PTH2R) is activated by PTH and by tuberoinfundibular peptide of 39 residues (TIP39), the latter likely acting as its natural ligand. Although the receptor is expressed at highest levels in the nervous system, we have observed that both PTH2R and TIP39 are expressed in the newborn mouse growth plate, with the receptor localizing in the resting zone and the ligand TIP39 localizing exclusively in prehypertrophic and hypertrophic chondrocytes. To address the role of PTH2R in postnatal skeletal growth and development, Col2a1-hPTH2R (PTH2R-Tg) transgenic mice were generated. The mice were viable and of nearly normal size at birth. Expression of the transgene in the growth plate was limited to chondrocytes. We found that chondrocyte proliferation was decreased, as determined by in vivo BrdU labeling of proliferating chondrocytes and CDK4 and p21 expression in the growth plate of Col2a1-hPTH2R transgenic mice. Similarly, the differentiation and maturation of chondrocytes was delayed, as characterized by decreased Sox9 expression and weaker immunostaining for the chondrocyte differentiation markers collagen type II and type X and proteoglycans. As well, there was altered expression of Gdf5, Wdr5, and β-catenin, factors implicated in chondrocyte maturation, proliferation, and differentiation.These effects impacted on the process of endochondral ossification, resulting in delayed formation of the secondary ossification center, and diminished trabecular bone volume. The findings substantiate a role for PTH2R signaling in postnatal growth plate development and subsequent bone mass acquisition.

Hypopituitarism in children with cerebral palsy.

PubMed

Uday, Suma; Shaw, Nick; Krone, Ruth; Kirk, Jeremy

2017-06-01

Poor growth and delayed puberty in children with cerebral palsy is frequently felt to be related to malnutrition. Although growth hormone deficiency is commonly described in these children, multiple pituitary hormone deficiency (MPHD) has not been previously reported. We present a series of four children with cerebral palsy who were born before 29 weeks gestation who were referred to the regional endocrinology service, three for delayed puberty and one for short stature, in whom investigations identified MPHD. All patients had a height well below -2 standard deviation score (2nd centile) at presentation and three who had MRI scans had an ectopic posterior pituitary gland. We therefore recommend that the possibility of MPHD should be considered in all children with cerebral palsy and poor growth or delayed puberty. Early diagnosis and treatment is essential to maximise growth and prevent associated morbidity and mortality. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Change or Durability? The Contribution of Metaconceptual Awareness in Preservice Early Childhood Teachers' Learning of Science Concepts

NASA Astrophysics Data System (ADS)

Saçkes, Mesut; Trundle, Kathy Cabe

2017-06-01

This longitudinal study examined the role of metaconceptual awareness in the change and the durability of preservice teachers' conceptual understandings over the course of several months. Sixteen preservice early childhood teachers participated in the study. Semi-structured interviews were conducted to reveal the participants' conceptual understandings of lunar phases (pre, post, and delayed-post) and level of metaconceptual awareness (delayed-post only). Based on the change and stability in participants' conceptual understandings from pre to post and from post to delayed-post interviews, participants' conceptual understandings were assigned into three groups that described the profile of their long-term conceptual understandings: " decay or stability", " continuous growth", and " growth and stability". The results indicated that participants in the " continuous growth" and " growth and stability" groups had significantly higher metaconceptual awareness scores than participants in the " decay or stability" group. The results provided evidence that metaconceptual awareness plays a more decisive role in the restructuring of conceptual understandings than the durability of conceptual understandings.

Seed-specific overexpression of an endogenous Arabidopsis phytoene synthase gene results in delayed germination and increased levels of carotenoids, chlorophyll, and abscisic acid.

PubMed

Lindgren, L Ove; Stålberg, Kjell G; Höglund, Anna-Stina

2003-06-01

Phytoene synthase catalyzes the dimerization of two molecules of geranylgeranyl pyrophosphate to phytoene and has been shown to be rate limiting for the synthesis of carotenoids. To elucidate if the capacity to produce phytoene is limiting also in the seed of Arabidopsis (Wassilewskija), a gene coding for an endogenous phytoene synthase was cloned and coupled to a seed-specific promoter, and the effects of the overexpression were examined. The resulting transgenic plants produced darker seeds, and extracts from the seed of five overexpressing plants had a 43-fold average increase of beta-carotene and a total average amount of beta-carotene of approximately 260 microg g-1 fresh weight. Lutein, violaxanthin, and chlorophyll were significantly increased, whereas the levels of zeaxanthin only increased by a factor 1.1. In addition, substantial levels of lycopene and alpha-carotene were produced in the seeds, whereas only trace amounts were found in the control plants. Seeds from the transgenic plants exhibited delayed germination, and the degree of delay was positively correlated with the increased levels of carotenoids. The abscisic acid levels followed the increase of the carotenoids, and plants having the highest carotenoid levels also had the highest abscisic acid content. Addition of gibberellic acid to the growth medium only partly restored germination of the transgenic seeds.

Effects of delayed metamorphosis on larval survival, metamorphosis, and juvenile performance of four closely related species of tropical sea urchins (genus Echinometra).

PubMed

Rahman, M Aminur; Yusoff, Fatimah Md; Arshad, A; Uehara, Tsuyoshi

2014-01-01

We report here, the effects of extended competency on larval survival, metamorphosis, and postlarval juvenile growth of four closely related species of tropical sea urchins, Echinometra sp. A (Ea), E. mathaei (Em), Echinometra sp. C (Ec), and E. oblonga (Eo). Planktotrophic larvae of all four species fed on cultured phytoplankton (Chaetoceros gracilis) attained metamorphic competence within 22-24 days after fertilization. Competent larvae were forced to delay metamorphosis for up to 5 months by preventing them from settling in culture bottles with continuous stirring on a set of 10 rpm rotating rollers and larval survival per monthly intervals was recorded. Larval survival was highest at 24 days, when competence was attained (0 delayed period), and there were no significant differences among the four species. Larvae that had experienced a prolonged delay had reduced survival rate, metamorphosis success, and juvenile survival, but among older larvae, Em had the highest success followed by Ea, Eo, and Ec. Juveniles from larvae of all four species that metamorphosed soon after becoming competent tended to have higher growth rates (test diameter and length of spines) than juveniles from larvae that metamorphosed after a prolonged period of competence with progressively slower growth the longer the prolonged period. Despite the adverse effects of delaying metamorphosis on growth parameters, competent larvae of all four species were able to survive up to 5 months and after metamorphosis grew into 1-month-old juveniles in lab condition. Overall, delayed larvae of Em showed significantly higher larval survival, metamorphosis, and juvenile survival than Ea and Eo, while Ec showed the lowest values in these performances. Em has the most widespread distribution of these species ranging from Africa to Hawaii, while Ec probably has the most restricted distribution. Consequently, differences in distribution may be related to differences in the ability to delay metamorphosis.

Effects of Delayed Metamorphosis on Larval Survival, Metamorphosis, and Juvenile Performance of Four Closely Related Species of Tropical Sea Urchins (Genus Echinometra)

PubMed Central

Rahman, M. Aminur; Yusoff, Fatimah Md.; Arshad, A.; Uehara, Tsuyoshi

2014-01-01

We report here, the effects of extended competency on larval survival, metamorphosis, and postlarval juvenile growth of four closely related species of tropical sea urchins, Echinometra sp. A (Ea), E. mathaei (Em), Echinometra sp. C (Ec), and E. oblonga (Eo). Planktotrophic larvae of all four species fed on cultured phytoplankton (Chaetoceros gracilis) attained metamorphic competence within 22–24 days after fertilization. Competent larvae were forced to delay metamorphosis for up to 5 months by preventing them from settling in culture bottles with continuous stirring on a set of 10 rpm rotating rollers and larval survival per monthly intervals was recorded. Larval survival was highest at 24 days, when competence was attained (0 delayed period), and there were no significant differences among the four species. Larvae that had experienced a prolonged delay had reduced survival rate, metamorphosis success, and juvenile survival, but among older larvae, Em had the highest success followed by Ea, Eo, and Ec. Juveniles from larvae of all four species that metamorphosed soon after becoming competent tended to have higher growth rates (test diameter and length of spines) than juveniles from larvae that metamorphosed after a prolonged period of competence with progressively slower growth the longer the prolonged period. Despite the adverse effects of delaying metamorphosis on growth parameters, competent larvae of all four species were able to survive up to 5 months and after metamorphosis grew into 1-month-old juveniles in lab condition. Overall, delayed larvae of Em showed significantly higher larval survival, metamorphosis, and juvenile survival than Ea and Eo, while Ec showed the lowest values in these performances. Em has the most widespread distribution of these species ranging from Africa to Hawaii, while Ec probably has the most restricted distribution. Consequently, differences in distribution may be related to differences in the ability to delay metamorphosis. PMID:24624048

The POU transcription factor UNC-86 controls the timing and ventral guidance of C. elegans axon growth

PubMed Central

Olsson-Carter, Katherine; Slack, Frank J.

2012-01-01

The in vivo mechanisms that coordinate the timing of axon growth and guidance are not well understood. In the C. elegans hermaphrodite specific neurons, the lin-4 microRNA controls the stage of axon initiation independent of the UNC-40 and SAX-3 ventral guidance receptors. lin-4 loss-of-function mutants exhibit marked delays in axon outgrowth, while lin-4 overexpression, leads to precocious growth in the L3. Here we show that loss of the POU transcription factor UNC-86 not only results in penetrant ventral axon growth defects in the HSNs, but also causes processes to extend in the L1, three stages earlier than wild-type. This temporal shift is not dependent on UNC-40 or SAX-3, and does not require the presence of lin-4. We propose that unc-86(lf) HSN axons are misguided due to the temporal decoupling of axon initiation and ventral guidance responses. PMID:21656875

Cyclical cell stretching of skin-derived fibroblasts downregulates connective tissue growth factor (CTGF) production.

PubMed

Kanazawa, Yuichiro; Nomura, Jun; Yoshimoto, Shinya; Suzuki, Toshikazu; Kita, Kazuko; Suzuki, Nobuo; Ichinose, Masaharu

2009-01-01

Delayed healing of skin wounds can be caused by wound instability, whereas appropriate massage or exercise prevents sclerosis and scar contracture. However, the mechanism by which wound healing is related to mechanical stress has not been fully elucidated. The present study aimed to identify whether mechanical stretching of fibroblasts reduces their production of extracellular matrix. We transferred skin fibroblasts into collagen-coated elastic silicone chambers, cultured them on a stretching apparatus, and used RT-PCR to examine the effects of mechanical stretching on the expression levels of 17 genes related to extracellular matrix production and growth factor secretion. We found that connective tissue growth factor (CTGF) was downregulated after 24 hr of cell stretching. Specifically, the CTGF mRNA and protein levels were 50% and 48% of the control levels, respectively. These findings suggest that cyclic stretching of fibroblasts contributes to anti-fibrotic processes by reducing CTGF production.

Growth and development of children with congenital heart disease.

PubMed

Chen, Chi-Wen; Li, Chung-Yi; Wang, Jou-Kou

2004-08-01

Children with congenital heart disease (CHD) commonly experience delayed growth. Because growth and development are closely related, both should be considered when a child's progress is examined. This paper reports a study to evaluate and compare the growth and development of preschool children with CHD to those of normal preschool children. The heights and weights of 42 preschool children with CHD and 116 normal preschool children were compared with standard growth curves. Differences in development of personal and social skills, fine motor skills and adaptability, language, and gross motor skills were evaluated. Developmental skills were assessed using the Denver Developmental Screening Test II. A significant difference was found in both body height (P < 0.05) and weight (P < 0.05) between the two groups. More preschoolers with congenital hear disease were below the 50th percentile in height (P < 0.05) and weight (P < 0.001). Preschoolers with CHD had more suspicious interpretations than non-CHD preschoolers, specifically in the language (P < 0.01) and gross motor sections (P < 0.001). Nevertheless, there were two items in the personal-social section and one in the language section on which the children with heart disease passed in the range of 55.6-63.2%. Problems were encountered with the Denver II test because of differences in language, culture and childrearing methods between Taiwanese and Western societies. These cultural differences must be considered when the test is used to assess development. Learning about the growth and developmental differences between children with CHD and normal children may help parents of the former to detect problems associated with delayed growth and development earlier. These children and their families should have the opportunity to participate in a long-term, follow-up programme that provides information and encourages developmental progress. The results could serve as a reference for those in both clinical and community workers who provide nursing care to children with CHD.

Profitless delays for extinction in nonautonomous Lotka-Volterra system

NASA Astrophysics Data System (ADS)

Liu, Shengqiang; Chen, Lansun

2001-12-01

We study the delayed periodic n-species Lotka-Voterra systems where the growth rate of each species is not always positive. The sufficient conditions for the extinction that are independent of the delays are obtained. Some known results are improved and generalized. Our results suggest that under some conditions, the introduction and the variance of the time delays can be both harmless and profitless. Discussion about the effect of time delays on the extinction of the system is also advanced.

Postnatal hyperoxia or DEHP exposure leads to growth restriction and delayed lung development in newborn rats.

PubMed

Liang, Zhong-Jie; Wu, Qiu-Ping; Chen, Bei-Tao; Lin, Zhen-Lang; Lin, Jing; Chen, Shang-Qin

2018-02-01

Di-(2-ethylhexyl) phthalate (DEHP) is commonly used as a plasticizer in many medical devices. We previously showed that maternal DEHP exposure led to restricted growth and delayed lung maturation in newborn rats. As oxygen toxicity continues to be a major risk factor for bronchopulmonary dysplasia, the aim of this study was to examine the effect of hyperoxia, DEHP or DEHP combined with hyperoxia on the growth and lung maturation of newborn rats. Newborn rats received DEHP injection, hyperoxia exposure or DEHP injection combined with hyperoxia exposure for one week or two weeks. A control group received an equal volume of vehicle and was maintained in room air. Hyperoxia and hyperoxia + DEHP exposure for one week led to growth failure in newborn rats. Pups in the hyperoxia group showed catch-up growth after being maintained in room air for an additional 7 days but this was not the case with the latter group, which continued to receive DEHP. Hyperoxia and DEHP both delayed lung development, as evidenced by decreased radial alveolar count. Quantitative RT-PCR showed that hyperoxia decreased the transcripts of VEGF, VEGFR-2 and eNOS on days 7 and 14, and DEHP exposure alone also led to decreased expression of VEGF gene in 14-day-old rat pups. Postnatal hyperoxia and/or DEHP exposure lead to growth restriction and delayed lung alveolar development. The VEGF gene expression was altered and may be involved as one of the possible molecular mechanisms. Copyright © 2017. Published by Elsevier B.V.

Schedule Matters: Understanding the Relationship between Schedule Delays and Costs on Overruns

NASA Technical Reports Server (NTRS)

Majerowicz, Walt; Shinn, Stephen A.

2016-01-01

This paper examines the relationship between schedule delays and cost overruns on complex projects. It is generally accepted by many project practitioners that cost overruns are directly related to schedule delays. But what does "directly related to" actually mean? Some reasons or root causes for schedule delays and associated cost overruns are obvious, if only in hindsight. For example, unrealistic estimates, supply chain difficulties, insufficient schedule margin, technical problems, scope changes, or the occurrence of risk events can negatively impact schedule performance. Other factors driving schedule delays and cost overruns may be less obvious and more difficult to quantify. Examples of these less obvious factors include project complexity, flawed estimating assumptions, over-optimism, political factors, "black swan" events, or even poor leadership and communication. Indeed, is it even possible the schedule itself could be a source of delay and subsequent cost overrun? Through literature review, surveys of project practitioners, and the authors' own experience on NASA programs and projects, the authors will categorize and examine the various factors affecting the relationship between project schedule delays and cost growth. The authors will also propose some ideas for organizations to consider to help create an awareness of the factors which could cause or influence schedule delays and associated cost growth on complex projects.

Effects of delayed mating on the reproductive biology of the vine mealybug, Planococcus ficus (Hemiptera: Pseudococcidae).

PubMed

Lentini, A; Mura, A; Muscas, E; Nuvoli, M T; Cocco, A

2018-04-01

The effect of increasing mating delay on the reproductive performance and population growth rates of the vine mealybug, Planococcus ficus (Signoret) (Hemiptera: Pseudococcidae), was investigated under laboratory conditions. Virgin females were mated at 1, 3, 5, 7, 14, 21 and 28 days after emergence and reproductive and life table parameters were estimated. The pre-oviposition period (number of days between mating and the onset of oviposition) significantly decreased in females mated within 7 days, whereas females mated at older ages showed equivalent pre-oviposition periods (7 days, as shorter delays in mating did not reduce the population growth rates.

Early childhood neurodevelopment after intrauterine growth restriction: a systematic review.

PubMed

Levine, Terri A; Grunau, Ruth E; McAuliffe, Fionnuala M; Pinnamaneni, RagaMallika; Foran, Adrienne; Alderdice, Fiona A

2015-01-01

Children who experienced intrauterine growth restriction (IUGR) may be at increased risk for adverse developmental outcomes in early childhood. The objective of this study was to carry out a systematic review of neurodevelopmental outcomes from 6 months to 3 years after IUGR. PubMed, Embase, PsycINFO, Maternity and Infant Care, and CINAHL databases were searched by using the search terms intrauterine, fetal, growth restriction, child development, neurodevelopment, early childhood, cognitive, motor, speech, language. Studies were eligible for inclusion if participants met specified criteria for growth restriction, follow-up was conducted within 6 months to 3 years, methods were adequately described, non-IUGR comparison groups were included, and full English text of the article was available. A specifically designed data extraction form was used. The methodological quality of included studies was assessed using well-documented quality-appraisal guidelines. Of 731 studies reviewed, 16 were included. Poorer neurodevelopmental outcomes after IUGR were described in 11. Ten found motor, 8 cognitive, and 7 language delays. Other delays included social development, attention, and adaptive behavior. Only 8 included abnormal Doppler parameters in their definitions of IUGR. Evidence suggests that children are at risk for poorer neurodevelopmental outcomes following IUGR from 6 months to 3 years of age. The heterogeneity of primary outcomes, assessment measures, adjustment for confounding variables, and definitions of IUGR limits synthesis and interpretation. Sample sizes in most studies were small, and some examined preterm IUGR children without including term IUGR or AGA comparison groups, limiting the value of extant studies. Copyright © 2015 by the American Academy of Pediatrics.

Delayed soil thawing affects root and shoot functioning and growth in Scots pine.

PubMed

Repo, Tapani; Lehto, Tarja; Finér, Leena

2008-10-01

In boreal regions, soil can remain frozen after the start of the growing season. We compared relationships between root characteristics and water relations in Scots pine (Pinus sylvestris L.) saplings subjected to soil frost treatments before and during the first week of the growing period in a controlled environment experiment. Delayed soil thawing delayed the onset of sap flow or totally blocked it if soil thawing lagged the start of the growing period by 7 days. This effect was reflected in the electrical impedance of needles and trunks and in the relative electrolyte leakage of needles. Prolonged soil frost reduced or completely inhibited root growth. In unfrozen soil, limited trunk sap flow was observed despite unfavorable aboveground growing conditions (low temperature, low irradiance, short photoperiod). Following the earliest soil thaw, sap flow varied during the growing season, depending on light and temperature conditions, phenological stage of the plant and the amount of live needles in the canopy. The results suggest that delayed soil thawing can reduce tree growth, and if prolonged, it can be lethal.

Coexisting diseases modifying each other’s presentation - lack of growth failure in Turner syndrome due to the associated pituitary gigantism.

PubMed

Dragović, Tamara; Đuran, Zorana; Jelić, Svetlana; Marinković, Dejan; Kiković, Saša; Kuzmić-Janković, Snežana; Hajduković, Zoran

2016-10-01

Turner syndrome presents with one of the most frequent chromosomal aberrations in female, typically presented with growth retardation, ovarian insufficiency, facial dysmorphism, and numerous other somatic stigmata. Gigantism is an extremely rare condition resulting from an excessive growth hormone (GH) secretion that occurs during childhood before the fusion of epiphyseal growth plates. The major clinical feature of gigantism is growth acceleration, although these patients also suffer from hypogonadism and soft tissue hypertrophy. We presented a girl with mosaic Turner syndrome, delayed puberty and normal linear growth for the sex and age, due to the simultaneous GH hypersecretion by pituitary tumor. In the presented case all the typical phenotypic stigmata related to Turner syndrome were missing. Due to excessive pituitary GH secretion during the period while the epiphyseal growth plates of the long bones are still open, characteristic stagnation in longitudinal growth has not been demonstrated. The patient presented with delayed puberty and primary amenorrhea along with a sudden appearance of clinical signs of hypersomatotropinism, which were the reasons for seeking medical help at the age of 16. Physical examination of children presenting with delayed puberty but without growth arrest must include an overall hormonal and genetic testing even in the cases when typical clinical presentations of genetic disorder are absent. To the best of our knowledge, this is the first reported case of simultaneous presence of Turner syndrome and gigantism in the literature.

Time-delay-induced dynamical behaviors for an ecological vegetation growth system driven by cross-correlated multiplicative and additive noises.

PubMed

Wang, Kang-Kang; Ye, Hui; Wang, Ya-Jun; Li, Sheng-Hong

2018-05-14

In this paper, the modified potential function, the stationary probability distribution function (SPDF), the mean growth time and the mean degeneration time for a vegetation growth system with time delay are investigated, where the vegetation system is assumed to be disturbed by cross-correlated multiplicative and additive noises. The results reveal some fact that the multiplicative and additive noises can both reduce the stability and speed up the decline of the vegetation system, while the strength of the noise correlation and time delay can both enhance the stability of the vegetation and slow down the depression process of the ecological system. On the other hand, with regard to the impacts of noises and time delay on the mean development and degeneration processes of the ecological system, it is discovered that 1) in the development process of the vegetation population, the increase of the noise correlation strength and time delay will restrain the regime shift from the barren state to the boom one, while the increase of the additive noise can lead to the fast regime shift from the barren state to the boom one. 2) Conversely, in the depression process of the ecological system, the increase of the strength of the correlation noise and time delay will prevent the regime shift from the boom state to the barren one. Comparatively, the increase of the additive and multiplicative noises can accelerate the regime shift from the boom state to the barren state.

Delayed Adrenarche may be an Additional Feature of Immunoglobulin Super Family Member 1 Deficiency Syndrome.

PubMed

Van Hulle, Severine; Craen, Margarita; Callewaert, Bert; Joustra, Sjoerd; Oostdijk, Wilma; Losekoot, Monique; Wit, Jan Maarten; Turgeon, Marc Olivier; Bernard, Daniel J; De Schepper, Jean

2016-03-05

Immunoglobulin super family member 1 (IGSF1) deficiency syndrome is characterized by central hypothyroidism, delayed surge in testosterone during puberty, macro-orchidism, and in some cases, hypoprolactinemia and/or transient growth hormone (GH) deficiency. Our patient was a 19-year-old male adolescent who had been treated since the age of 9 years with GH and thyroxine for an idiopathic combined GH, thyroid-stimulating hormone (TSH), and prolactin (PRL) deficiency. His GH deficiency proved to be transient, but deficiencies of TSH and PRL persisted, and he had developed macro-orchidism since the end of puberty. Brain magnetic resonance imaging and PROP1 and POU1F1 sequencing were normal. A disharmonious puberty (delayed genital and pubic hair development, bone maturation, and pubertal growth spurt, despite normal testicular growth) was observed as well as a delayed adrenarche, as reflected by very low dehydroepiandrosterone sulfate and delayed pubarche. Direct sequencing of the IGSF1 gene revealed a novel hemizygous mutation, c.3127T>C, p.Cys1043Arg. Pathogenicity of the mutation was demonstrated in vitro. Male children with an idiopathic combined GH, PRL, and TSH deficiency, showing persistent central hypothyroidism but transient GH deficiency upon retesting at adult height, should be screened for mutations in the IGSF1 gene, especially when macro-orchidism and/or hypoprolactinemia are present. We suspect that delayed adrenarche, as a consequence of PRL deficiency, might be part of the clinical phenotype of patients with IGSF1 deficiency.

Delayed Adrenarche may be an Additional Feature of Immunoglobulin Super Family Member 1 Deficiency Syndrome

PubMed Central

Hulle, Severine Van; Craen, Margarita; Callewaert, Bert; Joustra, Sjoerd; Oostdijk, Wilma; Losekoot, Monique; Wit, Jan Maarten; Turgeon, Marc Olivier; Bernard, Daniel J.; Schepper, Jean De

2016-01-01

Immunoglobulin super family member 1 (IGSF1) deficiency syndrome is characterized by central hypothyroidism, delayed surge in testosterone during puberty, macro-orchidism, and in some cases, hypoprolactinemia and/or transient growth hormone (GH) deficiency. Our patient was a 19-year-old male adolescent who had been treated since the age of 9 years with GH and thyroxine for an idiopathic combined GH, thyroid-stimulating hormone (TSH), and prolactin (PRL) deficiency. His GH deficiency proved to be transient, but deficiencies of TSH and PRL persisted, and he had developed macro-orchidism since the end of puberty. Brain magnetic resonance imaging and PROP1 and POU1F1 sequencing were normal. A disharmonious puberty (delayed genital and pubic hair development, bone maturation, and pubertal growth spurt, despite normal testicular growth) was observed as well as a delayed adrenarche, as reflected by very low dehydroepiandrosterone sulfate and delayed pubarche. Direct sequencing of the IGSF1 gene revealed a novel hemizygous mutation, c.3127T>C, p.Cys1043Arg. Pathogenicity of the mutation was demonstrated in vitro. Male children with an idiopathic combined GH, PRL, and TSH deficiency, showing persistent central hypothyroidism but transient GH deficiency upon retesting at adult height, should be screened for mutations in the IGSF1 gene, especially when macro-orchidism and/or hypoprolactinemia are present. We suspect that delayed adrenarche, as a consequence of PRL deficiency, might be part of the clinical phenotype of patients with IGSF1 deficiency. PMID:26757742

Effects of lisdexamfetamine dimesylate treatment for ADHD on growth.

PubMed

Faraone, Stephen V; Spencer, Thomas J; Kollins, Scott H; Glatt, Stephen J

2010-01-01

To complete an exploratory uncontrolled study of the effects of lisdexamfetamine dimesylate (LDX) on growth of children treated for attention-deficit/hyperactivity disorder (ADHD). Height, weight, and body mass index (BMI) from 281 children ages 6 to 13 years from longitudinal assessments up to 15 months were compared to norms from the Centers for Disease Control. At study entry, children were taller and heavier than average. Growth delays were largest for weight and BMI, and there was a 13 percentile point decrease in height. Children continued to grow in terms of height while treated with LDX; we found no increase in raw weight or BMI during the study period. LDX treatment was significantly associated with diminished gains in height, weight, and BMI compared to levels that would be expected based on age-appropriate standards from the Centers for Disease Control. Growth delays were greatest for the heaviest and tallest children, for those who had not previously received stimulant therapy, and for those with a greater cumulative exposure to LDX. More work is needed to determine effects on ultimate adult height. Consistent with prior studies of stimulants, treatment with LDX leads to statistically significant reductions in expected height, weight, and BMI. Growth of patients with ADHD treated with LDX should be closely monitored and corrective action taken should growth delays be observed.

[Hepatomegaly due to glycogen storage disease and type 1 diabetes mellitus].

PubMed

Flotats Bastardas, M; Miserachs Barba, M; Ricart Cumeras, A; Clemente León, M; Gussinyer Canadell, M; Yeste Fernández, D; Albisu Aparicio, María A; Carrascosa Lezcano, A

2007-08-01

Patients with type 1 diabetes and poor metabolic control can develop hepatomegaly due to intrahepatic glycogen deposition. If these patients also have elevated liver enzymes, dyslipidemia, cushingoid features and delayed growth or sexual maturation, Mauriac syndrome can be diagnosed. This disorder is common and reversible with optimization of insulin therapy. We report three adolescents with type 1 diabetes and a long-standing history of poor glycemic control, who developed hepatomegaly, elevated liver enzymes and dyslipidemia with preserved liver function. One of these patients also had delayed growth and another had hypogonadotropic hypogonadism. Liver ultrasound showed changes suggestive of glycogenosis. In all three patients, optimization of insulin therapy achieved good glycemic control and reversed the manifestations within 2 weeks. The etiology of Mauriac syndrome is controversial since both prolonged hyperglycemia and hyperinsulinization produce glycogen accumulation in the liver. Hypercortisolism (due to ketosis or hypoglycemia) contributes to glycogen storage and also causes growth and sexual maturation delay.

[Delayed testing for the diagnosis of fungi in the urines. Evaluation of the BD Vacutainer C&S tubes for the storage of urine samples at room temperature].

PubMed

Baixench, M T; Al-Sheikh, M; Paugam, A

2005-01-01

The study included 37 urine samples which have been artificially infected with low levels (10(3) CFU/mL) of various fungi strains. We compared the effects of sample storage, up to 48 hours, at room temperature, in a urine evacuated tube containing specific additives with storage at + 4 degrees C, for the same length of time, in a urine evacuated tube without any additives. There have been no differences of results (speed of growth and colony size) between the 2 modes of storage. However, the experience has shown that samples needed a careful mixing before seeding to avoid underdetection of the strains. Based on the study results, the BD Vacutainer C&S tubes are suitable for delayed testing for the diagnosis of urine fungal infection.

Neonatal blood cultures: effect of delayed entry into the blood culture machine and bacterial concentration on the time to positive growth in a simulated model.

PubMed

Jardine, Luke Anthony; Sturgess, Barbara Ruth; Inglis, Garry Donald Trevor; Davies, Mark William

2009-04-01

To determine if: time from blood culture inoculation to positive growth (total time to positive) and time from blood culture machine entry to positive growth (machine time to positive) is altered by delayed entry into the automated blood culture machine, and if the total time to positive differs by the concentration of organisms inoculated into blood culture bottles. Staphylococcus epidermidis, Escherichia coli and group B beta-haemolytic streptococci were chosen as clinically significant representative organisms. Two concentrations (> or =10 colony-forming units per millilitre and <1 colony-forming units per millilitre) were inoculated into PEDS BacT/Alert blood culture bottles and randomly allocated to one of three delayed automated blood culture machine entry times (30 min/8.5 h/15.5 h). For all organisms at all concentrations, except the Staphylococcus epidermidis, the machine time to positive was significantly decreased by delayed entry. For all organisms at all concentrations, the mean total time to positive significantly increased with increasing delayed entry into the blood culture machine. Higher concentrations of group B beta-haemolytic streptococci and Escherichia coli grew significantly faster than lower concentrations. Bacterial growth in inoculated bottles, stored at room temperature, continues although at a slower rate than in those blood culture bottles immediately entered into the machine. If a blood culture specimen has been stored at room temperature for greater than 15.5 h, the currently allowed safety margin of 36 h (before declaring a result negative) may be insufficient.

Decreased growth rate of P. falciparum blood stage parasitemia with age in a holoendemic population.

PubMed

Pinkevych, Mykola; Petravic, Janka; Chelimo, Kiprotich; Vulule, John; Kazura, James W; Moormann, Ann M; Davenport, Miles P

2014-04-01

In malaria holoendemic settings, decreased parasitemia and clinical disease is associated with age and cumulative exposure. The relative contribution of acquired immunity against various stages of the parasite life cycle is not well understood. In particular, it is not known whether changes in infection dynamics can be best explained by decreasing rates of infection, or by decreased growth rates of parasites in blood. Here, we analyze the dynamics of Plasmodium falciparum infection after treatment in a cohort of 197 healthy study participants of different ages. We use both polymerase chain reaction (PCR) and microscopy detection of parasitemia in order to understand parasite growth rates and infection rates over time. The more sensitive PCR assay detects parasites earlier than microscopy, and demonstrates a higher overall prevalence of infection than microscopy alone. The delay between PCR and microscopy detection is significantly longer in adults compared with children, consistent with slower parasite growth with age. We estimated the parasite multiplication rate from delay to PCR and microscopy detections of parasitemia. We find that both the delay between PCR and microscopy infection as well as the differing reinfection dynamics in different age groups are best explained by a slowing of parasite growth with age.

Delayed cerebral development in twins with congenital hyperthyroidism.

PubMed

Kopelman, A E

1983-09-01

Twins had congenital hyperthyroidism and delayed cerebral development manifested as ventriculomegaly, increased space in the interhemispheric fissure, and an exaggerated gyral pattern on cranial computed tomographic scans. At 3 1/2 years of age, both children had delayed development. Fetal and neonatal hyperthyroidism may interfere with normal brain growth and maturation with both neuranatomic and developmental sequelae.

Intraspecific priority effects modify compensatory responses to changes in hatching phenology in an amphibian.

PubMed

Murillo-Rincón, Andrea P; Kolter, Nora A; Laurila, Anssi; Orizaola, Germán

2017-01-01

In seasonal environments, modifications in the phenology of life-history events can alter the strength of time constraints experienced by organisms. Offspring can compensate for a change in timing of hatching by modifying their growth and development trajectories. However, intra- and interspecific interactions may affect these compensatory responses, in particular if differences in phenology between cohorts lead to significant priority effects (i.e. the competitive advantage that early-hatching individuals have over late-hatching ones). Here, we conducted a factorial experiment to determine whether intraspecific priority effects can alter compensatory phenotypic responses to hatching delay in a synchronic breeder by rearing moor frog (Rana arvalis) tadpoles in different combinations of phenological delay and food abundance. Tadpoles compensated for the hatching delay by speeding up their development, but only when reared in groups of individuals with identical hatching phenology. In mixed phenology groups, strong competitive effects by non-delayed tadpoles prevented the compensatory responses and delayed larvae metamorphosed later than in single phenology treatments. Non-delayed individuals gained advantage from developing with delayed larvae by increasing their developmental and growth rates as compared to single phenology groups. Food shortage prolonged larval period and reduced mass at metamorphosis in all treatments, but it did not prevent compensatory developmental responses in larvae reared in single phenology groups. This study demonstrates that strong intraspecific priority effects can constrain the compensatory growth and developmental responses to phenological change, and that priority effects can be an important factor explaining the maintenance of synchronic life histories (i.e. explosive breeding) in seasonal environments. © 2016 The Authors. Journal of Animal Ecology © 2016 British Ecological Society.

What Are the Symptoms of Puberty, Precocious Puberty, and Delayed Puberty?

MedlinePlus

... puberty include: Growth of pubic and other body hair Growth spurt Breast development Onset of menstruation (after puberty ... of pubic hair, other body hair, and facial hair Enlargement of testicles and penis Muscle growth Growth spurt Acne Deepening of the voice Precocious ...

Growth and development of very low birth weight infants aged 18-24 months at Queen Sirikit National Institute of Child Health.

PubMed

Sangtawesin, Varaporn; Singarj, Yupayao; Kanjanapattanakul, Wiboon

2011-08-01

The number of very low birth weight (VLBW) births is increasing worldwide. Despite better care in recent years, they have a high incidence of delayed growth and development. There are no previous studies regarding the growth and development of these infants at Queen Sirikit National Institute of Child Health (QSNICH). To study growth and developmental outcome of VLBW infants, aged 18-24 months who were discharged from QSNICH. VLBW infants who were discharged from QSNICH during the year 2007 were recruited in the study. Patients with chromosomal abnormalities, major congenital anomalies, definite congenital infections and positive maternal anti-HIV tests were excluded. At the corrected age of 18-24 months, the parents were called upon to bring their infants for complete physical examination and developmental evaluation on 2 occasions, two months apart. There were 111 cases of VLBW infants who were discharged from QSNICH during the year 2007. Fifty-four patients were eligible for the present study. Thirty cases (55.56%) were contacted for the first examination. During this examination, there were 3 cases (10%) with low head circumference, 1 case (3.33%) with poor weight gain, 5 cases (16.67%) with visual defect, 1 case (3.33%) with moderately severe hearing loss, 1 case (3.33%) with cerebral palsy and 7 cases (23.33%) with delayed development. Twenty-one cases could be recalled for a second evaluation. Two of the 5 cases had delayed language development. There were no cases with hydrocephalous, blindness or profound hearing loss. VLBW infants at QSNICH had much better survival during recent years. Most of these survivors had normal growth and development. Those with delayed growth and development need aggressive intervention and long-term follow-up for enhancement of quality of their lives.

Positive parenting mitigates the effects of poor self-regulation on body mass index trajectories from ages 4-15 years.

PubMed

Connell, Lauren E; Francis, Lori A

2014-08-01

This study sought to determine whether parenting style moderates the effects of delay of gratification on body mass index (BMI) trajectories from ages 4-15 years. Longitudinal data were analyzed for 778 children drawn from the Study of Early Child Care and Youth Development. Parenting style (i.e., authoritative, authoritarian, permissive, and neglectful) was created from measures of mothers' sensitivity and expectations for self-control when children were age 4 years. Self-regulation was also measured at 4 years using a well-known delay of gratification protocol. BMI was calculated from measured height and weight at each time point. Mixed modeling was used to test the interaction of parenting styles and ability to delay gratification on BMI trajectories from 4-15 years. There was a significant interaction effect of parenting and ability to delay on BMI growth from 4-15 years for boys. Boys who had authoritarian mothers and failed to delay gratification had a significantly steeper rate of growth in BMI from childhood through adolescence than children in any other parenting by delay group. Authoritative and permissive parenting styles were protective against more rapid BMI gains for boys who could not delay gratification. Ability to delay gratification was protective against BMI gains for boys who had parents with authoritarian or neglectful parenting styles.

Positive parenting mitigates the effects of poor self-regulation on BMI trajectories from age 4 to 15 years

PubMed Central

Connell, Lauren E.; Francis, Lori A.

2014-01-01

Objective This study sought to determine whether parenting style moderated the effects of delay of gratification on BMI trajectories from age 4 to 15 years. Methods Longitudinal data were analyzed on 778 children drawn from the Study of Early Child Care and Youth Development. Parenting style (authoritative, authoritarian, permissive, neglectful) was created from measures of mothers’ sensitivity and expectations for self-control when children were age 4 years. Self-regulation was also measured at 4 years using a well-known delay of gratification protocol. BMI was calculated from measured height and weight at each time point. Mixed modeling was used to test the interaction of parenting styles and ability to delay gratification on BMI trajectories from 4 to 15 years. Results There was a significant interaction effect of parenting and ability to delay on BMI growth from 4 to 15 years for boys. Boys who had authoritarian mothers and failed to delay gratification had a significantly steeper rate of growth in BMI from childhood through adolescence than children in any other parenting x delay group. Conclusions Authoritative and permissive parenting styles were protective against more rapid BMI gains for boys who could not delay gratification. Ability to delay gratification was protective against BMI gains for boys who had parents with authoritarian or neglectful parenting styles. PMID:23977874

Chloromethyl chlorosulfate as a voltage delay inhibitor in lithium cells

DOEpatents

Delnick, F.M.

1993-04-13

Chloromethyl chlorosulfate (CMCS) is used as a passive film growth inhibitor in electrochemical cells to minimize voltage delay and low-voltage discharge. Film growth on lithium anodes is significantly diminished when CMCS is added to SOCl[sub 2] and SO[sub 2]Cl[sub 2] electrolytes of lithium batteries. The CMCS also has the effect of extending the shelf-life of Li/SOCl[sub 2] and Li/SO[sub 2]Cl[sub 2] batteries.

Chloromethyl chlorosulfate as a voltage delay inhibitor in lithium cells

DOEpatents

Delnick, Frank M.

1993-01-01

Chloromethyl chlorosulfate (CMCS) is used as a passive film growth inhibitor in electrochemical cells to minimize voltage delay and low-voltage discharge. Film growth on lithium anodes is significantly diminished when CMCS is added to SOCl.sub.2 and SO.sub.2 Cl.sub.2 electrolytes of lithium batteries. The CMCS also has the effect of extending the shelf-life of Li/SOCl.sub.2 and Li/SO.sub.2 Cl.sub.2 batteries.

Spontaneous Age-Related Neurite Branching in C. elegans

PubMed Central

Tank, Elizabeth M. H.; Rodgers, Kasey E.; Kenyon, Cynthia

2011-01-01

The analysis of morphological changes that occur in the nervous system during normal aging could provide insight into cognitive decline and neurodegenerative disease. Previous studies have suggested that the nervous system of C. elegans maintains its structural integrity with age despite the deterioration of surrounding tissues. Unexpectedly, we observed that neurons in aging animals frequently displayed ectopic branches, and that the prevalence of these branches increased with time. Within age-matched populations, the branching of mechnosensory neurons correlated with decreased response to light touch and decreased mobility. The incidence of branching was influenced by two pathways that can affect the rate of aging, the Jun kinase pathway and the insulin/IGF-1 pathway. Loss of Jun kinase signaling, which slightly shortens lifespan, dramatically increased and accelerated the frequency of neurite branching. Conversely, inhibition of the daf-2 insulin/IGF-1-like signaling pathway, which extends lifespan, delayed and suppressed branching, and this delay required DAF-16/FOXO activity. Both JNK-1 and DAF-16 appeared to act within neurons in a cell-autonomous manner to influence branching, and, through their tissue-specific expression, it was possible to disconnect the rate at which branching occurred from the overall rate of aging of the animal. Old age has generally been associated with the decline and deterioration of different tissues, except in the case of tumor cell growth. To our knowledge, this is the first indication that aging can potentiate another form of growth, the growth of neurite branches, in normal animals. PMID:21697377

Early-onset scoliosis: current treatment.

PubMed

Cunin, V

2015-02-01

Early-onset scoliosis, which appears before the age of 10, can be due to congenital vertebral anomalies, neuromuscular diseases, scoliosis-associated syndromes, or idiopathic causes. It can have serious consequences for lung development and significantly reduce the life expectancy compared to adolescent scoliosis. Extended posterior fusion must be avoided to prevent the crankshaft phenomenon, uneven growth of the trunk and especially restrictive lung disease. Conservative (non-surgical) treatment is used first. If this fails, fusionless surgery can be performed to delay the final fusion procedure until the patient is older. The gold standard delaying surgical treatment is the implantation of growing rods as described by Moe and colleagues in the mid-1980s. These rods, which are lengthened during short surgical procedures at regular intervals, curb the scoliosis progression until the patient reaches an age where fusion can be performed. Knowledge of this technique and its complications has led to several mechanical improvements being made, namely use of rods that can be distracted magnetically on an outpatient basis, without the need for anesthesia. Devices based on the same principle have been designed that preferentially attach to the ribs to specifically address chest wall and spine dysplasia. The second category of surgical devices consists of rods used to guide spinal growth that do not require repeated surgical procedures. The third type of fusionless surgical treatment involves slowing the growth of the scoliosis convexity to help reduce the Cobb angle. The indications are constantly changing. Improvements in surgical techniques and greater surgeon experience may help to reduce the number of complications and make this lengthy treatment acceptable to patients and their family. Long-term effects of surgery on the Cobb angle have not been compared to those involving conservative "delaying" treatments. Because the latter has fewer complications associated with it than surgery, it should be the first-line treatment for most cases of early-onset scoliosis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Effects of interstitial heating on the RIF-1 tumor using an Nd:YAG laser with multiple fibers.

PubMed

Tobin, K M; Waldow, S M

1996-01-01

Hyperthermia was induced in tumor-bearing C3H mice using a Nd:YAG laser emitting near-infrared radiation at 1,064 nm. The efficacy of multiple implanted fiberoptics in the control of the RIF-1 tumor was investigated. RIF-1 tumors in the right hind leg were heated interstitially at 42, 44, or 46 degrees C for 30 or 60 minutes. Two, three, or four 400-microns quartz fibers terminating in a 1.0-cm cylindrical diffusor were inserted into each tumor, as were five microthermocouples to monitor temperature during treatment. Laser Doppler Flow (LDF) was also recorded pre- and post-treatment to determine changes in red blood cell flux in overlying skin (42, 44, or 46 degrees C) and the center of the tumor (46 degrees C). These experiments indicated that interstitial heating at 42, 44, and 46 degrees C resulted in tumor growth delay, although long-term control of tumors was not achieved. Treatment using four fibers resulted in the greatest tumor growth delay at 42 and 44 degrees C, increasing tumor doubling time by 50% or greater compared to control tumors; tumor growth delay following 46 degrees C treatments was seven times greater than that in control tumors. Significant changes (decreases) in LDF (P < .05) were seen in four treatment groups, using two fibers at 42 degrees C for 30 minutes, four fibers at 44 and 46 degrees C for 60 minutes on the overlying skin, and 46 degrees C for 60 minutes in the center of the tumor. Initial data indicate that interstitial heating with multiple fibers increases tumor growth delay compared to previous single fiber treatments, with tumor growth delay increasing with increasing treatment temperature; however, long-term tumor control was not achieved under the conditions investigated. Follow-up studies will explore the use of higher temperatures and/or longer treatment times in order to optimize tumor response.

Ten new cases further delineate the syndromic intellectual disability phenotype caused by mutations in DYRK1A.

PubMed

Bronicki, Lucas M; Redin, Claire; Drunat, Severine; Piton, Amélie; Lyons, Michael; Passemard, Sandrine; Baumann, Clarisse; Faivre, Laurence; Thevenon, Julien; Rivière, Jean-Baptiste; Isidor, Bertrand; Gan, Grace; Francannet, Christine; Willems, Marjolaine; Gunel, Murat; Jones, Julie R; Gleeson, Joseph G; Mandel, Jean-Louis; Stevenson, Roger E; Friez, Michael J; Aylsworth, Arthur S

2015-11-01

The dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) gene, located on chromosome 21q22.13 within the Down syndrome critical region, has been implicated in syndromic intellectual disability associated with Down syndrome and autism. DYRK1A has a critical role in brain growth and development primarily by regulating cell proliferation, neurogenesis, neuronal plasticity and survival. Several patients have been reported with chromosome 21 aberrations such as partial monosomy, involving multiple genes including DYRK1A. In addition, seven other individuals have been described with chromosomal rearrangements, intragenic deletions or truncating mutations that disrupt specifically DYRK1A. Most of these patients have microcephaly and all have significant intellectual disability. In the present study, we report 10 unrelated individuals with DYRK1A-associated intellectual disability (ID) who display a recurrent pattern of clinical manifestations including primary or acquired microcephaly, ID ranging from mild to severe, speech delay or absence, seizures, autism, motor delay, deep-set eyes, poor feeding and poor weight gain. We identified unique truncating and non-synonymous mutations (three nonsense, four frameshift and two missense) in DYRK1A in nine patients and a large chromosomal deletion that encompassed DYRK1A in one patient. On the basis of increasing identification of mutations in DYRK1A, we suggest that this gene be considered potentially causative in patients presenting with ID, primary or acquired microcephaly, feeding problems and absent or delayed speech with or without seizures.

Tissue-specific Insulin Signaling in the Regulation of Metabolism and Aging

PubMed Central

Zhang, Jingjing

2014-01-01

In mammals, insulin signaling regulates glucose homeostasis and plays an essential role in metabolism, organ growth, development, fertility, and lifespan. Defects in this signaling pathway contribute to various metabolic diseases such as type 2 diabetes, polycystic ovarian disease, hypertension, hyperlipidemia, and atherosclerosis. However, reducing the insulin signaling pathway has been found to increase longevity and delay the aging-associated diseases in various animals, ranging from nematodes to mice. These seemly paradoxical findings raise an interesting question as to how modulation of the insulin signaling pathway could be an effective approach to improve metabolism and aging. In this review, we summarize current understanding on tissue-specific functions of insulin signaling in the regulation of metabolism and lifespan. We also discuss potential benefits and limitations in modulating tissue-specific insulin signaling pathway to improve metabolism and healthspan. PMID:25087968

Direct in situ observation of ZnO nucleation and growth via transmission X-ray microscopy

NASA Astrophysics Data System (ADS)

Tay, S. E. R.; Goode, A. E.; Nelson Weker, J.; Cruickshank, A. A.; Heutz, S.; Porter, A. E.; Ryan, M. P.; Toney, M. F.

2016-01-01

The nucleation and growth of a nanostructure controls its size and morphology, and ultimately its functional properties. Hence it is crucial to investigate growth mechanisms under relevant growth conditions at the nanometer length scale. Here we image the nucleation and growth of electrodeposited ZnO nanostructures in situ, using a transmission X-ray microscope and specially designed electrochemical cell. We show that this imaging technique leads to new insights into the nucleation and growth mechanisms in electrodeposited ZnO including direct, in situ observations of instantaneous versus delayed nucleation.The nucleation and growth of a nanostructure controls its size and morphology, and ultimately its functional properties. Hence it is crucial to investigate growth mechanisms under relevant growth conditions at the nanometer length scale. Here we image the nucleation and growth of electrodeposited ZnO nanostructures in situ, using a transmission X-ray microscope and specially designed electrochemical cell. We show that this imaging technique leads to new insights into the nucleation and growth mechanisms in electrodeposited ZnO including direct, in situ observations of instantaneous versus delayed nucleation. Electronic supplementary information (ESI) available: Methods and videos of nanoparticle growth. See DOI: 10.1039/c5nr07019h

A model of economic growth with physical and human capital: The role of time delays.

PubMed

Gori, Luca; Guerrini, Luca; Sodini, Mauro

2016-09-01

This article aims at analysing a two-sector economic growth model with discrete delays. The focus is on the dynamic properties of the emerging system. In particular, this study concentrates on the stability properties of the stationary solution, characterised by analytical results and geometrical techniques (stability crossing curves), and the conditions under which oscillatory dynamics emerge (through Hopf bifurcations). In addition, this article proposes some numerical simulations to illustrate the behaviour of the system when the stationary equilibrium is unstable.

The Effect of Nb Micro-alloying on the Bainitic Phase Transformation Under Strip Casting Conditions

NASA Astrophysics Data System (ADS)

Stanford, N.; Dorin, T.; Hodgson, P. D.

2018-04-01

The effect of Nb concentration on the transformation from austenite to bainitic ferrite has been examined under simulated strip casting conditions. Nb concentration was found to delay the nucleation of bainite, but accelerated its growth. It is suggested that the delay in nucleation increases the driving force for transformation, which results in an increase in the growth rate of the bainite. The bainite/austenite interfaces are proposed to move too quickly to suffer appreciable solute drag.

Forecasting the timing of peak mandibular growth in males by using skeletal age.

PubMed

Hunter, W Stuart; Baumrind, Sheldon; Popovich, Frank; Jorgensen, Gertrud

2007-03-01

It is generally believed that the orthodontic treatment of a patient with a Class II malocclusion and a small mandible is enhanced by good growth at puberty, so that the timing of peak mandibular growth at puberty becomes of interest. To test the belief that skeletal age, whether early, average, or late, can be used to predict the timing of maximum growth of the mandible, whether early, average, or late, the predictive relationship between skeletal age and peak mandibular growth velocity (PMdV) at puberty was evaluated in 94 boys by using their longitudinal records from 4 to 18 years of age. Skeletal age was determined for each subject at ages 9 through 14 by using the method of Greulich and Pyle. At age 9, the Greulich and Pyle measurements predicted that 30 of the 94 subjects would have delayed PMdV equal to or exceeding 1 SD (of the mean age for PMdV), and 10 would have advanced PMdV equal to or exceeding 1 SD. When the actual age of PMdV was determined retrospectively from plots of annual mandibular growth increments, it was found that only 4 of the 30 in the delayed group had actually experienced delays in PMdV, and only 2 of the 10 in the advanced group had experienced accelerated PMdV. Skeletal age is not a reliable predictor of the timing of PMdV.

AKT delays the early-activated apoptotic pathway in UVB-irradiated keratinocytes via BAD translocation.

PubMed

Claerhout, Sofie; Decraene, David; Van Laethem, An; Van Kelst, Sofie; Agostinis, Patrizia; Garmyn, Marjan

2007-02-01

Upon irradiation with a high dose of UVB, keratinocytes undergo apoptosis as a protective mechanism. In previous work, we demonstrated the existence of an early-activated UVB-induced apoptotic pathway in growth factor-depleted human keratinocytes, which can be substantially delayed by the exclusive supplementation of IGF-1. We now show that in human keratinocytes, IGF-1 inhibits the onset of UVB-triggered apoptosis through a transcriptional independent, AKT-mediated mechanism, involving BAD serine 136 phosphorylation. Our results show that the early UVB-induced apoptosis in growth factor-depleted human keratinocytes is exclusively triggered through the mitochondrial pathway. It is accompanied by BAX translocation, cytochrome c release, and procaspase-9 cleavage, but not by procaspase-8 or BID cleavage. In human keratinocytes, IGF-1 supplementation inhibits these events in a transcription-independent manner. Both IGF-1 supplementation and the transduction of a membrane-targeted form of AKT result in a shift of the BH3-only protein BAD from the mitochondria to the cytoplasm, paralleled by an increase of AKT-specific Ser136 phospho-BAD bound to 14-3-3zeta protein. These data indicate that AKT-induced BAD phosphorylation and its subsequent cytoplasmic sequestration by 14-3-3zeta is a major mechanism responsible for the postponement of UVB-induced apoptosis in human keratinocytes.

Plasma growth hormone (GH), insulin and amino acid responses to arginine with or without aspartic acid in pigs. Effect of the dose.

PubMed

Cochard, A; Guilhermet, R; Bonneau, M

1998-01-01

The aim of the present study was to examine, for the first time in pigs, the dose-dependent effect of arginine (ARG) on growth hormone (GH) and insulin release and the effect of the combined ARG and aspartic acid (ASP) treatment on GH and insulin release. ARG (0.5 or 1 g/kg body weight) with or without an equimolar supplement of ASP (0.38 or 0.76 g/kg, respectively) was administered in piglets via the duodenum. ARG increased plasma arginine, ornithine, urea, proline and branched chain amino acid concentrations. ASP increased specifically plasma aspartic acid, glutamic acid, alanine and citrulline concentrations. Plasma insulin increased with no apparent difference between treatments. Maximum GH level and the area under the GH curve (AUC) were increased in a dose-dependent manner in response to ARG treatment. GH response to the combined ARG and ASP treatment (ARGASP) was delayed compared to ARG alone and was not dose-dependent. AUC for GH after ARGASP treatments were intermediate between those observed after the two ARG doses. Our data suggest that high ASP doses transiently inhibit and delay ARG-induced GH release in pigs and that an equimolar supplement of ASP stimulates or inhibits ARG-induced GH release depending on the dose used.

Peer victimization during adolescence: concurrent and prospective impact on symptoms of depression and anxiety.

PubMed

Stapinski, Lexine A; Araya, Ricardo; Heron, Jon; Montgomery, Alan A; Stallard, Paul

2015-01-01

Peer victimization is ubiquitous across schools and cultures, and has the potential for long-lasting effects on the well-being of victims. To date, research has focused on the consequences of peer victimization during childhood but neglected adolescence. Peer relationships and approval become increasingly important during adolescence; thus, peer victimization at this age may have a damaging psychological impact. Participants were 5030 adolescents aged 11-16 recruited from secondary schools in the UK. Self-report measures of victimization and symptoms of anxiety and depression were administered on three occasions over a 12-month period. Latent growth models examined concurrent and prospective victimization-related elevations in anxiety and depression symptoms above individual-specific growth trajectories. Peer victimization was associated with a concurrent elevation of 0.64 and 0.56 standard deviations in depression and anxiety scores, respectively. There was an independent delayed effect, with additional elevations in depression and anxiety (0.28 and 0.25 standard deviations) six months later. These concurrent and prospective associations were independent of expected symptom trajectories informed by individual risk factors. Adolescent peer victimization was associated with immediate and delayed elevations in anxiety and depression. Early intervention aimed at identifying and supporting victimized adolescents may prevent the development of these disorders.

Cartilage-Specific and Cre-Dependent Nkx3.2 Overexpression In Vivo Causes Skeletal Dwarfism by Delaying Cartilage Hypertrophy.

PubMed

Jeong, Da-Un; Choi, Je-Yong; Kim, Dae-Won

2017-01-01

Nkx3.2, the vertebrate homologue of Drosophila bagpipe, has been implicated as playing a role in chondrogenic differentiation. In brief, Nkx3.2 is initially expressed in chondrocyte precursor cells and later during cartilage maturation, its expression is diminished in hypertrophic chondrocytes. In addition to Nkx3.2 expression analyses, previous studies using ex vivo chick embryo cultures and in vitro cell cultures have suggested that Nkx3.2 can suppress chondrocyte hypertrophy. However, it has never been demonstrated that Nkx3.2 functions in regulating chondrocyte hypertrophy during cartilage development in vivo. Here, we show that cartilage-specific and Cre-dependent Nkx3.2 overexpression in mice results in significant postnatal dwarfism in endochondral skeletons, while intramembranous bones remain unaltered. Further, we observed significant delays in cartilage hypertrophy in conditional transgenic ciTg-Nkx3.2 mice. Together, these findings confirm that Nkx3.2 is capable of controlling hypertrophic maturation of cartilage in vivo, and this regulation plays a significant role in endochondral ossification and longitudinal bone growth. J. Cell. Physiol. 232: 78-90, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The 7q11.23 Microduplication Syndrome: A Clinical Report with Review of Literature

PubMed Central

Abbas, Elham; Cox, Devin M.; Smith, Teri; Butler, Merlin G.

2016-01-01

We report a 14-year-old adolescent girl with selective mutism (SM) and a 7q11.23 microduplication detected by chromosomal microarray (CMA) analysis and reviewed the literature from 18 published clinical reports. Our patient had specific phobias, SM, extreme anxiety, obesity, cutis marmorata, and a round appearing face with a short neck and over folded ears. We reviewed the published clinical, cognitive, behavioral, and cytogenetic findings grouped by speech and language delay, growth and development, craniofacial, clinical, and behavior and cognitive features due to the 7q11.23 microduplication. This microduplication syndrome is characterized by speech delay (91%), social anxiety (42%), attention deficit hyperactivity disorder (ADHD, 37%), autism spectrum disorder (29%), and separation anxiety (13%). Other findings include abnormal brain imaging (80%), congenital heart and vascular defects (54%), and mild intellectual disability (38%). We then compared the phenotype with Williams–Beuren syndrome (WBS) which is due to a deletion of the same chromosome region. Both syndromes have abnormal brain imaging, hypotonia, delayed motor development, joint laxity, mild intellectual disability, ADHD, autism, and poor visuospatial skills but opposite or dissimilar findings regarding speech and behavioral patterns, cardiovascular problems, and social interaction. Those with WBS are prone to have hyperverbal speech, lack of stranger anxiety, and supravalvular aortic stenosis while those with the 7q11.23 microduplication have speech delay, SM, social anxiety, and are prone to aortic dilatation. PMID:27617154

The 7q11.23 Microduplication Syndrome: A Clinical Report with Review of Literature.

PubMed

Abbas, Elham; Cox, Devin M; Smith, Teri; Butler, Merlin G

2016-09-01

We report a 14-year-old adolescent girl with selective mutism (SM) and a 7q11.23 microduplication detected by chromosomal microarray (CMA) analysis and reviewed the literature from 18 published clinical reports. Our patient had specific phobias, SM, extreme anxiety, obesity, cutis marmorata, and a round appearing face with a short neck and over folded ears. We reviewed the published clinical, cognitive, behavioral, and cytogenetic findings grouped by speech and language delay, growth and development, craniofacial, clinical, and behavior and cognitive features due to the 7q11.23 microduplication. This microduplication syndrome is characterized by speech delay (91%), social anxiety (42%), attention deficit hyperactivity disorder (ADHD, 37%), autism spectrum disorder (29%), and separation anxiety (13%). Other findings include abnormal brain imaging (80%), congenital heart and vascular defects (54%), and mild intellectual disability (38%). We then compared the phenotype with Williams-Beuren syndrome (WBS) which is due to a deletion of the same chromosome region. Both syndromes have abnormal brain imaging, hypotonia, delayed motor development, joint laxity, mild intellectual disability, ADHD, autism, and poor visuospatial skills but opposite or dissimilar findings regarding speech and behavioral patterns, cardiovascular problems, and social interaction. Those with WBS are prone to have hyperverbal speech, lack of stranger anxiety, and supravalvular aortic stenosis while those with the 7q11.23 microduplication have speech delay, SM, social anxiety, and are prone to aortic dilatation.

Biological response modifiers: their possibilities for cancer treatment.

PubMed

Franz, G

1989-01-01

Immunotherapy with the so-called 'Biological Response Modifiers' is based on the concept that the immune system can be activated to control neoplastic growth. Immunotherapy gained popularity as a treatment in the 1960's because of data from experimental tumor models. This indicated that mainly nonspecific stimulation with products of bacterial or fungal origine could prevent recurrence of, or delay growth of experimentally transplanted tumors. Since immunotherapy was most effective against relatively small tumors, clinical investigators began to view it mainly as a post-surgical treatment for a inhibition of micrometastasis. Mainly the activation of the non specific killer cells, macrophages and lymphocytes seems very promising to target an immune stimulant in the tumor site with a relatively high specificity. In the present study a whole series of biological polymers were tested in view of their capacity to enhance the immune system. However, the relatively small number of such compounds which can be applied therapeutically demonstrates that the ability of a compound to stimulate the immune systems is dependent on several conditions, such as the molecular dimension, the structure type and the solubility criteria. It will be shown that specific fungal glucans are very promising candidates for a successful cancer treatment.

Lambda phage-based vaccine induces antitumor immunity in hepatocellular carcinoma.

PubMed

Iwagami, Yoshifumi; Casulli, Sarah; Nagaoka, Katsuya; Kim, Miran; Carlson, Rolf I; Ogawa, Kosuke; Lebowitz, Michael S; Fuller, Steve; Biswas, Biswajit; Stewart, Solomon; Dong, Xiaoqun; Ghanbari, Hossein; Wands, Jack R

2017-09-01

Hepatocellular carcinoma (HCC) is a difficult to treat tumor with a poor prognosis. Aspartate β-hydroxylase (ASPH) is a highly conserved enzyme overexpressed on the cell surface of both murine and human HCC cells. We evaluated therapeutic effects of nanoparticle lambda (λ) phage vaccine constructs against ASPH expressing murine liver tumors. Mice were immunized before and after subcutaneous implantation of a syngeneic BNL HCC cell line. Antitumor actively was assessed by generation of antigen specific cellular immune responses and the identification of tumor infiltrating lymphocytes. Prophylactic and therapeutic immunization significantly delayed HCC growth and progression. ASPH-antigen specific CD4+ and CD8+ lymphocytes were identified in the spleen of tumor bearing mice and cytotoxicity was directed against ASPH expressing BNL HCC cells. Furthermore, vaccination generated antigen specific Th1 and Th2 cytokine secretion by immune cells. There was widespread necrosis with infiltration of CD3+ and CD8+ T cells in HCC tumors of λ phage vaccinated mice compared to controls. Moreover, further confirmation of anti-tumor effects on ASPH expressing tumor cell growth were obtained in another murine syngeneic vaccine model with pulmonary metastases. These observations suggest that ASPH may serve as a highly antigenic target for immunotherapy.

Digestive efficiency, free amino acid pools and quality of growth performance in Atlantic salmon (Salmo salar L.) affected by light regimes and vaccine types.

PubMed

Rungruangsak-Torrissen, Krisna; Sunde, Jan; Berg, Arne Erik; Nordgarden, Ulla; Fjelldal, Per Gunnar; Oppedal, Frode

2009-06-01

This study comprised the results of three different seawater trials using unique combination of techniques to study protease digestive efficiency and growth performance quality to illustrate the effects of light regimes and vaccine types in Atlantic salmon (Salmo salar L.). Fish with higher growth had higher trypsin (T) and chymotrypsin (C) specific activities with higher T/C ratio or slope T/C ratio [calculated from the regression between trypsin (y) and chymotrypsin (x) specific activities] in the pyloric caeca. The T/C ratios indicated fish growth rates over a period of 1-2 months, while the slope T/C ratios indicated fish growth rates at sampling. Adaptation period for adjustment to the new environment of continuous light was 70 days, indicated by the differences in trypsin specific activities and the crossing of slope T/C ratio regressions following with the changes in growth rate directions between the control and the treated group. Vaccine types affected fish vertebral growth, and additional continuous light enhanced the impact of vaccines on fish growth during springtime, indicated by differences in slope T/C ratios. Continuous light stimulated fish growth during winter to spring, when the natural day length was short, without significantly changing white muscle and oocyte qualities in the fish of about 500 g, except for significantly increased white muscle RNA concentration. Continuous light also reduced fish growth rate later during summer, when the natural day length was long, by precedently decreasing the T/C ratio in late spring. Interestingly, plasma levels of free lysine related to tryptic digestion were correlated with trypsin specific activity levels. Continuous light caused higher levels of most free amino acids (FAA) involved in nitrogen metabolism, higher incorporation of essential FAA for protein synthesis, and higher protein turnover rate (free hydroxyproline levels) in both plasma and white muscle. However, continuous light did not affect higher protein content, intracellular buffering capacity and RNA levels in the white muscle of the fish of about 1 kg, probably due to limitation of FAA available for protein synthesis. It is therefore suggested that enhancing fish growth by continuous light stimulation should be accompanied by increasing availability or content of dietary protein (and probably minerals), which in turn would improve the quality of fish growth performance through increasing fillet protein concentration, strengthening vertebral growth, and delaying oocyte development.

Slow Physical Growth, Delayed Reflex Ontogeny, and Permanent Behavioral as Well as Cognitive Impairments in Rats Following Intra-generational Protein Malnutrition

PubMed Central

Naik, Aijaz A.; Patro, Ishan K.; Patro, Nisha

2015-01-01

Environmental stressors including protein malnutrition (PMN) during pre-, neo- and post-natal age have been documented to affect cognitive development and cause increased susceptibility to neuropsychiatric disorders. Most studies have addressed either of the three windows and that does not emulate the clinical conditions of intra-uterine growth restriction (IUGR). Such data fail to provide a complete picture of the behavioral alterations in the F1 generation. The present study thus addresses the larger window from gestation to F1 generation, a new model of intra-generational PMN. Naive Sprague Dawley (SD) dams pre-gestationally switched to LP (8% protein) or HP (20% protein) diets for 45 days were bred and maintained throughout gestation on same diets. Pups born (HP/LP dams) were maintained on the respective diets post-weaningly. The present study aimed to show the sex specific differences in the neurobehavioral evolution and behavioral phenotype of the HP/LP F1 generation pups. A battery of neurodevelopmental reflex tests, behavioral (Open field and forelimb gripstrength test), and cognitive [Elevated plus maze (EPM) and Morris water maze (MWM)] assays were performed. A decelerated growth curve with significantly restricted body and brain weight, delays in apparition of neuro-reflexes and poor performance in the LP group rats was recorded. Intra-generational PMN induced poor habituation-with-time in novel environment exploration, low anxiety and hyperactive like profile in open field test in young and adult rats. The study revealed poor forelimb neuromuscular strength in LP F1 pups till adulthood. Group occupancy plots in MWM test revealed hyperactivity with poor learning, impaired memory retention and integration, thus modeling the signs of early onset Alzehemier phenotype. In addition, a gender specific effect of LP diet with severity in males and favoring female sex was also noticed. PMID:26696810

A review on high-resolution CMOS delay lines: towards sub-picosecond jitter performance.

PubMed

Abdulrazzaq, Bilal I; Abdul Halin, Izhal; Kawahito, Shoji; Sidek, Roslina M; Shafie, Suhaidi; Yunus, Nurul Amziah Md

2016-01-01

A review on CMOS delay lines with a focus on the most frequently used techniques for high-resolution delay step is presented. The primary types, specifications, delay circuits, and operating principles are presented. The delay circuits reported in this paper are used for delaying digital inputs and clock signals. The most common analog and digitally-controlled delay elements topologies are presented, focusing on the main delay-tuning strategies. IC variables, namely, process, supply voltage, temperature, and noise sources that affect delay resolution through timing jitter are discussed. The design specifications of these delay elements are also discussed and compared for the common delay line circuits. As a result, the main findings of this paper are highlighting and discussing the followings: the most efficient high-resolution delay line techniques, the trade-off challenge found between CMOS delay lines designed using either analog or digitally-controlled delay elements, the trade-off challenge between delay resolution and delay range and the proposed solutions for this challenge, and how CMOS technology scaling can affect the performance of CMOS delay lines. Moreover, the current trends and efforts used in order to generate output delayed signal with low jitter in the sub-picosecond range are presented.

Biohydrogen production by purple non-sulfur bacteria Rhodobacter sphaeroides: Effect of low-intensity electromagnetic irradiation.

PubMed

Gabrielyan, Lilit; Sargsyan, Harutyun; Trchounian, Armen

2016-09-01

The present work was focused on the effects of low-intensity (the flux capacity was of 0.06mWcm(-2)) electromagnetic irradiation (EMI) of extremely high frequencies or millimeter waves on the growth and hydrogen (H2) photoproduction by purple non-sulfur bacteria Rhodobacter sphaeroides MDC6521 (from Armenian mineral springs). After exposure of R. sphaeroides, grown under anaerobic conditions upon illumination, to EMI (51.8GHz and 53.0GHz) for 15min an increase of specific growth rate by ~1.2-fold, in comparison with control (non-irradiated cells), was obtained. However, the effect of EMI depends on the duration of irradiation: the exposure elongation up to 60min caused the delay of the growth lag phase and the decrease specific growth rate by ~1.3-fold, indicating the bactericidal effect of EMI. H2 yield of the culture, irradiated by EMI for 15min, determined during 72h growth, was ~1.2-fold higher than H2 yield of control cells, whereas H2 production by cultures, irradiated by EMI for 60min was not observed during 72h growth. This difference in the effects of extremely high frequency EMI indicates a direct effect of radiation on the membrane transfer and the enzymes of these bacteria. Moreover, EMI increased DCCD-inhibited H(+) fluxes across the bacterial membrane and DCCD-sensitive ATPase activity of membrane vesicles, indicating that the proton FoF1-ATPase is presumably a basic target for extremely high frequency EMI related to H2 production by cultures. Copyright © 2016 Elsevier B.V. All rights reserved.

Diversity of Pubertal Development in Cartilage-Hair Hypoplasia; Two Illustrative Cases.

PubMed

Holopainen, Elina; Vakkilainen, Svetlana; Mäkitie, Outi

2018-08-01

Cartilage-hair hypoplasia (CHH) is a rare chondrodysplasia, including disproportionate short stature, hypoplastic hair, immunodeficiency, and increased risk of malignancies. Absent pubertal growth spurt and absent pubic hair complicate monitoring of pubertal development in these patients. Two CHH patients with delayed puberty and excessive growth failure are described. One of the girls had hypogonadotropic hypogonadism whereas the other had hyponormogonadotropic hypogonadism with no spontaneous pubertal development and slow response to estrogen therapy, both requiring permanent replacement therapy. Careful follow-up of pubertal development in individuals with CHH and other growth-restricting bone diseases is needed. In delayed pubertal development timely hormone therapy is essential to ensure maximal growth and well developed secondary sex characteristics. Copyright © 2018 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Small head size and delayed body weight growth in wild Japanese monkey fetuses after the Fukushima Daiichi nuclear disaster.

PubMed

Hayama, Shin-Ichi; Tsuchiya, Moe; Ochiai, Kazuhiko; Nakiri, Sachie; Nakanishi, Setsuko; Ishii, Naomi; Kato, Takuya; Tanaka, Aki; Konno, Fumiharu; Kawamoto, Yoshi; Omi, Toshinori

2017-06-14

To evaluate the biological effect of the Fukushima Daiichi nuclear disaster, relative differences in the growth of wild Japanese monkeys (Macaca fuscata) were measured before and after the disaster of 2011 in Fukushima City, which is approximately 70 km from the nuclear power plant, by performing external measurements on fetuses collected from 2008 to 2016. Comparing the relative growth of 31 fetuses conceived prior to the disaster and 31 fetuses conceived after the disaster in terms of body weight and head size (product of the occipital frontal diameter and biparietal diameter) to crown-rump length ratio revealed that body weight growth rate and proportional head size were significantly lower in fetuses conceived after the disaster. No significant difference was observed in nutritional indicators for the fetuses' mothers. Accordingly, radiation exposure could be one factor contributed to the observed growth delay in this study.

Impact of dyeing industry effluent on germination and growth of pea (Pisum sativum).

PubMed

Malaviya, Piyush; Hali, Rajesh; Sharma, Neeru

2012-11-01

Dye industry effluent was analyzed for physico-chemical characteristics and its impact on germination and growth behaviour of Pea (Pisum sativum). The 100% effluent showed high pH (10.3) and TDS (1088 mg l(-1)). The germination parameters included percent germination, delay index, speed of germination, peak value and germination period while growth parameters comprised of root and shoot length, root and shootweight, root-shoot ratio and number of stipules. The study showed the maximum values of positive germination parameters viz. speed of germination (7.85), peak value (3.28), germination index (123.87) and all growth parameters at 20% effluent concentration while the values of negative germination parameters viz. delay index (-0.14) and percent inhibition (-8.34) were found to be minimum at 20% effluent concentration. The study demonstrated that at lower concentrations the dyeing industry effluent caused a positive impact on germination and growth of Pisum sativum.

DNA Damage as a Driver for Growth Delay: Chromosome Instability Syndromes with Intrauterine Growth Retardation

PubMed Central

Hernández-Gómez, Mariana

2017-01-01

DNA is constantly exposed to endogenous and exogenous mutagenic stimuli that are capable of producing diverse lesions. In order to protect the integrity of the genetic material, a wide array of DNA repair systems that can target each specific lesion has evolved. Despite the availability of several repair pathways, a common general program known as the DNA damage response (DDR) is stimulated to promote lesion detection, signaling, and repair in order to maintain genetic integrity. The genes that participate in these pathways are subject to mutation; a loss in their function would result in impaired DNA repair and genomic instability. When the DDR is constitutionally altered, every cell of the organism, starting from development, will show DNA damage and subsequent genomic instability. The cellular response to this is either uncontrolled proliferation and cell cycle deregulation that ensues overgrowth, or apoptosis and senescence that result in tissue hypoplasia. These diverging growth abnormalities can clinically translate as cancer or growth retardation; both features can be found in chromosome instability syndromes (CIS). The analysis of the clinical, cellular, and molecular phenotypes of CIS with intrauterine growth retardation allows inferring that replication alteration is their unifying feature. PMID:29238724

Effect of time between x-irradiation and chemotherapy on the growth of three solid mouse tumors. II. Cyclophosphamide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Twentyman, P.R.; Kallman, R.F.; Brown, J.M.

1979-09-01

Experiments have been carried out to determine the effect of different time intervals between the administration of x-radiation (1200 rad) and cyclophosphamide (100 mg/kg) on the growth delay produced in 3 mouse tumors. The tumors used were the EMT6 tumor in BALB/c mice and the KHT and RIF-1 sarcomas in C3H mice. All tumors were grown intramuscularly in the gastrocnemius muscle and treatment was carried out at a mean tumor weight of 450 mg. Time to reach 2X (for KHT) or 4X (for EMT6 and RIF-1) treatment volume was used as the endpoint of response. The drug was administered intraperitoneallymore » either 24, 6, or 2 hr before radiation, immediately before the start of radiation, or 3, 6, or 24 hr after radiation. All irradiations were carried out in unanesthetized mice. For the RIF-1, EMT6, and KHT tumors, the growth delays due to the drug alone were 11, 4.5, and 12 days, respectively. In the RIF-1 system, the growth delays following combination treatment tended to be longer than predicted by the addition of the single agent delays. For the KHT tumor, the opposite trend was seen, whereas in EMT6, there was no significant trend in either direction. No consistent dependence upon the timing between irradiation and drug administration was seen from system to system.« less

Prader-Willi-like phenotype: investigation of 1p36 deletion in 41 patients with delayed psychomotor development, hypotonia, obesity and/or hyperphagia, learning disabilities and behavioral problems.

PubMed

D'Angelo, Carla S; Da Paz, José A; Kim, Chong A; Bertola, Débora R; Castro, Claudia I E; Varela, Monica C; Koiffmann, Célia P

2006-01-01

Monosomy 1p36 is one of the most commonly observed mental retardation (MR) syndromes that results in a clinically recognizable phenotype including delayed psychomotor development and/or MR, hypotonia, epilepsy, hearing loss, growth delay, microcephaly, deep-set eyes, flat nasal bridge and pointed chin. Besides, a Prader-Willi syndrome (PWS)-like phenotype has been described in patients with 1p36 monosomy. Forty-one patients presenting hypotonia, developmental delay, obesity and/or hyperphagia and behavioral problems who tested negative for PWS were investigated by FISH and/or microsatellite markers. Twenty-six were analyzed with a 1p-specific subtelomeric probe, and one terminal deletion was identified. Thirty patients (15 of which also studied by FISH) were investigated by microsatellite markers, and no interstitial 1p36 deletion was found. Our patient presenting the 1p36 deletion did not have the striking features of this monosomy, but her clinical and behavioral features were quite similar to those observed in patients with PWS, except for the presence of normal sucking at birth. The extent of the deletion could be limited to the most terminal 2.5 Mb of 1p36, within the chromosomal region 1p36.33-1p36.32, that is smaller than usually seen in monosomy 1p36 patients. Therefore, chromosome 1p36.33 deletion should be investigated in patients with hypotonia, developmental delay, obesity and/or hyperphagia and behavioral problems who test negative for PWS.

Effect of time between x-irradiation and chemotherapy on the growth of three solid mouse tumours. VI. BCNU

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lelieveld, P.; Twentyman, P.R.; Kallman, R.F.

1979-09-01

Experiments have been carried out to determine the effect of different time intervals between the administration of x-irradiation (1200 rad) and BCNU (15 mg/kg) on the growth delay produced in three mouse tumors. The tumors used were the EMT6 tumor in BALB/c mice and the KHT and RIF-1 sarcomas in C3H mice. All tumors were grown intramuscularly in the gastrocnemius muscle and treatment was carried out at a mean tumor weight of 450 mg. Time to reach 2X (for KHT) or 4X (for EMT6 and RIF-1) treatment volume was used as the endpoint of response. The drug was administered bymore » the intraperitoneal route either 24, 6, or 2 hr before radiation. All irradiations were carried out in unanesthetized mice. The growth delays due to the drug alone were 2,6, and 11 days for the RIF-1, EMT6, and KHT tumors, respectively. No consistent general pattern emerged from the results of combination treatments. For the RIF-1 tumor, the growth delays following combination treatments were generally less than predicted by the simple addition of the growth delays for the single modalities. For EMT6 this was true when BCNU was administered immediately before x-rays, but not for other timings. In the KHT tumor an unexpectedly high incidence of long-term tumor controls was seen in the group which received BCNU at 2 hr before x-rays. In addition to the single dose studies (above), fractionated regimens in which radiation and BCNU were combined in several different ways were tested with the RIF-1 tumor. None of the combination schedules tested showed a greater-than-additive effect.« less

Refinement of the 12q14 microdeletion syndrome: primordial dwarfism and developmental delay with or without osteopoikilosis

PubMed Central

Mari, Francesca; Hermanns, Pia; Giovannucci-Uzielli, Maria L; Galluzzi, Fiorella; Scott, Daryl; Lee, Brendan; Renieri, Alessandra; Unger, Sheila; Zabel, Bernhard; Superti-Furga, Andrea

2009-01-01

In their studies on the molecular basis of osteopoikilosis, Menten et al have identified three individuals with microdeletions on chromosome 12q14.4, which removed several genes including LEMD3, the osteopoikilosis gene. In addition to osteopoikilosis, affected individuals had growth retardation and developmental delay. We now report a smaller 12q14.4 microdeletion in a boy with severe pre and postnatal growth failure, and mild developmental delay; the patient was small at birth and presented with poor feeding and failure to thrive during the first 2 years of life, similar to the phenotype of primordial dwarfism or severe Silver-Russell syndrome (SRS). The 12q14 deletion did not include LEMD3, and no signs of osteopoikilosis were observed on skeletal radiographs. Among the deleted genes, HMGA2 is of particular interest in relationship to the aberrant somatic growth in our patient, as HMGA2 variants have been linked to stature variations in the general population and loss of function of Hmga2 in the mouse results in the pygmy phenotype that combines pre and postnatal growth failure, with resistance to the adipogenic effect of overfeeding. Sequencing of the remaining HMGA2 allele in our patient showed a normal sequence, suggesting that HMGA2 haploinsufficiency may be sufficient to produce the aberrant growth phenotype. We conclude that the 12q14.4 microdeletion syndrome can occur with or without deletion of LEMD3 gene; in LEMD3-intact cases, the phenotype includes primordial short stature and failure to thrive with moderate developmental delay, but osteopoikilosis is absent. Such cases will likely be diagnosed as Silver-Russell-like or as primordial dwarfism. PMID:19277063

Mitigating delay and non-payment in the Malaysian construction industry

NASA Astrophysics Data System (ADS)

Mohamad, N.; Suman, A. S.; Harun, H.; Hashim, H.

2018-02-01

Construction industry is one of the industries that have contributed towards the rapid growth of development and economics in Malaysia. However, the industry is inundated with delay and non-payment issues between the two parties in contract that is the clients and contractors Even though there are contractual and administrative provisions in the standard forms of contract in Malaysia regarding payments, delay and non-payment issues still occur between them. The aim of the study is to develop measures to mitigate delay and non-payment issues between contractors and clients in the Malaysian construction industry. Questionnaire survey was conducted with clients and contractors in Klang Valley. Results from data analysis identified significant measures to mitigate delay and non-payment issues between contractors and clients which include contractors should submit their progress work invoicing with adequate documents; contractors should follow up constantly with client regarding payment; proper understanding of requirements with regards to payment; mutual discussion of problems with client to address problems in a timely manner and proper use of payment provisions in the standard form of contract. This study is significant to contractors and clients and to other construction players in order to reduce and minimise delay and non-payment issues for the growth of economy in the Malaysian construction industry.

Irx1 regulates dental outer enamel epithelial and lung alveolar type II epithelial differentiation

PubMed Central

Yu, Wenjie; Li, Xiao; Eliason, Steven; Romero-Bustillos, Miguel; Ries, Ryan J.; Cao, Huojun; Amendt, Brad A.

2017-01-01

The Iroquois genes (Irx) appear to regulate fundamental processes that lead to cell proliferation, differentiation, and maturation during development. In this report, the Iroquois homeobox 1 (Irx1) transcription factor was functionally disrupted using a LacZ insert and LacZ expression demonstrated stage-specific expression during embryogenesis. Irx1 is highly expressed in the brain, lung, digits, kidney, testis and developing teeth. Irx1 null mice are neonatal lethal and this lethality it due to pulmonary immaturity. Irx1−/− mice show delayed lung maturation characterized by defective surfactant protein secretion and Irx1 marks a population of SP-C expressing alveolar type II cells. Irx1 is specifically expressed in the outer enamel epithelium (OEE), stellate reticulum (SR) and stratum intermedium (SI) layers of the developing tooth. Irx1 mediates dental epithelial cell differentiation in the lower incisors resulting in delayed growth of the lower incisors. Irx1 is specifically and temporally expressed during developmental stages and we have focused on lung and dental development in this report. Irx1+ cells are unique to the development of the incisor outer enamel epithelium, patterning of Lef-1+ and Sox2+ cells as well as a new marker for lung alveolar type II cells. Mechanistically, Irx1 regulates Foxj1 and Sox9 to control cell differentiation during development. PMID:28746823

Irx1 regulates dental outer enamel epithelial and lung alveolar type II epithelial differentiation.

PubMed

Yu, Wenjie; Li, Xiao; Eliason, Steven; Romero-Bustillos, Miguel; Ries, Ryan J; Cao, Huojun; Amendt, Brad A

2017-09-01

The Iroquois genes (Irx) appear to regulate fundamental processes that lead to cell proliferation, differentiation, and maturation during development. In this report, the Iroquois homeobox 1 (Irx1) transcription factor was functionally disrupted using a LacZ insert and LacZ expression demonstrated stage-specific expression during embryogenesis. Irx1 is highly expressed in the brain, lung, digits, kidney, testis and developing teeth. Irx1 null mice are neonatal lethal and this lethality it due to pulmonary immaturity. Irx1 -/- mice show delayed lung maturation characterized by defective surfactant protein secretion and Irx1 marks a population of SP-C expressing alveolar type II cells. Irx1 is specifically expressed in the outer enamel epithelium (OEE), stellate reticulum (SR) and stratum intermedium (SI) layers of the developing tooth. Irx1 mediates dental epithelial cell differentiation in the lower incisors resulting in delayed growth of the lower incisors. Irx1 is specifically and temporally expressed during developmental stages and we have focused on lung and dental development in this report. Irx1+ cells are unique to the development of the incisor outer enamel epithelium, patterning of Lef-1+ and Sox2+ cells as well as a new marker for lung alveolar type II cells. Mechanistically, Irx1 regulates Foxj1 and Sox9 to control cell differentiation during development. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Impact of prematurity and nutrition on the developing gut microbiome and preterm infant growth.

PubMed

Grier, Alex; Qiu, Xing; Bandyopadhyay, Sanjukta; Holden-Wiltse, Jeanne; Kessler, Haeja A; Gill, Ann L; Hamilton, Brooke; Huyck, Heidie; Misra, Sara; Mariani, Thomas J; Ryan, Rita M; Scholer, Lori; Scheible, Kristin M; Lee, Yi-Horng; Caserta, Mary T; Pryhuber, Gloria S; Gill, Steven R

2017-12-11

Identification of factors that influence the neonatal gut microbiome is urgently needed to guide clinical practices that support growth of healthy preterm infants. Here, we examined the influence of nutrition and common practices on the gut microbiota and growth in a cohort of preterm infants. With weekly gut microbiota samples spanning postmenstrual age (PMA) 24 to 46 weeks, we developed two models to test associations between the microbiota, nutrition and growth: a categorical model with three successive microbiota phases (P1, P2, and P3) and a model with two periods (early and late PMA) defined by microbiota composition and PMA, respectively. The more significant associations with phase led us to use a phase-based framework for the majority of our analyses. Phase transitions were characterized by rapid shifts in the microbiota, with transition out of P1 occurring nearly simultaneously with the change from meconium to normal stool. The rate of phase progression was positively associated with gestational age at birth, and delayed transition to a P3 microbiota was associated with growth failure. We found distinct bacterial metabolic functions in P1-3 and significant associations between nutrition, microbiota phase, and infant growth. The phase-dependent impact of nutrition on infant growth along with phase-specific metabolic functions suggests a pioneering potential for improving growth outcomes by tailoring nutrient intake to microbiota phase.

Rho GTPase protein Cdc42 is critical for postnatal cartilage development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nagahama, Ryo; Department of Orthodontics, School of Dentistry, Showa University, Tokyo; Yamada, Atsushi, E-mail: yamadaa@dent.showa-u.ac.jp

2016-02-19

Cdc42, a small Rho GTPase family member, has been shown to regulate multiple cellular functions in vitro, including actin cytoskeletal reorganization, cell migration, proliferation, and gene expression. However, its tissue-specific roles in vivo remain largely unknown, especially in postnatal cartilage development, as cartilage-specific Cdc42 inactivated mice die within a few days after birth. In this study, we investigated the physiological functions of Cdc42 during cartilage development after birth using tamoxifen-induced cartilage-specific inactivated Cdc42 conditional knockout (Cdc42 {sup fl/fl}; Col2-CreERT) mice, which were generated by crossing Cdc42 flox mice (Cdc42 {sup fl/fl}) with tamoxifen-induced type II collagen (Col2) Cre transgenic mice using a Cre/loxP system.more » The gross morphology of the Cdc42 cKO mice was shorter limbs and body, as well as reduced body weight as compared with the controls. In addition, severe defects were found in growth plate chondrocytes of the long bones, characterized by a shorter proliferating zone (PZ), wider hypertrophic zone (HZ), and loss of columnar organization of proliferating chondrocytes, resulting in delayed endochondral bone formation associated with abnormal bone growth. Our findings demonstrate the importance of Cdc42 for cartilage development during both embryonic and postnatal stages. - Highlights: • Tamoxifen-induced cartilage specific inactivated Cdc42 mutant mice were generated. • Cdc42 mutant mice were shorter limbs and body. • Severe defects were found in growth plate chondrocytes.« less

Inhibitory effects of omega-3 fatty acids on injury-induced epidermal growth factor receptor transactivation contribute to delayed wound healing

PubMed Central

Turk, Harmony F.; Monk, Jennifer M.; Fan, Yang-Yi; Callaway, Evelyn S.; Weeks, Brad

2013-01-01

Epidermal growth factor receptor (EGFR)-mediated signaling is required for optimal intestinal wound healing. Since n-3 polyunsaturated fatty acids (PUFA), specifically docosahexaenoic acid (DHA), alter EGFR signaling and suppress downstream activation of key signaling pathways, we hypothesized that DHA would be detrimental to the process of intestinal wound healing. Using a mouse immortalized colonocyte model, DHA uniquely reduced EGFR ligand-induced receptor activation, whereas DHA and its metabolic precursor eicosapentaenoic acid (EPA) reduced wound-induced EGFR transactivation compared with control (no fatty acid or linoleic acid). Under wounding conditions, the suppression of EGFR activation was associated with a reduction in downstream activation of cytoskeletal remodeling proteins (PLCγ1, Rac1, and Cdc42). Subsequently, DHA and EPA reduced cell migration in response to wounding. Mice were fed a corn oil-, DHA-, or EPA-enriched diet prior to intestinal wounding (2.5% dextran sodium sulfate for 5 days followed by termination after 0, 3, or 6 days of recovery). Mortality was increased in EPA-fed mice and colonic histological injury scores were increased in EPA- and DHA-fed mice compared with corn oil-fed (control) mice. Although kinetics of colonic EGFR activation and downstream signaling (PLCγ1, Rac1, and Cdc42) were delayed by both n-3 PUFA, colonic repair was increased in EPA- relative to DHA-fed mice. These results indicate that, during the early response to intestinal wounding, DHA and EPA uniquely delay the activation of key wound-healing processes in the colon. This effect is mediated, at least in part, via suppression of EGFR-mediated signaling and downstream cytoskeletal remodeling. PMID:23426968

Effects of Growth Hormone and Nutritional Therapy in Boys with Constitutional Growth Delay: A Randomized Controlled Trial

PubMed Central

Han, Joan C.; Damaso, Ligeia; Welch, Susan; Balagopal, Prabhakaran; Hossain, Jobayer; Mauras, Nelly

2010-01-01

Objective To examine whether supplemental nutrition augments the anabolic actions of growth hormone (GH) in boys with constitutional delay of growth and maturation (CDGM). Study design We conducted a randomized, controlled trial at an outpatient clinical research center. Subjects were 20 prepubertal boys (age 9.3±1.3y) with CDGM (height-SDS -2.0±0.5, bone age delay 1.8±0.8y, BMI-SDS -1.2±1.0, peak stimulated GH 15.7±7.7ng/mL), who were randomized (N=10/group) to 6 months observation or daily nutritional supplementation, followed by additional daily GH therapy in all for another 12 months. T-tests and repeated measures ANOVAs compared energy intake, total energy expenditure (TEE), growth, hormones and nutrition markers. Results Energy intake was increased at 6 months within the Nutrition (p=0.04) but not the Observation group, and TEE was not statistically different within either group at 6 months. Addition of 6 months GH resulted in higher energy intake and TEE in the GH/Nutrition group at 12 months (p<0.01), but not in the GH group vs. baseline. Height, weight, lean body mass, hormones and nutrition markers increased comparably in both groups throughout 18 months. Conclusions Boys with CDGM utilize energy at an accelerated rate, an imbalance not overcome with added nutrition. GH therapy increases growth comparably with or without added nutrition in these patients. PMID:20961566

Predicting the probability of abnormal stimulated growth hormone response in children after radiotherapy for brain tumors.

PubMed

Hua, Chiaho; Wu, Shengjie; Chemaitilly, Wassim; Lukose, Renin C; Merchant, Thomas E

2012-11-15

To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n=72), low-grade glioma (n=28) or craniopharyngioma (n=6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test≥7 ng/mL. Independent predictor variables identified by multivariate logistic regression with high statistical significance (p<0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency. Copyright © 2012 Elsevier Inc. All rights reserved.

Growth of human colon cancer cells in nude mice is delayed by ketogenic diet with or without omega-3 fatty acids and medium-chain triglycerides.

PubMed

Hao, Guang-Wei; Chen, Yu-Sheng; He, De-Ming; Wang, Hai-Yu; Wu, Guo-Hao; Zhang, Bo

2015-01-01

Tumors are largely unable to metabolize ketone bodies for energy due to various deficiencies in one or both of the key mitochondrial enzymes, which may provide a rationale for therapeutic strategies that inhibit tumor growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat. Thirty-six male BALB/C nude mice were injected subcutaneously with tumor cells of the colon cancer cell line HCT116. The animals were then randomly split into three feeding groups and fed either a ketogenic diet rich in omega-3 fatty acids and MCT (MKD group; n=12) or lard only (LKD group; n=12) or a standard diet (SD group; n=12) ad libitum. Experiments were ended upon attainment of the target tumor volume of 600 mm3 to 700 mm3. The three diets were compared for tumor growth and survival time (interval between tumor cell injection and attainment of target tumor volume). The tumor growth in the MKD and LKD groups was significantly delayed compared to that in the SD group. Application of an unrestricted ketogenic diet delayed tumor growth in a mouse xenograft model. Further studies are needed to address the mechanism of this diet intervention and the impact on other tumor-relevant parameters such as invasion and metastasis.

Intensity coding in electric hearing: effects of electrode configurations and stimulation waveforms.

PubMed

Chua, Tiffany Elise H; Bachman, Mark; Zeng, Fan-Gang

2011-01-01

Current cochlear implants typically stimulate the auditory nerve with biphasic pulses and monopolar electrode configurations. Tripolar stimulation can increase spatial selectivity and potentially improve place pitch related perception but requires higher current levels to elicit the same loudness as monopolar stimulation. The present study combined delayed pseudomonophonasic pulses, which produce lower thresholds, with tripolar stimulation in an attempt to solve the power-performance tradeoff problem. The present study systematically measured thresholds, dynamic range, loudness growth, and intensity discrimination using either biphasic or delayed pseudomonophonasic pulses under both monopolar and tripolar stimulation. Participants were five Clarion cochlear implant users. For each subject, data from apical, middle, and basal electrode positions were collected when possible. Compared with biphasic pulses, delayed pseudomonophonasic pulses increased the dynamic range by lowering thresholds while maintaining comparable maximum allowable levels under both electrode configurations. However, delayed pseudomonophonasic pulses did not change the shape of loudness growth function and actually increased intensity discrimination limens, especially at lower current levels. The present results indicate that delayed pseudomonophonasic pulses coupled with tripolar stimulation cannot provide significant power savings nor can it increase the functional dynamic range. Whether this combined stimulation could improve functional spectral resolution remains to be seen.

Neural activation during delay discounting is associated with 6-month change in risky sexual behavior in adolescents.

PubMed

Gardiner, Casey K; Karoly, Hollis C; Thayer, Rachel E; Gillman, Arielle S; Sabbineni, Amithrupa; Bryan, Angela D

2018-04-19

Identifying cognitive and neural mechanisms of decision making in adolescence can enhance understanding of, and interventions to reduce, risky health behaviors in adolescence. Delay discounting, or the propensity to discount the magnitude of temporally distal rewards, has been associated with diverse health risk behaviors, including risky sex. This cognitive process involves recruitment of reward and cognitive control brain regions, which develop on different trajectories in adolescence and are also implicated in real-world risky decision making. However, no extant research has examined how neural activation during delay discounting is associated with adolescents' risky sexual behavior. To determine whether a relationship exists between adolescents' risky sexual behavior and neural activation during delay discounting. Adolescent participants completed a delay discounting paradigm during functional magnetic resonance imaging (fMRI) scanning, and they reported risky sexual behavior at baseline, 3-, 6-, 9-, and 12-month follow-up time points. Latent growth curve models were employed to determine relationships between brain activation during delay discounting and change in risky sexual behavior over time. Greater activation in brain regions associated with reward and cognitive control (caudate, putamen, nucleus accumbens, anterior cingulate, insula, orbitofrontal cortex, inferior frontal gyrus, dorsolateral prefrontal cortex) during delay discounting was associated with lower mean levels of risky sexual behavior but greater growth over the period from baseline to 6 months. Neural activation during delay discounting is cross-sectionally and prospectively associated with risky sexual behavior in adolescence, highlighting a neural basis of risky decision-making as well as opportunities for early identification and intervention.

Constrained growth flips the direction of optimal phenological responses among annual plants.

PubMed

Lindh, Magnus; Johansson, Jacob; Bolmgren, Kjell; Lundström, Niklas L P; Brännström, Åke; Jonzén, Niclas

2016-03-01

Phenological changes among plants due to climate change are well documented, but often hard to interpret. In order to assess the adaptive value of observed changes, we study how annual plants with and without growth constraints should optimize their flowering time when productivity and season length changes. We consider growth constraints that depend on the plant's vegetative mass: self-shading, costs for nonphotosynthetic structural tissue and sibling competition. We derive the optimal flowering time from a dynamic energy allocation model using optimal control theory. We prove that an immediate switch (bang-bang control) from vegetative to reproductive growth is optimal with constrained growth and constant mortality. Increasing mean productivity, while keeping season length constant and growth unconstrained, delayed the optimal flowering time. When growth was constrained and productivity was relatively high, the optimal flowering time advanced instead. When the growth season was extended equally at both ends, the optimal flowering time was advanced under constrained growth and delayed under unconstrained growth. Our results suggests that growth constraints are key factors to consider when interpreting phenological flowering responses. It can help to explain phenological patterns along productivity gradients, and links empirical observations made on calendar scales with life-history theory. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Prolonged survival of dendritic cell-vaccinated melanoma patients correlates with tumor-specific delayed type IV hypersensitivity response and reduction of tumor growth factor beta-expressing T cells.

PubMed

López, Mercedes N; Pereda, Cristian; Segal, Gabriela; Muñoz, Leonel; Aguilera, Raquel; González, Fermín E; Escobar, Alejandro; Ginesta, Alexandra; Reyes, Diego; González, Rodrigo; Mendoza-Naranjo, Ariadna; Larrondo, Milton; Compán, Alvaro; Ferrada, Carlos; Salazar-Onfray, Flavio

2009-02-20

The aim of this work was to assess immunologic response, disease progression, and post-treatment survival of melanoma patients vaccinated with autologous dendritic cells (DCs) pulsed with a novel allogeneic cell lysate (TRIMEL) derived from three melanoma cell lines. Forty-three stage IV and seven stage III patients were vaccinated four times with TRIMEL/DC vaccine. Specific delayed type IV hypersensitivity (DTH) reaction, ex vivo cytokine production, and regulatory T-cell populations were determined. Overall survival and disease progression rates were analyzed using Kaplan-Meier curves and compared with historical records. The overall survival for stage IV patients was 15 months. More than 60% of patients showed DTH-positive reaction against the TRIMEL. Stage IV/DTH-positive patients displayed a median survival of 33 months compared with 11 months observed for DTH-negative patients (P = .0014). All stage III treated patients were DTH positive and remained alive and tumor free for a median follow-up period of 48 months (range, 33 to 64 months). DTH-positive patients showed a marked reduction in the proportion of CD4+ transforming growth factor (TGF) beta+ regulatory T cells compared to DTH-negative patients (1.54% v 5.78%; P < .0001). Our findings strongly suggest that TRIMEL-pulsed DCs provide a standardized and widely applicable source of melanoma antigens, very effective in evoking antimelanoma immune response. To our knowledge, this is the first report describing a correlation between vaccine-induced reduction of CD4+TGFbeta+ regulatory T cells and in vivo antimelanoma immune response associated to improved patient survival and disease stability.

Two copies of mthmg1, encoding a novel mitochondrial HMG-like protein, delay accumulation of mitochondrial DNA deletions in Podospora anserina.

PubMed

Dequard-Chablat, Michelle; Allandt, Cynthia

2002-08-01

In the filamentous fungus Podospora anserina, two degenerative processes which result in growth arrest are associated with mitochondrial genome (mitochondrial DNA [mtDNA]) instability. Senescence is correlated with mtDNA rearrangements and amplification of specific regions (senDNAs). Premature death syndrome is characterized by the accumulation of specific mtDNA deletions. This accumulation is due to indirect effects of the AS1-4 mutation, which alters a cytosolic ribosomal protein gene. The mthmg1 gene has been identified as a double-copy suppressor of premature death. It greatly delays premature death and the accumulation of deletions when it is present in two copies in an ASI-4 context. The duplication of mthmg1 has no significant effect on the wild-type life span or on senDNA patterns. In anAS1+ context, deletion of the mthmg1 gene alters germination, growth, and fertility and reduces the life span. The deltamthmg1 senescent strains display a particular senDNA pattern. This deletion is lethal in an AS1-4 context. According to its physical properties (very basic protein with putative mitochondrial targeting sequence and HMG-type DNA-binding domains) and the cellular localization of an mtHMG1-green fluorescent protein fusion, mtHMG1 appears to be a mitochondrial protein possibly associated with mtDNA. It is noteworthy that it is the first example of a protein combining the two DNA-binding domains, AT-hook motif and HMG-1 boxes. It may be involved in the stability and/or transmission of the mitochondrial genome. To date, no structural homologues have been found in other organisms. However, mtHMG1 displays functional similarities with the Saccharomyces cerevisiae mitochondrial HMG-box protein Abf2.

DNA-dependent protein kinase is a molecular target for the development of noncytotoxic radiation-sensitizing drugs.

PubMed

Shinohara, Eric T; Geng, Ling; Tan, Jiahui; Chen, Heidi; Shir, Yu; Edwards, Eric; Halbrook, James; Kesicki, Edward A; Kashishian, Adam; Hallahan, Dennis E

2005-06-15

DNA-dependent protein kinase (DNA-PK)-defective severe combined immunodeficient (SCID) mice have a greater sensitivity to ionizing radiation compared with wild-type mice due to deficient repair of DNA double-strand break. SCID cells were therefore studied to determine whether radiosensitization by the specific inhibitor of DNA-PK, IC87361, is eliminated in the absence of functional DNA-PK. IC87361 enhanced radiation sensitivity in wild-type C57BL6 endothelial cells but not in SCID cells. The tumor vascular window model was used to assess IC87361-induced radiosensitization of SCID and wild-type tumor microvasculature. Vascular density was 5% in irradiated SCID host compared with 50% in C57BL6 mice (P < 0.05). IC87361 induced radiosensitization of tumor microvasculature in wild-type mice that resembled the radiosensitive phenotype of tumor vessels in SCID mice. Radiosensitization by IC87361 was eliminated in SCID tumor vasculature, which lack functional DNA-PK. Irradiated LLC and B16F0 tumors implanted into SCID mice showed greater tumor growth delay compared with tumors implanted into either wild-type C57BL6 or nude mice. Furthermore, LLC tumors treated with radiation and IC87361 showed tumor growth delay that was significantly greater than tumors treated with radiation alone (P < 0.01 for 3 Gy alone versus 3 Gy + IC87361). DNA-PK inhibitors induced no cytotoxicity and no toxicity in mouse normal tissues. Mouse models deficient in enzyme activity are useful to assess the specificity of novel kinase inhibitors. DNA-PK is an important target for the development of novel radiation-sensitizing drugs that have little intrinsic cytotoxicity.

The use of autologous concentrated growth factors to promote syndesmosis fusion in the Agility total ankle replacement. A preliminary study.

PubMed

Coetzee, J Chris; Pomeroy, Gregory C; Watts, J David; Barrow, Craig

2005-10-01

The Agility (DePuy, Warsaw, Indiana) total ankle replacement has been in use since 1984. One of the most common complications continues to be delayed union or nonunions of the distal tibiofibular syndesmosis. In the reported studies on the Agility ankle the delayed union and nonunion rate can be as high as 38%. Since 1999, 114 Agility total ankle replacements were done at two centers in the United States without the use of autologous concentrated growth factors. Since July of 2001, 66 Agility ankles were implanted with Symphony (DePuy, Warsaw, Indiana) augmented bone grafting. The standard operative technique was followed in all the patients. Prospective data was collected on all patients. The standard ankle radiographs were taken preoperatively and postoperative at 8 weeks, 12 weeks, 16 weeks, 6 months, and yearly. CT scans were obtained at 6 months if fusion at the syndesmosis was questionable. The Graphpad Instat software (Graphpad Software Inc., San Diego, CA) was used for statistical analysis. The two-tailed unpaired t-test was used, and the value <0.05 was considered significant. There was no statistical difference in the demographic data for the two groups. In 114 ankle replacements without autologous concentrated growth factors 70 fused at 8 weeks (61%), 14 fused at 12 weeks (12%), 13 fused at 6 months (12%). There were 17 nonunions (15%); delayed unions (3 to 6 months) and nonunions, therefore, equaled 27%. The syndesmosis fused in 50 of the 66 ankle replacements (76%) that had autologous concentrated growth fractures at 8 weeks (76%); 12 fused at 3 months (18%), 2 fused at 6 months (3%), 2 had nonunions (3%). Delayed unions (3 to 6 months) and nonunions equaled 6%. There was a statistically significant improvement in the 8- and 12-week fusion rates, and a statistically significant reduction in delayed unions and nonunions. Autologous concentrated growth factors appear to make a significant positive difference in the syndesmosis union rate in total ankle replacements.

Effects of Acute and Chronic Cocaine Administration on Titrating-Delay Matching-to-Sample Performance

ERIC Educational Resources Information Center

Kangas, Brian D.; Branch, Marc N.

2012-01-01

The effects of cocaine were examined under a titrating-delay matching-to-sample procedure. In this procedure, the delay between sample stimulus offset and comparison stimuli onset adjusts as a function of the subject's performance. Specifically, matches increase the delay and mismatches decrease the delay. Titrated delay values served as the…

Dealing with delays does not transfer across sensorimotor tasks.

PubMed

de la Malla, Cristina; López-Moliner, Joan; Brenner, Eli

2014-10-09

It is known that people can learn to deal with delays between their actions and the consequences of such actions. We wondered whether they do so by adjusting their anticipations about the sensory consequences of their actions or whether they simply learn to move in certain ways when performing specific tasks. To find out, we examined details of how people learn to intercept a moving target with a cursor that follows the hand with a delay and examined the transfer of learning between this task and various other tasks that require temporal precision. Subjects readily learned to intercept the moving target with the delayed cursor. The compensation for the delay generalized across modifications of the task, so subjects did not simply learn to move in a certain way in specific circumstances. The compensation did not generalize to completely different timing tasks, so subjects did not generally expect the consequences of their motor commands to be delayed. We conclude that people specifically learn to control the delayed visual consequences of their actions to perform certain tasks. © 2014 ARVO.

Impact of TBI on late effects in children treated by megatherapy for Stage IV neuroblastoma. A study of the French Society of Pediatric oncology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Flandin, Isabelle; Department of Radiotherapy/Oncology, Hospital Lyon Sud, Lyon; Hartmann, Olivier

2006-04-01

Purpose: To determine the contribution of total body irradiation (TBI) to late sequelae in children treated with high-dose chemotherapy and autologous bone marrow transplantation for Stage IV neuroblastoma. Patients and Methods: We compared two populations that were similar with regard to age, stage, pre-autologous bone marrow transplantation chemotherapy (CT) regimen, period of treatment, and follow-up (12 years). The TBI group (n = 32) received TBI as part of the megatherapy procedure (1982-1993), whereas the CT group (n 30) received conditioning without TBI (1985-1992). Analysis 12 years later focused on growth, weight and corpulence (body mass index) delay; hormonal deficiencies; liver,more » kidney, heart, ear, eye, and dental sequelae; school performance; and the incidence of secondary tumors. Results: Impact of TBI was most marked in relation to growth and weight delay, although the mean delay was not severe, probably because of treatment with growth hormones. Other consequences of TBI were thyroid insufficiency, cataracts, and a high incidence of secondary tumors. Hearing loss and dental agenesis were more prominent in the group treated with CT alone. No differences were observed in school performance. Conclusion: The most frequent side effects of TBI were cataracts, thyroid insufficiency, and growth delay, but more worrying is the risk of secondary tumors. Because of the young mean age of patients and the toxicity of TBI regimens without any survival advantage, regimens without TBI are preferable in the management of Stage IV neuroblastoma.« less

Somatotropic Signaling: Trade-Offs Between Growth, Reproductive Development, and Longevity

PubMed Central

Sun, Liou Y.; Longo, Valter

2013-01-01

Growth hormone (GH) is a key determinant of postnatal growth and plays an important role in the control of metabolism and body composition. Surprisingly, deficiency in GH signaling delays aging and remarkably extends longevity in laboratory mice. In GH-deficient and GH-resistant animals, the “healthspan” is also extended with delays in cognitive decline and in the onset of age-related disease. The role of hormones homologous to insulin-like growth factor (IGF, an important mediator of GH actions) in the control of aging and lifespan is evolutionarily conserved from worms to mammals with some homologies extending to unicellular yeast. The combination of reduced GH, IGF-I, and insulin signaling likely contributes to extended longevity in GH or GH receptor-deficient organisms. Diminutive body size and reduced fecundity of GH-deficient and GH-resistant mice can be viewed as trade-offs for extended longevity. Mechanisms responsible for delayed aging of GH-related mutants include enhanced stress resistance and xenobiotic metabolism, reduced inflammation, improved insulin signaling, and various metabolic adjustments. Pathological excess of GH reduces life expectancy in men as well as in mice, and GH resistance or deficiency provides protection from major age-related diseases, including diabetes and cancer, in both species. However, there is yet no evidence of increased longevity in GH-resistant or GH-deficient humans, possibly due to non-age-related deaths. Results obtained in GH-related mutant mice provide striking examples of mutations of a single gene delaying aging, reducing age-related disease, and extending lifespan in a mammal and providing novel experimental systems for the study of mechanisms of aging. PMID:23589828

Cognitive Function in Individuals with Atypical Pubertal Development.

ERIC Educational Resources Information Center

Rovet, Joanne F.; And Others

A study of 55 growth-disturbed children, aged 8-17, was conducted to assess how rate of physical maturation and pubertal development influences cognitive and neuropsychological functioning. The sample included 27 boys with short stature and delayed pubertal development (SSB), 15 girls with delayed puberty (DPG), and 13 girls with precocious…

Can the observed association between serum perfluoroalkyl substances and delayed menarche be explained on the basis of puberty-related changes in physiology and pharmacokinetics?

PubMed

Wu, Huali; Yoon, Miyoung; Verner, Marc-André; Xue, Jianping; Luo, Man; Andersen, Melvin E; Longnecker, Matthew P; Clewell, Harvey J

2015-09-01

An association between serum levels of two perfluoroalkyl substances (PFAS) and delayed age at menarche was reported in a cross-sectional study of adolescents. Because perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have half-lives of years, growth dilution and the development of a new route of excretion (menstruation) could account for some or all of the reported association. To assess how much of the epidemiologic association between PFAS and delayed menarche can be explained by the correlation of growth and maturation with PFAS body burden. We developed a Monte Carlo (MC) physiologically-based pharmacokinetic (PBPK) model of PFAS to simulate plasma PFAS levels in a hypothetical female population aged 2 to 20years old. Realistic distributions of physiological parameters as well as timing of growth spurts and menarche were incorporated in the model. The association between PFAS level and delayed menarche in the simulated data was compared with the reported association. The prevalence of menarche, distributions of age-dependent physiological parameters, and quartiles of serum PFAS concentrations in the simulated subjects were comparable to those reported in the epidemiologic study. The delay of menarche in days per natural log increase in PFAS concentrations in the simulated data were about one third as large as the observed values. The reported relationship between PFAS and age at menarche appears to be at least partly explained by pharmacokinetics rather than a toxic effect of these substances. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of triploidy on growth and protein degradation in skeletal muscle during recovery from feed deprivation in juvenile rainbow trout (Oncorhynchus mykiss).

PubMed

Cleveland, Beth M; Weber, Gregory M

2013-09-01

Identifying physiological differences between diploid and triploid rainbow trout will help define how ploidy affects mechanisms that impact growth and nutrient utilization. Juvenile diploid and triploid female rainbow trout (Oncorhynchus mykiss) were either continually fed or fasted for one week, followed by four weeks of refeeding, and indices of growth and proteolysis-related gene expression in skeletal muscle were measured. Fasting reduced growth, and based on gene expression analysis, increased capacity for protein degradation. Regardless of feeding treatment, triploids displayed slightly greater feed intake and specific growth rates than diploids. Continually fed triploids displayed lower expression of several autophagy-related genes than diploids, suggesting that reduced rates of protein degradation contributed to their faster growth. Reduced expression of ubiquitin ligases fbxo32 and fbxo25 and autophagy-related genes during refeeding implicates reduced proteolysis in recovery growth. At one week of refeeding triploids exhibited greater gains in eviscerated body weight and length, whereas diploids exhibited greater gains in gastrointestinal tract weights. During refeeding two autophagy-related genes, atg4b and lc3b, decreased within one week to continually fed levels in the triploids, but in diploids overshot in expression at one and two weeks of refeeding then rebounding above continually fed levels by week four, suggesting a delayed return to basal levels of proteolysis. Published by Elsevier Inc.

Effect of irrigation on needle morphology, shoot and stem growth in a drought-exposed Pinus sylvestris forest.

PubMed

Dobbertin, Matthias; Eilmann, Britta; Bleuler, Peter; Giuggiola, Arnaud; Graf Pannatier, Elisabeth; Landolt, Werner; Schleppi, Patrick; Rigling, Andreas

2010-03-01

In Valais, Switzerland, Scots pines (Pinus sylvestris L.) are declining, mainly following drought. To assess the impact of drought on tree growth and survival, an irrigation experiment was initiated in 2003 in a mature pine forest, approximately doubling the annual precipitation. Tree crown transparency (lack of foliage) and leaf area index (LAI) were annually assessed. Seven irrigated and six control trees were felled in 2006, and needles, stem discs and branches were taken for growth analysis. Irrigation in 2004 and 2005, both with below-average precipitation, increased needle size, area and mass, stem growth and, with a 1-year delay, shoot length. This led to a relative decrease in tree crown transparency (-14%) and to an increase in stand LAI (+20%). Irrigation increased needle length by 70%, shoot length by 100% and ring width by 120%, regardless of crown transparency. Crown transparency correlated positively with mean needle size, shoot length and ring width and negatively with specific leaf area. Trees with high crown transparency (low growth, short needles) experienced similar increases in needle mass and growth with irrigation than trees with low transparency (high growth, long needles), indicating that seemingly declining trees were able to 'recover' when water supply became sufficient. A simple drought index before and during the irrigation explained most of the variation found in the parameters for both irrigated and control trees.

Delayed White Matter Growth Trajectory in Young Nonpsychotic Siblings of Patients With Childhood-Onset Schizophrenia

PubMed Central

Gogtay, Nitin; Hua, Xue; Stidd, Reva; Boyle, Christina P.; Lee, Suh; Weisinger, Brian; Chavez, Alex; Giedd, Jay N.; Clasen, Liv; Toga, Arthur W.; Rapoport, Judith L.; Thompson, Paul M.

2013-01-01

Context Nonpsychotic siblings of patients with childhood-onset schizophrenia (COS) share cortical gray matter abnormalities with their probands at an early age; these normalize by the time the siblings are aged 18 years, suggesting that the gray matter abnormalities in schizophrenia could be an age-specific endophenotype. Patients with COS also show significant white matter (WM) growth deficits, which have not yet been explored in nonpsychotic siblings. Objective To study WM growth differences in non-psychotic siblings of patients with COS. Design Longitudinal (5-year) anatomic magnetic resonance imaging study mapping WM growth using a novel tensor-based morphometry analysis. Setting National Institutes of Health Clinical Center, Bethesda, Maryland. Participants Forty-nine healthy siblings of patients with COS (mean [SD] age, 16.1[5.3] years; 19 male, 30 female) and 57 healthy persons serving as controls (age, 16.9[5.3] years; 29 male, 28 female). Intervention Magnetic resonance imaging. Main Outcome Measure White matter growth rates. Results We compared the WM growth rates in 3 age ranges. In the youngest age group (7 to <14 years), we found a significant difference in growth rates, with siblings of patients with COS showing slower WM growth rates in the parietal lobes of the brain than age-matched healthy controls (false discovery rate, q = 0.05; critical P = .001 in the bilateral parietal WM; a post hoc analysis identified growth rate differences only on the left side, critical P =.004). A growth rate difference was not detectable at older ages. In 3-dimensional maps, growth rates in the siblings even appeared to surpass those of healthy individuals at later ages, at least locally in the brain, but this effect did not survive a multiple comparisons correction. Conclusions In this first longitudinal study of nonpsychotic siblings of patients with COS, the siblings showed early WM growth deficits, which normalized with age. As reported before for gray matter, WM growth may also be an age-specific endophenotype that shows compensatory normalization with age. PMID:22945617

Delay dynamics of neuromorphic optoelectronic nanoscale resonators: Perspectives and applications

NASA Astrophysics Data System (ADS)

Romeira, Bruno; Figueiredo, José M. L.; Javaloyes, Julien

2017-11-01

With the recent exponential growth of applications using artificial intelligence (AI), the development of efficient and ultrafast brain-like (neuromorphic) systems is crucial for future information and communication technologies. While the implementation of AI systems using computer algorithms of neural networks is emerging rapidly, scientists are just taking the very first steps in the development of the hardware elements of an artificial brain, specifically neuromorphic microchips. In this review article, we present the current state of the art of neuromorphic photonic circuits based on solid-state optoelectronic oscillators formed by nanoscale double barrier quantum well resonant tunneling diodes. We address, both experimentally and theoretically, the key dynamic properties of recently developed artificial solid-state neuron microchips with delayed perturbations and describe their role in the study of neural activity and regenerative memory. This review covers our recent research work on excitable and delay dynamic characteristics of both single and autaptic (delayed) artificial neurons including all-or-none response, spike-based data encoding, storage, signal regeneration and signal healing. Furthermore, the neural responses of these neuromorphic microchips display all the signatures of extended spatio-temporal localized structures (LSs) of light, which are reviewed here in detail. By taking advantage of the dissipative nature of LSs, we demonstrate potential applications in optical data reconfiguration and clock and timing at high-speeds and with short transients. The results reviewed in this article are a key enabler for the development of high-performance optoelectronic devices in future high-speed brain-inspired optical memories and neuromorphic computing.

Analysis of an age structured model for tick populations subject to seasonal effects

NASA Astrophysics Data System (ADS)

Liu, Kaihui; Lou, Yijun; Wu, Jianhong

2017-08-01

We investigate an age-structured hyperbolic equation model by allowing the birth and death functions to be density dependent and periodic in time with the consideration of seasonal effects. By studying the integral form solution of this general hyperbolic equation obtained through the method of integration along characteristics, we give a detailed proof of the uniqueness and existence of the solution in light of the contraction mapping theorem. With additional biologically natural assumptions, using the tick population growth as a motivating example, we derive an age-structured model with time-dependent periodic maturation delays, which is quite different from the existing population models with time-independent maturation delays. For this periodic differential system with seasonal delays, the basic reproduction number R0 is defined as the spectral radius of the next generation operator. Then, we show the tick population tends to die out when R0 < 1 while remains persistent if R0 > 1. When there is no intra-specific competition among immature individuals due to the sufficient availability of immature tick hosts, the global stability of the positive periodic state for the whole model system of four delay differential equations can be obtained with the observation that a scalar subsystem for the adult stage size can be decoupled. The challenge for the proof of such a global stability result can be overcome by introducing a new phase space, based on which, a periodic solution semiflow can be defined which is eventually strongly monotone and strictly subhomogeneous.

Delay dynamics of neuromorphic optoelectronic nanoscale resonators: Perspectives and applications.

PubMed

Romeira, Bruno; Figueiredo, José M L; Javaloyes, Julien

2017-11-01

With the recent exponential growth of applications using artificial intelligence (AI), the development of efficient and ultrafast brain-like (neuromorphic) systems is crucial for future information and communication technologies. While the implementation of AI systems using computer algorithms of neural networks is emerging rapidly, scientists are just taking the very first steps in the development of the hardware elements of an artificial brain, specifically neuromorphic microchips. In this review article, we present the current state of the art of neuromorphic photonic circuits based on solid-state optoelectronic oscillators formed by nanoscale double barrier quantum well resonant tunneling diodes. We address, both experimentally and theoretically, the key dynamic properties of recently developed artificial solid-state neuron microchips with delayed perturbations and describe their role in the study of neural activity and regenerative memory. This review covers our recent research work on excitable and delay dynamic characteristics of both single and autaptic (delayed) artificial neurons including all-or-none response, spike-based data encoding, storage, signal regeneration and signal healing. Furthermore, the neural responses of these neuromorphic microchips display all the signatures of extended spatio-temporal localized structures (LSs) of light, which are reviewed here in detail. By taking advantage of the dissipative nature of LSs, we demonstrate potential applications in optical data reconfiguration and clock and timing at high-speeds and with short transients. The results reviewed in this article are a key enabler for the development of high-performance optoelectronic devices in future high-speed brain-inspired optical memories and neuromorphic computing.

Links between ammonia oxidizer species composition, functional diversity and nitrification kinetics in grassland soils.

PubMed

Webster, Gordon; Embley, T Martin; Freitag, Thomas E; Smith, Zena; Prosser, James I

2005-05-01

Molecular approaches have revealed considerable diversity and uncultured novelty in natural prokaryotic populations, but not direct links between the new genotypes detected and ecosystem processes. Here we describe the influence of the structure of communities of ammonia-oxidizing bacteria on nitrogen cycling in microcosms containing natural and managed grasslands and amended with artificial sheep urine, a major factor determining local ammonia concentrations in these environments. Nitrification kinetics were assessed by analysis of changes in urea, ammonia, nitrite and nitrate concentrations and ammonia oxidizer communities were characterized by analysis of 16S rRNA genes amplified from extracted DNA using ammonia oxidizer-specific primers. In natural soils, ammonia oxidizer community structure determined the delay preceding nitrification, which depended on the relative abundance of two Nitrosospira clusters, termed 3a and 3b. In batch cultures, pure culture and enrichment culture representatives of Nitrosospira 3a were sensitive to high ammonia concentration, while Nitrosospira cluster 3b representatives and Nitrosomonas europaea were tolerant. Delays in nitrification occurred in natural soils dominated by Nitrosospira cluster 3a and resulted from the time required for growth of low concentrations of Nitrosospira cluster 3b. In microcosms dominated by Nitrosospira cluster 3b and Nitrosomonas, no substantial delays were observed. In managed soils, no delays in nitrification were detected, regardless of initial ammonia oxidizer community structure, most probably resulting from higher ammonia oxidizer cell concentrations. The data therefore demonstrate a direct link between bacterial community structure, physiological diversity and ecosystem function.

Plant hormone jasmonate prioritizes defense over growth by interfering with gibberellin signaling cascade.

PubMed

Yang, Dong-Lei; Yao, Jian; Mei, Chuan-Sheng; Tong, Xiao-Hong; Zeng, Long-Jun; Li, Qun; Xiao, Lang-Tao; Sun, Tai-ping; Li, Jigang; Deng, Xing-Wang; Lee, Chin Mei; Thomashow, Michael F; Yang, Yinong; He, Zuhua; He, Sheng Yang

2012-05-08

Plants must effectively defend against biotic and abiotic stresses to survive in nature. However, this defense is costly and is often accompanied by significant growth inhibition. How plants coordinate the fluctuating growth-defense dynamics is not well understood and remains a fundamental question. Jasmonate (JA) and gibberellic acid (GA) are important plant hormones that mediate defense and growth, respectively. Binding of bioactive JA or GA ligands to cognate receptors leads to proteasome-dependent degradation of specific transcriptional repressors (the JAZ or DELLA family of proteins), which, at the resting state, represses cognate transcription factors involved in defense (e.g., MYCs) or growth [e.g. phytochrome interacting factors (PIFs)]. In this study, we found that the coi1 JA receptor mutants of rice (a domesticated monocot crop) and Arabidopsis (a model dicot plant) both exhibit hallmark phenotypes of GA-hypersensitive mutants. JA delays GA-mediated DELLA protein degradation, and the della mutant is less sensitive to JA for growth inhibition. Overexpression of a selected group of JAZ repressors in Arabidopsis plants partially phenocopies GA-associated phenotypes of the coi1 mutant, and JAZ9 inhibits RGA (a DELLA protein) interaction with transcription factor PIF3. Importantly, the pif quadruple (pifq) mutant no longer responds to JA-induced growth inhibition, and overexpression of PIF3 could partially overcome JA-induced growth inhibition. Thus, a molecular cascade involving the COI1-JAZ-DELLA-PIF signaling module, by which angiosperm plants prioritize JA-mediated defense over growth, has been elucidated.

On the delay factors of the private construction projects in Medan city

NASA Astrophysics Data System (ADS)

Perwira Mulia Tarigan, A.; Subroto

2018-03-01

The delay in construction projects undertaken by contractors is impeding the economic growth of a region. Medan city which is one of the big cities in Indonesia is suffering from it. This study aims to identify the dominant factors causing delays in construction projects conducted by private contractors. The interview method with questionnaires is used to involve 20 contractors, 10 consultants, and 10 owner representatives in the study. From the 45 identified factors causing delays, the highest ranking is the change of work demand by the project owners with 71.84% importance index.

Fitted Fourier-pseudospectral methods for solving a delayed reaction-diffusion partial differential equation in biology

NASA Astrophysics Data System (ADS)

Adam, A. M. A.; Bashier, E. B. M.; Hashim, M. H. A.; Patidar, K. C.

2017-07-01

In this work, we design and analyze a fitted numerical method to solve a reaction-diffusion model with time delay, namely, a delayed version of a population model which is an extension of the logistic growth (LG) equation for a food-limited population proposed by Smith [F.E. Smith, Population dynamics in Daphnia magna and a new model for population growth, Ecology 44 (1963) 651-663]. Seeing that the analytical solution (in closed form) is hard to obtain, we seek for a robust numerical method. The method consists of a Fourier-pseudospectral semi-discretization in space and a fitted operator implicit-explicit scheme in temporal direction. The proposed method is analyzed for convergence and we found that it is unconditionally stable. Illustrative numerical results will be presented at the conference.

Evaluating within-population variability in behavior and demography for the adaptive potential of a dispersal-limited species to climate change

USGS Publications Warehouse

Muñoz, David J.; Miller Hesed, Kyle; Grant, Evan H. Campbell; Miller, David A.W.

2016-01-01

Multiple pathways exist for species to respond to changing climates. However, responses of dispersal-limited species will be more strongly tied to ability to adapt within existing populations as rates of environmental change will likely exceed movement rates. Here, we assess adaptive capacity in Plethodon cinereus, a dispersal-limited woodland salamander. We quantify plasticity in behavior and variation in demography to observed variation in environmental variables over a 5-year period. We found strong evidence that temperature and rainfall influence P. cinereus surface presence, indicating changes in climate are likely to affect seasonal activity patterns. We also found that warmer summer temperatures reduced individual growth rates into the autumn, which is likely to have negative demographic consequences. Reduced growth rates may delay reproductive maturity and lead to reductions in size-specific fecundity, potentially reducing population-level persistence. To better understand within-population variability in responses, we examined differences between two common color morphs. Previous evidence suggests that the color polymorphism may be linked to physiological differences in heat and moisture tolerance. We found only moderate support for morph-specific differences for the relationship between individual growth and temperature. Measuring environmental sensitivity to climatic variability is the first step in predicting species' responses to climate change. Our results suggest phenological shifts and changes in growth rates are likely responses under scenarios where further warming occurs, and we discuss possible adaptive strategies for resulting selective pressures.

Dissecting the Genetic Architecture of Shoot Growth in Carrot (Daucus carota L.) Using a Diallel Mating Design

PubMed Central

Turner, Sarah D.; Maurizio, Paul L.; Valdar, William; Yandell, Brian S.; Simon, Philipp W.

2017-01-01

Crop establishment in carrot (Daucus carota L.) is limited by slow seedling growth and delayed canopy closure, resulting in high management costs for weed control. Varieties with improved growth habit (i.e., larger canopy and increased shoot biomass) may help mitigate weed control, but the underlying genetics of these traits in carrot is unknown. This project used a diallel mating design coupled with recent Bayesian analytical methods to determine the genetic basis of carrot shoot growth. Six diverse carrot inbred lines with variable shoot size were crossed in WI in 2014. F1 hybrids, reciprocal crosses, and parental selfs were grown in a randomized complete block design with two blocks in WI (2015) and CA (2015, 2016). Measurements included canopy height, canopy width, shoot biomass, and root biomass. General and specific combining abilities were estimated using Griffing’s Model I, which is a common analysis for plant breeding experiments. In parallel, additive, inbred, cross-specific, and maternal effects were estimated from a Bayesian mixed model, which is robust to dealing with data imbalance and outliers. Both additive and nonadditive effects significantly influenced shoot traits, with nonadditive effects playing a larger role early in the growing season, when weed control is most critical. Results suggest the presence of heritable variation and thus potential for improvement of these phenotypes in carrot. In addition, results present evidence of heterosis for root biomass, which is a major component of carrot yield. PMID:29187419

De morseir syndrome presenting as ambiguous genitalia.

PubMed

Thukral, Anubhav; Chitra, S; Chakraborty, Partho P; Roy, Ajitesh; Goswami, Soumik; Bhattacharjee, Rana; Dutta, Deep; Maisnam, Indira; Ghosh, Sujoy; Mukherjee, Satinath; Chowdhury, Subhankar

2012-12-01

A 10-year-old boy presented with genital ambiguity, poor linear growth, and delayed milestones. The aim and to highlight that although rare but congenital, hypogonadotropic hypogonadism may rarely present as ambiguity. The patient was found to have bilateral cryptorchidism with proximal penile hypospadias, microphallus with a proportionate dwarfism with mildly delayed bone age, and karyotype 46XY. Euthyroid with normal steroid axis, growth hormone insufficient as suggested by auxology, low IGF1, and poor response to clonidine stimulation. MRI brain shows hypoplastic corpus callosum, hypoplastic anterior pituitary, and ectopic posterior pituitary bright spot. The patient underwent laparoscopic removal of right intrabdominal testis and orchidoplexy was performed on the left one. Testicular biopsy revealed no malignancy and growth hormone replacement was initiated. The patient awaits definitive repair of hypospadias. As a provisional diagnosis of combined growth hormone and gonadotropin deficiency, most probable diagnosis is septo-optic dysplasia or de moseir syndrome leading to genital ambiguity.

The effect of a short-term delay of puberty on trabecular bone mass and structure in female rats: A texture-based and histomorphometric analysis.

PubMed Central

Yingling, Vanessa R; Xiang, Yongqing; Raphan, Theodore; Schaffler, Mitchell; Koser, Karen; Malique, Rumena

2007-01-01

Accrual of bone mass and strength during development is imperative in order to reduce the risk of fracture later in life. Although delayed pubertal onset is associated with an increased incidence of stress fracture, evidence supports the concept of “catch up” growth. It remains unclear if deficits in bone mass associated with delayed puberty have long term effects on trabecular bone structure and strength. The purpose of this study was to use texture-based analysis and histomorphometry to investigate the effect of a delay in puberty on trabecular bone mass and structure immediately post-puberty and at maturity in female rats. Forty-eight female Sprague Dawley rats (25 days) were randomly assigned to one of four groups; 1) short-term control (C-ST), 2) long-term control (C-LT), 3) short-term GnRH antagonist (G-ST) and 4) long-term GnRH antagonist (G-LT). Injections of either saline or gonadotropin-releasing hormone antagonist (GnRH-a) (100 μg/day) (Cetrotide™, Serono, Inc) were given intraperitoneally for 18 days (day 35–42) to both ST and LT. The ST groups were sacrificed after the last injection (day 43) and the LT groups at 6 months of age. Pubertal and gonadal development was retarded by the GnRA antagonist injections as indicated by a delay in vaginal opening, lower ovarian and uterine weights and suppressed estradiol levels in the short-term experimental animals (G-ST). Delayed puberty caused a transient reduction in trabecular bone area as assessed by histomorphometry. Specifically, the significant deficit in bone area resulted from a decreased number of trabecula and an increase in trabecular separation. Texture analysis, a new method to assess bone density and structural anisotropy, correlated well with the standard histomorphometry and measured significant deficits in the density measure (MDensity) in the G-ST group that remained at maturity (6 months). The texture energy deficit in the G-ST group was primarily in the 0° orientation (−13.2 %), which measures the longitudinal trabeculae in the proximal tibia. However, the deficit in the G-LT group was in the 45° and 135° orientations. These results suggest that any “catch-up” growth following the cessation of the GnRH-antagonist injection protocol may be directed in trabeculae oriented perpendicular to 0° at the expense of trabeculae in other orientations. PMID:16979963

Decrease in hematopoietic stem cell domains as a delayed effect of x-irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maloney, M.A.; Lamela, R.A.; Patt, H.M.

Although the hematopoietic integrity of locally X-irradiated sites can be restored for a time even after fairly large doses, a secondary aplasia often occurs some months later. To gain further insight into this delayed effect within the framework of the stem cell regulatory domain hypothesis, we characterized the growth kinetics of spleen colony forming units (CFU-S) in WBB6FI-+/+ bone marrow transplanted into WBB6FI-W/WV mice in which one leg had been exposed to 10-30 Gy of X rays 4-5 months previously. Compared to unirradiated contralateral marrow, fewer CFU-S either reached the previously irradiated marrow or were seeded into sites that couldmore » support growth. The initial exponential growth of effectively seeded CFU-S was unchanged, but growth deceleration (inflection point) occurred at a lower level of CFU-S in marrow previously irradiated with 20-30 Gy. This change in the inflection point indicates a radiation dose-dependent decrease consistent with the decrease in bone marrow cellularity. The decrease in effective stem cell domains after 20 Gy was calculated to be about 35%. We interpret these results to reflect the highly localized nature of delayed radiation damage to the marrow microenvironment.« less

Cloud condensation nuclei droplet growth kinetics of ultrafine particles during anthropogenic nucleation events

NASA Astrophysics Data System (ADS)

Shantz, N. C.; Pierce, J. R.; Chang, R. Y.-W.; Vlasenko, A.; Riipinen, I.; Sjostedt, S.; Slowik, J. G.; Wiebe, A.; Liggio, J.; Abbatt, J. P. D.; Leaitch, W. R.

2012-02-01

Evolution of the cloud condensation nucleus (CCN) activity of 36 ± 4 nm diameter anthropogenic aerosol particles at a water supersaturation of 1.0 ± 0.1% is examined for particle nucleation and growth. During the early stages of one event, relatively few of the anthropogenic particles at 36 nm were CCN active and their growth rates by water condensation were delayed relative to ammonium sulphate particles. As the event progressed, the particle size distribution evolved to larger sizes and the relative numbers of particles at 36 nm that were CCN active increased until all the 36 nm particles were activating at the end of the event. Based on the chemistry of larger particles and the results from an aerosol chemical microphysics box model, the increase in CCN activity of the particles was most likely the result of the condensation of sulphate in this case. Despite the increased CCN activity, a delay was observed in the initial growth of these particles into cloud droplets, which persisted even when the aerosol was most CCN active later in the afternoon. Simulations show that the delay in water uptake is explained by a reduction of the mass accommodation coefficient assuming that the composition of the 36 nm particles is the same as the measured composition of the 60-100 nm particles.

Effect of Multiple Delays in an Eco-Epidemiological Model with Strong Allee Effect

NASA Astrophysics Data System (ADS)

Ghosh, Kakali; Biswas, Santanu; Samanta, Sudip; Tiwari, Pankaj Kumar; Alshomrani, Ali Saleh; Chattopadhyay, Joydev

In the present article, we make an attempt to investigate the effect of two time delays, logistic delay and gestation delay, on an eco-epidemiological model. In the proposed model, strong Allee effect is considered in the growth term of the prey population. We incorporate two time lags and inspect elementary mathematical characteristic of the proposed model such as boundedness, uniform persistence, stability and Hopf-bifurcation for all possible combinations of both delays at the interior equilibrium point of the system. We observe that increase in gestation delay leads to chaotic solutions through the limit cycle. We also observe that the Allee effect play a major role in controlling the chaos. We execute several numerical simulations to illustrate the proposed mathematical model and our analytical findings.

Effects of PSAG12-IPT Gene Expression on Development and Senescence in Transgenic Lettuce1

PubMed Central

McCabe, Matthew S.; Garratt, Lee C.; Schepers, Frank; Jordi, Wilco J.R.M.; Stoopen, Geert M.; Davelaar, Evert; van Rhijn, J. Hans A.; Power, J. Brian; Davey, Michael R.

2001-01-01

An ipt gene under control of the senescence-specific SAG12 promoter from Arabidopsis (PSAG12-IPT) significantly delayed developmental and postharvest leaf senescence in mature heads of transgenic lettuce (Lactuca sativa L. cv Evola) homozygous for the transgene. Apart from retardation of leaf senescence, mature, 60-d-old plants exhibited normal morphology with no significant differences in head diameter or fresh weight of leaves and roots. Induction of senescence by nitrogen starvation rapidly reduced total nitrogen, nitrate, and growth of transgenic and azygous (control) plants, but chlorophyll was retained in the lower (outer) leaves of transgenic plants. Harvested PSAG12-IPT heads also retained chlorophyll in their lower leaves. During later development (bolting and preflowering) of transgenic plants, the decrease in chlorophyll, total protein, and Rubisco content in leaves was abolished, resulting in a uniform distribution of these components throughout the plants. Homozygous PSAG12-IPT lettuce plants showed a slight delay in bolting (4–6 d), a severe delay in flowering (4–8 weeks), and premature senescence of their upper leaves. These changes correlated with significantly elevated concentrations of cytokinin and hexoses in the upper leaves of transgenic plants during later stages of development, implicating a relationship between cytokinin and hexose concentrations in senescence. PMID:11598225

Postnatal effects of intrauterine treatment of the growth-restricted ovine fetus with intra-amniotic insulin-like growth factor-1.

PubMed

Spiroski, A M; Oliver, M H; Jaquiery, A L; Prickett, T C R; Espiner, E A; Harding, J E; Bloomfield, F H

2017-12-12

Fetal growth restriction increases the risk of fetal and neonatal mortality and morbidity, and contributes to increased risk of chronic disease later in life. Intra-amniotic insulin-like growth factor-1 (IGF1) treatment of the growth-restricted ovine fetus improves fetal growth, but postnatal effects are unknown. Here we report that intra-amniotic IGF1 treatment of the growth-restricted ovine fetus alters size at birth and mechanisms of early postnatal growth in a sex-specific manner. We also show that maternal plasma C-type natriuretic peptide (CNP) products are related to fetal oxygenation and size at birth, and hence may be useful for non-invasive monitoring of fetal growth restriction. Intrauterine IGF1 treatment in late gestation is a potentially clinically relevant intervention that may ameliorate the postnatal complications of fetal growth restriction. Placental insufficiency-mediated fetal growth restriction (FGR) is associated with altered postnatal growth and metabolism, which are, in turn, associated with increased risk of adult disease. Intra-amniotic insulin-like growth factor-1 (IGF1) treatment of ovine FGR increases growth rate in late gestation, but the effects on postnatal growth and metabolism are unknown. We investigated the effects of intra-amniotic IGF1 administration to ovine fetuses with uteroplacental embolisation-induced FGR on phenotypical and physiological characteristics in the 2  weeks after birth. We measured early postnatal growth velocity, amino-terminal propeptide of C-type natriuretic peptide (NTproCNP), body composition, tissue-specific mRNA expression, and milk intake in singleton lambs treated weekly with 360 μg intra-amniotic IGF1 (FGRI; n = 13 females, 19 males) or saline (FGRS; n = 18 females, 12 males) during gestation, and in controls (CON; n = 15 females, 22 males). There was a strong positive correlation between maternal NTproCNP and fetal oxygenation, and size at birth in FGR lambs. FGR lambs were ∼20% lighter at birth and demonstrated accelerated postnatal growth velocity. IGF1 treatment did not alter perinatal mortality, partially abrogated the reduction in newborn size in females, but not males, and reduced accelerated growth in both sexes. IGF1-mediated upregulation of somatotrophic genes in males during the early postnatal period could suggest that treatment effects are associated with delayed axis maturation, whilst treatment outcomes in females may rely on the reprogramming of nutrient-dependent mechanisms of growth. These data suggest that the growth-restricted fetus is responsive to intra-amniotic intervention with IGF1, and that sex-specific somatotrophic effects persist in the early postnatal period. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Latent Class Analysis of Early Developmental Trajectory in Baby Siblings of Children with Autism

PubMed Central

Landa, Rebecca J.; Gross, Alden L.; Stuart, Elizabeth A.; Bauman, Margaret

2012-01-01

Background Siblings of children with autism (sibs-A) are at increased genetic risk for autism spectrum disorders (ASD) and milder impairments. To elucidate diversity and contour of early developmental trajectories exhibited by sibs-A, regardless of diagnostic classification, latent class modeling was used. Methods Sibs-A (n=204) were assessed with the Mullen Scales of Early Learning from age 6–36 months. Mullen T scores served as dependent variables. Outcome classifications at age 36 months included: ASD (n=52); non-ASD social/communication delay (broader autism phenotype; BAP) (n=31); and unaffected (n=121). Child-specific patterns of performance were studied using latent class growth analysis. Latent class membership was then related to diagnostic outcome through estimation of within-class proportions of children assigned to each diagnostic classification. Results A 4-class model was favored. Class 1 represented accelerated development and consisted of 25.7% of the sample, primarily unaffected children. Class 2 (40.0% of the sample), was characterized by normative development with above-average nonverbal cognitive outcome. Class 3 (22.3% of the sample) was characterized by receptive language, and gross and fine motor delay. Class 4 (12.0% of the sample), was characterized by widespread delayed skill acquisition, reflected by declining trajectories. Children with an outcome diagnosis of ASD were spread across Classes 2, 3, and 4. Conclusions Results support a category of ASD that involves slowing in early non-social development. Receptive language and motor development is vulnerable to early delay in sibs-A with and without ASD outcomes. Non-ASD sibs-A are largely distributed across classes depicting average or accelerated development. Developmental trajectories of motor, language, and cognition appear independent of communication and social delays in non-ASD sibs-A. PMID:22574686

Growth retardation and reduced growth hormone secretion in cystic fibrosis. Clinical observations from three CF centers.

PubMed

Ciro, D'Orazio; Padoan, Rita; Blau, Hannah; Marostica, Anna; Fuoti, Maurizio; Volpi, Sonia; Pilotta, Alba; Meyerovitch, Joseph; Sher, Daniel; Assael, Baroukh M

2013-03-01

Growth delay in cystic fibrosis is frequent and is usually the result of several interacting causes. It most often derives from severe respiratory impairment and severe malabsorption. There are however patients whose clinical condition is not severe enough to be held accountable for this phenomenon. We aimed at describing patients who showed growth delay, who were not affected by severe pulmonary disease or malabsorption and who, when tested, showed a reduced GH secretion after stimulation with conventional agents. We noticed a disproportionately large prevalence of growth hormone (GH) release deficit (GHRD) in pediatric cystic fibrosis (CF) patients. We examined all patients under our care in the period 2006-11, who were older than 5 and younger than 16 years old. We focussed on those who fell below the 3rd height percentile, or whose growth during the previous 18 months faltered by >2SD, and who did not present clinical conditions that could reasonably explain their failure to thrive. These patients were subjected to standard GH provocative tests. Out of 285 who matched the age criterion, 33 patients also matched the height percentile criterion. While 15/33 suffered clinical conditions that could reasonably explain their failure to thrive, 18/33 underwent GH release provocative tests and 12/18 showed a release deficit. We conclude that impaired GH secretion is more frequent among CF patients compared to the prevalence of GH deficiency in the general population and that GH release impairment may be an independent cause of growth delay in CF. Our findings are in agreement with recent studies that have described low GH levels in CF piglets and in neonates with CF [1]. Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Floating-Harbor syndrome: description of a further patient, review of the literature, and suggestion of autosomal dominant inheritance.

PubMed

Lacombe, D; Patton, M A; Elleau, C; Battin, J

1995-08-01

The Floating-Harbor syndrome is a growth retardation syndrome with delayed bone age, speech development, and typical facial features. The face is triangular with deep-set eyes, long eyelashes, bulbous nose, wide columella, short philtrum, and thin lips. We present an additional patient and review 16 cases from the literature. The possible phenotype in the patient's mother suggests a dominant mode of inheritance for the syndrome. The Floating Harbor syndrome is a growth deficiency syndrome characterized by proportionate short stature, characteristic face and delayed speech development. Inheritance is possibly autosomal dominant.

[Basic results of an experiment with mammals on the Kosmos-782 biosatellite].

PubMed

Gazenko, O G; Genin, A M; Il'in, E A; Portugalov, V V; Serova, L V

1978-01-01

The rat experiments carried out onboard the biosatellite Cosmos-782 contributed to our understanding of mechanisms of animal adaption to prolonged weightlessness. Postflight analysis helped to study nonspecific changes related to the stress-reaction accompanying space flight and return to the Earth gravity as well as specific changes associated with functional unloading of the musculoskeletal system in weightlessness. The flight results confirmed the previously made conclusions concerning possible adaptation of mammals to prolonged weightlessness and lack of pathological changes in vital weightlessness. They included: metabolic and hormonal changes, muscle atrophy, osteoporosis and delayed bone growth, decrease of ATPase activity of myocardial myosin, inhibition of erythropoiesis.

Defective angiogenesis delays thrombus resolution: a potential pathogenetic mechanism underlying chronic thromboembolic pulmonary hypertension

PubMed Central

Panzenboeck, Adelheid; Winter, Max P; Schubert, Uwe; Voswinckel, Robert; Frey, Maria K; Jakowitsch, Johannes; Alimohammadi, Arman; Hobohm, Lukas; Mangold, Andreas; Bergmeister, Helga; Sibilia, Maria; Wagner, Erwin F; Mayer, Eckhard; Klepetko, Walter; Hoelzenbein, Thomas J; Preissner, Klaus T; Lang, Irene M

2015-01-01

Objective Restoration of patency is a natural target of vascular remodeling following venous thrombosis that involves vascular endothelial cells and smooth muscle cells as well as leukocytes. Acute pulmonary emboli usually resolve within six months. However, in some instances, thrombi transform into fibrous vascular obstructions, resulting in occlusion of the deep veins, or in chronic thromboembolic pulmonary hypertension (CTEPH). We proposed that dysregulated thrombus angiogenesis may contribute to thrombus persistence. Approach and Results Mice with an endothelial-cell-specific conditional deletion of vascular endothelial growth factor receptor 2/kinase insert domain protein receptor (VEGF-R2/Kdr) were utilized in a model of stagnant flow venous thrombosis closely resembling human deep vein thrombosis. Biochemical and functional analyses were performed on pulmonary endarterectomy specimens from patients with CTEPH, a human model of non-resolving venous thromboembolism. Endothelial cell-specific deletion of Kdr and subsequent ablation of thrombus vascularization delayed thrombus resolution. In accordance with these findings, organized human CTEPH thrombi were largely devoid of vascular structures. Several vessel-specific genes such as KDR, vascular endothelial cadherin and podoplanin were expressed at lower levels in white CTEPH thrombi than in organizing deep vein thrombi and organizing thrombi from aortic aneurysms. In addition, red CTEPH thrombi attenuated the angiogenic response induced by VEGF. Conclusions In the present work, we propose a mechanism of thrombus non-resolution demonstrating that endothelial cell-specific deletion of Kdr abates thrombus vessel formation, misguiding thrombus resolution. Medical conditions associated with the development of CTEPH may be compromising early thrombus angiogenesis. PMID:24526692

Periodic and chaotic oscillations in a tumor and immune system interaction model with three delays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bi, Ping; Center for Partial Differential Equations, East China Normal University, 500 Dongchuan Rd., Shanghai 200241; Ruan, Shigui, E-mail: ruan@math.miami.edu

2014-06-15

In this paper, a tumor and immune system interaction model consisted of two differential equations with three time delays is considered in which the delays describe the proliferation of tumor cells, the process of effector cells growth stimulated by tumor cells, and the differentiation of immune effector cells, respectively. Conditions for the asymptotic stability of equilibria and existence of Hopf bifurcations are obtained by analyzing the roots of a second degree exponential polynomial characteristic equation with delay dependent coefficients. It is shown that the positive equilibrium is asymptotically stable if all three delays are less than their corresponding critical valuesmore » and Hopf bifurcations occur if any one of these delays passes through its critical value. Numerical simulations are carried out to illustrate the rich dynamical behavior of the model with different delay values including the existence of regular and irregular long periodic oscillations.« less

The Role of Convection and Growth Competition in Phase Selection in Microgravity: Controlled Convection in the Containerless Processing of Steel Alloys

NASA Technical Reports Server (NTRS)

Matson, D. M.; Loser, W.; Rogers, J. R.; Flemings, M. C.

2001-01-01

Containerless processing using electromagnetic levitation (EML) is a powerful technique in the investigation of reactive molten metal systems. On ground, the power required to overcome the weight of the sample is sufficient to cause significant heating and induce substantial melt convection. In microgravity, the heating and positioning fields may be decoupled and the field strength may be varied to achieve the desired level of convection within the limits set by the geometry of the levitation coil and the sample size. From high-speed digital images of the double recalescence behavior of Fe-Cr-Ni alloys in ground-based testing and in reduced-gravity aboard the NASA KC-135 parabolic aircraft, we have shown that phase selection can be predicted based on a growth competition model. An important parameter in this model is the delay time between primary nucleation and subsequent nucleation of the stable solid within the liquid/metastable solid array. This delay time is a strong function of composition and a weak function of the undercooling of the melt below the metastable liquidus. From the results obtained during the first Microgravity Sciences Laboratory (MSL-1) mission, we also know that convection may significantly influence the delay time, especially at low undercoolings. Currently, it is unclear what mechanism controls the formation of a heterogeneous site that allows nucleation of the austenitic phase on the pre-existing ferrite skeleton. By examining the behavior of the delay time under different convective conditions, we hypothesize that we can differentiate between several of these mechanisms to gain an understanding of how to control microstructural. evolution. We will anchor these predictions by examining samples quenched at different times following primary recalescence in microgravity. A second important parameter in the growth competition model is the identification of the growth rate of the stable phase into the semi-solid array that formed during primary recalescence. Current dendritic growth theory is inadequate in predicting solidification behavior under these conditions as metallographic analyses show that stable phase growth proceeds along the interface between the metastable solid and residual liquid. Since growth velocity is independent of the initial undercooling relative to the metastable liquidus, we hypothesize that purely thermal effects can be separated from other important growth model parameters by careful selection of the liquid composition in a ternary system.

Pak and Rac GTPases promote oncogenic KIT–induced neoplasms

PubMed Central

Martin, Holly; Mali, Raghuveer Singh; Ma, Peilin; Chatterjee, Anindya; Ramdas, Baskar; Sims, Emily; Munugalavadla, Veerendra; Ghosh, Joydeep; Mattingly, Ray R.; Visconte, Valeria; Tiu, Ramon V.; Vlaar, Cornelis P.; Dharmawardhane, Suranganie; Kapur, Reuben

2013-01-01

An acquired somatic mutation at codon 816 in the KIT receptor tyrosine kinase is associated with poor prognosis in patients with systemic mastocytosis and acute myeloid leukemia (AML). Treatment of leukemic cells bearing this mutation with an allosteric inhibitor of p21–activated kinase (Pak) or its genetic inactivation results in growth repression due to enhanced apoptosis. Inhibition of the upstream effector Rac abrogates the oncogene-induced growth and activity of Pak. Although both Rac1 and Rac2 are constitutively activated via the guanine nucleotide exchange factor (GEF) Vav1, loss of Rac1 or Rac2 alone moderately corrected the growth of KIT-bearing leukemic cells, whereas the combined loss resulted in 75% growth repression. In vivo, the inhibition of Vav or Rac or Pak delayed the onset of myeloproliferative neoplasms (MPNs) and corrected the associated pathology in mice. To assess the role of Rac GEFs in oncogene-induced transformation, we used an inhibitor of Rac, EHop-016, which specifically targets Vav1 and found that EHop-016 was a potent inhibitor of human and murine leukemic cell growth. These studies identify Pak and Rac GTPases, including Vav1, as potential therapeutic targets in MPN and AML involving an oncogenic form of KIT. PMID:24091327

10-Minute Delayed Recall from the Modified Mini-Mental State Test Predicts Alzheimer’s Disease Pathology

PubMed Central

Lyness, Scott A.; Lee, Ae Young; Zarow, Chris; Teng, Evelyn L.; Chui, Helena C.

2014-01-01

We compared the sensitivity and specificity of two delayed recall scores from the Modified Mini-Mental State (3MS) test with consensus clinical diagnosis to differentiate cognitive impairment due to Alzheimer’s disease (AD) versus non-AD pathologies. At a memory disorders clinic, 117 cognitively impaired patients were administered a baseline 3MS test and received a contemporaneous consensus clinical diagnosis. Their brains were examined after death about 5 years later. Using logistic regression with forward selection to predict pathologically defined AD versus non-AD, 10-min delayed recall entered first (p = 0.001), followed by clinical diagnosis (p = 0.02); 1-min delayed recall did not enter. 10-min delayed recall scores ≤4 (score range = 0–9) were 87% sensitive and 47% specific in predicting AD pathology; consensus clinical diagnosis was 82% sensitive and 45% specific. For the 57 patients whose initial Mini-Mental State Examination scores were ≥19 (the median), 3MS 10-min delayed recall scores ≤4 showed some loss of sensitivity (80%) but a substantial gain in specificity (77%). In conclusion, 10-min delayed recall score on the brief 3MS test distinguished between AD versus non-AD pathology about 5 years before death at least as well as consensus clinical diagnosis that requires much more comprehensive information and complex deliberation. PMID:24240637

10-minute delayed recall from the modified mini-mental state test predicts Alzheimer's disease pathology.

PubMed

Lyness, Scott A; Lee, Ae Young; Zarow, Chris; Teng, Evelyn L; Chui, Helena C

2014-01-01

We compared the sensitivity and specificity of two delayed recall scores from the Modified Mini-Mental State (3MS) test with consensus clinical diagnosis to differentiate cognitive impairment due to Alzheimer's disease (AD) versus non-AD pathologies. At a memory disorders clinic, 117 cognitively impaired patients were administered a baseline 3MS test and received a contemporaneous consensus clinical diagnosis. Their brains were examined after death about 5 years later. Using logistic regression with forward selection to predict pathologically defined AD versus non-AD, 10-min delayed recall entered first (p = 0.001), followed by clinical diagnosis (p = 0.02); 1-min delayed recall did not enter. 10-min delayed recall scores ≤4 (score range = 0-9) were 87% sensitive and 47% specific in predicting AD pathology; consensus clinical diagnosis was 82% sensitive and 45% specific. For the 57 patients whose initial Mini-Mental State Examination scores were ≥19 (the median), 3MS 10-min delayed recall scores ≤4 showed some loss of sensitivity (80%) but a substantial gain in specificity (77%). In conclusion, 10-min delayed recall score on the brief 3MS test distinguished between AD versus non-AD pathology about 5 years before death at least as well as consensus clinical diagnosis that requires much more comprehensive information and complex deliberation.

Personality-Targeted Interventions Delay the Growth of Adolescent Drinking and Binge Drinking

ERIC Educational Resources Information Center

Conrod, Patricia J.; Castellanos, Natalie; Mackie, Clare

2008-01-01

Background: Personality factors are implicated in the vulnerability to adolescent alcohol misuse. This study examined whether providing personality-targeted interventions in early adolescence can delay drinking and binge drinking in high-risk youth. Methods: A randomised control trial was carried out with 368 adolescents recruited from years 9 and…

Trajectories of Developmental Functioning among Children of Adolescent Mothers: Factors Associated with Risk for Delay

ERIC Educational Resources Information Center

Jahromi, Laudan B.; Umaña-Taylor, Adriana J.; Updegraff, Kimberly A.; Zeiders, Katharine H.

2016-01-01

Children of adolescent mothers are at risk for developmental delays. Less is known about the heterogeneity in these children's developmental trajectories, and factors associated with different patterns of development. This longitudinal study used latent class growth analysis (LCGA) to identify distinct trajectories in children of Mexican-origin…

The case for delaying planting of bottomland oaks: an example involving Nuttall oaks

Treesearch

David C. Mercker; David S. Buckley; John P. Conn

2013-01-01

A prominent difficulty during bottomland hardwood afforestation in the southeastern United States is that sites are often flooded during the preferred months of planting (January - March), which results in delayed planting (April - June) and reduced survival. We monitored growth and survival of Nuttall oak (Quercus texana Buckley) seedlings planted...

Decreased head circumference velocity as related to developmental deficit in infancy.

PubMed

Tal, Galit; Cohen, Ayala; Habib, Sonia; Tirosh, Emanuel

2012-11-01

We evaluated the significance of head circumference growth velocity as related to developmental deficits during infancy. Head circumferences, lengths, and developmental diagnoses were retrieved in a standard manner at ≥ 2 time points from 437 infants with developmental deficits, and 3909 normally developing infants. Infants' ages ranged from 1-24 months, with final diagnoses ascertained at age 24 months. Increased velocity during the first 2 months in typical infants was evident in the study group during the period 2-4 months. A differential head circumference growth velocity was observed, and infants diagnosed with motor delay presented decreased velocity between ages 2-4 months, compared with infants receiving other nonmotor developmental diagnoses. These differences remained after controlling for birth weight and length. No significant sex effect was evident. Infants with developmental deficits demonstrate delayed acceleration of head circumference velocity, compared with typical infants in the first 2 months. Infants with motor delay manifest decreased velocity, compared with infants presenting other developmental deficits. These differences may be related to delayed white matter maturation. Copyright © 2012 Elsevier Inc. All rights reserved.

Prime-boost immunization by both DNA vaccine and oncolytic adenovirus expressing GM-CSF and shRNA of TGF-β2 induces anti-tumor immune activation.

PubMed

Kim, So Young; Kang, Dongxu; Choi, Hye Jin; Joo, Yeonsoo; Kim, Joo-Hang; Song, Jae J

2017-02-28

A successful DNA vaccine for the treatment of tumors should break established immune tolerance to tumor antigen. However, due to the relatively low immunogenicity of DNA vaccines, compared to other kinds of vaccines using live virus or protein, a recombinant viral vector was used to enhance humoral and cellular immunity. In the current study, we sought to develop a novel anti-cancer agent as a complex of DNA and oncolytic adenovirus for the treatment of malignant melanoma in the C57BL/6 mouse model. MART1, a human melanoma-specific tumor antigen, was used to induce an increased immune reaction, since a MART1-protective response is required to overcome immune tolerance to the melanoma antigen MelanA. Because GM-CSF is a potent inducer of anti-tumor immunity and TGF-β2 is involved in tumor survival and host immune suppression, mouse GM-CSF (mGM-CSF) and shRNA of mouse TGF-β2 (shmTGF-β2) genes were delivered together with MART1 via oncolytic adenovirus. MART1 plasmid was also used for antigen-priming. To compare the anti-tumor effect of oncolytic adenovirus expressing both mGM-CSF and shmTGF-β2 (AdGshT) with that of oncolytic adenovirus expressing mGM-CSF only (AdG), each virus was intratumorally injected into melanoma-bearing C57BL/6 mice. As a result, mice that received AdGshT showed delayed tumor growth than those that received AdG. Heterologous prime-boost immunization was combined with oncolytic AdGshT and MART1 expression to result in further delayed tumor growth. This regression is likely due to the following 4 combinations: MART1-derived mouse melanoma antigen-specific immune reaction, immune stimulation by mGM-CSF/shmTGF-β2, tumor growth inhibition by shmTGF-β2, and tumor cell-specific lysis via an oncolytic adenovirus. Immune activation was mainly induced by mature tumor-infiltrating dendritic cell (TIDC) and lowered regulatory T cells in tumor-infiltrating lymphocytes (TIL). Taken together, these findings demonstrate that human MART1 induces a mouse melanoma antigen-specific immune reaction. In addition, the results also indicate that combination therapy of MART1 plasmid, together with an oncolytic adenovirus expressing MART1, mGM-CSF, and shmTGF-β2, is a promising candidate for the treatment of malignant melanoma.

Prime-boost immunization by both DNA vaccine and oncolytic adenovirus expressing GM-CSF and shRNA of TGF-β2 induces anti-tumor immune activation

PubMed Central

Choi, Hye Jin; Joo, Yeonsoo; Kim, Joo-Hang; Song, Jae J.

2017-01-01

A successful DNA vaccine for the treatment of tumors should break established immune tolerance to tumor antigen. However, due to the relatively low immunogenicity of DNA vaccines, compared to other kinds of vaccines using live virus or protein, a recombinant viral vector was used to enhance humoral and cellular immunity. In the current study, we sought to develop a novel anti-cancer agent as a complex of DNA and oncolytic adenovirus for the treatment of malignant melanoma in the C57BL/6 mouse model. MART1, a human melanoma-specific tumor antigen, was used to induce an increased immune reaction, since a MART1-protective response is required to overcome immune tolerance to the melanoma antigen MelanA. Because GM-CSF is a potent inducer of anti-tumor immunity and TGF-β2 is involved in tumor survival and host immune suppression, mouse GM-CSF (mGM-CSF) and shRNA of mouse TGF-β2 (shmTGF-β2) genes were delivered together with MART1 via oncolytic adenovirus. MART1 plasmid was also used for antigen-priming. To compare the anti-tumor effect of oncolytic adenovirus expressing both mGM-CSF and shmTGF-β2 (AdGshT) with that of oncolytic adenovirus expressing mGM-CSF only (AdG), each virus was intratumorally injected into melanoma-bearing C57BL/6 mice. As a result, mice that received AdGshT showed delayed tumor growth than those that received AdG. Heterologous prime-boost immunization was combined with oncolytic AdGshT and MART1 expression to result in further delayed tumor growth. This regression is likely due to the following 4 combinations: MART1-derived mouse melanoma antigen-specific immune reaction, immune stimulation by mGM-CSF/shmTGF-β2, tumor growth inhibition by shmTGF-β2, and tumor cell-specific lysis via an oncolytic adenovirus. Immune activation was mainly induced by mature tumor-infiltrating dendritic cell (TIDC) and lowered regulatory T cells in tumor-infiltrating lymphocytes (TIL). Taken together, these findings demonstrate that human MART1 induces a mouse melanoma antigen-specific immune reaction. In addition, the results also indicate that combination therapy of MART1 plasmid, together with an oncolytic adenovirus expressing MART1, mGM-CSF, and shmTGF-β2, is a promising candidate for the treatment of malignant melanoma. PMID:28178658

Development of Phonological Processing Skills in Children with Specific Language Impairment with and without Literacy Delay: A 3-Year Longitudinal Study

ERIC Educational Resources Information Center

Vandewalle, Ellen; Boets, Bart; Ghesquiere, Pol; Zink, Inge

2012-01-01

Purpose: To compare the development of phonological skills in children with specific language impairment (SLI) with and without literacy delay and to examine whether kindergarten phonological skills could discriminate these 2 groups. Method: In a longitudinal study, 8 children with SLI and literacy delay, 10 children with SLI and normal literacy,…

Optimization of combination therapy of arsenic trioxide and fractionated radiotherapy for malignant glioma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ning Shoucheng; Knox, Susan J.

2006-06-01

Purpose: The primary objective was to optimize the combined treatment regimen using arsenic trioxide (ATO) and fractionated radiotherapy for the treatment of malignant glioma. Methods and Materials: Nude mice with human glioma xenograft tumors were treated with fractionated local tumor radiation of 250 cGy/fraction/day and 5 mg/kg ATO for 5-10 days. Results: Time course experiments demonstrated that maximal tumor growth delay occurred when ATO was administered between 0 and 4 h after radiation. The combination treatment of ATO and radiation synergistically inhibited tumor growth and produced a tumor growth delay time of 13.2 days, compared with 1.4 days and 6.5more » days for ATO and radiation alone (p < 0.01), respectively. The use of concurrent therapy of radiation and ATO initially, followed by ATO as maintenance therapy, was superior to the use of preloading with ATO before combined therapy and produced a tumor growth delay time of 22.7 days as compared with 11.7 days for the ATO preloading regimen (p < 0.01). The maintenance dose of ATO after concurrent therapy was effective and important for continued inhibition of tumor growth. Conclusions: The combined use of fractionated radiation and ATO is effective for the treatment of glioma xenograft tumors. ATO was most effective when administered 0-4 h after radiation without pretreatment with ATO. These results have important implications for the optimization of treatment regimen using ATO and fractionated radiotherapy for the treatment of brain tumors.« less

A new kink in an old theory of carcinogenesis.

PubMed

Prehn, Richmond T; Prehn, Liisa M

2013-02-18

According to Berenblum's two-stage hypothesis, the first stage in carcinogenesis is the production of benign premalignant lesions. Between this initiation stage and the formation of a malignant tumor there is often a long lag phase. We propose that this lag is caused by the delay in the formation of a new and rare tumor-specific antigen, which induces an immune response that stimulates tumor growth. Such tumor-specific antigens could arise as a result of a mutator-like phenotype, which is supposedly present in the benign initial stage of carcinogenesis. According to this hypothesis, the first stage lesion provides a weakly mutagenic environment conducive to the formation of the new antigen(s). If no such new antigens appear so there is no consequent immune response, it is argued that carcinogenesis would seldom if ever ensue.

A new kink in an old theory of carcinogenesis

PubMed Central

2013-01-01

According to Berenblum’s two-stage hypothesis, the first stage in carcinogenesis is the production of benign premalignant lesions. Between this initiation stage and the formation of a malignant tumor there is often a long lag phase. We propose that this lag is caused by the delay in the formation of a new and rare tumor-specific antigen, which induces an immune response that stimulates tumor growth. Such tumor-specific antigens could arise as a result of a mutator-like phenotype, which is supposedly present in the benign initial stage of carcinogenesis. According to this hypothesis, the first stage lesion provides a weakly mutagenic environment conducive to the formation of the new antigen(s). If no such new antigens appear so there is no consequent immune response, it is argued that carcinogenesis would seldom if ever ensue. PMID:23414486

Intensity coding in electric hearing: Effects of electrode configurations and stimulation waveforms

PubMed Central

Chua, Tiffany Elise H.; Bachman, Mark; Zeng, Fan-Gang

2011-01-01

Objectives Current cochlear implants typically stimulate the auditory nerve with biphasic pulses and monopolar electrode configurations. Tripolar stimulation can increase spatial selectivity and potentially improve place pitch related perception, but requires higher current levels to elicit the same loudness as monopolar stimulation. The present study combined delayed pseudomonophonasic pulses, which produce lower thresholds, with tripolar stimulation in an attempt to solve the power-performance tradeoff problem. Design The present study systematically measured thresholds, dynamic range, loudness growth, and intensity discrimination using either biphasic or delayed pseudomonophonasic pulses under both monopolar and tripolar stimulation. Participants were 5 Clarion cochlear implant users. For each subject, data from apical, middle and basal electrode positions were collected when possible. Results Compared with biphasic pulses, delayed pseudomonophonasic pulses increased the dynamic range by lowering thresholds while maintaining comparable maximum allowable levels under both electrode configurations. However, delayed pseudomonophonasic pulses did not change the shape of loudness growth function and actually increased intensity discrimination limens, especially at lower current levels. Conclusions The present results indicate that delayed pseudomonophonasic pulses coupled with tripolar stimulation cannot provide significant power savings, nor can it increase the functional dynamic range. Whether this combined stimulation could improve functional spectral resolution remains to be seen. PMID:21610498

Adipose-specific ablation of Nrf2 transiently delayed high-fat diet-induced obesity by altering glucose, lipid and energy metabolism of male mice.

PubMed

Zhang, Le; Dasuri, Kalavathi; Fernandez-Kim, Sun-Ok; Bruce-Keller, Annadora J; Keller, Jeffrey N

2016-01-01

Nuclear factor E2-related factor 2 (NRF2) is a well-known master controller of the cellular adaptive antioxidant and detoxification response. Recent studies demonstrated altered glucose, lipid and energy metabolism in mice with a global Nrf2 knockout. In the present study, we aim to determine the effects of an adipose-specific ablation of Nrf2 (ASAN) on diet-induced obesity (DIO) in male mice. The 6-week-old adipose-specific Nrf2 knockout (NK) and its Nrf2 control (NC) mice were fed with either control diet (CD) or high-fat diet (HFD) for 14 weeks. NK mice exhibited transiently delayed body weight (BW) growth from week 5 to week 11 of HFD feeding, higher daily physical activity levels and preferential use of fat over carbohydrates as a source of energy at week 8 of the CD-feeding period. After 14 weeks of feeding, NK mice showed comparable results with NC mice with respect to the overall BW and body fat content, but exhibited reduced blood glucose, reduced number but increased size of adipocytes, accompanied with elevated expression of many genes and proteins in the visceral fat related to glucose, lipid and energy metabolism (e.g. Fgf21 , Pgc1a ). These results indicated that NRF2 is an important mediator for glucose, lipid and energy metabolism in adipose tissue, and ASAN could have beneficial effect for prevention of DIO during the early development of mice.

Growth and development of children aged 1-5 years in low-intensity armed conflict areas in Southern Thailand: a community-based survey.

PubMed

Jeharsae, Rohani; Sangthong, Rassamee; Wichaidit, Wit; Chongsuvivatwong, Virasakdi

2013-04-04

A low-intensity armed conflict has been occurring for nearly a decade in southernmost region of Thailand. However, its impact on child health has not yet been investigated. This study aimed to estimate the prevalence of delayed child growth and development in the affected areas and to determine the association between the violence and health among children aged 1-5 years. A total of 498 children aged 1-5 years were recruited. Intensity of conflict for each sub-district was calculated as the 6-year average number of incidents per 100,000 population per year and classified into quartiles. Growth indices were weight-for-age, height-for-age, and weight-for-height, while development was measured by the Denver Development Screening Test II (Thai version). Food insecurity, child-rearing practice, health service accessibility, household sanitation, and depression among the caregivers were assessed using screening scales and questionnaires. Contextual information such as average income and numbers of violent events in each sub-district was obtained from external sources. Growth retardation was highly prevalent in the area as reported by rates of underweight, stunting, and wasting at 19.3%, 27.6% and 7.4%, respectively. The prevalence of developmental delay was also substantially high (37.1%). Multi-level analysis found no evidence of association between insurgency and health outcomes. However, children in areas with higher intensity of violence had a lower risk of delay in personal-social development (OR = 0.4; 95% CI = 0.2 - 0.9; p-value = 0.05). Unlike war refugees and internally-displaced persons in camp-like settings, the relationship between level of armed conflict and growth and developmental delay among children aged 1-5 years could not be demonstrated in the community setting of this study where food supply had been minimally perturbed.

Predicting the Probability of Abnormal Stimulated Growth Hormone Response in Children After Radiotherapy for Brain Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hua Chiaho, E-mail: Chia-Ho.Hua@stjude.org; Wu Shengjie; Chemaitilly, Wassim

Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6),more » who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test {>=}7 ng/mL. Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.« less

FGFR3 gene mutation plus GRB10 gene duplication in a patient with achondroplasia plus growth delay with prenatal onset.

PubMed

Yuan, Haiming; Huang, Linhuan; Hu, Xizi; Li, Qian; Sun, Xiaofang; Xie, Yingjun; Kong, Shu; Wang, Xiaoman

2016-07-02

Achondroplasia is a well-defined and common bone dysplasia. Genotype- and phenotype-level correlations have been found between the clinical symptoms of achondroplasia and achondroplasia-specific FGFR3 mutations. A 2-year-old boy with clinical features consistent with achondroplasia and Silver-Russell syndrome-like symptoms was found to carry a mutation in the fibroblast growth factor receptor-3 (FGFR3) gene at c.1138G > A (p.Gly380Arg) and a de novo 574 kb duplication at chromosome 7p12.1 that involved the entire growth-factor receptor bound protein 10 (GRB10) gene. Using quantitative real-time PCR analysis, GRB10 was over-expressed, and, using enzyme-linked immunosorbent assays for IGF1 and IGF-binding protein-3 (IGFBP3), we found that IGF1 and IGFBP3 were low-expressed in this patient. We demonstrate that a combination of uncommon, rare and exceptional molecular defects related to the molecular bases of particular birth defects can be analyzed and diagnosed to potentially explain the observed variability in the combination of molecular defects.

An epidemiological study of urban and rural children in Pakistan: examining the relationship between delayed psychomotor development, low birth weight and postnatal growth failure.

PubMed

Avan, Bilal I; Raza, Syed A; Kirkwood, Betty R

2015-03-01

Low birth weight is known to be associated with postnatal growth failure. It is not yet established that both conditions are determinants of psychomotor development. The study investigated whether or not low birth weight leads to delayed psychomotor development of a child, and whether it can be mitigated by adequate postnatal growth. A cross-sectional study was conducted in 2002 in 15 rural and 11 urban communities of Sindh province, Pakistan. Assessment of 1234 children less than 3 years of age included Bayley's Scale of Infant Development II, socioeconomic questionnaire and anthropometry; WHO standards were used to calculate z-scores of height-for-age, weight-for-height and weight-for-age. The underlying study hypotheses were tested through multiple regression modelling. Out of 1219 children, 283 (23.2%) had delayed psychomotor development and 639 (52.4%) were undernourished according to the composite index of anthropometric failure. Strong negative associations with the psychomotor development index were detected between stunting and being underweight, with a larger magnitude of effect for stunting (p<0.001). The strong relationship persisted even when the analysis was restricted to non-malnourished children. The psychomotor index increased by 2.07 points with every unit increase in height-for-age z-score. The relationship between low birth weight and psychomotor development appears to be mediated largely by postnatal growth and nutritional status. This association suggests that among undernourished children there is significant likelihood of a group that is developmentally delayed. It is important to emphasize developmental needs in programmes that target underprivileged children. © The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Targeting MPS1 Enhances Radiosensitization of Human Glioblastoma by Modulating DNA Repair Proteins.

PubMed

Maachani, Uday Bhanu; Kramp, Tamalee; Hanson, Ryan; Zhao, Shuping; Celiku, Orieta; Shankavaram, Uma; Colombo, Riccardo; Caplen, Natasha J; Camphausen, Kevin; Tandle, Anita

2015-05-01

To ensure faithful chromosome segregation, cells use the spindle assembly checkpoint (SAC), which can be activated in aneuploid cancer cells. Targeting the components of SAC machinery required for the growth of aneuploid cells may offer a cancer cell-specific therapeutic approach. In this study, the effects of inhibiting Monopolar spindle 1, MPS1 (TTK), an essential SAC kinase, on the radiosensitization of glioblastoma (GBM) cells were analyzed. Clonogenic survival was used to determine the effects of the MPS1 inhibitor NMS-P715 on radiosensitivity in multiple model systems, including GBM cell lines, a normal astrocyte, and a normal fibroblast cell line. DNA double-strand breaks (DSB) were evaluated using γH2AX foci, and cell death was measured by mitotic catastrophe evaluation. Transcriptome analysis was performed via unbiased microarray expression profiling. Tumor xenografts grown from GBM cells were used in tumor growth delay studies. Inhibition of MPS1 activity resulted in reduced GBM cell proliferation. Furthermore, NMS-P715 enhanced the radiosensitivity of GBM cells by decreased repair of DSBs and induction of postradiation mitotic catastrophe. NMS-P715 in combination with fractionated doses of radiation significantly enhanced the tumor growth delay. Molecular profiling of MPS1-silenced GBM cells showed an altered expression of transcripts associated with DNA damage, repair, and replication, including the DNA-dependent protein kinase (PRKDC/DNAPK). Next, inhibition of MPS1 blocked two important DNA repair pathways. In conclusion, these results not only highlight a role for MPS1 kinase in DNA repair and as prognostic marker but also indicate it as a viable option in glioblastoma therapy. Inhibition of MPS1 kinase in combination with radiation represents a promising new approach for glioblastoma and for other cancer therapies. ©2015 American Association for Cancer Research.

Targeting MPS1 Enhances Radiosensitization of Human Glioblastoma by Modulating DNA Repair Proteins

PubMed Central

Maachani, Uday B.; Kramp, Tamalee; Hanson, Ryan; Zhao, Shuping; Celiku, Orieta; Shankavaram, Uma; Colombo, Riccardo; Caplen, Natasha J.; Camphausen, Kevin; Tandle, Anita

2015-01-01

To ensure faithful chromosome segregation, cells use the spindle assembly checkpoint (SAC), which can be activated in aneuploid cancer cells. Targeting the components of SAC machinery required for the growth of aneuploid cells may offer a cancer cell specific therapeutic approach. In this study, the effects of inhibiting Monopolar spindle 1, MPS1 (TTK), an essential SAC kinase, on the radiosensitization of glioblastoma (GBM) cells was analyzed. Clonogenic survival was used to determine the effects of the MPS1 inhibitor, NMS-P715 on radiosensitivity in multiple model systems including: GBM cell lines, a normal astrocyte and a normal fibroblast cell line. DNA double strand breaks (DSBs) were evaluated using γH2AX foci and cell death was measured by mitotic catastrophe evaluation. Transcriptome analysis was performed via unbiased microarray expression profiling. Tumor xenografts grown from GBM cells were used in tumor growth delay studies. Inhibition of MPS1 activity resulted in reduced GBM cell proliferation. Further, NMS-P715 enhanced the radiosensitivity of GBM cells by decreased repair of DSBs and induction of post-radiation mitotic catastrophe. MNS-P715 in combination with fractionated doses of radiation significantly enhanced the tumor growth delay. Molecular profiling of MPS1 silenced GBM cells showed an altered expression of transcripts associated with DNA damage, repair and replication including the DNA-dependent protein kinase (PRKDC/DNAPK). Next, inhibition of MPS1 blocked two important DNA repair pathways. In conclusion, these results not only highlight a role for MPS1 kinase in DNA repair and as prognostic marker but also indicate it as a viable option in glioblastoma therapy. PMID:25722303

Impact of Sodium Tungstate and Tungsten Alloys on the Growth of Selected Microorganisms with Environmental Significance

DTIC Science & Technology

2010-07-30

TUNGSTEN ALLOYS ON THE GROWTH OF SELECTED MICROORGANISMS WITH ENVIROMENTAL SIGNIFICANCE 5a. Contract Number: 5b. Grant Number: 5c. Program Element...lower tolerances. Interestingly, bacteria cultivated from the environment displayed only minor delays and reduction in growth relative to pure...settings where nutrients may be limited. 15. SUBJECT TERMS Tungsten, sodium tungstate, microbial growth , environmental microbiology, bacteria , Shewanella

Downregulation of miRNAs during Delayed Wound Healing in Diabetes: Role of Dicer

PubMed Central

Bhattacharya, Sushant; Aggarwal, Rangoli; Singh, Vijay Pal; Ramachandran, Srinivasan; Datta, Malabika

2015-01-01

Delayed wound healing is a major complication associated with diabetes and is a result of a complex interplay among diverse deregulated cellular parameters. Although several genes and pathways have been identified to be mediating impaired wound closure, the role of microRNAs (miRNAs) in these events is not very well understood. Here, we identify an altered miRNA signature in the prolonged inflammatory phase in a wound during diabetes, with increased infiltration of inflammatory cells in the basal layer of the epidermis. Nineteen miRNAs were downregulated in diabetic rat wounds (as compared with normal rat wound, d 7 postwounding) together with inhibited levels of the central miRNA biosynthesis enzyme, Dicer, suggesting that in wounds of diabetic rats, the decreased levels of Dicer are presumably responsible for miRNA downregulation. Compared with unwounded skin, Dicer levels were significantly upregulated 12 d postwounding in normal rats, and this result was notably absent in diabetic rats that showed impaired wound closure. In a wound-healing specific quantitative reverse transcriptase–polymerase chain reaction (RT-PCR) array, 10 genes were significantly altered in the diabetic rat wound and included growth factors and collagens. Network analyses demonstrated significant interactions and correlations between the miRNA predicted targets (regulators) and the 10 wound-healing specific genes, suggesting altered miRNAs might fine-tune the levels of these genes that determine wound closure. Dicer inhibition prevented HaCaT cell migration and affected wound closure. Altered levels of Dicer and miRNAs are critical during delayed wound closure and offer promising targets to address the issue of impaired wound healing. PMID:26602065

Ecotype-specific improvement of nitrogen status in European grasses after drought combined with rewetting

NASA Astrophysics Data System (ADS)

Arfin Khan, Mohammed A. S.; Kreyling, Juergen; Beierkuhnlein, Carl; Jentsch, Anke

2016-11-01

Drought stress and associated low soil moisture can decrease N status of forage plants by reducing nitrogen (N) uptake. Conversely, rainfall and associated favorable soil moisture can improve plant N status. Yet, it is unclear to which degree drought combined with rewetting can buffer negative effects of drought on N status of forage plants and their populations. Here, we compared shoot N status (N concentration, total N uptake and C/N ratio) of four temperate grass species. Particularly, we investigated ecotypes (populations) grown from seeds from four to six European provenances/species after a drought treatment combined with rewetting (10 day harvest delay) versus continuously watered conditions for control. The experimental combination of drought and rewetting significantly increased shoot N concentration (+96%), N uptake (+31%); and decreased C/N ratio (-46%), biomass production (-29%) and C concentration (-1.4%) compared to control. Shoot N status was found to be different between target grass species and also within their populations under drought combined with rewetting treatment. Presumably drought-adapted populations did not perform better than populations from moist sites indicating no evidence of local adaptation. The drought combined with rewetting event could buffer the negative effects of drought. Shoot N status of grasses after drought and rewetting even exceeded control plants. This surprising finding can potentially be explained by higher N uptake, lack of growth dilution effects or delayed plant maturation. Furthermore, within-species shoot N status responses to drought combined with rewetting event were ecotype-specific, hinting at diverse responses of different population. For rangeland management, we recommend that if a drought event occurs during the growing season, harvesting should be delayed beyond a following rain event.

The relation between the cell-mediated immunological response and the induction of circulating antibodies to collagen in guinea-pigs.

PubMed Central

Gentner, G J; Adelmann, B C

1976-01-01

Cutaneous delayed hypersensitivity reactions to collagen in guinea-pigs were partially but specifically suppressed if the animals had been pretreated with collagen and Freund's incomplete adjuvant. Such animals responded normally to skin-reactive factor prepared with ovalbumin. Lymphoid cells from animals with normal delayed hypersensitivity to collagen functioned normally in animals with suppressed skin reactivity. Cells from animals with suppressed delayed hypersensitivity were specifically, functionally impaired since they transferred delayed hypersensitivity into neutral recipients efficiently for PPD but not for collagen. Suppression could be induced in Cy-treated animals, and it persisted for at least 143 days. It is concluded that guinea-pigs with depressed delayed hypersensitivity to collagen are functionally impaired with respect to those T cells normally generated by induction of delayed hypersensitivity. PMID:1088420

Delay-induced rebounds in CO2 emissions and critical time-scales to meet global warming targets

NASA Astrophysics Data System (ADS)

Manoli, Gabriele; Katul, Gabriel G.; Marani, Marco

2016-12-01

While climate science debates are focused on the attainment of peak anthropogenic CO2 emissions and policy tools to reduce peak temperatures, the human-energy-climate system can hold "rebound" surprises beyond this peak. Following the second industrial revolution, global per capita CO2 emissions (cc) experienced a punctuated growth of about 100% every 60 years, mainly attributable to technological development and its global spread. A model of the human-energy-climate system capable of reproducing past punctuated dynamics shows that rebounds in global CO2 emissions emerge due to delays intrinsic to the diffusion of innovations. Such intrinsic delays in the adoption and spread of low-carbon emitting technologies, together with projected population growth, upset the warming target set by the Paris Agreement. To avoid rebounds and their negative climate effects, model calculations show that the diffusion of climate-friendly technologies must occur with lags one-order of magnitude shorter (i.e., ˜6 years) than the characteristic timescale of past punctuated growth in cc. Radically new strategies to globally implement the technological advances at unprecedented rates are needed if the current emission goals are to be achieved.

Intraperitoneal photodynamic therapy of the rat CC531 adenocarcinoma.

PubMed Central

Veenhuizen, R. B.; Marijnissen, J. P.; Kenemans, P.; Ruevekamp-Helmers, M. C.; 't Mannetje, L. W.; Helmerhorst, T. J.; Stewart, F. A.

1996-01-01

The goal of this study was to investigate the efficacy of photodynamic therapy (PDT) of a single tumour growing intraperitoneally. For this purpose the CC531 colon carcinoma, implanted in an intraperitoneal fat pad of Wag/RijA rats, was treated with intraperitoneal photodynamic therapy (IPPDT) using Photofrin as the photosensitiser. Two illumination techniques have been compared. An invasive illumination technique using Perspex blocks to illuminate 30 cm2 of the lower abdomen gave a significant delay in tumour growth with 25 J cm-2 applied 1 day after Photofrin. A minimally invasive illumination technique using a balloon catheter to illuminate 14 cm2 resulted in an equivalent growth delay with 75 J cm-2. The route of administration of the photosensitiser did not influence regrowth times of the tumour. Mitomycin C (MMC), a bioreductive agent, was used to exploit the known PDT-induced hypoxia. The combination of IPPDT with MMC resulted in an increased tumoricidal effect. In conclusion, IPPDT led to a significant growth delay for a single tumour implanted intraperitoneally and repetition of the PDT treatment was possible using a minimally invasive illumination technique. Repeated treatments resulted in increased tumour response. PMID:8645584

Antiphase light and temperature cycles affect PHYTOCHROME B-controlled ethylene sensitivity and biosynthesis, limiting leaf movement and growth of Arabidopsis.

PubMed

Bours, Ralph; van Zanten, Martijn; Pierik, Ronald; Bouwmeester, Harro; van der Krol, Alexander

2013-10-01

In the natural environment, days are generally warmer than the night, resulting in a positive day/night temperature difference (+DIF). Plants have adapted to these conditions, and when exposed to antiphase light and temperature cycles (cold photoperiod/warm night [-DIF]), most species exhibit reduced elongation growth. To study the physiological mechanism of how light and temperature cycles affect plant growth, we used infrared imaging to dissect growth dynamics under +DIF and -DIF in the model plant Arabidopsis (Arabidopsis thaliana). We found that -DIF altered leaf growth patterns, decreasing the amplitude and delaying the phase of leaf movement. Ethylene application restored leaf growth in -DIF conditions, and constitutive ethylene signaling mutants maintain robust leaf movement amplitudes under -DIF, indicating that ethylene signaling becomes limiting under these conditions. In response to -DIF, the phase of ethylene emission advanced 2 h, but total ethylene emission was not reduced. However, expression analysis on members of the 1-aminocyclopropane-1-carboxylic acid (ACC) synthase ethylene biosynthesis gene family showed that ACS2 activity is specifically suppressed in the petiole region under -DIF conditions. Indeed, petioles of plants under -DIF had reduced ACC content, and application of ACC to the petiole restored leaf growth patterns. Moreover, acs2 mutants displayed reduced leaf movement under +DIF, similar to wild-type plants under -DIF. In addition, we demonstrate that the photoreceptor PHYTOCHROME B restricts ethylene biosynthesis and constrains the -DIF-induced phase shift in rhythmic growth. Our findings provide a mechanistic insight into how fluctuating temperature cycles regulate plant growth.

Growth and development in internationally adopted children: extent and timing of recovery after early adversity.

PubMed

Palacios, Jesús; Román, Maite; Camacho, Carlos

2011-03-01

Following initial adversity, internationally adopted children arrive with significant growth and developmental delays. Post-placement recovery has been widely documented, but little has been known about its extent and timing several years after placement and in children with diverse pre-adoptive experiences. A total of 289 children adopted from six countries into Spanish families were studied. Growth and psychological development were considered on arrival and after an average of over 3 years. Growth and developmental initial delays affected a substantial percentage of the children. Post-adoption recovery seemed quicker and more complete in weight and height than in head circumference and psychological development. Initial and later values were correlated, but growth-development relation on arrival subsequently lost significance. Most of the catch-up happened in the first three post-adoption years. Adoption offers an impressive opportunity for recovery after previous adversity, although continuity between past and present persists. The improvement is more marked in some areas than in others and more substantial in the first post-adoption years. © 2010 Blackwell Publishing Ltd.

Reduction of Weather-Related Terminal Area Delays in the Free-Flight Era

NASA Technical Reports Server (NTRS)

Johnson, Sally C.; Chin, David K.; Rovinsky, Robert B.; Kostiuk, Peter F.; Lee, David A.; Hemm, Robert V.; Wingrove, Earl R., III

1996-01-01

While much of the emphasis of the free-flight movement has been concentrated on reducing en-route delays, airport capacity is a major bottleneck in the current airspace system, particularly during bad weather. According to the Air Transport Association (ATA) Air Carrier Delay Reports, ground delays (gate-hold, taxi-in, and taxi-out) comprise 75 percent of total delays. It is likely that the projected steady growth in traffic will only exacerbate these losses. Preliminary analyses show that implementation of the terminal area technologies and procedures under development in NASA s Terminal Area Productivity program can potentially save the airlines at least $350M annually in weather-related delays by the year 2005 at Boston Logan and Detroit airports alone. This paper briefly describes the Terminal Area Productivity program, outlines the costhenefit analyses that are being conducted in support of the program, and presents some preliminary analysis results.

Malaria infection and feather growth rate predict reproductive success in house martins.

PubMed

Marzal, Alfonso; Reviriego, Maribel; Hermosell, Ignacio G; Balbontín, Javier; Bensch, Staffan; Relinque, Carmen; Rodríguez, Laura; Garcia-Longoria, Luz; de Lope, Florentino

2013-04-01

Carry-over effects take place when events occurring in one season influence individual performance in a subsequent season. Blood parasites (e.g. Plasmodium and Haemoproteus) have strong negative effects on the body condition of their hosts and could slow the rate of feather growth on the wintering grounds. In turn, these winter moult costs could reduce reproductive success in the following breeding season. In house martins Delichon urbica captured and studied at a breeding site in Europe, we used ptilochronology to measure growth rate of tail feathers moulted on the winter range in Africa, and assessed infection status of blood parasites transmitted on the wintering grounds. We found a negative association between haemosporidian parasite infection status and inferred growth rate of tail feathers. A low feather growth rate and blood parasite infections were related to a delay in laying date in their European breeding quarters. In addition, clutch size and the number of fledglings were negatively related to a delayed laying date and blood parasite infection. These results stress the importance of blood parasites and feather growth rate as potentially mechanisms driving carry-over effects to explain fitness differences in wild populations of migratory birds.

Effect of growth hormone deficiency on brain MRI findings among children with growth restrictions.

PubMed

Naderi, Fariba; Eslami, Samira Rajabi; Mirak, Sohrab Afshari; Khak, Mohammad; Amiri, Jalaladin; Beyrami, Bahram; Shekarchi, Babak; Poureisa, Masoud

2015-01-01

Growth hormone deficiency (GHD) is a major problem among children with short stature. In this study, the role of brain magnetic resonance imaging (MRI) in defining the underlying defects among short children with GHD is evaluated. In a cross-sectional study, data of 158 children were evaluated. Growth hormone (GH) levels were measured using stimulating tests and brain MRI with gadolinium contrast was applied, as well. Some 25.3% of patients had GHD with a mean age of 8.01±3.40 years. MRI results showed 35 as normal, four with pituitary hypoplasia, and one with microadenoma. The MRI results were significantly associated with GH levels and presence of other endocrine disorders. There was a significant association between prenatal disorders and patients' bone age delay. In patients with severe GHD and patients with multiple pituitary hormone deficiencies, MRI is more likely to be abnormal, and bone age is much delayed in patients with history of prenatal disorders.

Enhancing dendritic cell immunotherapy for melanoma using a simple mathematical model.

PubMed

Castillo-Montiel, E; Chimal-Eguía, J C; Tello, J Ignacio; Piñon-Zaráte, G; Herrera-Enríquez, M; Castell-Rodríguez, A E

2015-06-09

The immunotherapy using dendritic cells (DCs) against different varieties of cancer is an approach that has been previously explored which induces a specific immune response. This work presents a mathematical model of DCs immunotherapy for melanoma in mice based on work by Experimental Immunotherapy Laboratory of the Medicine Faculty in the Universidad Autonoma de Mexico (UNAM). The model is a five delay differential equation (DDEs) which represents a simplified view of the immunotherapy mechanisms. The mathematical model takes into account the interactions between tumor cells, dendritic cells, naive cytotoxic T lymphocytes cells (inactivated cytotoxic cells), effector cells (cytotoxic T activated cytotoxic cells) and transforming growth factor β cytokine (T G F-β). The model is validated comparing the computer simulation results with biological trial results of the immunotherapy developed by the research group of UNAM. The results of the growth of tumor cells obtained by the control immunotherapy simulation show a similar amount of tumor cell population than the biological data of the control immunotherapy. Moreover, comparing the increase of tumor cells obtained from the immunotherapy simulation and the biological data of the immunotherapy applied by the UNAM researchers obtained errors of approximately 10 %. This allowed us to use the model as a framework to test hypothetical treatments. The numerical simulations suggest that by using more doses of DCs and changing the infusion time, the tumor growth decays compared with the current immunotherapy. In addition, a local sensitivity analysis is performed; the results show that the delay in time " τ", the maximal growth rate of tumor "r" and the maximal efficiency of tumor cytotoxic cells rate "aT" are the most sensitive model parameters. By using this mathematical model it is possible to simulate the growth of the tumor cells with or without immunotherapy using the infusion protocol of the UNAM researchers, to obtain a good approximation of the biological trials data. It is worth mentioning that by manipulating the different parameters of the model the effectiveness of the immunotherapy may increase. This last suggests that different protocols could be implemented by the Immunotherapy Laboratory of UNAM in order to improve their results.

An analysis of dental development in Pleistocene Homo using skeletal growth and chronological age.

PubMed

Šešelj, Maja

2017-07-01

This study takes a new approach to interpreting dental development in Pleistocene Homo in comparison with recent modern humans. As rates of dental development and skeletal growth are correlated given age in modern humans, using age and skeletal growth in tandem yields more accurate dental development estimates. Here, I apply these models to fossil Homo to obtain more individualized predictions and interpretations of their dental development relative to recent modern humans. Proportional odds logistic regression models based on three recent modern human samples (N = 181) were used to predict permanent mandibular tooth development scores in five Pleistocene subadults: Homo erectus/ergaster, Neanderthals, and anatomically modern humans (AMHs). Explanatory variables include a skeletal growth indicator (i.e., diaphyseal femoral length), and chronological age. AMHs Lagar Velho 1 and Qafzeh 10 share delayed incisor development, but exhibit considerable idiosyncratic variation within and across tooth types, relative to each other and to the reference samples. Neanderthals Dederiyeh 1 and Le Moustier 1 exhibit delayed incisor coupled with advanced molar development, but differences are reduced when femoral diaphysis length is considered. Dental development in KNM-WT 15,000 Homo erectus/ergaster, while advanced for his age, almost exactly matches the predictions once femoral length is included in the models. This study provides a new interpretation of dental development in KNM-WT 15000 as primarily reflecting his faster rates of skeletal growth. While the two AMH specimens exhibit considerable individual variation, the Neanderthals exhibit delayed incisor development early and advanced molar development later in ontogeny. © 2017 Wiley Periodicals, Inc.

Endocrine Dysfunction and Slipped Capital Femoral Epiphysis 1

PubMed Central

Ogden, John A.; Southwick, Wayne O.

1977-01-01

Five patients with concomitant endocrinopathy and slipped capital femoral epiphysis were studied in detail. One had diabetes and hypothyroidism, one had hypothyroidism, one had hypergonadotropic hypogonadism and two had a craniopharyngioma (one of whom had severe panhypopituitarism post-operatively). An additional seven patients with cranio-pharyngioma revealed marked delay in closure of epiphyses and an additional undiagnosed case of slipped capital femoral epiphysis. Of the six patients with slipped capital femoral epiphysis, three had bilateral and three unilateral involvement. Of the five patients undergoing surgical stabilization, there was significant delay of epiphyseodesis, prompting us to recommend concomitant bone grafting. Histological examination of the femoral head from a three year old child with panhypopituitarism showed marked irregularity of the growth plate and loss of columnar integrity, which may be a predisposing factor to slipping in older children with endocrinopathies. The effects of various hormones on the physis are specifically discussed, especially as they relate to the possible etiology of slipped capital femoral epiphysis. ImagesFIG. 1A and 1BFIG. 2FIG. 3A and 3BFIG. 4A and 4BFIG. 5 PMID:191998

Photonic modulation of EGFR: 280nm low level light arrests cancer cell activation and migration

NASA Astrophysics Data System (ADS)

Botelho, Cláudia M.; Marques, Rogério; Viruthachalam, Thiagarajan; Gonçalves, Odete; Vorum, Henrik; Gomes, Andreia C.; Neves-Petersen, Maria Teresa

2017-02-01

Overexpression of the Epidermal Growth Factor Receptor (EGFR) by cancer cells is associated with a poor prognosis for the patient. For several decades, therapies targeting EGFR have been designed, including the use of monoclonal antibodies and small molecule tyrosine kinase inhibitors. The use of these molecules had good clinical results, although its efficiency (and specificity) is still far from being optimal. In this paper, we present a new approach for a possible new cancer therapy targeting EGFR and using low intensity 280nm light. The influence of 280nm UVB illumination on cancer cells stimulated with 2nM of EGF was followed by time-lapse confocal microscopy. The 280nm illumination of the cancer cells blocks EGFR activation, inhibiting EGFR internalization and cell migration thus inhibiting the transition to the metastatic phenotype. Exposure time is a very important factor. The higher the illumination time the more significant differences were observed: 280nm light delayed or completely halted EGFR activation in the cell membrane, mainly at the cell junction level, and delayed or halted EGFR endocytic internalization, filopodia formation and cell migration.

Spread of hatch and delayed feed access affect post hatch performance of female broiler chicks up to day 5.

PubMed

Wang, Y; Li, Y; Willems, E; Willemsen, H; Franssens, L; Koppenol, A; Guo, X; Tona, K; Decuypere, E; Buyse, J; Everaert, N

2014-04-01

It is not rare that newly hatched chicks remain without feed for about 24 to 48 h before they are placed on farms due to a series of logistic operations. Furthermore, the spread in hatching time can also mount up to 30 to 48 h for late v. early hatchers. In other words, the practice is a complex combination of spread of hatch and delayed feed access. The present study was aimed to investigate the combined effects of hatching time with a delay in feed access of 48 h, starting from their hatch-time (biological age). When chicks had access to feed immediately after hatch, late hatchers had a higher feed intake and relative growth rate up to day 5 compared with their early hatched counterparts. Feed deprivation during the first 48 h resulted in retarded early growth rate, which was further aggravated by an impaired feed intake after refeeding. In addition, the differential effects of hatching time on relative growth rate and feed intake observed in immediately fed chicks were eliminated by the 48 h feed delay. The yolk utilization after hatch was faster for the late hatchers up to biological day 2 regardless of the feeding treatments. Hatching muscle glycogen content was higher in the late hatchers compared with that of their early counterparts at hatch and at biological day 2 independent of feeding treatment. Moreover, the liver glycogen content of the late hatchers was also higher at hatch. For the immediately fed chicks, the proportional breast muscle weight of the late hatchers was higher at biological day 2 and 5. For the starved chicks, on the other hand, this effect was only observed after they had access to feed (biological day 5). The different plasma T3 levels at hatch may have contributed to the different post hatch performance. It is concluded that the spread of hatch influenced post hatch performance, especially appetite and growth at least until day 5. Moreover, the delay in feed access interacted with the hatching time and caused adverse effects on the post hatch performance.

Identifying ingredients that delay outgrowth of Listeria monocytogenes in natural, organic, and clean-label ready-to-eat meat and poultry products.

PubMed

McDonnell, Lindsey M; Glass, Kathleen A; Sindelar, Jeffrey J

2013-08-01

The objective of this study was to identify ingredients that inhibit Listeria monocytogenes in natural, organic, or clean-label ready-to-eat meat and poultry products. Fourteen ingredients were screened in uncured (no-nitrate-or-nitrite-added), traditional-cured (156 ppm of purified sodium nitrite), cultured (alternative cured, natural nitrate source, and Staphylococcus carnosus), or preconverted (alternative cured, natural nitrite source) turkey slurries. Slurries were cooked, cooled, inoculated to yield 3 log CFU/ml L. monocytogenes, stored at 4°C, and tested weekly for 4 weeks. Three antimicrobial ingredients, 1.5 % vinegar-lemon-cherry powder blend, 2.5 % buffered vinegar, and 3.0 % cultured sugar-vinegar blend, were incorporated into alternative-cured ham and uncured roast beef and deli-style turkey breast. Controls included all three meat products without antimicrobial ingredients and a traditional-cured ham with 2.8 % sodium lactate-diacetate. Cooked, sliced products were inoculated with 3 log CFU/g L. monocytogenes, vacuum packed, and stored at 4 or 7°C, for up to 12 weeks. For control products without antimicrobial agents stored at 4°C, a 2-log L. monocytogenes increase was observed at 2 weeks for ham and turkey and at 4 weeks for roast beef. Growth (>1-log increase) in the sodium lactate-diacetate was delayed until week 6. Compared with the control, the addition of either vinegar-lemon-cherry powder blend or buffered vinegar delayed L. monocytogenes growth for an additional 2 weeks, while the addition of cultured sugar-vinegar blend delayed growth for an additional 4 weeks for both ham and turkey. The greatest L. monocytogenes delay was observed in roast beef containing any of the three antimicrobial ingredients, with no growth detected through 12 weeks at 4°C for all the treatments. As expected, L. monocytogenes grew substantially faster in products stored at 7°C than at 4°C. These data suggest that antimicrobial ingredients from a natural source can enhance the safety of ready-to-eat meat and poultry products, but their efficacy is improved in products containing nitrite and with lower moisture and pH.

Specific recognition and inhibition of Ewing tumour growth by antigen-specific allo-restricted cytotoxic T cells

PubMed Central

Thiel, U; Pirson, S; Müller-Spahn, C; Conrad, H; Busch, D H; Bernhard, H; Burdach, S; Richter, G H S

2011-01-01

Background: The development of a successful immunotherapy is hampered by an ineffective T-cell repertoire against tumour antigens and the inability of the patient's immune system to overcome tolerance-inducing mechanisms. Here, we test the specific recognition and lytical potential of allo-restricted CD8+ T cells against Ewing tumour (ET) associated antigens Enhancer of Zeste, Drosophila Homolog 2 (EZH2), and Chondromodulin-I (CHM1) identified through previous microarray analysis. Methods: Following repetitive CHM1319 (VIMPCSWWV) and EZH2666 (YMCSFLFNL) peptide-driven stimulations with HLA-A*0201+ dendritic cells (DC), allo-restricted HLA-A*0201− CD8+ T cells were stained with HLA-A*0201/peptide multimers, sorted and expanded by limiting dilution. Results: Expanded T cells specifically recognised peptide-pulsed target cells or antigen-transfected cells in the context of HLA-A*0201 and killed HLA-A*0201+ ET lines expressing the antigen while HLA-A*0201– ET lines were not affected. Furthermore, adoptively transferred T cells caused significant ET growth delay in Rag2−/−γC−/− mice. Within this context, we identified the CHM1319 peptide as a new candidate target antigen for ET immunotherapy. Conclusion: These results clearly identify the ET-derived antigens, EZH2666 and CHM1319, as suitable targets for protective allo-restricted human CD8+ T-cell responses against non-immunogenic ET and may benefit new therapeutic strategies in ET patients treated with allogeneic stem cell transplantation. PMID:21407224

Integration and scaling of UV-B radiation effects on plants: from molecular interactions to whole plant responses.

PubMed

Suchar, Vasile Alexandru; Robberecht, Ronald

2016-07-01

A process based model integrating the effects of UV-B radiation to molecular level processes and their consequences to whole plant growth and development was developed from key parameters in the published literature. Model simulations showed that UV-B radiation induced changes in plant metabolic and/or photosynthesis rates can result in plant growth inhibitions. The costs of effective epidermal UV-B radiation absorptive compounds did not result in any significant changes in plant growth, but any associated metabolic costs effectively reduced the potential plant biomass. The model showed significant interactions between UV-B radiation effects and temperature and any factor leading to inhibition of photosynthetic production or plant growth during the midday, but the effects were not cumulative for all factors. Vegetative growth were significantly delayed in species that do not exhibit reproductive cycles during a growing season, but vegetative growth and reproductive yield in species completing their life cycle in one growing season did not appear to be delayed more than 2-5 days, probably within the natural variability of the life cycles for many species. This is the first model to integrate the effects of increased UV-B radiation through molecular level processes and their consequences to whole plant growth and development.

Uncertainty: A little bit not sure. Parental concern about child growth or development.

PubMed

Mulcahy, Helen; Savage, Eileen

2016-09-01

Delays in child growth or development are significant problems for children, their families and population health. Eliciting parental concerns as early as possible to promote child growth and development requires close collaborative working with parents. There is evidence that parents delay expressing concern and that health-care professionals are not always effective at eliciting and attending to parental concerns. The aim of this study was to understand the experiences of parents of preschool children who had expressed a child growth or development concern. An Interpretative Phenomenological Analysis (IPA) study design was used with a purposive sample of parents of 15 preschool children in Ireland. Data were collected by semi-structured interviews and analysed using IPA. One key superordinate theme - Uncertainty - 'a little bit not sure' captured how parents made sense of their concerns about their child's growth and development. In addition to watching, comparing and wondering, parents assessed whether their child could 'do other things' or if something in particular could have caused the growth or development problem. Parents, particularly mothers, grapple with uncertainty associated with unfamiliar cues in the complex and multifaceted nature of child growth and development in their efforts to make sense of what is happening with their child. © The Author(s) 2015.

Sensitivity and specificity of the 3-item memory test in the assessment of post traumatic amnesia.

PubMed

Andriessen, Teuntje M J C; de Jong, Ben; Jacobs, Bram; van der Werf, Sieberen P; Vos, Pieter E

2009-04-01

To investigate how the type of stimulus (pictures or words) and the method of reproduction (free recall or recognition after a short or a long delay) affect the sensitivity and specificity of a 3-item memory test in the assessment of post traumatic amnesia (PTA). Daily testing was performed in 64 consecutively admitted traumatic brain injured patients, 22 orthopedically injured patients and 26 healthy controls until criteria for resolution of PTA were reached. Subjects were randomly assigned to a test with visual or verbal stimuli. Short delay reproduction was tested after an interval of 3-5 minutes, long delay reproduction was tested after 24 hours. Sensitivity and specificity were calculated over the first 4 test days. The 3-word test showed higher sensitivity than the 3-picture test, while specificity of the two tests was equally high. Free recall was a more effortful task than recognition for both patients and controls. In patients, a longer delay between registration and recall resulted in a significant decrease in the number of items reproduced. Presence of PTA is best assessed with a memory test that incorporates the free recall of words after a long delay.

Time-delayed feedback control of diffusion in random walkers.

PubMed

Ando, Hiroyasu; Takehara, Kohta; Kobayashi, Miki U

2017-07-01

Time delay in general leads to instability in some systems, while specific feedback with delay can control fluctuated motion in nonlinear deterministic systems to a stable state. In this paper, we consider a stochastic process, i.e., a random walk, and observe its diffusion phenomenon with time-delayed feedback. As a result, the diffusion coefficient decreases with increasing delay time. We analytically illustrate this suppression of diffusion by using stochastic delay differential equations and justify the feasibility of this suppression by applying time-delayed feedback to a molecular dynamics model.

Theory-of-Mind Development in Oral Deaf Children with Cochlear Implants or Conventional Hearing Aids

ERIC Educational Resources Information Center

Peterson, Candida C.

2004-01-01

Background: In the context of the established finding that theory-of-mind (ToM) growth is seriously delayed in late-signing deaf children, and some evidence of equivalent delays in those learning speech with conventional hearing aids, this study's novel contribution was to explore ToM development in deaf children with cochlear implants. Implants…

Growth dominates choice in network percolation

NASA Astrophysics Data System (ADS)

Vijayaraghavan, Vikram S.; Noël, Pierre-André; Waagen, Alex; D'Souza, Raissa M.

2013-09-01

The onset of large-scale connectivity in a network (i.e., percolation) often has a major impact on the function of the system. Traditionally, graph percolation is analyzed by adding edges to a fixed set of initially isolated nodes. Several years ago, it was shown that adding nodes as well as edges to the graph can yield an infinite order transition, which is much smoother than the traditional second-order transition. More recently, it was shown that adding edges via a competitive process to a fixed set of initially isolated nodes can lead to a delayed, extremely abrupt percolation transition with a significant jump in large but finite systems. Here we analyze a process that combines both node arrival and edge competition. If started from a small collection of seed nodes, we show that the impact of node arrival dominates: although we can significantly delay percolation, the transition is of infinite order. Thus, node arrival can mitigate the trade-off between delay and abruptness that is characteristic of explosive percolation transitions. This realization may inspire new design rules where network growth can temper the effects of delay, creating opportunities for network intervention and control.

Length distributions of nanowires: Effects of surface diffusion versus nucleation delay

NASA Astrophysics Data System (ADS)

Dubrovskii, Vladimir G.

2017-04-01

It is often thought that the ensembles of semiconductor nanowires are uniform in length due to the initial organization of the growth seeds such as lithographically defined droplets or holes in the substrate. However, several recent works have already demonstrated that most nanowire length distributions are broader than Poissonian. Herein, we consider theoretically the length distributions of non-interacting nanowires that grow by the material collection from the entire length of their sidewalls and with a delay of nucleation of the very first nanowire monolayer. The obtained analytic length distribution is controlled by two parameters that describe the strength of surface diffusion and the nanowire nucleation rate. We show how the distribution changes from the symmetrical Polya shape without the nucleation delay to a much broader and asymmetrical one for longer delays. In the continuum limit (for tall enough nanowires), the length distribution is given by a power law times an incomplete gamma-function. We discuss interesting scaling properties of this solution and give a recipe for analyzing and tailoring the experimental length histograms of nanowires which should work for a wide range of material systems and growth conditions.

Response inhibition difficulties in preterm children aged 9-12 years: Relations with emotion and behavior.

PubMed

Réveillon, Morgane; Borradori Tolsa, Cristina; Monnier, Maryline; Hüppi, Petra S; Barisnikov, Koviljka

2016-01-01

Previous studies with children have demonstrated inhibition difficulties associated with prematurity, but the question of potentially catching up with a delay in inhibition processes before adolescence still remains. Moreover, preterm adolescents are more at risk than their term-born peers for presenting behavioral problems such as emotional difficulties and attention deficit/hyperactivity disorder. In addition to examining response inhibition, this study addressed, for the first time, the impact of an emotional context on response inhibition abilities and its relation to behavioral problems in late school-aged preterm children. Fifty-eight preterm children aged 9-12 years were compared with 61 controls on two versions of a stop-signal task, the Delay Frustration Task, and the Strengths and Difficulties Questionnaire. Results showed general difficulties in inhibiting a response, rather than a specific impact of emotional context in preterm children. Compared with controls, these children exhibited more and longer button presses in a delay situation, as well as faster go reaction times associated with lower probability of inhibition in the stop-signal tasks. These difficulties reflected impulsivity and were associated with higher hyperactivity/inattention and conduct problems. Additionally, intrauterine growth restriction was found to be an additional perinatal risk factor for hyperactivity/inattention symptoms. These findings suggest that remaining inhibition difficulties in the preterm population at preadolescence could reveal increasing behavioral issues.

Systematic Analysis of γ-Aminobutyric Acid (GABA) Metabolism and Function in the Social Amoeba Dictyostelium discoideum*

PubMed Central

Wu, Yuantai; Janetopoulos, Chris

2013-01-01

While GABA has been suggested to regulate spore encapsulation in the social amoeba Dictyostelium discoideum, the metabolic profile and other potential functions of GABA during development remain unclear. In this study, we investigated the homeostasis of GABA metabolism by disrupting genes related to GABA metabolism and signaling. Extracellular levels of GABA are tightly regulated during early development, and GABA is generated by the glutamate decarboxylase, GadB, during growth and in early development. However, overexpression of the prespore-specific homologue, GadA, in the presence of GadB reduces production of extracellular GABA. Perturbation of extracellular GABA levels delays the process of aggregation. Cytosolic GABA is degraded by the GABA transaminase, GabT, in the mitochondria. Disruption of a putative vesicular GABA transporter (vGAT) homologue DdvGAT reduces secreted GABA. We identified the GABAB receptor-like family member GrlB as the major GABA receptor during early development, and either disruption or overexpression of GrlB delays aggregation. This delay is likely the result of an abolished pre-starvation response and late expression of several “early” developmental genes. Distinct genes are employed for GABA generation during sporulation. During sporulation, GadA alone is required for generating GABA and DdvGAT is likely responsible for GABA secretion. GrlE but not GrlB is the GABA receptor during late development. PMID:23548898

Maternal, social and abiotic environmental effects on growth vary across life stages in a cooperative mammal

PubMed Central

English, Sinead; Bateman, Andrew W; Mares, Rafael; Ozgul, Arpat; Clutton-Brock, Tim H

2014-01-01

Resource availability plays a key role in driving variation in somatic growth and body condition, and the factors determining access to resources vary considerably across life stages. Parents and carers may exert important influences in early life, when individuals are nutritionally dependent, with abiotic environmental effects having stronger influences later in development as individuals forage independently. Most studies have measured specific factors influencing growth across development or have compared relative influences of different factors within specific life stages. Such studies may not capture whether early-life factors continue to have delayed effects at later stages, or whether social factors change when individuals become nutritionally independent and adults become competitors for, rather than providers of, food. Here, we examined variation in the influence of the abiotic, social and maternal environment on growth across life stages in a wild population of cooperatively breeding meerkats. Cooperatively breeding vertebrates are ideal for investigating environmental influences on growth. In addition to experiencing highly variable abiotic conditions, cooperative breeders are typified by heterogeneity both among breeders, with mothers varying in age and social status, and in the number of carers present. Recent rainfall had a consistently marked effect on growth across life stages, yet other seasonal terms only influenced growth during stages when individuals were growing fastest. Group size and maternal dominance status had positive effects on growth during the period of nutritional dependence on carers, but did not influence mass at emergence (at 1 month) or growth at independent stages (>4 months). Pups born to older mothers were lighter at 1 month of age and subsequently grew faster as subadults. Males grew faster than females during the juvenile and subadult stage only. Our findings demonstrate the complex ways in which the external environment influences development in a cooperative mammal. Individuals are most sensitive to social and maternal factors during the period of nutritional dependence on carers, whereas direct environmental effects are relatively more important later in development. Understanding the way in which environmental sensitivity varies across life stages is likely to be an important consideration in predicting trait responses to environmental change. PMID:24102215

Delayed-enhanced cardiac MRI for differentiation of Fabry's disease from symmetric hypertrophic cardiomyopathy.

PubMed

De Cobelli, Francesco; Esposito, Antonio; Belloni, Elena; Pieroni, Maurizio; Perseghin, Gianluca; Chimenti, Cristina; Frustaci, Andrea; Del Maschio, Alessandro

2009-03-01

Fabry's disease may be difficult to differentiate from symmetric hypertrophic cardiomyopathy. Our aim was to compare the myocardial location and distribution patterns of delayed enhancement between patients with Fabry's disease who are affected by symmetric myocardial hypertrophy and patients with symmetric hypertrophic cardiomyopathy in order to identify a specific sign to best differentiate the two diseases. Patients with Fabry's disease-related hypertrophy showed left ventricular (LV) delayed enhancement with a typical and consistently found pattern characterized by the involvement of the inferolateral basal or mid basal segments and a mesocardial distribution that spared the subendocardium. This pattern seems to be specific to Fabry's disease; in fact, patients with symmetric hypertrophic cardiomyopathy had variable locations and distributions of delayed enhancement. These observations may contribute to identifying Fabry's disease as a specific cause of symmetric hypertrophy.

Bilateral insufficiency fracture of the femoral head and neck in a case of oncogenic osteomalacia.

PubMed

Chouhan, V; Agrawal, K; Vinothkumar, T K; Mathesul, A

2010-07-01

We describe a case of oncogenic osteomalacia in an adult male who presented with low back pain and bilateral hip pain. Extensive investigations had failed to find a cause. A plain pelvic radiograph showed Looser's zones in both femoral necks. MRI confirmed the presence of insufficiency fractures bilaterally in the femoral head and neck. Biochemical investigations confirmed osteomalacia which was unresponsive to treatment with vitamin D and calcium. A persistently low serum phosphate level suggested a diagnosis of hypophosphataemic osteomalacia. The level of fibroblast growth factor-23 was highly raised, indicating the cause as oncogenic osteomalacia. This was confirmed on positron-emission tomography, MRI and excision of a benign fibrous histiocytoma following a rapid recovery. The diagnosis of oncogenic osteomalacia may be delayed due to the non-specific presenting symptoms. Subchondral insufficiency fractures of the femoral head may be missed unless specifically looked for.

ISO-66, a novel inhibitor of macrophage migration, shows efficacy in melanoma and colon cancer models.

PubMed

Ioannou, Kyriaki; Cheng, Kai Fan; Crichlow, Gregg V; Birmpilis, Anastasios I; Lolis, Elias J; Tsitsilonis, Ourania E; Al-Abed, Yousef

2014-10-01

Macrophage migration inhibitory factor (MIF) is a pleiotropic pro-inflammatory cytokine, which possesses a contributing role in cancer progression and metastasis and, thus, is now considered a promising anticancer drug target. Many MIF-inactivating strategies have proven successful in delaying cancer growth. Here, we report on the synthesis of ISO-66, a novel, highly stable, small-molecule MIF inhibitor, an analog of ISO-1 with improved characteristics. The MIF:ISO-66 co-crystal structure demonstrated that ISO-66 ligates the tautomerase active site of MIF, which has previously been shown to play an important role in its biological functions. In vitro, ISO-66 enhanced specific and non-specific anticancer immune responses, whereas prolonged administration of ISO-66 in mice with established syngeneic melanoma or colon cancer was non-toxic and resulted in a significant decrease in tumor burden. Subsequent ex vivo analysis of mouse splenocytes revealed that the observed decrease in tumor growth rates was likely mediated by the selective in vivo expansion of antitumor-reactive effector cells induced by ISO-66. Compared to other MIF-inactivating strategies employed in vivo, the anticancer activity of ISO-66 is demonstrated to be of equal or better efficacy. Our findings suggest that targeting MIF, via highly specific and stable compounds, such as ISO-66, may be effective for cancer treatment and stimulation of anticancer immune responses.

Oral Language and Narrative Skills in Children with Specific Language Impairment with and without Literacy Delay: A Three-Year Longitudinal Study

ERIC Educational Resources Information Center

Vandewalle, Ellen; Boets, Bart; Boons, Tinne; Ghesquiere, Pol; Zink, Inge

2012-01-01

This longitudinal study compared the development of oral language and more specifically narrative skills (storytelling and story retelling) in children with specific language impairment (SLI) with and without literacy delay. Therefore, 18 children with SLI and 18 matched controls with normal literacy were followed from the last year of…

Auditory processing and speech perception in children with specific language impairment: relations with oral language and literacy skills.

PubMed

Vandewalle, Ellen; Boets, Bart; Ghesquière, Pol; Zink, Inge

2012-01-01

This longitudinal study investigated temporal auditory processing (frequency modulation and between-channel gap detection) and speech perception (speech-in-noise and categorical perception) in three groups of 6 years 3 months to 6 years 8 months-old children attending grade 1: (1) children with specific language impairment (SLI) and literacy delay (n = 8), (2) children with SLI and normal literacy (n = 10) and (3) typically developing children (n = 14). Moreover, the relations between these auditory processing and speech perception skills and oral language and literacy skills in grade 1 and grade 3 were analyzed. The SLI group with literacy delay scored significantly lower than both other groups on speech perception, but not on temporal auditory processing. Both normal reading groups did not differ in terms of speech perception or auditory processing. Speech perception was significantly related to reading and spelling in grades 1 and 3 and had a unique predictive contribution to reading growth in grade 3, even after controlling reading level, phonological ability, auditory processing and oral language skills in grade 1. These findings indicated that speech perception also had a unique direct impact upon reading development and not only through its relation with phonological awareness. Moreover, speech perception seemed to be more associated with the development of literacy skills and less with oral language ability. Copyright © 2011 Elsevier Ltd. All rights reserved.

Asymmetric effects of cooler and warmer winters on beech phenology last beyond spring

NASA Astrophysics Data System (ADS)

Signarbieux, Constant; Toledano, Ester; Sangines, Paula; Fu, Yongshuo; Schlaepfer, Rodolphe; Buttler, Alexandre; Vitasse, Yann

2017-04-01

In temperate trees, the timing of plant growth onset and cessation affect biogeochemical cycles, water and energy balance. Currently, phenological studies largely focus on specific phenophases and on their responses to warming. How differently spring phenology responds to the warming and cooling, and affects the subsequent phases, has not been well investigated. Here, we exposed saplings of Fagus sylvatica L. to warmer and cooler climate during the winter 2013-2014 by conducting a reciprocal transplant experiment between two elevations (1340 vs. 371 m.a.s.l., ca. 6°C difference) in the Swiss Jura mountains. To test the legacy effects of earlier or later budburst on the budset timing, saplings were moved back to their original elevation shortly after the occurrence of budburst in spring 2014. One degree decrease of air temperature resulted in a delay of 10.9 days in budburst dates, whereas one degree of warming advanced the date by 8.8 days. Interestingly, we found an asymmetric effect of the warmer winter vs. cooler winter on the budset timing in autumn: saplings experiencing a cooler winter showed a delay of 31 days in their budset timing compared to the control, whereas saplings experiencing a warmer winter showed 10 days earlier budset. The dependency of spring over autumn phenophases might be partly explained by the building up of the non-structural carbohydrate storage and suggests that the potential delay in growth cessation due to global warming might be smaller than expected. We did not find a significant correlation in budburst dates between 2014 and 2015, indicating that the legacy effects of the different phenophases might be reset during each winter. Adapting phenological models to the whole annual phenological cycle, and considering the different response to cooling and warming, would improve predictions of tree phenology under future climate warming conditions.

Identification of three signaling molecules required for calcineurin-dependent monopolar growth induced by the DNA replication checkpoint in fission yeast.

PubMed

Kume, Kazunori; Hashimoto, Tomoyo; Suzuki, Masashi; Mizunuma, Masaki; Toda, Takashi; Hirata, Dai

2017-09-30

Cell polarity is coordinately regulated with the cell cycle. Growth polarity of the fission yeast Schizosaccharomyces pombe transits from monopolar to bipolar during G2 phase, termed NETO (new end take off). Upon perturbation of DNA replication, the checkpoint kinase Cds1/CHK2 induces NETO delay through activation of Ca 2+ /calmodulin-dependent protein phosphatase calcineurin (CN). CN in turn regulates its downstream targets including the microtubule (MT) plus-end tracking CLIP170 homologue Tip1 and the Casein kinase 1γ Cki3. However, whether and which Ca 2+ signaling molecules are involved in the NETO delay remains elusive. Here we show that 3 genes (trp1322, vcx1 and SPAC6c3.06c encoding TRP channel, antiporter and P-type ATPase, respectively) play vital roles in the NETO delay. Upon perturbation of DNA replication, these 3 genes are required for not only the NETO delay but also for the maintenance of cell viability. Trp1322 and Vcx1 act downstream of Cds1 and upstream of CN for the NETO delay, whereas SPAC6c3.06c acts downstream of CN. Consistently, Trp1322 and Vcx1, but not SPAC6c3.06c, are essential for activation of CN. Interestingly, we have found that elevated extracellular Ca 2+ per se induces a NETO delay, which depends on CN and its downstream target genes. These findings imply that Ca 2+ -CN signaling plays a central role in cell polarity control by checkpoint activation. Copyright © 2017 Elsevier Inc. All rights reserved.

Functional brain development in growth-restricted and constitutionally small fetuses: a fetal magnetoencephalography case-control study.

PubMed

Morin, E C; Schleger, F; Preissl, H; Braendle, J; Eswaran, H; Abele, H; Brucker, S; Kiefer-Schmidt, I

2015-08-01

Fetal magnetoencephalography records fetal brain activity non-invasively. Delayed brain responses were reported for fetuses weighing below the tenth percentile. To investigate whether this delay indicates delayed brain maturation resulting from placental insufficiency, this study distinguished two groups of fetuses below the tenth percentile: growth-restricted fetuses with abnormal umbilical artery Doppler velocity (IUGR) and constitutionally small-for-gestational-age fetuses with normal umbilical artery Doppler findings (SGA) were compared with fetuses of adequate weight for gestational age (AGA), matched for age and behavioural state. A case-control study of matched pairs. Fetal magnetoencephalography-Center at the University Hospital of Tuebingen. Fourteen IUGR fetuses and 23 SGA fetuses were matched for gestational age and fetal behavioural state with 37 healthy, normal-sized fetuses. A 156-channel fetal magentoencephalography system was used to record fetal brain activity. Light flashes as visual stimulation were applied to the fetus. The Student's t-test for paired groups was performed. Latency of fetal visual evoked magnetic responses (VER). The IUGR fetuses showed delayed VERs compared with controls (IUGR, 233.1 ms; controls, 184.6 ms; P = 0.032). SGA fetuses had similar evoked response latencies compared with controls (SGA, 216.1 ms; controls, 219.9 ms; P = 0.828). Behavioural states were similarly distributed. Visual evoked responses are delayed in IUGR fetuses, but not in SGA. Fetal behavioural state as an influencing factor of brain response latency was accounted for in the comparison. This reinforces that delayed brain maturation is the result of placental insufficiency. © 2015 Royal College of Obstetricians and Gynaecologists.

One level up: abnormal proteolytic regulation of IGF activity plays a role in human pathophysiology.

PubMed

Argente, Jesús; Chowen, Julie A; Pérez-Jurado, Luis A; Frystyk, Jan; Oxvig, Claus

2017-10-01

The discovery of a mutation in a specific gene can be very important for determining the pathophysiology underlying the disease of a patient and may also help to decide the best treatment protocol on an individual basis. However, sometimes the discovery of mutations in new proteins advances our comprehension in a more widespread manner. The growth hormone (GH)/insulin-like growth factor (IGF)-1 axis is fundamental for systemic growth, but is also involved in many other important processes. Our understanding of this system in physiology and pathophysiology has advanced throughout the years with each discovery of mutations in members of this axis. This review focuses on the most recent discovery: mutations in the metalloproteinase pregnancy-associated plasma protein-A2 (PAPP-A2), one of the proteases involved in liberating IGF-1 from the complexes in which it circulates, in patients with delayed growth failure. We also discuss the advances in the stanniocalcins (STC1 and STC2), proteins that modulate PAPP-A2, as well as PAPP-A. These new advances not only bring us one step closer to understanding the strict spatial and temporal control of this axis in systemic growth and maturation, but also highlight possible therapeutic targets when this system goes awry. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Acute exposure to tris (2-butoxyethyl) phosphate (TBOEP) affects growth and development of embryo-larval zebrafish.

PubMed

Liu, Yiran; Wu, Ding; Xu, Qinglong; Yu, Liqin; Liu, Chunsheng; Wang, Jianghua

2017-10-01

Tris (2-butoxyethyl) phosphate (TBOEP), is used as a flame retardant worldwide. It is an additive in materials and can be easily discharged into the surrounding environment. There is evidence linking TBOEP exposure to abnormal development and growth in zebrafish embryos/larvae. Here, using zebrafish embryo as a model, we investigated toxicological effects on developing zebrafish (Danio rerio) caused by TBOEP at concentrations of 0, 20, 200, 1000, 2000μg/L starting from 2h post-fertilization (hpf). Our findings revealed that TBOEP exposure caused developmental toxicity, such as malformation, growth delay and decreased heart rate in zebrafish larvae. Correlation analysis indicated that inhibition of growth was possibly due to down-regulation of expression of genes related to the growth hormone/insulin-like growth factor (GH/IGF) axis. Furthermore, exposure to TBOEP significantly increased thyroxine (T4) and 3,5,3'-triiodothyronine (T3) in whole larvae. In addition, changed expression of genes involved in the hypothalamic-pituitary-thyroid (HPT) axis was observed, indicating that perturbation of HPT axis might be responsible for the developmental damage and growth delay induced by TBOEP. The present study provides a new set of evidence that exposure of embryo-larval zebrafish to TBOEP can cause perturbation of GH/IGF axis and HPT axis, which could result in developmental impairment and growth inhibition. Copyright © 2017. Published by Elsevier B.V.

Fetal growth from mid- to late pregnancy is associated with infant development: the Generation R Study.

PubMed

Henrichs, Jens; Schenk, Jacqueline J; Barendregt, Charlotte S; Schmidt, Henk G; Steegers, Eric Ap; Hofman, Albert; Jaddoe, Vincent W V; Moll, Henriette A; Verhulst, Frank C; Tiemeier, Henning

2010-07-01

The aim of this study was to investigate within a population-based cohort of 4384 infants (2182 males, 2202 females) whether fetal growth from early pregnancy onwards is related to infant development and whether this potential relationship is independent of postnatal growth. Ultrasound measurements were performed in early, mid-, and late pregnancy. Estimated fetal weight was calculated using head and abdominal circumference and femur length. Infant development was measured with the Minnesota Infant Development Inventory at 12 months (SD 1.1mo, range 10-17mo). Information on postnatal head size and body weight at 7 months was obtained from medical records. After adjusting for potential confounders and for postnatal growth, faster fetal weight gain from mid- to late pregnancy predicted a reduced risk of delayed social development (odds ratio [OR] 0.82; 95% confidence interval [CI] 0.71-0.95, p=0.008), self-help abilities (OR 0.84; 95% CI 0.73-0.98, p=0.023), and overall infant development (OR 0.65; 95% CI 0.49-0.87, p=0.003). Similar findings were observed for fetal head growth from mid- to late pregnancy. Faster fetal growth predicts a lower risk of delayed infant development independent of postnatal growth. These results suggest that reduced fetal growth between mid- and late pregnancy may determine subsequent developmental outcomes.

Deregulation of the growth hormone/insulin-like growth factor-1 axis in adults with cystic fibrosis.

PubMed

Pascucci, C; De Biase, R V; Savi, D; Quattrucci, S; Isidori, A M; Lubrano, C; Gnessi, L; Lenzi, A

2018-05-01

Patients with cystic fibrosis (CF) present with signs and symptoms that overlap with those of adult growth hormone deficiency (GHD) syndrome: loss of muscle mass, bone fragility and lower stress tolerance. In literature, the prevalence of GHD in pediatric CF patients is higher than general population, but these studies have been performed on children with growth delay. To our knowledge, there are no studies on adult patients. The aim of this paper is to evaluate GH-IGF1 axis in an adult CF population. Fifty clinically stable adult patients, 30 males; age 36 ± 2 years; BMI 21.39 ± 0.22 kg/m 2 and FEV 1 67 ± 4% were studied. Data regarding glycometabolic status and results of pituitary, thyroid, parathyroid, gonadal and adrenal function tests were recorded. All patients underwent a GH releasing hormone (GHRH) + Arginine stimulation test to confirm a GHD. GHRH + Arginine test revealed the presence of GHD in 16 patients (32%); specifically 7 patients had a severe deficiency and 9 a partial deficiency. Adult patients with CF may show GHD. These patients should be followed over time to assess if the GHD could impact the clinical progression of CF.

Two synthetic Sp1-binding sites functionally substitute for the 21-base-pair repeat region to activate simian virus 40 growth in CV-1 cells.

PubMed Central

Lednicky, J; Folk, W R

1992-01-01

The 21-bp repeat region of simian virus 40 (SV40) activates viral transcription and DNA replication and contains binding sites for many cellular proteins, including Sp1, LSF, ETF, Ap2, Ap4, GT-1B, H16, and p53, and for the SV40 large tumor antigen. We have attempted to reduce the complexity of this region while maintaining its growth-promoting capacity. Deletion of the 21-bp repeat region from the SV40 genome delays the expression of viral early proteins and DNA replication and reduces virus production in CV-1 cells. Replacement of the 21-bp repeat region with two copies of DNA sequence motifs bound with high affinities by Sp1 promotes SV40 growth in CV-1 cells to nearly wild-type levels, but substitution by motifs bound less avidly by Sp1 or bound by other activator proteins does not restore growth. This indicates that Sp1 or a protein with similar sequence specificity is primarily responsible for the function of the 21-bp repeat region. We speculate about how Sp1 activates both SV40 transcription and DNA replication. Images PMID:1328672

Short stature in genetic syndromes: Selected issues.

PubMed

Łaczmańska, Izabela; Kuliczkowska-Płaksej, Justyna; Stembalska, Agnieszka

2018-03-14

Short stature, which is defined as height below 2 standard deviations of the mean height for the age and sex, is one of the most frequent reasons for medical consultations in children. Short stature may occur due to a constitutional delay in growth, familial short stature or chronic diseases, including many genetic syndromes, metabolic and endocrine disorders. In this article the authors provide a mini-review of the most frequent genetic syndromes associated with short stature that should be taken into account in the differential diagnosis process. Syndromes caused by chromosomal aberrations and gene mutations were divided into 2 main groups: syndromes that are associated with intrauterine growth retardation (IUGR) and those in which IUGR does not occur in the natural history of the patient. The authors described the most important anomalies in each syndrome. Metabolic diseases and skeletal dysplasias were omitted, as they are major separate groups of diseases involving growth delay.

Cushing disease in a toddler: not all obese children are just fat.

PubMed

Moriarty, Megan; Hoe, Francis

2009-08-01

Cushing disease is exceedingly rare in children, especially in those under the age of 2 years. This case report describes an 18-month-old female child who presented with morbid obesity, decreased linear growth, and reversal of developmental milestones. Her diagnosis was delayed; however, she was successfully treated by surgical excision of the microadenoma. This was followed by resolution of signs and symptoms of Cushing syndrome. Although the patient's hypertension resolved, linear growth improved and development began to progress, she is still developmentally delayed and now has hypopituitarism. Review of this case, as well as a handful of other cases of infantile Cushing disease in the literature, suggests that features such as hypertension and slowed linear growth, which are rare in nutritional causes of obesity in infants, can help identify this rare, but life-threatening, illness among an increasing number of overweight infants.

Elongator promotes germination and early post-germination growth.

PubMed

Woloszynska, Magdalena; Gagliardi, Olimpia; Vandenbussche, Filip; Van Lijsebettens, Mieke

2018-01-02

The Elongator complex interacts with RNA polymerase II and via histone acetylation and DNA demethylation facilitates epigenetically the transcription of genes involved in diverse processes in plants, including growth, development, and immune response. Recently, we have shown that the Elongator complex promotes hypocotyl elongation and photomorphogenesis in Arabidopsis thaliana by regulating the photomorphogenesis and growth-related gene network that converges on genes implicated in cell wall biogenesis and hormone signaling. Here, we report that germination in the elo mutant was delayed by 6 h in the dark when compared to the wild type in a time lapse and germination assay. A number of germination-correlated genes were down-regulated in the elo transcriptome, suggesting a transcriptional regulation by Elongator. We also show that the hypocotyl elongation defect observed in the elo mutants in darkness originates very early in the post-germination development and is independent from the germination delay.

A rare presentation of craniopharyngioma: delayed puberty

PubMed Central

İnci, Mehmet Fatih; Özkan, Fuat; Bozkurt, Selim; Demir, Caner Feyzi

2012-01-01

Craniopharyngiomas are the most frequently encountered suprasellar tumours in children. Owing to the slow growth rate of these tumours, they are often quite large before becoming symptomatic. They are more common among children and older adults (55–74 years). Depending upon the direction of growth and tumour size, craniopharyngiomas can affect the hypothalamus, pituitary stalk, optic nerves and chiasm and carotid arteries. Compression of these neural and vascular structures frequently precipitates endocrine disorders, visual loss and an increased intracranial pressure. Hypopituitarism leading to a delayed puberty is a rare presentation of craniopharyngioma. The diagnosis of craniopharyngioma is usually made with the classic radiological imaging features based on CT and MRI. PMID:23195827

A unique case of growth hormone and human chorionic gonadotropin treatment in a 45,X male with Y: autosome translocation and literature review.

PubMed

Mareri, Arianna; Iezzi, MariaLaura; Salvatore, Alessia; Ligas, Claudio; D'Alessandro, Elvira

2016-07-01

Maleness associated with a 45,X karyotype is a rare condition in childhood. It is usually diagnosed in adult age because of infertility. We report a unique case of an unbalanced translocation t(Y;21) in a 14-year-old boy with 45,X karyotype referred because of short stature, thin habitus and puberty delay. Hormone analysis showed low serum levels of basal testosterone, insulin-like growth factor (IGF-I) and gonadotrophins. Diagnosis of GH deficiency and puberty delay were made. He was treated with human chorionic gonadotropin (hCG) and GH therapy, respectively, for 6 and 24 months.

BLACK SPOT INFESTATION IN JUVENILE COHO SALMON AND THE INFLUENCE OF OREGON COASTAL STREAM SUMMER TEMPERATURES

EPA Science Inventory

Freshwater survival and growth of juvenile salmon are affected by many factors, including high summer temperatures and other stressors such as parasitism. Delayed or suppressed growth related to stress can influence subsequent survival of juvenile salmonids in freshwater and mar...

Non-invasive Imaging of Sendai Virus Infection in Pharmacologically Immunocompromised Mice: NK and T Cells, but not Neutrophils, Promote Viral Clearance after Therapy with Cyclophosphamide and Dexamethasone

PubMed Central

Mostafa, Heba H.; Vogel, Peter; Srinivasan, Ashok; Russell, Charles J.

2016-01-01

In immunocompromised patients, parainfluenza virus (PIV) infections have an increased potential to spread to the lower respiratory tract (LRT), resulting in increased morbidity and mortality. Understanding the immunologic defects that facilitate viral spread to the LRT will help in developing better management protocols. In this study, we immunosuppressed mice with dexamethasone and/or cyclophosphamide then monitored the spread of viral infection into the LRT by using a noninvasive bioluminescence imaging system and a reporter Sendai virus (murine PIV type 1). Our results show that immunosuppression led to delayed viral clearance and increased viral loads in the lungs. After cessation of cyclophosphamide treatment, viral clearance occurred before the generation of Sendai-specific antibody responses and coincided with rebounds in neutrophils, T lymphocytes, and natural killer (NK) cells. Neutrophil suppression using anti-Ly6G antibody had no effect on infection clearance, NK-cell suppression using anti-NK antibody delayed clearance, and T-cell suppression using anti-CD3 antibody resulted in no clearance (chronic infection). Therapeutic use of hematopoietic growth factors G-CSF and GM-CSF had no effect on clearance of infection. In contrast, treatment with Sendai virus—specific polysera or a monoclonal antibody limited viral spread into the lungs and accelerated clearance. Overall, noninvasive bioluminescence was shown to be a useful tool to study respiratory viral progression, revealing roles for NK and T cells, but not neutrophils, in Sendai virus clearance after treatment with dexamethasone and cyclophosphamide. Virus-specific antibodies appear to have therapeutic potential. PMID:27589232

Mild Wolf-Hirschhorn phenotype and partial GH deficiency in a patient with a 4p terminal deletion.

PubMed

Titomanlio, L; Romano, A; Conti, A; Genesio, R; Salerno, M; De Brasi, D; Nitsch, L; Del Giudice, E

2004-06-01

Wolf-Hirschhorn syndrome (WHS) is caused by a variably-sized deletion of chromosome 4 involving band 4p16 whose typical craniofacial features are "Greek warrior helmet appearance" of the nose, microcephaly, and prominent glabella. Almost all patients show mental retardation and pre- and post-natal growth delay. Patient was born at term, after a pregnancy characterized by intra-uterine growth retardation (IUGR). Delivery was uneventful. Developmental delay was evident since the first months of life. At 2 years, he developed generalized tonic-clonic seizures. Because of short stature, low growth velocity and delayed bone age, at 4 years he underwent growth hormone (GH) evaluation. Peak GH after two provocative tests revealed a partial GH deficiency. Clinical observation at 7 years disclosed a distinctive facial appearance, with microcephaly, prominent eyes, and beaked nose. Brain MRI showed left temporal mesial sclerosis. GTG banded karyotype was normal. Because of mental retardation, subtelomeric fluorescence in situ hybridization (FISH) analysis was performed, disclosing a relatively large deletion involving 4p16.2 --> pter (about 4.5 Mb), in the proband, not present in the parents. The smallest deletion detected in a WHS patient thus far includes two candidate genes, WHSC1 and WHSC2. Interestingly, that patient did not show shortness of stature, and that could be due to the haploinsufficiency of other genes localized in the flanking regions. Contribution of GH alterations and possible GH therapy should be further considered in WHS patients. Copyright 2004 Wiley-Liss, Inc.

Advances in Tissue Engineering Techniques for Articular Cartilage Repair

PubMed Central

Haleem, AM; Chu, CR

2010-01-01

The limited repair potential of human articular cartilage contributes to development of debilitating osteoarthritis and remains a great clinical challenge. This has led to evolution of cartilage treatment strategies from palliative to either reconstructive or reparative methods in an attempt to delay or “bridge the gap” to joint replacement. Further development of tissue engineering-based cartilage repair methods have been pursued to provide a more functional biological tissue. Currently, tissue engineering of articular cartilage has three cornerstones; a cell population capable of proliferation and differentiation into mature chondrocytes, a scaffold that can host these cells, provide a suitable environment for cellular functioning and serve as a sustained-release delivery vehicle of chondrogenic growth factors and thirdly, signaling molecules and growth factors that stimulate the cellular response and the production of a hyaline extracellular matrix (ECM). The aim of this review is to summarize advances in each of these three fields of tissue engineering with specific relevance to surgical techniques and technical notes. PMID:29430164

MSW Variable Time-Delay Techniques.

DTIC Science & Technology

1982-07-01

21 I, 5. RITAXIAL GEOWTH O COG FILKS G0 film growth by lpe was Investigated as a possible nouagnetic, dielectric spacer sediun between two YG fls...using two yttrium iron garnet films sandwiching simple single finger transducers. Difficulties In exciting the symetric forward volume mode are explained...direction. Measurements of time delay versus frequency are presented for epitaxially grown Yttrium Iron Garnet (YIG) films . Finally, transducer coupling

Source-sink regulation of cotyledonary reserve mobilization during cashew (Anacardium occidentale) seedling establishment under NaCl salinity.

PubMed

Voigt, Eduardo Luiz; Almeida, Tânia Dias; Chagas, Roberta Magalhães; Ponte, Luiz Ferreira Aguiar; Viégas, Ricardo Almeida; Silveira, Joaquim Albenísio Gomes

2009-01-01

Seedling establishment is a critical process to crop productivity, especially under saline conditions. This work was carried out to investigate the hypothesis that reserve mobilization is coordinated with salt-induced inhibition of seedling growth due to changes in source-sink relations. To test this hypothesis, cashew nuts (Anacardium occidentale) were sown in vermiculite irrigated daily with distilled water (control) or 50mM NaCl and they were evaluated at discrete developmental stages from the seed germination until the whole seedling establishment. The salt treatment coordinately delayed the seedling growth and the cotyledonary reserve mobilization. However, these effects were more pronounced at late seedling establishment than in earlier stages. The storage protein mobilization was affected by salt stress before the lipid and starch breakdown. The globulin fraction represented the most important storage proteins of cashew cotyledons, and its mobilization was markedly delayed by NaCl along the seedling establishment. Free amino acids were mostly retained in the cotyledons of salt-treated seedlings when the mobilization of storage proteins, lipids and starch was strongly delayed. Proline was not considerably accumulated in the cotyledons of cashew seedlings as a response to NaCl salinity. According to these results it is noteworthy that the salt-induced inhibition of seedling growth is narrowly coordinated with the delay of reserve mobilization and the accumulation of hydrolysis products in cotyledons. Also, it was evidenced that free amino acids, especially those related to nitrogen transport, are potential signals involved in the regulation of storage protein hydrolysis during cashew seedling establishment under NaCl salinity.

Chronic unilateral ureteral obstruction in the neonatal mouse delays maturation of both kidneys and leads to late formation of atubular glomeruli

PubMed Central

Forbes, Michael S.; Thornhill, Barbara A.; Galarreta, Carolina I.; Minor, Jordan J.; Gordon, Katherine A.

2013-01-01

Unilateral ureteral obstruction (UUO) in the adult mouse is the most widely used model of progressive renal disease: the proximal tubule is the nephron segment most severely affected and atubular glomeruli are formed after only 7 days of UUO. To determine the proximal nephron response to UUO in the maturing kidney, neonatal mice were examined 7 to 28 days following complete UUO under general anesthesia. Proximal tubular mass and maturation were determined by staining with Lotus tetragolonobus lectin. Superoxide was localized by nitroblue tetrazolium and collagen by Sirius red. Cell proliferation, cell death, PAX-2, megalin, α-smooth muscle actin (α-SMA), renin, and fibronectin were identified by immunohistochemistry. During the first 14 days of ipsilateral UUO, despite oxidative stress (4-hydroxynonenal staining), glomerulotubular continuity was maintained and mitochondrial superoxide production persisted. However, from 14 to 28 days, papillary growth was impaired and proximal tubules collapsed with increased apoptosis, autophagy, mitochondrial loss, and formation of atubular glomeruli. Fibronectin, α-SMA, and collagen increased in the obstructed kidney. Oxidative stress was present also in the contralateral kidney: renin was decreased, glomerulotubular maturation and papillary growth were delayed, followed by increased cortical and medullary growth. We conclude that neonatal UUO initially delays renal maturation and results in oxidative stress in both kidneys. In contrast to the adult, proximal tubular injury in the neonatal obstructed kidney is delayed at 14 days, followed only later by the formation of atubular glomeruli. Antioxidant therapies directed at proximal tubular mitochondria during early renal maturation may slow progression of congenital obstructive nephropathy. PMID:24107422

Assessment of sella turcica area and skeletal maturation patterns of children with unilateral cleft lip and palate.

PubMed

Cesur, E; Altug, A T; Toygar-Memikoglu, U; Gumru-Celikel, D; Tagrikulu, B; Erbay, E

2018-05-01

The aim of this case-control study was to assess sella turcica area and skeletal maturity in children with unilateral cleft lip and palate (UCLP) and compare with those of non-cleft children. A total of 85 UCLP patients aged 7.5-17.08 years (Group 1: age 7-11 years, Group 2: age 11-14 years and Group 3: age 14-18 years) were compared with 85 control subjects without clefts who were divided into similar age groups. Hand-wrist radiographs and cervical vertebra maturation stages (CVMS) were used to evaluate growth. Lateral cephalograms were traced, and reference points of sella were determined. Sella turcica area was measured using a digital planimeter. Comparison of overall growth on hand-wrist radiographs revealed no significant difference between cleft and non-cleft subjects. However, according to the chronological age groups, Group 1-UCLP showed statistically significant delay in skeletal maturation when compared with the age-matched control subjects (P = .05). This difference was due to the delay among male subjects (P = .05). As for CVMS, more significant maturation delay was observed in Group 1-UCLP (P = .001) and was attributable to both male and female subjects (P = .05). Comparison of sella turcica area showed no significant difference between UCLP patients and controls. Although children with CLP showed significant delay in growth when they are younger compared with the non-cleft children, sella turcica area measurements were similar for individuals in both groups. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

ZRBA1, a Mixed EGFR/DNA Targeting Molecule, Potentiates Radiation Response Through Delayed DNA Damage Repair Process in a Triple Negative Breast Cancer Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heravi, Mitra; Department of Radiation Oncology, McGill University, Montreal; Segal Cancer Center, Jewish General Hospital, Montreal

2015-06-01

Purpose: ZRBA1 is a combi-molecule designed to induce DNA alkylating lesions and to block epidermal growth factor receptor (EGFR) TK domain. Inasmuch as ZRBA1 downregulates the EGFR TK-mediated antisurvival signaling and induces DNA damage, we postulated that it might be a radiosensitizer. The aim of this study was to further investigate the potentiating effect of ZRBA1 in combination with radiation and to elucidate the possible mechanisms of interaction between these 2 treatment modalities. Methods and Materials: The triple negative human breast MDA-MB-468 cancer cell line and mouse mammary cancer 4T1 cell line were used in this study. Clonogenic assay, Westernmore » blot analysis, and DNA damage analysis were performed at multiple time points after treatment. To confirm our in vitro findings, in vivo tumor growth delay assay was performed. Results: Our results show that a combination of ZRBA1 and radiation increases the radiation sensitivity of both cell lines significantly with a dose enhancement factor of 1.56, induces significant numbers of DNA strand breaks, prolongs higher DNA damage up to 24 hours after treatment, and significantly increases tumor growth delay in a syngeneic mouse model. Conclusions: Our data suggest that the higher efficacy of this combination could be partially due to increased DNA damage and delayed DNA repair process and to the inhibition of EGFR. The encouraging results of this combination demonstrated a significant improvement in treatment efficiency and therefore could be applicable in early clinical trial settings.« less

Speech-Language Evaluation and Rehabilitation Treatment in Floating-Harbor Syndrome: A Case Study

ERIC Educational Resources Information Center

Angelillo, Nicola; Di Costanzo, Brigida; Barillari, Umberto

2010-01-01

Floating-Harbor syndrome is a rare congenital disorder characterized by specific facial features, short stature associated with significantly delayed bone age and language impairment. Although language delay is a cardinal manifestation of this syndrome, few reports describe the specific language difficulties of these patients, particularly the…

Growth curve for Propionibacterium acnes.

PubMed

Hall, G S; Pratt-Rippin, K; Meisler, D M; Washington, J A; Roussel, T J; Miller, D

1994-06-01

We established growth curves for Propionibacterium acnes isolates recovered from eyes with chronic postoperative endophthalmitis. The growth curve plotted the average of the duplicate bacterial concentration against time. The generation time for P. acnes calculated from the growth curves was approximately 5.1 hours. The growth of P. acnes is slower than other anaerobic bacteria. This may account for its delayed appearance in culture of ocular specimens. It may also explain treatment failure if the concentration of an antibiotic injected into the vitreous does not remain at an effective level during the critical replicative phase of the organism.

Tumour volume response, initial cell kill and cellular repopulation in B16 melanoma treated with cyclophosphamide and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea.

PubMed Central

Stephens, T. C.; Peacock, J. H.

1977-01-01

The relationship between tumour volume response and cell kill in B16 melanoma following treatment in vivo with cyclophosphamide (CY) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) was investigated. Tumour volume response, expressed as growth delay, was estimated from measurements of tumour dimensions. Depression of in vitro colony-forming ability of cells from treated tumours was used as the measure of tumour cell kill. The relationship between these parameters was clearly different for the two agents studied. CY produced more growth delay (7.5 days) per decade of tumour cell kill than CCNU (2 to 3.5 days). The possibility that this was due to a technical artefact was rejected in favour of an alternative explanation that different rates of cellular repopulation in tumours treated with CY and CCNU might be responsible. Cellular repopulation was measured directly, by performing cell-survival assays at various times after treatment with doses of CY and CCNU which produced about 3 decades of cell kill. The rate of repopulation by clonogenic cells was much slower after treatment with CY than with CCNU, and this appears to account for the longer duration of the growth delay obtained with CY. PMID:921888

Irradiation combined with SU5416: Microvascular changes and growth delay in a human xenograft glioblastoma tumor line

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schuuring, Janneke; Department of Neurology, Groene Hart Hospital, Gouda; Bussink, Johan

Purpose: The combination of irradiation and the antiangiogenic compound SU5416 was tested and compared with irradiation alone in a human glioblastoma tumor line xenografted in nude mice. The aim of this study was to monitor microenvironmental changes and growth delay. Methods and materials: A human glioblastoma xenograft tumor line was implanted in nude mice. Irradiations consisted of 10 Gy or 20 Gy with and without SU5416. Several microenvironmental parameters (tumor cell hypoxia, tumor blood perfusion, vascular volume, and microvascular density) were analyzed after imunohistochemical staining. Tumor growth delay was monitored for up to 200 days after treatment. Results: SU5416, whenmore » combined with irradiation, has an additive effect over treatment with irradiation alone. Analysis of the tumor microenvironment showed a decreased vascular density during treatment with SU5416. In tumors regrowing after reaching only a partial remission, vascular characteristics normalized shortly after cessation of SU5416. However, in tumors regrowing after reaching a complete remission, permanent microenvironmental changes and an increase of tumor necrosis with a subsequent slower tumor regrowth was found. Conclusions: Permanent vascular changes were seen after combined treatment resulting in complete remission. Antiangiogenic treatment with SU5416 when combined with irradiation has an additive effect over treatment with irradiation or antiangiogenic treatment alone.« less

Gender and socio-cultural determinants of delay to diagnosis of TB in Bangladesh, India and Malawi.

PubMed

Gosoniu, G D; Ganapathy, S; Kemp, J; Auer, C; Somma, D; Karim, F; Weiss, M G

2008-07-01

Tuberculosis (TB) control programmes in Bangladesh, India and Malawi. To compare the interval from symptom onset to diagnosis of TB for men and women, and to assess socio-cultural and gender-related features of illness explaining diagnostic delay. Semi-structured Explanatory Model Interview Catalogue (EMIC) interviews were administered to 100 or more patients at each site, assessing categories of distress, perceived causes and help seeking. Based on time from initial symptoms to diagnosis of TB, patients were classified with problem delay (>90 days), timely diagnosis (< or =30 days) or moderate delay. EMIC interview data were analysed to explain problem delay. The median interval from symptom onset to diagnosis was longest in India and shortest in Malawi. With adjustment for confounding, female sex (Bangladesh), and status of married woman (India) and housewife (Malawi) were associated with problem delay. Prominent non-specific symptoms--chest pain (Bangladesh) and breathlessness (Malawi)--were also significant. Cough in India, widely associated with TB, was associated with timely diagnosis. Sanitation as a perceived cause linked to poor urban conditions was associated with delayed diagnosis in India. Specific prior help seeking with circuitous referral patterns was identified. The study identified gender- and illness-related features of diagnostic delay. Further research distinguishing patient and provider delay is needed.

Tumor regression induced by intratumor therapy with a disabled infectious single cycle (DISC) herpes simplex virus (HSV) vector, DISC/HSV/murine granulocyte-macrophage colony-stimulating factor, correlates with antigen-specific adaptive immunity.

PubMed

Ali, Selman A; Lynam, June; McLean, Cornelia S; Entwisle, Claire; Loudon, Peter; Rojas, José M; McArdle, Stephanie E B; Li, Geng; Mian, Shahid; Rees, Robert C

2002-04-01

Direct intratumor injection of a disabled infectious single cycle HSV-2 virus encoding the murine GM-CSF gene (DISC/mGM-CSF) into established murine colon carcinoma CT26 tumors induced a significant delay in tumor growth and complete tumor regression in up to 70% of animals. Pre-existing immunity to HSV did not reduce the therapeutic efficacy of DISC/mGM-CSF, and, when administered in combination with syngeneic dendritic cells, further decreased tumor growth and increased the incidence of complete tumor regression. Direct intratumor injection of DISC/mGM-CSF also inhibited the growth of CT26 tumor cells implanted on the contralateral flank or seeded into the lungs following i.v. injection of tumor cells (experimental lung metastasis). Proliferation of splenocytes in response to Con A was impaired in progressor and tumor-bearer, but not regressor, mice. A potent tumor-specific CTL response was generated from splenocytes of all mice with regressing, but not progressing tumors following in vitro peptide stimulation; this response was specific for the gp70 AH-1 peptide SPSYVYHQF and correlated with IFN-gamma, but not IL-4 cytokine production. Depletion of CD8(+) T cells from regressor splenocytes before in vitro stimulation with the relevant peptide abolished their cytolytic activity, while depletion of CD4(+) T cells only partially inhibited CTL generation. Tumor regression induced by DISC/mGM-CSF virus immunotherapy provides a unique model for evaluating the immune mechanism(s) involved in tumor rejection, upon which tumor immunotherapy regimes may be based.

Characterization of In Vivo Resistance to Osimertinib and JNJ-61186372, an EGFR/Met Bispecific Antibody, Reveals Unique and Consensus Mechanisms of Resistance.

PubMed

Emdal, Kristina B; Dittmann, Antje; Reddy, Raven J; Lescarbeau, Rebecca S; Moores, Sheri L; Laquerre, Sylvie; White, Forest M

2017-11-01

Approximately 10% of non-small cell lung cancer (NSCLC) patients in the United States and 40% of NSCLC patients in Asia have activating epidermal growth factor receptor (EGFR) mutations and are eligible to receive targeted anti-EGFR therapy. Despite an extension of life expectancy associated with this treatment, resistance to EGFR tyrosine kinase inhibitors and anti-EGFR antibodies is almost inevitable. To identify additional signaling routes that can be cotargeted to overcome resistance, we quantified tumor-specific molecular changes that govern resistant cancer cell growth and survival. Mass spectrometry-based quantitative proteomics was used to profile in vivo signaling changes in 41 therapy-resistant tumors from four xenograft NSCLC models. We identified unique and tumor-specific tyrosine phosphorylation rewiring in tumors resistant to treatment with the irreversible third-generation EGFR-inhibitor, osimertinib, or the novel dual-targeting EGFR/Met antibody, JNJ-61186372. Tumor-specific increases in tyrosine-phosphorylated peptides from EGFR family members, Shc1 and Gab1 or Src family kinase (SFK) substrates were observed, underscoring a differential ability of tumors to uniquely escape EGFR inhibition. Although most resistant tumors within each treatment group displayed a marked inhibition of EGFR as well as SFK signaling, the combination of EGFR inhibition (osimertinib) and SFK inhibition (saracatinib or dasatinib) led to further decrease in cell growth in vitro This result suggests that residual SFK signaling mediates therapeutic resistance and that elimination of this signal through combination therapy may delay onset of resistance. Overall, analysis of individual resistant tumors captured unique in vivo signaling rewiring that would have been masked by analysis of in vitro cell population averages. Mol Cancer Ther; 16(11); 2572-85. ©2017 AACR . ©2017 American Association for Cancer Research.

Size Matters: Individual Variation in Ectotherm Growth and Asymptotic Size

PubMed Central

King, Richard B.

2016-01-01

Body size, and, by extension, growth has impacts on physiology, survival, attainment of sexual maturity, fecundity, generation time, and population dynamics, especially in ectotherm animals that often exhibit extensive growth following attainment of sexual maturity. Frequently, growth is analyzed at the population level, providing useful population mean growth parameters but ignoring individual variation that is also of ecological and evolutionary significance. Our long-term study of Lake Erie Watersnakes, Nerodia sipedon insularum, provides data sufficient for a detailed analysis of population and individual growth. We describe population mean growth separately for males and females based on size of known age individuals (847 captures of 769 males, 748 captures of 684 females) and annual growth increments of individuals of unknown age (1,152 males, 730 females). We characterize individual variation in asymptotic size based on repeated measurements of 69 males and 71 females that were each captured in five to nine different years. The most striking result of our analyses is that asymptotic size varies dramatically among individuals, ranging from 631–820 mm snout-vent length in males and from 835–1125 mm in females. Because female fecundity increases with increasing body size, we explore the impact of individual variation in asymptotic size on lifetime reproductive success using a range of realistic estimates of annual survival. When all females commence reproduction at the same age, lifetime reproductive success is greatest for females with greater asymptotic size regardless of annual survival. But when reproduction is delayed in females with greater asymptotic size, lifetime reproductive success is greatest for females with lower asymptotic size when annual survival is low. Possible causes of individual variation in asymptotic size, including individual- and cohort-specific variation in size at birth and early growth, warrant further investigation. PMID:26730712

Size Matters: Individual Variation in Ectotherm Growth and Asymptotic Size.

PubMed

King, Richard B; Stanford, Kristin M; Jones, Peter C; Bekker, Kent

2016-01-01

Body size, and, by extension, growth has impacts on physiology, survival, attainment of sexual maturity, fecundity, generation time, and population dynamics, especially in ectotherm animals that often exhibit extensive growth following attainment of sexual maturity. Frequently, growth is analyzed at the population level, providing useful population mean growth parameters but ignoring individual variation that is also of ecological and evolutionary significance. Our long-term study of Lake Erie Watersnakes, Nerodia sipedon insularum, provides data sufficient for a detailed analysis of population and individual growth. We describe population mean growth separately for males and females based on size of known age individuals (847 captures of 769 males, 748 captures of 684 females) and annual growth increments of individuals of unknown age (1,152 males, 730 females). We characterize individual variation in asymptotic size based on repeated measurements of 69 males and 71 females that were each captured in five to nine different years. The most striking result of our analyses is that asymptotic size varies dramatically among individuals, ranging from 631-820 mm snout-vent length in males and from 835-1125 mm in females. Because female fecundity increases with increasing body size, we explore the impact of individual variation in asymptotic size on lifetime reproductive success using a range of realistic estimates of annual survival. When all females commence reproduction at the same age, lifetime reproductive success is greatest for females with greater asymptotic size regardless of annual survival. But when reproduction is delayed in females with greater asymptotic size, lifetime reproductive success is greatest for females with lower asymptotic size when annual survival is low. Possible causes of individual variation in asymptotic size, including individual- and cohort-specific variation in size at birth and early growth, warrant further investigation.

Antifungal Activity of Phenyllactic Acid against Molds Isolated from Bakery Products

PubMed Central

Lavermicocca, Paola; Valerio, Francesca; Visconti, Angelo

2003-01-01

Phenyllactic acid (PLA) has recently been found in cultures of Lactobacillus plantarum that show antifungal activity in sourdough breads. The fungicidal activity of PLA and growth inhibition by PLA were evaluated by using a microdilution test and 23 fungal strains belonging to 14 species of Aspergillus, Penicillium, and Fusarium that were isolated from bakery products, flours, or cereals. Less than 7.5 mg of PLA ml−1 was required to obtain 90% growth inhibition for all strains, while fungicidal activity against 19 strains was shown by PLA at levels of ≤10 mg ml−1. Levels of growth inhibition of 50 to 92.4% were observed for all fungal strains after incubation for 3 days in the presence of 7.5 mg of PLA ml−1 in buffered medium at pH 4, which is a condition more similar to those in real food systems. Under these experimental conditions PLA caused an unpredictable delaying effect that was more than 2 days long for 12 strains, including some mycotoxigenic strains of Penicillium verrucosum and Penicillium citrinum and a strain of Penicillium roqueforti (the most widespread contaminant of bakery products); a growth delay of about 2 days was observed for seven other strains. The effect of pH on the inhibitory activity of PLA and the combined effects of the major organic acids produced by lactic acid bacteria isolated from sourdough bread (PLA, lactic acid, and acetic acid) were also investigated. The ability of PLA to act as a fungicide and delay the growth of a variety of fungal contaminants provides new perspectives for possibly using this natural antimicrobial compound to control fungal contaminants and extend the shelf lives of foods and/or feedstuffs. PMID:12514051

Active surveillance for small renal masses diagnosed in elderly or comorbid patients: looking for the best treatment strategy.

PubMed

Brunocilla, E; Borghesi, M; Schiavina, R; Palmieri, F; Pernetti, R; Monti, C; Martorana, G

2014-01-01

Aim of this study is to provide our results after long-term active surveillance (AS) protocol for small renal masses (SRMs), and to report the outcomes of patients who remained in AS compared to those who underwent delayed surgical intervention. We retrospectively reviewed our database of 58 patients diagnosed with 60 contrast enhancing SRMs suspicious for renal cell carcinoma (RCC). All patients had clinical and radiological follow-up every 6 months. We evaluated the differences between patients who remained on AS and those who underwent surgical delayed intervention. The mean age was 75 years, the mean follow-up was 88.5 months. The median initial tumor size at presentation was 2.6cm, and the median estimated tumor volume was 8.7cm(3). The median linear growth rate of the cohort was 0.7cm/year, and the median volumetric growth rate was 8.8 cm(3)/year. Death for metastatic disease occurred in 2 patients (3.4%). No correlation was found between initial tumor size and size growth rate. The mean linear and volumetric growth rates of the group of patients who underwent surgery was higher than in those who remained on surveillance (1.9 vs. 0.4cm/year and 16.1 vs. 4.6 cm(3)/year, respectively; P<.001). Most of SRMs demonstrate to have an indolent course and low metastatic potential. Malignant disease could have faster linear and volumetric growth rates, thus suggesting the need for a delayed surgical intervention. In properly selected patients with low life-expectancy, AS could be a reasonable option in the management of SRMs. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

Brain injury and altered brain growth in preterm infants: predictors and prognosis.

PubMed

Kidokoro, Hiroyuki; Anderson, Peter J; Doyle, Lex W; Woodward, Lianne J; Neil, Jeffrey J; Inder, Terrie E

2014-08-01

To define the nature and frequency of brain injury and brain growth impairment in very preterm (VPT) infants by using MRI at term-equivalent age and to relate these findings to perinatal risk factors and 2-year neurodevelopmental outcomes. MRI scans at term-equivalent age from 3 VPT cohorts (n = 325) were reviewed. The severity of brain injury, including periventricular leukomalacia and intraventricular and cerebellar hemorrhage, was graded. Brain growth was assessed by using measures of biparietal width (BPW) and interhemispheric distance. Neurodevelopmental outcome at age 2 years was assessed across all cohorts (n = 297) by using the Bayley Scales of Infant Development, Second Edition (BSID-II) or Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), and evaluation for cerebral palsy. Of 325 infants, 107 (33%) had some grade of brain injury and 33 (10%) had severe injury. Severe brain injury was more common in infants with lower Apgar scores, necrotizing enterocolitis, inotropic support, and patent ductus arteriosus. Severe brain injury was associated with delayed cognitive and motor development and cerebral palsy. Decreased BPW was related to lower gestational age, inotropic support, patent ductus arteriosus, necrotizing enterocolitis, prolonged parenteral nutrition, and oxygen at 36 weeks and was associated with delayed cognitive development. In contrast, increased interhemispheric distance was related to male gender, dexamethasone use, and severe brain injury. It was also associated with reduced cognitive development, independent of BPW. At term-equivalent age, VPT infants showed both brain injury and impaired brain growth on MRI. Severe brain injury and impaired brain growth patterns were independently associated with perinatal risk factors and delayed cognitive development. Copyright © 2014 by the American Academy of Pediatrics.

Power-law Growth and Punctuated Equilibrium Dynamics in Water Resources Systems

NASA Astrophysics Data System (ADS)

Parolari, A.; Katul, G. G.; Porporato, A. M.

2015-12-01

The global rise in population-driven water scarcity and recent appreciation of strong dynamic coupling between human and natural systems has called for new approaches to predict the future sustainability of regional and global water resources systems. The dynamics of coupled human-water systems are driven by a complex set of social, environmental, and technological factors. Present projections of water resources systems range from a finite carrying capacity regulated by accessible freshwater, or `peak renewable water,' to punctuated evolution with new supplied and improved efficiency gained from technological and social innovation. However, these projections have yet to be quantified from observations or in a comprehensive theoretical framework. Using data on global water withdrawals and storage capacity of regional water supply systems, non-trivial dynamics are identified in water resources systems development over time, including power-law growth and punctuated equilibria. Two models are introduced to explain this behavior: (1) a delay differential equation and (2) a power-law with log-periodic oscillations, both of which rely on past conditions (or system memory) to describe the present rate of growth in the system. In addition, extension of the first model demonstrates how system delays and punctuated equilibria can emerge from coupling between human population growth and associated resource demands. Lastly, anecdotal evidence is used to demonstrate the likelihood of power-law growth in global water use from the agricultural revolution 3000 BC to the present. In a practical sense, the presence of these patterns in models with delayed oscillations suggests that current decision-making related to water resources development results from the historical accumulation of resource use decisions, technological and social changes, and their consequences.

Fibrin glue inhibits migration of ocular surface epithelial cells

PubMed Central

Yeung, A M; Faraj, L A; McIntosh, O D; Dhillon, V K; Dua, H S

2016-01-01

Purpose Fibrin glue has been used successfully in numerous ophthalmic surgical procedures. Recently, fibrin glue has been used in limbal stem cell transplantation to reduce both operative time and to negate the need for sutures. The aim of this study was to determine the effects of fibrin glue on epithelial cell migration in vitro. Methods Corneoscleral rims were split to retain the epithelial layer, Bowman's layer, and anterior stroma. Rims were cut into eight equal-sized pieces and were placed directly on culture plates or affixed with fibrin glue. Rims were maintained in culture for 25 days and epithelial cell growth was monitored. Cells were photographed to measure area or growth and immunofluorescence staining of explants for fibrin was performed. Results Explants that were glued demonstrated significantly delayed epithelial cell growth and migration as compared with explants without glue. By day 16, all fibrin glue had dissolved and coincided with onset of cell growth from glued explants. Cell growth commenced between days 3 and 4 for control explants without glue and around days 14–16 for explants with fibrin glue. Conclusions Fibrin glue delays epithelial cell migration by acting as a physical barrier and can potentially interfere with explant-derived limbal epithelial cell migration on to the corneal surface. We propose that glue should be used to attach the conjunctival frill of the limbal explant but care should be taken to ensure that the glue does not wrap around the explant if used to secure the explant as well. Strategic use of glue, to attach the recessed conjunctiva, can be advantageous in delaying conjunctival cell migration and reducing the need for sequential sector conjunctival epitheliectomy. PMID:27367746

INTERACTIONS BETWEEN SOIL TEMPERATURE AND PLANT GROWTH STAGE ON NITROGEN UPTAKE AND AMINO ACID CONTENT OF APPLE NURSERY STOCK DURING EARLY SPRING GROWTH

EPA Science Inventory

In the spring, nitrogen (N) uptake by apple roots is known to be delayed about three weeks after bud break. We used one-year-old 'Fuji' (Malus domestica Borkh) on M26 bare-root apple trees to determine whether timing of N uptake in the spring is dependant solely on the growth st...

Piloted simulator study of allowable time delay in pitch flight control system of a transport airplane with negative static stability

NASA Technical Reports Server (NTRS)

Grantham, William D.; Smith, Paul M.; Person, Lee H., Jr.; Meyer, Robert T.; Tingas, Stephen A.

1987-01-01

A piloted simulation study was conducted to determine the permissible time delay in the flight control system of a 10-percent statically unstable transport airplane during cruise flight conditions. The math model used for the simulation was a derivative Lockheed L-1011 wide-body jet transport. Data were collected and analyzed from a total of 137 cruising flights in both calm- and turbulent-air conditions. Results of this piloted simulation study verify previous findings that show present military specifications for allowable control-system time delay may be too stringent when applied to transport-size airplanes. Also, the degree of handling-qualities degradation due to time delay is shown to be strongly dependent on the source of the time delay in an advanced flight control system. Maximum allowable time delay for each source of time delay in the control system, in addition to a less stringent overall maximum level of time delay, should be considered for large aircraft. Preliminary results also suggest that adverse effects of control-system time delay may be at least partially offset by variations in control gearing. It is recommended that the data base include different airplane baselines, control systems, and piloting tasks with many pilots participating, so that a reasonable set of limits for control-system time delay can be established to replace the military specification limits currently being used.

Wnt-mediated reciprocal regulation between cartilage and bone development during endochondral ossification.

PubMed

Lu, Cheng; Wan, Yong; Cao, Jingjing; Zhu, Xuming; Yu, Jian; Zhou, Rujiang; Yao, Yiyun; Zhang, Lingling; Zhao, Haixia; Li, Hanjun; Zhao, Jianzhi; He, Lin; Ma, Gang; Yang, Xiao; Yao, Zhengju; Guo, Xizhi

2013-04-01

The role of Wnt signaling is extensively studied in skeletal development and postnatal bone remodeling, mostly based on the genetic approaches of β-catenin manipulation. However, given their independent function, a requirement for β-catenin is not the same as that for Wnt. Here, we investigated the effect of Wnt proteins in both tissues through generating cartilage- or bone-specific Wls null mice, respectively. Depletion of Wls by Col2-Cre, which would block Wnt secretion in the chondrocytes and perichondrium, delayed chondrocyte hypertrophy in the growth plate and impaired perichondrial osteogenesis. Loss of Wls in chondrocytes also disturbed the proliferating chondrocyte morphology and division orientation, which was similar to the defect observed in Wnt5a null mice. On the other hand, inactivation of Wls in osteoblasts by Col1-Cre resulted in a shorter hypertrophic zone and an increase of TRAP positive cell number in the chondro-osseous junction of growth plate, coupled with a decrease in bone mass. Taken together, our studies reveal that Wnt proteins not only modulate differentiation and cellular communication within populations of chondrocytes, but also mediate the cross regulation between the chondrocytes and osteoblasts in growth plate. Copyright © 2012 Elsevier Inc. All rights reserved.

Latent class analysis of early developmental trajectory in baby siblings of children with autism.

PubMed

Landa, Rebecca J; Gross, Alden L; Stuart, Elizabeth A; Bauman, Margaret

2012-09-01

Siblings of children with autism (sibs-A) are at increased genetic risk for autism spectrum disorders (ASD) and milder impairments. To elucidate diversity and contour of early developmental trajectories exhibited by sibs-A, regardless of diagnostic classification, latent class modeling was used. Sibs-A (N = 204) were assessed with the Mullen Scales of Early Learning from age 6 to 36 months. Mullen T scores served as dependent variables. Outcome classifications at age 36 months included: ASD (N = 52); non-ASD social/communication delay (broader autism phenotype; BAP; N = 31); and unaffected (N = 121). Child-specific patterns of performance were studied using latent class growth analysis. Latent class membership was then related to diagnostic outcome through estimation of within-class proportions of children assigned to each diagnostic classification. A 4-class model was favored. Class 1 represented accelerated development and consisted of 25.7% of the sample, primarily unaffected children. Class 2 (40.0% of the sample), was characterized by normative development with above-average nonverbal cognitive outcome. Class 3 (22.3% of the sample) was characterized by receptive language, and gross and fine motor delay. Class 4 (12.0% of the sample), was characterized by widespread delayed skill acquisition, reflected by declining trajectories. Children with an outcome diagnosis of ASD were spread across Classes 2, 3, and 4. Results support a category of ASD that involves slowing in early non-social development. Receptive language and motor development is vulnerable to early delay in sibs-A with and without ASD outcomes. Non-ASD sibs-A are largely distributed across classes depicting average or accelerated development. Developmental trajectories of motor, language, and cognition appear independent of communication and social delays in non-ASD sibs-A. © 2012 The Authors. Journal of Child Psychology and Psychiatry © 2012 Association for Child and Adolescent Mental Health.

Performance of South African children on the Communication and Symbolic Behavior Scales-Developmental Profile (CSBS DP).

PubMed

Chambers, Nola; Stronach, Sheri T; Wetherby, Amy M

2016-05-01

Substantial development in social communication skills occurs in the first two years of life. Growth should be evident in sharing emotion and eye gaze; rate of communication, communicating for a variety of functions; using gestures, sounds and words; understanding language, and using functional and pretend actions with objects in play. A delay in these early social communication skills may be the first sign of a developmental delay in young children in nearly all categories of disabilities-including specific language impairment, autism spectrum disorder, HIV/AIDS, lack of environmental stimulation or institutionalization, and global developmental delays-and early detection of these delays is critical for enrolment in appropriate early intervention services. No standardized tests of early social communication skills exist for very young children in South Africa (SA). An existing evaluation tool that has the potential to be culturally fair for children from cultural backgrounds different to the standardization group is the Communication and Symbolic Behaviour Scales-Developmental Profile (CSBS DP). This study aimed to document the performance of a group of English-speaking SA children ranging in age from 12 to 24 months on the CSBS DP and to compare this performance with the original standardization sample. Sixty-seven English-speaking SA children from a range of cultural and linguistic backgrounds were assessed on the CSBS DP Behaviour Sample. Group scores were compared with the original standardization sample using inferential statistics. The results provide preliminary support for the suitability and validity of the face-to-face Behaviour Sample as a measure of early social communication skills in this sample of English-speaking SA children from a range of cultural groups between 12 and 24 months of age. While further research in the SA population is needed, these findings are a first step towards validating a culturally appropriate measure for early detection of social communication delays in a sample of SA toddlers. © 2015 Royal College of Speech and Language Therapists.

A clinical approach to developmental delay and intellectual disability.

PubMed

Vasudevan, Pradeep; Suri, Mohnish

2017-12-01

Global developmental delay and intellectual disability are phenotypically and genetically heterogeneous and a specific diagnosis is not reached in many cases. This paper outlines a systematic approach to global developmental delay and intellectual disability. © Royal College of Physicians 2017. All rights reserved.

The influence of prefire tree growth and crown condition on postfire mortality of sugar pine following prescribed fire in Sequoia National Park

USGS Publications Warehouse

Nesmith, Jonathan C. B.; Das, Adrian J.; O'Hara, Kevin L.; van Mantgem, Phillip J.

2015-01-01

Tree mortality is a vital component of forest management in the context of prescribed fires; however, few studies have examined the effect of prefire tree health on postfire mortality. This is especially relevant for sugar pine (Pinus lambertiana Douglas), a species experiencing population declines due to a suite of anthropogenic factors. Using data from an old-growth mixed-conifer forest in Sequoia National Park, we evaluated the effects of fire, tree size, prefire radial growth, and crown condition on postfire mortality. Models based only on tree size and measures of fire damage were compared with models that included tree size, fire damage, and prefire tree health (e.g., measures of prefire tree radial growth or crown condition). Immediately following the fire, the inclusion of different metrics of prefire tree health produced variable improvements over the models that included only tree size and measures of fire damage, as models that included measures of crown condition performed better than fire-only models, but models that included measures of prefire radial growth did not perform better. However, 5 years following the fire, sugar pine mortality was best predicted by models that included measures of both fire damage and prefire tree health, specifically, diameter at breast height (DBH, 1.37 m), crown scorch, 30-year mean growth, and the number of sharp declines in growth over a 30-year period. This suggests that factors that influence prefire tree health (e.g., drought, competition, pathogens, etc.) may partially determine postfire mortality, especially when accounting for delayed mortality following fire.

WE-G-BRE-07: Proton Therapy Enhanced by Tumor-Targeting Gold Nanoparticles: A Pilot in Vivo Experiment at The Proton Therapy Center at MD Anderson Cancer Center

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolfe, T; Grant, J; Wolfe, A

Purpose: Assess tumor-growth delay and survival in a mouse model of prostate cancer treated with tumor-targeting gold nanoparticles (AuNPs) and proton therapy. Methods: We first examined the accumulation of targeting nanoparticles within prostate tumors by imaging AuNPs with ultrasound-guided photoacoustics at 24h after the intravenous administration of goserelin-conjugated AuNPs (gAuNP) in three mice. Nanoparticles were also imaged at the cellular level with TEM in PC3 cells incubated with gAuNP for 24h. Pegylated AuNPs (pAuNP) were also imaged in vivo and in vitro for comparison. PC3 cells were then implanted subcutaneously in nude mice; 51mice with 8–10mm tumors were included. AuNPsmore » were injected intravenously at 0.2%w/w final gold concentration 24h before irradiation. A special jig was designed to facilitate tumor irradiation perpendicular to the proton beam. Proton energy was set to 180MeV, the radiation field was 18×18cm{sup 2}, and 9cm or 13.5cm thick solid-water compensators were used to position the tumors at either the beam entrance (BE) or the SOBP. Physical doses of 5Gy were delivered to all tumors on a patient beam line at MD Anderson's Proton Therapy Center. Results: The photoacoustic experiment reveled that our nanoparticles leak from the tumor-feeding vasculature and accumulate within the tumor volume over time. Additionally, TEM images showed gAuNP are internalized in cancer cells, accumulating within the cytoplasm, whereas pAuNP are not. Tumor-growth was delayed by 11 or 32days in mice receiving gAuNP irradiated at the BE or the SOBP, relative to proton radiation alone. Survival curves (ongoing experiment) reveal that gAuNPs improved survival by 36% or 74% for tumors irradiated at the BE or SOBP. Conclusion: These important, albeit preliminary, in vivo findings reveal nanoparticles to be potent sensitizers to proton therapy. Further, conjugation of AuNPs to tumor-specific antigens that promote enhanced cellular internalization improved both tumor-growth delay and survival of mice after proton therapy.« less

KinD is a checkpoint protein linking spore formation to extracellular-matrix production in Bacillus subtilis biofilms.

PubMed

Aguilar, Claudio; Vlamakis, Hera; Guzman, Alejandra; Losick, Richard; Kolter, Roberto

2010-05-18

Bacillus subtilis cells form multicellular biofilm communities in which spatiotemporal regulation of gene expression occurs, leading to differentiation of multiple coexisting cell types. These cell types include matrix-producing and sporulating cells. Extracellular matrix production and sporulation are linked in that a mutant unable to produce matrix is delayed for sporulation. Here, we show that the delay in sporulation is not due to a growth advantage of the matrix-deficient mutant under these conditions. Instead, we show that the link between matrix production and sporulation is through the Spo0A signaling pathway. Both processes are regulated by the phosphorylated form of the master transcriptional regulator Spo0A. When cells have low levels of phosphorylated Spo0A (Spo0A~P), matrix genes are expressed; however, at higher levels of Spo0A~P, sporulation commences. We have found that Spo0A~P levels are maintained at low levels in the matrix-deficient mutant, thereby delaying expression of sporulation-specific genes. This is due to the activity of one of the components of the Spo0A phosphotransfer network, KinD. A deletion of kinD suppresses the sporulation defect of matrix mutants, while its overproduction delays sporulation. Our data indicate that KinD displays a dual role as a phosphatase or a kinase and that its activity is linked to the presence of extracellular matrix in the biofilms. We propose a novel role for KinD in biofilms as a checkpoint protein that regulates the onset of sporulation by inhibiting the activity of Spo0A until matrix, or a component therein, is sensed.

KinD Is a Checkpoint Protein Linking Spore Formation to Extracellular-Matrix Production in Bacillus subtilis Biofilms

PubMed Central

Aguilar, Claudio; Vlamakis, Hera; Guzman, Alejandra; Losick, Richard; Kolter, Roberto

2010-01-01

ABSTRACT Bacillus subtilis cells form multicellular biofilm communities in which spatiotemporal regulation of gene expression occurs, leading to differentiation of multiple coexisting cell types. These cell types include matrix-producing and sporulating cells. Extracellular matrix production and sporulation are linked in that a mutant unable to produce matrix is delayed for sporulation. Here, we show that the delay in sporulation is not due to a growth advantage of the matrix-deficient mutant under these conditions. Instead, we show that the link between matrix production and sporulation is through the Spo0A signaling pathway. Both processes are regulated by the phosphorylated form of the master transcriptional regulator Spo0A. When cells have low levels of phosphorylated Spo0A (Spo0A~P), matrix genes are expressed; however, at higher levels of Spo0A~P, sporulation commences. We have found that Spo0A~P levels are maintained at low levels in the matrix-deficient mutant, thereby delaying expression of sporulation-specific genes. This is due to the activity of one of the components of the Spo0A phosphotransfer network, KinD. A deletion of kinD suppresses the sporulation defect of matrix mutants, while its overproduction delays sporulation. Our data indicate that KinD displays a dual role as a phosphatase or a kinase and that its activity is linked to the presence of extracellular matrix in the biofilms. We propose a novel role for KinD in biofilms as a checkpoint protein that regulates the onset of sporulation by inhibiting the activity of Spo0A until matrix, or a component therein, is sensed. PMID:20689749

Use of Fenbendazole-Containing Therapeutic Diets for Mice in Experimental Cancer Therapy Studies

PubMed Central

Duan, Qiwen; Liu, Yanfeng; Booth, Carmen J; Rockwell, Sara

2012-01-01

Pinworm infection (oxyuriasis) is a common problem in rodent colonies. Facility-wide prophylactic treatment of all mice with a diet containing therapeutic levels of fenbendazole for several weeks is often used to control pinworm outbreaks. We examined the effect of feeding a therapeutic diet containing 150 ppm fenbendazole on the growth of EMT6 mouse mammary tumors implanted into BALB/c Rw mice. Mice were randomized to receive either a fenbendazole-containing or control diet for 1 wk before tumor cells were injected intradermally in the flanks and throughout tumor growth. Tumor growth was monitored by serial measurements of tumor diameters from the time tumors became palpable until they reached 1000 mm3. The medicated diet did not alter tumor growth, invasion, or metastasis. When tumors reached volumes of approximately 100 mm3, some were irradiated locally with 10 Gy of X-rays. Irradiation significantly delayed tumor growth; fenbendazole did not alter the radiation-induced growth delay. However, cell culture studies showed that fenbendazole concentrations not far above those expected in the tissues of mice on this diet altered the growth of the tumor cells in culture. Recent data from other laboratories also have demonstrated effects of fenbendazole that could complicate experiments. Care should therefore be exercised in deciding whether chow containing fenbendazole should be administered to mouse colonies being used in cancer research. PMID:22776123

Use of fenbendazole-containing therapeutic diets for mice in experimental cancer therapy studies.

PubMed

Duan, Qiwen; Liu, Yanfeng; Booth, Carmen J; Rockwell, Sara

2012-03-01

Pinworm infection (oxyuriasis) is a common problem in rodent colonies. Facility-wide prophylactic treatment of all mice with a diet containing therapeutic levels of fenbendazole for several weeks is often used to control pinworm outbreaks. We examined the effect of feeding a therapeutic diet containing 150 ppm fenbendazole on the growth of EMT6 mouse mammary tumors implanted into BALB/c Rw mice. Mice were randomized to receive either a fenbendazole-containing or control diet for 1 wk before tumor cells were injected intradermally in the flanks and throughout tumor growth. Tumor growth was monitored by serial measurements of tumor diameters from the time tumors became palpable until they reached 1000 mm3. The medicated diet did not alter tumor growth, invasion, or metastasis. When tumors reached volumes of approximately 100 mm3, some were irradiated locally with 10 Gy of X-rays. Irradiation significantly delayed tumor growth; fenbendazole did not alter the radiation-induced growth delay. However, cell culture studies showed that fenbendazole concentrations not far above those expected in the tissues of mice on this diet altered the growth of the tumor cells in culture. Recent data from other laboratories also have demonstrated effects of fenbendazole that could complicate experiments. Care should therefore be exercised in deciding whether chow containing fenbendazole should be administered to mouse colonies being used in cancer research.

Consequences of Feeder Delays for the Success of A380 Operations

NASA Technical Reports Server (NTRS)

Ruehle, Jens; Goetsch, Bjoern; Koch, Benjamin

2006-01-01

Due to existing slot and infrastructure constraints at international hub-and-spoke airports, an increase in feeder traffic seems only possible if larger feeder aircraft are used. Using a case study of Lufthansa German Airlines at Frankfurt International Airport, three possible A380 routes (Beijing, Tokyo-Narita, Los Angeles) were examined to assess the extent to which delays of feeder traffic may impact the economic performance of very large aircraft. On the basis of today s delays and anticipated traffic growth in the future, we found that between 9.5% and 13.5% of connecting passengers are unable to transfer to their respective intercontinental flights. In addition, the results demonstrate that a further increase in delays can be detrimental to the profitable operation of very large aircraft, as demonstrated by two out of three simulated routes. We suggest options for airlines operating very large aircraft to counteract the negative impacts of feeder delays.

Steady states and outbreaks of two-phase nonlinear age-structured model of population dynamics with discrete time delay.

PubMed

Akimenko, Vitalii; Anguelov, Roumen

2017-12-01

In this paper we study the nonlinear age-structured model of a polycyclic two-phase population dynamics including delayed effect of population density growth on the mortality. Both phases are modelled as a system of initial boundary values problem for semi-linear transport equation with delay and initial problem for nonlinear delay ODE. The obtained system is studied both theoretically and numerically. Three different regimes of population dynamics for asymptotically stable states of autonomous systems are obtained in numerical experiments for the different initial values of population density. The quasi-periodical travelling wave solutions are studied numerically for the autonomous system with the different values of time delays and for the system with oscillating death rate and birth modulus. In both cases it is observed three types of travelling wave solutions: harmonic oscillations, pulse sequence and single pulse.

Chilling and chipping influence plant growth and reproduction of star-of-Bethlehem (Ornithogalum umbellatum)

USDA-ARS?s Scientific Manuscript database

Greenhouse studies were conducted on two southern Illinois star-of-Bethlehem biotypes to determine the influence of chilling and bulb chipping on plant growth and reproduction. Chilling was not required for leaf emergence of dormant bulbs, but an increase to 10 weeks of chilling proportionally delay...

Lactoferrin and lysozyme to reduce environmental enteric dysfunction and stunting in Malawian children: Study protocol for a randomized controlled trial

USDA-ARS?s Scientific Manuscript database

Chronic childhood malnutrition, as manifested by stunted linear growth, remains a persistent barrier to optimal child growth and societal development. Environmental enteric dysfunction (EED) is a significant underlying factor in the causal pathway to stunting, delayed cognitive development, and ulti...

Typology of nonlinear activity waves in a layered neural continuum.

PubMed

Koch, Paul; Leisman, Gerry

2006-04-01

Neural tissue, a medium containing electro-chemical energy, can amplify small increments in cellular activity. The growing disturbance, measured as the fraction of active cells, manifests as propagating waves. In a layered geometry with a time delay in synaptic signals between the layers, the delay is instrumental in determining the amplified wavelengths. The growth of the waves is limited by the finite number of neural cells in a given region of the continuum. As wave growth saturates, the resulting activity patterns in space and time show a variety of forms, ranging from regular monochromatic waves to highly irregular mixtures of different spatial frequencies. The type of wave configuration is determined by a number of parameters, including alertness and synaptic conditioning as well as delay. For all cases studied, using numerical solution of the nonlinear Wilson-Cowan (1973) equations, there is an interval in delay in which the wave mixing occurs. As delay increases through this interval, during a series of consecutive waves propagating through a continuum region, the activity within that region changes from a single-frequency to a multiple-frequency pattern and back again. The diverse spatio-temporal patterns give a more concrete form to several metaphors advanced over the years to attempt an explanation of cognitive phenomena: Activity waves embody the "holographic memory" (Pribram, 1991); wave mixing provides a plausible cause of the competition called "neural Darwinism" (Edelman, 1988); finally the consecutive generation of growing neural waves can explain the discontinuousness of "psychological time" (Stroud, 1955).

Delayed bet-hedging resilience strategies under environmental fluctuations

NASA Astrophysics Data System (ADS)

Ogura, Masaki; Wakaiki, Masashi; Rubin, Harvey; Preciado, Victor M.

2017-05-01

Many biological populations, such as bacterial colonies, have developed through evolution a protection mechanism, called bet hedging, to increase their probability of survival under stressful environmental fluctuation. In this context, the concept of preadaptation refers to a common type of bet-hedging protection strategy in which a relatively small number of individuals in a population stochastically switch their phenotypes to a dormant metabolic state in which they increase their probability of survival against potential environmental shocks. Hence, if an environmental shock took place at some point in time, preadapted organisms would be better adapted to survive and proliferate once the shock is over. In many biological populations, the mechanisms of preadaptation and proliferation present delays whose influence in the fitness of the population are not well understood. In this paper, we propose a rigorous mathematical framework to analyze the role of delays in both preadaptation and proliferation mechanisms in the survival of biological populations, with an emphasis on bacterial colonies. Our theoretical framework allows us to analytically quantify the average growth rate of a bet-hedging bacterial colony with stochastically delayed reactions with arbitrary precision. We verify the accuracy of the proposed method by numerical simulations and conclude that the growth rate of a bet-hedging population shows a nontrivial dependency on their preadaptation and proliferation delays. Contrary to the current belief, our results show that faster reactions do not, in general, increase the overall fitness of a biological population.

A de novo KMT2D mutation in a girl with Kabuki syndrome associated with endocrine symptoms: a case report.

PubMed

Moon, Jung-Eun; Lee, Su-Jeong; Ko, Cheol Woo

2018-06-18

Kabuki syndrome is characterized by distinctive facial features and varying degrees of growth retardation. It leads to malformations in skeletal, urogenital and cardiac structures; moreover, endocrine conditions such as premature thelarche, precocious puberty, growth hormone deficiency, diabetes insipidus, thyroid dysfunction and obesity have been reported. Kabuki syndrome is caused by a heterozygous mutation in the KMT2D or KDM6A genes. An 11-year-old girl with the typical facial features of Kabuki syndrome visited our hospital due to her short stature. She was found to have the de novo heterozygous mutation of c.8200C > T, p(Arg2734*) in exon 32 of the KMT2D gene and was diagnosed with Kabuki syndrome. The patient also exhibited endocrine abnormalities such as a constitutional delay of puberty, transiently congenial hypothyroidism, obesity and growth hormone deficiency. This is a case of a mutation in the KMT2D gene in a girl with Kabuki syndrome who presented with endocrine symptoms (constitutional delay of puberty, hypothyroidism, obesity and growth hormone deficiency).

Cognitive person variables in the delay of gratification of older children at risk.

PubMed

Rodriguez, M L; Mischel, W; Shoda, Y

1989-08-01

The components of self-regulation were analyzed, extending the self-imposed delay of gratification paradigm to older children with social adjustment problems. Delay behavior was related to a network of conceptually relevant cognitive person variables, consisting of attention deployment strategies during delay, knowledge of delay rules, and intelligence. A positive relationship was demonstrated between concurrent indexes of intelligence, attention deployment, and actual delay time. Moreover, attention deployment, measured as an individual differences variable during the delay process, had a direct, positive effect on delay behavior. Specifically, as the duration of delay and the frustration of the situation increased, children who spent a higher proportion of the time distracting themselves from the tempting elements of the delay situation were able to delay longer. The effect of attention deployment on delay behavior was significant even when age, intelligence, and delay rule knowledge were controlled. Likewise, delay rule knowledge significantly predicted delay time, even when age, attention deployment, and intelligence were controlled.

A comparative study of ethylene growth response kinetics in eudicots and monocots reveals a role for gibberellin in growth inhibition and recovery.

PubMed

Kim, Joonyup; Wilson, Rebecca L; Case, J Brett; Binder, Brad M

2012-11-01

Time-lapse imaging of dark-grown Arabidopsis (Arabidopsis thaliana) hypocotyls has revealed new aspects about ethylene signaling. This study expands upon these results by examining ethylene growth response kinetics of seedlings of several plant species. Although the response kinetics varied between the eudicots studied, all had prolonged growth inhibition for as long as ethylene was present. In contrast, with continued application of ethylene, white millet (Panicum miliaceum) seedlings had a rapid and transient growth inhibition response, rice (Oryza sativa 'Nipponbare') seedlings had a slow onset of growth stimulation, and barley (Hordeum vulgare) had a transient growth inhibition response followed, after a delay, by a prolonged inhibition response. Growth stimulation in rice correlated with a decrease in the levels of rice ETHYLENE INSENSTIVE3-LIKE2 (OsEIL2) and an increase in rice F-BOX DOMAIN AND LRR CONTAINING PROTEIN7 transcripts. The gibberellin (GA) biosynthesis inhibitor paclobutrazol caused millet seedlings to have a prolonged growth inhibition response when ethylene was applied. A transient ethylene growth inhibition response has previously been reported for Arabidopsis ethylene insensitive3-1 (ein3-1) eil1-1 double mutants. Paclobutrazol caused these mutants to have a prolonged response to ethylene, whereas constitutive GA signaling in this background eliminated ethylene responses. Sensitivity to paclobutrazol inversely correlated with the levels of EIN3 in Arabidopsis. Wild-type Arabidopsis seedlings treated with paclobutrazol and mutants deficient in GA levels or signaling had a delayed growth recovery after ethylene removal. It is interesting to note that ethylene caused alterations in gene expression that are predicted to increase GA levels in the ein3-1 eil1-1 seedlings. These results indicate that ethylene affects GA levels leading to modulation of ethylene growth inhibition kinetics.

Urban sprawl and delayed ambulance arrival in the U.S.

PubMed

Trowbridge, Matthew J; Gurka, Matthew J; O'Connor, Robert E

2009-11-01

Minimizing emergency medical service (EMS) response time is a central objective of prehospital care, yet the potential influence of built environment features such as urban sprawl on EMS system performance is often not considered. This study measures the association between urban sprawl and EMS response time to test the hypothesis that features of sprawling development increase the probability of delayed ambulance arrival. In 2008, EMS response times for 43,424 motor-vehicle crashes were obtained from the Fatal Analysis Reporting System, a national census of crashes involving > or =1 fatality. Sprawl at each crash location was measured using a continuous county-level index previously developed by Ewing et al. The association between sprawl and the probability of a delayed ambulance arrival (> or =8 minutes) was then measured using generalized linear mixed modeling to account for correlation among crashes from the same county. Urban sprawl is significantly associated with increased EMS response time and a higher probability of delayed ambulance arrival (p=0.03). This probability increases quadratically as the severity of sprawl increases while controlling for nighttime crash occurrence, road conditions, and presence of construction. For example, in sprawling counties (e.g., Fayette County GA), the probability of a delayed ambulance arrival for daytime crashes in dry conditions without construction was 69% (95% CI=66%, 72%) compared with 31% (95% CI=28%, 35%) in counties with prominent smart-growth characteristics (e.g., Delaware County PA). Urban sprawl is significantly associated with increased EMS response time and a higher probability of delayed ambulance arrival following motor-vehicle crashes in the U.S. The results of this study suggest that promotion of community design and development that follows smart-growth principles and regulates urban sprawl may improve EMS performance and reliability.

Ventricular septal defect

MedlinePlus

... causing an irregular or slow heart rhythm) Delayed growth and development ( failure to thrive in infancy) Heart failure Infective endocarditis (bacterial infection of the heart) Pulmonary hypertension (high blood ...

An optimized small animal tumour model for experimentation with low energy protons.

PubMed

Beyreuther, Elke; Brüchner, Kerstin; Krause, Mechthild; Schmidt, Margret; Szabo, Rita; Pawelke, Jörg

2017-01-01

The long-term aim of developing laser based particle acceleration towards clinical application requires not only substantial technological progress, but also the radiobiological characterization of the resulting ultra-short and ultra-intensive particle beam pulses. After comprehensive cell studies a mouse ear tumour model was established allowing for the penetration of low energy protons (~20 MeV) currently available at laser driven accelerators. The model was successfully applied for a first tumour growth delay study with laser driven electrons, whereby the need of improvements crop out. To optimise the mouse ear tumour model with respect to a stable, high take rate and a lower number of secondary tumours, Matrigel was introduced for tumour cell injection. Different concentrations of two human tumour cell lines (FaDu, LN229) and Matrigel were evaluated for stable tumour growth and fulfilling the allocation criteria for irradiation experiments. The originally applied cell injection with PBS was performed for comparison and to assess the long-term stability of the model. Finally, the optimum suspension of cells and Matrigel was applied to determine applicable dose ranges for tumour growth delay studies by 200 kV X-ray irradiation. Both human tumour models showed a high take rate and exponential tumour growth starting at a volume of ~10 mm3. As disclosed by immunofluorescence analysis these small tumours already interact with the surrounding tissue and activate endothelial cells to form vessels. The formation of delimited, solid tumours at irradiation size was shown by standard H&E staining and a realistic dose range for inducing tumour growth delay without permanent tumour control was obtained for both tumour entities. The already established mouse ear tumour model was successfully upgraded now providing stable tumour growth with high take rate for two tumour entities (HNSCC, glioblastoma) that are of interest for future irradiation experiments at experimental accelerators.

Experimental drought and heat can delay phenological development and reduce foliar and shoot growth in semiarid trees

DOE PAGES

Adams, Henry D.; Collins, Adam D.; Briggs, Samuel P.; ...

2015-09-22

Higher temperatures associated with climate change are anticipated to trigger an earlier start to the growing season, which could increase the terrestrial C sink strength. Greater variability in the amount and timing of precipitation is also expected with higher temperatures, bringing increased drought stress to many ecosystems. We experimentally assessed the effects of higher temperature and drought on the foliar phenology and shoot growth of mature trees of two semiarid conifer species. We exposed field-grown trees to a ~45% reduction in precipitation with a rain-out structure (‘drought’), a ~4.8 °C temperature increase with open-top chambers (‘heat’), and a combination ofmore » both simultaneously (‘drought + heat’). Over the 2013 growing season, drought, heat, and drought + heat treatments reduced shoot and needle growth in piñon pine ( Pinus edulis) by ≥39%, while juniper ( Juniperus monosperma) had low growth and little response to these treatments. Needle emergence on primary axis branches of piñon pine was delayed in heat, drought, and drought + heat treatments by 19–57 days, while secondary axis branches were less likely to produce needles in the heat treatment, and produced no needles at all in the drought + heat treatment. Growth of shoots and needles, and the timing of needle emergence correlated inversely with xylem water tension and positively with nonstructural carbohydrate concentrations. Our findings demonstrate the potential for delayed phenological development and reduced growth with higher temperatures and drought in tree species that are vulnerable to drought and reveal potential mechanistic links to physiological stress responses. Furthermore, climate change projections of an earlier and longer growing season with higher temperatures, and consequent increases in terrestrial C sink strength, may be incorrect for regions where plants will face increased drought stress with climate change.« less

Experimental drought and heat can delay phenological development and reduce foliar and shoot growth in semiarid trees.

PubMed

Adams, Henry D; Collins, Adam D; Briggs, Samuel P; Vennetier, Michel; Dickman, L Turin; Sevanto, Sanna A; Garcia-Forner, Núria; Powers, Heath H; McDowell, Nate G

2015-11-01

Higher temperatures associated with climate change are anticipated to trigger an earlier start to the growing season, which could increase the terrestrial C sink strength. Greater variability in the amount and timing of precipitation is also expected with higher temperatures, bringing increased drought stress to many ecosystems. We experimentally assessed the effects of higher temperature and drought on the foliar phenology and shoot growth of mature trees of two semiarid conifer species. We exposed field-grown trees to a ~45% reduction in precipitation with a rain-out structure ('drought'), a ~4.8 °C temperature increase with open-top chambers ('heat'), and a combination of both simultaneously ('drought + heat'). Over the 2013 growing season, drought, heat, and drought + heat treatments reduced shoot and needle growth in piñon pine (Pinus edulis) by ≥39%, while juniper (Juniperus monosperma) had low growth and little response to these treatments. Needle emergence on primary axis branches of piñon pine was delayed in heat, drought, and drought + heat treatments by 19-57 days, while secondary axis branches were less likely to produce needles in the heat treatment, and produced no needles at all in the drought + heat treatment. Growth of shoots and needles, and the timing of needle emergence correlated inversely with xylem water tension and positively with nonstructural carbohydrate concentrations. Our findings demonstrate the potential for delayed phenological development and reduced growth with higher temperatures and drought in tree species that are vulnerable to drought and reveal potential mechanistic links to physiological stress responses. Climate change projections of an earlier and longer growing season with higher temperatures, and consequent increases in terrestrial C sink strength, may be incorrect for regions where plants will face increased drought stress with climate change. © 2015 John Wiley & Sons Ltd.

Experimental drought and heat can delay phenological development and reduce foliar and shoot growth in semiarid trees

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adams, Henry D.; Collins, Adam D.; Briggs, Samuel P.

Higher temperatures associated with climate change are anticipated to trigger an earlier start to the growing season, which could increase the terrestrial C sink strength. Greater variability in the amount and timing of precipitation is also expected with higher temperatures, bringing increased drought stress to many ecosystems. We experimentally assessed the effects of higher temperature and drought on the foliar phenology and shoot growth of mature trees of two semiarid conifer species. We exposed field-grown trees to a ~45% reduction in precipitation with a rain-out structure (‘drought’), a ~4.8 °C temperature increase with open-top chambers (‘heat’), and a combination ofmore » both simultaneously (‘drought + heat’). Over the 2013 growing season, drought, heat, and drought + heat treatments reduced shoot and needle growth in piñon pine ( Pinus edulis) by ≥39%, while juniper ( Juniperus monosperma) had low growth and little response to these treatments. Needle emergence on primary axis branches of piñon pine was delayed in heat, drought, and drought + heat treatments by 19–57 days, while secondary axis branches were less likely to produce needles in the heat treatment, and produced no needles at all in the drought + heat treatment. Growth of shoots and needles, and the timing of needle emergence correlated inversely with xylem water tension and positively with nonstructural carbohydrate concentrations. Our findings demonstrate the potential for delayed phenological development and reduced growth with higher temperatures and drought in tree species that are vulnerable to drought and reveal potential mechanistic links to physiological stress responses. Furthermore, climate change projections of an earlier and longer growing season with higher temperatures, and consequent increases in terrestrial C sink strength, may be incorrect for regions where plants will face increased drought stress with climate change.« less

The effect of recombinant growth hormone on intestinal anastomotic wound healing in rats with obstructive jaundice.

PubMed

Cağlikülekçi, Mehmet; Ozçay, Necdet; Oruğ, Taner; Aydoğ, Gülden; Renda, Nurten; Atalay, Fuat

2002-03-01

Several clinical and experimental studies have shown that obstructive jaundice delays wound healing. Growth hormone may prevent delayed wound healing, since it has effects on the release of mediators in jaundice, as well as increasing the protein synthesis. Forty male Wistar rats were allocated to four groups: Group I (n=10): intestinal anastomosis to normal small bowel, Group II (n=10): intestinal anastomosis to normal small bowel followed by growth hormone therapy (2mg/kg/day, subcutaneously), Group III (n=10): intestinal anastomosis to obstructive jaundice rat's small bowel, Group IV (n=10): intestinal anastomosis to obstructive jaundice rat's small bowel followed by growth hormone therapy at the same dosage The animals were observed for seven days then killed. Intraabdominal adhesions, anastomotic complications and anastomotic bursting pressures were recorded and tissue samples from the anastomotic site were obtained to measure hydroxyproline levels and for histopathologic examination. Growth hormone had a beneficial effect on the healing of intestinal anastomosis in both jaundiced and non-jaundiced rats. This was demonstrated by clinical and mechanical parameters such as a significant increase in anastomotic bursting pressure, hydroxyproline content and histopathological scores. Growth hormone reverses the adverse effects of obstructive jaundice on small bowel anastomotic healing. It can be hypothesized that this effect is due to augmentation of insulin-like growth factors, protection of hepatocytes, enhancement of intestinal epithelization, and reversal of the resultant malnutritional state caused by growth hormone in obstructive jaundice.

Human tumor xenografts in mouse as a model for evaluating therapeutic efficacy of monoclonal antibodies or antibody-drug conjugate targeting receptor tyrosine kinases.

PubMed

Feng, Liang; Wang, Wei; Yao, Hang-Ping; Zhou, Jianwei; Zhang, Ruiwen; Wang, Ming-Hai

2015-01-01

Targeting receptor tyrosine kinases by therapeutic monoclonal antibodies and antibody-drug conjugates has met with tremendous success in clinical oncology. Currently, numerous therapeutic monoclonal antibodies are under preclinical development. The potential for moving candidate antibodies into clinical trials relies heavily on therapeutic efficacy validated by human tumor xenografts in mice. Here we describe methods used to determine therapeutic efficacy of monoclonal antibodies or antibody-drug conjugates specific to human receptor tyrosine kinase using human tumor xenografts in mice as the model. The end point of the study is to determine whether treatment of tumor-bearing mice with a monoclonal antibody or antibody-drug conjugates results in significant delay of tumor growth.

[Features of sexual development of adolescent boys in cities of Caspian region of the Republic of Kazakhstan].

PubMed

Kurmangaliev, O M; Gumarova, Zh Zh; Zasorin, B V

2014-01-01

The complex estimation of parameters of the sexual development of adolescent boys aged 14-16 years had been done in cities of Aktay and Atyrau, in Caspian region of Western Kazakhstan. Adolescent boys in cities of Caspian region of the Republic of Kazakhstan were found to have tendency to the delayed puberty according to Tanner score. Retarded sexual development is manifested by the some retardation in growth of genitals and escutcheon, in comparison with their peers from control group. The absence of differences in general physical development, as evidenced by anthropometry data, does not exclude the specific (elective) character of the impact of urbanogenic factors on growing male body, which is typical impact of hard metals salts.

Genetics Home Reference: SADDAN

MedlinePlus

... CLOSE navigation Home Page Search Home Health ... delay and acanthosis nigricans) is a rare disorder of bone growth characterized by skeletal, brain, and skin abnormalities. All people with this ...

Casualty Evacuation Delay and Outcomes

DTIC Science & Technology

2003-01-01

consequences of delay in therapy on wounded individuals. The contractor was charged with studying the effect of delay on evacuation on outcome of...process. 3 There are a remarkably small proportion of patient diagnoses and states in which time has an effect on outcome . This is because the vast...emphasis on estimating the effect of delayed evacuation on injury outcome and means to mitigating such effects . Since some of the Specific Aims were

Metabolic interrogation as a tool to optimize chemotherapeutic regimens.

PubMed

Sandulache, Vlad C; Chen, Yunyun; Feng, Lei; William, William N; Skinner, Heath D; Myers, Jeffrey N; Meyn, Raymond E; Li, Jinzhong; Mijiti, Ainiwaer; Bankson, James A; Fuller, Clifton D; Konopleva, Marina Y; Lai, Stephen Y

2017-03-14

Platinum-based (Pt) chemotherapy is broadly utilized in the treatment of cancer. Development of more effective, personalized treatment strategies require identification of novel biomarkers of treatment response. Since Pt compounds are inactivated through cellular metabolic activity, we hypothesized that metabolic interrogation can predict the effectiveness of Pt chemotherapy in a pre-clinical model of head and neck squamous cell carcinoma (HNSCC).We tested the effects of cisplatin (CDDP) and carboplatin (CBP) on DNA damage, activation of cellular death cascades and tumor cell metabolism, specifically lactate production. Pt compounds induced an acute dose-dependent, transient drop in lactate generation in vitro, which correlated with effects on DNA damage and cell death. Neutralization of free radical stress abrogated these effects. The magnitude of this effect on lactate production correlated with the differential sensitivity of HNSCC cells to Pt compounds (CDDP vs CBP) and p53-driven Pt chemotherapy resistance. Using dual flank xenograft tumors, we demonstrated that Pt-driven effects on lactate levels correlate with effects on tumor growth delay in a dose-dependent manner and that lactate levels can define the temporal profile of Pt chemotherapy-induced metabolic stress. Lactate interrogation also predicted doxorubicin effects on cell death in both solid tumor (HNSCC) and acute myelogenous leukemia (AML) cell lines.Real-time metabolic interrogation of acute changes in cell and tumor lactate levels reflects chemotherapy effects on DNA damage, cell death and tumor growth delay. We have identified a real-time biomarker of chemotherapy effectiveness which can be used to develop adaptive, iterative and personalized treatment regimens against a variety of solid and hematopoietic malignancies.

Metabolic interrogation as a tool to optimize chemotherapeutic regimens

PubMed Central

Feng, Lei; William, William N.; Skinner, Heath D.; Myers, Jeffrey N.; Meyn, Raymond E.; Li, Jinzhong; Mijiti, Ainiwaer; Bankson, James A.; Fuller, Clifton D.; Konopleva, Marina Y.; Lai, Stephen Y.

2017-01-01

Platinum-based (Pt) chemotherapy is broadly utilized in the treatment of cancer. Development of more effective, personalized treatment strategies require identification of novel biomarkers of treatment response. Since Pt compounds are inactivated through cellular metabolic activity, we hypothesized that metabolic interrogation can predict the effectiveness of Pt chemotherapy in a pre-clinical model of head and neck squamous cell carcinoma (HNSCC). We tested the effects of cisplatin (CDDP) and carboplatin (CBP) on DNA damage, activation of cellular death cascades and tumor cell metabolism, specifically lactate production. Pt compounds induced an acute dose-dependent, transient drop in lactate generation in vitro, which correlated with effects on DNA damage and cell death. Neutralization of free radical stress abrogated these effects. The magnitude of this effect on lactate production correlated with the differential sensitivity of HNSCC cells to Pt compounds (CDDP vs CBP) and p53-driven Pt chemotherapy resistance. Using dual flank xenograft tumors, we demonstrated that Pt-driven effects on lactate levels correlate with effects on tumor growth delay in a dose-dependent manner and that lactate levels can define the temporal profile of Pt chemotherapy-induced metabolic stress. Lactate interrogation also predicted doxorubicin effects on cell death in both solid tumor (HNSCC) and acute myelogenous leukemia (AML) cell lines. Real-time metabolic interrogation of acute changes in cell and tumor lactate levels reflects chemotherapy effects on DNA damage, cell death and tumor growth delay. We have identified a real-time biomarker of chemotherapy effectiveness which can be used to develop adaptive, iterative and personalized treatment regimens against a variety of solid and hematopoietic malignancies. PMID:28184025

Expression and inhibition of aquaporins in germinating Arabidopsis seeds.

PubMed

Vander Willigen, Clare; Postaire, Olivier; Tournaire-Roux, Colette; Boursiac, Yann; Maurel, Christophe

2006-09-01

Extensive and kinetically well-defined water exchanges occur during germination of seeds. A putative role for aquaporins in this process was investigated in Arabidopsis. Macro-arrays carrying aquaporin gene-specific tags and antibodies raised against aquaporin subclasses revealed two distinct aquaporin expression programs between dry seeds and young seedlings. High expression levels of a restricted number of tonoplast intrinsic protein (TIP) isoforms (TIP3;1 and/or TIP3;2, and TIP5;1) together with a low expression of all 13 plasma membrane aquaporin (PIP) isoforms was observed in dry and germinating materials. In contrast, prevalent expression of aquaporins of the TIP1, TIP2 and PIP subgroups was induced during seedling establishment. Mercury (5 microM HgCl(2)), a general blocker of aquaporins in various organisms, reduced the speed of seed germination and induced a true delay in maternal seed coat (testa) rupture and radicle emergence, by 8-9 and 25-30 h, respectively. Most importantly, mercury did not alter seed lot homogeneity nor the seed germination developmental sequence, and its effects were largely reversed by addition of 2 mM dithiothreitol, suggesting that these effects were primarily due to oxidation of cell components, possibly aquaporins, without irreversible alteration of cell integrity. Measurements of water uptake in control and mercury-treated seeds suggested that aquaporin functions are not involved in early seed imbibition (phase I) but would rather be associated with a delayed initiation of phase III, i.e. water uptake accompanying expansion and growth of the embryo. A possible role for aquaporins in germinating seeds and more generally in plant tissue growth is discussed.

Vision Loss in Older Adults.

PubMed

Pelletier, Allen L; Rojas-Roldan, Ledy; Coffin, Janis

2016-08-01

Vision loss affects 37 million Americans older than 50 years and one in four who are older than 80 years. The U.S. Preventive Services Task Force concludes that current evidence is insufficient to assess the balance of benefits and harms of screening for impaired visual acuity in adults older than 65 years. However, family physicians play a critical role in identifying persons who are at risk of vision loss, counseling patients, and referring patients for disease-specific treatment. The conditions that cause most cases of vision loss in older patients are age-related macular degeneration, glaucoma, ocular complications of diabetes mellitus, and age-related cataracts. Vitamin supplements can delay the progression of age-related macular degeneration. Intravitreal injection of a vascular endothelial growth factor inhibitor can preserve vision in the neovascular form of macular degeneration. Medicated eye drops reduce intraocular pressure and can delay the progression of vision loss in patients with glaucoma, but adherence to treatment is poor. Laser trabeculoplasty also lowers intraocular pressure and preserves vision in patients with primary open-angle glaucoma, but long-term studies are needed to identify who is most likely to benefit from surgery. Tight glycemic control in adults with diabetes slows the progression of diabetic retinopathy, but must be balanced against the risks of hypoglycemia and death in older adults. Fenofibrate also slows progression of diabetic retinopathy. Panretinal photocoagulation is the mainstay of treatment for diabetic retinopathy, whereas vascular endothelial growth factor inhibitors slow vision loss resulting from diabetic macular edema. Preoperative testing before cataract surgery does not improve outcomes and is not recommended.

Vascular delay and administration of basic fibroblast growth factor augment latissimus dorsi muscle flap perfusion and function.

PubMed

Carroll, S M; Carroll, C M; Stremel, R W; Heilman, S J; Steffen, J M; Tobin, G R; Barker, J H

2000-03-01

Ischemia of the distal latissimus dorsi muscle flap occurs when the entire muscle is acutely elevated. Although this level of ischemia may not be critical if the muscle is to be used as a conventional muscle flap, the ischemia causes decreased distal muscle function if it is used for dynamic muscle flap transfer. This experiment was designed to determine whether or not the administration of exogenous basic fibroblast growth factor (bFGF), combined with a sublethal ischemic insult (i.e., vascular delay), would further augment muscle perfusion and function. Both latissimus dorsi muscles of nine canines were subjected to a bipedicle vascular delay procedure immediately followed by thoracodorsal intraarterial injection of 100 microg of bFGF on one side and by intraarterial injection of vehicle on the other. Ten days later, both latissimus dorsi muscles were raised as thoracodorsally based island flaps, with perfusion determined by laser-Doppler fluximetry. The muscles were wrapped around silicone chambers, simulating cardiomyoplasty, and stimulating electrodes were placed around each thoracodorsal nerve. The muscles were then subjected to an experimental protocol to determine muscle contractile function. At the end of the experiment, latissimus dorsi muscle biopsies were obtained for measurement of bFGF expression. The results demonstrated that the administration of 100 microg of bFGF immediately after the vascular delay procedure increases expression of native bFGF. In the distal and middle muscle segments, it also significantly increased muscle perfusion by approximately 20 percent and fatigue resistance by approximately 300 percent. The administration of growth factors may serve as an important adjuvant to surgical procedures using dynamic muscle flap transfers.

A cross-sectional study of growth, nutritional status and body proportions in children and adolescents at a medical center specializing in the treatment of cystic fibrosis in Poland.

PubMed

Sands, Dorota; Umławska, Wioleta; Zielińska, Anna

2015-03-16

Malnutrition, delayed growth and delayed puberty are commonly seen in children with cystic fibrosis. The aim of this study was to evaluate growth, nutritional status and body proportions in children and adolescents suffering from cystic fibrosis. The evaluation was based on 19 somatic measurements and indices calculated from these measurements. Somatic development was evaluated in relation to several factors connected to the clinical picture or the course of the disease. Anthropometric data were extracted from the medical histories of 41 boys and 48 girls diagnosed and treated at the Institute of Mother and Child in Warsaw (Poland). Mean values for somatic parameters and body build indices for the children suffering from CF were compared to those for the reference group. The results revealed that growth in these children was significantly delayed in comparison to that seen in the healthy population (Z-score = -0.56, p < 0.001). Nutritional status was also adversely affected (Z-score = -0.85, p < 0.001). The children suffered more from a deficit in muscularity than in adiposity (Z-score = -0.75 and Z-score = -0.34, p < 0.01, respectively). This was especially true for boys. The children had infantile body proportions and defects in trunk and chest structure. The factors that most affected somatic development were infection by Pseudomonas aeruginosa and the time at which the disease was diagnosed. Chronic infection by P. aeruginosa and type of CFTR mutation were the factors that most affected pulmonary function parameters.

Lack of hepcidin ameliorates anemia and improves growth in an adenine-induced mouse model of chronic kidney disease

PubMed Central

Sureshbabu, Angara; Doty, Steve B.; Zhu, Yuan-Shan; Patino, Edwin; Cunningham-Rundles, Susanna; Choi, Mary E.; Boskey, Adele; Rivella, Stefano

2016-01-01

Growth delay is common in children with chronic kidney disease (CKD), often associated with poor quality of life. The role of anemia in uremic growth delay is poorly understood. Here we describe an induction of uremic growth retardation by a 0.2% adenine diet in wild-type (WT) and hepcidin gene (Hamp) knockout (KO) mice, compared with their respective littermates fed a regular diet. Experiments were started at weaning (3 wk). After 8 wk, blood was collected and mice were euthanized. Adenine-fed WT mice developed CKD (blood urea nitrogen 82.8 ± 11.6 mg/dl and creatinine 0.57 ± 0.07 mg/dl) and were 2.1 cm shorter compared with WT controls. WT adenine-fed mice were anemic and had low serum iron, elevated Hamp, and elevated IL6 and TNF-α. WT adenine-fed mice had advanced mineral bone disease (serum phosphorus 16.9 ± 3.1 mg/dl and FGF23 204.0 ± 115.0 ng/ml) with loss of cortical and trabecular bone volume seen on microcomputed tomography. Hamp disruption rescued the anemia phenotype resulting in improved growth rate in mice with CKD, thus providing direct experimental evidence of the relationship between Hamp pathway and growth impairment in CKD. Hamp disruption ameliorated CKD-induced growth hormone-insulin-like growth factor 1 axis derangements and growth plate alterations. Disruption of Hamp did not mitigate the development of uremia, inflammation, and mineral and bone disease in this model. Taken together, these results indicate that an adenine diet can be successfully used to study growth in mice with CKD. Hepcidin appears to be related to pathways of growth retardation in CKD suggesting that investigation of hepcidin-lowering therapies in juvenile CKD is warranted. PMID:27440777

Stage-specific apoptosis, developmental delay, and embryonic lethality in mice homozygous for a targeted disruption in the murine Bloom's syndrome gene.

PubMed

Chester, N; Kuo, F; Kozak, C; O'Hara, C D; Leder, P

1998-11-01

Bloom's syndrome is a human autosomal genetic disorder characterized at the cellular level by genome instability and increased sister chomatid exchanges (SCEs). Clinical features of the disease include proportional dwarfism and a predisposition to develop a wide variety of malignancies. The human BLM gene has been cloned recently and encodes a DNA helicase. Mouse embryos homozygous for a targeted mutation in the murine Bloom's syndrome gene (Blm) are developmentally delayed and die by embryonic day 13.5. The fact that the interrupted gene is the homolog of the human BLM gene was confirmed by its homologous sequence, its chromosomal location, and by demonstrating high numbers of SCEs in cultured murine Blm-/- fibroblasts. The proportional dwarfism seen in the human is consistent with the small size and developmental delay (12-24 hr) seen during mid-gestation in murine Blm-/- embryos. Interestingly, the growth retardation in mutant embryos can be accounted for by a wave of increased apoptosis in the epiblast restricted to early post-implantation embryogenesis. Mutant embryos do not survive past day 13.5, and at this time exhibit severe anemia. Red blood cells and their precursors from Blm-/- embryos are heterogeneous in appearance and have increased numbers of macrocytes and micronuclei. Both the apoptotic wave and the appearance of micronuclei in red blood cells are likely cellular consequences of damaged DNA caused by effects on replicating or segregating chromosomes.

Specific and Nonspecific Neural Activity during Selective Processing of Visual Representations in Working Memory

ERIC Educational Resources Information Center

Oh, Hwamee; Leung, Hoi-Chung

2010-01-01

In this fMRI study, we investigated prefrontal cortex (PFC) and visual association regions during selective information processing. We recorded behavioral responses and neural activity during a delayed recognition task with a cue presented during the delay period. A specific cue ("Face" or "Scene") was used to indicate which one of the two…

Catch-up Growth: Cellular and Molecular Mechanisms

PubMed Central

Finkielstain, GP; Lui, JC; Baron, J

2012-01-01

In mammals, after a period of growth inhibition, body growth often does not just return to a normal rate but actually exceeds the normal rate, resulting in catch-up growth. Recent evidence suggests that catch-up growth occurs because growth-inhibiting conditions delay progression of the physiological mechanisms that normally cause body growth to slow and cease with age. As a result, following the period of growth inhibition, tissues retain a greater proliferative capacity than normal, and therefore grow more rapidly than normal for age. There is evidence that this mechanism contributes both to catch-up growth in terms of body length, which involves proliferation in the growth plate, and to catch-up growth in terms of organ mass, which involves proliferation in multiple non-skeletal tissues. PMID:23428687

Pure culture response of ectomycorrhizal fungi to imposed water stress

Treesearch

Mark D. Coleman; Caroline S. Bledsoe; William Lopushinsky

1989-01-01

The ability of ectomycorrhizal fungal isolates to tolerate imposed water stress in pure culture was examined in 55 isolates of 18 species. Water potential treatments, adjusted with polyethylene glycol, were applied to Petri dish units. These units allowed colony diameter measurements of fungi grown on liquid media. Delayed growth initiation and inhibition of growth...

76 FR 414 - Tier 1 Environmental Impact Statement for the Los Angeles to San Luis Obispo (LOSSAN North) Rail...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-04

... expected growth in population and resulting increases in intercity travel demand between Los Angeles and San Luis Obispo. As a result of this growth in travel demand, their travel delays from the growing... environmental analysis to help make corridor level decisions regarding the level of intercity passenger rail...

Screening for Language Delay: Growth Trajectories of Language Ability in Low- and High-Performing Children

ERIC Educational Resources Information Center

Klem, Marianne; Hagtvet, Bente; Hulme, Charles; Gustafsson, Jan-Eric

2016-01-01

Purpose: This study investigated the stability and growth of preschool language skills and explores latent class analysis as an approach for identifying children at risk of language impairment. Method: The authors present data from a large-scale 2-year longitudinal study, in which 600 children were assessed with a language-screening tool…

Effects of prolonged storage on survival and growth of outplanted bottomland oaks

Treesearch

David C. Mercker; David S. Buckley; John P. Conn

2011-01-01

A prominent difficulty during bottomland hardwood afforestation is that sites are often flooded during the preferred months of planting (January-March), which results in delayed planting (April-June) and reduced survival. We monitored growth and survival of oak seedlings planted in 11 different months (February through December) after varying periods of humidified cold...

Unstable Resonator Mid-Infrared Laser Sources

DTIC Science & Technology

2016-02-26

of individual materials depending on metal species and growth temperatures . Fig. 8 (a) Average power consumption and (b) delay of C2MOS and double...feedback lasers, chirped gratings, interferometric lithography, nanowire transistors, tunnel field- effect transistors, nanoscale epitaxial growth, nanowire...technical approaches. Approaches to wavelength tuning include thermal/operation temperature tuning [1], variable cavity length with cantilever/piezo

Brown-Spot Needle Blight of Pines

Treesearch

W.R. Phelps; A.G. Kais; T.H. Nicholls

1978-01-01

Brown-spot needle blight, caused by Scirrhia acicola (Dearn.) Siggers, delays growth and causes mortality of longleaf pine (Pinus palustris Mill.). Brown spot reduces total annual growth of southern pines by more than 16 million cubic feet (0.453 million cubic meters) of timber. Damage is most severe on longleaf seedlings in the grass stage; i.e., those that have not...

Economics of replacing young-growth ponderosa pine stands . . . a case study

Treesearch

Dennis E. Teeguarden

1968-01-01

Compares the expected capital value growth of five ponderosa pine stands (70 to 80 years old) on the Challenge Experimental Forest, Yuba County, Calif., with the cost of delaying harvest (defined as sum of stock-holding and land-holding costs). Suggests that replacement of all five stands would be financially desirable under constant stumpage prices. Recommends...

MSH1 Is a Plant Organellar DNA Binding and Thylakoid Protein under Precise Spatial Regulation to Alter Development

DOE PAGES

Virdi, Kamaldeep S.; Wamboldt, Yashitola; Kundariya, Hardik; ...

2015-11-14

As metabolic centers, plant organelles participate in maintenance, defense, and signaling. MSH1 is a plant-specific protein involved in organellar genome stability in mitochondria and plastids. Plastid depletion of MSH1 causes heritable, non-genetic changes in development and DNA methylation. We investigated the msh1 phenotype using hemi-complementation mutants and transgene-null segregants from RNAi suppression lines to sub-compartmentalize MSH1 effects. We show that MSH1 expression is spatially regulated, specifically localizing to plastids within the epidermis and vascular parenchyma. The protein binds DNA and localizes to plastid and mitochondrial nucleoids, but fractionation and protein–protein interactions data indicate that MSH1 also associates with the thylakoidmore » membrane. Plastid MSH1 depletion results in variegation, abiotic stress tolerance, variable growth rate, and delayed maturity. Depletion from mitochondria results in 7%–10% of plants altered in leaf morphology, heat tolerance, and mitochondrial genome stability. MSH1 does not localize within the nucleus directly, but plastid depletion produces non-genetic changes in flowering time, maturation, and growth rate that are heritable independent of MSH1. MSH1 depletion alters non-photoactive redox behavior in plastids and a sub-set of mitochondrially altered lines. Ectopic expression produces deleterious effects, underlining its strict expression control. Unraveling the complexity of the MSH1 effect offers insight into triggers of plant-specific, transgenerational adaptation behaviors.« less

Influence of growth hormone therapy on selected dental and skeletal system parameters.

PubMed

Partyka, Małgorzata; Chałas, Renata; Dunin-Wilczyńska, Izabella; Drohomyretska, Myroslava; Klatka, Maria

2018-03-14

Growth hormone deficiency (GHD) is one of the main indications for growth hormone therapy. One characteristic of this disease is bone age delay in relation to the chronological age. Pituitary dysfunction negatively affects the growth and development of the jaws and teeth of the child. The secretion of endocrine glands regulates growth, development, and gender differentiation. It also controls the growth of bones and teeth, regulates metabolism of calcium and phosphate, proteins, lipids and carbohydrates. The primary role in the endocrine system is played by the pituitary gland which is responsible for the production of somatotropin [1]. Dysfunction of the pituitary gland has a negative effect on the growth and development of long bones in the body, and may have an adverse effect on the development of maxilla, mandible and dentition of a child. There is some information in the literature that dental age is delayed in short stature children; the replacement of deciduous teeth by permanent teeth is also delayed, and newly erupted permanent teeth often require orthodontic treatment. Applying hormonal therapy positively affects the process of replacement of dentition [2, 3, 4, 5, 6]. The aim of the study was to assess bone and dental age, as well as analyze the state of dentition in children diagnosed with GH deficiency treated with growth hormone, depending on the duration of treatment. The study material consisted of 110 children (27 males, 83 females), hospitalized for somatotropin hypopituitarism in the Department of Paediatric Endocrinology and Diabetology at the Medical University of Lublin, Poland. The mean birth age was 13 years (156 months) with a standard deviation of 2 years and 6 months (30 months). 47 children (43%) started treatment with the growth hormone (group starting treatment) and 63 children (57%) whose treatment was started 2-3 years previously (group in the course of treatment). The control group consisted of 41 generally healthy children (15males, 25 females) with ENT problems, such as hypoacusis and a condition after nasal injury, hospitalized in the Department of Paediatric Otolaryngology at the Medical University of Lublin, Poland. The mean age was 11 years and 5 months (137 months) with standard deviation of 2 years and 5 months (29 months). Informed consent was obtained from the parents. The study was approved by the Bioethical Committee at the Medical University of Lublin (Resolution No. KE-0254 /216 /2012).

Species-specific and transgenerational responses to increasing salinity in sympatric freshwater gastropods

USGS Publications Warehouse

Suski, Jamie G.; Salice, Christopher J.; Patino, Reynaldo

2012-01-01

Freshwater salinization is a global concern partly attributable to anthropogenic salt contamination. The authors examined the effects of increased salinity (as NaCl, 250-4,000 µS/cm, specific conductance) on two sympatric freshwater gastropods (Helisoma trivolvis and Physa pomillia). Life stage sensitivities were determined by exposing naive eggs or naive juveniles (through adulthood and reproduction). Additionally, progeny eggs from the juvenile-adult exposures were maintained at their respective parental salinities to examine transgenerational effects. Naive H. trivolvis eggs experienced delayed development at specific conductance > 250 µS/cm; reduced survivorship and reproduction were also seen in juvenile H. trivolvis at 4,000 µS/cm. Survival and growth of P. pomilia were not affected by increased salinity following egg or juvenile exposures. Interestingly, the progeny of H. trivolvis exposed to higher salinity may have gained tolerance to increased salinity whereas P. pomilia progeny may have experienced negative transgenerational effects. The present study demonstrates that freshwater snail species vary in their tolerance to salinization and also highlights the importance of multigenerational studies, as stressor impacts may not be readily apparent from shorter term exposures.

An actidione resistant Candida tropicalis from custard apple juice.

PubMed

Onkarayya, H; Suresh, E R; Ethiraj, S

1981-01-01

An actidione resistant yeast, Candida tropicalis, was isolated from fermenting custard apple juice. Though a slight inhibition of growth was observed on the first day with 5000 ppm of actidione, growth was equal to control after one week. Sorbic acid at 500 ppm and above inhibited the growth of this yeast while sodium benzoate and potassium metabisulphite were unable to suppress the growth even at 1000 ppm. Fermentation and assimilation of different carbon sources were delayed in the presence of 1000 ppm of actidione suggesting the disruption of protein synthesis by actidione.

How should we investigate children with growth failure?

PubMed

Léger, Juliane

2017-06-01

The early diagnosis of short stature is essential for effective management and treatment. Investigations for children with growth failure are required to distinguish between idiopathic short stature due to physiological variants (familial short stature, and constitutional delays of growth and puberty, or both), primary causes of short stature, such as syndromic and/or genetic defects and skeletal dysplasia, and secondary growth deficits due to endocrine or other chronic disorders such as celiac disease, Crohn's disease, malnutrition, renal, anorexia nervosa or other chronic diseases. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

How the early sporulation sigma factor sigmaF delays the switch to late development in Bacillus subtilis.

PubMed

Karmazyn-Campelli, Céline; Rhayat, Lamya; Carballido-López, Rut; Duperrier, Sandra; Frandsen, Niels; Stragier, Patrick

2008-03-01

Sporulation in Bacillus subtilis is a primitive differentiation process involving two cell types, the forespore and the mother cell. Each cell implements two successive transcription programmes controlled by specific sigma factors. We report that activity of sigma(G), the late forespore sigma factor, is kept in check by Gin, the product of csfB, a gene controlled by sigma(F), the early forespore sigma factor. Gin abolishes sigma(G) transcriptional activity when sigma(G) is artificially synthesized during growth, but has no effect on sigma(F). Gin interacts strongly with sigma(G) but not with sigma(F) in a yeast two-hybrid experiment. The absence of Gin allows sigma(G) to be active during sporulation independently of the mother-cell development to which it is normally coupled. Premature sigma(G) activity leads to the formation of slow-germinating spores, and complete deregulation of sigma(G) synthesis is lethal when combined with gin inactivation. Gin allows sigma(F) to delay the switch to the late forespore transcription programme by preventing sigma(G) to take over before the cell has reached a critical stage of development. A similar strategy, following a completely unrelated route, is used by the mother cell.

Distinct cerebellar foliation anomalies in a CHD7 haploinsufficient mouse model of CHARGE syndrome

PubMed Central

Whittaker, Danielle E.; Kasah, Sahrunizam; Donovan, Alex P. A.; Ellegood, Jacob; Riegman, Kimberley L. H.; Volk, Holger A.; McGonnell, Imelda; Lerch, Jason P.

2017-01-01

Mutations in the gene encoding the ATP dependent chromatin‐remodeling factor, CHD7 are the major cause of CHARGE (Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital‐urinary anomalies, and Ear defects) syndrome. Neurodevelopmental defects and a range of neurological signs have been identified in individuals with CHARGE syndrome, including developmental delay, lack of coordination, intellectual disability, and autistic traits. We previously identified cerebellar vermis hypoplasia and abnormal cerebellar foliation in individuals with CHARGE syndrome. Here, we report mild cerebellar hypoplasia and distinct cerebellar foliation anomalies in a Chd7 haploinsufficient mouse model. We describe specific alterations in the precise spatio‐temporal sequence of fissure formation during perinatal cerebellar development responsible for these foliation anomalies. The altered cerebellar foliation pattern in Chd7 haploinsufficient mice show some similarities to those reported in mice with altered Engrailed, Fgf8 or Zic1 gene expression and we propose that mutations or polymorphisms in these genes may modify the cerebellar phenotype in CHARGE syndrome. Our findings in a mouse model of CHARGE syndrome indicate that a careful analysis of cerebellar foliation may be warranted in patients with CHARGE syndrome, particularly in patients with cerebellar hypoplasia and developmental delay. PMID:29168327

Local requirement of the Drosophila insulin binding protein imp-L2 in coordinating developmental progression with nutritional conditions.

PubMed

Sarraf-Zadeh, Ladan; Christen, Stefan; Sauer, Uwe; Cognigni, Paola; Miguel-Aliaga, Irene; Stocker, Hugo; Köhler, Katja; Hafen, Ernst

2013-09-01

In Drosophila, growth takes place during the larval stages until the formation of the pupa. Starvation delays pupariation to allow prolonged feeding, ensuring that the animal reaches an appropriate size to form a fertile adult. Pupariation is induced by a peak of the steroid hormone ecdysone produced by the prothoracic gland (PG) after larvae have reached a certain body mass. Local downregulation of the insulin/insulin-like growth factor signaling (IIS) activity in the PG interferes with ecdysone production, indicating that IIS activity in the PG couples the nutritional state to development. However, the underlying mechanism is not well understood. In this study we show that the secreted Imaginal morphogenesis protein-Late 2 (Imp-L2), a growth inhibitor in Drosophila, is involved in this process. Imp-L2 inhibits the activity of the Drosophila insulin-like peptides by direct binding and is expressed by specific cells in the brain, the ring gland, the gut and the fat body. We demonstrate that Imp-L2 is required to regulate and adapt developmental timing to nutritional conditions by regulating IIS activity in the PG. Increasing Imp-L2 expression at its endogenous sites using an Imp-L2-Gal4 driver delays pupariation, while Imp-L2 mutants exhibit a slight acceleration of development. These effects are strongly enhanced by starvation and are accompanied by massive alterations of ecdysone production resulting most likely from increased Imp-L2 production by neurons directly contacting the PG and not from elevated Imp-L2 levels in the hemolymph. Taken together our results suggest that Imp-L2-expressing neurons sense the nutritional state of Drosophila larvae and coordinate dietary information and ecdysone production to adjust developmental timing under starvation conditions. Copyright © 2013 Elsevier Inc. All rights reserved.

Prepubertal exposure to arsenic(III) suppresses circulating insulin-like growth factor-1 (IGF-1) delaying sexual maturation in female rats.

PubMed

Reilly, Michael P; Saca, James C; Hamilton, Alina; Solano, Rene F; Rivera, Jesse R; Whitehouse-Innis, Wendy; Parsons, Jason G; Dearth, Robert K

2014-04-01

Arsenic (As) is a prevalent environmental toxin readily accessible for human consumption and has been identified as an endocrine disruptor. However, it is not known what impact As has on female sexual maturation. Therefore, in the present study, we investigated the effects of prepubertal exposure on mammary gland development and pubertal onset in female rats. Results showed that prepubertal exposure to 10 mg/kg of arsenite (As(III)) delayed vaginal opening (VO) and prepubertal mammary gland maturation. We determined that As accumulates in the liver, disrupts hepatocyte function and suppresses serum levels of the puberty related hormone insulin-like growth factor 1 (IGF-1) in prepubertal animals. Overall, this is the first study to show that prepubertal exposure to As(III) acts peripherally to suppress circulating levels of IGF-1 resulting in delayed sexual maturation. Furthermore, this study identifies a critical window of increased susceptibility to As(III) that may have a lasting impact on female reproductive function. Copyright © 2013 Elsevier Inc. All rights reserved.

Prevention of Tartrate Crystallization in Wine by Hydrocolloids: The Mechanism Studied by Dynamic Light Scattering.

PubMed

Lankhorst, Peter P; Voogt, Benjamin; Tuinier, Remco; Lefol, Blandine; Pellerin, Patrice; Virone, Cristiana

2017-10-11

Young wines are supersaturated in potassium bitartrate, which induces rather uncontrolled crystallization processes. Delayed crystallization may occur even after bottling of the young wines, which is undesirable because it gives rise to a visual defect in the wine. Colloids such as mannoproteins, metatartaric acid, and carboxymethylcellulose are available on the market and may be added to delay crystallization. It has been a matter of debate whether such hydrocolloids prevent nucleation, growth of crystals, or both. It was the objective of this investigation to study the crystallization event by a new approach using dynamic light scattering and to clarify the mode of action of these hydrocolloids. To achieve this, model solutions and standardized wines were enriched with potassium bitartrate (KHT) to trigger crystallization. In this way, it was possible to distinguish between the influence of the hydrocolloids on nucleation and on crystal growth. It was found that the hydrocolloids do not prevent KHT nucleation. Instead, these compounds delay or even arrest the outgrowth of the crystals to a macroscopic, visual size.

Growth and development of children prenatally exposed to telbivudine administered for the treatment of chronic hepatitis B in their mothers.

PubMed

Zeng, Huihui; Cai, Haodong; Wang, Ying; Shen, Ying

2015-04-01

We studied the growth and development of children prenatally exposed to telbivudine used to treat chronic hepatitis B virus (HBV) infection in their mothers. Maternal abnormalities during pregnancy and delivery and infant congenital anomalies, physical development status, developmental quotient (DQ), HBV vertical transmission status, and HBV vaccination outcomes of 54 infants were evaluated (2010-2013). No fetal abnormalities were observed during pregnancy or delivery. Postpartum, three infants (5.56%) had abnormalities: ankyloglossia, cutaneous hemangioma, and vaginal canal leak. Height and weight were within the normal range at birth and at 6 weeks, but were higher than the reference at 12 months (p<0.05). Body mass index increased gradually with age (p<0.05). DQ scores were normal (84.81%, 229/270) in 37 children (68.52%), abnormal or suspicious for a developmental delay (15.19%, 41/270) in 17 children (31.48%), and indicated a developmental delay (4.07%, 11/270) in seven children (12.96%). There were no significant differences in developmental delay between children prenatally exposed to telbivudine and controls (p>0.05). HBV vertical transmission was successfully blocked in all infants. The effective HBV vaccination rate was 98.15% (53/54). The growth and development of children prenatally exposed to telbivudine was normal, indicating that telbivudine treatment during pregnancy is safe and effective. Copyright © 2015. Published by Elsevier Ltd.

In vivo combination of misonidazole and the chemotherapeutic agent CCNU.

PubMed Central

Siemann, D. W.

1981-01-01

The response of intramuscularly growing KHT sarcomas to the chemotherapeutic agent (1-(2-cloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) alone or simultaneously with the chemical radio-sensitizer misonidazole (MISO) was assessed using either a tumour growth-delay assay or an in vivo-in vitro tumour-excision assay. Median tumour growth delay following the combination of 20 mg/kg CCNU and either 0.5 or 1.0 mg/g MISO was 19.5 and 21.5 days, compared to 10 days for this CCNU dose alone. A similar degree of enhanced tumour response by MISO (factor of approximately 2 in tumour growth delay) was seen in RIF-1 tumours treated with 20 mg/kg CCNU plus 1.0 mg/g MISO. Clonogenic cell-survival studies with KHT sarcomas demonstrated that MISO at doses of 0.25, 0.5 or 1.0 mg/g given simultaneously with a range of CCNU doses produced dose-modifying factors (DMFs) of 1.9, 2.1 and 2.4 respectively. Normal tissue toxicity assessed by an LD50/7 assay led to DMFs of 1.2 and 1.4 for CCNU doses combined with 0.5 and 1.0 mg/g MISO. Thus in this animal tumour model the combination of CCNU and MISO appears to lead to a potential gain by a factor of approximately 1.7. PMID:7225287

Comparison of Progressive Prompt Delay with and without Instructive Feedback

ERIC Educational Resources Information Center

Reichow, Brian; Wolery, Mark

2011-01-01

We examined the effectiveness and efficiency of 2 instructional arrangements using progressive prompt delay (PPD) with 3 young children with autism and 1 child with developmental delays. Specifically, we compared PPD with instructive feedback (IF) to PPD without IF in an adapted alternating treatment design. The results suggested that (a) children…

Improved On-Chip Measurement of Delay in an FPGA or ASIC

NASA Technical Reports Server (NTRS)

Chen, Yuan; Burke, Gary; Sheldon, Douglas

2007-01-01

An improved design has been devised for on-chip-circuitry for measuring the delay through a chain of combinational logic elements in a field-programmable gate array (FPGA) or application-specific integrated circuit (ASIC). In the improved design, the delay chain does not include input and output buffers and is not configured as an oscillator. Instead, the delay chain is made part of the signal chain of an on-chip pulse generator. The duration of the pulse is measured on-chip and taken to equal the delay.

Innovative virtual reality measurements for embryonic growth and development.

PubMed

Verwoerd-Dikkeboom, C M; Koning, A H J; Hop, W C; van der Spek, P J; Exalto, N; Steegers, E A P

2010-06-01

Innovative imaging techniques, using up-to-date ultrasonic equipment, necessitate specific biometry. The aim of our study was to test the possibility of detailed human embryonic biometry using a virtual reality (VR) technique. In a longitudinal study, three-dimensional (3D) measurements were performed from 6 to 14 weeks gestational age in 32 pregnancies (n = 16 spontaneous conception, n = 16 IVF/ICSI). A total of 125 3D volumes were analysed in the I-Space VR system, which allows binocular depth perception, providing a realistic 3D illusion. Crown-rump length (CRL), biparietal diameter (BPD), occipito-frontal diameter (OFD), head circumference (HC) and abdominal circumference (AC) were measured as well as arm length, shoulder width, elbow width, hip width and knee width. CRL, BPD, OFD and HC could be measured in more than 96% of patients, and AC in 78%. Shoulder width, elbow width, hip width and knee width could be measured in more than 95% of cases, and arm length in 82% of cases. Growth curves were constructed for all variables. Ear and foot measurements were only possible beyond 9 weeks gestation. This study provides a detailed, longitudinal description of normal human embryonic growth, facilitated by a VR system. Growth curves were created for embryonic biometry of the CRL, BPD, HC and AC early in pregnancy and also of several 'new' biometric measurements. Applying virtual embryoscopy will enable us to diagnose growth and/or developmental delay earlier and more accurately. This is especially important for pregnancies at risk of severe complications, such as recurrent late miscarriage and early growth restriction.

Delayed puberty in girls

MedlinePlus

... the ovaries A tumor in the pituitary gland Turner syndrome , a genetic disorder ... child's growth: The MAGIC Foundation -- www.magicfoundation.org Turner Syndrome Society of the United States -- www.turnersyndrome.org

N-cadherin Regulation of Bone Growth and Homeostasis is Osteolineage Stage-Specific

PubMed Central

Fontana, Francesca; Hickman-Brecks, Cynthia L.; Salazar, Valerie S.; Revollo, Leila; Abou-Ezzi, Grazia; Grimston, Susan K.; Jeong, Sung Yeop; Watkins, Marcus; Fortunato, Manuela; Alippe, Yael; Link, Daniel C.; Mbalaviele, Gabriel; Civitelli, Roberto

2017-01-01

N-cadherin inhibits osteogenic cell differentiation and canonical Wnt/β-catenin signaling in vitro. However, in vivo both conditional Cdh2 ablation and overexpression in osteoblasts lead to low bone mass. We tested the hypothesis that N-cadherin has different effects on osteolineage cells depending upon their differentiation stage. Embryonic conditional osteolineage Cdh2 deletion in mice results in defective growth, low bone mass and reduced osteoprogenitor number. These abnormalities are prevented by delaying Cdh2 ablation until 1 month of age, thus targeting only committed and mature osteoblasts, suggesting they are the consequence of N-cadherin deficiency in osteoprogenitors. Indeed, diaphyseal trabecularization actually increases when Cdh2 is ablated postnatally. The sclerostin-insensitive Lrp5A214V mutant, associated with high bone mass, does not rescue the growth defect, but it overrides the low bone mass of embryonically Cdh2 deleted mice, suggesting N-cadherin interacts with Wnt signaling to control bone mass. Finally, bone accrual and β-catenin accumulation after administration of an anti-Dkk1 antibody are enhanced in N-cadherin deficient mice. Thus, while lack of N-cadherin in embryonic and perinatal age is detrimental to bone growth and bone accrual, in adult mice loss of N-cadherin in osteolineage cells favors bone formation. Hence, N-cadherin inhibition may widen the therapeutic window of osteoanabolic agents. PMID:28240364

Embryonic delay in growth and development related to confined placental trisomy 16 mosaicism, diagnosed by I-Space Virtual Reality.

PubMed

Verwoerd-Dikkeboom, Christine M; van Heesch, Peter N A C M; Koning, Anton H J; Galjaard, Robert-Jan H; Exalto, Niek; Steegers, Eric A P

2008-11-01

To demonstrate the use of a novel three-dimensional (3D) virtual reality (VR) system in the visualization of first trimester growth and development in a case of confined placental trisomy 16 mosaicism (CPM+16). Case report. Prospective study on first trimester growth using a 3D VR system. A 34-year-old gravida 1, para 0 was seen weekly in the first trimester for 3D ultrasound examinations. Chorionic villus sampling was performed because of an enlarged nuchal translucency (NT) measurement and low pregnancy-associated plasma protein-A levels, followed by amniocentesis. Amniocentesis revealed a CPM+16. On two-dimensional (2D) and 3D ultrasound no structural anomalies were found with normal fetal Dopplers. Growth remained below the 2.3 percentile. At 37 weeks, a female child of 2010 g (<2.5 percentile) was born. After birth, growth climbed to the 50th percentile in the first 2 months. The I-Space VR system provided information about phenotypes not obtainable by standard 2D ultrasound. In this case, the delay in growth and development could be observed very early in pregnancy. Since first trimester screening programs are still improving and becoming even more important, systems such as the I-Space open a new era for in vivo studies on the physiologic and pathologic processes involved in embryogenesis.

[Jaw osteosarcomas].

PubMed

Steve, M; Ernenwein, D; Chaine, A; Bertolus, C; Goudot, P; Ruhin-Poncet, B

2011-11-01

Osteosarcoma (OS) is the most frequent bone malignant tumor. It is usually found on long bones, 5 to 10% are located on jaws, accounting for 0.5 to 1% of all facial tumors. There is little published data which concerns only few patients. Our aim was to study retrospectively cases of facial bone OS in adults, and to compare our results with published data to suggest an optimal management scheme. Thirty-three patients were managed for an OS, from January 1997 to January 2007. Fourteen patients with a maxillary and mandibular OS, treated in first-intention in our unit, were included. The following data were analyzed: age; personal history; circumstance of discovery; clinical, functional, and physical signs; loco-regional extension and metastasis radiological investigation. The histological slides were systematically reviewed. The protocol, therapeutic outcome, and follow-up were studied. The mean age at diagnosis was 43. Swelling was the most frequent functional sign. The mean delay before management was 3.4 months. The most frequent radiological presentation was a lytic and hyperdense image. The diagnosis was suggested after CT scan in 57.1% of cases. The biopsy was correlated to the anatomopathological analysis in 78.6% of cases. The most common treatment was surgical exeresis completed by chemotherapy. The 5-year survival rate was 50%. Jaw OS are specific because of their localization and specific bone ultrastructure. Their management remains controversial: should they be managed like limb OS or treated more specifically? Neoadjuvant chemotherapy, even if it delays exeresis for 3 months, seems to stop the growth or reduce the tumor. An early anatomopathological analysis of the surgical piece determines adjuvant therapy. The negative prognostic factors are: maxillary localization because of limited exeresis margins, tumoral size, and osteoblastic sub-type. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Roles of germination-specific lytic enzymes CwlJ and SleB in Bacillus anthracis.

PubMed

Heffron, Jared D; Orsburn, Benjamin; Popham, David L

2009-04-01

The structural characteristics of a spore enable it to withstand stresses that typically kill a vegetative cell. Spores remain dormant until small molecule signals induce them to germinate into vegetative bacilli. Germination requires degradation of the thick cortical peptidoglycan by germination-specific lytic enzymes (GSLEs). Bacillus anthracis has four putative GSLEs, based upon sequence similarities with enzymes in other species: SleB, CwlJ1, CwlJ2, and SleL. In this study, the roles of SleB, CwlJ1, and CwlJ2 were examined. The expression levels of all three genes peak 3.5 h into sporulation. Genetic analysis revealed that, similar to other known GSLEs, none of these gene products are individually required for growth, sporulation, or triggering of germination. However, later germination events are affected in spores lacking CwlJ1 or SleB. Compared to the wild type, germinating spores without CwlJ1 suffer a delay in optical density loss and cortex peptidoglycan release. The absence of SleB also causes a delay in cortex fragment release. A double mutant lacking both SleB and CwlJ1 is completely blocked in cortex hydrolysis and progresses through outgrowth to produce colonies at a frequency 1,000-fold lower than that of the wild-type strain. A null mutation eliminating CwlJ2 has no effect on germination. High-performance liquid chromatography and mass spectroscopy analysis revealed that SleB is required for lytic transglycosylase activity. CwlJ1 also clearly participates in cortex hydrolysis, but its specific mode of action remains unclear. Understanding the lytic germination activities that naturally diminish spore resistance can lead to methods for prematurely inducing them, thus simplifying the process of treating contaminated sites.

Stage-specific disruption of Stat3 demonstrates a direct requirement during both the initiation and promotion stages of mouse skin tumorigenesis.

PubMed

Kataoka, Ken; Kim, Dae Joon; Carbajal, Steve; Clifford, John L; DiGiovanni, John

2008-06-01

Constitutive activation of signal transducer and activator of transcription 3 (Stat3) has been found in a variety of human malignancies and has been suggested to play an important role in carcinogenesis. Recently, our laboratory demonstrated that Stat3 is required for the development of skin tumors via two-stage carcinogenesis using skin-specific loss-of-function transgenic mice. To investigate further the role of Stat3 in each stage of chemical carcinogenesis in mouse skin, i.e. initiation and promotion stages, we generated inducible Stat3-deficient mice (K5.Cre-ER(T2) x Stat3(fl/fl)) that show epidermal-specific disruption of Stat3 following topical treatment with 4-hydroxytamoxifen (TM). The epidermis of inducible Stat3-deficient mice treated with TM showed a significant increase in apoptosis induced by 7,12-dimethylbenz[a]anthracene (DMBA) and reduced proliferation following exposure to 12-O-tetradecanoylphorbol-13-acetate. In two-stage skin carcinogenesis assays, inducible Stat3-deficient mice treated with TM during the promotion stage showed a significant delay of tumor development and a significantly reduced number of tumors compared with control groups. Inducible Stat3-deficient mice treated with TM before initiation with DMBA also showed a significant delay in tumor development and a significantly reduced number of tumors compared with control groups. Finally, treatment of inducible Stat3-deficient mice that had existing skin tumors generated by the two-stage carcinogenesis protocol with TM (by intraperitoneal injection) led to inhibition of tumor growth compared with tumors formed in control groups. Collectively, these results directly demonstrate that Stat3 is required for skin tumor development during both the initiation and promotion stages of skin carcinogenesis in vivo.

CDK10 Mutations in Humans and Mice Cause Severe Growth Retardation, Spine Malformations, and Developmental Delays.

PubMed

Windpassinger, Christian; Piard, Juliette; Bonnard, Carine; Alfadhel, Majid; Lim, Shuhui; Bisteau, Xavier; Blouin, Stéphane; Ali, Nur'Ain B; Ng, Alvin Yu Jin; Lu, Hao; Tohari, Sumanty; Talib, S Zakiah A; van Hul, Noémi; Caldez, Matias J; Van Maldergem, Lionel; Yigit, Gökhan; Kayserili, Hülya; Youssef, Sameh A; Coppola, Vincenzo; de Bruin, Alain; Tessarollo, Lino; Choi, Hyungwon; Rupp, Verena; Roetzer, Katharina; Roschger, Paul; Klaushofer, Klaus; Altmüller, Janine; Roy, Sudipto; Venkatesh, Byrappa; Ganger, Rudolf; Grill, Franz; Ben Chehida, Farid; Wollnik, Bernd; Altunoglu, Umut; Al Kaissi, Ali; Reversade, Bruno; Kaldis, Philipp

2017-09-07

In five separate families, we identified nine individuals affected by a previously unidentified syndrome characterized by growth retardation, spine malformation, facial dysmorphisms, and developmental delays. Using homozygosity mapping, array CGH, and exome sequencing, we uncovered bi-allelic loss-of-function CDK10 mutations segregating with this disease. CDK10 is a protein kinase that partners with cyclin M to phosphorylate substrates such as ETS2 and PKN2 in order to modulate cellular growth. To validate and model the pathogenicity of these CDK10 germline mutations, we generated conditional-knockout mice. Homozygous Cdk10-knockout mice died postnatally with severe growth retardation, skeletal defects, and kidney and lung abnormalities, symptoms that partly resemble the disease's effect in humans. Fibroblasts derived from affected individuals and Cdk10-knockout mouse embryonic fibroblasts (MEFs) proliferated normally; however, Cdk10-knockout MEFs developed longer cilia. Comparative transcriptomic analysis of mutant and wild-type mouse organs revealed lipid metabolic changes consistent with growth impairment and altered ciliogenesis in the absence of CDK10. Our results document the CDK10 loss-of-function phenotype and point to a function for CDK10 in transducing signals received at the primary cilia to sustain embryonic and postnatal development. Copyright © 2017 American Society of Human Genetics. All rights reserved.

Interact to Survive: Phyllobacterium brassicacearum Improves Arabidopsis Tolerance to Severe Water Deficit and Growth Recovery

PubMed Central

Bresson, Justine; Vasseur, François; Dauzat, Myriam; Labadie, Marc; Varoquaux, Fabrice; Touraine, Bruno; Vile, Denis

2014-01-01

Mutualistic bacteria can alter plant phenotypes and confer new abilities to plants. Some plant growth-promoting rhizobacteria (PGPR) are known to improve both plant growth and tolerance to multiple stresses, including drought, but reports on their effects on plant survival under severe water deficits are scarce. We investigated the effect of Phyllobacterium brassicacearum STM196 strain, a PGPR isolated from the rhizosphere of oilseed rape, on survival, growth and physiological responses of Arabidopsis thaliana to severe water deficits combining destructive and non-destructive high-throughput phenotyping. Soil inoculation with STM196 greatly increased the survival rate of A. thaliana under several scenarios of severe water deficit. Photosystem II efficiency, assessed at the whole-plant level by high-throughput fluorescence imaging (F v/F m), was related to the probability of survival and revealed that STM196 delayed plant mortality. Inoculated surviving plants tolerated more damages to the photosynthetic tissues through a delayed dehydration and a better tolerance to low water status. Importantly, STM196 allowed a better recovery of plant growth after rewatering and stressed plants reached a similar biomass at flowering than non-stressed plants. Our results highlight the importance of plant-bacteria interactions in plant responses to severe drought and provide a new avenue of investigations to improve drought tolerance in agriculture. PMID:25226036

Relationship between cervical vertebral maturation and mandibular growth.

PubMed

Ball, Gina; Woodside, Donald; Tompson, Bryan; Hunter, W Stuart; Posluns, James

2011-05-01

The cervical vertebrae have been proposed as a method of determining biologic maturity. The purposes of this study were to establish a pattern of mandibular growth and to relate this pattern to the stages of cervical vertebral maturation. Cephalometric radiographs, taken annually from ages 9 to 18 years, were evaluated for 90 boys from the Burlington Growth Center, Toronto, Ontario, Canada. Mandibular lengths were measured from articulare to gnathion, and incremental growth was determined. Cervical vertebral maturation stages were assessed by using a 6-stage method. Advanced, average, and delayed maturation groups were established. The prepubertal mandibular growth minimum velocity occurred during cervical stages 1 through 4 (P = 0.7327). Peak mandibular growth velocity occurred most frequently during stage 4 in all 3 maturation groups, with a statistical difference in the average and delayed groups (P <0.0001) and the advanced group (P = 0.0143). The average number of years spent in stage 4 was 3.79 (P <0.0001). The average amount of mandibular growth occurring during stage 4 was 9.40 mm (P <0.0001). The average amount of growth in stages 5 and 6 combined was 7.09 mm. Progression from cervical stages 1 through 6 does not occur annually; time spent in each stage varies depending on the stage and the maturation group. Cervical vertebral maturation stages cannot accurately identify the mandibular prepubertal growth minimum and therefore cannot predict the onset of the peak in mandibular growth. The cervical vertebral maturation stages should be used with other methods of biologic maturity assessment when considering both dentofacial orthopedic treatment and orthognathic surgery. Copyright © 2011 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Radiologic manifestations in the musculoskeletal system of miscellaneous endocrine disorders.

PubMed

Chew, F S

1991-01-01

The manifestations of endocrine derangements in the musculoskeletal system in infancy and childhood are disturbances in growth and maturation and in adulthood are disturbances in maintenance and metabolism. Hypercortisolism during skeletal immaturity suppresses growth. In the adult, hypercortisolism leads to osteoporosis, osteonecrosis, and muscle wasting. Deficiency of growth hormone during skeletal development results in short stature. An excess of growth hormone in a skeletally immature individual results in gigantism, an excess in a skeletally mature individual results in acromegaly. Patients with gigantism have extreme height with normal body proportions. Musculoskeletal manifestations of acromegaly include soft-tissue thickening, vertebral body enlargement, characteristic hand and foot changes, and enthesal bony proliferation. Hyperthyroidism causes catabolism of protein and loss of connective tissue, which manifest as muscle wasting. Deficient levels of thyroid hormone cause defects in growth and development. Severe growth retardation from congenital hypothyroidism is rare because neonatal screening recognizes the disorder and leads to early treatment. The skeletal manifestation of hypergonadism in children is precocious growth and early skeletal maturation. Although the initial precocious growth spurt results in a tall child, early closure of the growth plates results in a short adult. Hypogonadism in the prepubertal child results in delayed adolescence and delayed skeletal maturation. Diabetes mellitus in childhood results in decreased growth, a phenomenon presumed to be secondary to nutritional abnormalities. Generalized osteoporosis and short stature are common. In the adult, generalized osteoporosis may accompany insulin-dependent diabetes mellitus if obesity is absent. Calcification of interdigital arteries of the foot is common in diabetics and uncommon in other conditions. Additional skeletal manifestations relate to complications of diabetes such as peripheral neuropathy and diabetic foot disease.

Delay and probability discounting of sexual and monetary outcomes in individuals with cocaine use disorders and matched controls.

PubMed

Johnson, Matthew W; Johnson, Patrick S; Herrmann, Evan S; Sweeney, Mary M

2015-01-01

Individuals with cocaine use disorders are disproportionately affected by HIV/AIDS, partly due to higher rates of unprotected sex. Recent research suggests delay discounting of condom use is a factor in sexual HIV risk. Delay discounting is a behavioral economic concept describing how delaying an event reduces that event's value or impact on behavior. Probability discounting is a related concept describing how the uncertainty of an event decreases its impact on behavior. Individuals with cocaine use disorders (n = 23) and matched non-cocaine-using controls (n = 24) were compared in decision-making tasks involving hypothetical outcomes: delay discounting of condom-protected sex (Sexual Delay Discounting Task), delay discounting of money, the effect of sexually transmitted infection (STI) risk on likelihood of condom use (Sexual Probability Discounting Task), and probability discounting of money. The Cocaine group discounted delayed condom-protected sex (i.e., were more likely to have unprotected sex vs. wait for a condom) significantly more than controls in two of four Sexual Delay Discounting Task partner conditions. The Cocaine group also discounted delayed money (i.e., preferred smaller immediate amounts over larger delayed amounts) significantly more than controls. In the Sexual Probability Discounting Task, both groups showed sensitivity to STI risk, however the groups did not differ. The Cocaine group did not consistently discount probabilistic money more or less than controls. Steeper discounting of delayed, but not probabilistic, sexual outcomes may contribute to greater rates of sexual HIV risk among individuals with cocaine use disorders. Probability discounting of sexual outcomes may contribute to risk of unprotected sex in both groups. Correlations showed sexual and monetary results were unrelated, for both delay and probability discounting. The results highlight the importance of studying specific behavioral processes (e.g., delay and probability discounting) with respect to specific outcomes (e.g., monetary and sexual) to understand decision making in problematic behavior.

Delay and Probability Discounting of Sexual and Monetary Outcomes in Individuals with Cocaine Use Disorders and Matched Controls

PubMed Central

Johnson, Matthew W.; Johnson, Patrick S.; Herrmann, Evan S.; Sweeney, Mary M.

2015-01-01

Individuals with cocaine use disorders are disproportionately affected by HIV/AIDS, partly due to higher rates of unprotected sex. Recent research suggests delay discounting of condom use is a factor in sexual HIV risk. Delay discounting is a behavioral economic concept describing how delaying an event reduces that event’s value or impact on behavior. Probability discounting is a related concept describing how the uncertainty of an event decreases its impact on behavior. Individuals with cocaine use disorders (n = 23) and matched non-cocaine-using controls (n = 24) were compared in decision-making tasks involving hypothetical outcomes: delay discounting of condom-protected sex (Sexual Delay Discounting Task), delay discounting of money, the effect of sexually transmitted infection (STI) risk on likelihood of condom use (Sexual Probability Discounting Task), and probability discounting of money. The Cocaine group discounted delayed condom-protected sex (i.e., were more likely to have unprotected sex vs. wait for a condom) significantly more than controls in two of four Sexual Delay Discounting Task partner conditions. The Cocaine group also discounted delayed money (i.e., preferred smaller immediate amounts over larger delayed amounts) significantly more than controls. In the Sexual Probability Discounting Task, both groups showed sensitivity to STI risk, however the groups did not differ. The Cocaine group did not consistently discount probabilistic money more or less than controls. Steeper discounting of delayed, but not probabilistic, sexual outcomes may contribute to greater rates of sexual HIV risk among individuals with cocaine use disorders. Probability discounting of sexual outcomes may contribute to risk of unprotected sex in both groups. Correlations showed sexual and monetary results were unrelated, for both delay and probability discounting. The results highlight the importance of studying specific behavioral processes (e.g., delay and probability discounting) with respect to specific outcomes (e.g., monetary and sexual) to understand decision making in problematic behavior. PMID:26017273

Introducing time delay in the evolution of new technology: the case study of nanotechnology

NASA Astrophysics Data System (ADS)

Georgalis, Evangelos E.; Aifantis, Elias C.

2013-12-01

Starting with Feynman's "There's Plenty of Room at the Bottom" prophetic lecture at Caltech in the 1960s, the term "nanotechnology" was first coined in the scientific literature in the 1980s. This was followed by the unprecedented growth in the corresponding scientific field in 2000 due to the financial incentive provided by President Clinton in the US, followed up by similar efforts in Europe, Japan, China and Russia. Today, nanotechnology has become a driving force for economic development, with applications in all fields of engineering, information technology, transport and energy, as well as biology and medicine. Thus, it is important to forecast its future growth and evolution on the basis of two different criteria: (1) the government and private capital invested in related activities, and (2) the number of scientific publications and popular articles dedicated to this field. This article aims to extract forecasts on the evolution of nanotechnology, using the standard logistic equation that result in familiar sigmoid curves, as well as to explore the effect of time delay on its evolution. Time delay is commonly known from previous biological and ecological models, in which time lag is either already known or can be experimentally measured. In contrast, in the case of a new technology, we must first define the method for determining time delay and then interpret its existence and role. Then we describe the implications that time delay may have on the stability of the sigmoidal behavior of nanotechnology evolution and on the related oscillations that may appear.

Divergent effects of new cyclooxygenase inhibitors on gastric ulcer healing: Shifting the angiogenic balance

PubMed Central

Ma, Li; del Soldato, Piero; Wallace, John L.

2002-01-01

Delayed gastric ulcer healing is a well recognized problem associated with the use of cyclooxygenase (COX) inhibitors. In contrast, NO-releasing COX inhibitors do not interfere with ulcer healing. These divergent effects may in part be due to differences in their effects on platelets, which are known to influence ulcer healing. Therefore, we compared the effects of a nonselective COX inhibitor (flurbiprofen), a nitric oxide-releasing COX inhibitor (HCT-1026), and a selective COX-2 inhibitor (celecoxib) on gastric ulcer healing, angiogenesis, and platelet/serum levels of vascular endothelial growth factor (VEGF) and endostatin. Gastric ulcers were induced in rats by serosal application of acetic acid. Daily treatment with the test drugs was started 3 days later and continued for 1 week. Celecoxib and flurbiprofen impaired angiogenesis and delayed ulcer healing, as well as increasing serum endostatin levels relative to those of VEGF. HCT-1026 did not delay ulcer healing nor impair angiogenesis, and also did not change the ratio of serum endostatin to VEGF. Incubation of human umbilical vein endothelial cells with serum from celecoxib- or flurbiprofen-treated rats resulted in suppressed proliferation and increased apoptosis, effects that were reversed by an antiendostatin antibody. These results demonstrate a previously unrecognized mechanism through which nonsteroidal antiinflammatory drugs can delay ulcer healing, namely, through altering the balance of anti- and proangiogenic factors in the serum. The absence of a delaying effect of HCT-1026 on ulcer healing may be related to the maintenance of a more favorable balance in serum levels of pro- and antiangiogenic growth factors. PMID:12232050

Delayed changes in auditory status in cochlear implant users with preserved acoustic hearing.

PubMed

Scheperle, Rachel A; Tejani, Viral D; Omtvedt, Julia K; Brown, Carolyn J; Abbas, Paul J; Hansen, Marlan R; Gantz, Bruce J; Oleson, Jacob J; Ozanne, Marie V

2017-07-01

This retrospective review explores delayed-onset hearing loss in 85 individuals receiving cochlear implants designed to preserve acoustic hearing at the University of Iowa Hospitals and Clinics between 2001 and 2015. Repeated measures of unaided behavioral audiometric thresholds, electrode impedance, and electrically evoked compound action potential (ECAP) amplitude growth functions were used to characterize longitudinal changes in auditory status. Participants were grouped into two primary categories according to changes in unaided behavioral thresholds: (1) stable hearing or symmetrical hearing loss and (2) delayed loss of hearing in the implanted ear. Thirty-eight percent of this sample presented with delayed-onset hearing loss of various degrees and rates of change. Neither array type nor insertion approach (round window or cochleostomy) had a significant effect on prevalence. Electrode impedance increased abruptly for many individuals exhibiting precipitous hearing loss; the increase was often transient. The impedance increases were significantly larger than the impedance changes observed for individuals with stable or symmetrical hearing loss. Moreover, the impedance changes were associated with changes in behavioral thresholds for individuals with a precipitous drop in behavioral thresholds. These findings suggest a change in the electrode environment coincident with the change in auditory status. Changes in ECAP thresholds, growth function slopes, and suprathreshold amplitudes were not correlated with changes in behavioral thresholds, suggesting that neural responsiveness in the region excited by the implant is relatively stable. Further exploration into etiology of delayed-onset hearing loss post implantation is needed, with particular interest in mechanisms associated with changes in the intracochlear environment. Copyright © 2017 Elsevier B.V. All rights reserved.

Maternal, social and abiotic environmental effects on growth vary across life stages in a cooperative mammal.

PubMed

English, Sinead; Bateman, Andrew W; Mares, Rafael; Ozgul, Arpat; Clutton-Brock, Tim H

2014-03-01

Resource availability plays a key role in driving variation in somatic growth and body condition, and the factors determining access to resources vary considerably across life stages. Parents and carers may exert important influences in early life, when individuals are nutritionally dependent, with abiotic environmental effects having stronger influences later in development as individuals forage independently. Most studies have measured specific factors influencing growth across development or have compared relative influences of different factors within specific life stages. Such studies may not capture whether early-life factors continue to have delayed effects at later stages, or whether social factors change when individuals become nutritionally independent and adults become competitors for, rather than providers of, food. Here, we examined variation in the influence of the abiotic, social and maternal environment on growth across life stages in a wild population of cooperatively breeding meerkats. Cooperatively breeding vertebrates are ideal for investigating environmental influences on growth. In addition to experiencing highly variable abiotic conditions, cooperative breeders are typified by heterogeneity both among breeders, with mothers varying in age and social status, and in the number of carers present. Recent rainfall had a consistently marked effect on growth across life stages, yet other seasonal terms only influenced growth during stages when individuals were growing fastest. Group size and maternal dominance status had positive effects on growth during the period of nutritional dependence on carers, but did not influence mass at emergence (at 1 month) or growth at independent stages (>4 months). Pups born to older mothers were lighter at 1 month of age and subsequently grew faster as subadults. Males grew faster than females during the juvenile and subadult stage only. Our findings demonstrate the complex ways in which the external environment influences development in a cooperative mammal. Individuals are most sensitive to social and maternal factors during the period of nutritional dependence on carers, whereas direct environmental effects are relatively more important later in development. Understanding the way in which environmental sensitivity varies across life stages is likely to be an important consideration in predicting trait responses to environmental change. © 2013 The Authors. Journal of Animal Ecology published by John Wiley & Sons Ltd on behalf of the British Ecological Society.

Etanercept Injection

MedlinePlus

... own joints, causing pain, swelling, and loss of function) in adults, psoriatic arthritis (condition that causes joint ... its own joints, causing pain, swelling, loss of function, and delays in growth and development) in children ...

29 CFR 102.54 - Initiation of formal compliance proceedings; issuance of compliance specification and notice of...

Code of Federal Regulations, 2011 CFR

2011-07-01

... the purposes and policies of the Act or to avoid unnecessary costs or delay, the Regional Director may... policies of the Act or to avoid unnecessary costs or delay, the Regional Director may consolidate with a... formal proceeding, the Regional Director may issue and serve on all parties a compliance specification in...

29 CFR 102.54 - Initiation of formal compliance proceedings; issuance of compliance specification and notice of...

Code of Federal Regulations, 2010 CFR

2010-07-01

... the purposes and policies of the Act or to avoid unnecessary costs or delay, the Regional Director may... policies of the Act or to avoid unnecessary costs or delay, the Regional Director may consolidate with a... formal proceeding, the Regional Director may issue and serve on all parties a compliance specification in...

Language Delay in Severely Neglected Children: A Cumulative or Specific Effect of Risk Factors?

ERIC Educational Resources Information Center

Sylvestre, Audette; Merette, Chantal

2010-01-01

Objectives: This research sought to determine if the language delay (LD) of severely neglected children under 3 years old was better explained by a cumulative risk model or by the specificity of risk factors. The objective was also to identify the risk factors with the strongest impact on LD among various biological, psychological, and…

Maternal synthesis of abscisic acid controls seed development and yield in Nicotiana plumbaginifolia.

PubMed

Frey, Anne; Godin, Béatrice; Bonnet, Magda; Sotta, Bruno; Marion-Poll, Annie

2004-04-01

The role of maternally derived abscisic acid (ABA) during seed development has been studied using ABA-deficient mutants of Nicotiana plumbaginifolia Viviani. ABA deficiency induced seed abortion, resulting in reduced seed yield, and delayed growth of the remaining embryos. Mutant grafting onto wild-type stocks and reciprocal crosses indicated that maternal ABA, synthesized in maternal vegetative tissues and translocated to the seed, promoted early seed development and growth. Moreover ABA deficiency delayed both seed coat pigmentation and capsule dehiscence. Mutant grafting did not restore these phenotypes, indicating that ABA synthesized in the seed coat and capsule envelope may have a positive effect on capsule and testa maturation. Together these results shed light on the positive role of maternal ABA during N. plumbaginifolia seed development.

[Delayed adverse reactions to blood donation: From haemovigilance data to specific studies].

PubMed

Py, J-Y; Durieux, S; Barnoux, M; Sapey, T

2016-11-01

Delayed adverse reactions to blood donation occur after the donor left donation site. Their intrinsic gravity and possible complications can be increased by the fact the donor is alone. This can also increase bad memories, leading to a donation giving up. Blood transfusion centre is only aware in case of donor feedback, hence an event underrating. We choose to compare our data upon delayed adverse donor reactions with those we could find in past studies. A first data level comes from French haemovigilance data while serious adverse reactions declaration is mandatory. But a second level can be reached using blood transfusion centre computerized data because all the donation reactions are saved whatever the gravity is. In both cases, delayed reactions are only those reported by donors. We try to make an exhaustive search of specific studies upon the real delayed reactions incidence so as to compare with our data. There were 1957 serious adverse reactions declared in our regional haemovigilance database between 2011 and 2015: 49 % occurring during donation, 40 % after it but before donor departure, and 11 % delayed events. There were 16,050 adverse reactions recorded during the first trimester of 2016 in mainland France, with 2.7 % delayed ones. Proportion of delayed events rises when gravity rises, until 27.6 % for the most serious ones. It varies between 2.2 % and 2.7 % for vasovagal reactions, haematomas, and other local reactions, and reaches 16.2 % for other general reactions. Data found in other studies with a spontaneous donor notification are of the same kind. But four studies soliciting specifically donor notification give a dramatically higher delayed reactions incidence, with an understatement greater than three out of four. Moreover, these studies found a majority of delayed reactions, which are not included in haemovigilance like fatigue or bruising. Occurrence of a delayed donor reaction is clearly underrated in standard haemovigilance. It remains to be seen whether it have the same impact on donor return as immediate reactions. Considering that delayed reactions are much larger, it might be interesting to take them into account in the evaluation of strategies dedicated to lower immediate reactions. Copyright © 2016. Published by Elsevier SAS.

Early Generalized Overgrowth in Boys With Autism

PubMed Central

Chawarska, Katarzyna; Campbell, Daniel; Chen, Lisha; Shic, Frederick; Klin, Ami; Chang, Joseph

2016-01-01

Context Multiple studies have reported an overgrowth in head circumference (HC) in the first year of life in autism. However, it is unclear whether this phenomenon is independent of overall body growth and whether it is associated with specific social or cognitive features. Objectives To examine the trajectory of early HC growth in autism compared with control groups; to assess whether HC growth in autism is independent of height and weight growth during infancy; and to examine HC growth from birth to 24 months in relationship to social, verbal, cognitive, and adaptive functioning levels. Design Retrospective study. Setting A specialized university-based clinic. Participants Boys diagnosed as having autistic disorder (n=64), pervasive developmental disorder–not otherwise specified (n=34), global developmental delay (n=13), and other developmental problems (n=18) and typically developing boys (n=55). Main Outcome Measures Age-related changes in HC, height, and weight between birth and age 24 months; measures of social, verbal, and cognitive functioning at age 2 years. Results Compared with typically developing controls, boys with autism were significantly longer by age 4.8 months, had a larger HC by age 9.5 months, and weighed more by age 11.4 months (P=.05 for all). None of the other clinical groups showed a similar overgrowth pattern. Boys with autism who were in the top 10% of overall physical size in infancy exhibited greater severity of social deficits (P=.009) and lower adaptive functioning (P=.03). Conclusions Boys with autism experienced accelerated HC growth in the first year of life. However, this phenomenon reflected a generalized process affecting other morphologic features, including height and weight. The study highlights the importance of studying factors that influence not only neuronal development but also skeletal growth in autism. PMID:21969460

Rhomboid Enhancer Activity Defines a Subset of Drosophila Neural Precursors Required for Proper Feeding, Growth and Viability

PubMed Central

Gresser, Amy L.; Gutzwiller, Lisa M.; Gauck, Mackenzie K.; Hartenstein, Volker; Cook, Tiffany A.; Gebelein, Brian

2015-01-01

Organismal growth regulation requires the interaction of multiple metabolic, hormonal and neuronal pathways. While the molecular basis for many of these are well characterized, less is known about the developmental origins of growth regulatory structures and the mechanisms governing control of feeding and satiety. For these reasons, new tools and approaches are needed to link the specification and maturation of discrete cell populations with their subsequent regulatory roles. In this study, we characterize a rhomboid enhancer element that selectively labels four Drosophila embryonic neural precursors. These precursors give rise to the hypopharyngeal sensory organ of the peripheral nervous system and a subset of neurons in the deutocerebral region of the embryonic central nervous system. Post embryogenesis, the rhomboid enhancer is active in a subset of cells within the larval pharyngeal epithelium. Enhancer-targeted toxin expression alters the morphology of the sense organ and results in impaired larval growth, developmental delay, defective anterior spiracle eversion and lethality. Limiting the duration of toxin expression reveals differences in the critical periods for these effects. Embryonic expression causes developmental defects and partially penetrant pre-pupal lethality. Survivors of embryonic expression, however, ultimately become viable adults. In contrast, post-embryonic toxin expression results in fully penetrant lethality. To better define the larval growth defect, we used a variety of assays to demonstrate that toxin-targeted larvae are capable of locating, ingesting and clearing food and they exhibit normal food search behaviors. Strikingly, however, following food exposure these larvae show a rapid decrease in consumption suggesting a satiety-like phenomenon that correlates with the period of impaired larval growth. Together, these data suggest a critical role for these enhancer-defined lineages in regulating feeding, growth and viability. PMID:26252385

Growth form-dependent response to physical disturbance and thermal stress in Acropora corals

NASA Astrophysics Data System (ADS)

Muko, S.; Arakaki, S.; Nagao, M.; Sakai, Kazuhiko

2013-03-01

To predict the community structure in response to changing environmental conditions, it is necessary to know the species-specific reaction and relative impact strength of each disturbance. We investigated the coral communities in two sites, an exposed and a protected site, at Iriomote Island, Japan, from 2005 to 2008. During the study period, a cyclone and thermal stress were observed. All Acropora colonies, classified into four morphologies (arborescent, tabular, corymbose, and digitate), were identified and tracked through time to calculate the annual mortality and growth rate. The mortality of all Acropora colonies in the protected site was lower than that in the exposed site during the period without disturbances. Extremely higher mortality due to bleaching was observed in tabular and corymbose Acropora, compared to other growth forms, at the protected sites after thermal stress. In contrast, physical disturbance by a tropical cyclone induced the highest mortality in arborescent and digitate corals at the exposed site. Moreover, arborescent corals exhibited a remarkable decline 1 year after the tropical cyclone at the exposed site. The growth of colonies that survived coral bleaching did not decrease in the following year compared to previous year for all growth forms, but the growth of arborescent and tabular remnant corals at the exposed site declined severely after the tropical cyclone compared to previous year. The delayed mortality and lowered growth rate after the tropical cyclone were probably due to the damage caused by the tropical cyclone. These results indicate that the cyclone had a greater impact on fragile corals than expected. This study provides useful information for the evaluation of Acropora coral response to progressing global warming conditions, which are predicted to increase in frequency and intensity in the near future.

The effects of density dependent resource limitation on size of wild reindeer.

PubMed

Skogland, Terje

1983-11-01

A density-dependent decrement in size for wild reindeer from 12 different Norwegian herds at 16 different densities was shown using lower jawbone-length as the criterion of size. This criterion was tested and found to adequately predict body size of both bucks and does. Lactation in does did not affect jaw length but significantly affected dressed weights.A decrement in the size of does as a result of gross density was found. This size decrement was further analysed in relation to the habitat densities in winter (R 2 =0.85) and in summer (R 2 =0.75) separately, in order to estimate the relative effects of each factor. For herds with adequate food in winter (no signs of overgrazing of lichens) density in relation to summer habitat and mires yielded the highest predictive power in a multiple regression. For herds with adequate summer pastures, densities per winter habitat and lichen volumes showed likewise a highly significant correlation. The inclusion of the lichen volume data in the regression increased its predictive power. The major effect of resource limitation was to delay the time of calving because a maternal carry-over effect allowed the calf a shorter period of growth to be completed during its first summer. Neonate size at birth was highly correlated with maternal size regardless of the mean calving date although the latter was significantly delayed for small-sized does in food resource-limited herds. Likewise the postnatal growth rate of all calves were not significantly different during 50 days postpartum regardless of maternal conditions in winter feeding. The summer growth rates of bucks ≧1 year did not vary significantly between herds. The age of maturity of food resource-limited does was delayed by one year and growth ceased after the initiation of reproduction. This shows that under conditions of limited resources the does with delayed births of calves allocated less energy to body growth simply because they had less time to replenish body reserves once they were freed of the energetic demands of lactation. The overriding effects of such limitation of food resources is thus to produce a time-lag for the completition of all the important life-history events, such as growth, maintenance and reproduction. From a theoretical point of view, i.e. according to the reproductive effort model their only option is to try to overcome this time limitation to reproductive success.

Bayley-III Cognitive and Language Scales in Preterm Children.

PubMed

Spencer-Smith, Megan M; Spittle, Alicia J; Lee, Katherine J; Doyle, Lex W; Anderson, Peter J

2015-05-01

This study aimed to assess the sensitivity and specificity of the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), Cognitive and Language scales at 24 months for predicting cognitive impairments in preterm children at 4 years. Children born <30 weeks' gestation completed the Bayley-III at 24 months and the Differential Ability Scale, Second Edition (DAS-II), at 4 years to assess cognitive functioning. Test norms and local term-born reference data were used to classify delay on the Bayley-III Cognitive and Language scales. Impairment on the DAS-II Global Conceptual Ability, Verbal, and Nonverbal Reasoning indices was classified relative to test norms. Scores < -1 SD relative to the mean were classified as mild/moderate delay or impairment, and scores < -2 SDs were classified as moderate delay or impairment. A total of 105 children completed the Bayley-III and DAS-II. The sensitivity of mild/moderate cognitive delay on the Bayley-III for predicting impairment on DAS-II indices ranged from 29.4% to 38.5% and specificity ranged from 92.3% to 95.5%. The sensitivity of mild/moderate language delay on the Bayley-III for predicting impairment on DAS-II indices ranged from 40% to 46.7% and specificity ranged from 81.1% to 85.7%. The use of local reference data at 24 months to classify delay increased sensitivity but reduced specificity. Receiver operating curve analysis identified optimum cut-point scores for the Bayley-III that were more consistent with using local reference data than Bayley-III normative data. In our cohort of very preterm children, delay on the Bayley-III Cognitive and Language scales was not strongly predictive of future impairments. More children destined for later cognitive impairment were identified by using cut-points based on local reference data than Bayley-III norms. Copyright © 2015 by the American Academy of Pediatrics.

EGFR, HER2 and VEGF pathways: validated targets for cancer treatment.

PubMed

Press, Michael F; Lenz, Heinz-Josef

2007-01-01

Targeted therapies are rationally designed to interfere with specific molecular events that are important in tumour growth, progression or survival. Several targeted therapies with anti-tumour activity in human cancer cell lines and xenograft models have now been shown to produce objective responses, delay disease progression and, in some cases, improve survival of patients with advanced malignancies. These targeted therapies include cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody; gefitinib and erlotinib, EGFR-specific tyrosine kinase inhibitors; trastuzumab, an anti-human EGFR type 2 (HER2)-related monoclonal antibody; lapatinib, a dual inhibitor of both EGFR- and HER2-associated tyrosine kinases; and bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody. On the basis of preclinical and clinical evidence, EGFR, HER2 and VEGF represent validated targets for cancer therapy and remain the subject of intensive investigation. Both EGFR and HER2 are targets found on cancer cells, whereas VEGF is a target that acts in the tumour microenvironment. Clinical studies are focusing on how to best incorporate targeted therapy into current treatment regimens and other studies are exploring whether different strategies for inhibiting these targets will offer greater benefit. It is clear that optimal use of targeted therapy will depend on understanding how these drugs work mechanistically, and recognising that their activities may differ across patient populations, tumour types and disease stages, as well as when and how they are used in cancer treatment. The results achieved with targeted therapies to date are promising, although they illustrate the need for additional preclinical and clinical study.

Effect of bevacizumab on angiogenesis and growth of canine osteosarcoma cells xenografted in athymic mice.

PubMed

Scharf, Valery F; Farese, James P; Coomer, Alastair R; Milner, Rowan J; Taylor, David P; Salute, Marc E; Chang, Myron N; Neal, Dan; Siemann, Dietmar W

2013-05-01

Objective-To investigate the effects of bevacizumab, a human monoclonal antibody against vascular endothelial growth factor, on the angiogenesis and growth of canine osteosarcoma cells xenografted in mice. Animals-27 athymic nude mice. Procedures-To each mouse, highly metastasizing parent osteosarcoma cells of canine origin were injected into the left gastrocnemius muscle. Each mouse was then randomly allocated to 1 of 3 treatment groups: high-dose bevacizumab (4 mg/kg, IP), low-dose bevacizumab (2 mg/kg, IP), or control (no treatment). Tumor growth (the number of days required for the tumor to grow from 8 to 13 mm), vasculature, histomorphology, necrosis, and pulmonary metastasis were evaluated. Results-Mice in the high-dose bevacizumab group had significantly delayed tumor growth (mean ± SD, 13.4 ± 3.8 days; range, 9 to 21 days), compared with that for mice in the low-dose bevacizumab group (mean ± SD, 9.4 ± 1.5 days; range, 7 to 11 days) or control group (mean ± SD, 7. 2 ± 1.5 days; range, 4 to 9 days). Mice in the low-dose bevacizumab group also had significantly delayed tumor growth, compared with that for mice in the control group. Conclusions and Clinical Relevance-Results indicated that bevacizumab inhibited growth of canine osteosarcoma cells xenografted in mice, which suggested that vascular endothelial growth factor inhibitors may be clinically useful for the treatment of osteosarcoma in dogs. Impact for Human Medicine-Canine osteosarcoma is used as a research model for human osteosarcoma; therefore, bevacizumab may be clinically beneficial for the treatment of osteosarcoma in humans.

Engineering NK Cells Modified With an EGFRvIII-specific Chimeric Antigen Receptor to Overexpress CXCR4 Improves Immunotherapy of CXCL12/SDF-1α-secreting Glioblastoma.

PubMed

Müller, Nadja; Michen, Susanne; Tietze, Stefanie; Töpfer, Katrin; Schulte, Alexander; Lamszus, Katrin; Schmitz, Marc; Schackert, Gabriele; Pastan, Ira; Temme, Achim

2015-06-01

Natural killer (NK) cells are promising effector cells for adjuvant immunotherapy of cancer. So far, several preclinical studies have shown the feasibility of gene-engineered NK cells, which upon expression of chimeric antigen receptors (CARs) are redirected to otherwise NK cell-resistant tumors. Yet, we reasoned that the efficiency of an immunotherapy using CAR-modified NK cells critically relies on efficient migration to the tumor site and might be improved by the engraftment of a receptor specific for a chemokine released by the tumor. On the basis of the DNAX-activation protein 12 (DAP12), a signaling adapter molecule involved in signal transduction of activating NK cell receptors, we constructed an epidermal growth factor variant III (EGFRvIII)-CAR, designated MR1.1-DAP12 which confers specific cytotoxicity of NK cell towards EGFRvIII glioblastoma cells in vitro and to established subcutaneous U87-MG tumor xenografts. So far, infusion of NK cells with expression of MR1.1-DAP12 caused a moderate but significantly delayed tumor growth and increased median survival time when compared with NK cells transduced with an ITAM-defective CAR. Notably, the further genetic engineering of these EGFRvIII-specific NK cells with the chemokine receptor CXCR4 conferred a specific chemotaxis to CXCL12/SDF-1α secreting U87-MG glioblastoma cells. Moreover, the administration of such NK cells resulted in complete tumor remission in a number of mice and a significantly increased survival when compared with the treatment of xenografts with NK cells expressing only the EGFRvIII-specific CAR or mock control. We conclude that chemokine receptor-engineered NK cells with concomitant expression of a tumor-specific CAR are a promising tool to improve adoptive tumor immunotherapy.

Distributed delays in a hybrid model of tumor-immune system interplay.

PubMed

Caravagna, Giulio; Graudenzi, Alex; d'Onofrio, Alberto

2013-02-01

A tumor is kinetically characterized by the presence of multiple spatio-temporal scales in which its cells interplay with, for instance, endothelial cells or Immune system effectors, exchanging various chemical signals. By its nature, tumor growth is an ideal object of hybrid modeling where discrete stochastic processes model low-numbers entities, and mean-field equations model abundant chemical signals. Thus, we follow this approach to model tumor cells, effector cells and Interleukin-2, in order to capture the Immune surveillance effect. We here present a hybrid model with a generic delay kernel accounting that, due to many complex phenomena such as chemical transportation and cellular differentiation, the tumor-induced recruitment of effectors exhibits a lag period. This model is a Stochastic Hybrid Automata and its semantics is a Piecewise Deterministic Markov process where a two-dimensional stochastic process is interlinked to a multi-dimensional mean-field system. We instantiate the model with two well-known weak and strong delay kernels and perform simulations by using an algorithm to generate trajectories of this process. Via simulations and parametric sensitivity analysis techniques we (i) relate tumor mass growth with the two kernels, we (ii) measure the strength of the Immune surveillance in terms of probability distribution of the eradication times, and (iii) we prove, in the oscillatory regime, the existence of a stochastic bifurcation resulting in delay-induced tumor eradication.

The 12q14 microdeletion syndrome: six new cases confirming the role of HMGA2 in growth

PubMed Central

Lynch, Sally Ann; Foulds, Nicola; Thuresson, Ann-Charlotte; Collins, Amanda L; Annerén, Göran; Hedberg, Bernt-Oves; Delaney, Carol A; Iremonger, James; Murray, Caroline M; Crolla, John A; Costigan, Colm; Lam, Wayne; Fitzpatrick, David R; Regan, Regina; Ennis, Sean; Sharkey, Freddie

2011-01-01

We report six patients with array deletions encompassing 12q14. Out of a total of 2538 array investigations carried out on children with developmental delay and dysmorphism in three diagnostic testing centres, six positive cases yielded a frequency of 1 in 423 for this deletion syndrome. The deleted region in each of the six cases overlaps significantly with previously reported cases with microdeletions of this region. The chromosomal range of the deletions extends from 12q13.3q15. In the current study, we report overlapping deletions of variable extent and size but primarily comprising chromosomal bands 12q13.3q14.1. Four of the six deletions were confirmed as de novo events. Two cases had deletions that included HMGA2, and both children had significant short stature. Neither case had osteopoikilosis despite both being deleted for LEMD3. Four cases had deletions that ended proximal to HMGA2 and all of these had much better growth. Five cases had congenital heart defects, including two with atrial septal defects, one each with pulmonary stenosis, sub-aortic stenosis and a patent ductus. Four cases had moderate delay, two had severe developmental delay and a further two had a diagnosis of autism. All six cases had significant speech delay with subtle facial dysmorphism. PMID:21267005

Wide variation of prostate-specific antigen doubling time of untreated, clinically localized, low-to-intermediate grade, prostate carcinoma.

PubMed

Choo, Richard; Klotz, Laurence; Deboer, Gerrit; Danjoux, Cyril; Morton, Gerard C

2004-08-01

To assess the prostate specific antigen (PSA) doubling time of untreated, clinically localized, low-to-intermediate grade prostate carcinoma. A prospective single-arm cohort study has been in progress since November 1995 to assess the feasibility of a watchful-observation protocol with selective delayed intervention for clinically localized, low-to-intermediate grade prostate adenocarcinoma. The PSA doubling time was estimated from a linear regression of ln(PSA) against time, assuming a simple exponential growth model. As of March 2003, 231 patients had at least 6 months of follow-up (median 45) and at least three PSA measurements (median 8, range 3-21). The distribution of the doubling time was: < 2 years, 26 patients; 2-5 years, 65; 5-10 years, 42; 10-20 years, 26; 20-50 years, 16; >50 years, 56. The median doubling time was 7.0 years; 42% of men had a doubling time of >10 years. The doubling time of untreated clinically localized, low-to-intermediate grade prostate cancer varies widely.

Reversing the Signaled Magnitude Effect in Delayed Matching to Sample: Delay-Specific Remembering?

ERIC Educational Resources Information Center

White, K. Geoffrey; Brown, Glenn S.

2011-01-01

Pigeons performed a delayed matching-to-sample task in which large or small reinforcers for correct remembering were signaled during the retention interval. Accuracy was low when small reinforcers were signaled, and high when large reinforcers were signaled (the signaled magnitude effect). When the reinforcer-size cue was switched from small to…

Theory of time-dependent rupture in the Earth

NASA Technical Reports Server (NTRS)

Das, S.; Scholz, C. H.

1980-01-01

Fracture mechanics is used to develop a theory of earthquake mechanism which includes the phenomenon of subcritical crack growth. The following phenomena are predicted: slow earthquakes, multiple events, delayed multiple events (doublets), postseismic rupture growth and afterslip, foreshocks, and aftershocks. The theory predicts a nucleation stage prior to an earthquake, and suggests a physical mechanism by which one earthquake may 'trigger' another.

Delays in maturation among adolescents with hemophilia and a history of inhibitors

PubMed Central

Lynn, Henry S.; Lail, Alice E.; Hoots, W. Keith; Berntorp, Erik; Gomperts, Edward D.

2007-01-01

Inhibitory antibodies to factors VIII or IX have the potential to affect a broad range of outcomes among people with hemophilia; however, their possible effect on growth and maturation has not been explored. We evaluated skeletal maturation (bone age), pubertal progression, serum testosterone levels, height velocity, and stature in the multicenter Hemophilia Growth and Development Study. A total of 333 children and adolescents (mean age, 12.4 years) were enrolled from 1989 to 1990 and followed for 7 years. Of these, 18% (n = 60) had a history of inhibitors. Bone age among HIV− adolescents with a history of inhibitors lagged 9 or more months behind those without inhibitors at every age from 12 to 15 years. Those with a history of inhibitors were older at every Tanner stage transition, attained a lower maximum growth velocity, and their serum testosterone levels were significantly lower compared with those without inhibitors. Delays were greater among HIV+ patients with a history of inhibitors compared with those without inhibitors; however, the differences were generally small and not statistically significant. The results of this investigation underscore the importance of monitoring the growth and maturation of children and adolescents with hemophilia, particularly those with inhibitors. PMID:17715388

Tumor growth delay by adjuvant alternating electric fields which appears non-thermally mediated.

PubMed

Castellví, Quim; Ginestà, Mireia M; Capellà, Gabriel; Ivorra, Antoni

2015-10-01

Delivery of the so-called Tumor Treatment Fields (TTFields) has been proposed as a cancer therapy. These are low magnitude alternating electric fields at frequencies from 100 to 300 kHz which are applied continuously in a non-invasive manner. Electric field delivery may produce an increase in temperature which cannot be neglected. We hypothesized that the reported results obtained by applying TTFields in vivo could be due to heat rather than to electrical forces as previously suggested. Here, an in vivo study is presented in which pancreatic tumors subcutaneously implanted in nude mice were treated for a week either with mild hyperthermia (41 °C) or with TTFields (6 V/cm, 150 kHz) and tumor growth was assessed. Although the TTFields applied singly did not produce any significant effect, the combination with chemotherapy did show a delay in tumor growth in comparison to animals treated only with chemotherapy (median relative reduction=47%). We conclude that concomitant chemotherapy and TTFields delivery show a beneficial impact on pancreatic tumor growth. Contrary to our hypothesis, this impact is non-related with the induced temperature increase. Copyright © 2015 Elsevier B.V. All rights reserved.

Contribution of Schedule Delays to Cost Growth: How to Make Peace with a Marching Army

NASA Technical Reports Server (NTRS)

Majerowicz, Walt; Bitten, Robert; Emmons, Debra; Shinn, Stephen A.

2016-01-01

Numerous research papers have shown that cost and schedule growth are interrelated for NASA space science missions. Although there has shown to be a strong correlation of cost growth with schedule growth, it is unclear what percentage of cost growth is caused by schedule growth and how schedule growth can be controlled. This paper attempts to quantify this percentage by looking at historical data and show detailed examples of how schedule growth influences cost growth. The paper also addresses a methodology to show an alternate approach for assessing and setting a robust baseline schedule and use schedule performance metrics to help assess if the project is performing to plan. Finally, recommendations are presented to help control schedule growth in order to minimize cost growth for NASA space science missions.

Microstructure development in Kolmogorov, Johnson-Mehl, and Avrami nucleation and growth kinetics

NASA Astrophysics Data System (ADS)

Pineda, Eloi; Crespo, Daniel

1999-08-01

A statistical model with the ability to evaluate the microstructure developed in nucleation and growth kinetics is built in the framework of the Kolmogorov, Johnson-Mehl, and Avrami theory. A populational approach is used to compute the observed grain-size distribution. The impingement process which delays grain growth is analyzed, and the effective growth rate of each population is estimated considering the previous grain history. The proposed model is integrated for a wide range of nucleation and growth protocols, including constant nucleation, pre-existing nuclei, and intermittent nucleation with interface or diffusion-controlled grain growth. The results are compared with Monte Carlo simulations, giving quantitative agreement even in cases where previous models fail.

Laser activation of a nutrient medium and antibiotic solutions and its estimation by of bacteria growth dynamics

NASA Astrophysics Data System (ADS)

Malov, Alexander N.; Neupokoeva, Anna V.; Kokorina, Lubov A.; Simonova, Elena V.

2016-11-01

A laser photomodifacation of nutrient mediums and antibiotics results at the microbiological supervision of bacteria colonies growth are discussed. It is experimentally shown, that on the irradiated media there is a delay of bacterial colonies growth number. Influence of laser radiation on activity of an antibiotic also is experimentally studied. It is revealed, that laser photomodifacation increases antimicrobic activity of a preparation. The mechanism of biological solutions activation is connected with the phenomenon laser nanoclusterization. Parameters of bacteria growth bacteria growth dynamics allow to numerically estimate degree of laser activation of nutrient mediums and pharmaceutical preparations.

Analysing and modelling the growth behaviour of Listeria monocytogenes on RTE cooked meat products after a high pressure treatment at 400 MPa.

PubMed

Hereu, A; Dalgaard, P; Garriga, M; Aymerich, T; Bover-Cid, S

2014-09-01

Various predictive models are available for high pressure inactivation of Listeria monocytogenes in food, but currently available models do not consider the growth kinetics of surviving cells during the subsequent storage of products. Therefore, we characterised the growth of L. monocytogenes in sliced cooked meat products after a pressurization treatment. Two inoculum levels (10(7) or 10(4) CFU/g) and two physiological states before pressurization (freeze-stressed or cold-adapted) were evaluated. Samples of cooked ham and mortadella were inoculated, high pressure processed (400 MPa, 5 min) and subsequently stored at 4, 8 and 12 °C. The Logistic model with delay was used to estimate lag phase (λ) and maximum specific growth rate (μmax) values from the obtained growth curves. The effect of storage temperature on μmax and λ was modelled using the Ratkowsky square root model and the relative lag time (RLT) concept. Compared with cold-adapted cells the freeze-stressed cells were more pressure-resistant and showed a much longer lag phase during growth after the pressure treatment. Interestingly, for high-pressure inactivation and subsequent growth, the time to achieve a concentration of L. monocytogenes 100-fold (2-log) higher than the cell concentration prior to the pressure treatment was similar for the two studied physiological states of the inoculum. Two secondary models were necessary to describe the different growth behaviour of L. monocytogenes on ready-to-eat cooked ham (lean product) and mortadella (fatty product). This supported the need of a product-oriented approach to assess growth after high pressure processing. The performance of the developed predictive models for the growth of L. monocytogenes in high-pressure processed cooked ham and mortadella was evaluated by comparison with available data from the literature and by using the Acceptable Simulation Zone approach. Overall, 91% of the relative errors fell into the Acceptable Simulation Zone. Copyright © 2014 Elsevier B.V. All rights reserved.

Immediate memory for “when, where and what”: Short‐delay retrieval using dynamic naturalistic material

PubMed Central

Macaluso, Emiliano

2015-01-01

Abstract We investigated the neural correlates supporting three kinds of memory judgments after very short delays using naturalistic material. In two functional magnetic resonance imaging (fMRI) experiments, subjects watched short movie clips, and after a short retention (1.5–2.5 s), made mnemonic judgments about specific aspects of the clips. In Experiment 1, subjects were presented with two scenes and required to either choose the scene that happened earlier in the clip (“scene‐chronology”), or with a correct spatial arrangement (“scene‐layout”), or that had been shown (“scene‐recognition”). To segregate activity specific to seen versus unseen stimuli, in Experiment 2 only one probe image was presented (either target or foil). Across the two experiments, we replicated three patterns underlying the three specific forms of memory judgment. The precuneus was activated during temporal‐order retrieval, the superior parietal cortex was activated bilaterally for spatial‐related configuration judgments, whereas the medial frontal cortex during scene recognition. Conjunction analyses with a previous study that used analogous retrieval tasks, but a much longer delay (>1 day), demonstrated that this dissociation pattern is independent of retention delay. We conclude that analogous brain regions mediate task‐specific retrieval across vastly different delays, consistent with the proposal of scale‐invariance in episodic memory retrieval. Hum Brain Mapp 36:2495–2513, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:25773646

Piloted simulator study of allowable time delays in large-airplane response

NASA Technical Reports Server (NTRS)

Grantham, William D.; Bert T.?aetingas, Stephen A.dings with ran; Bert T.?aetingas, Stephen A.dings with ran

1987-01-01

A piloted simulation was performed to determine the permissible time delay and phase shift in the flight control system of a specific large transport-type airplane. The study was conducted with a six degree of freedom ground-based simulator and a math model similar to an advanced wide-body jet transport. Time delays in discrete and lagged form were incorporated into the longitudinal, lateral, and directional control systems of the airplane. Three experienced pilots flew simulated approaches and landings with random localizer and glide slope offsets during instrument tracking as their principal evaluation task. Results of the present study suggest a level 1 (satisfactory) handling qualities limit for the effective time delay of 0.15 sec in both the pitch and roll axes, as opposed to a 0.10-sec limit of the present specification (MIL-F-8785C) for both axes. Also, the present results suggest a level 2 (acceptable but unsatisfactory) handling qualities limit for an effective time delay of 0.82 sec and 0.57 sec for the pitch and roll axes, respectively, as opposed to 0.20 sec of the present specifications for both axes. In the area of phase shift between cockpit input and control surface deflection,the results of this study, flown in turbulent air, suggest less severe phase shift limitations for the approach and landing task-approximately 50 deg. in pitch and 40 deg. in roll - as opposed to 15 deg. of the present specifications for both axes.

Short- and long-term (final height) growth responses to growth hormone (GH) therapy in patients with Turner syndrome: correlation of growth response to stimulated GH levels, spontaneous GH secretion, and karyotype.

PubMed

Schmitt, K; Haeusler, G; Blümel, P; Plöchl, E; Frisch, H

1997-01-01

In 41 girls with Turner syndrome, the growth hormone (GH) peak values during stimulation tests and parameters of spontaneous nocturnal GH secretion were studied and compared with respect to different karyotypes, short-term growth response to GH therapy, and final height. 22.0% of the girls tested had a subnormal (peak < 11 ng/ml) and 9.7% a pathological (< 7 ng/ml) GH response. The spontaneous GH secretion showed a good correlation with the data of the provocation tests, providing no further information regarding GH capacity. Short-term growth response to GH treatment could not be predicted by any of the investigated parameters. Although patients with isochromosomes had frequent subnormal GH tests, their growth response to GH treatment after 1 year was comparable to that of girls with XO karyotype and mosaicism. In 18 patients who had reached final height, the height gain during treatment (calculated as final height minus projected adult height) was not different among patients with normal, subnormal, or pathological GH tests. In contrast, final height minus projected adult height in 4 girls with isochromosomes was 15.7 +/- 5.1 versus 7.6 +/- 3.3 cm in 14 patients with other karyotypes (p < 0.01). These girls had a more pronounced bone age delay (3.3 +/- 0.3 vs. 1.8 +/- 1.2 years) at the start of therapy and thus a better growth potential. We conclude that short- and long-term growth responses to GH treatment in Turner syndrome could not be predicted by GH testing. Patients with isochromosomes might represent a subpopulation which is more frequently GH deficient and shows a marked bone age delay.

Speech Inconsistency in Children With Childhood Apraxia of Speech, Language Impairment, and Speech Delay: Depends on the Stimuli.

PubMed

Iuzzini-Seigel, Jenya; Hogan, Tiffany P; Green, Jordan R

2017-05-24

The current research sought to determine (a) if speech inconsistency is a core feature of childhood apraxia of speech (CAS) or if it is driven by comorbid language impairment that affects a large subset of children with CAS and (b) if speech inconsistency is a sensitive and specific diagnostic marker that can differentiate between CAS and speech delay. Participants included 48 children ranging between 4;7 to 17;8 (years;months) with CAS (n = 10), CAS + language impairment (n = 10), speech delay (n = 10), language impairment (n = 9), or typical development (n = 9). Speech inconsistency was assessed at phonemic and token-to-token levels using a variety of stimuli. Children with CAS and CAS + language impairment performed equivalently on all inconsistency assessments. Children with language impairment evidenced high levels of speech inconsistency on the phrase "buy Bobby a puppy." Token-to-token inconsistency of monosyllabic words and the phrase "buy Bobby a puppy" was sensitive and specific in differentiating children with CAS and speech delay, whereas inconsistency calculated on other stimuli (e.g., multisyllabic words) was less efficacious in differentiating between these disorders. Speech inconsistency is a core feature of CAS and is efficacious in differentiating between children with CAS and speech delay; however, sensitivity and specificity are stimuli dependent.

A cross-sectional study of growth, nutritional status and body proportions in children and adolescents at a medical center specializing in the treatment of cystic fibrosis in Poland

PubMed Central

Sands, Dorota; Zielińska, Anna

2015-01-01

Introduction Malnutrition, delayed growth and delayed puberty are commonly seen in children with cystic fibrosis. The aim of this study was to evaluate growth, nutritional status and body proportions in children and adolescents suffering from cystic fibrosis. Material and methods The evaluation was based on 19 somatic measurements and indices calculated from these measurements. Somatic development was evaluated in relation to several factors connected to the clinical picture or the course of the disease. Anthropometric data were extracted from the medical histories of 41 boys and 48 girls diagnosed and treated at the Institute of Mother and Child in Warsaw (Poland). Mean values for somatic parameters and body build indices for the children suffering from CF were compared to those for the reference group. Results The results revealed that growth in these children was significantly delayed in comparison to that seen in the healthy population (Z-score = –0.56, p < 0.001). Nutritional status was also adversely affected (Z-score = –0.85, p < 0.001). The children suffered more from a deficit in muscularity than in adiposity (Z-score = –0.75 and Z-score = –0.34, p < 0.01, respectively). This was especially true for boys. The children had infantile body proportions and defects in trunk and chest structure. Conclusions The factors that most affected somatic development were infection by Pseudomonas aeruginosa and the time at which the disease was diagnosed. Chronic infection by P. aeruginosa and type of CFTR mutation were the factors that most affected pulmonary function parameters. PMID:25861303

Rapid Long-Range Disynaptic Inhibition Explains the Formation of Cortical Orientation Maps

PubMed Central

Antolík, Ján

2017-01-01

Competitive interactions are believed to underlie many types of cortical processing, ranging from memory formation, attention and development of cortical functional organization (e.g., development of orientation maps in primary visual cortex). In the latter case, the competitive interactions happen along the cortical surface, with local populations of neurons reinforcing each other, while competing with those displaced more distally. This specific configuration of lateral interactions is however in stark contrast with the known properties of the anatomical substrate, i.e., excitatory connections (mediating reinforcement) having longer reach than inhibitory ones (mediating competition). No satisfactory biologically plausible resolution of this conflict between anatomical measures, and assumed cortical function has been proposed. Recently a specific pattern of delays between different types of neurons in cat cortex has been discovered, where direct mono-synaptic excitation has approximately the same delay, as the combined delays of the disynaptic inhibitory interactions between excitatory neurons (i.e., the sum of delays from excitatory to inhibitory and from inhibitory to excitatory neurons). Here we show that this specific pattern of delays represents a biologically plausible explanation for how short-range inhibition can support competitive interactions that underlie the development of orientation maps in primary visual cortex. We demonstrate this statement analytically under simplifying conditions, and subsequently show using network simulations that development of orientation maps is preserved when long-range excitation, direct inhibitory to inhibitory interactions, and moderate inequality in the delays between excitatory and inhibitory pathways is added. PMID:28408869

Which Are the Best Predictors of Theory of Mind Delay in Children with Specific Language Impairment?

ERIC Educational Resources Information Center

Andrés-Roqueta, Clara; Adrian, Juan E.; Clemente, Rosa A.; Katsos, Napoleon

2013-01-01

Background: The relationship between language and theory of mind (ToM) development in participants with specific language impairment (SLI) it is far from clear due to there were differences in study design and methodologies of previous studies. Aims: This research consisted of an in-depth investigation of ToM delay in children with SLI during the…

The curative and palliative potential of the monoclonal antibody MOv18 labelled with 211At in nude mice with intraperitoneally growing ovarian cancer xenografts--a long-term study.

PubMed

Andersson, H; Lindegren, S; Bäck, T; Jacobsson, L; Leser, G; Horvath, G

2000-01-01

The purpose of the present study was to investigate the therapeutic efficacy of 211At-labelled specific monoclonal antibody MOv18 in nude mice with intraperitoneal growth of the human ovarian cancer cell line OVCAR3. In the first part of the study the antibody was injected intraperitoneally when the cancer growth was microscopic. The injected activity was 485-555 kBq. The median survival for treated mice was 213 days compared to 138 days for untreated mice (p < 0.014, log-rank test). No obvious toxicity was seen. Thirty-three percent of the mice were apparently free of cancer after 7 months and were probably cured. In the second part of the study mice with macroscopic cancer and signs of ascites were injected intraperitoneally with the same 211At-labelled antibody (377-389 kBq). This treatment possibly delayed the production of ascites. Hopefully radioimmunotherapy with regionally administered 211At-labelled antibody will be of value in women with ovarian cancer as well.

Mathematical modelling of prostate cancer growth and its application to hormone therapy.

PubMed

Tanaka, Gouhei; Hirata, Yoshito; Goldenberg, S Larry; Bruchovsky, Nicholas; Aihara, Kazuyuki

2010-11-13

Hormone therapy in the form of androgen deprivation is a major treatment for advanced prostate cancer. However, if such therapy is overly prolonged, tumour cells may become resistant to this treatment and result in recurrent fatal disease. Long-term hormone deprivation also is associated with side effects poorly tolerated by patients. In contrast, intermittent hormone therapy with alternating on- and off-treatment periods is a possible clinical strategy to delay progression to hormone-refractory disease with the advantage of reduced side effects during the off-treatment periods. In this paper, we first overview previous studies on mathematical modelling of prostate tumour growth under intermittent hormone therapy. The model is categorized into a hybrid dynamical system because switching between on-treatment and off-treatment intervals is treated in addition to continuous dynamics of tumour growth. Next, we present an extended model of stochastic differential equations and examine how well the model is able to capture the characteristics of authentic serum prostate-specific antigen (PSA) data. We also highlight recent advances in time-series analysis and prediction of changes in serum PSA concentrations. Finally, we discuss practical issues to be considered towards establishment of mathematical model-based tailor-made medicine, which defines how to realize personalized hormone therapy for individual patients based on monitored serum PSA levels.

Detection of Growth Hormone Deficiency in Adults with Chronic Traumatic Brain Injury

PubMed Central

Griesbach, Grace S.; Ashley, Mark J.

2016-01-01

Abstract This study examined the prevalence of growth hormone deficiency (GHD) in patients with traumatic brain injury (TBI) during the post-acute phase of recovery and whether GHD was associated with increased disability, decreased independence, and depression. A secondary objective was to determine the accuracy of insulin-like growth factor-1 (IGF-1) levels in predicting GHD in patients with TBI. Anterior pituitary function was assessed in 235 adult patients with TBI through evaluation of fasting morning hormone levels. GH levels were assessed through provocative testing, specifically the glucagon stimulation test. GHD was diagnosed in a significant number of patients, with 45% falling into the severe GHD (≤3 μg/L) category. IGF-1 levels were not predictive of GHD. Patients with GHD were more disabled and less independent compared with those patients who were not GHD. Those patients with more severe GHD also showed decreased levels of cortisol and testosterone. Symptoms of depression were also more prevalent in this group. In addition, patients with severe GHD had delayed admission to post-acute rehabilitation. This study confirms the high prevalence of GHD in patients with TBI and the necessity to monitor clinical symptoms and perform provocative testing to definitively diagnose GHD. PMID:26414093

The Armadillo Repeat Gene ZAK IXIK Promotes Arabidopsis Early Embryo and Endosperm Development through a Distinctive Gametophytic Maternal Effect[C][W][OA

PubMed Central

Ngo, Quy A.; Baroux, Celia; Guthörl, Daniela; Mozerov, Peter; Collinge, Margaret A.; Sundaresan, Venkatesan; Grossniklaus, Ueli

2012-01-01

The proper balance of parental genomic contributions to the fertilized embryo and endosperm is essential for their normal growth and development. The characterization of many gametophytic maternal effect (GME) mutants affecting seed development indicates that there are certain classes of genes with a predominant maternal contribution. We present a detailed analysis of the GME mutant zak ixik (zix), which displays delayed and arrested growth at the earliest stages of embryo and endosperm development. ZIX encodes an Armadillo repeat (Arm) protein highly conserved across eukaryotes. Expression studies revealed that ZIX manifests a GME through preferential maternal expression in the early embryo and endosperm. This parent-of-origin–dependent expression is regulated by neither the histone and DNA methylation nor the DNA demethylation pathways known to regulate some other GME mutants. The ZIX protein is localized in the cytoplasm and nucleus of cells in reproductive tissues and actively dividing root zones. The maternal ZIX allele is required for the maternal expression of MINISEED3. Collectively, our results reveal a reproductive function of plant Arm proteins in promoting early seed growth, which is achieved through a distinct GME of ZIX that involves mechanisms for maternal allele-specific expression that are independent of the well-established pathways. PMID:23064319

Divergent roles of growth factors in the GnRH regulation of puberty in mice

PubMed Central

DiVall, Sara A.; Williams, Tameeka R.; Carver, Sarah E.; Koch, Linda; Brüning, Jens C.; Kahn, C. Ronald; Wondisford, Fredric; Radovick, Sally; Wolfe, Andrew

2010-01-01

Pubertal onset, initiated by pulsatile gonadotropin-releasing hormone (GnRH), only occurs in a favorable, anabolic hormonal milieu. Anabolic factors that may signal nutritional status to the hypothalamus include the growth factors insulin and IGF-1. It is unclear which hypothalamic neuronal subpopulation these factors affect to ultimately regulate GnRH neuron function in puberty and reproduction. We examined the direct role of the GnRH neuron in growth factor regulation of reproduction using the Cre/lox system. Mice with the IR or IGF-1R deleted specifically in GnRH neurons were generated. Male and female mice with the IR deleted in GnRH neurons displayed normal pubertal timing and fertility, but male and female mice with the IGF-1R deleted in GnRH neurons experienced delayed pubertal development with normal fertility. With IGF-1 administration, puberty was advanced in control females, but not in females with the IGF-1R deleted in GnRH neurons, in control males, or in knockout males. These mice exhibited developmental differences in GnRH neuronal morphology but normal number and distribution of neurons. These studies define the role of IGF-1R signaling in the coordination of somatic development with reproductive maturation and provide insight into the mechanisms regulating pubertal timing in anabolic states. PMID:20628204

Use of hop extract as antifungal ingredient for bread making and selection of autochthonous resistant starters for sourdough fermentation.

PubMed

Nionelli, Luana; Pontonio, Erica; Gobbetti, Marco; Rizzello, Carlo Giuseppe

2018-02-02

Aiming at meeting the consumers' demand in terms of bio-preservation, the potential of the combination of the lactic acid bacteria fermentation and the addition of hop extract as natural preservative in breadmaking, was exploited. The antifungal properties of a hop (Humulus lupulus) extract were investigated, showing a significant inhibition of the hyphal growth of Aspergillus parasiticus, Penicillium carneum, Penicillium polonicum, Penicillium paneum, Penicillium chermesinum, Aspergillus niger, Penicillium roqueforti. Lactic acid bacteria belonging to species of Enterococcus feacium, Lactobacillus plantarum, Lactobacillus brevis, Lactobacillus helveticus, Lactobacillus curvatus, Pediococcus pentosaceus, and Pediococcus acidilactici were isolated from hop and subjected to selection based on kinetics of growth and acidification. The sourdough (hS) enriched with hop extract (hE), started with three selected strains, had phenols concentration and antioxidant activity higher than those obtained in the same condition but without the hE. Hop-sourdough used in breadmaking delayed the fungal growth (14 days), giving a bread characterized by free aminoacids concentration, antioxidant and phytase activities higher than bread started only with baker's yeast, with or without the addition of hE. Specific volume and cell-total area of the bread containing hE improved, and its sensory profile was characterized by typical sourdough attributes, and a moderate bitter/herbaceous perception.

Self-narrowing of size distributions of nanostructures by nucleation antibunching

NASA Astrophysics Data System (ADS)

Glas, Frank; Dubrovskii, Vladimir G.

2017-08-01

We study theoretically the size distributions of ensembles of nanostructures fed from a nanosize mother phase or a nanocatalyst that contains a limited number of the growth species that form each nanostructure. In such systems, the nucleation probability decreases exponentially after each nucleation event, leading to the so-called nucleation antibunching. Specifically, this effect has been observed in individual nanowires grown in the vapor-liquid-solid mode and greatly affects their properties. By performing numerical simulations over large ensembles of nanostructures as well as developing two different analytical schemes (a discrete and a continuum approach), we show that nucleation antibunching completely suppresses fluctuation-induced broadening of the size distribution. As a result, the variance of the distribution saturates to a time-independent value instead of growing infinitely with time. The size distribution widths and shapes primarily depend on the two parameters describing the degree of antibunching and the nucleation delay required to initiate the growth. The resulting sub-Poissonian distributions are highly desirable for improving size homogeneity of nanowires. On a more general level, this unique self-narrowing effect is expected whenever the growth rate is regulated by a nanophase which is able to nucleate an island much faster than it is refilled from a surrounding macroscopic phase.

Mathematical modeling of energy metabolism and hemodynamics of WHO grade II gliomas using in vivo MR data.

PubMed

Guillevin, Rémy; Menuel, Carole; Vallée, Jean-Noël; Françoise, Jean-Pierre; Capelle, Laurent; Habas, Christophe; De Marco, Giovanni; Chiras, Jacques; Costalat, Robert

2011-01-01

Therapeutic management of low-grade gliomas (LGG) is a challenge because they have undergone anaplastic transformation with variable delay. Today, only progressive volume growth on successive MRI allows an in vivo monitoring of this evolution. On the other hand, multinuclear spectroscopy and perfusion available during MRI may also provide assessment of metabolic changes underlying morphological modifications. To overcome this drawback, we developed a mathematical model of the metabolism and the hemodynamic of gliomas, based on a physiological model previously published, and including the MR parameters. This allows us to suggest that some specific profiles of metabolic and hemodynamic changes would be good indicators of potential anaplastic transformation. Copyright © 2010 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Algorithm Estimates Microwave Water-Vapor Delay

NASA Technical Reports Server (NTRS)

Robinson, Steven E.

1989-01-01

Accuracy equals or exceeds conventional linear algorithms. "Profile" algorithm improved algorithm using water-vapor-radiometer data to produce estimates of microwave delays caused by water vapor in troposphere. Does not require site-specific and weather-dependent empirical parameters other than standard meteorological data, latitude, and altitude for use in conjunction with published standard atmospheric data. Basic premise of profile algorithm, wet-path delay approximated closely by solution to simplified version of nonlinear delay problem and generated numerically from each radiometer observation and simultaneous meteorological data.

The transcription factor Nfix is essential for normal brain development.

PubMed

Campbell, Christine E; Piper, Michael; Plachez, Céline; Yeh, Yu-Ting; Baizer, Joan S; Osinski, Jason M; Litwack, E David; Richards, Linda J; Gronostajski, Richard M

2008-05-13

The Nuclear Factor I (NFI) multi-gene family encodes site-specific transcription factors essential for the development of a number of organ systems. We showed previously that Nfia-deficient mice exhibit agenesis of the corpus callosum and other forebrain defects; Nfib-deficient mice have defects in lung maturation and show callosal agenesis and forebrain defects resembling those seen in Nfia-deficient animals, while Nfic-deficient mice have defects in tooth root formation. Recently the Nfix gene has been disrupted and these studies indicated that there were largely uncharacterized defects in brain and skeletal development in Nfix-deficient mice. Here we show that disruption of Nfix by Cre-recombinase mediated excision of the 2nd exon results in defects in brain development that differ from those seen in Nfia and Nfib KO mice. In particular, complete callosal agenesis is not seen in Nfix-/- mice but rather there appears to be an overabundance of aberrant Pax6- and doublecortin-positive cells in the lateral ventricles of Nfix-/- mice, increased brain weight, expansion of the cingulate cortex and entire brain along the dorsal ventral axis, and aberrant formation of the hippocampus. On standard lab chow Nfix-/- animals show a decreased growth rate from ~P8 to P14, lose weight from ~P14 to P22 and die at ~P22. If their food is supplemented with a soft dough chow from P10, Nfix-/- animals show a lag in weight gain from P8 to P20 but then increase their growth rate. A fraction of the animals survive to adulthood and are fertile. The weight loss correlates with delayed eye and ear canal opening and suggests a delay in the development of several epithelial structures in Nfix-/- animals. These data show that Nfix is essential for normal brain development and may be required for neural stem cell homeostasis. The delays seen in eye and ear opening and the brain morphology defects appear independent of the nutritional deprivation, as rescue of perinatal lethality with soft dough does not eliminate these defects.

The Usefulness of M-B CDI-K Short Form as Screening Test in Children With Language Developmental Delay.

PubMed

Kim, Seong Woo; Jeon, Ha Ra; Park, Eun Ji; Kim, Hyo In; Jung, Da Wa; Woo, Mee Ryung

2014-06-01

To investigate the usefulness of MacArthur-Bates Communicative Development Inventories-Korean (M-B CDI-K) short form as a screening test in children with language developmental delay. From April 2010 to May 2012, a total of 87 patients visited the department of physical medicine and rehabilitation of National Health Insurance Service Ilsan Hospital with the complaint of language developmental delay and were enrolled in this study. All patients took M-B CDI-K short form and Sequenced Language Scale for Infants (SELSI) or Preschool Receptive-Expressive Language Scale (PRES) according to their age. The study group consisted of 58 male patients and 29 female patients and the mean age was 25.9 months. The diagnosis are global developmental delay in 26 patients, selective language impairment in 31 patients, articulation disorder in 7 patients, cerebral palsy in 8 patients, autism spectrum disorder in 4 patients, motor developmental delay in 4 patients, and others in 7 patients. Seventy-one patients are diagnosed with language developmental delay in SELSI or PRES and of them showed 69 patients a high risk in the M-B CDI-K short form. Sixteen patients are normal in SELSI or PRES and of them showed 14 patients non-high risk in the M-B CDI-K short form. The M-B CDI-K short form has 97.2% sensitivity, 87.5% specificity, a positive predictive value of 0.97, and a negative predictive value of 0.88. The M-B CDI-K short form has a high sensitivity and specificity so it is considered as an useful screening tool in children with language developmental delay. Additional researches targeting normal children will be continued to supply the specificity of the M-B CDI-K short form.

Contrasting Effects of Extreme Drought and Snowmelt Patterns on Mountain Plants along an Elevation Gradient.

PubMed

Rosbakh, Sergey; Leingärtner, Annette; Hoiss, Bernhard; Krauss, Jochen; Steffan-Dewenter, Ingolf; Poschlod, Peter

2017-01-01

Despite the evidence that increased frequency and magnitude of extreme climate events (ECE) considerably affect plant performance, there is still a lack of knowledge about how these events affect mountain plant biodiversity and mountain ecosystem functioning. Here, we assessed the short-term (one vegetation period) effects of simulated ECEs [extreme drought (DR), advanced and delayed snowmelt (AD and DE), respectively] on the performance of 42 plant species occurring in the Bavarian Alps (Germany) along an elevational gradient of 600-2000 m a.s.l. in terms of vegetative growth and reproduction performance. We demonstrate that plant vegetative and generative traits respond differently to the simulated ECEs, but the nature and magnitude treatment effects strongly depend on study site location along the elevational gradient, species' altitudinal origin and plant functional type (PFT) of the target species. For example, the negative effect of DR treatment on growth (e.g., lower growth rates and lower leaf nitrogen content) and reproduction (e.g., lower seed mass) was much stronger in upland sites, as compared to lowlands. Species' response to the treatments also differed according to their altitudinal origin. Specifically, upland species responded negatively to extreme DR (e.g., lower growth rates and lower leaf carbon concentrations, smaller seed set), whereas performance of lowland species remained unaffected (e.g., stable seed set and seed size) or even positively responded (e.g., higher growth rates) to that treatment. Furthermore, we were able to detect some consistent differences in responses to the ECEs among three PFTs (forbs, graminoids, and legumes). For instance, vegetative growth and sexual reproduction of highly adaptable opportunistic graminoids positively responded to nearly all ECEs, likely on the costs of other, more conservative, forbs and legumes. Our results suggest that ECEs can significantly modify the performance of specific plant groups and therefore lead to changes in plant community structure and composition under ongoing climate change. Our study therefore underlines the need for more experimental studies on the effects of extreme climate events to understand the potential consequences of climate change for the alpine ecosystem.

Biological mechanisms discriminating growth rate and adult body weight phenotypes in two Chinese indigenous chicken breeds.

PubMed

Dou, Tengfei; Zhao, Sumei; Rong, Hua; Gu, Dahai; Li, Qihua; Huang, Ying; Xu, Zhiqiang; Chu, Xiaohui; Tao, Linli; Liu, Lixian; Ge, Changrong; Te Pas, Marinus F W; Jia, Junjing

2017-06-20

Intensive selection has resulted in increased growth rates and muscularity in broiler chickens, in addition to adverse effects, including delayed organ development, sudden death syndrome, and altered metabolic rates. The biological mechanisms underlying selection responses remain largely unknown. Non-artificially-selected indigenous Chinese chicken breeds display a wide variety of phenotypes, including differential growth rate, body weight, and muscularity. The Wuding chicken breed is a fast growing large chicken breed, and the Daweishan mini chicken breed is a slow growing small chicken breed. Together they form an ideal model system to study the biological mechanisms underlying broiler chicken selection responses in a natural system. The objective of this study was to study the biological mechanisms underlying differential phenotypes between the two breeds in muscle and liver tissues, and relate these to the growth rate and body development phenotypes of the two breeds. The muscle tissue in the Wuding breed showed higher expression of muscle development genes than muscle tissue in the Daweishan chicken breed. This expression was accompanied by higher expression of acute inflammatory response genes in Wuding chicken than in Daweishan chicken. The muscle tissue of the Daweishan mini chicken breed showed higher expression of genes involved in several metabolic mechanisms including endoplasmic reticulum, protein and lipid metabolism, energy metabolism, as well as specific immune traits than in the Wuding chicken. The liver tissue showed fewer differences between the two breeds. Genes displaying higher expression in the Wuding breed than in the Daweishan breed were not associated with a specific gene network or biological mechanism. Genes highly expressed in the Daweishan mini chicken breed compared to the Wuding breed were enriched for protein metabolism, ABC receptors, signal transduction, and IL6-related mechanisms. We conclude that faster growth rates and larger body size are related to increased expression of genes involved in muscle development and immune response in muscle, while slower growth rates and smaller body size are related to increased general cellular metabolism. The liver of the Daweishan breed displayed increased expression of metabolic genes.

Will changes in phenology track climate change? A study of growth initiation timing in coast Douglas-fir.

PubMed

Ford, Kevin R; Harrington, Constance A; Bansal, Sheel; Gould, Peter J; St Clair, J Bradley

2016-11-01

Under climate change, the reduction of frost risk, onset of warm temperatures and depletion of soil moisture are all likely to occur earlier in the year in many temperate regions. The resilience of tree species will depend on their ability to track these changes in climate with shifts in phenology that lead to earlier growth initiation in the spring. Exposure to warm temperatures ('forcing') typically triggers growth initiation, but many trees also require exposure to cool temperatures ('chilling') while dormant to readily initiate growth in the spring. If warming increases forcing and decreases chilling, climate change could maintain, advance or delay growth initiation phenology relative to the onset of favorable conditions. We modeled the timing of height- and diameter-growth initiation in coast Douglas-fir (an ecologically and economically vital tree in western North America) to determine whether changes in phenology are likely to track changes in climate using data from field-based and controlled-environment studies, which included conditions warmer than those currently experienced in the tree's range. For high latitude and elevation portions of the tree's range, our models predicted that warming will lead to earlier growth initiation and allow trees to track changes in the onset of the warm but still moist conditions that favor growth, generally without substantially greater exposure to frost. In contrast, toward lower latitude and elevation range limits, the models predicted that warming will lead to delayed growth initiation relative to changes in climate due to reduced chilling, with trees failing to capture favorable conditions in the earlier parts of the spring. This maladaptive response to climate change was more prevalent for diameter-growth initiation than height-growth initiation. The decoupling of growth initiation with the onset of favorable climatic conditions could reduce the resilience of coast Douglas-fir to climate change at the warm edges of its distribution. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Will changes in phenology track climate change? A study of growth initiation timing in coast Douglas-fir

USGS Publications Warehouse

Ford, Kevin R.; Harrington, Constance A.; Bansal, Sheel; Gould, Petter J.; St. Clair, Bradley

2016-01-01

Under climate change, the reduction of frost risk, onset of warm temperatures and depletion of soil moisture are all likely to occur earlier in the year in many temperate regions. The resilience of tree species will depend on their ability to track these changes in climate with shifts in phenology that lead to earlier growth initiation in the spring. Exposure to warm temperatures (“forcing”) typically triggers growth initiation, but many trees also require exposure to cool temperatures (“chilling”) while dormant to readily initiate growth in the spring. If warming increases forcing and decreases chilling, climate change could maintain, advance or delay growth initiation phenology relative to the onset of favorable conditions. We modeled the timing of height- and diameter-growth initiation in coast Douglas-fir (an ecologically and economically vital tree in western North America) to determine whether changes in phenology are likely to track changes in climate using data from field-based and controlled-environment studies, which included conditions warmer than those currently experienced in the tree's range. For high latitude and elevation portions of the tree's range, our models predicted that warming will lead to earlier growth initiation and allow trees to track changes in the onset of the warm but still moist conditions that favor growth, generally without substantially greater exposure to frost. In contrast, towards lower latitude and elevation range limits, the models predicted that warming will lead to delayed growth initiation relative to changes in climate due to reduced chilling, with trees failing to capture favorable conditions in the earlier parts of the spring. This maladaptive response to climate change was more prevalent for diameter-growth initiation than height-growth initiation. The decoupling of growth initiation with the onset of favorable climatic conditions could reduce the resilience of coast Douglas-fir to climate change at the warm edges of its distribution.

A Comparative Study of Ethylene Growth Response Kinetics in Eudicots and Monocots Reveals a Role for Gibberellin in Growth Inhibition and Recovery1[W][OA

PubMed Central

Kim, Joonyup; Wilson, Rebecca L.; Case, J. Brett; Binder, Brad M.

2012-01-01

Time-lapse imaging of dark-grown Arabidopsis (Arabidopsis thaliana) hypocotyls has revealed new aspects about ethylene signaling. This study expands upon these results by examining ethylene growth response kinetics of seedlings of several plant species. Although the response kinetics varied between the eudicots studied, all had prolonged growth inhibition for as long as ethylene was present. In contrast, with continued application of ethylene, white millet (Panicum miliaceum) seedlings had a rapid and transient growth inhibition response, rice (Oryza sativa ‘Nipponbare’) seedlings had a slow onset of growth stimulation, and barley (Hordeum vulgare) had a transient growth inhibition response followed, after a delay, by a prolonged inhibition response. Growth stimulation in rice correlated with a decrease in the levels of rice ETHYLENE INSENSTIVE3-LIKE2 (OsEIL2) and an increase in rice F-BOX DOMAIN AND LRR CONTAINING PROTEIN7 transcripts. The gibberellin (GA) biosynthesis inhibitor paclobutrazol caused millet seedlings to have a prolonged growth inhibition response when ethylene was applied. A transient ethylene growth inhibition response has previously been reported for Arabidopsis ethylene insensitive3-1 (ein3-1) eil1-1 double mutants. Paclobutrazol caused these mutants to have a prolonged response to ethylene, whereas constitutive GA signaling in this background eliminated ethylene responses. Sensitivity to paclobutrazol inversely correlated with the levels of EIN3 in Arabidopsis. Wild-type Arabidopsis seedlings treated with paclobutrazol and mutants deficient in GA levels or signaling had a delayed growth recovery after ethylene removal. It is interesting to note that ethylene caused alterations in gene expression that are predicted to increase GA levels in the ein3-1 eil1-1 seedlings. These results indicate that ethylene affects GA levels leading to modulation of ethylene growth inhibition kinetics. PMID:22977279

Intratumoral Infection with Murine Cytomegalovirus Synergizes with PD-L1 Blockade to Clear Melanoma Lesions and Induce Long-term Immunity

PubMed Central

Erkes, Dan A; Xu, Guangwu; Daskalakis, Constantine; Zurbach, Katherine A; Wilski, Nicole A; Moghbeli, Toktam; Hill, Ann B; Snyder, Christopher M

2016-01-01

Cytomegalovirus is an attractive cancer vaccine platform because it induces strong, functional CD8+ T-cell responses that accumulate over time and migrate into most tissues. To explore this, we used murine cytomegalovirus expressing a modified gp100 melanoma antigen. Therapeutic vaccination by the intraperitoneal and intradermal routes induced tumor infiltrating gp100-specific CD8+ T-cells, but provided minimal benefit for subcutaneous lesions. In contrast, intratumoral infection of established tumor nodules greatly inhibited tumor growth and improved overall survival in a CD8+ T-cell-dependent manner, even in mice previously infected with murine cytomegalovirus. Although murine cytomegalovirus could infect and kill B16F0s in vitro, infection was restricted to tumor-associated macrophages in vivo. Surprisingly, the presence of a tumor antigen in the virus only slightly increased the efficacy of intratumoral infection and tumor-specific CD8+ T-cells in the tumor remained dysfunctional. Importantly, combining intratumoral murine cytomegalovirus infection with anti-PD-L1 therapy was synergistic, resulting in tumor clearance from over half of the mice and subsequent protection against tumor challenge. Thus, while a murine cytomegalovirus-based vaccine was poorly effective against established subcutaneous tumors, direct infection of tumor nodules unexpectedly delayed tumor growth and synergized with immune checkpoint blockade to promote tumor clearance and long-term protection. PMID:27434584

Delayed Puberty (For Teens)

MedlinePlus

... the chromosomes can interfere with normal growth processes. Turner syndrome is an example of a chromosome disorder. It ... production of sex hormones. Women who have untreated Turner syndrome are shorter than normal, are usually infertile, and ...

Effects of heparin-binding epidermal growth factor-like growth factor on cell repopulation and signal transduction in periodontal ligament cells after scratch wounding in vitro.

PubMed

Lee, J S; Kim, J M; Hong, E K; Kim, S-O; Yoo, Y-J; Cha, J-H

2009-02-01

A growing amount of attention has been placed on periodontal regeneration and wound healing for periodontal therapy. This study was conducted in an effort to determine the effects of heparin-binding epidermal growth factor-like growth factor on cell repopulation and signal transduction in periodontal ligament cells after scratch wounding in vitro. Human periodontal ligament cells were acquired from explant tissue of human healthy periodontal ligament. After the wounding of periodontal ligament cells, the change in expression of heparin-binding epidermal growth factor-like growth factor and epidermal growth factor receptors 1-4 mRNA was assessed. The effects of heparin-binding epidermal growth factor-like growth factor on periodontal ligament cell proliferation and repopulation were assessed in vitro via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and by photographing the injuries, respectively. Extracellular signal-regulated kinase (Erk)1/2, p38 and Akt phosphorylation was characterized via western blotting. Scratch wounding resulted in a significant up-regulation of heparin-binding epidermal growth factor-like growth factor mRNA expression, whereas wounding had no effect on the expression levels of epidermal growth factor receptors 1-4. Interestingly, no expression of epidermal growth factor receptors 2 and 4 was detectable prior to or after wounding. Heparin-binding epidermal growth factor-like growth factor treatment promoted the proliferation and repopulation of periodontal ligament cells. The scratch wounding also stimulated the phosphorylation of Erk1/2 and p38, but not of Akt, in periodontal ligament cells, and heparin-binding epidermal growth factor-like growth factor treatment applied after wounding amplified and extended the activations of Erk1/2 and p38, but not of Akt. Furthermore, Erk1/2 inhibition blocked the process of cell repopulation induced by heparin-binding epidermal growth factor-like growth factor, whereas the inhibition of p38 delayed the process. These results indicate that heparin-binding epidermal growth factor-like growth factor may constitute a critical factor in the wound healing of human periodontal ligament cells by a mechanism that requires the activation of Erk1/2 via specific interaction with epidermal growth factor receptor 1.

Correlation Between Mothers' Depression and Developmental Delay in Infants Aged 6-18 Months.

PubMed

Vameghi, Roshanak; Amir Ali Akbari, Sedigheh; Sajjadi, Homeira; Sajedi, Firoozeh; Alavimajd, Hamid

2015-08-23

Regarding the importance of children's developmental status and various factors that delay their development, this study was conducted to examine the correlation between mothers' depression levels and the developmental delay in infants. This descriptive study was performed on 1053 mothers and their infants' age 6 to18 month-old in medical centers affiliated with Shahid Beheshti University of Medical Sciences, Iran, in 2014-2015. The participants were selected through multi-stage random sampling. The following instruments were used in this study: A demographic and obstetric specification questionnaire, infant specification questionnaire, the Beck Depression Inventory, and the Ages and Stages Questionnaire to determine the status of the children's development. The data were analyzed using SPSS19 software, Mann-Whitney; independent T-test and logistic-Regression tests were used. The results showed that 491 mothers (46.7%) suffered mild to extremely severe depression. The delay in infant development was 11.8%. The Mann-Whitney test showed a correlation between mothers' depression levels and developmental delay in infants (P=0.001). Moreover, there was a significant correlation between mothers' depression and developmental delays in gross-motor and problem-solving skills (P<0/05). In logistic model age of infants showed significant correlation with developmental delay (P=0.004 OR=1.07), but unwanted pregnancy, gender of infants, type of delivery and socioeconomic status had no correlation with developmental delay. Given the correlation between mothers' depression and infant development, it is recommended to screen mothers for depression in order to perform early interventions in developmental delay.

A new method of applying a controlled soil water stress, and its effect on the growth of cotton and soybean seedlings at ambient and elevated carbon dioxide

USDA-ARS?s Scientific Manuscript database

While numerous studies have shown that elevated carbon dioxide can delay soil water depletion by causing partial stomatal closure, few studies have compared responses of plant growth to the same soil water deficits imposed at ambient and elevated carbon dioxide. We applied a vacuum to ceramic cups ...

Growing Pains from Rapid Growth: A Historical Case Study of George Fox University from 1983 to 2003

ERIC Educational Resources Information Center

Railsback, Gary L.

2007-01-01

This article is a historical case study of George Fox University (GFU) in Newberg, Oregon. Using organizational lifecycle as a theoretical framework, George Fox University had a long and delayed childhood in that it remained a small and struggling institution for most of the 20th century, and then experienced rapid growth in the late 1980s. This…

The Effects of Projected Future Demand Including Very Light Jet Air-Taxi Operations on U.S. National Airspace System Delays as a Function of Next Generation Air Transportation System Airspace Capacity

NASA Technical Reports Server (NTRS)

Smith, Jerry; Viken, Jeff; Dollyhigh, Samuel; Trani, Antonio; Baik, Hojong; Hinze, Nicholas; Ashiabor, Senanu

2007-01-01

This paper presents the results from a study which investigates the potential effects of the growth in air traffic demand including projected Very Light Jet (VLJ) air-taxi operations adding to delays experienced by commercial passenger air transportation in the year 2025. The geographic region studied is the contiguous United States (U.S.) of America, although international air traffic to and from the U.S. is included. The main focus of this paper is to determine how much air traffic growth, including VLJ air-taxi operations will add to enroute airspace congestion and determine what additional airspace capacity will be needed to accommodate the expected demand. Terminal airspace is not modeled and increased airport capacity is assumed.

Aurora A Is Critical for Survival in HPV-Transformed Cervical Cancer.

PubMed

Gabrielli, Brian; Bokhari, Fawzi; Ranall, Max V; Oo, Zay Yar; Stevenson, Alexander J; Wang, Weili; Murrell, Melanie; Shaikh, Mushfiq; Fallaha, Sora; Clarke, Daniel; Kelly, Madison; Sedelies, Karin; Christensen, Melinda; McKee, Sara; Leggatt, Graham; Leo, Paul; Skalamera, Dubravka; Soyer, H Peter; Gonda, Thomas J; McMillan, Nigel A J

2015-12-01

Human papillomavirus (HPV) is the causative agent in cervical cancer. HPV oncogenes are major drivers of the transformed phenotype, and the cancers remain addicted to these oncogenes. A screen of the human kinome has identified inhibition of Aurora kinase A (AURKA) as being synthetically lethal on the background of HPV E7 expression. The investigational AURKA inhibitor MLN8237/Alisertib selectively promoted apoptosis in the HPV cancers. The apoptosis was driven by an extended mitotic delay in the Alisertib-treated HPV E7-expressing cells. This had the effect of reducing Mcl-1 levels, which is destabilized in mitosis, and increasing BIM levels, normally destabilized by Aurora A in mitosis. Overexpression of Mcl-1 reduced sensitivity to the drug. The level of HPV E7 expression influenced the extent of Alisertib-induced mitotic delay and Mcl-1 reduction. Xenograft experiments with three cervical cancer cell lines showed Alisertib inhibited growth of HPV and non-HPV xenografts during treatment. Growth of non-HPV tumors was delayed, but in two separate HPV cancer cell lines, regression with no resumption of growth was detected, even at 50 days after treatment. A transgenic model of premalignant disease driven solely by HPV E7 also demonstrated sensitivity to drug treatment. Here, we show for the first time that targeting of the Aurora A kinase in mice using drugs such as Alisertib results in a curative sterilizing therapy that may be useful in treating HPV-driven cancers. ©2015 American Association for Cancer Research.

Omega-3 fatty acid supplementation delays the progression of neuroblastoma in vivo.

PubMed

Gleissman, Helena; Segerström, Lova; Hamberg, Mats; Ponthan, Frida; Lindskog, Magnus; Johnsen, John Inge; Kogner, Per

2011-04-01

Epidemiological and preclinical studies have revealed that omega-3 fatty acids have anticancer properties. We have previously shown that the omega-3 fatty acid docosahexaenoic acid (DHA) induces apoptosis of neuroblastoma cells in vitro by mechanisms involving intracellular peroxidation of DHA by means of 15-lipoxygenase or autoxidation. In our study, the effects of DHA supplementation on neuroblastoma tumor growth in vivo were investigated using two complementary approaches. For the purpose of prevention, DHA as a dietary supplement was fed to athymic rats before the rats were xenografted with human neuroblastoma cells. For therapeutic purposes, athymic rats with established neuroblastoma xenografts were given DHA daily by gavage and tumor growth was monitored. DHA levels in plasma and tumor tissue were analyzed by gas liquid chromatography. DHA delayed neuroblastoma xenograft development and inhibited the growth of established neuroblastoma xenografts in athymic rats. A revised version of the Pediatric Preclinical Testing Program evaluation scheme used as a measurement of treatment response showed that untreated control animals developed progressive disease, whereas treatment with DHA resulted in stable disease or partial response, depending on the DHA concentration. In conclusion, prophylactic treatment with DHA delayed neuroblastoma development, suggesting that DHA could be a potential agent in the treatment of minimal residual disease and should be considered for prevention in selected cases. Treatment results on established aggressive neuroblastoma tumors suggest further studies aiming at a clinical application in children with high-risk neuroblastoma. Copyright © 2010 UICC.

Photoperiod cues and patterns of genetic variation limit phenological responses to climate change in warm parts of species' range: Modeling diameter-growth cessation in coast Douglas-fir.

PubMed

Ford, Kevin R; Harrington, Constance A; St Clair, J Bradley

2017-08-01

The phenology of diameter-growth cessation in trees will likely play a key role in mediating species and ecosystem responses to climate change. A common expectation is that warming will delay cessation, but the environmental and genetic influences on this process are poorly understood. We modeled the effects of temperature, photoperiod, and seed-source climate on diameter-growth-cessation timing in coast Douglas-fir (an ecologically and economically vital tree) using high-frequency growth measurements across broad environmental gradients for a range of genotypes from different seed sources. Our model suggests that cool temperatures or short photoperiods can induce cessation in autumn. At cool locations (high latitude and elevation), cessation seems to be induced primarily by low temperatures in early autumn (under relatively long photoperiods), so warming will likely delay cessation and extend the growing season. But at warm locations (low latitude or elevation), cessation seems to be induced primarily by short photoperiods later in autumn, so warming will likely lead to only slight extensions of the growing season, reflecting photoperiod limitations on phenological shifts. Trees from seed sources experiencing frequent frosts in autumn or early winter tended to cease growth earlier in the autumn, potentially as an adaptation to avoid frost. Thus, gene flow into populations in warm locations with little frost will likely have limited potential to delay mean cessation dates because these populations already cease growth relatively late. In addition, data from an abnormal heat wave suggested that very high temperatures during long photoperiods in early summer might also induce cessation. Climate change could make these conditions more common in warm locations, leading to much earlier cessation. Thus, photoperiod cues, patterns of genetic variation, and summer heat waves could limit the capacity of coast Douglas-fir to extend its growing season in response to climate change in the warm parts of its range. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Expanding the clinical spectrum of chromosome 15q26 terminal deletions associated with IGF-1 resistance.

PubMed

O'Riordan, Aisling M; McGrath, Niamh; Sharif, Farhana; Murphy, Nuala P; Franklin, Orla; Lynch, Sally Ann; O'Grady, Michael J

2017-01-01

Haploinsufficiency of the insulin-like growth factor-1 receptor (IGF1R) gene on chromosome 15q26.3 is associated with impaired prenatal and postnatal growth, developmental delay, dysmorphic features and skeletal abnormalities. Terminal deletions of chromosome 15q26 arising more proximally may also be associated with congenital heart disease, epilepsy, diaphragmatic hernia and renal anomalies. We report three additional cases of 15q26 terminal deletions with novel features which may further expand the spectrum of this rarely reported contiguous gene syndrome. Phenotypic features including neonatal lymphedema, aplasia cutis congenita and aortic root dilatation have not been reported previously. Similarly, laboratory features of insulin-like growth factor 1 (IGF-1) resistance are described, including markedly elevated IGF-1 of up to +4.7 SDS. In one patient, the elevated IGF-1 declined over time and this coincided with a period of spontaneous growth acceleration. Deletions of 15q26 are a potential risk factor for aortic root dilatation, neonatal lymphedema and aplasia cutis in addition to causing growth restriction. What is Known: • Terminal deletions of chromosome 15q26 are associated with impaired prenatal and postnatal growth, developmental delay, dysmorphic features and skeletal abnormalities. What is New: • Neonatal lymphedema, aplasia cutis congenita and aortic root dilatation have not been previously described in 15q26 terminal deletions and may represent novel features. • IGF-1 levels may be increased up to 4.7 SDS.

Hypoxia Response Element-Regulated MMP-9 Promotes Neurological Recovery via Glial Scar Degradation and Angiogenesis in Delayed Stroke.

PubMed

Cai, Hongxia; Ma, Yuanyuan; Jiang, Lu; Mu, Zhihao; Jiang, Zhen; Chen, Xiaoyan; Wang, Yongting; Yang, Guo-Yuan; Zhang, Zhijun

2017-06-07

Matrix metalloproteinase 9 (MMP-9) plays a beneficial role in the delayed phase of middle cerebral artery occlusion (MCAO). However, the mechanism is obscure. Here, we constructed hypoxia response element (HRE)-regulated MMP-9 to explore its effect on glial scars and neurogenesis in delayed ischemic stroke. Adult male Institute of Cancer Research (ICR) mice underwent MCAO and received a stereotactic injection of lentivirus carrying HRE-MMP-9 or normal saline (NS)/lentivirus-GFP 7 days after ischemia. We found that HRE-MMP-9 improved neurological outcomes, reduced ischemia-induced brain atrophy, and degraded glial scars (p < 0.05). Furthermore, HRE-MMP-9 increased the number of microvessels in the peri-infarct area (p < 0.001), which may have been due to the accumulation of endogenous endothelial progenitor cells (EPCs) in the peri-infarct area after glial scar degradation. Finally, HRE-MMP-9 increased the number of bromodeoxyuridine-positive (BrdU + )/NeuN + cells and the expression of PSD-95 in the peri-infarct area (p < 0.01). These changes could be blocked by vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor SU5416 and MMP-9 inhibitor 2-[[(4-phenoxyphenyl)sulfonyl]methyl]-thiirane (SB-3CT). Our results provided a novel mechanism by which glial scar degradation and vascular endothelial growth factor (VEGF)/VEGFR2-dependent angiogenesis may be key procedures for neurological recovery in delayed ischemic stroke after HRE-MMP-9 treatment. Therefore, HRE-MMP-9 overexpression in the delayed ischemic brain is a promising approach for neurological recovery. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

BMP-2/PLGA delayed-release microspheres composite graft, selection of bone particulate diameters, and prevention of aseptic inflammation for bone tissue engineering.

PubMed

Ji, Ye; Xu, Gong Ping; Zhang, Zhi Peng; Xia, Jing Jun; Yan, Jing Long; Pan, Shang Ha

2010-03-01

Autogenous bone grafts are widely used in the repair of bone defects. Growth factors such as bone morphogenetic protein 2 (BMP-2) can induce bone regeneration and enhance bone growth. The combination of an autogenous bone graft and BMP-2 may provide a better osteogenic effect than either treatment alone, but BMP-2 is easily inactivated in body fluid. The objective of this study was to develop a technique that can better preserve the in vivo activity of BMP-2 incorporated in bone grafts. In this study, we first prepared BMP-2/poly(lactic-co-glycolic acid) (PLGA) delayed-release microspheres, and then combined collagen, the delayed-release microspheres, and rat autologous bone particulates to form four groups of composite grafts with different combinations: collagen in group A; collagen combined with bone particulates in group B; collagen combined with BMP-2/PLGA delayed-release microspheres in group C; and collagen combined with both bone particulates and BMP-2/PLGA delayed-release microspheres in group D. The four groups of composite grafts were implanted into the gluteus maximus pockets in rats. The ectopic osteogenesis and ALP level in group D (experimental group) were compared with those in groups A, B, and C (control groups) to study whether it had higher osteogenic capability. Results showed that the composite graft design increased the utility of BMP-2 and reduced the required dose of BMP-2 and volume of autologous bone. The selection of bone particulate diameter had an impact on the osteogenetic potential of bone grafts. Collagen prevented the occurrence of aseptic inflammation and improved the osteoinductivity of BMP-2. These results showed that this composite graft design is effective and feasible for use in bone repair.

The impact of delayed maternity on foetal growth in Spain: An assessment by population attributable fraction.

PubMed

Varea, Carlos; Terán, José Manuel; Bernis, Cristina; Bogin, Barry

2017-09-18

Delayed childbearing is considered a risk factor for maternal-foetal health. As in other higher-income countries, in Spain age at maternity has steadily increased during the last two decades. To quantify the impact of the delay in the age at maternity on small for gestational age (SGA) categories of <3rd, 3rd-5th and 5th-10th percentiles. 2,672,350 singleton live births born to Spanish mothers in 2007-2015 were analysed. Adjusted relative risk was calculated to estimate the adjusted partial population attributable fractions (PAF p ) for mothers aged 35-39 and ≥40 years for each category of SGA considering the interaction between age at maternity and parity. Primipara 35-39 years old mothers have the highest PAF p in the three categories of SGA, with the maximum value for SGA <3rd percentile (2.57%, 95% CI 2.25, 2.88). PAF p for both primipara and multipara ≥40 years old mothers were less than 1%. PAF p for primipara older mothers increased significantly in 2007-2015 for the three categories of SGA, more clearly among those aged 35-39 years. The contribution of multipara mothers of both age groups did not increase significantly during the period. Delayed maternity is a significant adjusted risk factor for SGA, contributing to the increase of its prevalence. However, results also suggest a limited clinical impact of delayed maternity on foetal growth. Positive changes in maternal profile associated with the shift in maternal age might contribute to explain the limited impact of mothers aged 35 years and older on negative birth outcome in Spain. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

Diabetes mellitus affects the biomechanical function of the callus and the expression of TGF-beta1 and BMP2 in an early stage of fracture healing.

PubMed

Xu, M T; Sun, S; Zhang, L; Xu, F; Du, S L; Zhang, X D; Wang, D W

2016-01-01

Transforming growth factor beta 1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2) are important regulators of bone repair and regeneration. In this study, we examined whether TGF-β1 and BMP-2 expressions were delayed during bone healing in type 1 diabetes mellitus. Tibial fractures were created in 95 diabetic and 95 control adult male Wistar rats of 10 weeks of age. At 1, 2, 3, 4, and 5 weeks after fracture induction, five rats were sacrificed from each group. The expressions of TGF-β1 and BMP2 in the fractured tibias were measured by immunohistochemistry and quantitative reverse-transcription polymerase chain reaction, weekly for the first 5 weeks post-fracture. Mechanical parameters (bending rigidity, torsional rigidity, destruction torque) of the healing bones were also assessed at 3, 4, and 5 weeks post-fracture, after the rats were sacrificed. The bending rigidity, torsional rigidity and destruction torque of the two groups increased continuously during the healing process. The diabetes group had lower mean values for bending rigidity, torsional rigidity and destruction torque compared with the control group (P<0.05). TGF-β1 and BMP-2 expression were significantly lower (P<0.05) in the control group than in the diabetes group at postoperative weeks 1, 2, and 3. Peak levels of TGF-β1 and BMP-2 expression were delayed by 1 week in the diabetes group compared with the control group. Our results demonstrate that there was a delayed recovery in the biomechanical function of the fractured bones in diabetic rats. This delay may be associated with a delayed expression of the growth factors TGF-β1 and BMP-2.

Drought-induced adaptation of the xylem in Scots pine and pubescent oak.

PubMed

Eilmann, Britta; Zweifel, Roman; Buchmann, Nina; Fonti, Patrick; Rigling, Andreas

2009-08-01

Drought impairs tree growth in the inner-Alpine valleys of Central Europe. We investigated species-specific responses to contrasting water supply, with Scots pine (Pinus sylvestris L.), threatened by drought-induced mortality, and pubescent oak (Quercus pubescens Willd.), showing no connection between drought events and mortality. The two co-occurring tree species were compared, growing either along an open water channel or at a site with naturally dry conditions. In addition, the growth response of Scots pine to a draining of a water channel was studied. We analysed the radial increment for the last 100 years and wood anatomical parameters for the last 45 years. Drought reduced the conduit area of pubescent oak, but increased the radial lumen diameter of the conduits in Scots pine. Both species decreased their radial increment under drought. In Scots pine, radial increment was generally more dependent on water availability than that in pubescent oak. Irrigated trees responded less negatively to high temperature as seen in the increase in the conduit area in pubescent oak and the removal of the limitation of cell division by high temperatures. After irrigation stopped, tree-ring width for Scots pine decreased within 1-year delay, whereas lumen diameter and cell-wall thickness responded with a 4-year delay. Scots pine seemed to optimize the carbon-per-conduit-costs under drought by increasing conduits diameter while decreasing cell numbers. This strategy might lead to a complete loss of tree rings under severe drought and thus to an impairment of water transport. In contrast, in pubescent oak tree-ring width is less affected by summer drought because parts of the earlywood are built in early spring. Thus, pubescent oak might have gradual advantages over pine in today's climate of the inner-Alpine valley.

The Chemokine CXCL12 Is Essential for the Clearance of the Filaria Litomosoides sigmodontis in Resistant Mice

PubMed Central

Attout, Tarik; Ehrhardt, Katharina; Lhermitte-Vallarino, Nathaly; Hachet-Haas, Muriel; Galzi, Jean Luc; Brotin, Emilie; Bachelerie, Françoise; Gavotte, Laurent; Moulia, Catherine; Bain, Odile; Martin, Coralie

2012-01-01

Litomosoides sigmodontis is a cause of filarial infection in rodents. Once infective larvae overcome the skin barrier, they enter the lymphatic system and then settle in the pleural cavity, causing soft tissue infection. The outcome of infection depends on the parasite's modulatory ability and also on the immune response of the infected host, which is influenced by its genetic background. The goal of this study was to determine whether host factors such as the chemokine axis CXCL12/CXCR4, which notably participates in the control of immune surveillance, can influence the outcome of the infection. We therefore set up comparative analyses of subcutaneous infection by L. sigmodontis in two inbred mouse strains with different outcomes: one susceptible strain (BALB/c) and one resistant strain (C57BL/6). We showed that rapid parasite clearance was associated with a L. sigmodontis-specific CXCL12-dependent cell response in C57BL/6 mice. CXCL12 was produced mainly by pleural mesothelial cells during infection. Conversely, the delayed parasite clearance in BALB/c mice was neither associated with an increase in CXCL12 levels nor with cell influx into the pleural cavity. Remarkably, interfering with the CXCL12/CXCR4 axis in both strains of mice delayed filarial development, as evidenced by the postponement of the fourth molting process. Furthermore, the in vitro growth of stage 4 filariae was favored by the addition of low amounts of CXCL12. The CXCL12/CXCR4 axis thus appears to have a dual effect on the L. sigmodontis life cycle: by acting as a host-cell restriction factor for infection, and as a growth factor for worms. PMID:22511975

Paracentric inversion of chromosome 2 associated with cryptic duplication of 2q14 and deletion of 2q37 in a patient with autism.

PubMed

Devillard, Françoise; Guinchat, Vincent; Moreno-De-Luca, Daniel; Tabet, Anne-Claude; Gruchy, Nicolas; Guillem, Pascale; Nguyen Morel, Marie-Ange; Leporrier, Nathalie; Leboyer, Marion; Jouk, Pierre-Simon; Lespinasse, James; Betancur, Catalina

2010-09-01

We describe a patient with autism and a paracentric inversion of chromosome 2q14.2q37.3, with a concurrent duplication of the proximal breakpoint at 2q14.1q14.2 and a deletion of the distal breakpoint at 2q37.3. The abnormality was derived from his mother with a balanced paracentric inversion. The inversion in the child appeared to be cytogenetically balanced but subtelomere FISH revealed a cryptic deletion at the 2q37.3 breakpoint. High-resolution single nucleotide polymorphism array confirmed the presence of a 3.5 Mb deletion that extended to the telomere, and showed a 4.2 Mb duplication at 2q14.1q14.2. FISH studies using a 2q14.2 probe showed that the duplicated segment was located at the telomeric end of chromosome 2q. This recombinant probably resulted from breakage of a dicentric chromosome. The child had autism, mental retardation, speech and language delay, hyperactivity, growth retardation with growth hormone deficiency, insulin-dependent diabetes, and mild facial dysmorphism. Most of these features have been previously described in individuals with simple terminal deletion of 2q37. Pure duplications of the proximal chromosome 2q are rare and no specific syndrome has been defined yet, so the contribution of the 2q14.1q14.2 duplication to the phenotype of the patient is unknown. These findings underscore the need to explore apparently balanced chromosomal rearrangements inherited from a phenotypically normal parent in subjects with autism and/or developmental delay. In addition, they provide further evidence indicating that chromosome 2q terminal deletions are among the most frequently reported cytogenetic abnormalities in individuals with autism.

Depressive and Anxiety Symptom Trajectories From School-Age Through Young Adulthood in Samples With Autism Spectrum Disorder and Developmental Delay

PubMed Central

Gotham, Katherine; Brunwasser, Steven M.; Lord, Catherine

2015-01-01

Objective To (1) model growth in anxiety and depressive symptoms from late school age through young adulthood in individuals with autism spectrum disorder (ASD) and controls with developmental delay (DD); and (2) assess relationships between internalizing growth patterns, participant characteristics, baseline predictors, and distal outcomes. Method Data were collected between 6-24 years of age in 165 participants (n=109 with ASD; n=56 with nonspectrum DD), most of whom received diagnostic evaluations in both childhood and early adulthood. Questionnaires were collected approximately every 3-6 months between ages 9-24. Parent-rated Child and Adult Behavior Checklists (CBCL; ABCL) and Developmental Behavior Checklist anxiety- and depression-related subscale distributions were modeled with mixed-effects Poisson models, covarying diagnosis, age, verbal IQ (VIQ), gender, and significant two- and three-way interactions. Results Anxiety was positively associated with VIQ, and controlling for VIQ, both anxiety and depressive symptoms were greater in ASD than nonspectrum participants. Female gender predicted greater increases over time in anxiety and depressive symptoms for both diagnostic groups. Lower maternal education was associated with increasing internalizing symptoms in a subset of less verbal individuals with ASD. In exploratory post-hoc analyses, internalizing symptoms were associated with poorer emotional regulation in school age, and with lower life satisfaction and greater social difficulties in early adulthood. Conclusion Findings support previous claims that individuals with ASD are at particular risk for affect- and anxiety-specific problems. While symptom levels in females increase at a faster rate throughout adolescence, males with ASD appear to have elevated levels of depressive symptoms in school age that are maintained into young adulthood. PMID:25901773

Depressive and anxiety symptom trajectories from school age through young adulthood in samples with autism spectrum disorder and developmental delay.

PubMed

Gotham, Katherine; Brunwasser, Steven M; Lord, Catherine

2015-05-01

The objectives of this study were to model growth in anxiety and depressive symptoms from late school age through young adulthood in individuals with autism spectrum disorder (ASD) and controls with developmental delay (DD), and to assess relationships among internalizing growth patterns, participant characteristics, baseline predictors, and distal outcomes. Data were collected between ages 6 and 24 years in 165 participants (n = 109 with ASD; n = 56 with nonspectrum DD), most of whom received diagnostic evaluations in both childhood and early adulthood. Questionnaires were collected approximately every 3 to 6 months between ages 9 and 24 years. Parent-rated Child Behavior Checklist (CBCL), Adult Behavior Checklist (ABCL), and Developmental Behaviour Checklist anxiety- and depression-related subscale distributions were modeled with mixed-effects Poisson models, covarying diagnosis, age, verbal IQ (VIQ), gender, and significant 2- and 3-way interactions. Anxiety was positively associated with VIQ, and controlling for VIQ, both anxiety and depressive symptoms were greater in ASD than nonspectrum participants. Female gender predicted greater increases over time in anxiety and depressive symptoms for both diagnostic groups. Lower maternal education was associated with increasing internalizing symptoms in a subset of less verbal individuals with ASD. In exploratory post hoc analyses, internalizing symptoms were associated with poorer emotional regulation in school age, and with lower life satisfaction and greater social difficulties in early adulthood. Findings support previous claims that individuals with ASD are at particular risk for affect- and anxiety-specific problems. Although symptom levels in females increase at a faster rate throughout adolescence, males with ASD appear to have elevated levels of depressive symptoms in school age that are maintained into young adulthood. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Impact of maternal smoking on birth size: effect of parity and sex dimorphism.

PubMed

Varvarigou, Anastasia A; Asimakopoulou, Aspasia; Beratis, Nicholas G

2009-01-01

Maternal smoking during pregnancy causes a delay of intrauterine growth. To examine the effect of maternal smoking during pregnancy on fetal growth in relationship to maternal parity, age and number of cigarettes smoked/day, and offspring's gender. We studied 2,108 term newborns (1,102 male, 1,006 female) delivered at the General University Hospital of Patras from 1994 to 2004. The 1,443 were born to mothers who did not smoke and 665 to mothers who smoked during pregnancy. Birth weight, length and head circumference were measured prospectively in all newborns. Also, maternal smoking status and number of cigarettes smoked per day, age, and parity were recorded. For the analysis, t test, one-way ANOVA, Mann-Whitney U test, Spearman rank correlation, and factorial MANOVA with covariates were used. With increasing parity, in the neonates of nonsmoking mothers there was a gradual increase of growth, whereas in neonates of smoking mothers there was a gradual decrease of growth. This effect was more pronounced in males. A significant negative main effect on growth resulted from the interaction of smoking with parity (p = 0.013), and with gender and parity (p = 0.001). There was a significant negative correlation between number of cigarettes smoked per day and growth, the strength of which increased with parity, mainly in males. Maternal smoking during pregnancy causes a delay in fetal growth, which is greater in male offspring, an effect that is enhanced with parity but is independent of maternal age. (c) 2008 S. Karger AG, Basel.

TIF-IA-dependent regulation of ribosome synthesis in drosophila muscle is required to maintain systemic insulin signaling and larval growth.

PubMed

Ghosh, Abhishek; Rideout, Elizabeth J; Grewal, Savraj S

2014-10-01

The conserved TOR kinase signaling network links nutrient availability to cell, tissue and body growth in animals. One important growth-regulatory target of TOR signaling is ribosome biogenesis. Studies in yeast and mammalian cell culture have described how TOR controls rRNA synthesis-a limiting step in ribosome biogenesis-via the RNA Polymerase I transcription factor TIF-IA. However, the contribution of TOR-dependent ribosome synthesis to tissue and body growth in animals is less clear. Here we show in Drosophila larvae that ribosome synthesis in muscle is required non-autonomously to maintain normal body growth and development. We find that amino acid starvation and TOR inhibition lead to reduced levels of TIF-IA, and decreased rRNA synthesis in larval muscle. When we mimic this decrease in muscle ribosome synthesis using RNAi-mediated knockdown of TIF-IA, we observe delayed larval development and reduced body growth. This reduction in growth is caused by lowered systemic insulin signaling via two endocrine responses: reduced expression of Drosophila insulin-like peptides (dILPs) from the brain and increased expression of Imp-L2-a secreted factor that binds and inhibits dILP activity-from muscle. We also observed that maintaining TIF-IA levels in muscle could partially reverse the starvation-mediated suppression of systemic insulin signaling. Finally, we show that activation of TOR specifically in muscle can increase overall body size and this effect requires TIF-IA function. These data suggest that muscle ribosome synthesis functions as a nutrient-dependent checkpoint for overall body growth: in nutrient rich conditions, TOR is required to maintain levels of TIF-IA and ribosome synthesis to promote high levels of systemic insulin, but under conditions of starvation stress, reduced muscle ribosome synthesis triggers an endocrine response that limits systemic insulin signaling to restrict growth and maintain homeostasis.

TIF-IA-Dependent Regulation of Ribosome Synthesis in Drosophila Muscle Is Required to Maintain Systemic Insulin Signaling and Larval Growth

PubMed Central

Ghosh, Abhishek; Rideout, Elizabeth J.; Grewal, Savraj S.

2014-01-01

The conserved TOR kinase signaling network links nutrient availability to cell, tissue and body growth in animals. One important growth-regulatory target of TOR signaling is ribosome biogenesis. Studies in yeast and mammalian cell culture have described how TOR controls rRNA synthesis—a limiting step in ribosome biogenesis—via the RNA Polymerase I transcription factor TIF-IA. However, the contribution of TOR-dependent ribosome synthesis to tissue and body growth in animals is less clear. Here we show in Drosophila larvae that ribosome synthesis in muscle is required non-autonomously to maintain normal body growth and development. We find that amino acid starvation and TOR inhibition lead to reduced levels of TIF-IA, and decreased rRNA synthesis in larval muscle. When we mimic this decrease in muscle ribosome synthesis using RNAi-mediated knockdown of TIF-IA, we observe delayed larval development and reduced body growth. This reduction in growth is caused by lowered systemic insulin signaling via two endocrine responses: reduced expression of Drosophila insulin-like peptides (dILPs) from the brain and increased expression of Imp-L2—a secreted factor that binds and inhibits dILP activity—from muscle. We also observed that maintaining TIF-IA levels in muscle could partially reverse the starvation-mediated suppression of systemic insulin signaling. Finally, we show that activation of TOR specifically in muscle can increase overall body size and this effect requires TIF-IA function. These data suggest that muscle ribosome synthesis functions as a nutrient-dependent checkpoint for overall body growth: in nutrient rich conditions, TOR is required to maintain levels of TIF-IA and ribosome synthesis to promote high levels of systemic insulin, but under conditions of starvation stress, reduced muscle ribosome synthesis triggers an endocrine response that limits systemic insulin signaling to restrict growth and maintain homeostasis. PMID:25356674

Congenital hypogonadotropic hypogonadism, functional hypogonadotropism or constitutional delay of growth and puberty? An analysis of a large patient series from a single tertiary center.

PubMed

Varimo, Tero; Miettinen, Päivi J; Känsäkoski, Johanna; Raivio, Taneli; Hero, Matti

2017-01-01

What diagnoses underlie delayed puberty (DP) and predict its outcome? A multitude of different diagnoses underlie DP, and in boys a history of cryptorchidism, small testicular size and slow growth velocity (GV) predict its clinical course. DP is caused by a variety of underlying etiologies. Hormonal markers can be used in the differential diagnosis of DP but none of them have shown complete diagnostic accuracy. Medical records of 589 patients evaluated for DP in a single tertiary care center between 2004 and 2014 were retrospectively reviewed. Clinical and biochemical data of 174 boys and 70 girls who fulfilled the criteria of DP were included in the analyses. We characterized the frequencies of underlying conditions and evaluated the predictive efficacy of selected clinical and hormonal markers. Thirty etiologies that underlie DP were identified. No markers of clinical value could be identified in the girls, whereas a history of cryptorchidism in the boys was associated with an increase in the risk of permanent hypogonadism (odds ratio 17.2 (95% CI; 3.4-85.4, P < 0.001)). The conditions that cause functional hypogonadotropic hypogonadism were more frequent in boys with a GV below 3 cm/yr than in those growing faster (19% vs 4%, P < 0.05). In this series, the most effective markers to discriminate the prepubertal boys with constitutional delay of growth and puberty (CDGP) from those with congenital hypogonadotropic hypogonadism (CHH) were testicular volume (cut-off 1.1 ml with a sensitivity of 100% and a specificity of 91%), GnRH-induced maximal LH (cut-off 4.3 IU/L; 100%, 75%) and basal inhibin B (INHB) level (cut-off 61 ng/L; 90%, 83%). The main limitation of the study is the retrospective design. Prior cryptorchidism and slow GV are two important clinical cues that may help clinicians to predict the clinical course of DP in boys, whereas markers of similar value could not be identified in girls. In prepubertal boys, testicular size appeared as effective as INHB and GnRH-induced LH levels in the differential diagnosis between CHH and CDGP. This study was supported by the Academy of Finland (268356), Foundation for Pediatric Research (7495), Sigrid Juselius Foundation (2613) and the Finnish Medical Foundation (011115). The authors have no competing interests to report. Not applicable. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Management of Men with Prostate-specific Antigen Failure After Prostate Radiotherapy: The Case Against Early Androgen Deprivation.

PubMed

Brand, Douglas; Parker, Chris

2018-04-01

In men with prostate-specific antigen failure after radical radiotherapy, androgen deprivation therapy should be delayed until the site of recurrence is known to allow consideration of curative treatment options, to delay androgen deprivation therapy-related morbidity, and to enable earlier access to abiraterone and docetaxel. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Stimulus-specific variability in color working memory with delayed estimation.

PubMed

Bae, Gi-Yeul; Olkkonen, Maria; Allred, Sarah R; Wilson, Colin; Flombaum, Jonathan I

2014-04-08

Working memory for color has been the central focus in an ongoing debate concerning the structure and limits of visual working memory. Within this area, the delayed estimation task has played a key role. An implicit assumption in color working memory research generally, and delayed estimation in particular, is that the fidelity of memory does not depend on color value (and, relatedly, that experimental colors have been sampled homogeneously with respect to discriminability). This assumption is reflected in the common practice of collapsing across trials with different target colors when estimating memory precision and other model parameters. Here we investigated whether or not this assumption is secure. To do so, we conducted delayed estimation experiments following standard practice with a memory load of one. We discovered that different target colors evoked response distributions that differed widely in dispersion and that these stimulus-specific response properties were correlated across observers. Subsequent experiments demonstrated that stimulus-specific responses persist under higher memory loads and that at least part of the specificity arises in perception and is eventually propagated to working memory. Posthoc stimulus measurement revealed that rendered stimuli differed from nominal stimuli in both chromaticity and luminance. We discuss the implications of these deviations for both our results and those from other working memory studies.

Topographical gradients of semantics and phonology revealed by temporal lobe stimulation.

PubMed

Miozzo, Michele; Williams, Alicia C; McKhann, Guy M; Hamberger, Marla J

2017-02-01

Word retrieval is a fundamental component of oral communication, and it is well established that this function is supported by left temporal cortex. Nevertheless, the specific temporal areas mediating word retrieval and the particular linguistic processes these regions support have not been well delineated. Toward this end, we analyzed over 1000 naming errors induced by left temporal cortical stimulation in epilepsy surgery patients. Errors were primarily semantic (lemon → "pear"), phonological (horn → "corn"), non-responses, and delayed responses (correct responses after a delay), and each error type appeared predominantly in a specific region: semantic errors in mid-middle temporal gyrus (TG), phonological errors and delayed responses in middle and posterior superior TG, and non-responses in anterior inferior TG. To the extent that semantic errors, phonological errors and delayed responses reflect disruptions in different processes, our results imply topographical specialization of semantic and phonological processing. Specifically, results revealed an inferior-to-superior gradient, with more superior regions associated with phonological processing. Further, errors were increasingly semantically related to targets toward posterior temporal cortex. We speculate that detailed semantic input is needed to support phonological retrieval, and thus, the specificity of semantic input increases progressively toward posterior temporal regions implicated in phonological processing. Hum Brain Mapp 38:688-703, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

An assessment of clinical pathways and missed opportunities for the diagnosis of nodular melanoma versus superficial spreading melanoma.

PubMed

Cicchiello, Mark; Lin, Matthew J; Pan, Yan; McLean, Catriona; Kelly, John W

2016-05-01

Missed opportunities in the diagnosis of nodular melanoma (NM) carry high prognostic penalties due to the rapid rate of NM growth. To date, an assessment of the pathways to diagnosis of NM versus superficial spreading melanoma (SSM) specifically comparing numbers of opportunities missed to undertake biopsy has not been performed. A retrospective questionnaire of 120 patients (60 NM patients, age and sex matched to 60 SSM patients) from the Victorian Melanoma Service (VMS) database was undertaken to assess pathways to diagnosis. The numbers of opportunities missed to undertake a biopsy and doctor behaviour at such encounters were recorded. Diagnostic delay (overall, patient's and doctor's delay) in terms of time was assessed. Significant differences in opportunities missed to make a diagnosis of NM compared to SSM were found. In all, 43% of NM were biopsied at a first encounter compared to 70% of SSM. All SSM were diagnosed within three reviews. Overall, 33% of NM required at least three and up six reviews until biopsy. Patients with NM were more likely than those with SSM to be reassured that their lesions were benign. No significant differences in terms of time delay to diagnosis between NM and SSM were found. NM contributes disproportionately to melanoma mortality in Australia. Addressing earlier diagnosis of NM with renewed focus may make the biggest impact on the overall mortality of melanoma. The message that a period of observation is not appropriate for patients re-presenting with lesions of concern must be more effectively communicated. © 2015 The Australasian College of Dermatologists.

Sirtuin 7 promotes cellular survival following genomic stress by attenuation of DNA damage, SAPK activation and p53 response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kiran, Shashi; Oddi, Vineesha; Ramakrishna, Gayatri, E-mail: gayatrirama1@gmail.com

2015-02-01

Maintaining the genomic integrity is a constant challenge in proliferating cells. Amongst various proteins involved in this process, Sirtuins play a key role in DNA damage repair mechanisms in yeast as well as mammals. In the present work we report the role of one of the least explored Sirtuin viz., SIRT7, under conditions of genomic stress when treated with doxorubicin. Knockdown of SIRT7 sensitized osteosarcoma (U2OS) cells to DNA damage induced cell death by doxorubicin. SIRT7 overexpression in NIH3T3 delayed cell cycle progression by causing delay in G1 to S transition. SIRT7 overexpressing cells when treated with low dose ofmore » doxorubicin (0.25 µM) showed delayed onset of senescence, lesser accumulation of DNA damage marker γH2AX and lowered levels of growth arrest markers viz., p53 and p21 when compared to doxorubicin treated control GFP expressing cells. Resistance to DNA damage following SIRT7 overexpression was also evident by EdU incorporation studies where cellular growth arrest was significantly delayed. When treated with higher dose of doxorubicin (>1 µM), SIRT7 conferred resistance to apoptosis by attenuating stress activated kinases (SAPK viz., p38 and JNK) and p53 response thereby shifting the cellular fate towards senescence. Interestingly, relocalization of SIRT7 from nucleolus to nucleoplasm together with its co-localization with SAPK was an important feature associated with DNA damage. SIRT7 mediated resistance to doxorubicin induced apoptosis and senescence was lost when p53 level was restored by nutlin treatment. Overall, we propose SIRT7 attenuates DNA damage, SAPK activation and p53 response thereby promoting cellular survival under conditions of genomic stress. - Highlights: • Knockdown of SIRT7 sensitized cells to DNA damage induced apoptosis. • SIRT7 delayed onset of premature senescence by attenuating DNA damage response. • Overexpression of SIRT7 delayed cell cycle progression by delaying G1/S transition. • Upon DNA damage SIRT7 attenuated p38/JNK activation and also p53 response. • Overall, SIRT7 promoted cellular survival in conditions of genomic stress.« less

The nature of adolescent competencies predicted by preschool delay of gratification.

PubMed

Mischel, W; Shoda, Y; Peake, P K

1988-04-01

Delay of gratification, assessed in a series of experiments when the subjects were in preschool, was related to parental personality ratings obtained a decade later for 95 of these children in adolescence. Clear and consistent patterns of correlations between self-imposed delay time in preschool and later ratings were found for both sexes over this time span. Delay behavior predicted a set of cognitive and social competencies and stress tolerance consistent with experimental analyses of the process underlying effective delay in the preschool delay situation. Specifically, children who were able to wait longer at age 4 or 5 became adolescents whose parents rated them as more academically and socially competent, verbally fluent, rational, attentive, planful, and able to deal well with frustration and stress. Comparisons with related longitudinal research using other delay situations help to clarify the important features of the situations and person variables involved in different aspects of delay of gratification.

Scaling induced performance challenges/limitations of on-chip metal interconnects and comparisons with optical interconnects

NASA Astrophysics Data System (ADS)

Kapur, Pawan

The miniaturization paradigm for silicon integrated circuits has resulted in a tremendous cost and performance advantage. Aggressive shrinking of devices provides faster transistors and a greater functionality for circuit design. However, scaling induced smaller wire cross-sections coupled with longer lengths owing to larger chip areas, result in a steady deterioration of interconnects. This degradation in interconnect trends threatens to slow down the rapid growth along Moore's law. This work predicts that the situation is worse than anticipated. It shows that in the light of technology and reliability constraints, scaling induced increase in electron surface scattering, fractional cross section area occupied by the highly resistive barrier, and realistic interconnect operation temperature will lead to a significant rise in effective resistivity of modern copper based interconnects. We start by discussing various technology factors affecting copper resistivity. We, next, develop simulation tools to model these effects. Using these tools, we quantify the increase in realistic copper resistivity as a function of future technology nodes, under various technology assumptions. Subsequently, we evaluate the impact of these technology effects on delay and power dissipation of global signaling interconnects. Modern long on-chip wires use repeaters, which dramatically improves their delay and bandwidth. We quantify the repeated wire delays and power dissipation using realistic resistance trends at future nodes. With the motivation of reducing power, we formalize a methodology, which trades power with delay very efficiently for repeated wires. Using this method, we find that although the repeater power comes down, the total power dissipation due to wires is still found to be very large at future nodes. Finally, we explore optical interconnects as a possible substitute, for specific interconnect applications. We model an optical receiver and waveguides. Using this we assess future optical system performance. Finally, we compare the delay and power of future metal interconnects with that of optical interconnects for global signaling application. We also compare the power dissipation of the two approaches for an upper level clock distribution application. We find that for long on-chip communication links, optical interconnects have lower latencies than future metal interconnects at comparable levels of power dissipation.

AZD1480 delays tumor growth in a melanoma model while enhancing the suppressive activity of myeloid-derived suppressor cells

PubMed Central

Maenhout, Sarah K.; Four, Stephanie Du; Corthals, Jurgen; Neyns, Bart; Thielemans, Kris; Aerts, Joeri L.

2014-01-01

AZD1480 is a potent, competitive small-molecule inhibitor of JAK1/2 kinase which inhibits STAT3 phosphorylation and tumor growth. Here we investigated the effects of AZD1480 on the function of different immune cell populations in a melanoma model. When MO4 tumor-bearing mice were treated with AZD1480 we observed a strong inhibition of tumor growth as well as a prolonged survival. Moreover, a significant decrease in the percentage of myeloid-derived suppressor cells (MDSCs) was observed after treatment with AZD1480. However, AZD1480 enhanced the suppressive capacity of murine MDSCs while at the same time impairing the proliferative as well as the IFN-γ secretion capacity of murine T cells. The addition of AZD1480 to co-cultures of human MDSCs and T cells does not affect the suppressive activity of MDSCs but it does reduce the IFN-γ secretion and the proliferative capacity of T cells. We showed that although AZD1480 has the ability to delay the tumor growth of MO4 tumor-bearing mice, this drug has detrimental effects on several aspects of the immune system. These data indicate that systemic targeting of the JAK/STAT pathway by JAK1/2 inhibition can have divergent effects on tumor growth and anti-tumor immune responses. PMID:25149535

Enhanced insulin sensitivity in prepubertal children with constitutional delay of growth and development.

PubMed

Wilson, Dyanne A; Hofman, Paul L; Miles, Harriet L; Sato, Tim A; Billett, Nathalie E; Robinson, Elizabeth M; Cutfield, Wayne S

2010-02-01

To test the hypothesis that prepubertal children with presumed constitutional delay of growth and development (CDGD) have enhanced insulin sensitivity and, therefore, insulin sensitivity is associated with later onset of puberty. Twenty-one prepubertal children with presumed CDGD and 23 prepubertal control children, underwent a frequently sampled intravenous glucose tolerance test to evaluate insulin sensitivity and other markers of insulin, glucose, and growth regulation. Children in the CDGD group were shorter and leaner than control subjects. Children with presumed CDGD were 40% more insulin sensitive (17.0 x 10(-4) min(-1)/[mU/L] versus 12.1 x 10(-4) min(-1)/[mU/L]; P = .0006) and had reduced acute insulin response, thus maintaining euglycemia (216 mU/L versus 330 mU/L; P = .02) compared with control subjects. In addition, the CDGD group had lower serum insulin-like growth factor binding protein 3 levels (3333 ng/mL versus 3775 ng/mL; P = .0004) and a trend toward lower serum insulin-like growth factor-II levels (794 ng/mL versus 911 ng/mL; P = .06). Prepubertal children with presumed CDGD have enhanced insulin sensitivity, supporting the hypothesis that insulin sensitivity is associated with timing of puberty. It may signify long-term biological advantages with lower risk of metabolic syndrome and malignancy. Copyright 2010 Mosby, Inc. All rights reserved.

A novel live cell imaging system reveals a reversible hydrostatic pressure impact on cell cycle progression.

PubMed

Brooker, Holly R; Gyamfi, Irene A; Wieckowska, Agnieszka; Brooks, Nicholas J; Mulvihill, Daniel P; Geeves, Michael A

2018-06-21

Life is dependent upon the ability of a cell to rapidly respond to changes in environment. Small perturbations in local environments change the ability of molecules to interact and hence communicate. Hydrostatic pressure provides a rapid non-invasive, fully-reversible method for modulating affinities between molecules both in vivo and in vitro We have developed a simple fluorescence imaging chamber that allows intracellular protein dynamics and molecular events to be followed at pressures up to 200 bar in living cells. Using yeast we investigate the impact of hydrostatic pressure upon cell growth and cell cycle progression. While 100 bar has no affect upon viability, it induces a delay in chromosome segregation, resulting in the accumulation of long-undivided-bent cells, consistent with disruption of the cytoskeletons. This delay is independent of stress signalling and induces synchronisation of cell-cycle progression. Equivalent affects were observed in Candida albicans , with pressure inducing a reversible cell-cycle delay and hyphal growth. We present a simple novel non-invasive fluorescence microscopy based approach to transiently impact molecular dynamics to visualise, dissect and study signalling pathways and cellular processes in living cells. © 2018. Published by The Company of Biologists Ltd.

Diversity of pubertal testosterone changes in boys with constitutional delay in growth and/or adolescence.

PubMed

Kulin, H E; Finkelstein, J W; D'Arcangelo, M R; Susman, E J; Chinchilli, V; Kunselman, S; Schwab, J; Demers, L; Lookingbill, G

1997-01-01

In a group of 22 boys with constitutional delay in growth and/or adolescence, intermittent testosterone enanthate treatment was employed in a randomized clinical trial at multiple doses ranging from 25-100 mg every two weeks for three month periods extending over 15-21 months. Twelve of the patients displayed a prompt increase in endogenous testosterone levels during the study period, reaching levels in the adult male range (> 250 ng/dl). The remaining 10 boys showed sluggish changes in endogenous testosterone during the investigation, ranging from 35-177 ng/dl. The bone ages and testicular sizes of the two groups at study initiation did not differ though urine LH was significantly less at study entry in the slowly maturing group. The data reveal a great diversity in the pace and pattern of endogenous testosterone changes in the study population. The results also suggest that exogenous sex steroid treatment of such patients does not speed up the central nervous system processes controlling the onset and progression of puberty. Boys with delayed puberty should be followed until endogenous testosterone levels reach the adult male range in order to rule out mild gonadotropin deficits.

CXCR4 regulates growth of both primary and metastatic breast cancer.

PubMed

Smith, Matthew C P; Luker, Kathryn E; Garbow, Joel R; Prior, Julie L; Jackson, Erin; Piwnica-Worms, David; Luker, Gary D

2004-12-01

The chemokine receptor CXCR4 and its cognate ligand CXCL12 recently have been proposed to regulate the directional trafficking and invasion of breast cancer cells to sites of metastases. However, effects of CXCR4 on the growth of primary breast cancer tumors and established metastases and survival have not been determined. We used stable RNAi to reduce expression of CXCR4 in murine 4T1 cells, a highly metastatic mammary cancer cell line that is a model for stage IV human breast cancer. Using noninvasive bioluminescence and magnetic resonance imaging, we showed that knockdown of CXCR4 significantly limited the growth of orthotopically transplanted breast cancer cells. Mice in which parental 4T1 cells were implanted had progressively enlarging tumors that spontaneously metastasized, and these animals all died from metastatic disease. Remarkably, RNAi of CXCR4 prevented primary tumor formation in some mice, and all mice transplanted with CXCR RNAi cells survived without developing macroscopic metastases. To analyze effects of CXCR4 on metastases to the lung, an organ commonly affected by metastatic breast cancer, we injected tumor cells intravenously and monitored cell growth with bioluminescence imaging. Inhibiting CXCR4 with RNAi, or the specific antagonist AMD3100, substantially delayed the growth of 4T1 cells in the lung, although neither RNAi nor AMD3100 prolonged overall survival in mice with experimental lung metastases. These data indicate that CXCR4 is required to initiate proliferation and/or promote survival of breast cancer cells in vivo and suggest that CXCR4 inhibitors will improve treatment of patients with primary and metastatic breast cancer.

Ultraviolet irradiation of herpes simplex virus (type 1): delayed transcription and comparative sensitivites of virus functions.

PubMed

Eglin, R P; Gugerli, P; Wildy, P

1980-07-01

The delay in the replication of herpes simplex virus surviving u.v. irradiation occurs after the uncoating of virus, as judged by sensitivity to DNase. It occurs before translation, judged by the kinetics of appearance of various virus-specific proteins, and before transcription, judged by the detection of virus-specific RNA by in situ hybridization. Since the delays in both transcription and translation are reversed by photoreactivation, the simplest hypothesis is that pyrimidine dimers directly obstruct transcription;unless these are broken by photoreactivating enzymes, there will be transcriptional delay until reactivating processes have repaired the lesion. The u.v. sensitivities of the abilities to induce various enzymes (thymidine kinase, DNase and DNA polymerase) were only about four times less than that of infectivity. The The ability to induce the three enzymes was three times less sensitive than that of the structural antigen (Band II).

Opto-VLSI-based photonic true-time delay architecture for broadband adaptive nulling in phased array antennas.

PubMed

Juswardy, Budi; Xiao, Feng; Alameh, Kamal

2009-03-16

This paper proposes a novel Opto-VLSI-based tunable true-time delay generation unit for adaptively steering the nulls of microwave phased array antennas. Arbitrary single or multiple true-time delays can simultaneously be synthesized for each antenna element by slicing an RF-modulated broadband optical source and routing specific sliced wavebands through an Opto-VLSI processor to a high-dispersion fiber. Experimental results are presented, which demonstrate the principle of the true-time delay unit through the generation of 5 arbitrary true-time delays of up to 2.5 ns each. (c) 2009 Optical Society of America

Time delays in flight simulator visual displays

NASA Technical Reports Server (NTRS)

Crane, D. F.

1980-01-01

It is pointed out that the effects of delays of less than 100 msec in visual displays on pilot dynamic response and system performance are of particular interest at this time because improvements in the latest computer-generated imagery (CGI) systems are expected to reduce CGI displays delays to this range. Attention is given to data which quantify the effects of display delays in the range of 0-100 msec on system stability and performance, and pilot dynamic response for a particular choice of aircraft dynamics, display, controller, and task. The conventional control system design methods are reviewed, the pilot response data presented, and data for long delays, all suggest lead filter compensation of display delay. Pilot-aircraft system crossover frequency information guides compensation filter specification.

12q14 microdeletion associated with HMGA2 gene disruption and growth restriction.

PubMed

Alyaqoub, Fadel; Pyatt, Robert E; Bailes, Andrea; Brock, Amanda; Deeg, Carol; McKinney, Aimee; Astbury, Caroline; Reshmi, Shalini; Shane, Kate P; Thrush, Devon Lamb; Sommer, Annemarie; Gastier-Foster, Julie M

2012-11-01

The 12q14 microdeletion syndrome is a rare condition that has previously been characterized by pre- and postnatal growth restriction, proportionate short stature, failure to thrive, developmental delay, and osteopoikilosis. Previously reported microdeletions within this region have ranged in size from 1.83 to 10.12 Mb with a proposed 2.61 Mb smallest region of overlap containing the LEMD3, HMGA2, and GRIP1 genes. Here, we report on the identification of a 12q14 microdeletion in a female child presenting with proportionate short stature, failure to thrive, and speech delay. The genomic loss (minimum size 4.17 Mb, maximum size 4.21 Mb) contained 25 RefSeq genes including IRAK3, GRIP1, and the 3' portion of the HMGA2 gene. This is the first partial deletion of HMGA2 associated with the 12q14 microdeletion syndrome. This case further clarifies the association of LEMD3 deletions with the 12q14 microdeletion syndrome and provides additional support for the role of the HMGA2 gene in human growth. Copyright © 2012 Wiley Periodicals, Inc.

1.5Mb deletion of chromosome 4p16.3 associated with postnatal growth delay, psychomotor impairment, epilepsy, impulsive behavior and asynchronous skeletal development.

PubMed

Misceo, D; Barøy, T; Helle, J R; Braaten, O; Fannemel, M; Frengen, E

2012-10-01

Several Wolf-Hirschhorn syndrome patients have been studied, mouse models for a few candidate genes have been constructed and two WHS critical regions have been postulated, but the molecular basis of the syndrome remains poorly understood. Single gene contributions to phenotypes of microdeletion syndromes have often been based on the study of patients carrying small, atypical deletions. We report a 5-year-old girl harboring an atypical 1.5Mb del4p16.3 and review seven previously published patients carrying a similar deletion. They show a variable clinical presentation and the only consistent feature is post-natal growth delay. However, four of eight patients carry a ring (4), and ring chromosomes in general are associated with growth deficiency. The Greek helmet profile is absent, although a trend towards common dysmorphic features exists. Variable expressivity and incomplete penetrance might play a role in WHS, resulting in difficult clinical diagnosis and challenge in understanding of the genotype/phenotype correlation. Copyright © 2012 Elsevier B.V. All rights reserved.

Inhibitor of p52 NF-κB subunit and androgen receptor (AR) interaction reduces growth of human prostate cancer cells by abrogating nuclear translocation of p52 and phosphorylated ARser81

PubMed Central

Mehraein-Ghomi, Farideh; Church, Dawn R.; Schreiber, Cynthia L.; Weichmann, Ashley M.; Basu, Hirak S.; Wilding, George

2015-01-01

Accumulating evidence shows that androgen receptor (AR) activation and signaling plays a key role in growth and progression in all stages of prostate cancer, even under low androgen levels or in the absence of androgen in the castration-resistant prostate cancer. Sustained activation of AR under androgen-deprived conditions may be due to its interaction with co-activators, such as p52 NF-κB subunit, and/or an increase in its stability by phosphorylation that delays its degradation. Here we identified a specific inhibitor of AR/p52 interaction, AR/p52-02, via a high throughput screen based on the reconstitution of Gaussia Luciferase. We found that AR/p52-02 markedly inhibited growth of both castration-resistant C4-2 (IC50 ∼6 μM) and parental androgen-dependent LNCaP (IC50 ∼4 μM) human prostate cancer cells under low androgen conditions. Growth inhibition was associated with significantly reduced nuclear p52 levels and DNA binding activity, as well as decreased phosphorylation of AR at serine 81, increased AR ubiquitination, and decreased AR transcriptional activity as indicated by decreased prostate-specific antigen (PSA) mRNA levels in both cell lines. AR/p52-02 also caused a reduction in levels of p21WAF/CIP1, which is a direct AR targeted gene in that its expression correlates with androgen stimulation and mitogenic proliferation in prostate cancer under physiologic levels of androgen, likely by disrupting the AR signaling axis. The reduced level of cyclinD1 reported previously for this compound may be due to the reduction in nuclear presence and activity of p52, which directly regulates cyclinD1 expression, as well as the reduction in p21WAF/CIP1, since p21WAF/CIP1 is reported to stabilize nuclear cyclinD1 in prostate cancer. Overall, the data suggest that specifically inhibiting the interaction of AR with p52 and blocking activity of p52 and pARser81 may be an effective means of reducing castration-resistant prostate cancer cell growth. PMID:26622945

Toddler Growth and Development

MedlinePlus

... to Raise Concerns about a Child’s Speech and Language Development: Do’s and Don’ts How to Share Books ... Old Language Delays in Toddlers: Information for Parents Language Development: 1 Year Olds Language Development: 2 Year Olds ...

Cystic fibrosis

MedlinePlus

... in newborns may include: Delayed growth Failure to gain weight normally during childhood No bowel movements in first 24 to 48 hours of life Salty-tasting skin Symptoms related to bowel function may include: Belly pain from severe constipation Increased ...

Delay-aware adaptive sleep mechanism for green wireless-optical broadband access networks

NASA Astrophysics Data System (ADS)

Wang, Ruyan; Liang, Alei; Wu, Dapeng; Wu, Dalei

2017-07-01

Wireless-Optical Broadband Access Network (WOBAN) is capacity-high, reliable, flexible, and ubiquitous, as it takes full advantage of the merits from both optical communication and wireless communication technologies. Similar to other access networks, the high energy consumption poses a great challenge for building up WOBANs. To shot this problem, we can make some load-light Optical Network Units (ONUs) sleep to reduce the energy consumption. Such operation, however, causes the increased packet delay. Jointly considering the energy consumption and transmission delay, we propose a delay-aware adaptive sleep mechanism. Specifically, we develop a new analytical method to evaluate the transmission delay and queuing delay over the optical part, instead of adopting M/M/1 queuing model. Meanwhile, we also analyze the access delay and queuing delay of the wireless part. Based on such developed delay models, we mathematically derive ONU's optimal sleep time. In addition, we provide numerous simulation results to show the effectiveness of the proposed mechanism.

An Empirical Study of Synchrophasor Communication Delay in a Utility TCP/IP Network

NASA Astrophysics Data System (ADS)

Zhu, Kun; Chenine, Moustafa; Nordström, Lars; Holmström, Sture; Ericsson, Göran

2013-07-01

Although there is a plethora of literature dealing with Phasor Measurement Unit (PMU) communication delay, there has not been any effort made to generalize empirical delay results by identifying the distribution with the best fit. The existing studies typically assume a distribution or simply build on analogies to communication network routing delay. Specifically, this study provides insight into the characterization of the communication delay of both unprocessed PMU data and synchrophasors sorted by a Phasor Data Concentrator (PDC). The results suggest that a bi-modal distribution containing two normal distributions offers the best fit of the delay of the unprocessed data, whereas the delay profile of the sorted synchrophasors resembles a normal distribution based on these results, the possibility of evaluating the reliability of a synchrophasor application with respect to a particular choice of PDC timeout is discussed.

Adaptive output-feedback control for switched stochastic uncertain nonlinear systems with time-varying delay.

PubMed

Song, Zhibao; Zhai, Junyong

2018-04-01

This paper addresses the problem of adaptive output-feedback control for a class of switched stochastic time-delay nonlinear systems with uncertain output function, where both the control coefficients and time-varying delay are unknown. The drift and diffusion terms are subject to unknown homogeneous growth condition. By virtue of adding a power integrator technique, an adaptive output-feedback controller is designed to render that the closed-loop system is bounded in probability, and the state of switched stochastic nonlinear system can be globally regulated to the origin almost surely. A numerical example is provided to demonstrate the validity of the proposed control method. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides

PubMed Central

Otto, Christoph; Kaemmerer, Ulrike; Illert, Bertram; Muehling, Bettina; Pfetzer, Nadja; Wittig, Rainer; Voelker, Hans Ullrich; Thiede, Arnulf; Coy, Johannes F

2008-01-01

Background Among the most prominent metabolic alterations in cancer cells are the increase in glucose consumption and the conversion of glucose to lactic acid via the reduction of pyruvate even in the presence of oxygen. This phenomenon, known as aerobic glycolysis or the Warburg effect, may provide a rationale for therapeutic strategies that inhibit tumour growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat enriched with omega-3 fatty acids and medium-chain triglycerides (MCT). Methods Twenty-four female NMRI nude mice were injected subcutaneously with tumour cells of the gastric adenocarcinoma cell line 23132/87. The animals were then randomly split into two feeding groups and fed either a ketogenic diet (KD group; n = 12) or a standard diet (SD group; n = 12) ad libitum. Experiments were ended upon attainment of the target tumor volume of 600 mm3 to 700 mm3. The two diets were compared based on tumour growth and survival time (interval between tumour cell injection and attainment of target tumour volume). Results The ketogenic diet was well accepted by the KD mice. The tumour growth in the KD group was significantly delayed compared to that in the SD group. Tumours in the KD group reached the target tumour volume at 34.2 ± 8.5 days versus only 23.3 ± 3.9 days in the SD group. After day 20, tumours in the KD group grew faster although the differences in mean tumour growth continued significantly. Importantly, they revealed significantly larger necrotic areas than tumours of the SD group and the areas with vital tumour cells appear to have had fewer vessels than tumours of the SD group. Viable tumour cells in the border zone surrounding the necrotic areas of tumours of both groups exhibited a glycolytic phenotype with expression of glucose transporter-1 and transketolase-like 1 enzyme. Conclusion Application of an unrestricted ketogenic diet enriched with omega-3 fatty acids and MCT delayed tumour growth in a mouse xenograft model. Further studies are needed to address the impact of this diet on other tumour-relevant functions such as invasive growth and metastasis. PMID:18447912

A nitrogen response pathway regulates virulence in plant pathogenic fungi: role of TOR and the bZIP protein MeaB.

PubMed

López-Berges, Manuel S; Rispail, Nicolas; Prados-Rosales, Rafael C; Di Pietro, Antonio

2010-12-01

Virulence in plant pathogenic fungi is controlled through a variety of cellular pathways in response to the host environment. Nitrogen limitation has been proposed to act as a key signal to trigger the in planta expression of virulence genes. Moreover, a conserved Pathogenicity mitogen activated protein kinase (MAPK) cascade is strictly required for plant infection in a wide range of pathogens. We investigated the relationship between nitrogen signaling and the Pathogenicity MAPK cascade in controlling infectious growth of the vascular wilt fungus Fusarium oxysporum. Several MAPK-activated virulence functions such as invasive growth, vegetative hyphal fusion and host adhesion were strongly repressed in the presence of the preferred nitrogen source ammonium. Repression of these functions by ammonium was abolished by L-Methionine sulfoximine (MSX) or rapamycin, two specific inhibitors of Gln synthetase and the protein kinase TOR (Target Of Rapamycin), respectively, and was dependent on the bZIP protein MeaB. Supplying tomato plants with ammonium rather than nitrate resulted in a significant delay of vascular wilt symptoms caused by the F. oxysporum wild type strain, but not by the ΔmeaB mutant. Ammonium also repressed invasive growth in two other pathogens, the rice blast fungus Magnaporthe oryzae and the wheat head blight pathogen Fusarium graminearum. Our results suggest the presence of a conserved nitrogen-responsive pathway that operates via TOR and MeaB to control infectious growth in plant pathogenic fungi.

Delayed-Choice Experiments and the Metaphysics of Entanglement

NASA Astrophysics Data System (ADS)

Egg, Matthias

2013-09-01

Delayed-choice experiments in quantum mechanics are often taken to undermine a realistic interpretation of the quantum state. More specifically, Healey has recently argued that the phenomenon of delayed-choice entanglement swapping is incompatible with the view that entanglement is a physical relation between quantum systems. This paper argues against these claims. It first reviews two paradigmatic delayed-choice experiments and analyzes their metaphysical implications. It then applies the results of this analysis to the case of entanglement swapping, showing that such experiments pose no threat to realism about entanglement.

Detecting points as developmental delay based on the life-history development and urosome deformity of the harpacticoid copepod, Tigriopus japonicus sensu lato, following exposure to benzo(a)pyrene.

PubMed

Bang, Hyun Woo; Lee, Wonchoel; Kwak, Inn-Sil

2009-09-01

To identify ecotoxicological responses to an endocrine disrupter, benzo(a)pyrene, we examined the life-history of the harpacticoid copepod, Tigriopus japonicus sensu lato. Based on the life-history of copepods, survival rate of nauplii (NSR) and copepodites (CSR), copepodite emergence day (CED) and adult male emergence day (AMED), sex ratio (MER), brooding success rate (BSR), and first brooding day of adult females (FBD) were measured. Significant differences were observed in the survival and development of nauplii (NSR and CED) and sex ratio (MER) of exposed and non-exposed copepods. Moreover, high concentration of BaP can be lethal to copepodite and exhibited a delay of growth. In this study, the CED and AMED among ecotoxicological response based on life-history developments were delayed and the body characteristics decreased in response to exposure to benzo(a)pyrene. The dwarfism and urosome deformity of the T. japonicus s.l. was exhibited in response to chemical exposure. Specifically, the body characteristics and biomass of dwarf copepods that had been exposed to benzo(a)pyrene were 30% and 50% lower than the control group, respectively. The incidence of abnormal urosomes was divided into two types. The first deformity type was signs of shrinkage in the middle of the urosome or the entire urosome was narrower than those of the control organisms. In the second type, the anal somite and the distal side of the urosome had abnormally swelled. Taken together, the nauplii and copepodid development of T. japonicus s.l. can be used as a useful biomaker for detecting developmental delay based on their entire life-history. In addition, the urosome deformity was used a good potential monitoring tool invading various chemicals and environmental contamination into water system.

Whole Exome Sequencing and Heterologous Cellular Electrophysiology Studies Elucidate a Novel Loss-of-Function Mutation in the CACNA1A-Encoded Neuronal P/Q-Type Calcium Channel in a Child With Congenital Hypotonia and Developmental Delay.

PubMed

Weyhrauch, Derek L; Ye, Dan; Boczek, Nicole J; Tester, David J; Gavrilova, Ralitza H; Patterson, Marc C; Wieben, Eric D; Ackerman, Michael J

2016-02-01

A 4-year-old boy born at 37 weeks' gestation with intrauterine growth retardation presented with developmental delay with pronounced language and gross motor delay, axial hypotonia, and dynamic hypertonia of the extremities. Investigations including the Minnesota Newborn Screen, thyroid stimulating hormone/thyroxin, and inborn errors of metabolism screening were negative. Cerebral magnetic resonance imaging and spectroscopy were normal. Genetic testing was negative for coagulopathy, Smith-Lemli-Opitz, fragile X, and Prader-Willi/Angelman syndromes. Whole genome array analysis was unremarkable. Whole exome sequencing was performed through a commercial testing laboratory to elucidate the underlying etiology for the child's presentation. A de novo mutation was hypothesized. In attempt to establish pathogenicity of our candidate variant, cellular electrophysiologic functional analysis of the putative de novo mutation was performed using patch-clamp technology. Whole exome sequencing revealed a p.P1353L variant in the CACNA1A gene, which encodes for the α1-subunit of the brain-specific P/Q-type calcium channel (CaV2.1). This presynaptic high-voltage-gated channel couples neuronal excitation to the vesicular release of neurotransmitter and is implicated in several neurologic disorders. DNA Sanger sequencing confirmed that the de novo mutation was absent in both parents and present in the child only. Electrophysiologic analysis of P1353L-CACNA1A demonstrated near complete loss of function, with a 95% reduction in peak current density. Whole exome sequencing coupled with cellular electrophysiologic functional analysis of a de novoCACNA1A missense mutation has elucidated the probable underlying pathophysiologic mechanism responsible for the child's phenotype. Genetic testing of CACNA1A in patients with congenital hypotonia and developmental delay may be warranted. Copyright © 2016. Published by Elsevier Inc.

Differential responses of EGFR-/AGT-expressing cells to the "combi-triazene" SMA41.

PubMed

Matheson, Stephanie L; McNamee, James P; Jean-Claude, Bertrand J

2003-01-01

Previous studies have demonstrated enhanced potency associated with the binary [DNA/epidermal growth factor receptor (EGFR)] targeting properties of SMA41 (a chimeric 3-(alkyl)-1,2,3-triazene linked to a 4-anilinoquinazoline backbone) in the A431 (epidermal carcinoma of the vulva) cell line. We now report on the dependence of its antiproliferative effects (e.g. DNA damage, cell survival) on the EGFR and the DNA repair protein O6-alkylguanine DNA alkyltransferase (AGT) contents of 12 solid tumor cell lines, two of which, NIH3T3 and NIH3T3 HER14 (engineered to overexpress EGFR), were isogenic. Receptor type specificity was determined using ELISA for competitive binding, as well as growth factor-stimulation assays. DNA damage was studied using single-cell microelectrophoresis (comet) assays, and levels of EGFR were determined by Western blotting. The effects of SMA41 on the cell cycle of NIH3T3 cells were investigated using univariate flow cytometry. Studies of receptor type specificity showed that SMA41: (a) preferentially inhibited the kinase activity of EGFR over those of Src, insulin receptor and protein kinase C (PKC, a serine/threonine kinase), (b) induced stronger inhibition of growth stimulated with EGF than of growth stimulated with platelet-derived growth factor (PDGF) or fetal bovine serum (FBS). Despite the EGFR specificity of SMA41, there was an absence of a linear correlation between the EGFR status of our solid tumor cell lines and levels of DNA damage induced by the alkylating component. Similarly, EGFR levels did not correlate with IC(50) values. The antiproliferative activities of SMA41 correlated more with the AGT status of these cells and paralleled those of the clinical triazene temozolomide (TEM). However, throughout the panel, tumor cell sensitivity to SMA41 was consistently stronger than to its closest analogue TEM. Experiments performed with the isogenic cells showed that SMA41 was capable of inducing twofold higher levels of DNA damage in the EGFR transfectant and delayed cell entry to G(2)/M in both cell types. When the cells were starved and growth-stimulated with FBS (conditions under which both cell types were growth-stimulated), in contrast to TEM, SMA41 and its hydrolytic metabolite SMA52 exhibited approximately nine- and threefold stronger inhibition of growth of the EGFR transfectant. These results suggest that, in addition to its ability to induce DNA damage and cell cycle perturbations, SMA41 is capable of selectively targeting the cells with a growth advantage conferred by EGFR transfection. When compared with the monoalkyltriazene prodrug TEM, its potency may be further enhanced by its ability to hydrolyze to another signal transduction inhibitor (SMA52) plus a DNA alkylating agent that may further contribute to chemosensitivity. Thus, our new "combi-targeting" strategy may well represent a tandem approach to selectively blocking receptor tyrosine kinase-mediated growth signaling while inducing significant levels of cytotoxic DNA lesions in refractory tumors.

Inhibitory effects of anethole and eugenol on the growth and toxin production of Aspergillus parasiticus.

PubMed

Karapinar, M

1990-05-01

The antifungal and antiaflatoxigenic activity of anethole and eugenol which are active components of commonly used spices was studied against two strains of Aspergillus parasiticus. Anethole, up to concentration of 400 micrograms/ml where complete inhibition was observed, delayed growth and reduced mycelial weight but it showed a stimulative effect on the toxin production of both strains. At a concentration of 300 micrograms/ml, eugenol inhibited the growth of both strains; levels of eugenol below 200 micrograms/ml enhanced production of aflatoxin particularly by A. parasiticus NRRL 299.

All about running: synaptic plasticity, growth factors and adult hippocampal neurogenesis.

PubMed

Vivar, Carmen; Potter, Michelle C; van Praag, Henriette

2013-01-01

Accumulating evidence from animal and human research shows exercise benefits learning and memory, which may reduce the risk of neurodegenerative diseases, and could delay age-related cognitive decline. Exercise-induced improvements in learning and memory are correlated with enhanced adult hippocampal neurogenesis and increased activity-dependent synaptic plasticity. In this present chapter we will highlight the effects of physical activity on cognition in rodents, as well as on dentate gyrus (DG) neurogenesis, synaptic plasticity, spine density, neurotransmission and growth factors, in particular brain-derived nerve growth factor (BDNF).

Effects of growth hormone over-expression on reproduction in the common carp Cyprinus carpio L.

PubMed

Cao, Mengxi; Chen, Ji; Peng, Wei; Wang, Yaping; Liao, Lanjie; Li, Yongming; Trudeau, Vance L; Zhu, Zuoyan; Hu, Wei

2014-01-01

To study the complex interaction between growth and reproduction we have established lines of transgenic common carp (Cyprinus carpio) carrying a grass carp (Ctenopharyngodon idellus) growth hormone (GH) transgene. The GH-transgenic fish showed delayed gonadal development compared with non-transgenic common carp. To gain a better understanding of the phenomenon, we studied body growth, gonad development, changes of reproduction related genes and hormones of GH-transgenic common carp for 2years. Over-expression of GH elevated peripheral gh transcription, serum GH levels, and inhibited endogenous GH expression in the pituitary. Hormone analyses indicated that GH-transgenic common carp had reduced pituitary and serum level of luteinizing hormone (LH). Among the tested genes, pituitary lhβ was inhibited in GH-transgenic fish. Further analyses in vitro showed that GH inhibited lhβ expression. Localization of ghr with LH indicates the possibility of direct regulation of GH on gonadotrophs. We also found that GH-transgenic common carp had reduced pituitary sensitivity to stimulation by co-treatments with a salmon gonadotropin-releasing hormone (GnRH) agonist and a dopamine antagonist. Together these results suggest that the main cause of delayed reproductive development in GH transgenic common carp is reduced LH production and release. Copyright © 2013 Elsevier Inc. All rights reserved.

Control of reed canarygrass promotes wetland herb and tree seedling establishment in an upper Mississippi River Floodplain forest

USGS Publications Warehouse

Thomsen, Meredith; Brownell, Kurt; Groshek, Matthew; Kirsch, Eileen

2012-01-01

Phalaris arundinacea (reed canarygrass) is recognized as a problematic invader of North American marshes, decreasing biodiversity and persisting in the face of control efforts. Less is known about its ecology or management in forested wetlands, providing an opportunity to apply information about factors critical to an invader's control in one wetland type to another. In a potted plant experiment and in the field, we documented strong competitive effects of reed canarygrass on the establishment and early growth of tree seedlings. In the field, we demonstrated the effectiveness of a novel restoration strategy, combining site scarification with late fall applications of pre-emergent herbicides. Treatments delayed reed canarygrass emergence the following spring, creating a window of opportunity for the early growth of native plants in the absence of competition from the grass. They also allowed for follow-up herbicide treatments during the growing season. We documented greater establishment of wetland herbs and tree seedlings in treated areas. Data from small exclosures suggest, however, that deer browsing can limit tree seedling height growth in floodplain restorations. Slower tree growth will delay canopy closure, potentially allowing reed canarygrass re-invasion. Thus, it may be necessary to protect tree seedlings from herbivory to assure forest regeneration.

Delayed frost growth on jumping-drop superhydrophobic surfaces.

PubMed

Boreyko, Jonathan B; Collier, C Patrick

2013-02-26

Self-propelled jumping drops are continuously removed from a condensing superhydrophobic surface to enable a micrometric steady-state drop size. Here, we report that subcooled condensate on a chilled superhydrophobic surface are able to repeatedly jump off the surface before heterogeneous ice nucleation occurs. Frost still forms on the superhydrophobic surface due to ice nucleation at neighboring edge defects, which eventually spreads over the entire surface via an interdrop frost wave. The growth of this interdrop frost front is shown to be up to 3 times slower on the superhydrophobic surface compared to a control hydrophobic surface, due to the jumping-drop effect dynamically minimizing the average drop size and surface coverage of the condensate. A simple scaling model is developed to relate the success and speed of interdrop ice bridging to the drop size distribution. While other reports of condensation frosting on superhydrophobic surfaces have focused exclusively on liquid-solid ice nucleation for isolated drops, these findings reveal that the growth of frost is an interdrop phenomenon that is strongly coupled to the wettability and drop size distribution of the surface. A jumping-drop superhydrophobic condenser minimized frost formation relative to a conventional dropwise condenser in two respects: preventing heterogeneous ice nucleation by continuously removing subcooled condensate, and delaying frost growth by limiting the success of interdrop ice bridge formation.

Is Breast Best? Examining the effects of alcohol and cannabis use during lactation.

PubMed

Brown, R A; Dakkak, H; Seabrook, J A

2018-05-23

Maternal drug use during lactation may have adverse effects on the health of their children. Two common drugs used during this period are alcohol and cannabis. A literature search was conducted using PubMed, CINAHL, Nursing and Allied Health, and Google Scholar with the following search terms: marijuana, cannabis, THC, alcohol, ethanol, breastfeeding, lactation, and breastmilk. The search strategy was restricted to papers since the year 2000, and limited to English language journals. Reference lists were also used to capture any articles that were missed from the database searches. In total, 19 articles were found related to alcohol and breastfeeding (n = 17 original research papers; n = 2 systematic reviews), and 4 articles were specific to cannabis (n = 2 original papers; n = 2 systematic reviews). The most common outcomes associated with alcohol consumption and breastfeeding included changes in sleep patterns, reduced milk production and flow, lower milk intake, and impaired immune function. Maternal outcomes related to cannabis consumption included panic attacks, delayed response time, increased heart rate, reduced short-term memory, dizziness, and impaired motor performance; infant outcomes associated with maternal cannabis use and breastfeeding were reduced muscular tonus, poor sucking, and growth delay and restriction. Mothers should be advised to refrain from substance use during the lactation period for the health and safety of their children.

Sculpting Silica Colloids by Etching Particles with Nonuniform Compositions

PubMed Central

2017-01-01

We present the synthesis of new shapes of colloidal silica particles by manipulating their chemical composition and subsequent etching. Segments of silica rods, prepared by the ammonia catalyzed hydrolysis and condensation of tetraethylorthosilicate (TEOS) from polyvinylpyrrolidone loaded water droplets, were grown under different conditions. Upon decreasing temperature, delaying ethanol addition, or increasing monomer concentration, the rate of dissolution of the silica segment subsequently formed decreased. A watery solution of NaOH (∼mM) selectively etched these segments. Further tuning the conditions resulted in rod–cone or cone–cone shapes. Deliberately modulating the composition along the particle’s length by delayed addition of (3-aminopropyl)-triethoxysilane (APTES) also allowed us to change the composition stepwise. The faster etching of this coupling agent in neutral conditions or HF afforded an even larger variety of particle morphologies while in addition changing the chemical functionality. A comparable step in composition was applied to silica spheres. Biamine functional groups used in a similar way as APTES caused a charge inversion during the growth, causing dumbbells and higher order aggregates to form. These particles etched more slowly at the neck, resulting in a biconcave silica ring sandwiched between two silica spheres, which could be separated by specifically etching the functionalized layer using HF. PMID:28413261

A Drosophila model for fetal alcohol syndrome disorders: role for the insulin pathway

PubMed Central

McClure, Kimberly D.; French, Rachael L.; Heberlein, Ulrike

2011-01-01

SUMMARY Prenatal exposure to ethanol in humans results in a wide range of developmental abnormalities, including growth deficiency, developmental delay, reduced brain size, permanent neurobehavioral abnormalities and fetal death. Here we describe the use of Drosophila melanogaster as a model for exploring the effects of ethanol exposure on development and behavior. We show that developmental ethanol exposure causes reduced viability, developmental delay and reduced adult body size. We find that flies reared on ethanol-containing food have smaller brains and imaginal discs, which is due to reduced cell division rather than increased apoptosis. Additionally, we show that, as in mammals, flies reared on ethanol have altered responses to ethanol vapor exposure as adults, including increased locomotor activation, resistance to the sedating effects of the drug and reduced tolerance development upon repeated ethanol exposure. We have found that the developmental and behavioral defects are largely due to the effects of ethanol on insulin signaling; specifically, a reduction in Drosophila insulin-like peptide (Dilp) and insulin receptor expression. Transgenic expression of Dilp proteins in the larval brain suppressed both the developmental and behavioral abnormalities displayed by ethanol-reared adult flies. Our results thus establish Drosophila as a useful model system to uncover the complex etiology of fetal alcohol syndrome. PMID:21303840

A de novo Mutation in KMT2A (MLL) in monozygotic twins with Wiedemann-Steiner syndrome.

PubMed

Dunkerton, Sophie; Field, Matthew; Cho, Vicki; Bertram, Edward; Whittle, Belinda; Groves, Alexandra; Goel, Himanshu

2015-09-01

Growth deficiency, psychomotor delay, and facial dysmorphism was originally described in a male patient in 1989 by Wiedemann et al. and later in 2000 by Steiner et al. Wiedemann-Steiner syndrome (WSS) has since been described only a few times in the literature, with the phenotypic spectrum both expanding and becoming more delineated with each patient reported. We report on the clinical and molecular features of monozygotic twins with a de novo mutation in KMT2A. Single nucleotide polymorphism (SNP) microarray was done on both twins and whole-exome sequencing was done using both parents and one of the affected twins. SNP microarray confirmed that they were monozygotic twins. A de novo heterozygous variant (p. Arg1083*) in the KMT2A gene was identified through whole-exome sequencing, confirming the diagnosis of WSS. In this study, we have identified a de novo mutation in KMT2A associated with psychomotor developmental delay, facial dysmorphism, short stature, hypertrichosis cubiti, and small kidneys. This finding in monozygotic twins gives specificity to the WSS. The description of more cases of WSS is needed for further delineation of this condition. Small kidneys with normal function have not been described in this condition in the medical literature before. © 2015 Wiley Periodicals, Inc.

Distinct cerebellar foliation anomalies in a CHD7 haploinsufficient mouse model of CHARGE syndrome.

PubMed

Whittaker, Danielle E; Kasah, Sahrunizam; Donovan, Alex P A; Ellegood, Jacob; Riegman, Kimberley L H; Volk, Holger A; McGonnell, Imelda; Lerch, Jason P; Basson, M Albert

2017-12-01

Mutations in the gene encoding the ATP dependent chromatin-remodeling factor, CHD7 are the major cause of CHARGE (Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital-urinary anomalies, and Ear defects) syndrome. Neurodevelopmental defects and a range of neurological signs have been identified in individuals with CHARGE syndrome, including developmental delay, lack of coordination, intellectual disability, and autistic traits. We previously identified cerebellar vermis hypoplasia and abnormal cerebellar foliation in individuals with CHARGE syndrome. Here, we report mild cerebellar hypoplasia and distinct cerebellar foliation anomalies in a Chd7 haploinsufficient mouse model. We describe specific alterations in the precise spatio-temporal sequence of fissure formation during perinatal cerebellar development responsible for these foliation anomalies. The altered cerebellar foliation pattern in Chd7 haploinsufficient mice show some similarities to those reported in mice with altered Engrailed, Fgf8 or Zic1 gene expression and we propose that mutations or polymorphisms in these genes may modify the cerebellar phenotype in CHARGE syndrome. Our findings in a mouse model of CHARGE syndrome indicate that a careful analysis of cerebellar foliation may be warranted in patients with CHARGE syndrome, particularly in patients with cerebellar hypoplasia and developmental delay. © 2017 The Authors. American Journal of Medical Genetics Part C Published by Wiley Periodicals, Inc.

Development and validation of a parent-report measure for detection of cognitive delay in infancy.

PubMed

Schafer, Graham; Genesoni, Lucia; Boden, Greg; Doll, Helen; Jones, Rosamond A K; Gray, Ron; Adams, Eleri; Jefferson, Ros

2014-12-01

To develop a brief, parent-completed instrument (ERIC - Early Report by Infant Caregivers) for detection of cognitive delay in 10- to 24-month-olds born preterm, or of low birthweight, or with perinatal complications, and to establish ERIC's diagnostic properties. Scores for ERIC were collected from the parents of 317 children meeting ≥inclusion criterion (birthweight <1500 g, gestational age <34 completed weeks, 5 min Apgar score <7, or presence of hypoxic-ischaemic encephalopathy) and no exclusion criteria. Children were assessed using a criterion score of below 80 on the Bayley Scales of Infant and Toddler Development-III cognitive scale. Items were retained according to their individual associations with delay. Sensitivity, specificity, and positive and negative predictive values were estimated and a truncated ERIC was developed for use in children <14 months old. ERIC correctly detected developmental delay in 17 out of 18 children in the sample, with 94.4% sensitivity, 76.9% specificity, 19.8% positive predictive value, 99.6% negative predictive value, 4.09 likelihood ratio positive, and 0.07 likelihood ratio negative. ERIC has potential value as a quickly administered diagnostic instrument for the absence of early cognitive delay in 10- to 24-month-old preterm infants and as a screen for cognitive delay. © 2014 Mac Keith Press.

Pathogenesis of growth failure and partial reversal with gene therapy in murine and canine Glycogen Storage Disease type Ia.

PubMed

Brooks, Elizabeth Drake; Little, Dianne; Arumugam, Ramamani; Sun, Baodong; Curtis, Sarah; Demaster, Amanda; Maranzano, Michael; Jackson, Mark W; Kishnani, Priya; Freemark, Michael S; Koeberl, Dwight D

2013-06-01

Glycogen Storage Disease type Ia (GSD-Ia) in humans frequently causes delayed bone maturation, decrease in final adult height, and decreased growth velocity. This study evaluates the pathogenesis of growth failure and the effect of gene therapy on growth in GSD-Ia affected dogs and mice. Here we found that homozygous G6pase (-/-) mice with GSD-Ia have normal growth hormone (GH) levels in response to hypoglycemia, decreased insulin-like growth factor (IGF) 1 levels, and attenuated weight gain following administration of GH. Expression of hepatic GH receptor and IGF 1 mRNAs and hepatic STAT5 (phospho Y694) protein levels are reduced prior to and after GH administration, indicating GH resistance. However, restoration of G6Pase expression in the liver by treatment with adeno-associated virus 8 pseudotyped vector expressing G6Pase (AAV2/8-G6Pase) corrected body weight, but failed to normalize plasma IGF 1 in G6pase (-/-) mice. Untreated G6pase (-/-) mice also demonstrated severe delay of growth plate ossification at 12 days of age; those treated with AAV2/8-G6Pase at 14 days of age demonstrated skeletal dysplasia and limb shortening when analyzed radiographically at 6 months of age, in spite of apparent metabolic correction. Moreover, gene therapy with AAV2/9-G6Pase only partially corrected growth in GSD-Ia affected dogs as detected by weight and bone measurements and serum IGF 1 concentrations were persistently low in treated dogs. We also found that heterozygous GSD-Ia carrier dogs had decreased serum IGF 1, adult body weights and bone dimensions compared to wild-type littermates. In sum, these findings suggest that growth failure in GSD-Ia results, at least in part, from hepatic GH resistance. In addition, gene therapy improved growth in addition to promoting long-term survival in dogs and mice with GSD-Ia. Copyright © 2013 Elsevier Inc. All rights reserved.

Pathogenesis of growth failure and partial reversal with gene therapy in murine and canine Glycogen Storage Disease type Ia

PubMed Central

Brooks, Elizabeth Drake; Little, Dianne; Arumugam, Ramamani; Sun, Baodong; Curtis, Sarah; DeMaster, Amanda; Maranzano, Michael; Jackson, Mark W.; Kishnani, Priya; Freemark, Michael S.; Koeberl, Dwight D.

2013-01-01

Glycogen Storage Disease type Ia (GSD-Ia) in humans frequently causes delayed bone maturation, decrease in final adult height, and decreased growth velocity. This study evaluates the pathogenesis of growth failure and the effect of gene therapy on growth in GSD-Ia affected dogs and mice. Here we found that homozygous G6pase (−/−) mice with GSD-Ia have normal growth hormone (GH) levels in response to hypoglycemia, decreased insulin-like growth factor (IGF) 1 levels, and attenuated weight gain following administration of GH. Expression of hepatic GH receptor and IGF 1 mRNAs and hepatic STAT5 (phospho Y694) protein levels are reduced prior to and after GH administration, indicating GH resistance. However, restoration of G6Pase expression in the liver by treatment with adeno-associated virus 8 pseudotyped vector expressing G6Pase (AAV2/8-G6Pase) corrected body weight, but failed to normalize plasma IGF 1 in G6pase (−/−) mice. Untreated G6pase (−/−) mice also demonstrated severe delay of growth plate ossification at 12 days of age; those treated with AAV2/8-G6Pase at 14 days of age demonstrated skeletal dysplasia and limb shortening when analyzed radiographically at 6 months of age, in spite of apparent metabolic correction. Moreover, gene therapy with AAV2/9-G6Pase only partially corrected growth in GSD-Ia affected dogs as detected by weight and bone measurements and serum IGF 1 concentrations were persistently low in treated dogs. We also found that heterozygous GSD-Ia carrier dogs had decreased serum IGF 1, adult body weights and bone dimensions compared to wild-type littermates. In sum, these findings suggest that growth failure in GSD-Ia results, at least in part, from hepatic GH resistance. In addition, gene therapy improved growth in addition to promoting long-term survival in dogs and mice with GSD-Ia. PMID:23623482