High early cardiovascular mortality following liver transplantation

PubMed Central

VanWagner, Lisa B.; Lapin, Brittany; Levitsky, Josh; Wilkins, John T.; Abecassis, Michael M.; Skaro, Anton I.; Lloyd-Jones, Donald M.

2014-01-01

Cardiovascular disease (CVD) contributes to excess long-term mortality after liver transplantation (LT), however little is known about early post-operative CVD mortality in the current era. In addition, there is no model to predict early post-operative CVD mortality across centers. We analyzed adult recipients of primary LT in the Organ Procurement and Transplantation Network (OPTN) database between February 2002 and December 2012 to assess prevalence and predictors of early (30-day) CVD mortality, defined as death from arrhythmia, heart failure, myocardial infarction, cardiac arrest, thromboembolism, and/or stroke. We performed logistic regression with stepwise selection to develop a predictive model of early CVD mortality. Sex and center volume were forced into the final model, which was validated using bootstrapping techniques. Among 54,697 LT recipients, there were 1576 (2.9%) deaths within 30 days. CVD death was the leading cause of 30-day mortality (42.1%), followed by infection (27.9%) and graft failure (12.2%). In multivariate analysis, 9 (6 recipient, 2 donor, 1 operative) significant covariates were identified: age, pre-operative hospitalization, ICU and ventilator status, calculated MELD score, portal vein thrombosis, national organ sharing, donor BMI and cold ischemia time. The model showed moderate discrimination (c-statistic 0.66, 95% CI: 0.63–0.68). We provide the first multicenter prognostic model for the prediction of early post-LT CVD death, the most common cause of early post-LT mortality in the current transplant era. However, evaluation of additional CVD-related variables not collected by the OPTN are needed in order to improve model accuracy and potential clinical utility. PMID:25044256

[Establishment of sprouting embryoid body model mimicking early embryonic vasculogenesis in human embryo].

PubMed

Jiang, Hua; Feng, You-Ji; Xie, Yi; Han, Jin-Lan; Wang, Zack; Chen, Tong

2008-10-14

To establish a sprouting embryoid body model mimicking early embryonic vasculogenesis in human embryo. Human embryonic stem were (hESCs) were cultured on the mouse embryo fibroblasts and then were induced to differentiate to form three-dimensional EB. The hEBs were cultured in media containing various angiogenesis-related factors: vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), endostatin, angiostatin, and platelet factor (PF)-4 of different concentrations for 3 days to observe the sprouting of the hEBs. 3, 3, 3', 3'-tetramethylindo-carbocyanine perchlorate labeled acetylated low density lipoprotein (Dil-AcLDL) was added onto the hEBs foe 4 h Immunofluorescence assay was used to observe if Dil-AcLDL was absorbed and if CD31 was expressed so as to determine the existence of embryonic endothelial cells in the sprouting structures. The ideal culturing condition was analyzed. The differentiated EBs formed sprouting structures in the collagen I matrix containing VEGF and FGF. The sprouts among individual EBs were able to link to each other and form vascular network-like structures. In the presence of VEGF and FGF, the sprouts branching from the EBs assimilated Dil-AcLDL, expressed CD31 and formed a 3-dimensional cylindrical organization. The concentrations of growth factors ideally stimulating sprouting growth were 100 ng/ml of VEGF and 50 ng/ml of FGF. The networks among the EBs were abolished by the angiostatin, endostatin, and PF4. The sprouting from hEBs accumulates embryonic endothelial cells and the sprouting network-like structures are indeed endothelial in nature. Inducing of sprouting EBs is an ideal model that mimics early embryonic vasculogenesis in humans.

Embryonic development during chronic acceleration

NASA Technical Reports Server (NTRS)

Smith, A. H.; Abbott, U. K.

1982-01-01

Experiments carried out on chicken eggs indicate that the embryo is affected during very early development, especially over the first four days, and during hatching. In the first four days, the brain develops as well as the anlage for all other organs. In addition, the heart commences to function and the extraembryonic membranes that compartmentalize the egg contents form. The latter require an appreciable extension and folding of tissue which may be disrupted by the mechanical load. Observations of embryonic abnormalities that occur during chronic acceleration suggest an inhibition of development of the axial skeleton, which is rarely seen otherwise, a general retardation of embryonic growth, and circulatory problems. The final stages of development (after 18 days) involve the uptake of fluids, the transition to aerial respiration, and the reorientation of the embryo into a normal hatching position. At 4 G mortality is very high during this period, with a majority of embryos failing to reorient into the normal hatching position.

Effects of breed, parity, and folic Acid supplement on the expression of folate metabolism genes in endometrial and embryonic tissues from sows in early pregnancy.

PubMed

Vallée, Maud; Guay, Frédéric; Beaudry, Danièle; Matte, Jacques; Blouin, Richard; Laforest, Jean-Paul; Lessard, Martin; Palin, Marie-France

2002-10-01

Folic acid and glycine are factors of great importance in early gestation. In sows, folic acid supplement can increase litter size through a decrease in embryonic mortality, while glycine, the most abundant amino acid in the sow oviduct, uterine, and allantoic fluids, is reported to act as an organic osmoregulator. In this study, we report the characterization of cytoplasmic serine hydroxymethyltransferase (cSHMT), T-protein, and vT-protein (variant T-protein) mRNA expression levels in endometrial and embryonic tissues in gestating sows on Day 25 of gestation according to the breed, parity, and folic acid + glycine supplementation. Expression levels of cSHMT, T-protein, and vT-protein mRNA in endometrial and embryonic tissues were performed using semiquantitative reverse transcription-polymerase chain reaction. We also report, for the first time, an alternative splicing event in the porcine T-protein gene. Results showed that a T-protein splice variant, vT-protein, is present in all the tested sow populations. Further characterizations revealed that this T-protein splice variant contains a coding intron that can adopt a secondary structure. Results demonstrated that cSHMT mRNA expression levels were significantly higher in sows receiving the folic acid + glycine supplementation, independently of the breed or parity and in both endometrial and embryonic tissues. Upon receiving the same treatment, the vT-protein and T-protein mRNA expression levels were significantly reduced in the endometrial tissue of Yorkshire-Landrace sows only. These results indicate that modulation of specific gene expression levels in endometrial and embryonic tissues of sows in early gestation could be one of the mechanism involved with the role of folic acid on improving swine reproduction traits.

Chromosomal Aneuploidies and Early Embryonic Developmental Arrest.

PubMed

Maurer, Maria; Ebner, Thomas; Puchner, Manuela; Mayer, Richard Bernhard; Shebl, Omar; Oppelt, Peter; Duba, Hans-Christoph

2015-01-01

Selecting the best embryo for transfer, with the highest chance of achieving a vital pregnancy, is a major goal in current in vitro fertilization (IVF) technology. The high rate of embryonic developmental arrest during IVF treatment is one of the limitations in achieving this goal. Chromosomal abnormalities are possibly linked with chromosomal arrest and selection against abnormal fertilization products. The objective of this study was to evaluate the frequency and type of chromosomal abnormalities in preimplantation embryos with developmental arrest. This cohort study included blastomeres of embryos with early developmental arrest that were biopsied and analyzed by fluorescence in-situ hybridization (FISH) with probes for chromosomes 13, 16, 18, 21 and 22. Forty-five couples undergoing IVF treatment were included, and 119 arrested embryos were biopsied. All probes were obtained from the Kinderwunsch Zentrum, Linz, Austria, between August 2009 and August 2011. Of these embryos, 31.6% were normal for all chromosomes tested, and 68.4% were abnormal. Eleven embryos were uniformly aneuploid, 20 were polyploid, 3 were haploid, 11 displayed mosaicism and 22 embryos exhibited chaotic chromosomal complement. Nearly 70% of arrested embryos exhibit chromosomal errors, making chromosomal abnormalities a major cause of embryonic arrest and may be a further explanation for the high developmental failure rates during culture of the embryos in the IVF setting.

Chromosomal Aneuploidies and Early Embryonic Developmental Arrest

PubMed Central

Maurer, Maria; Ebner, Thomas; Puchner, Manuela; Mayer, Richard Bernhard; Shebl, Omar; Oppelt, Peter; Duba, Hans-Christoph

2015-01-01

Background Selecting the best embryo for transfer, with the highest chance of achieving a vital pregnancy, is a major goal in current in vitro fertilization (IVF) technology. The high rate of embryonic developmental arrest during IVF treatment is one of the limitations in achieving this goal. Chromosomal abnormalities are possibly linked with chromosomal arrest and selection against abnormal fertilization products. The objective of this study was to evaluate the frequency and type of chromosomal abnormalities in preimplantation embryos with developmental arrest. Materials and Methods This cohort study included blastomeres of embryos with early developmental arrest that were biopsied and analyzed by fluorescence in-situ hybridization (FISH) with probes for chromosomes 13, 16, 18, 21 and 22. Forty-five couples undergoing IVF treatment were included, and 119 arrested embryos were biopsied. All probes were obtained from the Kinderwunsch Zentrum, Linz, Austria, between August 2009 and August 2011. Results Of these embryos, 31.6% were normal for all chromosomes tested, and 68.4% were abnormal. Eleven embryos were uniformly aneuploid, 20 were polyploid, 3 were haploid, 11 displayed mosaicism and 22 embryos exhibited chaotic chromosomal complement. Conclusion Nearly 70% of arrested embryos exhibit chromosomal errors, making chromosomal abnormalities a major cause of embryonic arrest and may be a further explanation for the high developmental failure rates during culture of the embryos in the IVF setting. PMID:26644858

Behavioral development in embryonic and early juvenile cuttlefish (Sepia officinalis).

PubMed

O'Brien, Caitlin E; Mezrai, Nawel; Darmaillacq, Anne-Sophie; Dickel, Ludovic

2017-03-01

Though a mollusc, the cuttlefish Sepia officinalis possesses a sophisticated brain, advanced sensory systems, and a large behavioral repertoire. Cuttlefish provide a unique perspective on animal behavior due to their phylogenic distance from more traditional (vertebrate) models. S. officinalis is well-suited to addressing questions of behavioral ontogeny. As embryos, they can perceive and learn from their environment and experience no direct parental care. A marked progression in learning and behavior is observed during late embryonic and early juvenile development. This improvement is concomitant with expansion and maturation of the vertical lobe, the cephalopod analog of the mammalian hippocampus. This review synthesizes existing knowledge regarding embryonic and juvenile development in this species in an effort to better understand cuttlefish behavior and animal behavior in general. It will serve as a guide to future researchers and encourage greater awareness of the utility of this species to behavioral science. © 2016 Wiley Periodicals, Inc.

Early embryonic programming of neuronal left/right asymmetry in C. elegans.

PubMed

Poole, Richard J; Hobert, Oliver

2006-12-05

Nervous systems are largely bilaterally symmetric on a morphological level but often display striking degrees of functional left/right (L/R) asymmetry. How L/R asymmetric functional features are superimposed onto an essentially bilaterally symmetric structure and how nervous-system laterality relates to the L/R asymmetry of internal organs are poorly understood. We address these questions here by using the establishment of L/R asymmetry in the ASE chemosensory neurons of C. elegans as a paradigm. This bilaterally symmetric neuron pair is functionally lateralized in that it senses a distinct class of chemosensory cues and expresses a putative chemoreceptor family in a L/R asymmetric manner. We show that the directionality of the asymmetry of the two postmitotic ASE neurons ASE left (ASEL) and ASE right (ASER) in adults is dependent on a L-/R-symmetry-breaking event at a very early embryonic stage, the six-cell stage, which also establishes the L/R asymmetric placement of internal organs. However, the L/R asymmetry of the ASE neurons per se is dependent on an even earlier anterior-posterior (A/P) Notch signal that specifies embryonic ABa/ABp blastomere identities at the four-cell stage. This Notch signal, which functions through two T box genes, acts genetically upstream of a miRNA-controlled bistable feedback loop that regulates the L/R asymmetric gene-expression program in the postmitotic ASE cells. Our results link adult neuronal laterality to the generation of the A/P axis at the two-cell stage and raise the possibility that neural asymmetries observed across the animal kingdom are similarly established by very early embryonic interactions.

Importance of the pluripotency factor LIN28 in the mammalian nucleolus during early embryonic development.

PubMed

Vogt, Edgar J; Meglicki, Maciej; Hartung, Kristina Ilka; Borsuk, Ewa; Behr, Rüdiger

2012-12-01

The maternal nucleolus is required for proper activation of the embryonic genome (EGA) and early embryonic development. Nucleologenesis is characterized by the transformation of a nucleolar precursor body (NPB) to a mature nucleolus during preimplantation development. However, the function of NPBs and the involved molecular factors are unknown. We uncover a novel role for the pluripotency factor LIN28, the biological significance of which was previously demonstrated in the reprogramming of human somatic cells to induced pluripotent stem (iPS) cells. Here, we show that LIN28 accumulates at the NPB and the mature nucleolus in mouse preimplantation embryos and embryonic stem cells (ESCs), where it colocalizes with the nucleolar marker B23 (nucleophosmin 1). LIN28 has nucleolar localization in non-human primate (NHP) preimplantation embryos, but is cytoplasmic in NHP ESCs. Lin28 transcripts show a striking decline before mouse EGA, whereas LIN28 protein localizes to NPBs at the time of EGA. Following knockdown with a Lin28 morpholino, the majority of embryos arrest between the 2- and 4-cell stages and never develop to morula or blastocyst. Lin28 morpholino-injected embryos arrested at the 2-cell stage were not enriched with nucleophosmin at presumptive NPB sites, indicating that functional NPBs were not assembled. Based on these results, we propose that LIN28 is an essential factor of nucleologenesis during early embryonic development.

Early life mortality and height in Indian states

PubMed Central

Coffey, Diane

2014-01-01

Height is a marker for health, cognitive ability and economic productivity. Recent research on the determinants of height suggests that postneonatal mortality predicts height because it is a measure of the early life disease environment to which a cohort is exposed. This article advances the literature on the determinants of height by examining the role of early life mortality, including neonatal mortality, in India, a large developing country with a very short population. It uses state level variation in neonatal mortality, postneonatal mortality, and pre-adult mortality to predict the heights of adults born between 1970 and 1983, and neonatal and postneonatal mortality to predict the heights of children born between 1995 and 2005. In contrast to what is found in the literature on developed countries, I find that state level variation in neonatal mortality is a strong predictor of adult and child heights. This may be due to state level variation in, and overall poor levels of, pre-natal nutrition in India. PMID:25499239

High-Frequency Ultrasound for the Study of Early Mouse Embryonic Cardiovascular System.

PubMed

Greco, Adelaide; Coda, Anna Rita Daniela; Albanese, Sandra; Ragucci, Monica; Liuzzi, Raffaele; Auletta, Luigi; Gargiulo, Sara; Lamagna, Francesco; Salvatore, Marco; Mancini, Marcello

2015-12-01

An accurate diagnosis of congenital heart defects during fetal development is critical for interventional planning. Mice can be used to generate animal models with heart defects, and high-frequency ultrasound (HFUS) imaging enables in utero imaging of live mouse embryos. A wide range of physiological measurements is possible using Doppler-HFUS imaging; limitations of any single measurement warrant a multiparameter approach to characterize cardiovascular function. Doppler-HFUS was used to explore the embryonic (heart, aorta) and extraembryonic (umbilical blood flow) circulatory systems to create a database in normal mouse embryos between 9.5 and 16.5 days of gestation. Multivariate analyses were performed to explore correlations between gestational age and embryo echocardiographic parameters. Heart rate and peak velocity in the aorta were positively correlated with gestational time, whereas cardiac cycle length, isovolumetric relaxation time, myocardial performance index, and arterial deceleration time of the umbilical cord were negatively correlated with it. Doppler-HFUS facilitated detailed characterization of the embryonic mouse circulation and represents a useful tool for investigation of the early mouse embryonic cardiovascular system. © The Author(s) 2015.

Negative regulation of early polyomavirus expression in mouse embryonal carcinoma cells.

PubMed Central

Cremisi, C; Babinet, C

1986-01-01

Embryonal carcinoma cells are resistant to infection by polyomavirus (Py). We showed that this block was partially removed by inhibiting protein synthesis temporarily. The block was also partially removed when Py was coinfected with simian virus 40. Cycloheximide treatment of cells infected with Py mutants able to grow on PCC4 embryonal carcinoma cells led to 3- to 10-fold increases in the production of T-antigen-positive cells. At 31 degrees C, Py T-antigen expression was enhanced when the cells were treated with cycloheximide. We suggest that a negative labile regulatory protein(s) is synthesized in PCC4 cells, preventing the initiation of early Py transcription by binding to the noncoding sequence, especially the enhancer element B and perhaps also element A, and that the Py mutants retained a binding site(s). PMID:3016339

Early mortality in acute promyelocytic leukemia: Potential predictors

PubMed Central

Chen, Can; Huang, Xilian; Wang, Kaile; Chen, Kuang; Gao, Danquan; Qian, Shenxian

2018-01-01

Acute promyelocytic leukemia (APL) is a rare leukemia characterized by the balanced reciprocal translocation between the promyelocytic leukemia gene on chromosome 15 and the retinoic acid receptor α (RARα) gene on chromosome 17, and accounts for 10–15% of newly diagnosed acute myeloid leukemia each year. The combined use of all-trans retinoic acid and arsenic trioxide (ATO) as primary therapy has markedly improved the survival rate of patients with APL. Mortality in the first 30 days following therapy remains a major contribution to treatment failure. In the present study, published data was reviewed with a focus on the factors associated with early mortality. When treated with ATO as a primary treatment, the fms-like tyrosine kinase-internal tandem deletion has no impact on early mortality. Low lymphoid enhancer binding factor-1 expression may be a reliable marker for early mortality and the target of therapy if it could be proven by further studies. Cluster of differentiation (CD)56+ and CD34+/CD2+ may be candidates to select high-risk patients. The risk of early mortality in APL still cannot be predicted via the cell surface makers, despite multiple studies on their prognostic significance. Typically, a complex translocation did not alter the survival rate in patients with APL; however, if an abnormal karyotype [e.g., Ide(17), ZBTB16/RARα and STAT5B/RARα] appeared singularly or as part of a complex mutation, there is a high possibility of early mortality if clinicians are unable to identify or monitor it. PMID:29541170

Early first trimester maternal 'high fish and olive oil and low meat' dietary pattern is associated with accelerated human embryonic development.

PubMed

Parisi, Francesca; Rousian, Melek; Steegers-Theunissen, Régine P M; Koning, Anton H J; Willemsen, Sten P; de Vries, Jeanne H M; Cetin, Irene; Steegers, Eric A P

2018-04-20

Maternal dietary patterns were associated with embryonic growth and congenital anomalies. We aim to evaluate associations between early first trimester maternal dietary patterns and embryonic morphological development among pregnancies with non-malformed outcome. A total of 228 strictly dated, singleton pregnancies without congenital malformations were enrolled in a periconceptional hospital-based cohort. Principal component analysis was performed to extract early first trimester maternal dietary patterns from food frequency questionnaires. Serial transvaginal three-dimensional ultrasound (3D US) scans were performed between 6 +0 and 10 +2 gestational weeks and internal and external morphological criteria were used to define Carnegie stages in a virtual reality system. Associations between dietary patterns and Carnegie stages were investigated using linear mixed models. A total of 726 3D US scans were included (median: three scans per pregnancy). The 'high fish and olive oil and low meat' dietary pattern was associated with accelerated embryonic development in the study population (β = 0.12 (95%CI: 0.00; 0.24), p < 0.05). Weak adherence to this dietary pattern delayed embryonic development by 2.1 days (95%CI: 1.6; 2.6) compared to strong adherence. The 'high vegetables, fruit and grain' dietary pattern accelerated embryonic development in the strictly dated spontaneous pregnancy subgroup without adjustment for energy intake. Early first trimester maternal dietary patterns impacts human embryonic morphological development among pregnancies without congenital malformations. The clinical meaning of delayed embryonic development needs further investigation.

Gene function in early mouse embryonic stem cell differentiation

PubMed Central

Sene, Kagnew Hailesellasse; Porter, Christopher J; Palidwor, Gareth; Perez-Iratxeta, Carolina; Muro, Enrique M; Campbell, Pearl A; Rudnicki, Michael A; Andrade-Navarro, Miguel A

2007-01-01

Background Little is known about the genes that drive embryonic stem cell differentiation. However, such knowledge is necessary if we are to exploit the therapeutic potential of stem cells. To uncover the genetic determinants of mouse embryonic stem cell (mESC) differentiation, we have generated and analyzed 11-point time-series of DNA microarray data for three biologically equivalent but genetically distinct mESC lines (R1, J1, and V6.5) undergoing undirected differentiation into embryoid bodies (EBs) over a period of two weeks. Results We identified the initial 12 hour period as reflecting the early stages of mESC differentiation and studied probe sets showing consistent changes of gene expression in that period. Gene function analysis indicated significant up-regulation of genes related to regulation of transcription and mRNA splicing, and down-regulation of genes related to intracellular signaling. Phylogenetic analysis indicated that the genes showing the largest expression changes were more likely to have originated in metazoans. The probe sets with the most consistent gene changes in the three cell lines represented 24 down-regulated and 12 up-regulated genes, all with closely related human homologues. Whereas some of these genes are known to be involved in embryonic developmental processes (e.g. Klf4, Otx2, Smn1, Socs3, Tagln, Tdgf1), our analysis points to others (such as transcription factor Phf21a, extracellular matrix related Lama1 and Cyr61, or endoplasmic reticulum related Sc4mol and Scd2) that have not been previously related to mESC function. The majority of identified functions were related to transcriptional regulation, intracellular signaling, and cytoskeleton. Genes involved in other cellular functions important in ESC differentiation such as chromatin remodeling and transmembrane receptors were not observed in this set. Conclusion Our analysis profiles for the first time gene expression at a very early stage of mESC differentiation, and

Mortality in children with early detected congenital central hypothyroidism.

PubMed

Zwaveling-Soonawala, Nitash; Naafs, Jolanda C; Verkerk, Paul H; van Trotsenburg, A S Paul

2018-06-07

Approximately 60-80% of patients with congenital central hypothyroidism (CH-C) have multiple pituitary hormone deficiencies (MPHD), making CH-C a potentially life-threatening disease. Data on mortality in CH-C patients, however, are lacking. To study mortality rate in early detected and treated pediatric CH-C patients in the Netherlands and to investigate whether causes of death were related to pituitary hormone deficiencies. Overall mortality rate, infant mortality rate and under-5 mortality rate were calculated in all children with CH-C detected by neonatal screening between 1-1-1995 and 1-1-2013. Medical charts were reviewed to establish causes of death. 139 children with CH-C were identified, of which 138 could be traced (82 MPHD/56 isolated CHC). Total observation time was 1414 years with a median follow up duration of 10.2 years. The overall mortality rate was 10.9% (15/138). Infant mortality rate (IMR) and under-5 mortality rate were 65.2/1000 (9/138) and 101.4/1000 (14/138), respectively, compared to an IMR of 4.7/1000 and under-5 mortality of 5.4/1000 live born children in the Netherlands during the same time period (p<0.0001). Main causes of death were severe congenital malformations in six patients, asphyxia in two patients, and congenital or early neonatal infection in two patients. Pituitary hormone deficiency was noted as cause of death in only one infant. We report an increased mortality rate in early detected CH-C patients which does not seem to be related to endocrine disease. This suggests that mortality due to pituitary insufficiency is low in an early detected and treated CH-C population.

Elevated temperature enhances normal early embryonic development in the coral Platygyra acuta under low salinity conditions

NASA Astrophysics Data System (ADS)

Chui, Apple Pui Yi; Ang, Put

2015-06-01

To better understand the possible consequences of climate change on reef building scleractinian corals in a marginal environment, laboratory experiments were conducted to examine the interactive effects of changes in salinity and temperature on percent fertilization success and early embryonic development of the coral Platygyra acuta. In the present study, a salinity of 24 psu (ambient 32 psu) reduced fertilization success by 60 %. Normal embryonic development was reduced by >80 % at 26 psu (ambient 33 psu) with 100 % abnormal development at 22 psu under ambient temperature. Elevated temperature (+3 °C) above the ambient spawning temperature did not show any negative effects on fertilization success. However, there was a trend for more abnormal embryos to develop at elevated temperature in the 2 d of the spawning event. The interactive effects between salinity and temperature are statistically significant only on normal embryonic development of P. acuta, but not on its fertilization success. Salinity was revealed to be the main factor affecting both fertilization success and normal embryonic development. Interestingly, the much lower fertilization success (76 %) observed in the second day of spawning (Trial 2) under ambient temperature recovered to 99 % success under elevated (+3 °C) temperature conditions. Moreover, elevated temperature enhanced normal early embryonic development under lowered salinity (26 psu). This antagonistic interactive effect was consistently observed in two successive nights of spawning. Overall, our results indicate that, in terms of its fertilization success and embryonic development, P. acuta is the most tolerant coral species to reduced salinity thus far reported in the literature. Elevated temperature, at least that within the tolerable range of the corals, could apparently alleviate the potential negative effects from salinity stresses. This mitigating role of elevated temperature appears not to have been reported on corals before.

Selection and dynamics of embryonic stem cell integration into early mouse embryos

PubMed Central

Alexandrova, Stoyana; Kalkan, Tuzer; Humphreys, Peter; Riddell, Andrew; Scognamiglio, Roberta; Trumpp, Andreas; Nichols, Jennifer

2016-01-01

The process by which pluripotent cells incorporate into host embryos is of interest to investigate cell potency and cell fate decisions. Previous studies suggest that only a minority of the embryonic stem cell (ESC) inoculum contributes to the adult chimaera. How incoming cells are chosen for integration or elimination remains unclear. By comparing a heterogeneous mix of undifferentiated and differentiating ESCs (serum/LIF) with more homogeneous undifferentiated culture (2i/LIF), we examine the role of cellular heterogeneity in this process. Time-lapse ex vivo imaging revealed a drastic elimination of serum/LIF ESCs during early development in comparison with 2i/LIF ESCs. Using a fluorescent reporter for naive pluripotency (Rex1-GFP), we established that the acutely eliminated serum/LIF ESCs had started to differentiate. The rejected cells were apparently killed by apoptosis. We conclude that a selection process exists by which unwanted differentiating cells are eliminated from the embryo. However, occasional Rex1− cells were able to integrate. Upregulation of Rex1 occurred in a proportion of these cells, reflecting the potential of the embryonic environment to expedite diversion from differentiation priming to enhance the developing embryonic epiblast. PMID:26586221

Single-Cell RNA-Seq Reveals Dynamic Early Embryonic-like Programs during Chemical Reprogramming.

PubMed

Zhao, Ting; Fu, Yao; Zhu, Jialiang; Liu, Yifang; Zhang, Qian; Yi, Zexuan; Chen, Shi; Jiao, Zhonggang; Xu, Xiaochan; Xu, Junquan; Duo, Shuguang; Bai, Yun; Tang, Chao; Li, Cheng; Deng, Hongkui

2018-06-12

Chemical reprogramming provides a powerful platform for exploring the molecular dynamics that lead to pluripotency. Although previous studies have uncovered an intermediate extraembryonic endoderm (XEN)-like state during this process, the molecular underpinnings of pluripotency acquisition remain largely undefined. Here, we profile 36,199 single-cell transcriptomes at multiple time points throughout a highly efficient chemical reprogramming system using RNA-sequencing and reconstruct their progression trajectories. Through identifying sequential molecular events, we reveal that the dynamic early embryonic-like programs are key aspects of successful reprogramming from XEN-like state to pluripotency, including the concomitant transcriptomic signatures of two-cell (2C) embryonic-like and early pluripotency programs and the epigenetic signature of notable genome-wide DNA demethylation. Moreover, via enhancing the 2C-like program by fine-tuning chemical treatment, the reprogramming process is remarkably accelerated. Collectively, our findings offer a high-resolution dissection of cell fate dynamics during chemical reprogramming and shed light on mechanistic insights into the nature of induced pluripotency. Copyright © 2018 Elsevier Inc. All rights reserved.

Triennial Reproduction Symposium: influence of follicular characteristics at ovulation on early embryonic survival.

PubMed

Geary, T W; Smith, M F; MacNeil, M D; Day, M L; Bridges, G A; Perry, G A; Abreu, F M; Atkins, J A; Pohler, K G; Jinks, E M; Madsen, C A

2013-07-01

Reproductive failure in livestock can result from failure to fertilize the oocyte or embryonic loss during gestation. Although fertilization failure occurs, embryonic mortality represents a greater contribution to reproductive failure. Reproductive success varies among species and production goals but is measured as a binomial trait (i.e., pregnancy), derived by the success or failure of multiple biological steps. This review focuses primarily on follicular characteristics affecting oocyte quality, fertilization, and embryonic health that lead to pregnancy establishment in beef cattle. When estrous cycles are manipulated with assisted reproductive technologies and ovulation is induced, duration of proestrus (i.e., interval from induced luteolysis to induced ovulation), ovulatory follicle growth rate, and ovulatory follicle size are factors that affect the maturation of the follicle and oocyte at induced ovulation. The most critical maturational component of the ovulatory follicle is the production of sufficient estradiol to prepare follicular cells for luteinization and progesterone synthesis and prepare the uterus for pregnancy. The exact roles of estradiol in oocyte maturation remain unclear, but cows that have lesser serum concentrations of estradiol have decreased fertilization rates and decreased embryo survival on d 7 after induced ovulation. When length of proestrus is held constant, perhaps the most practical follicular measure of fertility is ovulatory follicle size because it is an easily measured attribute of the follicle that is highly associated with its ability to produce estradiol.

Effects of temperature on embryonic and early larval growth and development in the rough-skinned newt (Taricha granulosa).

PubMed

Smith, Geoffrey D; Hopkins, Gareth R; Mohammadi, Shabnam; M Skinner, Heather; Hansen, Tyler; Brodie, Edmund D; French, Susannah S

2015-07-01

We investigated the effects of temperature on the growth and development of embryonic and early larval stages of a western North American amphibian, the rough-skinned newt (Taricha granulosa). We assigned newt eggs to different temperatures (7, 14, or 21°C); after hatching, we re-assigned the newt larvae into the three different temperatures. Over the course of three to four weeks, we measured total length and developmental stage of the larvae. Our results indicated a strong positive relationship over time between temperature and both length and developmental stage. Importantly, individuals assigned to cooler embryonic temperatures did not achieve the larval sizes of individuals from the warmer embryonic treatments, regardless of larval temperature. Our investigation of growth and development at different temperatures demonstrates carry-over effects and provides a more comprehensive understanding of how organisms respond to temperature changes during early development. Copyright © 2015 Elsevier Ltd. All rights reserved.

Patterns of late embryonic and fetal mortality and association with several factors in sheep.

PubMed

Dixon, A B; Knights, M; Winkler, J L; Marsh, D J; Pate, J L; Wilson, M E; Dailey, R A; Seidel, G; Inskeep, E K

2007-05-01

Embryonic and fetal mortality reduce lambing rates and litter sizes, thus contributing to economic losses in the sheep industry. In the current study, the timing of late embryonic and fetal loss in ewes and the factors with which these losses were associated were examined. Ewes lambing and lambs born were compared with pregnancy diagnosis and counts of embryos by ultrasonography near d 25, 45, 65, or 85 of gestation. Approximately 19.9% of the ewes experienced late embryonic loss, fetal loss, or both; and 21.2% of the embryos or fetuses were lost from d 25 to term. Potential offspring were lost throughout gestation; 3.7% of embryos from d 25 to 45, 4.3% of fetuses from d 45 to 65, 3.3% from d 65 to 85, and 11.5% from d 85 to parturition; thus, approximately 3 to 4% of the potential offspring were lost for each 20-d period of pregnancy beyond d 25. A greater proportion of ewes lost one (36.7%) rather than all (20.5% single; 3.8% multiple) embryos or fetuses. The patterns of loss were similar in ewes mated during the anestrous season and the transitional period and did not vary with service period within breeding season or method of synchronization of estrus. Late embryonic or fetal losses were not related to the temperature-humidity index. Maternal serum collected near d 25, 45, 65, or 85 of gestation was assayed for concentrations of progesterone, estradiol-17beta , and vascular endothelial growth factor (VEGF). The proportions of embryos or fetuses lost were associated with breed type (P < 0.05), as were concentrations of progesterone (P < 0.01), estradiol (P < 0.05), and VEGF (P < 0.01). The relationships of loss or retention of pregnancy to hormonal variables at the 4 stages studied were limited. Complete and partial losses increased rapidly as maternal progesterone at d 25 decreased below 2 ng/mL (P < 0.05). Survival of fetuses within a litter from d 25 to 65 was greater for ewes with medium concentrations of VEGF near d 25 and from d 65 to parturition was

Early-Life Origins of the Race Gap in Men's Mortality

ERIC Educational Resources Information Center

Warner, David F.; Hayward, Mark D.

2006-01-01

Using a life course framework, we examine the early life origins of the race gap in men's all-cause mortality. Using the National Longitudinal Survey of Older Men (1966-1990), we evaluate major social pathways by which early life conditions differentiate the mortality experiences of blacks and whites. Our findings indicate that early life…

Stage-dependent remodeling of the nuclear envelope and lamina during rabbit early embryonic development.

PubMed

Popken, Jens; Schmid, Volker J; Strauss, Axel; Guengoer, Tuna; Wolf, Eckhard; Zakhartchenko, Valeri

2016-04-22

Utilizing 3D structured illumination microscopy, we investigated the quality and quantity of nuclear invaginations and the distribution of nuclear pores during rabbit early embryonic development and identified the exact time point of nucleoporin 153 (NUP153) association with chromatin during mitosis. Contrary to bovine early embryonic nuclei, featuring almost exclusively nuclear invaginations containing a small volume of cytoplasm, nuclei in rabbit early embryonic stages show additionally numerous invaginations containing a large volume of cytoplasm. Small-volume invaginations frequently emanated from large-volume nuclear invaginations but not vice versa, indicating a different underlying mechanism. Large- and small-volume nuclear envelope invaginations required the presence of chromatin, as they were restricted to chromatin-positive areas. The chromatin-free contact areas between nucleolar precursor bodies (NPBs) and large-volume invaginations were free of nuclear pores. Small-volume invaginations were not in contact with NPBs. The number of invaginations and isolated intranuclear vesicles per nucleus peaked at the 4-cell stage. At this stage, the nuclear surface showed highly concentrated clusters of nuclear pores surrounded by areas free of nuclear pores. Isolated intranuclear lamina vesicles were usually NUP153 negative. Cytoplasmic, randomly distributed NUP153-positive clusters were highly abundant at the zygote stage and decreased in number until they were almost absent at the 8-cell stage and later. These large NUP153 clusters may represent a maternally provided NUP153 deposit, but they were not visible as clusters during mitosis. Major genome activation at the 8- to 16-cell stage may mark the switch from a necessity for a deposit to on-demand production. NUP153 association with chromatin is initiated during metaphase before the initiation of the regeneration of the lamina. To our knowledge, the present study demonstrates for the first time major remodeling

Embryonated chicken eggs: An experimental model for Pythium insidiosum infection.

PubMed

Verdi, Camila M; Jesus, Francielli P K; Kommers, Glaucia; Ledur, Pauline C; Azevedo, Maria I; Loreto, Erico S; Tondolo, Juliana S M; Andrade, Eduardo N C; Schlemmer, Karine B; Alves, Sydney H; Santurio, Janio M

2018-02-01

Pythiosis is a severe disease caused by Pythium insidiosum. Currently, the research on the treatment of pythiosis uses rabbits as an experimental infection model. To reduce the use of animals in scientific experimentation, alternative models are increasingly necessary options. The objective of this study was to establish a new experimental infection model for pythiosis using embryonated chicken eggs. First, we tested the inoculation of 4 zoospore concentrations into the egg allantoic cavity at 3 embryonic days. We observed that increased zoospore concentration causes a decrease in survival time, and at a later embryonic day (the 14th) of infection, embryos showed delayed mortality. To confirm the reproducibility of the model, we chose the 14th embryonic day for the inoculation of 50 zoospores/egg, and the experiment was repeated twice. Mortality began with 30% embryos 48 hours after inoculation, and 95% embryos died within 72 hours. There was no mortality in the uninfected control group. The infection was confirmed by culture, PCR and histopathology. Immunohistochemistry confirmed the presence of hyphae in blood vessels in the umbilical cords in 95% of embryos and only 1 liver (5%). Our results suggest that embryonated eggs can be a very useful alternative infection model to study pythiosis. © 2017 Blackwell Verlag GmbH.

The Potential Role of As-sumo-1 in the Embryonic Diapause Process and Early Embryo Development of Artemia sinica

PubMed Central

Chu, Bing; Yao, Feng; Cheng, Cheng; Wu, Yang; Mei, Yanli; Li, Xuejie; Liu, Yan; Wang, Peisheng; Hou, Lin; Zou, Xiangyang

2014-01-01

During embryonic development of Artemia sinica, environmental stresses induce the embryo diapause phenomenon, required to resist apoptosis and regulate cell cycle activity. The small ubiquitin-related modifier-1 (SUMO), a reversible post-translational protein modifier, plays an important role in embryo development. SUMO regulates multiple cellular processes, including development and other biological processes. The molecular mechanism of diapause, diapause termination and the role of As-sumo-1 in this processes and in early embryo development of Artemia sinica still remains unknown. In this study, the complete cDNA sequences of the sumo-1 homolog, sumo ligase homolog, caspase-1 homolog and cyclin B homolog from Artemia sinica were cloned. The mRNA expression patterns of As-sumo-1, sumo ligase, caspase-1, cyclin B and the location of As-sumo-1 were investigated. SUMO-1, p53, Mdm2, Caspase-1, Cyclin B and Cyclin E proteins were analyzed during different developmental stages of the embryo of A. sinica. Small interfering RNA (siRNA) was used to verify the function of sumo-1 in A. sinica. The full-length cDNA of As-sumo-1 was 476 bp, encoding a 92 amino acid protein. The As-caspases-1 cDNA was 966 bp, encoding a 245 amino-acid protein. The As-sumo ligase cDNA was 1556 bp encoding, a 343 amino acid protein, and the cyclin B cDNA was 739 bp, encoding a 133 amino acid protein. The expressions of As-sumo-1, As-caspase-1 and As-cyclin B were highest at the 10 h stage of embryonic development, and As-sumo ligase showed its highest expression at 0 h. The expression of As-SUMO-1 showed no tissue or organ specificity. Western blotting showed high expression of As-SUMO-1, p53, Mdm2, Caspase-1, Cyclin B and Cyclin E at the 10 h stage. The siRNA caused abnormal development of the embryo, with increased malformation and mortality. As-SUMO-1 is a crucial regulation and modification protein resumption of embryonic diapause and early embryo development of A. sinica. PMID:24404204

Influence of follicle characteristics at ovulation on early embryo survival

USDA-ARS?s Scientific Manuscript database

Reproductive losses are significant in domestic animals and represent huge economic inefficiencies in livestock production. Across livestock species, embryonic mortality is the greatest contributor to reproductive losses. In most livestock species, early pregnancy diagnosis is an impediment to mak...

Kinase-dead ATM protein causes genomic instability and early embryonic lethality in mice.

PubMed

Yamamoto, Kenta; Wang, Yunyue; Jiang, Wenxia; Liu, Xiangyu; Dubois, Richard L; Lin, Chyuan-Sheng; Ludwig, Thomas; Bakkenist, Christopher J; Zha, Shan

2012-08-06

Ataxia telangiectasia (A-T) mutated (ATM) kinase orchestrates deoxyribonucleic acid (DNA) damage responses by phosphorylating numerous substrates implicated in DNA repair and cell cycle checkpoint activation. A-T patients and mouse models that express no ATM protein undergo normal embryonic development but exhibit pleiotropic DNA repair defects. In this paper, we report that mice carrying homozygous kinase-dead mutations in Atm (Atm(KD/KD)) died during early embryonic development. Atm(KD/-) cells exhibited proliferation defects and genomic instability, especially chromatid breaks, at levels higher than Atm(-/-) cells. Despite this increased genomic instability, Atm(KD/-) lymphocytes progressed through variable, diversity, and joining recombination and immunoglobulin class switch recombination, two events requiring nonhomologous end joining, at levels comparable to Atm(-/-) lymphocytes. Together, these results reveal an essential function of ATM during embryogenesis and an important function of catalytically inactive ATM protein in DNA repair.

Early mortality and complications in hospitalized adult Californians with acute myeloid leukaemia.

PubMed

Ho, Gwendolyn; Jonas, Brian A; Li, Qian; Brunson, Ann; Wun, Ted; Keegan, Theresa H M

2017-06-01

Few studies have evaluated the impact of complications, sociodemographic and clinical factors on early mortality (death ≤60 days from diagnosis) in acute myeloid leukaemia (AML) patients. Using data from the California Cancer Registry linked to hospital discharge records from 1999 to 2012, we identified patients aged ≥15 years with AML who received inpatient treatment (N = 6359). Multivariate logistic regression analyses were used to assess the association of complications with early mortality, adjusting for sociodemographic factors, comorbidities and hospital type. Early mortality decreased over time (25·3%, 1999-2000; 16·8%, 2011-2012) across all age groups, but was higher in older patients (6·9%, 15-39, 11·4%, 40-54, 18·6% 55-65, and 35·8%, >65 years). Major bleeding [Odds ratio (OR) 1·5, 95% confidence interval (CI) 1·3-1·9], liver failure (OR 1·9, 95% CI 1·1-3·1), renal failure (OR 2·4, 95% CI 2·0-2·9), respiratory failure (OR 7·6, 95% CI 6·2-9·3) and cardiac arrest (OR 15·8, 95% CI 8·7-28·6) were associated with early mortality. Higher early mortality was also associated with single marital status, low neighbourhood socioeconomic status, lack of health insurance and comorbidities. Treatment at National Cancer Institute-designated cancer centres was associated with lower early mortality (OR 0·5, 95% CI 0·4-0·6). In conclusion, organ dysfunction, hospital type and sociodemographic factors impact early mortality. Further studies should investigate how differences in healthcare delivery affect early mortality. © 2017 John Wiley & Sons Ltd.

Polo-like kinase 1 is essential for early embryonic development and tumor suppression.

PubMed

Lu, Lin-Yu; Wood, Jamie L; Minter-Dykhouse, Katherine; Ye, Lin; Saunders, Thomas L; Yu, Xiaochun; Chen, Junjie

2008-11-01

Polo-like kinases (Plks) are serine/threonine kinases that are highly conserved in organisms from yeasts to humans. Previous reports have shown that Plk1 is critical for all stages of mitosis and may play a role in DNA replication during S phase. While much work has focused on Plk1, little is known about the physiological function of Plk1 in vivo. To address this question, we generated Plk1 knockout mice. Plk1 homozygous null mice were embryonic lethal, and early Plk1(-/-) embryos failed to survive after the eight-cell stage. Immunocytochemistry studies revealed that Plk1-null embryos were arrested outside the mitotic phase, suggesting that Plk1 is important for proper cell cycle progression. It has been postulated that Plk1 is a potential oncogene, due to its overexpression in a variety of tumors and tumor cell lines. While the Plk1 heterozygotes were healthy at birth, the incidence of tumors in these animals was threefold greater than that in their wild-type counterparts, demonstrating that the loss of one Plk1 allele accelerates tumor formation. Collectively, our data support that Plk1 is important for early embryonic development and may function as a haploinsufficient tumor suppressor.

Embryonic death and the creation of human embryonic stem cells.

PubMed

Landry, Donald W; Zucker, Howard A

2004-11-01

The creation of human embryonic stem cells through the destruction of a human embryo pits the value of a potential therapeutic tool against that of an early human life. This contest of values has resulted in a polarized debate that neglects areas of common interest and perspective. We suggest that a common ground for pursuing research on human embryonic stem cells can be found by reconsidering the death of the human embryo and by applying to this research the ethical norms of essential organ donation.

Early events in xenograft development from the human embryonic stem cell line HS181--resemblance with an initial multiple epiblast formation.

PubMed

Gertow, Karin; Cedervall, Jessica; Jamil, Seema; Ali, Rouknuddin; Imreh, Marta P; Gulyas, Miklos; Sandstedt, Bengt; Ahrlund-Richter, Lars

2011-01-01

Xenografting is widely used for assessing in vivo pluripotency of human stem cell populations. Here, we report on early to late events in the development of mature experimental teratoma from a well-characterized human embryonic stem cell (HESC) line, HS181. The results show an embryonic process, increasingly chaotic. Active proliferation of the stem cell derived cellular progeny was detected already at day 5, and characterized by the appearance of multiple sites of engraftment, with structures of single or pseudostratified columnar epithelium surrounding small cavities. The striking histological resemblance to developing embryonic ectoderm, and the formation of epiblast-like structures was supported by the expression of the markers OCT4, NANOG, SSEA-4 and KLF4, but a lack of REX1. The early neural marker NESTIN was uniformly expressed, while markers linked to gastrulation, such as BMP-4, NODAL or BRACHYURY were not detected. Thus, observations on day 5 indicated differentiation comparable to the most early transient cell populations in human post implantation development. Confirming and expanding on previous findings from HS181 xenografts, these early events were followed by an increasingly chaotic development, incorporated in the formation of a benign teratoma with complex embryonic components. In the mature HS181 teratomas not all types of organs/tissues were detected, indicating a restricted differentiation, and a lack of adequate spatial developmental cues during the further teratoma formation. Uniquely, a kinetic alignment of rare complex structures was made to human embryos at diagnosed gestation stages, showing minor kinetic deviations between HS181 teratoma and the human counterpart.

Early onset epilepsy is associated with increased mortality: a population-based study

PubMed Central

Moseley, Brian D.; Wirrell, Elaine C.; Wong-Kisiel, Lily C.; Nickels, Katherine

2013-01-01

SUMMARY We examined mortality in early onset (age <12 months) epilepsy in a population-based group of children. Children with early onset epilepsy were significantly more likely to die (case fatality, CF 8/60 versus 8/407, p<0.001; mortality rate, MR 14.5/1000 versus 2/1000 person years; standardized mortality ratio, SMR 22.25 versus 5.67). Mortality was greater in children with malignant neonatal (age <1 month) epilepsy (CF 4/12 versus 12/450, p<0.001; MR 54/1000 person years versus 2.7/1000 person year; SMR 46.55 versus 7.22). Given that only 1/8 early onset epilepsy deaths was seizure-related, mortality appears to be more affected by underlying etiology. PMID:23582606

Risk factors for early infant mortality in Sarlahi district, Nepal.

PubMed Central

Katz, Joanne; West, Keith P.; Khatry, Subarna K.; Christian, Parul; LeClerq, Steven C.; Pradhan, Elizabeth Kimbrough; Shrestha, Sharada Ram

2003-01-01

OBJECTIVES: Early infant mortality has not declined as rapidly as child mortality in many countries. Identification of risk factors for early infant mortality may help inform the design of intervention strategies. METHODS: Over the period 1994-97, 15,469 live-born, singleton infants in rural Nepal were followed to 24 weeks of age to identify risk factors for mortality within 0-7 days, 8-28 days, and 4-24 weeks after the birth. FINDINGS: In multivariate models, maternal and paternal education reduced mortality between 4 and 24 weeks only: odds ratios (OR) 0.28 (95% confidence interval (CI) = 0.12-0.66) and 0.63 (95% CI = 0.44-0.88), respectively. Miscarriage in the previous pregnancy predicted mortality in the first week of life (OR = 1.98, 95% CI = 1.37-2.87), whereas prior child deaths increased the risk of post-neonatal death (OR = 1.85, 95% CI 1.24-2.75). A larger maternal mid-upper arm circumference reduced the risk of infant death during the first week of life (OR = 0.88, 95% CI = 0.81-0.95). Infants of women who did not receive any tetanus vaccinations during pregnancy or who had severe illness during the third trimester were more likely to die in the neonatal period. Maternal mortality was strongly associated with infant mortality (OR = 6.43, 95% CI = 2.35-17.56 at 0-7 days; OR = 11.73, 95% CI = 3.82-36.00 at 8-28 days; and OR = 51.68, 95% CI = 20.26-131.80 at 4-24 weeks). CONCLUSION: Risk factors for early infant mortality varied with the age of the infant. Factors amenable to intervention included efforts aimed at maternal morbidity and mortality and increased arm circumference during pregnancy. PMID:14758431

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

Early pregnancy factor (EPF) as a marker for detecting subclinical embryonic loss in clomiphene citrate-treated women.

PubMed

Shahani, S K; Moniz, C L; Gokral, J S; Meherji, P K

1995-05-01

A discrepancy exists between the apparently normal ovulation and the pregnancy rates in women treated with clomiphene citrate (CC). Our previous studies have indicated that immuno-suppressive "early pregnancy factor" (EPF) is a novel marker to detect subclinical embryonic loss in infertile women. In the present study EPF was used as a marker to detect subclinical embryonic loss in women treated with CC with/without gonadotropins. In some of the women treated with CC, conception was assisted by artificial insemination with husband's semen (AIH). Our results have indicated that fertilization occurred (EPF + ve) in 47.7% (52/109) of women treated with CC with/without gonadotropins; 13.46% (7/52) retained the fetus and continued pregnancy till full term, whereas 78.9% (41/52) did not retain the fetuses. In the group where after stimulation, conception was assisted by AIH, fertilization was observed in 38.24% (26/68), retention in 11.54% (3/26) but subclinical embryonic loss was observed in 80.8% (21/26) cases. Thus, our results have indicated that subclinical embryonic loss may account for some of the discrepancy observed between the apparently normal ovulation and the pregnancy rates in women treated with clomiphene citrate.

A never-ending succession of epidemics? Mortality in early-modern York.

PubMed

Galley, C

1994-04-01

Early-modern cities are often perceived to be centres of high mortality and under constant siege from a barrage of epidemics. However, few urban mortality rates have been calculated and by employing parish register evidence from the regional capital of York, the thesis that the city was subjected to continual sudden increases in mortality can be firmly rejected. Infant mortality was high but remained virtually constant between 1561 and 1700. About a quarter of all infants did not survive to reach their first birthday and neonatal mortality was especially severe. From the mid-seventeenth century a series of epidemics increased child mortality although overall levels of mortality were not significantly affected. Relatively little can be said about adult mortality and apart from two periods of 'crisis' mortality there is little to suggest that adults were greatly affected by epidemics. Indeed, for many adults the urban environment appears to have posed no great threat to health and most could look forward to a relatively long life in the city. York's mortality regime was very similar to that of the smaller market town of Gainsborough where high levels of mortality remained stable throughout much of the early-modern period.

Student Learning of Early Embryonic Development via the Utilization of Research Resources from the Nematode "Caenorhabditis elegans"

ERIC Educational Resources Information Center

Lu, Fong-Mei; Eliceiri, Kevin W.; Squirrell, Jayne M.; White, John G.; Stewart, James

2008-01-01

This study was undertaken to gain insights into undergraduate students' understanding of early embryonic development, specifically, how well they comprehend the concepts of volume constancy, cell lineages, body plan axes, and temporal and spatial dimensionality in development. To study student learning, a curriculum was developed incorporating…

Identification of positional candidates for bovine placental genes responsible for early embryonic death during cloning-attempted pregnancy.

PubMed

Yamada, Takahisa; Muramatsu, Youji; Taniguchi, Yukio; Sasaki, Yoshiyuki

Our previous study detected 291 and 77 genes showing early embryonic death-associated elevation and reduction of expression, respectively, in the fetal placenta of the cow carrying somatic nuclear transfer-derived cloned embryo. In this study, we mapped the 10 genes showing the elevation and the 10 genes doing the reduction most significantly, using somatic cell hybrid and bovine draft genome sequence. We then compared the mapped positions for these genes with the genomic locations of bovine quantitative trait loci for still-birth and/or abortion. Among the mapped genes, peptidylglycine alpha-amidating monooxygenase (PAM), spectrin, beta, nonerythrocytic 1 (SPTBNI), and an unknown novel gene containing AU277832 expressed sequence tag were intriguing, in that the mapped positions were consistent with the genomic locations of bovine still-birth and/or abortion quantitative trait loci, and thus identified as positional candidates for bovine placental genes responsible for the early embryonic death during the pregnancy attempted by somatic nuclear transfer-derived cloning.

Exogenous determinants of early-life conditions, and mortality later in life.

PubMed

van den Berg, Gerard J; Doblhammer, Gabriele; Christensen, Kaare

2009-05-01

We analyze causal effects of conditions early in life on the individual mortality rate later in life. Conditions early in life are captured by transitory features of the macro-environment around birth, notably the state of the business cycle around birth, but also food price deviations, weather indicators, and demographic indicators. We argue that these features can only affect high-age mortality by way of the individual early-life conditions. Moreover, they are exogenous from the individual point of view, which is a methodological advantage compared to the use of unique characteristics of the newborn individual or his or her family or household as early-life indicators. We collected national annual time-series data on the above-mentioned indicators, and we combine these to the individual data records from the Danish Twin Registry covering births in 1873-1906. The empirical analyses (mostly based on the estimation of duration models) indicate a significant negative causal effect of economic conditions early in life on individual mortality rates at higher ages. If the national economic performance in the year of birth exceeds its trend value (i.e., if the business cycle is favorable) then the mortality rate later in life is lower. The implied effect on the median lifetime of those who survive until age 35 is about 10 months. A systematic empirical exploration of all macro-indicators reveals that economic conditions in the first years after birth also affect mortality rates later in life.

Physiology and Endocrinology Symposium: The current status of heat shock in early embryonic survival and reproductive efficiency

USDA-ARS?s Scientific Manuscript database

The Physiology and Endocrinology Symposium entitled “The Current Status of Heat Shock in Early Embryonic Survival and Reproductive Efficiency” was held at the Joint ADSA-CSAS-AMPA-WSAS-ASAS Meeting in Phoenix, Arizona, July 15 to 19, 2012. In recent years, data has accumulated suggesting a role for...

Embryonic vaccines against cancer: an early history.

PubMed

Brewer, Bradley G; Mitchell, Robert A; Harandi, Amir; Eaton, John W

2009-06-01

Almost 100 years have passed since the seminal observations of Schöne showing that vaccination of animals with fetal tissue would prevent the growth of transplantable tumors. Many subsequent reports have affirmed the general idea that immunologic rejection of transplantable tumors, as well as prevention of carcinogenesis, may be affected by vaccination with embryonic/fetal material. Following a decade of intense research on this phenomenon during approximately 1964-1974, interest appears to have waned. This earlier experimental work may be particularly pertinent in view of the rising interest in so-called cancer stem cells. We believe that further work - perhaps involving the use of embryonic stem cells as immunogens - is warranted and that the results reviewed herein support the concept that vaccination against the appearance of cancers of all kinds is a real possibility.

Florfenicol induces early embryonic death in eggs collected from treated hens.

PubMed

Al-Shahrani, S; Naidoo, V

2015-08-18

Florfenicol, a commonly used veterinary antibiotic, was reported to have caused a severe drop in egg hatchability following its off-label use on a broiler breeder farm in South Africa. According to the pharmacovigilance report, hatchability dropped by 80 % for up to a week following a five day course at 10 mg/kg (both males and females treated metaphylactically) to manage an Escherichia coli infection. While mammalian toxicity studies indicate the potential for early embryonic death in utero or testicular damage, no literature is available on the avian toxicity of florfenicol. For this study we investigated the effects of florfenicol at various doses from 10 to 90 mg/kg on the egg hatchability in a breeder flock we kept and established under controlled conditions, with the same cockerels and hens being exposed in a phased manner. Following five days of oral exposure, no toxic signs were evident in any of the cockerels or hens treated at doses up to 90 mg/kg. Treatment of only the cockerels had no effect on egg hatchability, while treatment of only the hens at doses of 60 and 90 mg/kg resulted in decreased hatchability of 0 % in comparison to 70 % of the control as early 24 h after treatment. In all cases, decreased hatchability was associated with embryonic death at 5 days of development. The toxic effects of florfenicol were completely reversible with comparable hatchability being present by day 4 post-treatment withdrawal. Toxicity correlated with total egg florfenicol concentrations with an LC50 of 1.07 μg/g. Florfenicol appears to be toxic to the developing chick embryo at around day 5 of incubation, in the absence of related toxicity in the hen or cockerel.

Postnatal growth rates covary weakly with embryonic development rates and do not explain adult mortality probability among songbirds on four continents.

PubMed

Martin, Thomas E; Oteyza, Juan C; Mitchell, Adam E; Potticary, Ahva L; Lloyd, Penn

2015-03-01

Growth and development rates may result from genetic programming of intrinsic processes that yield correlated rates between life stages. These intrinsic rates are thought to affect adult mortality probability and longevity. However, if proximate extrinsic factors (e.g., temperature, food) influence development rates differently between stages and yield low covariance between stages, then development rates may not explain adult mortality probability. We examined these issues based on study of 90 songbird species on four continents to capture the diverse life-history strategies observed across geographic space. The length of the embryonic period explained little variation (ca. 13%) in nestling periods and growth rates among species. This low covariance suggests that the relative importance of intrinsic and extrinsic influences on growth and development rates differs between stages. Consequently, nestling period durations and nestling growth rates were not related to annual adult mortality probability among diverse songbird species within or among sites. The absence of a clear effect of faster growth on adult mortality when examined in an evolutionary framework across species may indicate that species that evolve faster growth also evolve physiological mechanisms for ameliorating costs on adult mortality. Instead, adult mortality rates of species in the wild may be determined more strongly by extrinsic environmental causes.

Postnatal growth rates covary weakly with embryonic development rates and do not explain adult mortality probability among songbirds on four continents

USGS Publications Warehouse

Martin, Thomas E.; Oteyza, Juan C.; Mitchell, Adam E.; Potticary, Ahva L.; Lloyd, P.

2016-01-01

Growth and development rates may result from genetic programming of intrinsic processes that yield correlated rates between life stages. These intrinsic rates are thought to affect adult mortality probability and longevity. However, if proximate extrinsic factors (e.g., temperature, food) influence development rates differently between stages and yield low covariance between stages, then development rates may not explain adult mortality probability. We examined these issues based on study of 90 songbird species on four continents to capture the diverse life-history strategies observed across geographic space. The length of the embryonic period explained little variation (ca. 13%) in nestling periods and growth rates among species. This low covariance suggests that the relative importance of intrinsic and extrinsic influences on growth and development rates differs between stages. Consequently, nestling period durations and nestling growth rates were not related to annual adult mortality probability among diverse songbird species within or among sites. The absence of a clear effect of faster growth on adult mortality when examined in an evolutionary framework across species may indicate that species that evolve faster growth also evolve physiological mechanisms for ameliorating costs on adult mortality. Instead, adult mortality rates of species in the wild may be determined more strongly by extrinsic environmental causes.

Optical mapping of conduction in early embryonic quail hearts with light-sheet microscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Ma, Pei; Gu, Shi; Wang, Yves T.; Jenkins, Michael W.; Rollins, Andrew M.

2016-03-01

Optical mapping (OM) using fluorescent voltage-sensitive dyes (VSD) to measure membrane potential is currently the most effective method for electrophysiology studies in early embryonic hearts due to its noninvasiveness and large field-of-view. Conventional OM acquires bright-field images, collecting signals that are integrated in depth and projected onto a 2D plane, not capturing the 3D structure of the sample. Early embryonic hearts, especially at looping stages, have a complicated, tubular geometry. Therefore, conventional OM cannot provide a full picture of the electrical conduction circumferentially around the heart, and may result in incomplete and inaccurate measurements. Here, we demonstrate OM of Hamburger and Hamilton stage 14 embryonic quail hearts using a new commercially-available VSD, Fluovolt, and depth sectioning using a custom built light-sheet microscopy system. Axial and lateral resolution of the system is 14µm and 8µm respectively. For OM imaging, the field-of-view was set to 900µm×900µm to cover the entire heart. 2D over time OM image sets at multiple cross-sections through the looping-stage heart were recorded. The shapes of both atrial and ventricular action potentials acquired were consistent with previous reports using conventional VSD (di-4-ANNEPS). With Fluovolt, signal-to-noise ratio (SNR) is improved significantly by a factor of 2-10 (compared with di-4-ANNEPS) enabling light-sheet OM, which intrinsically has lower SNR due to smaller sampling volumes. Electrophysiologic parameters are rate dependent. Optical pacing was successfully integrated into the system to ensure heart rate consistency. This will also enable accurately gated reconstruction of full four dimensional conduction maps and 3D conduction velocity measurements.

When Is Embryonic Arrest Broken in Turtle Eggs?

PubMed

Williamson, Sean A; Evans, Roger G; Reina, Richard D

Turtle embryos enter a state of arrested development in the oviduct, allowing the mother greater flexibility in her reproductive schedule. Development recommences once eggs transition from the hypoxic oviduct to the normoxic nest. Significant mortality can occur if turtle eggs are moved between 12 h and 20 d after oviposition, and this is linked to the recommencement of embryonic development. To better understand the timing of developmental arrest and to determine how movement-induced mortality might be avoided, we determined the latency (i.e., time elapsed since oviposition) to recommencement of development following oviposition by exposing the eggs of green turtles (Chelonia mydas) to hypoxia (oxygen tension <8 mmHg) for 3 d, commencing 30 min to 48 h after oviposition. Embryonic development-including development of the characteristic opaque white spot on the eggshell-was halted by hypoxic incubation. When the delay before hypoxic incubation was 12 h or less, hatching success did not differ from a control group. If the hypoxic treatment began after 16 h or more in normoxia, then all embryos died. Thus, by returning eggs to a hypoxic environment before they have broken from arrest (i.e., within 12 h of oviposition), it is possible to extend embryonic arrest for at least 3 d, with no apparent detriment to hatching success. Therefore, hypoxic incubation may provide a new approach for avoidance of movement-induced mortality when conservation or research efforts require the relocation of eggs. Our findings also suggest that movement-induced mortality may have constrained the evolution of viviparity in turtles.

Autophagy in Human Embryonic Stem Cells

PubMed Central

Tra, Thien; Gong, Lan; Kao, Lin-Pin; Li, Xue-Lei; Grandela, Catarina; Devenish, Rodney J.; Wolvetang, Ernst; Prescott, Mark

2011-01-01

Autophagy (macroautophagy) is a degradative process that involves the sequestration of cytosolic material including organelles into double membrane vesicles termed autophagosomes for delivery to the lysosome. Autophagy is essential for preimplantation development of mouse embryos and cavitation of embryoid bodies. The precise roles of autophagy during early human embryonic development, remain however largely uncharacterized. Since human embryonic stem cells constitute a unique model system to study early human embryogenesis we investigated the occurrence of autophagy in human embryonic stem cells. We have, using lentiviral transduction, established multiple human embryonic stem cell lines that stably express GFP-LC3, a fluorescent marker for the autophagosome. Each cell line displays both a normal karyotype and pluripotency as indicated by the presence of cell types representative of the three germlayers in derived teratomas. GFP expression and labelling of autophagosomes is retained after differentiation. Baseline levels of autophagy detected in cultured undifferentiated hESC were increased or decreased in the presence of rapamycin and wortmannin, respectively. Interestingly, autophagy was upregulated in hESCs induced to undergo differentiation by treatment with type I TGF-beta receptor inhibitor SB431542 or removal of MEF secreted maintenance factors. In conclusion we have established hESCs capable of reporting macroautophagy and identify a novel link between autophagy and early differentiation events in hESC. PMID:22110659

Distance to Care, Facility Delivery and Early Neonatal Mortality in Malawi and Zambia

PubMed Central

Lohela, Terhi J.; Campbell, Oona M. R.; Gabrysch, Sabine

2012-01-01

Background Globally, approximately 3 million babies die annually within their first month. Access to adequate care at birth is needed to reduce newborn as well as maternal deaths. We explore the influence of distance to delivery care and of level of care on early neonatal mortality in rural Zambia and Malawi, the influence of distance (and level of care) on facility delivery, and the influence of facility delivery on early neonatal mortality. Methods and Findings National Health Facility Censuses were used to classify the level of obstetric care for 1131 Zambian and 446 Malawian delivery facilities. Straight-line distances to facilities were calculated for 3771 newborns in the 2007 Zambia DHS and 8842 newborns in the 2004 Malawi DHS. There was no association between distance to care and early neonatal mortality in Malawi (OR 0.97, 95%CI 0.58–1.60), while in Zambia, further distance (per 10 km) was associated with lower mortality (OR 0.55, 95%CI 0.35–0.87). The level of care provided in the closest facility showed no association with early neonatal mortality in either Malawi (OR 1.02, 95%CI 0.90–1.16) or Zambia (OR 1.02, 95%CI 0.82–1.26). In both countries, distance to care was strongly associated with facility use for delivery (Malawi: OR 0.35 per 10km, 95%CI 0.26–0.46). All results are adjusted for available confounders. Early neonatal mortality did not differ by frequency of facility delivery in the community. Conclusions While better geographic access and higher level of care were associated with more frequent facility delivery, there was no association with lower early neonatal mortality. This could be due to low quality of care for newborns at health facilities, but differential underreporting of early neonatal deaths in the DHS is an alternative explanation. Improved data sources are needed to monitor progress in the provision of obstetric and newborn care and its impact on mortality. PMID:23300599

Early embryonic androgen exposure induces transgenerational epigenetic and metabolic changes.

PubMed

Xu, Ning; Chua, Angela K; Jiang, Hong; Liu, Ning-Ai; Goodarzi, Mark O

2014-08-01

Androgen excess is a central feature of polycystic ovary syndrome (PCOS), which affects 6% to 10% of young women. Mammals exposed to elevated androgens in utero develop PCOS-like phenotypes in adulthood, suggesting fetal origins of PCOS. We hypothesize that excess androgen exposure during early embryonic development may disturb the epigenome and disrupt metabolism in exposed and unexposed subsequent generations. Zebrafish were used to study the underlying mechanism of fetal origins. Embryos were exposed to androgens (testosterone and dihydrotestosterone) early at 26 to 56 hours post fertilization or late at 21 to 28 days post fertilization. Exposed zebrafish (F0) were grown to adults and crossed to generate unexposed offspring (F1). For both generations, global DNA methylation levels were examined in ovaries using a luminometric methylation assay, and fasting and postprandial blood glucose levels were measured. We found that early but not late androgen exposure induced changes in global methylation and glucose homeostasis in both generations. In general, F0 adult zebrafish exhibited altered global methylation levels in the ovary; F1 zebrafish had global hypomethylation. Fasting blood glucose levels were decreased in F0 but increased in F1; postprandial glucose levels were elevated in both F0 and F1. This androgenized zebrafish study suggests that transient excess androgen exposure during early development can result in transgenerational alterations in the ovarian epigenome and glucose homeostasis. Current data cannot establish a causal relationship between epigenetic changes and altered glucose homeostasis. Whether transgenerational epigenetic alteration induced by prenatal androgen exposure plays a role in the development of PCOS in humans deserves study.

Monoamine Oxidases Regulate Telencephalic Neural Progenitors in Late Embryonic and Early Postnatal Development

PubMed Central

Cheng, Aiwu; Scott, Anna L.; Ladenheim, Bruce; Chen, Kevin; Ouyang, Xin; Lathia, Justin D.; Mughal, Mohamed; Cadet, Jean Lud; Mattson, Mark P.; Shih, Jean C.

2010-01-01

Monoamine neurotransmitters play major roles in regulating a range of brain functions in adults and increasing evidence suggests roles for monoamines in brain development. Here we show that mice lacking the monoamine metabolic enzymes MAO A and MAO B (MAO AB-deficient mice) exhibit diminished proliferation of neural stem cells (NSC) in the developing telencephalon beginning in late gestation [embryonic day (E) 17.5], a deficit that persists in neonatal and adult mice. These mice showed significantly increased monoamine levels and anxiety-like behaviors as adults. Assessments of markers of intermediate progenitor cells (IPC) and mitosis showed that NSC in the subventricular zone (SVZ), but not in the ventricular zone, are reduced in MAO AB-deficient mice. A developmental time course of monoamines in frontal cortical tissues revealed increased serotonin levels as early as E14.5, and a further large increase was found between E17.5 and postnatal day 2. Administration of an inhibitor of serotonin synthesis (parachlorophenylalanine) between E14.5 and E19.5 restored the IPC numbers and SVZ thickness, suggesting the role of serotonin in the suppression of IPC proliferation. Studies of neurosphere cultures prepared from the telencephalon at different embryonic and postnatal ages showed that serotonin stimulates proliferation in wild-type, but not in MAO AB-deficient, NSC. Together, these results suggest that a MAO-dependent long-lasting alteration in the proliferation capacity of NSC occurs late in embryonic development and is mediated by serotonin. Our findings reveal novel roles for MAOs and serotonin in the regulation of IPC proliferation in the developing brain. PMID:20702706

Sub-lethal and lethal toxicities of elevated CO2 on embryonic, juvenile, and adult stages of marine medaka Oryzias melastigma.

PubMed

Lee, Changkeun; Kwon, Bong-Oh; Hong, Seongjin; Noh, Junsung; Lee, Junghyun; Ryu, Jongseong; Kang, Seong-Gil; Khim, Jong Seong

2018-06-06

The potential leakage from marine CO 2 storage sites is of increasing concern, but few studies have evaluated the probable adverse effects on marine organisms. Fish, one of the top predators in marine environments, should be an essential representative species used for water column toxicity testing in response to waterborne CO 2 exposure. In the present study, we conducted fish life cycle toxicity tests to fully elucidate CO 2 toxicity mechanism effects. We tested sub-lethal and lethal toxicities of elevated CO 2 concentrations on marine medaka (Oryzias melastigma) at different developmental stages. At each developmental stage, the test species was exposed to varying concentrations of gaseous CO 2 (control air, 5%, 10%, 20%, and 30%), with 96 h of exposure at 0-4 d (early stage), 4-8 d (middle stage), and 8-12 d (late stage). Sub-lethal and lethal effects, including early developmental delays, cardiac edema, tail abnormalities, abnormal pigmentation, and mortality were monitored daily during the 14 d exposure period. At the embryonic stage, significant sub-lethal and lethal effects were observed at pH < 6.30. Hypercapnia can cause long-term and/or delayed developmental embryonic problems, even after transfer back to clean seawater. At fish juvenile and adult stages, significant mortality was observed at pH < 5.70, indicating elevated CO 2 exposure might cause various adverse effects, even during short-term exposure periods. It should be noted the early embryonic stage was found more sensitive to CO 2 exposure than other developmental stages of the fish life cycle. Overall, the present study provided baseline information for potential adverse effects of high CO 2 concentration exposure on fish developmental processes at different life cycle stages in marine ecosystems. Copyright © 2018 Elsevier Ltd. All rights reserved.

Early Embryonic Androgen Exposure Induces Transgenerational Epigenetic and Metabolic Changes

PubMed Central

Xu, Ning; Chua, Angela K.; Jiang, Hong; Liu, Ning-Ai

2014-01-01

Androgen excess is a central feature of polycystic ovary syndrome (PCOS), which affects 6% to 10% of young women. Mammals exposed to elevated androgens in utero develop PCOS-like phenotypes in adulthood, suggesting fetal origins of PCOS. We hypothesize that excess androgen exposure during early embryonic development may disturb the epigenome and disrupt metabolism in exposed and unexposed subsequent generations. Zebrafish were used to study the underlying mechanism of fetal origins. Embryos were exposed to androgens (testosterone and dihydrotestosterone) early at 26 to 56 hours post fertilization or late at 21 to 28 days post fertilization. Exposed zebrafish (F0) were grown to adults and crossed to generate unexposed offspring (F1). For both generations, global DNA methylation levels were examined in ovaries using a luminometric methylation assay, and fasting and postprandial blood glucose levels were measured. We found that early but not late androgen exposure induced changes in global methylation and glucose homeostasis in both generations. In general, F0 adult zebrafish exhibited altered global methylation levels in the ovary; F1 zebrafish had global hypomethylation. Fasting blood glucose levels were decreased in F0 but increased in F1; postprandial glucose levels were elevated in both F0 and F1. This androgenized zebrafish study suggests that transient excess androgen exposure during early development can result in transgenerational alterations in the ovarian epigenome and glucose homeostasis. Current data cannot establish a causal relationship between epigenetic changes and altered glucose homeostasis. Whether transgenerational epigenetic alteration induced by prenatal androgen exposure plays a role in the development of PCOS in humans deserves study. PMID:24992182

The effect of early-life education on later-life mortality.

PubMed

Black, Dan A; Hsu, Yu-Chieh; Taylor, Lowell J

2015-12-01

Many studies link cross-state variation in compulsory schooling laws to early-life educational attainment, thereby providing a plausible way to investigate the causal impact of education on various lifetime outcomes. We use this strategy to estimate the effect of education on older-age mortality of individuals born in the early twentieth century U.S. Our key innovation is to combine U.S. Census data and the complete Vital Statistics records to form precise mortality estimates by sex, birth cohort, and birth state. In turn we find that virtually all of the variation in these mortality rates is captured by cohort effects and state effects alone, making it impossible to reliably tease out any additional impact due to changing educational attainment induced by state-level changes in compulsory schooling. Copyright © 2015. Published by Elsevier B.V.

Ca2+ signaling and early embryonic patterning during the blastula and gastrula periods of zebrafish and Xenopus development.

PubMed

Webb, Sarah E; Miller, Andrew L

2006-11-01

It has been proposed that Ca(2+) signaling, in the form of pulses, waves and steady gradients, may play a crucial role in key pattern forming events during early vertebrate development [L.F. Jaffe, Organization of early development by calcium patterns, BioEssays 21 (1999) 657-667; M.J. Berridge, P. Lipp, M.D. Bootman, The versatility and universality of calcium signaling, Nat. Rev. Mol. Cell Biol. 1 (2000) 11-21; S.E. Webb, A.L. Miller, Calcium signalling during embryonic development, Nat. Rev. Mol. Cell Biol. 4 (2003) 539-551]. With reference to the embryos of zebrafish (Danio rerio) and the frog, Xenopus laevis, we review the Ca(2+) signals reported during the Blastula and Gastrula Periods. This developmental window encompasses the major pattern forming events of epiboly, involution, and convergent extension, which result in the establishment of the basic germ layers and body axes [C.B. Kimmel, W.W. Ballard, S.R. Kimmel, B. Ullmann, T.F. Schilling, Stages of embryonic development of the zebrafish, Dev. Dyn. 203 (1995) 253-310]. Data will be presented to support the suggestion that propagating waves (both long and short range) of Ca(2+) release, followed by sequestration, may play a crucial role in: (1) Coordinating cell movements during these pattern forming events and (2) Contributing to the establishment of the basic embryonic axes, as well as (3) Helping to define the morphological boundaries of specific tissue domains and embryonic structures, including future organ anlagen [E. Gilland, A.L. Miller, E. Karplus, R. Baker, S.E. Webb, Imaging of multicellular large-scale rhythmic calcium waves during zebrafish gastrulation, Proc. Natl. Acad. Sci. USA 96 (1999) 157-161; J.B. Wallingford, A.J. Ewald, R.M. Harland, S.E. Fraser, Calcium signaling during convergent extension in Xenopus, Curr. Biol. 11 (2001) 652-661]. The various potential targets of these Ca(2+) transients will also be discussed, as well as how they might integrate with other known pattern forming

Comparative proteome analysis of Milnesium tardigradum in early embryonic state versus adults in active and anhydrobiotic state.

PubMed

Schokraie, Elham; Warnken, Uwe; Hotz-Wagenblatt, Agnes; Grohme, Markus A; Hengherr, Steffen; Förster, Frank; Schill, Ralph O; Frohme, Marcus; Dandekar, Thomas; Schnölzer, Martina

2012-01-01

Tardigrades have fascinated researchers for more than 300 years because of their extraordinary capability to undergo cryptobiosis and survive extreme environmental conditions. However, the survival mechanisms of tardigrades are still poorly understood mainly due to the absence of detailed knowledge about the proteome and genome of these organisms. Our study was intended to provide a basis for the functional characterization of expressed proteins in different states of tardigrades. High-throughput, high-accuracy proteomics in combination with a newly developed tardigrade specific protein database resulted in the identification of more than 3000 proteins in three different states: early embryonic state and adult animals in active and anhydrobiotic state. This comprehensive proteome resource includes protein families such as chaperones, antioxidants, ribosomal proteins, cytoskeletal proteins, transporters, protein channels, nutrient reservoirs, and developmental proteins. A comparative analysis of protein families in the different states was performed by calculating the exponentially modified protein abundance index which classifies proteins in major and minor components. This is the first step to analyzing the proteins involved in early embryonic development, and furthermore proteins which might play an important role in the transition into the anhydrobiotic state.

Comparative proteome analysis of Milnesium tardigradum in early embryonic state versus adults in active and anhydrobiotic state

PubMed Central

Schokraie, Elham; Warnken, Uwe; Hotz-Wagenblatt, Agnes; Grohme, Markus A.; Hengherr, Steffen; Förster, Frank; Schill, Ralph O.; Frohme, Marcus; Dandekar, Thomas; Schnölzer, Martina

2012-01-01

Tardigrades have fascinated researchers for more than 300 years because of their extraordinary capability to undergo cryptobiosis and survive extreme environmental conditions. However, the survival mechanisms of tardigrades are still poorly understood mainly due to the absence of detailed knowledge about the proteome and genome of these organisms. Our study was intended to provide a basis for the functional characterization of expressed proteins in different states of tardigrades. High-throughput, high-accuracy proteomics in combination with a newly developed tardigrade specific protein database resulted in the identification of more than 3000 proteins in three different states: early embryonic state and adult animals in active and anhydrobiotic state. This comprehensive proteome resource includes protein families such as chaperones, antioxidants, ribosomal proteins, cytoskeletal proteins, transporters, protein channels, nutrient reservoirs, and developmental proteins. A comparative analysis of protein families in the different states was performed by calculating the exponentially modified protein abundance index which classifies proteins in major and minor components. This is the first step to analyzing the proteins involved in early embryonic development, and furthermore proteins which might play an important role in the transition into the anhydrobiotic state. PMID:23029181

How the embryonic chick brain twists.

PubMed

Chen, Zi; Guo, Qiaohang; Dai, Eric; Forsch, Nickolas; Taber, Larry A

2016-11-01

During early development, the tubular embryonic chick brain undergoes a combination of progressive ventral bending and rightward torsion, one of the earliest organ-level left-right asymmetry events in development. Existing evidence suggests that bending is caused by differential growth, but the mechanism for the predominantly rightward torsion of the embryonic brain tube remains poorly understood. Here, we show through a combination of in vitro experiments, a physical model of the embryonic morphology and mechanics analysis that the vitelline membrane (VM) exerts an external load on the brain that drives torsion. Our theoretical analysis showed that the force is of the order of 10 micronewtons. We also designed an experiment to use fluid surface tension to replace the mechanical role of the VM, and the estimated magnitude of the force owing to surface tension was shown to be consistent with the above theoretical analysis. We further discovered that the asymmetry of the looping heart determines the chirality of the twisted brain via physical mechanisms, demonstrating the mechanical transfer of left-right asymmetry between organs. Our experiments also implied that brain flexure is a necessary condition for torsion. Our work clarifies the mechanical origin of torsion and the development of left-right asymmetry in the early embryonic brain. © 2016 The Author(s).

Is a sedentary lifestyle an independent predictor for hospital and early mortality after elective cardiac surgery?

PubMed

Noyez, L; Biemans, I; Verkroost, M; van Swieten, H

2013-10-01

This study evaluates whether a sedentary lifestyle is an independent predictor for increased mortality after elective cardiac surgery. Three thousand one hundred fifty patients undergoing elective cardiac surgery between January 2007 and June 2012 completed preoperatively the Corpus Christi Heart Project questionnaire concerning physical activity (PA). Based on this questionnaire, 1815 patients were classified as active and 1335 patients were classified as sedentary. The endpoints of the study were hospital mortality and early mortality. The study population had a mean age of 69.7 ± 10.1 (19-95) years and a mean logistic EuroSCORE risk of 5.1 ± 5.6 (0.88-73.8). Sedentary patients were significantly older (p = 0.001), obese (p = 0.001), had a higher EuroSCORE risk (p = 0.001), and a higher percentage of complications. Hospital mortality (1.1 % versus 0.4 % (p = 0.014)) and early mortality (1.5 % versus 0.6 % (p = 0.006)) were significantly higher in the sedentary group compared with the active group. However, a sedentary lifestyle was not identified as an independent predictor for hospital mortality (p = 0.61) or early mortality (p = 0.70). Sedentary patients were older, obese and had a higher EuroSCORE risk. They had significantly more postoperative complications, higher hospital mortality and early mortality. Despite these results, sedentary behaviour could not be identified as an independent predictor for hospital or early mortality.

Lethal Dysregulation of Energy Metabolism During Embryonic Vitamin E Deficiency

PubMed Central

McDougall, Melissa; Choi, Jaewoo; Kim, Hye-Kyeong; Bobe, Gerd; Stevens, J. Frederik; Cadenas, Enrique; Tanguay, Robert; Traber, Maret G.

2017-01-01

Vitamin E (α-tocopherol, VitE) was discovered in 1922 for its role in preventing embryonic mortality. We investigated the underlying mechanisms causing lethality using targeted metabolomics analyses of zebrafish VitE-deficient embryos over five days of development, which coincided with their increased morbidity and mortality. VitE deficiency resulted in peroxidation of docosahexaenoic acid (DHA), depleting DHA-containing phospholipids, especially phosphatidylcholine, which also caused choline depletion. This increased lipid peroxidation also increased NADPH oxidation, which depleted glucose by shunting it to the pentose phosphate pathway. VitE deficiency was associated with mitochondrial dysfunction with concomitant impairment of energy homeostasis. The observed morbidity and mortality outcomes could be attenuated, but not fully reversed, by glucose injection into VitE-deficient embryos at developmental day one. Thus, embryonic VitE deficiency in vertebrates leads to a metabolic reprogramming that adversely affects methyl donor status and cellular energy homeostasis with lethal outcomes. PMID:28095320

Conditional deletion of Dicer in vascular smooth muscle cells leads to the developmental delay and embryonic mortality

PubMed Central

Pan, Yaoqian; Balazs, Louisa; Tigyi, Gabor; Yue, Junming

2013-01-01

Dicer is a RNAase III enzyme that cleaves double stranded RNA and generates small interfering RNA (siRNA) and microRNA (miRNA). The goal of this study is to examine the role of Dicer and miRNAs in vascular smooth muscle cells (VSMCs). We deleted Dicer in VSMCs of mice, which caused a developmental delay that manifested as early as embryonic day E12.5, leading to embryonic death between E14.5 and E15.5 due to extensive hemorrhage in the liver, brain, and skin. Dicer KO embryos showed dilated blood vessels and a disarray of vascular architecture between E14.5 and E15.5. VSMC proliferation was significantly inhibited in Dicer KOs. The expression of VSMC marker genes were significantly downregulated in Dicer cKO embryos. The vascular structure of the yolk sac and embryo in Dicer KOs was lost to an extent that no blood vessels could be identified after E15.5. Expression of most miRNAs examined was compromised in VSMCs of Dicer KO. Our results indicate that Dicer is required for vascular development and regulates vascular remodeling by modulating VSMC proliferation and differentiation. PMID:21371421

CNS embryonal tumours: WHO 2016 and beyond.

PubMed

Pickles, J C; Hawkins, C; Pietsch, T; Jacques, T S

2018-02-01

Embryonal tumours of the central nervous system (CNS) present a significant clinical challenge. Many of these neoplasms affect young children, have a very high mortality and therapeutic strategies are often aggressive with poor long-term outcomes. There is a great need to accurately diagnose embryonal tumours, predict their outcome and adapt therapy to the individual patient's risk. For the first time in 2016, the WHO classification took into account molecular characteristics for the diagnosis of CNS tumours. This integration of histological features with genetic information has significantly changed the diagnostic work-up and reporting of tumours of the CNS. However, this remains challenging in embryonal tumours due to their previously unaccounted tumour heterogeneity. We describe the recent revisions made to the 4th edition of the WHO classification of CNS tumours and review the main changes, while highlighting some of the more common diagnostic testing strategies. © 2017 British Neuropathological Society.

Large-scale production of embryonic red blood cells from human embryonic stem cells.

PubMed

Olivier, Emmanuel N; Qiu, Caihong; Velho, Michelle; Hirsch, Rhoda Elison; Bouhassira, Eric E

2006-12-01

To develop a method to produce in culture large number of erythroid cells from human embryonic stem cells. Human H1 embryonic stem cells were differentiated into hematopoietic cells by coculture with a human fetal liver cell line, and the resulting CD34-positive cells were expanded in vitro in liquid culture using a three-step method. The erythroid cells produced were then analyzed by light microscopy and flow cytometry. Globin expression was characterized by quantitative reverse-transcriptase polymerase chain reaction and by high-performance liquid chromatography. CD34-positive cells produced from human embryonic stem cells could be efficiently differentiated into erythroid cells in liquid culture leading to a more than 5000-fold increase in cell number. The erythroid cells produced are similar to primitive erythroid cells present in the yolk sac of early human embryos and did not enucleate. They are fully hemoglobinized and express a mixture of embryonic and fetal globins but no beta-globin. We have developed an experimental protocol to produce large numbers of primitive erythroid cells starting from undifferentiated human embryonic stem cells. As the earliest human erythroid cells, the nucleated primitive erythroblasts, are not very well characterized because experimental material at this stage of development is very difficult to obtain, this system should prove useful to answer a number of experimental questions regarding the biology of these cells. In addition, production of mature red blood cells from human embryonic stem cells is of great potential practical importance because it could eventually become an alternate source of cell for transfusion.

In-hospital and 1-year mortality in patients undergoing early surgery for prosthetic valve endocarditis.

PubMed

Lalani, Tahaniyat; Chu, Vivian H; Park, Lawrence P; Cecchi, Enrico; Corey, G Ralph; Durante-Mangoni, Emanuele; Fowler, Vance G; Gordon, David; Grossi, Paolo; Hannan, Margaret; Hoen, Bruno; Muñoz, Patricia; Rizk, Hussien; Kanj, Souha S; Selton-Suty, Christine; Sexton, Daniel J; Spelman, Denis; Ravasio, Veronica; Tripodi, Marie Françoise; Wang, Andrew

2013-09-09

There are limited prospective, controlled data evaluating survival in patients receiving early surgery vs medical therapy for prosthetic valve endocarditis (PVE). To determine the in-hospital and 1-year mortality in patients with PVE who undergo valve replacement during index hospitalization compared with patients who receive medical therapy alone, after controlling for survival and treatment selection bias. Participants were enrolled between June 2000 and December 2006 in the International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS), a prospective, multinational, observational cohort of patients with infective endocarditis. Patients hospitalized with definite right- or left-sided PVE were included in the analysis. We evaluated the effect of treatment assignment on mortality, after adjusting for biases using a Cox proportional hazards model that included inverse probability of treatment weighting and surgery as a time-dependent covariate. The cohort was stratified by probability (propensity) for surgery, and outcomes were compared between the treatment groups within each stratum. Valve replacement during index hospitalization (early surgery) vs medical therapy. In-hospital and 1-year mortality. Of the 1025 patients with PVE, 490 patients (47.8%) underwent early surgery and 535 individuals (52.2%) received medical therapy alone. Compared with medical therapy, early surgery was associated with lower in-hospital mortality in the unadjusted analysis and after controlling for treatment selection bias (in-hospital mortality: hazard ratio [HR], 0.44 [95% CI, 0.38-0.52] and lower 1-year mortality: HR, 0.57 [95% CI, 0.49-0.67]). The lower mortality associated with surgery did not persist after adjustment for survivor bias (in-hospital mortality: HR, 0.90 [95% CI, 0.76-1.07] and 1-year mortality: HR, 1.04 [95% CI, 0.89-1.23]). Subgroup analysis indicated a lower in-hospital mortality with early surgery in the highest surgical propensity quintile (21

Glycogen and Glucose Metabolism Are Essential for Early Embryonic Development of the Red Flour Beetle Tribolium castaneum

PubMed Central

Fraga, Amanda; Ribeiro, Lupis; Lobato, Mariana; Santos, Vitória; Silva, José Roberto; Gomes, Helga; da Cunha Moraes, Jorge Luiz; de Souza Menezes, Jackson

2013-01-01

Control of energy metabolism is an essential process for life. In insects, egg formation (oogenesis) and embryogenesis is dependent on stored molecules deposited by the mother or transcribed later by the zygote. In oviparous insects the egg becomes an isolated system after egg laying with all energy conversion taking place during embryogenesis. Previous studies in a few vector species showed a strong correlation of key morphogenetic events and changes in glucose metabolism. Here, we investigate glycogen and glucose metabolism in the red flour beetle Tribolium castaneum, an insect amenable to functional genomic studies. To examine the role of the key enzymes on glycogen and glucose regulation we cloned and analyzed the function of glycogen synthase kinase 3 (GSK-3) and hexokinase (HexA) genes during T. castaneum embryogenesis. Expression analysis via in situ hybridization shows that both genes are expressed only in the embryonic tissue, suggesting that embryonic and extra-embryonic cells display different metabolic activities. dsRNA adult female injection (parental RNAi) of both genes lead a reduction in egg laying and to embryonic lethality. Morphological analysis via DAPI stainings indicates that early development is impaired in Tc-GSK-3 and Tc-HexA1 RNAi embryos. Importantly, glycogen levels are upregulated after Tc-GSK-3 RNAi and glucose levels are upregulated after Tc-HexA1 RNAi, indicating that both genes control metabolism during embryogenesis and oogenesis, respectively. Altogether our results show that T. castaneum embryogenesis depends on the proper control of glucose and glycogen. PMID:23750237

Cloning, expression pattern, and potential role of apoptosis inhibitor 5 in the termination of embryonic diapause and early embryo development of Artemia sinica.

PubMed

Zhang, Shuang; Yao, Feng; Jing, Ting; Zhang, Mengchen; Zhao, Wei; Zou, Xiangyang; Sui, Linlin; Hou, Lin

2017-09-10

During the embryonic development of Artemia sinica, the diapause phenomenon can be induced by high salinity or low temperature conditions. The diapause embryo at the gastrula stage is maintained under the threat of apoptosis to guarantee the embryo's normal development. In this process, apoptosis inhibitor proteins play vital roles in protecting embryos against apoptosis. Apoptosis inhibitor5 (API5) plays a pivotal role in regulating the cell cycle and preventing programmed cell death after growth factor starvation. In the present study, we cloned the full-length cDNA representing the api5 gene from A. sinica (As-api5), which encodes a 372-amino acid protein. In situ hybridization experiments revealed that As-api5 expression is not tissue or organ specific. Quantitative real-time PCR analyses of the developmental expression of As-api5 showed that it reached its highest level at 10h, after which its expression decreased. High salinity and low temperature treatments increased the expression of As-api5. Western blotting was used to assess the abundance of As-API5 and related proteins (As-CyclinA, As-CyclinE, As-E2F1, As-CDK2, As-APAF1, and As-Caspase9). Downregulation of As-api5 expression using a short interfering RNA resulted in increased mortality and embryo malformation of A. sinica. Taken together, the results indicated that API5 plays a crucial role in embryonic diapause termination and early embryo development of A. sinica. Copyright © 2017. Published by Elsevier B.V.

Early embryonic demise: no evidence of abnormal spiral artery transformation or trophoblast invasion.

PubMed

Ball, E; Robson, S C; Ayis, S; Lyall, F; Bulmer, J N

2006-03-01

Invasion by extravillous trophoblast of uterine decidua and myometrium and the associated spiral artery 'transformation' are essential for the development of normal pregnancy. Small pilot studies of placental bed and basal plate tissues from miscarriages have suggested that impaired interstitial and endovascular trophoblast invasion may play a role in the pathogenesis of miscarriage. The hypothesis that early miscarriage is associated with reduced extravillous trophoblast invasion and spiral artery transformation was tested in a large series of placental bed biopsies containing decidua and myometrium and at least one spiral artery from early, karyotyped embryonic miscarriages (early miscarriage and also did not differ significantly from normal pregnancy. These findings suggest that failed trophoblast invasion and spiral artery transformation do not have a pivotal role in the pathogenesis of early miscarriage.

Premorbid (early life) IQ and later mortality risk: systematic review.

PubMed

Batty, G David; Deary, Ian J; Gottfredson, Linda S

2007-04-01

Studies of middle-aged and particularly older-aged adults found that those with higher scores on tests of IQ (cognitive function) had lower rates of later mortality. Interpretation of such findings potentially is hampered by the problem of reverse causality: such somatic diseases as diabetes or hypertension, common in older adults, can decrease cognitive function. Studies that provide extended follow-up of the health experience of individuals who had their (premorbid) IQ assessed in childhood and/or early adulthood minimize this concern. The purpose of the present report is to systematically locate, evaluate, and interpret the findings of all such studies. We systematically identified individual-level studies linking premorbid IQ with later mortality by using four approaches: search of electronic databases (MEDLINE, EMBASE, and PSYCHINFO); scrutiny of the reference sections of identified reports; search of our own files; and contact with researchers in the field. Study quality was assessed by using predefined criteria. Nine cohort studies met the inclusion criteria. Overall, study quality was moderate. All reports showed an inverse IQ-mortality relation; i.e., higher IQ scores were associated with decreased mortality risk. The nature of this relation (i.e., dose-response or threshold) and whether it differs by sex was unclear. The IQ-mortality association did not appear to be explained by reverse causality or selection bias. Confounding by other early-life factors also did not seem to explain the association, although some studies were not well characterized in this regard. Adult socioeconomic position appeared to mediate the IQ-mortality association in some studies, but this was not a universal finding. In all studies, higher IQ in the first two decades of life was related to lower rates of total mortality in middle to late adulthood. Some plausible mechanistic pathways exist, but further examination is required. The precise nature of the IQ-mortality relation

Effects of storage conditions on hatchability, embryonic survival and cytoarchitectural properties in broiler from young and old flocks.

PubMed

Pokhrel, N; Cohen, E Ben-Tal; Genin, O; Ruzal, M; Sela-Donenfeld, D; Cinnamon, Y

2018-04-01

Storing eggs at low temperature prior to incubation is common practice in the broiler hatchery industry; however, prolonged storage (beyond 7 d) is known to increase early embryonic mortality and reduce chick quality and performance. To better understand the basis of this mortality, we previously published milestone criteria to evaluate morphological and cellular properties of the freshly laid embryo. Using these criteria, in the present study we checked the effects of storage at 18°C and 12°C for up to 28 d on hatchability and chick quality. Furthermore, using a 3D high-resolution episcopic microscopy (HREM) imaging system combined with standard and confocal microscopy and cell viability markers, we analyzed the effects of the different storage conditions on embryonic developmental stage, cytoarchitectural properties, mitotic index and cell survival. A total of 1,483 eggs from a young flock were divided in 2 groups, 18°C and 12°C, and stored for 7, 14, 21, and 28 d. Following storage, randomly selected 1,222 eggs were incubated, and the hatched chicks were evaluated for chick quality parameters. Nonhatched eggs were also analyzed to determine the stage of embryonic mortality. The remaining 261 eggs were isolated and analyzed for developmental stage, cytoarchitecture, mitotic index, and cell death following storage. Hatchability rates beyond 7 d of storage at 12°C were significantly improved compared to 18°C, and chick quality remained high. Similar results were obtained for an old flock's eggs (n = 1,350). Analyzing the embryos, at each time point, we found that at 12°C, the developmental progression during storage slows significantly, mitotic index-which at this temperature may indicate mitotic arrest-increases and the rate of early apoptosis is half than at 18°C. Moreover, the HREM system and histological sections showed that embryos stored at 18°C for prolonged times undergo dramatic cytoarchitectural changes that may be maladaptive to resuming normal

Distinct requirements for C.elegans TAF(II)s in early embryonic transcription.

PubMed

Walker, A K; Rothman, J H; Shi, Y; Blackwell, T K

2001-09-17

TAF(II)s are conserved components of the TFIID, TFTC and SAGA-related mRNA transcription complexes. In yeast (y), yTAF(II)17 is required broadly for transcription, but various other TAF(II)s appear to have more specialized functions. It is important to determine how TAF(II)s contribute to transcription in metazoans, which have larger and more diverse genomes. We have examined TAF(II) functions in early Caenorhabditis elegans embryos, which can survive without transcription for several cell generations. We show that taf-10 (yTAF(II)17) and taf-11 (yTAF(II)25) are required for a significant fraction of transcription, but apparently are not needed for expression of multiple developmental and other metazoan-specific genes. In contrast, taf-5 (yTAF(II)48; human TAF(II)130) seems to be required for essentially all early embryonic mRNA transcription. We conclude that TAF-10 and TAF-11 have modular functions in metazoans, and can be bypassed at many metazoan-specific genes. The broad involvement of TAF-5 in mRNA transcription in vivo suggests a requirement for either TFIID or a TFTC-like complex.

Early and late mortality of spontaneous hemorrhagic transformation of ischemic stroke.

PubMed

D'Amelio, Marco; Terruso, Valeria; Famoso, Giorgia; Di Benedetto, Norma; Realmuto, Sabrina; Valentino, Francesca; Ragonese, Paolo; Savettieri, Giovanni; Aridon, Paolo

2014-04-01

Hemorrhagic transformation (HT), a complication of ischemic stroke (IS), might influence patient's prognosis. Our aim is to evaluate, in a hospital-based series of patients not treated with thrombolysis, the relationship between HT and mortality. We compared mortality of individuals with spontaneous HT with that of individuals without. Medical records of patients diagnosed with anterior IS were retrospectively reviewed. Outcome measures were 30- and 90-day survival after IS onset. Kaplan-Meier estimates were used to construct survival curves. Cox proportional hazards model was used to estimate hazard ratio (HR) for the main outcome measure (death). HT was stratified in hemorrhagic infarction and parenchymal hematoma (PH). We also evaluated the relationship between HT and the main mortality risk factors (gender, age, premorbid status, severity of stroke, and radiological features). Thirty days from stroke onset, 8.1% (19 of 233) of patients died. At multivariate analysis, PH (HR: 7.7, 95% confidence interval [CI]: 2.1, 27.8) and low level of consciousness at admission (HR: 5.0, 95% CI: 1.3, 18.6) were significantly associated with death. At 3-month follow-up, mortality rate was 12.1% (28 of 232). At multivariate analysis, large infarct size (HR: 2.7, 95% CI: 1.2, 6.0) and HT (HR: 2.3, 95% CI: 1.0, 5.4) were independent risk factors for mortality. Parenchymal hematoma was, however, the strongest predictor of late mortality (HR: 7.9, 95% CI: 2.9, 21.4). Neurological status and infarct size play a significant role, respectively, in early and late mortality after IS. Parenchymal hematoma independently predicts both early and late mortality. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Effect of recombinant-LH and hCG in the absence of FSH on in vitro maturation (IVM) fertilization and early embryonic development of mouse germinal vesicle (GV)-stage oocytes.

PubMed

Dinopoulou, Vasiliki; Drakakis, Peter; Kefala, Stella; Kiapekou, Erasmia; Bletsa, Ritsa; Anagnostou, Elli; Kallianidis, Konstantinos; Loutradis, Dimitrios

2016-06-01

During in vitro maturation (IVM), intrinsic and extrinsic factors must co-operate properly in order to ensure cytoplasmic and nuclear maturation. We examined the possible effect of LH/hCG in the process of oocyte maturation in mice with the addition of recombinant LH (r-LH) and hCG in our IVM cultures of mouse germinal vesicle (GV)-stage oocytes. Moreover, the effects of these hormones on fertilization, early embryonic development and the expression of LH/hCG receptor were examined. Nuclear maturation of GV-stage oocytes was evaluated after culture in the presence of r-LH or hCG. Fertilization rates and embryonic development were assessed after 24h. Total RNA was isolated from oocytes of different stages of maturation and from zygotes and embryos of different stages of development in order to examine the expression of LH/hCG receptor, using RT-PCR. The in vitro nuclear maturation rate of GV-stage oocytes that received hCG was significantly higher compared to the control group. Early embryonic development was increased in the hCG and LH cultures of GV oocytes when LH was further added. The LH/hCG receptor was expressed in all stages of in vitro matured mouse oocytes and in every stage of early embryonic development. Addition of hCG in IVM cultures of mouse GV oocytes increased maturation rates significantly. LH, however, was more beneficial to early embryonic development than hCG. This suggests a promising new technique in basic science research or in clinical reproductive medicine. Copyright © 2016 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

The ‘Ventral Organs’ of Pycnogonida (Arthropoda) Are Neurogenic Niches of Late Embryonic and Post-Embryonic Nervous System Development

PubMed Central

Brenneis, Georg; Scholtz, Gerhard

2014-01-01

Early neurogenesis in arthropods has been in the focus of numerous studies, its cellular basis, spatio-temporal dynamics and underlying genetic network being by now comparably well characterized for representatives of chelicerates, myriapods, hexapods and crustaceans. By contrast, neurogenesis during late embryonic and/or post-embryonic development has received less attention, especially in myriapods and chelicerates. Here, we apply (i) immunolabeling, (ii) histology and (iii) scanning electron microscopy to study post-embryonic ventral nerve cord development in Pseudopallene sp., a representative of the sea spiders (Pycnogonida), the presumable sister group of the remaining chelicerates. During early post-embryonic development, large neural stem cells give rise to additional ganglion cell material in segmentally paired invaginations in the ventral ectoderm. These ectodermal cell regions – traditionally designated as ‘ventral organs’ – detach from the surface into the interior and persist as apical cell clusters on the ventral ganglion side. Each cluster is a post-embryonic neurogenic niche that features a tiny central cavity and initially still houses larger neural stem cells. The cluster stays connected to the underlying ganglionic somata cortex via an anterior and a posterior cell stream. Cell proliferation remains restricted to the cluster and streams, and migration of newly produced cells along the streams seems to account for increasing ganglion cell numbers in the cortex. The pycnogonid cluster-stream-systems show striking similarities to the life-long neurogenic system of decapod crustaceans, and due to their close vicinity to glomerulus-like neuropils, we consider their possible involvement in post-embryonic (perhaps even adult) replenishment of olfactory neurons – as in decapods. An instance of a potentially similar post-embryonic/adult neurogenic system in the arthropod outgroup Onychophora is discussed. Additionally, we document two transient

Markers of pregnancy: how early can we detect pregnancies in cattle using pregnancy-associated glycoproteins (PAGs) and microRNAs?

USDA-ARS?s Scientific Manuscript database

Pregnancy detection has evolved over the last few decades and the importance of early pregnancy detection is critical to minimize the amount of time a cow spends not pregnant or open. Embryonic mortality (EM) is generally considered to be the primary factor limiting pregnancy rates in cattle and occ...

Organogenesis of heart-vascular system derived from mouse 2 cell stage embryos and from early embryonic stem cells in vitro.

PubMed

Ishiwata, Isamu; Tamagawa, Tomoharu; Tokieda, Yuko; Iguchi, Megumi; Sato, Kahei; Ishikawa, Hiroshi

2003-03-01

Regenerative medical treatment with embryonic stem cells (an ES cell) is a goal for organ transplantation. Structures that are tubular in nature (i.e. blood capillaries) were induced from early embryonic stem (EES) cells in vitro using embryotrophic factor (ETFs). In addition, cardiac muscle cells could be identified as well. However, differentiation of EES cells into a complete cardiovascular system was difficult because 3 germ layer primordial organs are directed embryologically in various ways and it is not possible to guide only cardiovascular organs. Thus, we introduced ETFs after the formation of an embryoid body and were successful in cloning cell clusters that beat, thus deriving only cardiovascular organs. The application of this to the treatment of various cardiovascular diseases is promising.

Early mortality in multiple myeloma: the time-dependent impact of comorbidity: A population-based study in 621 real-life patients.

PubMed

Ríos-Tamayo, Rafael; Sáinz, Juan; Martínez-López, Joaquín; Puerta, José Manuel; Chang, Daysi-Yoe-Ling; Rodríguez, Teresa; Garrido, Pilar; de Veas, José Luís García; Romero, Antonio; Moratalla, Lucía; López-Fernández, Elisa; González, Pedro Antonio; Sánchez, María José; Jiménez-Moleón, José Juan; Jurado, Manuel; Lahuerta, Juan José

2016-07-01

Multiple myeloma is a heterogeneous disease with variable survival; this variability cannot be fully explained by the current systems of risk stratification. Early mortality remains a serious obstacle to further improve the trend toward increased survival demonstrated in recent years. However, the definition of early mortality is not standardized yet. Importantly, no study has focused on the impact of comorbidity on early mortality in multiple myeloma to date. Therefore, we analyzed the role of baseline comorbidity in a large population-based cohort of 621 real-life myeloma patients over a 31-year period. To evaluate early mortality, a sequential multivariate regression model at 2, 6, and 12 months from diagnosis was performed. It was demonstrated that comorbidity had an independent impact on early mortality, which is differential and time-dependent. Besides renal failure, respiratory disease at 2 months, liver disease at 6 months, and hepatitis virus C infection at 12 months, were, respectively, associated with early mortality, adjusting for other well-established prognostic factors. On the other hand, the long-term monitoring in our study points out a modest downward trend in early mortality over time. This is the first single institution population-based study aiming to assess the impact of comorbidity on early mortality in multiple myeloma. It is suggested that early mortality should be analyzed at three key time points (2, 6, and 12 months), in order to allow comparisons between studies. Comorbidity plays a critical role in the outcome of myeloma patients in terms of early mortality. Am. J. Hematol. 91:700-704, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Detection of early warning signals of forest mortality in California

NASA Astrophysics Data System (ADS)

Liu, Y.; Kumar, M.; Katul, G. G.; Porporato, A. M.

2017-12-01

Massive forest mortality was observed in California during the most recent drought. Owing to complex interactions of physiological mechanisms under stress, prediction of climate-induced forest mortality using dynamic global vegetation models remains fraught with uncertainty. Given that forest ecosystems approaching mortality tend to exhibit reduction in resilience, we evaluate the time-varying resilience from time series of satellite images to detect early warning signals (EWSs) of mortality. Four metrics of EWSs are used: (1) low greenness, (2) high empirical autocorrelation of greenness, (3) high autocorrelation inferred using a Bayesian dynamic linear model considering the influence of seasonality and climate conditions, and (4) low recovery rate inferred from the drift term in the Langevin equation describing stochastic dynamics. Spatial accuracy and lead-time of these EWSs are evaluated by comparing the EWSs against observed mortality from aerial surveys conducted by the US Forest Service. Our results show that most forested areas in California that underwent mortality exhibit a EWS with a lead time of three months to two years ahead of observed mortality. Notably, EWS is also detected in some areas without mortality, suggesting reduced resilience during drought. Furthermore, the influence of the previous drought (2007-2009) may have propagated into the recent drought (2012-2016) through reduced resilience, hence contributing to the massive forest mortality observed recently. Methodologies developed in this study for detection of EWS will improve the near-term predictability of forest mortality, thus providing crucial information for forest and water resource management.

Early hospital mortality prediction of intensive care unit patients using an ensemble learning approach.

PubMed

Awad, Aya; Bader-El-Den, Mohamed; McNicholas, James; Briggs, Jim

2017-12-01

Mortality prediction of hospitalized patients is an important problem. Over the past few decades, several severity scoring systems and machine learning mortality prediction models have been developed for predicting hospital mortality. By contrast, early mortality prediction for intensive care unit patients remains an open challenge. Most research has focused on severity of illness scoring systems or data mining (DM) models designed for risk estimation at least 24 or 48h after ICU admission. This study highlights the main data challenges in early mortality prediction in ICU patients and introduces a new machine learning based framework for Early Mortality Prediction for Intensive Care Unit patients (EMPICU). The proposed method is evaluated on the Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC-II) database. Mortality prediction models are developed for patients at the age of 16 or above in Medical ICU (MICU), Surgical ICU (SICU) or Cardiac Surgery Recovery Unit (CSRU). We employ the ensemble learning Random Forest (RF), the predictive Decision Trees (DT), the probabilistic Naive Bayes (NB) and the rule-based Projective Adaptive Resonance Theory (PART) models. The primary outcome was hospital mortality. The explanatory variables included demographic, physiological, vital signs and laboratory test variables. Performance measures were calculated using cross-validated area under the receiver operating characteristic curve (AUROC) to minimize bias. 11,722 patients with single ICU stays are considered. Only patients at the age of 16 years old and above in Medical ICU (MICU), Surgical ICU (SICU) or Cardiac Surgery Recovery Unit (CSRU) are considered in this study. The proposed EMPICU framework outperformed standard scoring systems (SOFA, SAPS-I, APACHE-II, NEWS and qSOFA) in terms of AUROC and time (i.e. at 6h compared to 48h or more after admission). The results show that although there are many values missing in the first few hour of ICU admission

In vivo loss of function study reveals the short stature homeobox-containing (shox) gene plays indispensable roles in early embryonic growth and bone formation in zebrafish.

PubMed

Sawada, Rie; Kamei, Hiroyasu; Hakuno, Fumihiko; Takahashi, Shin-Ichiro; Shimizu, Toshiaki

2015-02-01

Congenital loss of the SHOX gene is considered to be a genetic cause of short stature phenotype in Turner syndrome and Leri-Weill dyschondrosteosis patients. Though SHOX expression initiates during early fetal development, little is known about the embryonic roles of SHOX. The evolutionary conservation of the zebrafish shox gene and the convenience of the early developmental stages for analyses make zebrafish a preferred model. Here, we characterized structure, expression, and developmental roles of zebrafish shox through a loss-of-function approach. We found a previously undiscovered Shox protein that has both a homeodomain and an OAR-domain in zebrafish. The shox transcript emerged during the segmentation period and it increased in later stages. The predominant domains of shox expression were mandibular arch, pectoral fin, anterior notochord, rhombencephalon, and mesencephalon, suggesting that Shox is involved in bone and neural development. Translational blockade of Shox mRNA by an antisense morpholino oligo delayed embryonic growth, which was restored by the co-overexpression of morpholino-resistant Shox mRNA. At later stages, impaired Shox expression markedly delayed the calcification process in the anterior vertebral column and craniofacial bones. Our data demonstrate evolutionarily conserved Shox plays roles in early embryonic growth and in later bone formation. © 2014 Wiley Periodicals, Inc.

High early life mortality in free-ranging dogs is largely influenced by humans

PubMed Central

Paul, Manabi; Sen Majumder, Sreejani; Sau, Shubhra; Nandi, Anjan K.; Bhadra, Anindita

2016-01-01

Free-ranging dogs are a ubiquitous part of human habitations in many developing countries, leading a life of scavengers dependent on human wastes for survival. The effective management of free-ranging dogs calls for understanding of their population dynamics. Life expectancy at birth and early life mortality are important factors that shape life-histories of mammals. We carried out a five year-long census based study in seven locations of West Bengal, India, to understand the pattern of population growth and factors affecting early life mortality in free-ranging dogs. We observed high rates of mortality, with only ~19% of the 364 pups from 95 observed litters surviving till the reproductive age; 63% of total mortality being human influenced. While living near people increases resource availability for dogs, it also has deep adverse impacts on their population growth, making the dog-human relationship on streets highly complex. PMID:26804633

Lactate clearance cut off for early mortality prediction in adult sepsis and septic shock patients

NASA Astrophysics Data System (ADS)

Sinto, R.; Widodo, D.; Pohan, H. T.

2018-03-01

Previous lactate clearance cut off for early mortality prediction in sepsis and septic shock patient was determined by consensus from small sample size-study. We investigated the best lactate clearance cut off and its ability to predict early mortality in sepsis and septic shock patients. This cohort study was conducted in Intensive Care Unit of CiptoMangunkusumo Hospital in 2013. Patients’ lactate clearance and eight other resuscitationendpoints were recorded, and theoutcome was observed during the first 120 hours. The clearance cut off was determined using receiver operating characteristic (ROC) analysis, and its ability was investigated with Cox’s proportional hazard regression analysis using other resuscitation endpoints as confounders. Total of 268 subjects was included, of whom 70 (26.11%) subjects died within the first 120 hours. The area under ROC of lactate clearance to predict early mortality was 0.78 (95% % confidence interval [CI] 0.71-0.84) with best cut off was <7.5% (sensitivity and specificity 88.99% and 81.4% respectively). Compared with group achieving lactate clearance target, group not achieving lactate clearance target had to increase early mortality risk (adjusted hazard ratio 13.42; 95%CI 7.19-25.07). In conclusion, the best lactate clearance cut off as anearly mortality predictor in sepsis and septic shock patients is 7.5%.

Early mortality among children and adults in antiretroviral therapy programs in Southwest Ethiopia, 2003-15.

PubMed

Gesesew, Hailay Abrha; Ward, Paul; Woldemichael, Kifle; Mwanri, Lillian

2018-01-01

Several studies reported that the majority of deaths in HIV-infected people are documented in their early antiretroviral therapy (ART) follow-ups. Early mortality refers to death of people on ART for follow up period of below 24 months due to any cause. The current study assessed predictors of early HIV mortality in Southwest Ethiopia. We have conducted a retrospective analysis of 5299 patient records dating from June 2003- March 2015. To estimate survival time and compare the time to event among the different groups of patients, we used a Kaplan Meir curve and log-rank test. To identify mortality predictors, we used a cox regression analysis. We used SPSS-20 for all analyses. A total of 326 patients died in the 12 years follow-up period contributing to 6.2% cumulative incidence and 21.7 deaths per 1000 person-year observations incidence rate. Eighty-nine percent of the total deaths were documented in the first two years follow up-an early-term ART follow up. Early HIV mortality rates among adults were 50% less in separated, divorced or widowed patients compared with never married patients, 1.6 times higher in patients with baseline CD4 count <200 cells/μL compared to baseline CD4 count ≥200 cells/μL, 1.5 times higher in patients with baseline WHO clinical stage 3 or 4 compared to baseline WHO clinical stage 1 or 2, 2.1 times higher in patients with immunologic failure compared with no immunologic failure, 60% less in patients with fair or poor compared with good adherence, 2.9 times higher in patients with bedridden functional status compared to working functional status, and 2.7 times higher with patients who had no history of HIV testing before diagnosis compared to those who had history of HIV testing. Most predictors of early mortality remained the same to the predictors of an overall HIV mortality. When discontinuation was assumed as an event, the predictors of an overall HIV mortality included age between 25-50 years, base line CD4 count, developing

Profiles of mRNA expression of related genes in the duck hypothalamus-pituitary growth axis during embryonic and early post-hatch development.

PubMed

Hu, Yan; Liu, Hongxiang; Song, Chi; Xu, Wenjuan; Ji, Gaige; Zhu, Chunhong; Shu, Jingting; Li, Huifang

2015-03-15

In this study, the ontogeny of body and liver weight and the pattern of related gene mRNA expression in the hypothalamus-pituitary growth axis (HPGA) of two different duck breeds (Anas platyrhynchos domestica) were compared during embryonic and post-hatch development. Duck hypothalamic growth hormone release hormone (GHRH), somatostatin (SS), pituitary growth hormone (GH), liver growth hormone receptor (GHR) and insulin-like growth factor-I (IGF-1) mRNA were first detected on the 13th embryonic day. During early duck development, SS maintained a lower expression status, whereas the other four genes exhibited highly significant variations in an age-specific manner. Highly significant breed specificity was observed with respect to hepatic IGF-1 mRNA expression, which showed a significant breed-age interaction effect. Compared with previous studies on chickens, significant species differences were observed regarding the mRNA expression of bird embryonic HPGA-related genes. During early development, highly significant breed and age specificity were observed with respect to developmental changes in body and liver weight, and varying degrees of significant linear correlation were found between these performances and the mRNA expression of HPGA-related genes in the duck HPGA. These results suggest that different genetic backgrounds may lead to differences in duck growth and HPGA-related gene mRNA expression, and the differential mRNA expression of related genes in the duck HPGA may be particularly important in the early growth of ducks. Furthermore, hepatic IGF-1 mRNA expression presented highly significant breed specificity, and evidence suggests the involvement of hepatic IGF-1 in mediating genetic effects on embryo and offspring growth in ducks. Copyright © 2015 Elsevier B.V. All rights reserved.

Evidence for conjugated linoleic acid-induced embryonic mortality that is independent of egg storage conditions and changes in egg relative fatty acids.

PubMed

Leone, V A; Stransky, D L; Aydin, R; Cook, M E

2009-09-01

Three experiments were performed to determine the effect of conjugated linoleic acid (CLA) on embryonic development in the absence of vitelline membrane disruption. In experiment 1, when eggs from control and CLA (0.5%)-fed hens were stored at 21 or 15 degrees C for 48 h, mineral movement between the yolk and albumen was not observed (with the exception of Mg and Na). Also, it was found that CLA-induced changes in yolk fatty acid content (e.g., increased saturated fatty acids and CLA) had begun to change after 5 d of feeding hens CLA, and no differences were detected in fatty acid composition after 14 d. In experiment 2, the hatchability of eggs incubated directly after oviposition or stored 24 h at 21 or 15 degrees C was determined from hens fed control or 0.5% CLA diets. Regardless of storage conditions, CLA reduced hatchability. These data showed that CLA elicits negative effects on hatchability independent of vitelline membrane disruption or egg storage condition. In experiment 3, eggs were collected from hens fed 0 or 1% CLA daily for 3 wk, stored at 21 degrees C for 24 h, and incubated. Not only did CLA decrease hatchability, the data showed as the days of CLA feeding increased, the days of survival during incubation decreased. Average days of embryonic survival during incubation for the CLA group diminished to 18.0, 13.4, and 6.3 d for wk 1, 2, and 3 of CLA feeding, respectively, and control remained at 20.6, 20.8, and 19.8 for the 3 wk. These studies suggested that without the disruption of the vitelline membrane, hatchability and embryonic days of survival were significantly reduced by maternal CLA feeding in comparison to control-fed hens. Evidence that embryos die earlier the longer the hens are fed CLA, even though no additional changes in the fatty acid content of eggs were found, suggested that factors other than storage and egg yolk fatty acid composition played a role in CLA-induced embryonic mortality.

Knockdown of Fanconi anemia genes in human embryonic stem cells reveals early developmental defects in the hematopoietic lineage.

PubMed

Tulpule, Asmin; Lensch, M William; Miller, Justine D; Austin, Karyn; D'Andrea, Alan; Schlaeger, Thorsten M; Shimamura, Akiko; Daley, George Q

2010-04-29

Fanconi anemia (FA) is a genetically heterogeneous, autosomal recessive disorder characterized by pediatric bone marrow failure and congenital anomalies. The effect of FA gene deficiency on hematopoietic development in utero remains poorly described as mouse models of FA do not develop hematopoietic failure and such studies cannot be performed on patients. We have created a human-specific in vitro system to study early hematopoietic development in FA using a lentiviral RNA interference (RNAi) strategy in human embryonic stem cells (hESCs). We show that knockdown of FANCA and FANCD2 in hESCs leads to a reduction in hematopoietic fates and progenitor numbers that can be rescued by FA gene complementation. Our data indicate that hematopoiesis is impaired in FA from the earliest stages of development, suggesting that deficiencies in embryonic hematopoiesis may underlie the progression to bone marrow failure in FA. This work illustrates how hESCs can provide unique insights into human development and further our understanding of genetic disease.

Function of FEZF1 during early neural differentiation of human embryonic stem cells.

PubMed

Liu, Xin; Su, Pei; Lu, Lisha; Feng, Zicen; Wang, Hongtao; Zhou, Jiaxi

2018-01-01

The understanding of the mechanism underlying human neural development has been hampered due to lack of a cellular system and complicated ethical issues. Human embryonic stem cells (hESCs) provide an invaluable model for dissecting human development because of unlimited self-renewal and the capacity to differentiate into nearly all cell types in the human body. In this study, using a chemical defined neural induction protocol and molecular profiling, we identified Fez family zinc finger 1 (FEZF1) as a potential regulator of early human neural development. FEZF1 is rapidly up-regulated during neural differentiation in hESCs and expressed before PAX6, a well-established marker of early human neural induction. We generated FEZF1-knockout H1 hESC lines using CRISPR-CAS9 technology and found that depletion of FEZF1 abrogates neural differentiation of hESCs. Moreover, loss of FEZF1 impairs the pluripotency exit of hESCs during neural specification, which partially explains the neural induction defect caused by FEZF1 deletion. However, enforced expression of FEZF1 itself fails to drive neural differentiation in hESCs, suggesting that FEZF1 is necessary but not sufficient for neural differentiation from hESCs. Taken together, our findings identify one of the earliest regulators expressed upon neural induction and provide insight into early neural development in human.

Early neonatal mortality in twin pregnancy: Findings from 60 low- and middle-income countries.

PubMed

Bellizzi, Saverio; Sobel, Howard; Betran, Ana Pilar; Temmerman, Marleen

2018-06-01

Around the world, the incidence of multiple pregnancies reaches its peak in the Central African countries and often represents an increased risk of death for women and children because of higher rates of obstetrical complications and poor management skills in those countries. We sought to assess the association between twins and early neonatal mortality compared with singleton pregnancies. We also assessed the role of skilled birth attendant and mode of delivery on early neonatal mortality in twin pregnancies. We conducted a secondary analysis of individual level data from 60 nationally-representative Demographic and Health Surveys including 521 867 singleton and 14 312 twin births. We investigated the occurrence of deaths within the first week of life in twins compared to singletons and the effect of place and attendance at birth; also, the role of caesarean sections against vaginal births was examined, globally and after countries stratification per caesarean sections rates. A multi-level logistic regression was used accounting for homogeneity within country, and homogeneity within twin pairs. Early neonatal mortality among twins was significantly higher when compared to singleton neonates (adjusted odds ratio (aOR) 7.6; 95% confidence interval (CI) = 7.0-8.3) in these 60 countries. Early neonatal mortality was also higher among twins than singletons when adjusting for birth weight in a subgroup analysis of those countries with data on birth weight (n = 20; less than 20% of missing values) (aOR = 2.8; 95% CI = 2.2-3.5). For countries with high rates (>15%) of caesarean sections (CS), twins delivered vaginally in health facility had a statistically significant (aOR = 4.8; 95% CI = 2.4-9.4) increased risk of early neonatal mortality compared to twins delivered through caesarean sections. Home twin births without SBA was associated with increased mortality compared with delivering at home with SBA (aOR = 1.3; 95% CI = 1.0-1.8) and

Early intrauterine embryonic development in Khawia sinensis Hsü, 1935 (Cestoda, Caryophyllidea, Lytocestidae), an invasive tapeworm of carp (Cyprinus carpio): an ultrastructural study.

PubMed

Bruňanská, Magdaléna; Mackiewicz, John S; Młocicki, Daniel; Swiderski, Zdzisław; Nebesářová, Jana

2012-02-01

Intrauterine embryonic development in the caryophyllidean tapeworm Khawia sinensis has been investigated using transmission electron microscopy and cytochemical staining with periodic acid-thiosemicarbazide-silver proteinate for glycogen. Contrary to previous light microscopy findings that reported the release of non-embryonated eggs of K. sinenesis to the external environment, the present study documents various stages of embryonation (ovoviviparity) within the intrauterine eggs of this cestode. At the initial stage of embryonic development, each fertilised oocyte is accompanied by several vitellocytes that become enclosed within the operculate, electrondense shell. Cleavage divisions result in formation of blastomeres (up to about 24 cells) of various sizes. Mitotic divisions and apparent rosette arrangment of the blastomeres, the latter atypical within the Eucestoda, are observed for the first time in the intrauterine eggs of K. sinenesis. The early embryo enclosed within the electrondense shell is surrounded by a thin membraneous layer which in some enlarged regions shows presence of nuclei. Simultaneously to multiplication and differentiation, some of the blastomeres undergo deterioration. A progressive degeneration of the vitellocytes within eggs provides nutritive reserves, including lipids, for the developing embryo. The possible significance of this atypical timing of the intrauterine embryonic development to (1) the ecology of K. sinensis and that of a recent introduction of another invasive tapeworm, the caryophyllidean Atractolytocestus huronensis Anthony, 1958 to Europe; and (2) the affiliation of caryophyllideans with other lower cestodes, are discussed.

Fine-tuning of chromatin composition and Polycomb recruitment by two Mi2 homologues during C. elegans early embryonic development.

PubMed

Käser-Pébernard, Stéphanie; Pfefferli, Catherine; Aschinger, Caroline; Wicky, Chantal

2016-01-01

The nucleosome remodeling and deacetylase complex promotes cell fate decisions throughout embryonic development. Its core enzymatic subunit, the SNF2-like ATPase and Helicase Mi2, is well conserved throughout the eukaryotic kingdom and can be found in multiple and highly homologous copies in all vertebrates and some invertebrates. However, the reasons for such duplications and their implications for embryonic development are unknown. Here we studied the two C. elegans Mi2 homologues, LET-418 and CHD-3, which displayed redundant activities during early embryonic development. At the transcriptional level, these two Mi2 homologues redundantly repressed the expression of a large gene population. We found that LET-418 physically accumulated at TSS-proximal regions on transcriptionally active genomic targets involved in growth and development. Moreover, LET-418 acted redundantly with CHD-3 to block H3K4me3 deposition at these genes. Our study also revealed that LET-418 was partially responsible for recruiting Polycomb to chromatin and for promoting H3K27me3 deposition. Surprisingly, CHD-3 displayed opposite activities on Polycomb, as it was capable of moderating its LET-418-dependent recruitment and restricted the amount of H3K27me3 on the studied target genes. Although closely homologous, LET-418 and CHD-3 showed both redundant and opposite functions in modulating the chromatin environment at developmental target genes. We identified the interplay between LET-418 and CHD-3 to finely tune the levels of histone marks at developmental target genes. More than just repressors, Mi2-containing complexes appear as subtle modulators of gene expression throughout development. The study of such molecular variations in vertebrate Mi2 counterparts might provide crucial insights to our understanding of the epigenetic control of early development.

Anthropogenic noise playback impairs embryonic development and increases mortality in a marine invertebrate

NASA Astrophysics Data System (ADS)

Nedelec, Sophie L.; Radford, Andrew N.; Simpson, Stephen D.; Nedelec, Brendan; Lecchini, David; Mills, Suzanne C.

2014-07-01

Human activities can create noise pollution and there is increasing international concern about how this may impact wildlife. There is evidence that anthropogenic noise may have detrimental effects on behaviour and physiology in many species but there are few examples of experiments showing how fitness may be directly affected. Here we use a split-brood, counterbalanced, field experiment to investigate the effect of repeated boat-noise playback during early life on the development and survival of a marine invertebrate, the sea hare Stylocheilus striatus at Moorea Island (French Polynesia). We found that exposure to boat-noise playback, compared to ambient-noise playback, reduced successful development of embryos by 21% and additionally increased mortality of recently hatched larvae by 22%. Our work, on an understudied but ecologically and socio-economically important taxon, demonstrates that anthropogenic noise can affect individual fitness. Fitness costs early in life have a fundamental influence on population dynamics and resilience, with potential implications for community structure and function.

The role of marriage in the causal pathway from economic conditions early in life to mortality.

PubMed

van den Berg, Gerard J; Gupta, Sumedha

2015-03-01

This paper analyzes the interplay between early-life conditions and marital status, as determinants of adult mortality. We use individual data from Dutch registers (years 1815-2000), combined with business cycle conditions in childhood as indicators of early-life conditions. The empirical analysis estimates bivariate duration models of marriage and mortality, allowing for unobserved heterogeneity. Results show that conditions around birth and school going ages are important for marriage and mortality. Men typically enjoy a protective effect of marriage, whereas women suffer during childbearing ages. However, having been born under favorable economic conditions reduces female mortality during childbearing ages. Copyright © 2014 Elsevier B.V. All rights reserved.

Radiation hazards of radio frequency waves on the early embryonic development of Zebrafish

NASA Astrophysics Data System (ADS)

Harkless, Ryan; Al-Quraishi, Muntather; Vagula, Mary C.

2014-06-01

With the growing use of wireless devices in almost all day-to-day activities, exposure to radio-frequency radiation has become an immediate health concern. It is imperative that the effects of such radiation not only on humans, but also on other organisms be well understood. In particular, it is critical to understand if RF radiation has any bearing on the gene expression during embryonic development, as this is a crucial and delicate phase for any organism. Owing to possible effects that RF radiation may have on gene expression, it is essential to explore the carcinogenic or teratogenic properties that it may show. This study observed the effects of RF radiation emitted from a cellular telephone on the embryonic development of zebra fish. The expression of the gene shha plays a key role in the early development of the fish. This gene has homologs in humans as well as in other model organisms. Additionally, several biomarkers indicative of cell stress were examined: including lactate dehydrogenase (LDH), superoxide dismutase (SOD), and lipid peroxidation (LPO). Results show a significant decrease in the expression of shha, a significant decrease in LDH activity. There was no significant increase in SOD and LPO activity. No morphological abnormalities were observed in the developing embryos. At present, these results indicate that exposure to cell phone radiation may have a suppressive effect on expression of shha in D. rerio, though such exposure does not appear to cause morphological detriments. More trials are underway to corroborate these results.

Impaired Embryonic Development in Mice Overexpressing the RNA-Binding Protein TIAR

PubMed Central

Kharraz, Yacine; Salmand, Pierre-Adrien; Camus, Anne; Auriol, Jacques; Gueydan, Cyril; Kruys, Véronique; Morello, Dominique

2010-01-01

Background TIA-1-related (TIAR) protein is a shuttling RNA-binding protein involved in several steps of RNA metabolism. While in the nucleus TIAR participates to alternative splicing events, in the cytoplasm TIAR acts as a translational repressor on specific transcripts such as those containing AU-Rich Elements (AREs). Due to its ability to assemble abortive pre-initiation complexes coalescing into cytoplasmic granules called stress granules, TIAR is also involved in the general translational arrest observed in cells exposed to environmental stress. However, the in vivo role of this protein has not been studied so far mainly due to severe embryonic lethality upon tiar invalidation. Methodology/Principal Findings To examine potential TIAR tissue-specificity in various cellular contexts, either embryonic or adult, we constructed a TIAR transgenic allele (loxPGFPloxPTIAR) allowing the conditional expression of TIAR protein upon Cre recombinase activity. Here, we report the role of TIAR during mouse embryogenesis. We observed that early TIAR overexpression led to low transgene transmission associated with embryonic lethality starting at early post-implantation stages. Interestingly, while pre-implantation steps evolved correctly in utero, in vitro cultured embryos were very sensitive to culture medium. Control and transgenic embryos developed equally well in the G2 medium, whereas culture in M16 medium led to the phosphorylation of eIF2α that accumulated in cytoplasmic granules precluding transgenic blastocyst hatching. Our results thus reveal a differential TIAR-mediated embryonic response following artificial or natural growth environment. Conclusions/Significance This study reports the importance of the tightly balanced expression of the RNA-binding protein TIAR for normal embryonic development, thereby emphasizing the role of post-transcriptional regulations in early embryonic programming. PMID:20596534

Early neonatal mortality in twin pregnancy: Findings from 60 low- and middle-income countries

PubMed Central

Bellizzi, Saverio; Sobel, Howard; Betran, Ana Pilar; Temmerman, Marleen

2018-01-01

Background Around the world, the incidence of multiple pregnancies reaches its peak in the Central African countries and often represents an increased risk of death for women and children because of higher rates of obstetrical complications and poor management skills in those countries. We sought to assess the association between twins and early neonatal mortality compared with singleton pregnancies. We also assessed the role of skilled birth attendant and mode of delivery on early neonatal mortality in twin pregnancies. Methods We conducted a secondary analysis of individual level data from 60 nationally-representative Demographic and Health Surveys including 521 867 singleton and 14 312 twin births. We investigated the occurrence of deaths within the first week of life in twins compared to singletons and the effect of place and attendance at birth; also, the role of caesarean sections against vaginal births was examined, globally and after countries stratification per caesarean sections rates. A multi-level logistic regression was used accounting for homogeneity within country, and homogeneity within twin pairs. Results Early neonatal mortality among twins was significantly higher when compared to singleton neonates (adjusted odds ratio (aOR) 7.6; 95% confidence interval (CI) = 7.0-8.3) in these 60 countries. Early neonatal mortality was also higher among twins than singletons when adjusting for birth weight in a subgroup analysis of those countries with data on birth weight (n = 20; less than 20% of missing values) (aOR = 2.8; 95% CI = 2.2-3.5). For countries with high rates (>15%) of caesarean sections (CS), twins delivered vaginally in health facility had a statistically significant (aOR = 4.8; 95% CI = 2.4-9.4) increased risk of early neonatal mortality compared to twins delivered through caesarean sections. Home twin births without SBA was associated with increased mortality compared with delivering at home with SBA (aOR = 1

Embryonic lethality is not sufficient to explain hourglass-like conservation of vertebrate embryos.

PubMed

Uchida, Yui; Uesaka, Masahiro; Yamamoto, Takayoshi; Takeda, Hiroyuki; Irie, Naoki

2018-01-01

Understanding the general trends in developmental changes during animal evolution, which are often associated with morphological diversification, has long been a central issue in evolutionary developmental biology. Recent comparative transcriptomic studies revealed that gene expression profiles of mid-embryonic period tend to be more evolutionarily conserved than those in earlier or later periods. While the hourglass-like divergence of developmental processes has been demonstrated in a variety of animal groups such as vertebrates, arthropods, and nematodes, the exact mechanism leading to this mid-embryonic conservation remains to be clarified. One possibility is that the mid-embryonic period (pharyngula period in vertebrates) is highly prone to embryonic lethality, and the resulting negative selections lead to evolutionary conservation of this phase. Here, we tested this "mid-embryonic lethality hypothesis" by measuring the rate of lethal phenotypes of three different species of vertebrate embryos subjected to two kinds of perturbations: transient perturbations and genetic mutations. By subjecting zebrafish ( Danio rerio ), African clawed frog ( Xenopus laevis ), and chicken ( Gallus gallus ) embryos to transient perturbations, namely heat shock and inhibitor treatments during three developmental periods [early (represented by blastula and gastrula), pharyngula, and late], we found that the early stages showed the highest rate of lethal phenotypes in all three species. This result was corroborated by perturbation with genetic mutations. By tracking the survival rate of wild-type embryos and embryos with genetic mutations induced by UV irradiation in zebrafish and African clawed frogs, we found that the highest decrease in survival rate was at the early stages particularly around gastrulation in both these species. In opposition to the "mid-embryonic lethality hypothesis," our results consistently showed that the stage with the highest lethality was not around the

Measurement of wall shear stress in chick embryonic heart using optical coherence tomography

NASA Astrophysics Data System (ADS)

Ma, Zhenhe; Dou, Shidan; Zhao, Yuqian; Wang, Yi; Suo, Yanyan; Wang, Fengwen

2015-03-01

The cardiac development is a complicated process affected by genetic and environmental factors. Wall shear stress (WSS) is one of the components which have been proved to influence the morphogenesis during early stages of cardiac development. To study the mechanism, WSS measurement is a step with significant importance. WSS is caused by blood flow imposed on the inner surface of the heart wall and it can be determined by calculating velocity gradients of blood flow in a direction perpendicular to the wall. However, the WSS of the early stage embryonic heart is difficult to measure since the embryonic heart is tiny and beating fast. Optical coherence tomography (OCT) is a non-invasive imaging modality with high spatial and temporal resolution, which is uniquely suitable for the study of early stage embryonic heart development. In this paper, we introduce a method to measure the WSS of early stage chick embryonic heart based on high speed spectral domain optical coherence tomography (SDOCT). 4D (x,y,z,t) scan was performed on the outflow tract (OFT) of HH18 (~3 days of incubation) chick embryonic heart. After phase synchronization, OFT boundary segmentation, and OFT center line calculation, Doppler angle of the blood flow in the OFT can be achieved (This method has been described in previous publications). Combining with the Doppler OCT results, we calculate absolute blood flow velocity distribution in the OFT. The boundary of the OFT was segmented at each cross-sectional structural image, then geometrical center of the OFT can be calculated. Thus, the gradients of blood flow in radial direction can be calculated. This velocity gradient near the wall is termed wall shear rate and the WSS value is proportional to the wall shear rate. Based on this method, the WSS at different heart beating phase are compare. The result demonstrates that OCT is capable of early stage chicken embryonic heart WSS study.

Does shared family background influence the impact of educational differences on early mortality?

PubMed

Søndergaard, Grethe; Mortensen, Laust H; Nybo Andersen, Anne-Marie; Andersen, Per Kragh; Dalton, Susanne Oksbjerg; Madsen, Mia; Osler, Merete

2012-10-15

The mechanisms behind social differences in mortality rates have been debated. The authors examined the extent to which shared family background and health in early life could explain the association between educational status and all-cause mortality rates using a sibling design. The study was register-based and included all individuals born in Denmark between 1950 and 1979 who had at least 1 full sibling born in the same time period (n = 1,381,436). All individuals were followed from 28 years of age until death, emigration, or December 2009. The authors used Cox regression analyses to estimate hazard ratios for mortality according to educational level. Conventional cohort and intersibling analyses were carried out and conducted separately for deaths occurring before and after the age of 45 years, respectively. The cohort analyses showed an inverse association between educational status and all-cause mortality that was strongest for males, increased with younger birth cohorts, and tended to be strongest in the analyses of death before 45 years of age. The associations were attenuated slightly in the intersibling analyses and after adjustment for serious health conditions in early life. Hence, health selection and confounding by factors shared by siblings explained only a minor part of the association between educational level and all-cause mortality.

Predicting Early Mortality After Hip Fracture Surgery: The Hip Fracture Estimator of Mortality Amsterdam.

PubMed

Karres, Julian; Kieviet, Noera; Eerenberg, Jan-Peter; Vrouenraets, Bart C

2018-01-01

Early mortality after hip fracture surgery is high and preoperative risk assessment for the individual patient is challenging. A risk model could identify patients in need of more intensive perioperative care, provide insight in the prognosis, and allow for risk adjustment in audits. This study aimed to develop and validate a risk prediction model for 30-day mortality after hip fracture surgery: the Hip fracture Estimator of Mortality Amsterdam (HEMA). Data on 1050 consecutive patients undergoing hip fracture surgery between 2004 and 2010 were retrospectively collected and randomly split into a development cohort (746 patients) and validation cohort (304 patients). Logistic regression analysis was performed in the development cohort to determine risk factors for the HEMA. Discrimination and calibration were assessed in both cohorts using the area under the receiver operating characteristic curve (AUC), the Hosmer-Lemeshow goodness-of-fit test, and by stratification into low-, medium- and high-risk groups. Nine predictors for 30-day mortality were identified and used in the final model: age ≥85 years, in-hospital fracture, signs of malnutrition, myocardial infarction, congestive heart failure, current pneumonia, renal failure, malignancy, and serum urea >9 mmol/L. The HEMA showed good discrimination in the development cohort (AUC = 0.81) and the validation cohort (AUC = 0.79). The Hosmer-Lemeshow test indicated no lack of fit in either cohort (P > 0.05). The HEMA is based on preoperative variables and can be used to predict the risk of 30-day mortality after hip fracture surgery for the individual patient. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Prognostic indices for early mortality in ischaemic stroke - meta-analysis.

PubMed

Mattishent, K; Kwok, C S; Mahtani, A; Pelpola, K; Myint, P K; Loke, Y K

2016-01-01

Several models have been developed to predict mortality in ischaemic stroke. We aimed to evaluate systematically the performance of published stroke prognostic scores. We searched MEDLINE and EMBASE in February 2014 for prognostic models (published between 2003 and 2014) used in predicting early mortality (<6 months) after ischaemic stroke. We evaluated discriminant ability of the tools through meta-analysis of the area under the curve receiver operating characteristic curve (AUROC) or c-statistic. We evaluated the following components of study validity: collection of prognostic variables, neuroimaging, treatment pathways and missing data. We identified 18 articles (involving 163 240 patients) reporting on the performance of prognostic models for mortality in ischaemic stroke, with 15 articles providing AUC for meta-analysis. Most studies were either retrospective, or post hoc analyses of prospectively collected data; all but three reported validation data. The iSCORE had the largest number of validation cohorts (five) within our systematic review and showed good performance in four different countries, pooled AUC 0.84 (95% CI 0.82-0.87). We identified other potentially useful prognostic tools that have yet to be as extensively validated as iSCORE - these include SOAR (2 studies, pooled AUC 0.79, 95% CI 0.78-0.80), GWTG (2 studies, pooled AUC 0.72, 95% CI 0.72-0.72) and PLAN (1 study, pooled AUC 0.85, 95% CI 0.84-0.87). Our meta-analysis has identified and summarized the performance of several prognostic scores with modest to good predictive accuracy for early mortality in ischaemic stroke, with the iSCORE having the broadest evidence base. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Early effects of embryonic movement: ‘a shot out of the dark’

PubMed Central

Pitsillides, Andrew A

2006-01-01

It has long been appreciated that studying the embryonic chick in ovo provides a variety of advantages, including the potential to control the embryo's environment and its movement independently of maternal influences. This allowed early workers to identify movement as a pivotal factor in the development of the locomotor apparatus. With an increasing focus on the earliest detectable movements, we have exploited this system by developing novel models and schemes to examine the influence of defined periods of movement during musculoskeletal development. Utilizing drugs with known neuromuscular actions to provoke hyperactivity (4-aminopyridine, AP) and either rigid (decamethonium bromide, DMB) or flaccid (pancuronium bromide, PB) paralysis, we have examined the role of movement in joint, osteochondral and muscle development. Our initial studies focusing on the joint showed that AP-induced hyperactivity had little, if any, effect on the timing or scope of joint cavity elaboration, suggesting that endogenous activity levels provide sufficient stimulus, and additional mobilization is without effect. By contrast, imposition of either rigid or flaccid paralysis prior to cavity formation completely blocked this process and, with time, produced fusion of cartilaginous elements and formation of continuous single cartilaginous rods across locations where joints would ordinarily form. The effect of these distinct forms of paralysis differed, however, when treatment was initiated after formation of an overt cavity; rigid, but not flaccid, paralysis partly conserved precavitated joints. This observation suggests that ‘static’ loading derived from ‘spastic’ rigidity can act to preserve joint cavities. Another facet of these studies was the observation that DMB-induced rigid paralysis produces a uniform and specific pattern of limb deformity whereas PB generated a diverse range of fixed positional deformities. Both also reduced limb growth, with different developmental

Natural selection and sex differences in morbidity and mortality in early life.

PubMed

Wells, J C

2000-01-07

Both morbidity and mortality are consistently reported to be higher in males than in females in early life, but no explanation for these findings has been offered. This paper argues that the sex difference in early vulnerability can be attributed to the natural selection of optimal maternal strategies for maximizing lifetime reproductive success, as modelled previously by Trivers and Willard. These authors theorized that males and females offer different returns on parental investment depending on the state of the environment. Natural selection has therefore favoured maternal ability to manipulate offspring sex in response to environmental conditions in early life, as shown in variation in the sex ratio at birth. This argument can be extended to the whole period of parental investment until weaning. Male vulnerability in response to environmental stress in early life is predicted to have been favoured by natural selection. This vulnerability is most evident in the harsh conditions resulting from pre-term birth, but can also be seen in term infants, and manifests as greater morbidity and mortality persisting into early childhood. Malnutrition, interacting with infection after birth, is suggested as the fundamental trigger mechanism. The model suggests that whatever improvements are made in medical care, any environmental stress will always affect males more severely than females in early life. Copyright 2000 Academic Press.

Predictors of early mortality after rabbit antithymocyte globulin as first-line treatment in severe aplastic anemia.

PubMed

Atta, Elias H; Lima, Carlos B L; Dias, Danielle S P; Clé, Diego V; Bonduel, Mariana M; Sciuccati, Gabriela B; Medeiros, Larissa A; Oliveira, Michel M; Salvino, Marco A; Garanito, Marlene P; Blum Fonseca, Patricia B; Saad, Sara Teresinha O; Calado, Rodrigo T; Scheinberg, Phillip

2017-11-01

Despite being recommended as first-line immunosuppressive therapy in severe aplastic anemia (SAA), horse antithymocyte globulin (ATG) is still unavailable in many countries outside the USA. Rabbit ATG is more lymphocytoxic than horse ATG, and this might result in a higher incidence of severe infections and early mortality. This study was designed to identify the risk factors for early mortality and overall survival (OS) after rabbit ATG in patients with SAA. We retrospectively reviewed 185 patients with SAA who underwent rabbit ATG and cyclosporine. The incidence of death in 3 months following rabbit ATG therapy was 15.1% (28/185). Early mortality was mainly related to infectious complications, despite adequate antibiotic and/or antifungal treatment. Age > 35 years (odds ratio [OR] 5.06, P = 0.001) and baseline absolute neutrophil count (ANC) ≤ 0.1 × 10 9 /L (OR 7.64, P < 0.001) were independent risk factors for early mortality after immunosuppressive therapy with this agent. Hematological response at 6 months was observed in only 29.7% of all patients. OS at 1 year after rabbit ATG was 75.3%; and age > 35 years (OR 1.88, P = 0.03), baseline ANC ≤ 0.1 × 10 9 /L (OR 2.65, P < 0.001), and lack of response to rabbit ATG (OR 11.40, P < 0.001) were independently associated with mortality. Alternative strategies are needed for the treatment of SAA patients in countries were horse ATG is unavailable, particularly for those at high risk for early mortality after rabbit ATG due to a higher age and very low pre-treatment neutrophil count.

Partitioning loss rates of early juvenile blue crabs from seagrass habitats into mortality and emigration

USGS Publications Warehouse

Etherington, L.L.; Eggleston, D.B.; Stockhausen, W.T.

2003-01-01

Determining how post-settlement processes modify patterns of settlement is vital in understanding the spatial and temporal patterns of recruitment variability of species with open populations. Generally, either single components of post-settlement loss (mortality or emigration) are examined at a time, or else the total loss is examined without discrimination of mortality and emigration components. The role of mortality in the loss of early juvenile blue crabs, Callinectes sapidus, has been addressed in a few studies; however, the relative contribution of emigration has received little attention. We conducted mark-recapture experiments to examine the relative contribution of mortality and emigration to total loss rates of early juvenile blue crabs from seagrass habitats. Loss was partitioned into emigration and mortality components using a modified version of Jackson's (1939) square-within-a-square method. The field experiments assessed the effects of two size classes of early instars (J1-J2, J3-J5), two densities of juveniles (low: 16 m-2, high: 64 m-2), and time of day (day, night) on loss rates. In general, total loss rates of experimental juveniles and colonization rates by unmarked juveniles were extremely high (range = 10-57 crabs m-2/6 h and 17-51 crabs m-2/6 h, for loss and colonization, respectively). Total loss rates were higher at night than during the day, suggesting that juveniles (or potentially their predators) exhibit increased nocturnal activity. While colonization rates did not differ by time of day, J3-J5 juveniles demonstrated higher rates of colonization than J1-J2 crabs. Overall, there was high variability in both mortality and emigration, particularly for emigration. Average probabilities of mortality across all treatment combinations ranged from 0.25-0.67/6 h, while probabilities of emigration ranged from 0.29-0.72/6 h. Although mean mortality rates were greater than emigration rates in most treatments, the proportion of experimental trials

A predictive model for early mortality after surgical treatment of heart valve or prosthesis infective endocarditis. The EndoSCORE.

PubMed

Di Mauro, Michele; Dato, Guglielmo Mario Actis; Barili, Fabio; Gelsomino, Sandro; Santè, Pasquale; Corte, Alessandro Della; Carrozza, Antonio; Ratta, Ester Della; Cugola, Diego; Galletti, Lorenzo; Devotini, Roger; Casabona, Riccardo; Santini, Francesco; Salsano, Antonio; Scrofani, Roberto; Antona, Carlo; Botta, Luca; Russo, Claudio; Mancuso, Samuel; Rinaldi, Mauro; De Vincentiis, Carlo; Biondi, Andrea; Beghi, Cesare; Cappabianca, Giangiuseppe; Tarzia, Vincenzo; Gerosa, Gino; De Bonis, Michele; Pozzoli, Alberto; Nicolini, Francesco; Benassi, Filippo; Rosato, Francesco; Grasso, Elena; Livi, Ugolino; Sponga, Sandro; Pacini, Davide; Di Bartolomeo, Roberto; De Martino, Andrea; Bortolotti, Uberto; Onorati, Francesco; Faggian, Giuseppe; Lorusso, Roberto; Vizzardi, Enrico; Di Giammarco, Gabriele; Marinelli, Daniele; Villa, Emmanuel; Troise, Giovanni; Picichè, Marco; Musumeci, Francesco; Paparella, Domenico; Margari, Vito; Tritto, Francesco; Damiani, Girolamo; Scrascia, Giuseppe; Zaccaria, Salvatore; Renzulli, Attilio; Serraino, Giuseppe; Mariscalco, Giovanni; Maselli, Daniele; Foschi, Massimiliano; Parolari, Alessandro; Nappi, Giannantonio

2017-08-15

The aim of this large retrospective study was to provide a logistic risk model along an additive score to predict early mortality after surgical treatment of patients with heart valve or prosthesis infective endocarditis (IE). From 2000 to 2015, 2715 patients with native valve endocarditis (NVE) or prosthesis valve endocarditis (PVE) were operated on in 26 Italian Cardiac Surgery Centers. The relationship between early mortality and covariates was evaluated with logistic mixed effect models. Fixed effects are parameters associated with the entire population or with certain repeatable levels of experimental factors, while random effects are associated with individual experimental units (centers). Early mortality was 11.0% (298/2715); At mixed effect logistic regression the following variables were found associated with early mortality: age class, female gender, LVEF, preoperative shock, COPD, creatinine value above 2mg/dl, presence of abscess, number of treated valve/prosthesis (with respect to one treated valve/prosthesis) and the isolation of Staphylococcus aureus, Fungus spp., Pseudomonas Aeruginosa and other micro-organisms, while Streptococcus spp., Enterococcus spp. and other Staphylococci did not affect early mortality, as well as no micro-organisms isolation. LVEF was found linearly associated with outcomes while non-linear association between mortality and age was tested and the best model was found with a categorization into four classes (AUC=0.851). The following study provides a logistic risk model to predict early mortality in patients with heart valve or prosthesis infective endocarditis undergoing surgical treatment, called "The EndoSCORE". Copyright © 2017. Published by Elsevier B.V.

Delayed embryonic development in the Indian short-nosed fruit bat, Cynopterus sphinx.

PubMed

Meenakumari, Karukayil J; Krishna, Amitabh

2005-01-01

The unusual feature of the breeding cycle of Cynopterus sphinx at Varanasi is the significant variation in gestation length of the two successive pregnancies of the year. The aim of this study was to investigate whether the prolongation of the first pregnancy in C. sphinx is due to delayed embryonic development. The first (winter) pregnancy commences in late October and lasts until late March and has a gestation period of about 150 days. The second (summer) pregnancy commences in April and lasts until the end of July or early August with a gestation period of about 125 days. Changes in the size and weight of uterine cornua during the two successive pregnancies suggest retarded embryonic growth during November and December. Histological analysis during the period of retarded embryonic development in November and December showed a slow gastrulation process. The process of amniogenesis was particularly slow. When the embryos attained the early primitive streak stage, their developmental rate suddenly increased considerably. During the summer pregnancy, on the other hand, the process of gastrulation was much faster and proceeded quickly. A comparison of the pattern of embryonic development for 4 consecutive years consistently showed retarded or delayed embryonic development during November and December. The time of parturition and post-partum oestrus showed only a limited variation from 1 year to another. This suggests that delayed embryonic development in C. sphinx may function to synchronize parturition among females. The period of delayed embryonic development in this species clearly coincides with the period of fat deposition. The significance of this correlation warrants further investigation.

Early embryonic sensitivity to cyclophosphamide in cardiac differentiation from human embryonic stem cells.

PubMed

Zhu, Ming-Xia; Zhao, Jin-Yuan; Chen, Gui-An; Guan, Li

2011-09-01

hESCs (human embryonic stem cells) can differentiate into tissue derivatives of all three germ layers in vitro and mimic the development of the embryo in vivo. In this study, we have investigated the potential of an hESC-based assay for the detection of toxicity to cardiac differentiation in embryonic development. First of all, we developed the protocol of cardiac induction from hESCs according to our previous work and distinguished cardiac precursor cells and late mature cardiomyocytes from differentiated cells, demonstrated by the Q-PCR (quantitative real-time PCR), immunocytochemistry and flow cytometry analysis. In order to test whether CPA (cyclophosphamide) induces developmental and cellular toxicity in the human embryo, we exposed the differentiating cells from hESCs to CPA (a well-known proteratogen) at different stages. We have found that a high concentration of CPA could inhibit cardiac differentiation of hESCs. Two separate exposure intervals were used to determine the effects of CPA on cardiac precursor cells and late mature cardiomyocytes respectively. The cardiac precursor cells were sensitive to CPA in non-cytotoxic concentrations for the expression of the cardiac-specific mRNA markers Nkx2.5 (NK2 transcription factor related, locus 5), GATA-4 (GATA binding protein 4 transcription factor) and TNNT2 (troponin T type 2). Non-cytotoxic CPA concentrations did not affect the mRNA markers' expression in late mature cardiomyocytes, indicating that cardiac precursors were more sensitive to CPA than late cardiomyocytes in cardiogenesis. We set up the in vitro developmental toxicity test model so as to reduce the number of test animals and expenses without compromising the safety of consumers and patients. Furthermore, such in vitro methods may be possibly suited to test a large number of chemicals than the classical employed in vivo tests.

Effect of tidal overwash on the embryonic development of leatherback turtles in French Guiana.

PubMed

Caut, Stéphane; Guirlet, Elodie; Girondot, Marc

2010-05-01

In marine turtles, the physical conditions experienced by eggs during incubation affect embryonic development. In the leatherback, hatching success is known to be low in relation to other marine turtles as a result of high embryonic mortality. Moreover, the hatching success on Yalimapo in French Guiana, one major nesting beach for this species, is lower compared to other nesting sites. We assessed the rate of leatherback turtle embryonic mortality in order to investigate the tolerance of leatherback turtle clutches laid on Yalimapo beach to tidal overwash, and we highlight causes of poor hatching success. Of the 89 nests studied, 27 were overlapped by tide at least once during the incubation period (of which five nests were lost by erosion). The hatching success was on average significantly lower in overwashed nests than in non-overwashed, highlighting the existence of embryonic developmental arrest linked to tidal inundation. The stages of developmental arrest and their proportion are linked with time, frequency and level of overwash events. In the context of global warming and associated sea-level rise, understanding the detrimental effect of tidal inundation on the development of marine turtle nests is of interest in nesting sites where turtles are likely to be forced to nest closer to the tide line, thus exposing their nests to greater risk of nest overlap with sea and tidal inundation. Copyright 2009 Elsevier Ltd. All rights reserved.

The influence of early embryo traits on human embryonic stem cell derivation efficiency.

PubMed

O'Leary, Thomas; Heindryckx, Björn; Lierman, Sylvie; Van der Jeught, Margot; Menten, Björn; Deforce, Dieter; Cornelissen, Ria; de Sousa Lopes, Susana Chuva; De Sutter, Petra

2011-05-01

Despite its prognostic value in in vitro fertilization, early embryo morphology is not reported on in the derivation of human embryonic stem cell (hESC) lines. Standard hESC derivation does rely on blastocyst development and its efficiency is highly correlated to inner cell mass (ICM) quality. Poor-quality embryos (PQEs) donated for hESC derivation may have a range of cleavage-stage abnormalities that are known to compromise further development. This study was implemented to determine whether specific PQEs traits influence the efficiency of good-quality ICMs to derive new hESC lines. We found that although the types of PQEs investigated were all able to make blastocysts with good-quality ICMs, the ICMs were unequal in their ability to derive hESCs. Good-quality ICMs from embryos with multiple poor-quality traits were unable to generate hESC lines, in contrast to good-quality ICMs from embryos with a single poor-quality trait. In addition, our data suggest a direct correlation between the number of ICM cells present in the blastocyst and its capacity to derive new hESC lines. This study is the first to demonstrate that ICM quality alone is an incomplete indicator of hESC derivation and that application of in vitro fertilization-based early embryo scoring can help predict hESC derivation efficiency. Experiments aiming to quantify, improve upon, or compare hESC derivation efficiency should thus take into consideration early embryo morphology scoring for the comparison of groups with equal developmental competence.

Association between Proximity to a Health Center and Early Childhood Mortality in Madagascar

PubMed Central

Kashima, Saori; Suzuki, Etsuji; Okayasu, Toshiharu; Jean Louis, Razafimahatratra; Eboshida, Akira; Subramanian, S. V.

2012-01-01

Objective To evaluate the association between proximity to a health center and early childhood mortality in Madagascar, and to assess the influence of household wealth, maternal educational attainment, and maternal health on the effects of distance. Methods From birth records of subjects in the Demographic and Health Survey, we identified 12565 singleton births from January 2004 to August 2009. After excluding 220 births that lacked global positioning system information for exposure assessment, odds ratios (ORs) and their 95% confidence intervals (CIs) for neonatal mortality and infant mortality were estimated using multilevel logistic regression models, with 12345 subjects (level 1), nested within 584 village locations (level 2), and in turn nested within 22 regions (level 3). We additionally stratified the subjects by the birth order. We estimated predicted probabilities of each outcome by a three-level model including cross-level interactions between proximity to a health center and household wealth, maternal educational attainment, and maternal anemia. Results Compared with those who lived >1.5–3.0 km from a health center, the risks for neonatal mortality and infant mortality tended to increase among those who lived further than 5.0 km from a health center; the adjusted ORs for neonatal mortality and infant mortality for those who lived >5.0–10.0 km away from a health center were 1.36 (95% CI: 0.92–2.01) and 1.42 (95% CI: 1.06–1.90), respectively. The positive associations were more pronounced among the second or later child. The distance effects were not modified by household wealth status, maternal educational attainment, or maternal health status. Conclusions Our study suggests that distance from a health center is a risk factor for early childhood mortality (primarily, infant mortality) in Madagascar by using a large-scale nationally representative dataset. The accessibility to health care in remote areas would be a key factor to achieve better

Chronology of early embryonic development and embryo uterine migration in alpacas.

PubMed

Picha, Y; Tibary, A; Memon, M; Kasimanickam, R; Sumar, J

2013-03-01

The objectives were to: (1) describe the chronology of early embryonic development from ovulation to entry into the uterus; and (2) to determine the timing of embryo migration to the left uterine horn when ovulation occurred from the right ovary. The experiment was conducted in Peru. Females (n = 132) were randomly assigned to 15 experimental groups. All females were mated to an intact male, given 50 μg GnRH im (Cystorelin) and ovulation time determined by transrectal ultrasonography, conducted every 6 hours, starting 24 hours postmating. Animals were slaughtered at a specific intervals postovulation and reproductive tracts were recovered and subjected to oviductal and uterine flushing for females slaughtered between 1 and 6 days postovulation (dpo; Day 0 = ovulation) and uterine flushing for females slaughtered from 7 to 15 dpo for recovery of oocytes/embryos. Season of mating did not influence the interval from mating to ovulation (winter: 29 ± 6 hours vs. summer: 30 ± 6 hours; P = 0.49). Ovulation rates for females mated during winter and summer were 92% versus 100%, respectively (P = 0.05). Fertilization rates for winter and summer mated females were 72% and 82% (P = 0.29). Unfertilized ova were not retained in the uterine tube. All embryos collected were in the uterine tube ipsilateral to the side of ovulation between 1 and 5 dpo. Embryos reached the uterus on 6 dpo. Embryos began to elongate on 9 dpo; at this time, 83% of embryos derived from right-ovary ovulations were collected from the left uterine horn. Embryos occupied the entire uterine cavity by 10 dpo. In conclusion, we characterized early embryo development and location of embryo during its early developmental stages in alpaca. This was apparently the first report regarding chronology of embryo development and migration to the left horn in alpaca which merits further investigation regarding its role in maternal recognition of pregnancy. Copyright © 2013 Elsevier Inc. All rights reserved.

Somatic Donor Cell Type Correlates with Embryonic, but Not Extra-Embryonic, Gene Expression in Postimplantation Cloned Embryos

PubMed Central

Inoue, Kimiko; Ogura, Atsuo

2013-01-01

The great majority of embryos generated by somatic cell nuclear transfer (SCNT) display defined abnormal phenotypes after implantation, such as an increased likelihood of death and abnormal placentation. To gain better insight into the underlying mechanisms, we analyzed genome-wide gene expression profiles of day 6.5 postimplantation mouse embryos cloned from three different cell types (cumulus cells, neonatal Sertoli cells and fibroblasts). The embryos retrieved from the uteri were separated into embryonic (epiblast) and extraembryonic (extraembryonic ectoderm and ectoplacental cone) tissues and were subjected to gene microarray analysis. Genotype- and sex-matched embryos produced by in vitro fertilization were used as controls. Principal component analysis revealed that whereas the gene expression patterns in the embryonic tissues varied according to the donor cell type, those in extraembryonic tissues were relatively consistent across all groups. Within each group, the embryonic tissues had more differentially expressed genes (DEGs) (>2-fold vs. controls) than did the extraembryonic tissues (P<1.0×10–26). In the embryonic tissues, one of the common abnormalities was upregulation of Dlk1, a paternally imprinted gene. This might be a potential cause of the occasional placenta-only conceptuses seen in SCNT-generated mouse embryos (1–5% per embryos transferred in our laboratory), because dysregulation of the same gene is known to cause developmental failure of embryos derived from induced pluripotent stem cells. There were also some DEGs in the extraembryonic tissues, which might explain the poor development of SCNT-derived placentas at early stages. These findings suggest that SCNT affects the embryonic and extraembryonic development differentially and might cause further deterioration in the embryonic lineage in a donor cell-specific manner. This could explain donor cell-dependent variations in cloning efficiency using SCNT. PMID:24146866

Early mortality and morbidity after total hip arthroplasty in patients with femoral neck fracture

PubMed Central

Hailer, Nils P; Garland, Anne; Rogmark, Cecilia; Garellick, Göran; Kärrholm, Johan

2016-01-01

Background and purpose — Early postoperative mortality is relatively high after total hip arthroplasty (THA) that has been performed due to femoral neck fracture. However, this has rarely been investigated after adjustment for medical comorbidity and comparison with the mortality in an age-matched population. We therefore assessed early mortality in hip fracture patients treated with a THA, in the setting of a nationwide matched cohort study. Patients and methods — 24,699 patients who underwent THA due to a femoral neck fracture between 1992 and 2012 were matched with 118,518 controls. Kaplan-Meier survival analysis was used to calculate cumulative unadjusted survival, and Cox regression models were fitted to compute hazard ratios (HRs) and 95% confidence intervals (CIs), with adjustment for age, sex, comorbidity, and socioeconomic background. Results — 90-day survival was 96.3% (95% CI: 96.0–96.5) for THA cases and 98.7% (95% CI: 98.6–98.8) for control individuals, giving an adjusted HR of 2.2 (95% CI: 2.0–2.4) for THA cases compared to control individuals. Comorbidity burden increased in THA cases over time, but the adjusted risk of death within 90 days did not differ statistically significantly between the time periods investigated (1992–1998, 1999–2005, and 2006–2012). A Charlson comorbidity index of 3 or more, an American Society of Anesthesiologists (ASA) grade of 3 and above, male sex, an age of 80 years and above, an income below the first quartile, and a lower level of education were all associated with an increased risk of 90-day mortality. Interpretation — The adjusted early mortality in femoral neck fracture patients who underwent THA was about double that in a matched control population. Patients with femoral neck fracture but with no substantial comorbidity and an age of less than 80 years appear to have a low risk of early death. Patients older than 80 years and those with a Charlson comorbidity index of more than 2 have a high

Human embryonic stem cell research: an intercultural perspective.

PubMed

Walters, LeRoy

2004-03-01

In 1998, researchers discovered that embryonic stem cells could be derived from early human embryos. This discovery has raised a series of ethical and public-policy questions that are now being confronted by multiple international organizations, nations, cultures, and religious traditions. This essay surveys policies for human embryonic stem cell research in four regions of the world, reports on the recent debate at the United Nations about one type of such research, and reviews the positions that various religious traditions have adopted regarding this novel type of research. In several instances the religious traditions seem to have influenced the public-policy debates.

[Correlation of the DNA fragmentation index and malformation rate of optimized sperm with embryonic development and early spontaneous abortion in IVF-ET].

PubMed

Jiang, Wei-Jie; Jin, Fan; Zhou, Li-Ming

2016-06-01

To investigate the effects of the DNA fragmentation index (DFI) and malformation rate (SMR) of optimized sperm on embryonic development and early spontaneous abortion in conventional in vitro fertilization and embryo transfer (IVF-ET). We selected 602 cycles of conventional IVF-ET for pure oviductal infertility that had achieved clinical pregnancies, including 505 cycles with ongoing pregnancy and 97 cycles with early spontaneous abortion. On the day of ovum retrieval, we examined the DNA integrity and morphology of the rest of the optimized sperm using the SCD and Diff-Quik methods, established the joint predictor (JP) by logistic equation, and assessed the value of DFI and SMR in predicting early spontaneous abortion using the ROC curve. The DFI, SMR, and high-quality embryo rate were (15.91±3.69)%, (82.85±10.24)%, and 46.53% (342/735) in the early spontaneous abortion group and (9.30±4.22)%, (77.32±9.19)%, and 56.43% (2263/4010) respectively in the ongoing pregnancy group, all with statistically significant differences between the two groups (P<0.05 ). Both the DFI and SMR were the risk factors of early spontaneous abortion (OR = 5.96 and 1.66; both P< 0.01). The areas under the ROC curve for DFI, SMR and JP were 0.893±0.019, 0.685±0.028, and 0.898±0.018, respectively. According to the Youden index, the optimal cut-off values of the DFI and SMR obtained for the prediction of early spontaneous abortion were approximately 15% and 80%. The DFI was correlated positively with SMR (r= 0.31, P<0.01) but the high-quality embryo rate negatively with both the DFI (r= －0.45, P<0.01) and SMR (r= －0.22, P<0.01). The DFI and SMR of optimized sperm are closely associated with embryonic development in IVF. The DFI has a certain value for predicting early spontaneous abortion with a threshold of approximately 15%, but SMR may have a lower predictive value.

Signs of eclampsia during singleton deliveries and early neonatal mortality in low- and middle-income countries from three WHO regions.

PubMed

Bellizzi, Saverio; Sobel, Howard L; Ali, Mohamed M

2017-10-01

To determine the prevalence of eclampsia symptoms and to explore associations between eclampsia and early neonatal mortality. The present secondary analysis included Demographic and Health Surveys data from 2005 to 2012; details of signs related to severe obstetric adverse events of singleton deliveries during interviewees' most recent delivery in the preceding 5 years were included. Data and delivery history were merged for pooled analyses. Convulsions-used as an indicator for having experienced eclampsia-and early neonatal mortality rates were compared, and a generalized random effect model, adjusted for heterogeneity between and within countries, was used to investigate the impact of presumed eclampsia on early neonatal mortality. The merged dataset included data from six surveys and 55 384 live deliveries that occurred in Colombia, Bangladesh, Indonesia, Mali, Niger, and Peru. Indications of eclampsia were recorded for 1.2% (95% confidence interval [CI] 1.0-1.3), 1.7% (95% CI 1.5-2.1), and 1.7% (95% CI 1.5-2.1) of deliveries reported from the American, South East Asian, and African regions, respectively. Pooled analyses demonstrated that eclampsia was associated with increased risk of early neonatal mortality (adjusted risk ratio 2.1 95% CI 1.4-3.2). Increased risk of early neonatal mortality indicates a need for strategies targeting the early detection of eclampsia and early interventions. © 2017 International Federation of Gynecology and Obstetrics.

Decreased early mortality associated with the treatment of acute myeloid leukemia at National Cancer Institute-designated cancer centers in California.

PubMed

Ho, Gwendolyn; Wun, Ted; Muffly, Lori; Li, Qian; Brunson, Ann; Rosenberg, Aaron S; Jonas, Brian A; Keegan, Theresa H M

2018-05-01

To the authors' knowledge, few population-based studies to date have evaluated the association between location of care, complications with induction therapy, and early mortality in patients with acute myeloid leukemia (AML). Using linked data from the California Cancer Registry and Patient Discharge Dataset (1999-2014), the authors identified adult (aged ≥18 years) patients with AML who received inpatient treatment within 30 days of diagnosis. A propensity score was created for treatment at a National Cancer Institute-designated cancer center (NCI-CC). Inverse probability-weighted, multivariable logistic regression models were used to determine associations between location of care, complications, and early mortality (death ≤60 days from diagnosis). Of the 7007 patients with AML, 1762 (25%) were treated at an NCI-CC. Patients with AML who were treated at NCI-CCs were more likely to be aged ≤65 years, live in higher socioeconomic status neighborhoods, have fewer comorbidities, and have public health insurance. Patients treated at NCI-CCs had higher rates of renal failure (23% vs 20%; P = .010) and lower rates of respiratory failure (11% vs 14%; P = .003) and cardiac arrest (1% vs 2%; P = .014). After adjustment for baseline characteristics, treatment at an NCI-CC was associated with lower early mortality (odds ratio, 0.46; 95% confidence interval, 0.38-0.57). The impact of complications on early mortality did not differ by location of care except for higher early mortality noted among patients with respiratory failure treated at non-NCI-CCs. The initial treatment of adult patients with AML at NCI-CCs is associated with a 53% reduction in the odds of early mortality compared with treatment at non-NCI-CCs. Lower early mortality may result from differences in hospital or provider experience and supportive care. Cancer 2018;124:1938-45. © 2018 American Cancer Society. © 2018 American Cancer Society.

Embryonic chirality and the evolution of spiralian left–right asymmetries

PubMed Central

2016-01-01

The group Spiralia includes species with one of the most significant cases of left–right asymmetries in animals: the coiling of the shell of gastropod molluscs (snails). In this animal group, an early event of embryonic chirality controlled by cytoskeleton dynamics and the subsequent differential activation of the genes nodal and Pitx determine the left–right axis of snails, and thus the direction of coiling of the shell. Despite progressive advances in our understanding of left–right axis specification in molluscs, little is known about left–right development in other spiralian taxa. Here, we identify and characterize the expression of nodal and Pitx orthologues in three different spiralian animals—the brachiopod Novocrania anomala, the annelid Owenia fusiformis and the nemertean Lineus ruber—and demonstrate embryonic chirality in the biradial-cleaving spiralian embryo of the bryozoan Membranipora membranacea. We show asymmetric expression of nodal and Pitx in the brachiopod and annelid, respectively, and symmetric expression of Pitx in the nemertean. Our findings indicate that early embryonic chirality is widespread and independent of the cleavage programme in the Spiralia. Additionally, our study illuminates the evolution of nodal and Pitx signalling by demonstrating embryonic asymmetric expression in lineages without obvious adult left–right asymmetries. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’. PMID:27821523

Early mortality experience in a large military cohort and a comparison of mortality data sources

PubMed Central

2010-01-01

Background Complete and accurate ascertainment of mortality is critically important in any longitudinal study. Tracking of mortality is particularly essential among US military members because of unique occupational exposures (e.g., worldwide deployments as well as combat experiences). Our study objectives were to describe the early mortality experience of Panel 1 of the Millennium Cohort, consisting of participants in a 21-year prospective study of US military service members, and to assess data sources used to ascertain mortality. Methods A population-based random sample (n = 256,400) of all US military service members on service rosters as of October 1, 2000, was selected for study recruitment. Among this original sample, 214,388 had valid mailing addresses, were not in the pilot study, and comprised the group referred to in this study as the invited sample. Panel 1 participants were enrolled from 2001 to 2003, represented all armed service branches, and included active-duty, Reserve, and National Guard members. Crude death rates, as well as age- and sex-adjusted overall and age-adjusted, category-specific death rates were calculated and compared for participants (n = 77,047) and non-participants (n = 137,341) based on data from the Social Security Administration Death Master File, Department of Veterans Affairs (VA) files, and the Department of Defense Medical Mortality Registry, 2001-2006. Numbers of deaths identified by these three data sources, as well as the National Death Index, were compared for 2001-2004. Results There were 341 deaths among the participants for a crude death rate of 80.7 per 100,000 person-years (95% confidence interval [CI]: 72.2,89.3) compared to 820 deaths and a crude death rate of 113.2 per 100,000 person-years (95% CI: 105.4, 120.9) for non-participants. Age-adjusted, category-specific death rates highlighted consistently higher rates among study non-participants. Although there were advantages and disadvantages for each data source

Essential Role of Chromatin Remodeling Protein Bptf in Early Mouse Embryos and Embryonic Stem Cells

PubMed Central

Landry, Joseph; Sharov, Alexei A.; Piao, Yulan; Sharova, Lioudmila V.; Xiao, Hua; Southon, Eileen; Matta, Jennifer; Tessarollo, Lino; Zhang, Ying E.; Ko, Minoru S. H.; Kuehn, Michael R.; Yamaguchi, Terry P.; Wu, Carl

2008-01-01

We have characterized the biological functions of the chromatin remodeling protein Bptf (Bromodomain PHD-finger Transcription Factor), the largest subunit of NURF (Nucleosome Remodeling Factor) in a mammal. Bptf mutants manifest growth defects at the post-implantation stage and are reabsorbed by E8.5. Histological analyses of lineage markers show that Bptf−/− embryos implant but fail to establish a functional distal visceral endoderm. Microarray analysis at early stages of differentiation has identified Bptf-dependent gene targets including homeobox transcriptions factors and genes essential for the development of ectoderm, mesoderm, and both definitive and visceral endoderm. Differentiation of Bptf−/− embryonic stem cell lines into embryoid bodies revealed its requirement for development of mesoderm, endoderm, and ectoderm tissue lineages, and uncovered many genes whose activation or repression are Bptf-dependent. We also provide functional and physical links between the Bptf-containing NURF complex and the Smad transcription factors. These results suggest that Bptf may co-regulate some gene targets of this pathway, which is essential for establishment of the visceral endoderm. We conclude that Bptf likely regulates genes and signaling pathways essential for the development of key tissues of the early mouse embryo. PMID:18974875

Geographic variation in avian incubation periods and parental influences on embryonic temperature

USGS Publications Warehouse

Martin, T.E.; Auer, S.K.; Bassar, R.D.; Niklison, Alina M.; Lloyd, P.

2007-01-01

Theory predicts shorter embryonic periods in species with greater embryo mortality risk and smaller body size. Field studies of 80 passerine species on three continents yielded data that largely conflicted with theory; incubation (embryonic) periods were longer rather than shorter in smaller species, and egg (embryo) mortality risk explained some variation within regions, but did not explain larger differences in incubation periods among geographic regions. Incubation behavior of parents seems to explain these discrepancies. Bird embryos are effectively ectothermic and depend on warmth provided by parents sitting on the eggs to attain proper temperatures for development. Parents of smaller species, plus tropical and southern hemisphere species, commonly exhibited lower nest attentiveness (percent of time spent on the nest incubating) than larger and northern hemisphere species. Lower nest attentiveness produced cooler minimum and average embryonic temperatures that were correlated with longer incubation periods independent of nest predation risk or body size. We experimentally tested this correlation by swapping eggs of species with cool incubation temperatures with eggs of species with warm incubation temperatures and similar egg mass. Incubation periods changed (shortened or lengthened) as expected and verified the importance of egg temperature on development rate. Slower development resulting from cooler temperatures may simply be a cost imposed on embryos by parents and may not enhance offspring quality. At the same time, incubation periods of transferred eggs did not match host species and reflect intrinsic differences among species that may result from nest predation and other selection pressures. Thus, geographic variation in embryonic development may reflect more complex interactions than previously recognized. ?? 2007 The Author(s).

Pipette-based Method to Study Embryoid Body Formation Derived from Mouse and Human Pluripotent Stem Cells Partially Recapitulating Early Embryonic Development Under Simulated Microgravity Conditions

NASA Astrophysics Data System (ADS)

Shinde, Vaibhav; Brungs, Sonja; Hescheler, Jürgen; Hemmersbach, Ruth; Sachinidis, Agapios

2016-06-01

The in vitro differentiation of pluripotent stem cells partially recapitulates early in vivo embryonic development. More recently, embryonic development under the influence of microgravity has become a primary focus of space life sciences. In order to integrate the technique of pluripotent stem cell differentiation with simulated microgravity approaches, the 2-D clinostat compatible pipette-based method was experimentally investigated and adapted for investigating stem cell differentiation processes under simulated microgravity conditions. In order to keep residual accelerations as low as possible during clinorotation, while also guaranteeing enough material for further analysis, stem cells were exposed in 1-mL pipettes with a diameter of 3.5 mm. The differentiation of mouse and human pluripotent stem cells inside the pipettes resulted in the formation of embryoid bodies at normal gravity (1 g) after 24 h and 3 days. Differentiation of the mouse pluripotent stem cells on a 2-D pipette-clinostat for 3 days also resulted in the formation of embryoid bodies. Interestingly, the expression of myosin heavy chain was downregulated when cultivation was continued for an additional 7 days at normal gravity. This paper describes the techniques for culturing and differentiation of pluripotent stem cells and exposure to simulated microgravity during culturing or differentiation on a 2-D pipette clinostat. The implementation of these methodologies along with -omics technologies will contribute to understand the mechanisms regulating how microgravity influences early embryonic development.

Influence of follicular characteristics at ovulation on early embryo survival

USDA-ARS?s Scientific Manuscript database

Reproductive failure in livestock can result from failure to fertilize the oocyte or embryonic loss during gestation. Although fertilization failure occurs, embryonic mortality represents a greater contribution to reproductive failure. Reproductive success varies between species and production goal...

Hazard Regression Models of Early Mortality in Trauma Centers

PubMed Central

Clark, David E; Qian, Jing; Winchell, Robert J; Betensky, Rebecca A

2013-01-01

Background Factors affecting early hospital deaths after trauma may be different from factors affecting later hospital deaths, and the distribution of short and long prehospital times may vary among hospitals. Hazard regression (HR) models may therefore be more useful than logistic regression (LR) models for analysis of trauma mortality, especially when treatment effects at different time points are of interest. Study Design We obtained data for trauma center patients from the 2008–9 National Trauma Data Bank (NTDB). Cases were included if they had complete data for prehospital times, hospital times, survival outcome, age, vital signs, and severity scores. Cases were excluded if pulseless on admission, transferred in or out, or ISS<9. Using covariates proposed for the Trauma Quality Improvement Program and an indicator for each hospital, we compared LR models predicting survival at 8 hours after injury to HR models with survival censored at 8 hours. HR models were then modified to allow time-varying hospital effects. Results 85,327 patients in 161 hospitals met inclusion criteria. Crude hazards peaked initially, then steadily declined. When hazard ratios were assumed constant in HR models, they were similar to odds ratios in LR models associating increased mortality with increased age, firearm mechanism, increased severity, more deranged physiology, and estimated hospital-specific effects. However, when hospital effects were allowed to vary by time, HR models demonstrated that hospital outliers were not the same at different times after injury. Conclusions HR models with time-varying hazard ratios reveal inconsistencies in treatment effects, data quality, and/or timing of early death among trauma centers. HR models are generally more flexible than LR models, can be adapted for censored data, and potentially offer a better tool for analysis of factors affecting early death after injury. PMID:23036828

Fucoidan promotes early step of cardiac differentiation from human embryonic stem cells and long-term maintenance of beating areas.

PubMed

Hamidi, Sofiane; Letourneur, Didier; Aid-Launais, Rachida; Di Stefano, Antonio; Vainchenker, William; Norol, Françoise; Le Visage, Catherine

2014-04-01

Somatic stem cells require specific niches and three-dimensional scaffolds provide ways to mimic this microenvironment. Here, we studied a scaffold based on Fucoidan, a sulfated polysaccharide known to influence morphogen gradients during embryonic development, to support human embryonic stem cells (hESCs) differentiation toward the cardiac lineage. A macroporous (pore 200 μm) Fucoidan scaffold was selected to support hESCs attachment and proliferation. Using a protocol based on the cardiogenic morphogen bone morphogenic protein 2 (BMP2) and transforming growth factor (TGFβ) followed by tumor necrosis factor (TNFα), an effector of cardiopoietic priming, we examined the cardiac differentiation in the scaffold compared to culture dishes and embryoid bodies (EBs). At day 8, Fucoidan scaffolds supported a significantly higher expression of the 3 genes encoding for transcription factors marking the early step of embryonic cardiac differentiation NKX2.5 (p<0.05), MEF2C (p<0.01), and GATA4 (p<0.01), confirmed by flow cytometry analysis for MEF2C and NKX2.5. The ability of Fucoidan scaffolds to locally concentrate and slowly release TGFβ and TNFα was confirmed by Luminex technology. We also found that Fucoidan scaffolds supported the late stage of embryonic cardiac differentiation marked by a significantly higher atrial natriuretic factor (ANF) expression (p<0.001), although only rare beating areas were observed. We postulated that absence of mechanical stress in the soft hydrogel impaired sarcomere formation, as confirmed by molecular analysis of the cardiac muscle myosin MYH6 and immunohistological staining of sarcomeric α-actinin. Nevertheless, Fucoidan scaffolds contributed to the development of thin filaments connecting beating areas through promotion of smooth muscle cells, thus enabling maintenance of beating areas for up to 6 months. In conclusion, Fucoidan scaffolds appear as a very promising biomaterial to control cardiac differentiation from hESCs that

Effectiveness of early detection on breast cancer mortality reduction in Catalonia (Spain)

PubMed Central

2009-01-01

Background At present, it is complicated to use screening trials to determine the optimal age intervals and periodicities of breast cancer early detection. Mathematical models are an alternative that has been widely used. The aim of this study was to estimate the effect of different breast cancer early detection strategies in Catalonia (Spain), in terms of breast cancer mortality reduction (MR) and years of life gained (YLG), using the stochastic models developed by Lee and Zelen (LZ). Methods We used the LZ model to estimate the cumulative probability of death for a cohort exposed to different screening strategies after T years of follow-up. We also obtained the cumulative probability of death for a cohort with no screening. These probabilities were used to estimate the possible breast cancer MR and YLG by age, period and cohort of birth. The inputs of the model were: incidence of, mortality from and survival after breast cancer, mortality from other causes, distribution of breast cancer stages at diagnosis and sensitivity of mammography. The outputs were relative breast cancer MR and YLG. Results Relative breast cancer MR varied from 20% for biennial exams in the 50 to 69 age interval to 30% for annual exams in the 40 to 74 age interval. When strategies differ in periodicity but not in the age interval of exams, biennial screening achieved almost 80% of the annual screening MR. In contrast to MR, the effect on YLG of extending screening from 69 to 74 years of age was smaller than the effect of extending the screening from 50 to 45 or 40 years. Conclusion In this study we have obtained a measure of the effect of breast cancer screening in terms of mortality and years of life gained. The Lee and Zelen mathematical models have been very useful for assessing the impact of different modalities of early detection on MR and YLG in Catalonia (Spain). PMID:19754959

Single-cell transcriptome of early embryos and cultured embryonic stem cells of cynomolgus monkeys

PubMed Central

Nakamura, Tomonori; Yabuta, Yukihiro; Okamoto, Ikuhiro; Sasaki, Kotaro; Iwatani, Chizuru; Tsuchiya, Hideaki; Saitou, Mitinori

2017-01-01

In mammals, the development of pluripotency and specification of primordial germ cells (PGCs) have been studied predominantly using mice as a model organism. However, divergences among mammalian species for such processes have begun to be recognized. Between humans and mice, pre-implantation development appears relatively similar, but the manner and morphology of post-implantation development are significantly different. Nevertheless, the embryogenesis just after implantation in primates, including the specification of PGCs, has been unexplored due to the difficulties in analyzing the embryos at relevant developmental stages. Here, we present a comprehensive single-cell transcriptome dataset of pre- and early post-implantation embryo cells, PGCs and embryonic stem cells (ESCs) of cynomolgus monkeys as a model of higher primates. The identities of each transcriptome were also validated rigorously by other way such as immunofluorescent analysis. The information reported here will serve as a foundation for our understanding of a wide range of processes in the developmental biology of primates, including humans. PMID:28649393

Detecting early warning signals of tree mortality in boreal North America using multiscale satellite data.

PubMed

Rogers, Brendan M; Solvik, Kylen; Hogg, Edward H; Ju, Junchang; Masek, Jeffrey G; Michaelian, Michael; Berner, Logan T; Goetz, Scott J

2018-06-01

Increasing tree mortality from global change drivers such as drought and biotic infestations is a widespread phenomenon, including in the boreal zone where climate changes and feedbacks to the Earth system are relatively large. Despite the importance for science and management communities, our ability to forecast tree mortality at landscape to continental scales is limited. However, two independent information streams have the potential to inform and improve mortality forecasts: repeat forest inventories and satellite remote sensing. Time series of tree-level growth patterns indicate that productivity declines and related temporal dynamics often precede mortality years to decades before death. Plot-level productivity, in turn, has been related to satellite-based indices such as the Normalized difference vegetation index (NDVI). Here we link these two data sources to show that early warning signals of mortality are evident in several NDVI-based metrics up to 24 years before death. We focus on two repeat forest inventories and three NDVI products across western boreal North America where productivity and mortality dynamics are influenced by periodic drought. These data sources capture a range of forest conditions and spatial resolution to highlight the sensitivity and limitations of our approach. Overall, results indicate potential to use satellite NDVI for early warning signals of mortality. Relationships are broadly consistent across inventories, species, and spatial resolutions, although the utility of coarse-scale imagery in the heterogeneous aspen parkland was limited. Longer-term NDVI data and annually remeasured sites with high mortality levels generate the strongest signals, although we still found robust relationships at sites remeasured at a typical 5 year frequency. The approach and relationships developed here can be used as a basis for improving forest mortality models and monitoring systems. © 2018 John Wiley & Sons Ltd.

Mitochondrial functionality in reproduction: from gonads and gametes to embryos and embryonic stem cells.

PubMed

Ramalho-Santos, João; Varum, Sandra; Amaral, Sandra; Mota, Paula C; Sousa, Ana Paula; Amaral, Alexandra

2009-01-01

Mitochondria are multitasking organelles involved in ATP synthesis, reactive oxygen species (ROS) production, calcium signalling and apoptosis; and mitochondrial defects are known to cause physiological dysfunction, including infertility. The goal of this review was to identify and discuss common themes in mitochondrial function related to mammalian reproduction. The scientific literature was searched for studies reporting on the several aspects of mitochondrial activity in mammalian testis, sperm, oocytes, early embryos and embryonic stem cells. ATP synthesis and ROS production are the most discussed aspects of mitochondrial function. Metabolic shifts from mitochondria-produced ATP to glycolysis occur at several stages, notably during gametogenesis and early embryo development, either reflecting developmental switches or substrate availability. The exact role of sperm mitochondria is especially controversial. Mitochondria-generated ROS function in signalling but are mostly described when produced under pathological conditions. Mitochondria-based calcium signalling is primarily important in embryo activation and embryonic stem cell differentiation. Besides pathologically triggered apoptosis, mitochondria participate in apoptotic events related to the regulation of spermatogonial cell number, as well as gamete, embryo and embryonic stem cell quality. Interestingly, data from knock-out (KO) mice is not always straightforward in terms of expected phenotypes. Finally, recent data suggests that mitochondrial activity can modulate embryonic stem cell pluripotency as well as differentiation into distinct cellular fates. Mitochondria-based events regulate different aspects of reproductive function, but these are not uniform throughout the several systems reviewed. Low mitochondrial activity seems a feature of 'stemness', being described in spermatogonia, early embryo, inner cell mass cells and embryonic stem cells.

Nitric oxide synthase during early embryonic development in silkworm Bombyx mori: Gene expression, enzyme activity, and tissue distribution.

PubMed

Kitta, Ryo; Kuwamoto, Marina; Yamahama, Yumi; Mase, Keisuke; Sawada, Hiroshi

2016-12-01

To elucidate the mechanism for embryonic diapause or the breakdown of diapause in Bombyx mori, we biochemically analyzed nitric oxide synthase (NOS) during the embryogenesis of B. mori. The gene expression and enzyme activity of B. mori NOS (BmNOS) were examined in diapause, non-diapause, and HCl-treated diapause eggs. In the case of HCl-treated diapause eggs, the gene expression and enzyme activity of BmNOS were induced by HCl treatment. However, in the case of diapause and non-diapause eggs during embryogenesis, changes in the BmNOS activity and gene expressions did not coincide except 48-60 h after oviposition in diapause eggs. The results imply that changes in BmNOS activity during the embryogenesis of diapause and non-diapause eggs are regulated not only at the level of transcription but also post-transcription. The distribution and localization of BmNOS were also investigated with an immunohistochemical technique using antibodies against the universal NOS; the localization of BmNOS was observed mainly in the cytoplasm of yolk cells in diapause eggs and HCl-treated diapause eggs. These data suggest that BmNOS has an important role in the early embryonic development of the B. mori. © 2016 Japanese Society of Developmental Biologists.

Relationship between delayed embryonic development and metabolic factors and fat deposition in fruit bat Cynopterus sphinx.

PubMed

Banerjee, Arnab; Meenakumari, K J; Krishna, Amitabh

2007-01-01

The present study was undertaken in the fruit bat Cynopterus sphinx, which breeds twice in quick succession at Varanasi, India. Its gestation period varies significantly in the two successive pregnancies of the year owing to delayed embryonic development during the first (winter) pregnancy. The primary aim of the present study was to determine the role of metabolic factors in delayed embryonic development in the fruit bat C. sphinx. Variation in bodyweight, fat deposition, oxygen (O(2)) consumption rate, basal metabolic rate (BMR), body temperature (Tb) and hepatic succinate dehydrogenase (SDH) activity, along with circulating levels of thyroid hormones (tri-iodothyronine and thyroxine), were examined as metabolic factors during the two successive pregnancies in C. sphinx. The increase in bodyweight observed in November was due to accumulation of white adipose tissue in the posterior abdominal region. A significant decline in O(2) consumption rate, BMR, Tb and SDH activity was found in early winter in November-December, which coincides closely with the period of fat accumulation and with the period of delayed embryonic development in C. sphinx. A significantly higher O(2) consumption rate, BMR, Tb and SDH activity was noted during the second pregnancy in, when embryonic development was relatively faster. Thyroid hormone levels were high during the period of embryonic delay compared with levels during the remaining months. The results of the present study suggest that the delayed embryonic development in C. sphinx during early winter may be due to a low O(2) consumption rate, BMR, Tb and SDH activity in November-December. The energy saved by suppressing embryonic development in this species may be advantageous for fat accumulation. Increased thyroid hormone levels during the early winter period might facilitate fat accumulation in C. sphinx.

A Two-Center Randomized Trial of an Additional Early Dose of Measles Vaccine: Effects on Mortality and Measles Antibody Levels.

PubMed

Fisker, Ane B; Nebie, Eric; Schoeps, Anja; Martins, Cesario; Rodrigues, Amabelia; Zakane, Alphonse; Kagone, Moubassira; Byberg, Stine; Thysen, Sanne M; Tiendrebeogo, Justin; Coulibaly, Boubacar; Sankoh, Osman; Becher, Heiko; Whittle, Hilton C; van der Klis, Fiona R M; Benn, Christine S; Sie, Ali; Müller, Olaf; Aaby, Peter

2018-05-02

In addition to protecting against measles, measles vaccine (MV) may have beneficial nonspecific effects. We tested the effect of an additional early MV on mortality and measles antibody levels. Children aged 4-7 months at rural health and demographic surveillance sites in Burkina Faso and Guinea-Bissau were randomized 1:1 to an extra early standard dose of MV (Edmonston-Zagreb strain) or no extra MV 4 weeks after the third diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine. All children received routine MV at 9 months. We assessed mortality through home visits and compared mortality from enrollment to age 3 years using Cox proportional hazards models, censoring for subsequent nontrial MV. Subgroups of participants had blood sampled to assess measles antibody levels. Among 8309 children enrolled from 18 July 2012 to 3 December 2015, we registered 145 deaths (mortality rate: 16/1000 person-years). The mortality was lower than anticipated and did not differ by randomization group (hazard ratio, 1.05; 95% confidence interval, 0.75-1.46). At enrollment, 4% (16/447) of children in Burkina Faso and 21% (90/422) in Guinea-Bissau had protective measles antibody levels. By age 9 months, no measles-unvaccinated/-unexposed child had protective levels, while 92% (306/333) of early MV recipients had protective levels. At final follow-up, 98% (186/189) in the early MV group and 97% (196/202) in the control group had protective levels. Early MV did not reduce all-cause mortality. Most children were susceptible to measles infection at age 4-7 months and responded with high antibody levels to early MV. NCT01644721.

Linking egg thiamine and fatty acid concentrations of Lake Michigan lake trout with early life stage mortality.

PubMed

Czesny, Sergiusz; Dettmers, John M; Rinchard, Jacques; Dabrowski, Konrad

2009-12-01

The natural reproduction of lake trout Salvelinus namaycush in Lake Michigan is thought to be compromised by nutritional deficiency associated with inadequate levels of thiamine (vitamin B1) in their eggs. However, mortality driven by thiamine deficiency (commonly referred to as early mortality syndrome [EMS]) is not the only significant cause of low lake trout survival at early life stages. In this study, we sought to better understand the combined effects of variable levels of thiamine and fatty acids in lake trout eggs on prehatch, posthatch, and swim-up-stage mortality. We sampled the eggs of 29 lake trout females from southwestern Lake Michigan. The concentrations of free thiamine and its vitamers (e.g., thiamine monophosphate [TMP] and thiamine pyrophosphate [TPP]) as well as fatty acid profiles were determined in sampled eggs. Fertilized eggs and embryos were monitored through the advanced swim-up stage (1,000 degree-days). Three distinct periods of mortality were identified: prehatch (0-400 degree-days), immediately posthatch (401-600 degree-days), and swim-up (601-1,000 degree-days). Stepwise multiple regression analysis revealed (1) that cis-7-hexadecenoic acid in both neutral lipids (NL) and phospholipids (PL) correlated with prehatch mortality, (2) that docosapentaenoic acid in PL and docosahexaenoic acid in NL correlated with posthatch mortality, and (3) that total lipids, TPP, and palmitoleic acid in NL, linoleic acid, and palmitic acid in PL correlated with the frequency of EMS. These results indicate the complexity of early life stage mortality in lake trout and suggest that inadequate levels of key fatty acids in eggs, along with variable thiamine content, contribute to the low survival of lake trout progeny in Lake Michigan.

Imprinted expression in cystic embryoid bodies shows an embryonic and not an extra-embryonic pattern

PubMed Central

Kulinski, Tomasz M.; Casari, M. Rita T.; Guenzl, Philipp M.; Wenzel, Daniel; Andergassen, Daniel; Hladik, Anastasiya; Datlinger, Paul; Farlik, Matthias; Theussl, H. -Christian; Penninger, Josef M.; Knapp, Sylvia; Bock, Christoph; Barlow, Denise P.; Hudson, Quanah J.

2015-01-01

A large subset of mammalian imprinted genes show extra-embryonic lineage (EXEL) specific imprinted expression that is restricted to placental trophectoderm lineages and to visceral yolk sac endoderm (ysE). Isolated ysE provides a homogenous in vivo model of a mid-gestation extra-embryonic tissue to examine the mechanism of EXEL-specific imprinted gene silencing, but an in vitro model of ysE to facilitate more rapid and cost-effective experiments is not available. Reports indicate that ES cells differentiated into cystic embryoid bodies (EBs) contain ysE, so here we investigate if cystic EBs model ysE imprinted expression. The imprinted expression pattern of cystic EBs is shown to resemble fetal liver and not ysE. To investigate the reason for this we characterized the methylome and transcriptome of cystic EBs in comparison to fetal liver and ysE, by whole genome bisulphite sequencing and RNA-seq. Cystic EBs show a fetal liver pattern of global hypermethylation and low expression of repeats, while ysE shows global hypomethylation and high expression of IAPEz retroviral repeats, as reported for placenta. Transcriptome analysis confirmed that cystic EBs are more similar to fetal liver than ysE and express markers of early embryonic endoderm. Genome-wide analysis shows that ysE shares epigenetic and repeat expression features with placenta. Contrary to previous reports, we show that cystic EBs do not contain ysE, but are more similar to the embryonic endoderm of fetal liver. This explains why cystic EBs reproduce the imprinted expression seen in the embryo but not that seen in the ysE. PMID:25912690

The importance of early life family factors in the association between cardiovascular risk factors and early cardiovascular mortality.

PubMed

Kjøllesdal, Marte K R; Ariansen, Inger; Mortensen, Laust H; Næss, Øyvind

2017-01-01

To explore the importance of early life factors shared by siblings, such as parental socioeconomic position, parental practices, housing and neighbourhood, for the association between cardiovascular disease (CVD) risk factors and mortality from CVD, ischaemic heart disease (IHD) and cerebrovascular disease. Norwegian health surveys (1974-2003) were linked with data from the Norwegian Family Based Life Course Study and the Cause of Death Registry. Participants with at least one full sibling among survey participants (n=2 71 643) were included. Data on CVD risk factors, body mass index (BMI), height, systolic blood pressure (SBP) and total cholesterol (TC) were stratified into 'low', 'medium' and 'high' risk, and smoking to 'daily smoking' and 'not daily smoking'. Mean age of participants was 41 years, mean follow-up time was 19 years and during follow-up 2512 died from CVD. For each category of increased risk factor level, the per step HR of CVD mortality was increased by 1.91 (95% CI 1.78 to 2.05) for SBP, 1.67 (1.58 to 1.76) for TC, 1.44 (1.36 to 1.53) for BMI, 1.26 (1.18 to 1.35) for height and 2.89 (2.66 to 3.14) for smoking. In analyses where each sibship (groups of full siblings) had a group-specific baseline hazard, these associations were attenuated to 1.74, 1.51, 1.29, 1.18 and 2.63, respectively. The associations between risk factors and IHD mortality followed the same pattern. Early life family factors explained a small part of the association between risk factors and mortality from CVD and IHD in a relatively young sample.

Epigenetic modulation by TFII-I during embryonic stem cell differentiation.

PubMed

Bayarsaihan, Dashzeveg; Makeyev, Aleksandr V; Enkhmandakh, Badam

2012-10-01

TFII-I transcription factors play an essential role during early vertebrate embryogenesis. Genome-wide mapping studies by ChIP-seq and ChIP-chip revealed that TFII-I primes multiple genomic loci in mouse embryonic stem cells and embryonic tissues. Moreover, many TFII-I-bound regions co-localize with H3K4me3/K27me3 bivalent chromatin within the promoters of lineage-specific genes. This minireview provides a summary of current knowledge regarding the function of TFII-I in epigenetic control of stem cell differentiation. Copyright © 2012 Wiley Periodicals, Inc.

Early detection of emerging zoonotic diseases with animal morbidity and mortality monitoring.

PubMed

Bisson, Isabelle-Anne; Ssebide, Benard J; Marra, Peter P

2015-03-01

Diseases transmitted between animals and people have made up more than 50% of emerging infectious diseases in humans over the last 60 years and have continued to arise in recent months. Yet, public health and animal disease surveillance programs continue to operate independently. Here, we assessed whether recent emerging zoonotic pathogens (n = 143) are known to cause morbidity or mortality in their animal host and if so, whether they were first detected with an animal morbidity/mortality event. We show that although sick or dead animals are often associated with these pathogens (52%), only 9% were first detected from an animal morbidity or mortality event prior to or concurrent with signs of illness in humans. We propose that an animal morbidity and mortality reporting program will improve detection and should be an essential component of early warning systems for zoonotic diseases. With the use of widespread low-cost technology, such a program could engage both the public and professionals and be easily tested and further incorporated as part of surveillance efforts by public health officials.

Early detection strategy and mortality reduction in severe sepsis.

PubMed

Westphal, Glauco Adrieno; Feijó, Janaína; Andrade, Patrícia Silva de; Trindade, Louise; Suchard, Cezar; Monteiro, Márcio Andrei Gil; Martins, Sheila Fonseca; Nunes, Fernanda; Caldeira Filho, Milton

2009-06-01

To evaluate the impact of implementing an institutional policy for detection of severe sepsis and septic shock. Study before (stage I), after (stage II) with prospective data collection in a 195 bed public hospital.. Stage I: Patients with severe sepsis or septic shock were included consecutively over 15 months and treated according to the Surviving Sepsis Campaign guidelines. Stage II: In the 10 subsequent months, patients with severe sepsis or septic shock were enrolled based on an active search for signs suggesting infection (SSI) in hospitalized patients. The two stages were compared for demographic variables, time needed for recognition of at least two signs suggesting infection (SSI-Δt), compliance to the bundles of 6 and 24 hours and mortality. We identified 124 patients with severe sepsis or septic shock, 68 in stage I and 56 in stage II. The demographic variables were similar in both stages. The Δt-SSI was 34 ± 54 hours in stage I and 7 ± 8.4 hours in stage II (p <0.001). There was no difference in compliance to the bundles. In parallel there was significant reduction of mortality rates at 28 days (54.4% versus 30%, p <0.02) and hospital (67.6% versus 41%, p <0.003). The strategy used helped to identify early risk of sepsis and resulted in decreased mortality associated with severe sepsis and septic shock.

Early Childbearing, Marital Status, and Women's Health and Mortality after Age 50

ERIC Educational Resources Information Center

Henretta, John C.

2007-01-01

This article examines the relationship between a woman's childbearing history and her later health and mortality, with primary focus on whether the association between them is due to early and later socioeconomic status. Data are drawn from the Health and Retirement Study birth cohort of 1931-1941. Results indicate that, conditional on reaching…

Spatial variations in mortality in pelagic early life stages of a marine fish (Gadus morhua)

NASA Astrophysics Data System (ADS)

Langangen, Øystein; Stige, Leif C.; Yaragina, Natalia A.; Ottersen, Geir; Vikebø, Frode B.; Stenseth, Nils Chr.

2014-09-01

Mortality of pelagic eggs and larvae of marine fish is often assumed to be constant both in space and time due to lacking information. This may, however, be a gross oversimplification, as early life stages are likely to experience large variations in mortality both in time and space. In this paper we develop a method for estimating the spatial variability in mortality of eggs and larvae. The method relies on survey data and physical-biological particle-drift models to predict the drift of ichthyoplankton. Furthermore, the method was used to estimate the spatially resolved mortality field in the egg and larval stages of Barents Sea cod (Gadus morhua). We analyzed data from the Barents Sea for the period between 1959 and 1993 when there are two surveys available: a spring and a summer survey. An individual-based physical-biological particle-drift model, tailored to the egg and larval stages of Barents Sea cod, was used to predict the drift trajectories from the observed stage-specific distributions in spring to the time of observation in the summer, a drift time of approximately 45 days. We interpreted the spatial patterns in the differences between the predicted and observed abundance distributions in summer as reflecting the spatial patterns in mortality over the drift period. Using the estimated mortality fields, we show that the spatial variations in mortality might have a significant impact on survival to later life stages and we suggest that there may be trade-offs between increased early survival in off shore regions and reduced probability of ending up in the favorable nursing grounds in the Barents Sea. In addition, we show that accounting for the estimated mortality field, improves the correlation between a simulated recruitment index and observation-based indices of juvenile abundance.

GLUT3 gene expression is critical for embryonic growth, brain development and survival.

PubMed

Carayannopoulos, Mary O; Xiong, Fuxia; Jensen, Penny; Rios-Galdamez, Yesenia; Huang, Haigen; Lin, Shuo; Devaskar, Sherin U

2014-04-01

Glucose is the primary energy source for eukaryotic cells and the predominant substrate for the brain. GLUT3 is essential for trans-placental glucose transport and highly expressed in the mammalian brain. To further elucidate the role of GLUT3 in embryonic development, we utilized the vertebrate whole animal model system of Danio rerio as a tractable system for defining the cellular and molecular mechanisms altered by impaired glucose transport and metabolism related to perturbed expression of GLUT3. The comparable orthologue of human GLUT3 was identified and the expression of this gene abrogated during early embryonic development. In a dose-dependent manner embryonic brain development was disrupted resulting in a phenotype of aberrant brain organogenesis, associated with embryonic growth restriction and increased cellular apoptosis. Rescue of the morphant phenotype was achieved by providing exogenous GLUT3 mRNA. We conclude that GLUT3 is critically important for brain organogenesis and embryonic growth. Disruption of GLUT3 is responsible for the phenotypic spectrum of embryonic growth restriction to demise and neural apoptosis with microcephaly. Copyright © 2014 Elsevier Inc. All rights reserved.

GLUT3 Gene Expression is Critical for Embryonic Growth, Brain Development and Survival

PubMed Central

Carayannopoulos, Mary O.; Xiong, Fuxia; Jensen, Penny; Rios-Galdamez, Yesenia; Huang, Haigen; Lin, Shuo; Devaskar, Sherin U.

2015-01-01

Glucose is the primary energy source for eukaryotic cells and the predominant substrate for the brain. GLUT3 is essential for trans-placental glucose transport and highly expressed in the mammalian brain. To further elucidate the role of GLUT3 in embryonic development, we utilized the vertebrate whole animal model system of Danio rerio as a tractable system for defining the cellular and molecular mechanisms altered by impaired glucose transport and metabolism related to perturbed expression of GLUT3. The comparable orthologue of human GLUT3 was identified and the expression of this gene abrogated during early embryonic development. In a dose-dependent manner embryonic brain development was disrupted resulting in a phenotype of aberrant brain organogenesis, associated with embryonic growth restriction and increased cellular apoptosis. Rescue of the morphant phenotype was achieved by providing exogenous GLUT3 mRNA. We conclude that GLUT3 is critically important for brain organogenesis and embryonic growth. Disruption of GLUT3 is responsible for the phenotypic spectrum of embryonic growth restriction to demise and neural apoptosis with microcephaly. PMID:24529979

Early embryonic survival and embryo development in two lines of rabbits divergently selected for uterine capacity.

PubMed

Peiró, R; Santacreu, M A; Climent, A; Blasco, A

2007-07-01

The aim of this work is to study early embryo survival and development in 2 lines divergently selected for high and low uterine capacity throughout 10 generations. A total of 162 female rabbits from the high line and 133 from the low line were slaughtered at 25, 48, or 62 h of gestation. There were no differences in ovulation rate and fertilization rate between lines in any of the 3 stages of gestation. Embryo survival, estimated as the number of normal embryos recovered at a constant ovulation rate, was similar in both lines at 25 and 48 h. Embryo survival was greater in the high line [D (posterior mean of the difference between the high and low lines) = 0.57 embryos] at 62 h of gestation. There was no difference in embryonic stage of development at 25 h, but at 48 and 62 h of gestation, the high line, compared with the low line, had a greater percentage of early morulae (83 vs. 72%) and compacted morulae (55 vs. 38%). Divergent selection for uterine capacity appeared to modify embryo development, at least from 48 h of gestation, and embryo survival from 62 h.

Expression analysis of the insulin-like growth factors I and II during embryonic and early larval development of turbot ( Scophthalmus maximus)

NASA Astrophysics Data System (ADS)

Wen, Haishen; Qi, Qian; Hu, Jian; Si, Yufeng; He, Feng; Li, Jifang

2015-04-01

The insulin-like growth factors I and II (IGF-I and IGF-II) are important proteins involved in fish growth and development. Here, we report the isolation of IGF-II and expression analysis of IGFs in turbot Scophthalmus maximus, aiming to clarify their function in embryonic and larval development of fish. The deduced IGF-II gene is 808 bp in full length, which encodes a protein of 219 amino acids and is 93% similar with that of Paralichthys olicaceus in amino acid sequence. The tissue abundance and the expression pattern of IGFs in a turbot at early development stages were investigated via reverse transcription-polymer chain reaction. Result showed that the IGF-I and IGF-II genes were widely expressed in tissues of S. maximus. IGF-I was detected in all tissues except intestines with the highest level in liver, while IGF-II transcript presented in all tissues except muscle. At the stages of embryonic and larval development, the mRNA levels of IGFs sharply increased from the stage of unfertilized egg to post larva, followed by a decrease with larval development. However, there was an increase in IGF-I at the embryonic stage and IGF-II at the gastrula stage, respectively. These results suggested that IGFs play important roles in cell growth and division of the turbot. Our study provides reference data for further investigation of growth regulation in turbot, which can guarantee better understanding of the physiological role that IGFs play in fish.

Epigenomic Analysis of Multi-lineage Differentiation of Human Embryonic Stem Cells

PubMed Central

Xie, Wei; Schultz, Matthew D.; Lister, Ryan; Hou, Zhonggang; Rajagopal, Nisha; Ray, Pradipta; Whitaker, John W.; Tian, Shulan; Hawkins, R. David; Leung, Danny; Yang, Hongbo; Wang, Tao; Lee, Ah Young; Swanson, Scott A.; Zhang, Jiuchun; Zhu, Yun; Kim, Audrey; Nery, Joseph R.; Urich, Mark A.; Kuan, Samantha; Yen, Chia-an; Klugman, Sarit; Yu, Pengzhi; Suknuntha, Kran; Propson, Nicholas E.; Chen, Huaming; Edsall, Lee E.; Wagner, Ulrich; Li, Yan; Ye, Zhen; Kulkarni, Ashwinikumar; Xuan, Zhenyu; Chung, Wen-Yu; Chi, Neil C.; Antosiewicz-Bourget, Jessica E.; Slukvin, Igor; Stewart, Ron; Zhang, Michael Q.; Wang, Wei; Thomson, James A.; Ecker, Joseph R.; Ren, Bing

2013-01-01

SUMMARY Epigenetic mechanisms have been proposed to play crucial roles in mammalian development, but their precise functions are only partially understood. To investigate epigenetic regulation of embryonic development, we differentiated human embryonic stem cells into mesendoderm, neural progenitor cells, trophoblast-like cells, and mesenchymal stem cells, and systematically characterized DNA methylation, chromatin modifications, and the transcriptome in each lineage. We found that promoters that are active in early developmental stages tend to be CG rich and mainly engage H3K27me3 upon silencing in non-expressing lineages. By contrast, promoters for genes expressed preferentially at later stages are often CG poor and primarily employ DNA methylation upon repression. Interestingly, the early developmental regulatory genes are often located in large genomic domains that are generally devoid of DNA methylation in most lineages, which we termed DNA methylation valleys (DMVs). Our results suggest that distinct epigenetic mechanisms regulate early and late stages of ES cell differentiation. PMID:23664764

Embryonic toxico-pathological effects of meglumine antimoniate using a chick embryo model.

PubMed

Khosravi, Ahmad; Sharifi, Iraj; Tavakkoli, Hadi; Derakhshanfar, Amin; Keyhani, Ali Reza; Salari, Zohreh; Mosallanejad, Seyedeh Saedeh; Bamorovat, Mehdi

2018-01-01

Leishmaniasis is one of the diverse and neglected tropical diseases. Embryo-toxicity of drugs has always been a major concern. Chick embryo is a preclinical model relevant in the assessment of adverse effects of drugs. The current study aimed to assess embryonic histopathological disorders and amniotic fluid biochemical changes following meglumine antimoniate treatment. The alteration of vascular branching pattern in the chick's extra-embryonic membrane and exploration of molecular cues to early embryonic vasculogenesis and angiogenesis were also quantified. Embryonated chicken eggs were treated with 75 or 150 mg/kg of meglumine antimoniate. Embryo malformations, growth retardation and haemorrhages on the external body surfaces were accompanied by histopathological lesions in the brain, kidney, liver and heart in a dose-dependent manner. Significant rise occurred in the biochemical indices of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and amylase in the amniotic fluid. Quantification of the extra-embryonic membrane vasculature showed that the anti-angiogenic and anti-vasculogenic effects of the drug were revealed by a significant decrease in fractal dimension value and mean capillary area. The relative expression levels of vascular endothelial growth factor A and vascular endothelial growth factor receptor 2 mRNA also significantly reduced. Concerns of a probable teratogenicity of meglumine antimoniate were established by data presented in this study. It is concluded that tissue lesions, amniotic fluid disturbance, altered early extra-embryonic vascular development and gene expression as well as the consecutive cascade of events, might eventually lead to developmental defects in embryo following meglumine antimoniate treatment. Therefore, the use of meglumine antimoniate during pregnancy should be considered as potentially embryo-toxic. Hence, physicians should be aware of such teratogenic effects and limit the use of this drug

Birth asphyxia: a major cause of early neonatal mortality in a Tanzanian rural hospital.

PubMed

Ersdal, Hege Langli; Mduma, Estomih; Svensen, Erling; Perlman, Jeffrey

2012-05-01

Early neonatal mortality within the first 24 hours contributes substantially to overall neonatal mortality rates. The definition of birth asphyxia (BA) is imprecise, and reliable cause-specific mortality data are limited; thus the estimated proportion of BA-related deaths globally remains questionable. The objective was to determine the presumed causes of neonatal death within the first 24 hours in a rural hospital in Northern Tanzania. This is a prospective descriptive observational study conducted in the delivery room and adjacent neonatal area. Research assistants were trained to observe and record events related to labor, neonatal resuscitation, and 24-hour postnatal course. BA was defined as failure to initiate spontaneous respirations and/or 5-minute Apgar score <7, prematurity as gestational age <36 weeks, and low birth weight (LBW) as birth weight <3rd centile for gestational age. Data were analyzed with χ(2) and Student's t tests. Over 1 year, 4720 infants were born and evaluated. Of these, 256 were admitted to the neonatal area. Forty-nine infants died secondary to BA (61%), prematurity (18%), LBW (8%), infection (2%), congenital abnormalities (8%), and unclear reason (2%). The 5-minute Apgar score was ≥7 in 50% of the infants who died secondary to BA. Most cases of early neonatal mortality were related to BA, and prematurity and LBW are additional important considerations. Reducing perinatal mortality requires a multifaceted approach with attention to issues related to BA, potential complications of prematurity, and LBW. The 5-minute Apgar score is a poor surrogate of BA.

Association between mild intellectual disability and early mortality in men and women: evidence from a population-based cohort study

PubMed Central

Maenner, Matthew J; Greenberg, Jan S; Mailick, Marsha R

2016-01-01

Lower (versus higher) IQ scores have been shown to increase the risk of early mortality, however, the underlying mechanisms are poorly understood and previous studies underrepresent individuals with intellectual disabilities and women. This study followed one-third of all senior-year students (approximately aged 17) attending public high school in Wisconsin, USA in 1957 (n=10,317) until 2011. Men and women with mild intellectual disabilities had increased rates of mortality compared to people with the highest IQs, particularly for cardiovascular disease. Importantly, when educational attainment was held constant, people with intellectual disabilities did not have higher mortality by age 70 than people with higher IQs. Individuals with intellectual disabilities likely experience multiple disadvantages throughout life that contribute to increased risk of early mortality. PMID:25928436

The importance of early life family factors in the association between cardiovascular risk factors and early cardiovascular mortality

PubMed Central

Kjøllesdal, Marte K R; Ariansen, Inger; Mortensen, Laust H; Næss, Øyvind

2017-01-01

Objective To explore the importance of early life factors shared by siblings, such as parental socioeconomic position, parental practices, housing and neighbourhood, for the association between cardiovascular disease (CVD) risk factors and mortality from CVD, ischaemic heart disease (IHD) and cerebrovascular disease. Methods Norwegian health surveys (1974–2003) were linked with data from the Norwegian Family Based Life Course Study and the Cause of Death Registry. Participants with at least one full sibling among survey participants (n=2 71 643) were included. Data on CVD risk factors, body mass index (BMI), height, systolic blood pressure (SBP) and total cholesterol (TC) were stratified into ‘low’, ‘medium’ and ‘high’ risk, and smoking to ‘daily smoking’ and ‘not daily smoking’. Results Mean age of participants was 41 years, mean follow-up time was 19 years and during follow-up 2512 died from CVD. For each category of increased risk factor level, the per step HR of CVD mortality was increased by 1.91 (95% CI 1.78 to 2.05) for SBP, 1.67 (1.58 to 1.76) for TC, 1.44 (1.36 to 1.53) for BMI, 1.26 (1.18 to 1.35) for height and 2.89 (2.66 to 3.14) for smoking. In analyses where each sibship (groups of full siblings) had a group-specific baseline hazard, these associations were attenuated to 1.74, 1.51, 1.29, 1.18 and 2.63, respectively. The associations between risk factors and IHD mortality followed the same pattern. Conclusion Early life family factors explained a small part of the association between risk factors and mortality from CVD and IHD in a relatively young sample. PMID:28878947

Causes of mortality in early infantile epileptic encephalopathy: A systematic review.

PubMed

Radaelli, Graciane; de Souza Santos, Francisco; Borelli, Wyllians Vendramini; Pisani, Leonardo; Nunes, Magda Lahorgue; Scorza, Fulvio Alexandre; da Costa, Jaderson Costa

2018-06-12

Early infantile epileptic encephalopathy syndrome (EIEE), also known as Ohtahara syndrome, is an age-dependent epileptic encephalopathy syndrome defined by clinical features and electroencephalographic findings. Epileptic disorders with refractory seizures beginning in the neonatal period and/or early infancy have a potential risk of premature mortality, including sudden death. We aimed to identify the causes of death in EIEE and conducted a literature survey of fatal outcomes. We performed a literature search in MEDLINE, EMBASE, and Web of Science for data from inception until September 2017. The terms "death sudden," "unexplained death," "SUDEP," "lethal," and "fatal" and the medical subject heading terms "epileptic encephalopathy," "mortality," "death," "sudden infant death syndrome," and "human" were used in the search strategy. The EIEE case report studies reporting mortality were included. The search yielded 1360 articles. After screening for titles and abstracts and removing duplicate entries, full texts of 15 articles were reviewed. After reading full texts, 11 articles met the inclusion criteria (9 articles in English and 2 in Japanese, dated from 1976 to 2015). The review comprised 38 unique cases of EIEE, 17 of which had death as an outcome. In all cases, the suppression-burst pattern on electroencephalographies (EEGs) was common. Most cases (55%) involved male infants. The mean (standard deviation [SD]) age at onset of seizure was 19.6 ± 33 days. The mean (SD) age at death was 12.9 ± 14.1 months. Most infants (58.8%) survived less than one year. The cause of death was described only in eight (47%) patients; the cause was pneumonia/respiratory illness or sudden unexpected death in epilepsy (SUDEP). The results show EIEE as a severe disease associated with a premature mortality, evidenced by a very young age at death. Increasing interest in the detection of new molecular bases of EIEE is leading us to a better understanding of this severe

Pneumonectomy for lung cancer: contemporary national early morbidity and mortality outcomes.

PubMed

Thomas, Pascal A; Berbis, Julie; Baste, Jean-Marc; Le Pimpec-Barthes, Françoise; Tronc, François; Falcoz, Pierre-Emmanuel; Dahan, Marcel; Loundou, Anderson

2015-01-01

The study objective was to determine contemporary early outcomes associated with pneumonectomy for lung cancer and to identify their predictors using a nationally representative general thoracic surgery database (EPITHOR). After discarding inconsistent files, a group of 4498 patients who underwent elective pneumonectomy for primary lung cancer between 2003 and 2013 was selected. Logistic regression analysis was performed on variables for mortality and major adverse events. Then, a propensity score analysis was adjusted for imbalances in baseline characteristics between patients with or without neoadjuvant treatment. Operative mortality was 7.8%. Surgical, cardiovascular, pulmonary, and infectious complications rates were 14.9%, 14.1%, 11.5%, and 2.7%, respectively. None of these complications were predicted by the performance of a neoadjuvant therapy. Operative mortality analysis, adjusted for the propensity scores, identified age greater than 65 years (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.5-2.9; P < .001), underweight body mass index category (OR, 2.2; 95% CI, 1.2-4.0; P = .009), American Society of Anesthesiologists score of 3 or greater (OR, 2.310; 95% CI, 1.615-3.304; P < .001), right laterality of the procedure (OR, 1.8; 95% CI, 1.1-2.4; P = .011), performance of an extended pneumonectomy (OR, 1.5; 95% CI, 1.1-2.1; P = .018), and absence of systematic lymphadenectomy (OR, 2.9; 95% CI, 1.1-7.8; P = .027) as risk predictors. Induction therapy (OR, 0.63; 95% CI, 0.5-0.9; P = .005) and overweight body mass index category (OR, 0.60; 95% CI, 0.4-0.9; P = .033) were protective factors. Several risk factors for major adverse early outcomes after pneumonectomy for cancer were identified. Overweight patients and those who received induction therapy had paradoxically lower adjusted risks of mortality. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Toxicity of o,p′-DDE to medaka d-rR strain after a one-time embryonic exposure by in ovo nanoinjection: An early through juvenile life cycle assessment

USGS Publications Warehouse

Villalobos, Sergio A.; Papoulias, Diana M.; Pastva, Stephanie D.; Blankenship, Alan L.; Meadows, John C.; Tillitt, Donald E.; Giesy, John P.

2003-01-01

The toxicity of o,p′-DDE (1,1-dichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl) ethylene) was evaluated in embryos of medaka (Oryzias latipes) following a one time exposure via nanoinjection. Medaka eggs (early gastrula) were injected with 0.5 nl of triolein (vehicle control) or 0.5 nl of 4 graded doses (0.0005-0.5 ng/egg) of o,p′-DDE in triolein. Embryos were allowed to develop, and fry were reared. Embryonic survival was monitored daily during the first 10 d until hatching and thereafter, on a weekly basis until day 59, at which time the fish were monitored for sexual maturity until day 107. In general, o,p′-DDE caused a dose- and time-dependent mortality. No changes in mortality were observed between the last two time points (day 38 and 59, respectively), and hence a 59 day-LD50 of 346 ng o,p′-DDE/egg was derived from the linear dose-response relationship. Prior to late stage death, only isolated cases of cardiovascular lesions and spinal deformities were observed, but were not dose-dependent. The lowest observable adverse effect level (LOAEL), based on upper 95% CI for regression line=0.0018 mg/kg, and the LOAEL based on exposure doses=0.5 mg/kg. Likewise, the no observable adverse effect level (NOAEL) based on linear extrapolation to 100% survival=0.0000388 mg/kg, while the NOAEL based on exposure doses=0.05 mg/kg. The nanoinjection medaka model has potential in the study of hormonally active compounds in the environment.

Prognostic capability of different liver disease scoring systems for prediction of early mortality after transjugular intrahepatic portosystemic shunt creation.

PubMed

Gaba, Ron C; Couture, Patrick M; Bui, James T; Knuttinen, M Grace; Walzer, Natasha M; Kallwitz, Eric R; Berkes, Jamie L; Cotler, Scott J

2013-03-01

To compare the performance of various liver disease scoring systems in predicting early mortality after transjugular intrahepatic portosystemic shunt (TIPS) creation. In this single-institution retrospective study, eight scoring systems were used to grade liver disease in 211 patients (male-to-female ratio = 131:80; mean age, 54 y) before TIPS creation from 1999-2011. Scoring systems included bilirubin level, Child-Pugh (CP) score, Model for End-Stage Liver Disease (MELD) and Model for End-Stage Liver Disease sodium (MELD-Na) score, Emory score, prognostic index (PI), Acute Physiology and Chronic Health Evaluation (APACHE) 2 score, and Bonn TIPS early mortality (BOTEM) score. Medical record review was used to identify 30-day and 90-day clinical outcomes. The relationship of scoring parameters with mortality outcomes was assessed with multivariate analysis, and the relative ability of systems to predict mortality after TIPS creation was evaluated by comparing area under receiver operating characteristic (AUROC) curves. TIPS were successfully created for variceal hemorrhage (n = 121), ascites (n = 72), hepatic hydrothorax (n = 15), and portal vein thrombosis (n = 3). All scoring systems had a significant association with 30-day and 90-day mortality (P<.050 in each case) on multivariate analysis. Based on 30-day and 90-day AUROC, MELD (0.878, 0.816) and MELD-Na (0.863, 0.823) scores had the best capability to predict early mortality compared with bilirubin (0.786, 0.749), CP (0.822, 0.771), Emory (0.786, 0.681), PI (0.854, 0.760), APACHE 2 (0.836, 0.735), and BOTEM (0.798, 0.698), with statistical superiority over bilirubin, Emory, and BOTEM scores. Several liver disease scoring systems have prognostic value for early mortality after TIPS creation. MELD and MELD-Na scores most effectively predict survival after TIPS creation. Copyright © 2013. Published by Elsevier Inc.

Complex life cycles and density dependence: assessing the contribution of egg mortality to amphibian declines.

PubMed

Vonesh, James R; De la Cruz, Omar

2002-11-01

In the last decade there has been increasing evidence of amphibian declines from relatively pristine areas. Some declines are hypothesized to be the result of egg mortality caused by factors such as elevated solar UV-B irradiation, chemical pollutants, pathogenic fungi, and climate change. However, the population-level consequences of egg mortality have not been examined explicitly, and may be complicated by density dependence in intervening life-history stages. Here we develop a demographic model for two amphibians with contrasting life-history strategies, Bufo boreas and Ambystoma macrodactylum. We then use the complementary approaches of elasticity and limitation to examine the relationships among stage-specific survival rates, larval-stage density dependence and amphibian population dynamics. Elasticity analyses showed that for a range of density dependence scenarios both species were more sensitive to changes in post-embryonic survival parameters, particularly juvenile survival, than to egg survival, suggesting that mortality of later stages may play an important role in driving declines. Limitation analyses revealed that larval density dependence can dramatically alter the consequences of early mortality, reducing or even reversing the expected population-level effects of egg mortality. Thus, greater focus on later life stages and density dependence is called for to accurately assess how stressors are likely to affect amphibian populations of conservation concern.

High- and low-temperature manipulation during late incubation: effects on embryonic development, the hatching process, and metabolism in broilers.

PubMed

Willemsen, H; Kamers, B; Dahlke, F; Han, H; Song, Z; Ansari Pirsaraei, Z; Tona, K; Decuypere, E; Everaert, N

2010-12-01

Temperatures continuously higher and lower than the standard incubation temperature by 3°C from embryonic d 16 until embryonic d 18.5 result in differential effects on embryonic development, the hatching process, and embryonic metabolism. Embryos in the high-temperature group were forced into a state of malnutrition by the temperature treatment, as reflected by reduced embryo growth and yolk consumption, resulting in a significantly lower chick weight at hatch. In addition, altered air cell and blood gases as well as a retarded hatching process further indicated reduced growth of embryos exposed to higher incubation temperatures during the latter part of incubation. In addition, hatchability was significantly reduced by the high-temperature treatment due to higher embryonic mortality during the treatment period and the hatching process. Levels of blood glucose, lactate, liver glycogen, plasma triglycerides, and nonesterified fatty acids indicated an altered carbohydrate and lipid metabolism for the high-temperature group. Although the hatching process of embryos exposed to lower incubation temperatures was also significantly retarded, their embryonic development and growth were strikingly similar to those of the control group.

Similar GABAergic inputs in dentate granule cells born during embryonic and adult neurogenesis.

PubMed

Laplagne, Diego A; Kamienkowski, Juan E; Espósito, M Soledad; Piatti, Verónica C; Zhao, Chunmei; Gage, Fred H; Schinder, Alejandro F

2007-05-01

Neurogenesis in the dentate gyrus of the hippocampus follows a unique temporal pattern that begins during embryonic development, peaks during the early postnatal stages and persists through adult life. We have recently shown that dentate granule cells born in early postnatal and adult mice acquire a remarkably similar afferent connectivity and firing behavior, suggesting that they constitute a homogeneous functional population [Laplagne et al. (2006)PLoS Biol., 4, e409]. Here we extend our previous study by comparing mature neurons born in the embryonic and adult hippocampus, with a focus on intrinsic membrane properties and gamma-aminobutyric acid (GABA)ergic synaptic inputs. For this purpose, dividing neuroblasts of the ventricular wall were retrovirally labeled with green fluorescent protein at embryonic day 15 (E15), and progenitor cells of the subgranular zone were labeled with red fluorescent protein in the same mice at postnatal day 42 (P42, adulthood). Electrophysiological properties of mature neurons born at either stage were then compared in the same brain slices. Evoked and spontaneous GABAergic postsynaptic responses of perisomatic and dendritic origin displayed similar characteristics in both neuronal populations. Miniature GABAergic inputs also showed similar functional properties and pharmacological profile. A comparative analysis of the present data with our previous observations rendered no significant differences among GABAergic inputs recorded from neurons born in the embryonic, early postnatal and adult mice. Yet, embryo-born neurons showed a reduced membrane excitability, suggesting a lower engagement in network activity. Our results demonstrate that granule cells of different age, location and degree of excitability receive GABAergic inputs of equivalent functional characteristics.

Muscular dystrophy begins early in embryonic development deriving from stem cell loss and disrupted skeletal muscle formation

PubMed Central

Merrick, Deborah; Stadler, Lukas Kurt Josef; Larner, Dean; Smith, Janet

2009-01-01

SUMMARY Examination of embryonic myogenesis of two distinct, but functionally related, skeletal muscle dystrophy mutants (mdx and cav-3−/−) establishes for the first time that key elements of the pathology of Duchenne muscular dystrophy (DMD) and limb-girdle muscular dystrophy type 1C (LGMD-1c) originate in the disruption of the embryonic cardiac and skeletal muscle patterning processes. Disruption of myogenesis occurs earlier in mdx mutants, which lack a functional form of dystrophin, than in cav-3−/− mutants, which lack the Cav3 gene that encodes the protein caveolin-3; this finding is consistent with the milder phenotype of LGMD-1c, a condition caused by mutations in Cav3, and the earlier [embryonic day (E)9.5] expression of dystrophin. Myogenesis is severely disrupted in mdx embryos, which display developmental delays; myotube morphology and displacement defects; and aberrant stem cell behaviour. In addition, the caveolin-3 protein is elevated in mdx embryos. Both cav-3−/− and mdx mutants (from E15.5 and E11.5, respectively) exhibit hyperproliferation and apoptosis of Myf5-positive embryonic myoblasts; attrition of Pax7-positive myoblasts in situ; and depletion of total Pax7 protein in late gestation. Furthermore, both cav-3−/− and mdx mutants have cardiac defects. In cav-3−/− mutants, there is a more restricted phenotype comprising hypaxial muscle defects, an excess of malformed hypertrophic myotubes, a twofold increase in myonuclei, and reduced fast myosin heavy chain (FMyHC) content. Several mdx mutant embryo pathologies, including myotube hypotrophy, reduced myotube numbers and increased FMyHC, have reciprocity with cav-3−/− mutants. In double mutant (mdxcav-3+/−) embryos that are deficient in dystrophin (mdx) and heterozygous for caveolin-3 (cav-3+/−), whereby caveolin-3 is reduced to 50% of wild-type (WT) levels, these phenotypes are severely exacerbated: intercostal muscle fibre density is reduced by 71%, and Pax7-positive

Embryonic cholecystitis and defective gallbladder contraction in the Sox17-haploinsufficient mouse model of biliary atresia

PubMed Central

Fujino, Ko; Igarashi, Hitomi; Imaimatsu, Kenya; Tsunekawa, Naoki; Hirate, Yoshikazu; Kurohmaru, Masamichi; Saijoh, Yukio; Kanai-Azuma, Masami

2017-01-01

The gallbladder excretes cytotoxic bile acids into the duodenum through the cystic duct and common bile duct system. Sox17 haploinsufficiency causes biliary atresia-like phenotypes and hepatitis in late organogenesis mouse embryos, but the molecular and cellular mechanisms underlying this remain unclear. In this study, transcriptomic analyses revealed the early onset of cholecystitis in Sox17+/− embryos, together with the appearance of ectopic cystic duct-like epithelia in their gallbladders. The embryonic hepatitis showed positive correlations with the severity of cholecystitis in individual Sox17+/− embryos. Embryonic hepatitis could be induced by conditional deletion of Sox17 in the primordial gallbladder epithelia but not in fetal liver hepatoblasts. The Sox17+/− gallbladder also showed a drastic reduction in sonic hedgehog expression, leading to aberrant smooth muscle formation and defective contraction of the fetal gallbladder. The defective gallbladder contraction positively correlated with the severity of embryonic hepatitis in Sox17+/− embryos, suggesting a potential contribution of embryonic cholecystitis and fetal gallbladder contraction in the early pathogenesis of congenital biliary atresia. PMID:28432216

The birth of embryonic pluripotency

PubMed Central

Boroviak, Thorsten; Nichols, Jennifer

2014-01-01

Formation of a eutherian mammal requires concurrent establishment of embryonic and extraembryonic lineages. The functions of the trophectoderm and primitive endoderm are to enable implantation in the maternal uterus, axis specification and delivery of nutrients. The pluripotent epiblast represents the founding cell population of the embryo proper, which is protected from ectopic and premature differentiation until it is required to respond to inductive cues to form the fetus. While positional information plays a major role in specifying the trophoblast lineage, segregation of primitive endoderm from epiblast depends upon gradual acquisition of transcriptional identity, directed but not initiated by fibroblast growth factor (FGF) signalling. Following early cleavage divisions and formation of the blastocyst, cells of the inner cell mass lose totipotency. Developing epiblast cells transiently attain the state of naive pluripotency and competence to self-renew in vitro as embryonic stem cells and in vivo by means of diapause. This property is lost after implantation as the epiblast epithelializes and becomes primed in preparation for gastrulation and subsequent organogenesis. PMID:25349450

Metabolic circadian rhythms in embryonic turtles.

PubMed

Loudon, Fiona Kay; Spencer, Ricky-John; Strassmeyer, Alana; Harland, Karen

2013-07-01

Oviparous species are model organisms for investigating embryonic development of endogenous physiological circadian rhythms without the influence of maternal biorhythms. Recent studies have demonstrated that heart rates and metabolic rates of embryonic turtles are not constant or always maximal and can be altered in response to the presence of embryos at a more advanced stage of development within the nest. A first step in understanding the physiological mechanisms underpinning these responses in embryonic ectothermic organisms is to develop metabolic profiles (e.g., heart rate) at different temperatures throughout incubation. Heart beat and rhythmic patterns or changes in development may represent important signals or cues within a nest and may be vital to coordinate synchronous hatching well in advance of the final stages of incubation. We developed baseline embryonic heart-rate profiles of embryos of the short-necked Murray River turtle (Emydura macquarii) to determine the stage of embryogenesis that metabolic circadian rhythms become established, if at all. Eggs were incubated at constant temperatures (26°C and 30°C) and heart rates were monitored at 6-h intervals over 24 h every 7-11 days until hatching. Circadian heart rate rhythms were detected at the mid-gestation period and were maintained until hatching. Heart rates throughout the day varied by up to 20% over 24 h and were not related to time of day. This study demonstrated that endogenous metabolic circadian rhythms in developing embryos in turtle eggs establish earlier in embryogenesis than those documented in other vertebrate taxa during embryogenesis. Early establishment of circadian rhythms in heart rates may be critical for communication among embryos and synchrony in hatching and emergence from the nest.

Derivation, propagation and differentiation of human embryonic stem cells.

PubMed

Conley, Brock J; Young, Julia C; Trounson, Alan O; Mollard, Richard

2004-04-01

Embryonic stem (ES) cells are in vitro cultivated pluripotent cells derived from the inner cell mass (ICM) of the embryonic blastocyst. Attesting to their pluripotency, ES cells can be differentiated into representative derivatives of all three embryonic germ layers (endoderm, ectoderm and mesoderm) both in vitro and in vivo. Although mouse ES cells have been studied for many years, human ES cells have only more recently been derived and successfully propagated. Many biochemical differences and culture requirements between mouse and human ES cells have been described, yet despite these differences the study of murine ES cells has provided important insights into methodologies aimed at generating a greater and more in depth understanding of human ES cell biology. One common feature of both mouse and human ES cells is their capacity to undergo controlled differentiation into spheroid structures termed embryoid bodies (EBs). EBs recapitulate several aspects of early development, displaying regional-specific differentiation programs into derivatives of all three embryonic germ layers. For this reason, EB formation has been utilised as an initial step in a wide range of studies aimed at differentiating both mouse and human ES cells into a specific and desired cell type. Recent reports utilising specific growth factor combinations and cell-cell induction systems have provided alternative strategies for the directed differentiation of cells into a desired lineage. According to each one of these strategies, however, a relatively high cell lineage heterogeneity remains, necessitating subsequent purification steps including mechanical dissection, selective media or fluorescent or magnetic activated cell sorting (FACS and MACS, respectively). In the future, the ability to specifically direct differentiation of human ES cells at 100% efficiency into a desired lineage will allow us to fully explore the potential of these cells in the analysis of early human development, drug

The first whole transcriptomic exploration of pre-oviposited early chicken embryos using single and bulked embryonic RNA-sequencing.

PubMed

Hwang, Young Sun; Seo, Minseok; Choi, Hee Jung; Kim, Sang Kyung; Kim, Heebal; Han, Jae Yong

2018-04-01

The chicken is a valuable model organism, especially in evolutionary and embryology research because its embryonic development occurs in the egg. However, despite its scientific importance, no transcriptome data have been generated for deciphering the early developmental stages of the chicken because of practical and technical constraints in accessing pre-oviposited embryos. Here, we determine the entire transcriptome of pre-oviposited avian embryos, including oocyte, zygote, and intrauterine embryos from Eyal-giladi and Kochav stage I (EGK.I) to EGK.X collected using a noninvasive approach for the first time. We also compare RNA-sequencing data obtained using a bulked embryo sequencing and single embryo/cell sequencing technique. The raw sequencing data were preprocessed with two genome builds, Galgal4 and Galgal5, and the expression of 17,108 and 26,102 genes was quantified in the respective builds. There were some differences between the two techniques, as well as between the two genome builds, and these were affected by the emergence of long intergenic noncoding RNA annotations. The first transcriptome datasets of pre-oviposited early chicken embryos based on bulked and single embryo sequencing techniques will serve as a valuable resource for investigating early avian embryogenesis, for comparative studies among vertebrates, and for novel gene annotation in the chicken genome.

Radiation Exposure and Mortality from Cardiovascular Disease and Cancer in Early NASA Astronauts.

PubMed

Elgart, S Robin; Little, Mark P; Chappell, Lori J; Milder, Caitlin M; Shavers, Mark R; Huff, Janice L; Patel, Zarana S

2018-05-31

Understanding space radiation health effects is critical due to potential increased morbidity and mortality following spaceflight. We evaluated whether there is evidence for excess cardiovascular disease or cancer mortality in early NASA astronauts and if a correlation exists between space radiation exposure and mortality. Astronauts selected from 1959-1969 were included and followed until death or February 2017, with 39 of 73 individuals still alive at that time. Calculated standardized mortality rates for tested outcomes were significantly below U.S. white male population rates, including all-cardiovascular disease (n = 7, SMR = 33; 95% CI, 14-65) and all-cancer (n = 7, SMR = 43; 95% CI, 18-83), as anticipated in a healthy worker population. Space radiation doses for cohort members ranged from 0-78 mGy. No significant associations between space radiation dose and mortality were found using logistic regression with an internal reference group, adjusting for medical radiation. Statistical power of the logistic regression was <6%, remaining <12% even when expected risk level or observed deaths were assumed to be 10 times higher than currently reported. While no excess radiation-associated cardiovascular or cancer mortality risk was observed, findings must be tempered by the statistical limitations of this cohort; notwithstanding, this small unique cohort provides a foundation for assessment of astronaut health.

Differentiation and Transplantation of Human Embryonic Stem Cell-Derived Hepatocytes

PubMed Central

Basma, Hesham; Soto-Gutiérrez, Alejandro; Yannam, Govardhana Rao; Liu, Liping; Ito, Ryotaro; Yamamoto, Toshiyuki; Ellis, Ewa; Carson, Steven D.; Sato, Shintaro; Chen, Yong; Muirhead, David; Navarro-Álvarez, Nalu; Wong, Ron; Roy-Chowdhury, Jayanta; Platt, Jeffrey L.; Mercer, David F.; Miller, John D.; Strom, Stephen C.; Kobayashi, Noaya; Fox, Ira J.

2009-01-01

Background & Aims The ability to obtain unlimited numbers of human hepatocytes would improve development of cell-based therapies for liver diseases, facilitate the study of liver biology and improve the early stages of drug discovery. Embryonic stem cells are pluripotent, can potentially differentiate into any cell type and could therefore be developed as a source of human hepatocytes. Methods To generate human hepatocytes, human embryonic stem cells were differentiated by sequential culture in fibroblast growth factor 2 and human Activin-A, hepatocyte growth factor, and dexamethasone. Functional hepatocytes were isolated by sorting for surface asialoglycoprotein receptor expression. Characterization was performed by real-time PCR, imunohistochemistry, immunoblot, functional assays and transplantation. Results Embryonic stem cell-derived hepatocytes expressed liver-specific genes but not genes representing other lineages, secreted functional human liver-specific proteins similar to those of primary human hepatocytes and demonstrated human hepatocyte cytochrome P450 metabolic activity. Serum from rodents given injections of embryonic stem cell-derived hepatocytes contained significant amounts of human albumin and alpha-1-antitrypsin. Colonies of cytokeratin-18 and human albumin-expressing cells were present in the livers of recipient animals. Conclusion Human embryonic stem cells can be differentiated into cells with many characteristics of primary human hepatocytes. Hepatocyte-like cells can be enriched and recovered based on asialoglycoprotein receptor expression and could potentially be used in drug discovery research and developed as therapeutics. PMID:19026649

Avian embryonic development in hyperdynamic environments

NASA Technical Reports Server (NTRS)

Abbott, U. K.; Smith, A. H.

1983-01-01

Embryos which developed for 24 hours in the oviduct of hens maintained at 2 G and which were subsequently incubated at Earth gravity had a 14% reduction in hatchability. Increased mortality during the first 4 days, and an increase in embryonic abnormalities were of the types usually found during the first mortality peak (2-3 days). Embryos in eggs that were produced at Earth gravity and continued their development on the centrifuge at fields of 2 G or less did not appear to be greatly affected by the treatment. At 4 G, 91% of the embryos died, mostly on the first and second days of incubation. Abnormalities prominent in the centrifuged eggs include: (a) a failure of the primitive streak to develop; (b) interference with the development of the axial skeleton; (c) multiple hemorrhages, mostly petechial which is consistent with capillary fragility; and (d) retardation of embryo growth, possibly caused by an interference with gaseous diffusion, the result of an acceleration-induced increase in gas density in the centrifuging incubator.

Inducible overexpression of RUNX1b/c in human embryonic stem cells blocks early hematopoiesis from mesoderm.

PubMed

Chen, B; Teng, Jiawen; Liu, Hongwei; Pan, X; Zhou, Y; Huang, Shu; Lai, Mowen; Bian, Guohui; Mao, Bin; Sun, Wencui; Zhou, Qiongxiu; Yang, Shengyong; Nakahata, Tatsutoshi; Ma, Feng

2017-08-01

RUNX1 is absolutely required for definitive hematopoiesis, but the function of RUNX1b/c, two isoforms of human RUNX1, is unclear. We established inducible RUNX1b/c-overexpressing human embryonic stem cell (hESC) lines, in which RUNX1b/c overexpression prevented the emergence of CD34+ cells from early stage, thereby drastically reducing the production of hematopoietic stem/progenitor cells. Simultaneously, the expression of hematopoiesis-related factors was downregulated. However, such blockage effect disappeared from day 6 in hESC/AGM-S3 cell co-cultures, proving that the blockage occurred before the generation of hemogenic endothelial cells. This blockage was partially rescued by RepSox, an inhibitor of the transforming growth factor (TGF)-β signaling pathway, indicating a close relationship between RUNX1b/c and TGF-β pathway. Our results suggest a unique inhibitory function of RUNX1b/c in the development of early hematopoiesis and may aid further understanding of its biological function in normal and diseased models. © The Author (2017). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

miR-203 modulates epithelial differentiation of human embryonic stem cells towards epidermal stratification.

PubMed

Nissan, Xavier; Denis, Jérôme Alexandre; Saidani, Manoubia; Lemaitre, Gilles; Peschanski, Marc; Baldeschi, Christine

2011-08-15

The molecular mechanisms controlling the differentiation of human basal keratinocyte stem cells towards the epidermis are well characterized, whereas the earliest process leading to the specification of embryonic stem cells into keratinocytes is still not well understood. MicroRNAs are regulators of many cellular events, but evidence for microRNA acting on the differentiation of human embryonic stem cells into a specific lineage has been elusive. By using our recent protocol for obtaining functional keratinocytes from hESC, we attempted to analyze the role of microRNAs in the early stages of epidermal differentiation. Thus, we identified a set of 5 microRNAs, namely miR-200a, miR-200b, miR-203, miR-205 and miR-429, that are specifically overexpressed during the early stages of the differentiation process. Interestingly, our functional analyses revealed an instrumental role of miR-203, which had been previously shown to play a key role during the formation of the pluristratified epidermis by basal keratinocyte stem cells, in the early keratinocyte commitment. These results highlight the determinant and unique role of miR-203 during the entire process of epidermal development by extending its spectrum of action from the early commitment of embryonic stem cells to ultimate differentiation of the organ. Copyright © 2011 Elsevier Inc. All rights reserved.

Mechanical signaling coordinates the embryonic heartbeat.

PubMed

Chiou, Kevin K; Rocks, Jason W; Chen, Christina Yingxian; Cho, Sangkyun; Merkus, Koen E; Rajaratnam, Anjali; Robison, Patrick; Tewari, Manorama; Vogel, Kenneth; Majkut, Stephanie F; Prosser, Benjamin L; Discher, Dennis E; Liu, Andrea J

2016-08-09

In the beating heart, cardiac myocytes (CMs) contract in a coordinated fashion, generating contractile wave fronts that propagate through the heart with each beat. Coordinating this wave front requires fast and robust signaling mechanisms between CMs. The primary signaling mechanism has long been identified as electrical: gap junctions conduct ions between CMs, triggering membrane depolarization, intracellular calcium release, and actomyosin contraction. In contrast, we propose here that, in the early embryonic heart tube, the signaling mechanism coordinating beats is mechanical rather than electrical. We present a simple biophysical model in which CMs are mechanically excitable inclusions embedded within the extracellular matrix (ECM), modeled as an elastic-fluid biphasic material. Our model predicts strong stiffness dependence in both the heartbeat velocity and strain in isolated hearts, as well as the strain for a hydrogel-cultured CM, in quantitative agreement with recent experiments. We challenge our model with experiments disrupting electrical conduction by perfusing intact adult and embryonic hearts with a gap junction blocker, β-glycyrrhetinic acid (BGA). We find this treatment causes rapid failure in adult hearts but not embryonic hearts-consistent with our hypothesis. Last, our model predicts a minimum matrix stiffness necessary to propagate a mechanically coordinated wave front. The predicted value is in accord with our stiffness measurements at the onset of beating, suggesting that mechanical signaling may initiate the very first heartbeats.

Mechanical signaling coordinates the embryonic heartbeat

PubMed Central

Chiou, Kevin K.; Rocks, Jason W.; Chen, Christina Yingxian; Cho, Sangkyun; Merkus, Koen E.; Rajaratnam, Anjali; Robison, Patrick; Tewari, Manorama; Vogel, Kenneth; Majkut, Stephanie F.; Prosser, Benjamin L.; Discher, Dennis E.; Liu, Andrea J.

2016-01-01

In the beating heart, cardiac myocytes (CMs) contract in a coordinated fashion, generating contractile wave fronts that propagate through the heart with each beat. Coordinating this wave front requires fast and robust signaling mechanisms between CMs. The primary signaling mechanism has long been identified as electrical: gap junctions conduct ions between CMs, triggering membrane depolarization, intracellular calcium release, and actomyosin contraction. In contrast, we propose here that, in the early embryonic heart tube, the signaling mechanism coordinating beats is mechanical rather than electrical. We present a simple biophysical model in which CMs are mechanically excitable inclusions embedded within the extracellular matrix (ECM), modeled as an elastic-fluid biphasic material. Our model predicts strong stiffness dependence in both the heartbeat velocity and strain in isolated hearts, as well as the strain for a hydrogel-cultured CM, in quantitative agreement with recent experiments. We challenge our model with experiments disrupting electrical conduction by perfusing intact adult and embryonic hearts with a gap junction blocker, β-glycyrrhetinic acid (BGA). We find this treatment causes rapid failure in adult hearts but not embryonic hearts—consistent with our hypothesis. Last, our model predicts a minimum matrix stiffness necessary to propagate a mechanically coordinated wave front. The predicted value is in accord with our stiffness measurements at the onset of beating, suggesting that mechanical signaling may initiate the very first heartbeats. PMID:27457951

Early mortality in SCN8A-related epilepsies.

PubMed

Johannesen, Katrine M; Gardella, Elena; Scheffer, Ingrid; Howell, Katherine; Smith, Douglas M; Helbig, Ingo; Møller, Rikke S; Rubboli, Guido

2018-07-01

SCN8A-related epilepsies are often severe developmental and epileptic encephalopathies. Seizures can be treatment resistant, and patients suffer from severe intellectual disability. Reports have suggested that SCN8A-related epilepsies have a high mortality with SUDEP as the major underlying cause. SUDEP is a catastrophic event, and the risk of occurrence should be correctly and carefully discussed with patients and families. We tested the hypothesis of SUDEP as the main cause of death in SCN8A-related epilepsies by reviewing all the currently reported patients with SCN8A. In addition, we collected unpublished patients through an international network. In total, we reviewed the data of 190 patients. In our cohort, 10 patients were deceased, and the overall mortality was 5.3%. Within the ten deceased patients, age at death ranged from 16 months to 17 years; the majority (7/10) of them died in early childhood. Three patients died of probable or definite SUDEP. Thus, our data do not indicate an increased risk when compared to other DEEs. Indeed, death in SCN8A-related epilepsies seems to occur most often in children experiencing a relentless worsening of their epilepsy and neurological condition, rendering them susceptible to pulmonary infections and respiratory distress that ultimately can be fatal. Copyright © 2018 Elsevier B.V. All rights reserved.

Investigating the Flow and Biomechanics of the Embryonic Zebrafish Heart

NASA Astrophysics Data System (ADS)

Johnson, Brennan; Garrity, Deborah; Dasi, Lakshmi

2010-11-01

Understanding flow and kinematic characteristics of the embryonic heart is a prerequisite to devise early intervention or detection methods in the context of congenital heart defects. In this study, the kinematics and fluid dynamics of the embryonic zebrafish heart were analyzed through the early stages of cardiac development (24-48 hours post-fertilization) in vivo using optical microscopy and high-speed video. Endocardial walls and individual blood cells were segmented from raw images and were tracked through the cardiac cycle. Particle tracking velocimetry analysis yielded quantitative blood cell velocity field, chamber volume, and flow rate information. It was seen that the pumping mechanism starts as a combined peristaltic and suction pump while the heart is in the tube configuration and transforms into a positive displacement pump after cardiac looping. Strong two-phase nature of the fluid is evident. This work provides us new understanding of the spatio-temporal characteristics of kinematics and blood cell velocity field inside the developing heart.

Scaling up implementation of ART: Organizational culture and early mortality of patients initiated on ART in Nairobi, Kenya.

PubMed

Ayah, Richard

2018-01-01

Scaling up the antiretroviral (ART) program in Kenya has involved a strategy of using clinical guidelines coupled with decentralization of treatment sites. However decentralization pushes clinical responsibility downwards to health facilities run by lower cadre staff. Whether the organizational culture in health facilities affects the outcomes despite the use of clinical guidelines has not been explored. This study aimed to demonstrate the relationship between organizational culture and early mortality and those lost to follow up (LTFU) among patients enrolled for HIV care. A stratified sample of 31 health facilities in Nairobi County offering ART services were surveyed. Data of patients enrolled on ART and LTFU for the 12 months ending 30th June 2013 were abstracted. Mortality and LTFU were determined and used to rank health facilities. In the facilities with the lowest and highest mortality and LTFU key informant interviews were conducted using a tool adapted from team climate assessment measurement questionnaire and competing value framework tool to assess organizational culture. The strength of association between early mortality, LTFU and organizational culture was tested. Half (51.8%) of the 5,808 patients enrolled into care in 31 health facilities over the 12-month study period were started on ART. Of these 48 (1.6% 95% CI 0.8%-2.4%) died within three months of starting treatment, while a further 125 (4.2% 95% CI 2.1%-6.6%) were LTFU giving an attrition rate of 5.7% (95% CI 3.3%-8.6%). Tuberculosis was the most common comorbidity associated with high early mortality and high LTFU. Organizational culture, specifically an adhocratic type was found to be associated with low early mortality and low LTFU of patients enrolled for HIV care (P = 0.034). The use of ART clinical guidelines in a decentralized health systems are not sufficient to achieve required service delivery outcomes. The attrition rate above would mean 85,000 Kenyans missing care based on current

Embryonic health: new insights, mHealth and personalised patient care.

PubMed

Steegers-Theunissen, Régine P M; Steegers, Eric A P

2015-05-01

The worldwide epidemic of non-communicable diseases (NCD), including obesity, is a burden to which poor lifestyles contribute significantly. Events in early life may enhance susceptibility to NCD, with transmission into succeeding generations. This may also explain, in part, why interventions in adulthood are less effective to reduce NCD risk. New insights reveal that the early embryo, in particular, is extremely sensitive to signals from gametes, trophoblastic tissue and periconception maternal lifestyles. Embryonic size and growth as determinants of embryonic health seem to impact future health. A relatively small embryo for gestational age is associated with pregnancy complications, as well as with the risk of early features of NCD in childhood. Although personal lifestyles are modifiable, they are extremely difficult to change. Therefore, adopting a life course approach from the periconception period onwards and integrated into patient care with short-term reproductive health benefits may have important implications for future prevention of NCD. The current reproductive population is used to Internet and social media. Therefore, they can be reached via mobile phone (mHealth) platforms that provide personalised lifestyle (pre)pregnancy programs. This will offer opportunities and possibly great benefits for the health of current and succeeding generations.

Novel Metrics to Characterize Embryonic Elongation of the Nematode Caenorhabditis elegans.

PubMed

Martin, Emmanuel; Rocheleau-Leclair, Olivier; Jenna, Sarah

2016-03-28

Dissecting the signaling pathways that control the alteration of morphogenic processes during embryonic development requires robust and sensitive metrics. Embryonic elongation of the nematode Caenorhabditis elegans is a late developmental stage consisting of the elongation of the embryo along its longitudinal axis. This developmental stage is controlled by intercellular communication between hypodermal cells and underlying body-wall muscles. These signaling mechanisms control the morphology of hypodermal cells by remodeling the cytoskeleton and the cell-cell junctions. Measurement of embryonic lethality and developmental arrest at larval stages as well as alteration of cytoskeleton and cell-cell adhesion structures in hypodermal and muscle cells are classical phenotypes that have been used for more than 25 years to dissect these signaling pathways. Recent studies required the development of novel metrics specifically targeting either early or late elongation and characterizing morphogenic defects along the antero-posterior axis of the embryo. Here, we provide detailed protocols enabling the accurate measurement of the length and the width of the elongating embryos as well as the length of synchronized larvae. These methods constitute useful tools to identify genes controlling elongation, to assess whether these genes control both early and late phases of this stage and are required evenly along the antero-posterior axis of the embryo.

Zeb1-Hdac2-eNOS circuitry identifies early cardiovascular precursors in naive mouse embryonic stem cells.

PubMed

Cencioni, Chiara; Spallotta, Francesco; Savoia, Matteo; Kuenne, Carsten; Guenther, Stefan; Re, Agnese; Wingert, Susanne; Rehage, Maike; Sürün, Duran; Siragusa, Mauro; Smith, Jacob G; Schnütgen, Frank; von Melchner, Harald; Rieger, Michael A; Martelli, Fabio; Riccio, Antonella; Fleming, Ingrid; Braun, Thomas; Zeiher, Andreas M; Farsetti, Antonella; Gaetano, Carlo

2018-03-29

Nitric oxide (NO) synthesis is a late event during differentiation of mouse embryonic stem cells (mESC) and occurs after release from serum and leukemia inhibitory factor (LIF). Here we show that after release from pluripotency, a subpopulation of mESC, kept in the naive state by 2i/LIF, expresses endothelial nitric oxide synthase (eNOS) and endogenously synthesizes NO. This eNOS/NO-positive subpopulation (ESNO+) expresses mesendodermal markers and is more efficient in the generation of cardiovascular precursors than eNOS/NO-negative cells. Mechanistically, production of endogenous NO triggers rapid Hdac2 S-nitrosylation, which reduces association of Hdac2 with the transcriptional repression factor Zeb1, allowing mesendodermal gene expression. In conclusion, our results suggest that the interaction between Zeb1, Hdac2, and eNOS is required for early mesendodermal differentiation of naive mESC.

Tree mortality from fire and bark beetles following early and late season prescribed fires in a Sierra Nevada mixed-conifer forest

USGS Publications Warehouse

Schwilk, Dylan W.; Knapp, Eric E.; Ferrenberg, Scott; Keeley, Jon E.; Caprio, Anthony C.

2006-01-01

Over the last century, fire exclusion in the forests of the Sierra Nevada has allowed surface fuels to accumulate and has led to increased tree density. Stand composition has also been altered as shade tolerant tree species crowd out shade intolerant species. To restore forest structure and reduce the risk of large, intense fires, managers have increasingly used prescription burning. Most fires prior to EuroAmerican settlement occurred during the late summer and early fall and most prescribed burning has taken place during the latter part of this period. Poor air quality and lack of suitable burn windows during the fall, however, have resulted in a need to conduct more prescription burning earlier in the season. Previous reports have suggested that burning during the time when trees are actively growing may increase mortality rates due to fine root damage and/or bark beetle activity. This study examines the effects of fire on tree mortality and bark beetle attacks under prescription burning during early and late season. Replicated early season burn, late season burn and unburned control plots were established in an old-growth mixed conifer forest in the Sierra Nevada that had not experienced a fire in over 120 years. Although prescribed burns resulted in significant mortality of particularly the smallest tree size classes, no difference between early and late season burns was detected. Direct mortality due to fire was associated with fire intensity. Secondary mortality due to bark beetles was not significantly correlated with fire intensity. The probability of bark beetle attack on pines did not differ between early and late season burns, while the probability of bark beetle attack on firs was greater following early season burns. Overall tree mortality appeared to be primarily the result of fire intensity rather than tree phenology at the time of the burns. Early season burns are generally conducted under higher fuel moisture conditions, leading to less fuel

Verbal memory and search speed in early midlife are associated with mortality over 25 years' follow-up, independently of health status and early life factors: a British birth cohort study.

PubMed

Davis, Daniel; Cooper, Rachel; Terrera, Graciela Muniz; Hardy, Rebecca; Richards, Marcus; Kuh, Diana

2016-08-01

Cognitive capabilities in childhood and in late life are inversely associated with mortality rates. However, it is unclear if adult cognition, at a time still relatively free from comorbidity, is associated with subsequent mortality, and whether this explains the associations of early life factors with adult mortality. We used data from the MRC National Survey of Health and Development, a birth cohort study prospectively assessing 5362 participants born in 1946. The present analysis includes participants followed up from age 43 and undergoing cognitive assessment (verbal memory and search speed). Mortality outcomes were notified through linkage with a national register. Cox regression was used to estimate mortality hazards in relation to cognitive performance at age 43, adjusting for early life factors, socioeconomic position and health status. Data were available on 3192 individuals. Univariable analyses indicated that adult verbal memory and search speed, parental factors, childhood cognition and educational attainment were associated with mortality. However, multivariable models showed that the mortality associations with earlier life factors were explained by adult cognitive capability. A standard deviation increase in verbal memory and search speed scores was associated with lower mortality rates [hazard ratio (HR) = 0.86, 95% confidence interval (CI) 0.77-0.97, P = 0.02; HR = 0.88, 95% CI 0.78-1.00, P = 0.05, respectively), after adjustment for adult health. Cognitive capability in early midlife was inversely associated with mortality rates over 25 years and accounted for the associations of family background, childhood cognitive ability and educational attainment with mortality. These findings, in a nationally representative cohort with long-term follow-up, suggest that building cognitive reserve may improve later life health and survival chances. © The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological

Early mortality of alcoholic hepatitis: a review of data from placebo-controlled clinical trials.

PubMed

Yu, Chao-Hui; Xu, Cheng-Fu; Ye, Hua; Li, Lan; Li, You-Ming

2010-05-21

To investigate the early mortality of placebo-treated alcoholic hepatitis patients. Mortality data about alcoholic hepatitis patients who participated in randomized placebo-controlled trials were searched from PubMed, EMBASE, and Cochrane Library, extracted and analyzed. A total of 661 placebo-treated patients in 19 trials were included. The overall mortality rate was 34.19% with a median observation time of 160 d (range 21-720 d). Hepatic failure, gastrointestinal bleeding and infection were the three main causes of death, accounting for 55.47%, 21.17% and 7.30% of all deaths, respectively. One-month mortality data about 324 placebo-treated alcoholic hepatitis patients in 10 trials were reported with a pooled mortality rate of 20.37%. The one-month mortality rate of patients with moderate to severe alcoholic hepatitis tended to be higher than that of general patients (22.69% vs 10.93%, P < 0.05), whereas no significant difference was observed between the patients from North America or Europe (22.43% vs 18.45%, P > 0.05), neither any difference was found between the studies published before and after 1990 (18.18% vs 21.88%, P > 0.05). Alcoholic hepatitis is a severe liver disease with a high mortality rate, and hepatic failure, gastrointestinal bleeding and infection are the three main causes of death.

PTBP1 Is Required for Embryonic Development before Gastrulation

PubMed Central

Suckale, Jakob; Wendling, Olivia; Masjkur, Jimmy; Jäger, Melanie; Münster, Carla; Anastassiadis, Konstantinos; Stewart, A. Francis; Solimena, Michele

2011-01-01

Polypyrimidine-tract binding protein 1 (PTBP1) is an important cellular regulator of messenger RNAs influencing the alternative splicing profile of a cell as well as its mRNA stability, location and translation. In addition, it is diverted by some viruses to facilitate their replication. Here, we used a novel PTBP1 knockout mouse to analyse the tissue expression pattern of PTBP1 as well as the effect of its complete removal during development. We found evidence of strong PTBP1 expression in embryonic stem cells and throughout embryonic development, especially in the developing brain and spinal cord, the olfactory and auditory systems, the heart, the liver, the kidney, the brown fat and cartilage primordia. This widespread distribution points towards a role of PTBP1 during embryonic development. Homozygous offspring, identified by PCR and immunofluorescence, were able to implant but were arrested or retarded in growth. At day 7.5 of embryonic development (E7.5) the null mutants were about 5x smaller than the control littermates and the gap in body size widened with time. At mid-gestation, all homozygous embryos were resorbed/degraded. No homozygous mice were genotyped at E12 and the age of weaning. Embryos lacking PTBP1 did not display differentiation into the 3 germ layers and cavitation of the epiblast, which are hallmarks of gastrulation. In addition, homozygous mutants displayed malformed ectoplacental cones and yolk sacs, both early supportive structure of the embryo proper. We conclude that PTBP1 is not required for the earliest isovolumetric divisions and differentiation steps of the zygote up to the formation of the blastocyst. However, further post-implantation development requires PTBP1 and stalls in homozygous null animals with a phenotype of dramatically reduced size and aberration in embryonic and extra-embryonic structures. PMID:21423341

PTBP1 is required for embryonic development before gastrulation.

PubMed

Suckale, Jakob; Wendling, Olivia; Masjkur, Jimmy; Jäger, Melanie; Münster, Carla; Anastassiadis, Konstantinos; Stewart, A Francis; Solimena, Michele

2011-02-17

Polypyrimidine-tract binding protein 1 (PTBP1) is an important cellular regulator of messenger RNAs influencing the alternative splicing profile of a cell as well as its mRNA stability, location and translation. In addition, it is diverted by some viruses to facilitate their replication. Here, we used a novel PTBP1 knockout mouse to analyse the tissue expression pattern of PTBP1 as well as the effect of its complete removal during development. We found evidence of strong PTBP1 expression in embryonic stem cells and throughout embryonic development, especially in the developing brain and spinal cord, the olfactory and auditory systems, the heart, the liver, the kidney, the brown fat and cartilage primordia. This widespread distribution points towards a role of PTBP1 during embryonic development. Homozygous offspring, identified by PCR and immunofluorescence, were able to implant but were arrested or retarded in growth. At day 7.5 of embryonic development (E7.5) the null mutants were about 5x smaller than the control littermates and the gap in body size widened with time. At mid-gestation, all homozygous embryos were resorbed/degraded. No homozygous mice were genotyped at E12 and the age of weaning. Embryos lacking PTBP1 did not display differentiation into the 3 germ layers and cavitation of the epiblast, which are hallmarks of gastrulation. In addition, homozygous mutants displayed malformed ectoplacental cones and yolk sacs, both early supportive structure of the embryo proper. We conclude that PTBP1 is not required for the earliest isovolumetric divisions and differentiation steps of the zygote up to the formation of the blastocyst. However, further post-implantation development requires PTBP1 and stalls in homozygous null animals with a phenotype of dramatically reduced size and aberration in embryonic and extra-embryonic structures.

What doesn't kill you makes you poorer: Adult wages and early-life mortality in India.

PubMed

Lawson, Nicholas; Spears, Dean

2016-05-01

A growing literature indicates that effects of early-life health on adult economic outcomes could be substantial in developing countries, but the magnitude of this effect is debated. We document a robust gradient between the early-life mortality environment to which men in India were locally exposed in their district and year of birth and the wages that they earn as adults. A 1 percentage point reduction in infant mortality (or 10 point reduction in IMR) in an infant's district and year of birth is associated with an approximately 2 percent increase in his subsequent adult wages. Consistent with theories and evidence in the literature, we find that the level of schooling chosen for a child does not mediate this association. Because of its consequences for subsequent wages, early-life health could also have considerable fiscal externalities; if so, public health investments could come at very low net present cost. Copyright © 2015 Elsevier B.V. All rights reserved.

Association Between Low IQ Scores and Early Mortality in Men and Women: Evidence From a Population-Based Cohort Study.

PubMed

Maenner, Matthew J; Greenberg, Jan S; Mailick, Marsha R

2015-05-01

Lower (versus higher) IQ scores have been shown to increase the risk of early mortality, however, the underlying mechanisms are poorly understood and previous studies underrepresent individuals with intellectual disability (ID) and women. This study followed one third of all senior-year students (approximately aged 17) attending public high school in Wisconsin, U.S. in 1957 (n  =  10,317) until 2011. Men and women with the lowest IQ test scores (i.e., IQ scores ≤ 85) had increased rates of mortality compared to people with the highest IQ test scores, particularly for cardiovascular disease. Importantly, when educational attainment was held constant, people with lower IQ test scores did not have higher mortality by age 70 than people with higher IQ test scores. Individuals with lower IQ test scores likely experience multiple disadvantages throughout life that contribute to increased risk of early mortality.

Mortality throughout early childhood for Michigan children born with congenital anomalies, 1992-1998.

PubMed

Berger, Katherine H; Zhu, Bao-Ping; Copeland, Glenn

2003-09-01

Congenital anomalies are a leading cause of infant deaths, accounting for almost a fifth of all infant deaths. Few studies have researched the survival experience of infants born with congenital anomalies past the infant stage. Using birth and death files routinely linked to the Michigan Birth Defects Registry, we identified all singleton infants during calendar years 1992 through 1998 with reportable congenital anomalies for our study. A comparative file of children born without congenital anomalies during the same time period was developed using linked birth and death files. The mortality data were assessed by age at death (through age six) and race to determine mortality rates, relative risks, hazard ratios, and survival trends. Throughout early childhood, children born with congenital anomalies had a high risk of mortality compared with all other children. The overall 7-year hazard ratio comparing children with congenital anomalies with all other children was 7.2. Overall mortality rates for black children were significantly higher than white children through the age of seven, irrespective of whether they had congenital anomalies. Among children with congenital anomalies, this disparity disappeared after adjusting for birth weight, sex, mother's age, mother's education, and number of organ systems affected. Compared with children without congenital anomalies, children born with congenital anomalies had a higher risk of mortality well beyond the infant period. Racial disparities in mortality rates among children with congenital anomalies were due to confounding factors.

Functional optical coherence tomography for live dynamic analysis of mouse embryonic cardiogenesis

NASA Astrophysics Data System (ADS)

Wang, Shang; Lopez, Andrew L.; Larina, Irina V.

2018-02-01

Blood flow, heart contraction, and tissue stiffness are important regulators of cardiac morphogenesis and function during embryonic development. Defining how these factors are integrated is critically important to advance prevention, diagnostics, and treatment of congenital heart defects. Mammalian embryonic development is taking place deep within the female body, which makes cardiodynamic imaging and analysis during early developmental stages in humans inaccessible. With thousands of mutant lines available and well-established genetic manipulation tools, mouse is a great model to understand how biomechanical factors are integrated with molecular pathways to regulate cardiac function and development. Dynamic imaging and quantitative analysis of the biomechanics of live mouse embryos have become increasingly important, which demands continuous advancements in imaging techniques and live assessment approaches. This has been one of the major drives to keep pushing the frontier of embryonic imaging for better resolution, higher speed, deeper penetration, and more diverse and effective contrasts. Optical coherence tomography (OCT) has played a significant role in addressing such demands, and its features in non-labeling imaging, 3D capability, a large working distance, and various functional derivatives allow OCT to cover a number of specific applications in embryonic imaging. Recently, our group has made several technical improvements in using OCT to probe the biomechanical aspects of live developing mouse embryos at early stages. These include the direct volumetric structural and functional imaging of the cardiodynamics, four-dimensional quantitative Doppler imaging and analysis of the cardiac blood flow, and fourdimensional blood flow separation from the cardiac wall tissue in the beating embryonic heart. Here, we present a short review of these studies together with brief descriptions of the previous work that demonstrate OCT as a valuable and useful imaging tool

Sodium Butyrate Improves Locomotor Impairment and Early Mortality in a Rotenone-Induced Drosophila Model of Parkinson’s Disease

PubMed Central

St. Laurent, Robyn; O’Brien, Liam M.; Ahmad, S. Tariq

2013-01-01

Parkinson’s disease (PD) is a neurodegenerative disorder primarily affecting the dopaminergic neurons in the nigrastriatal pathway resulting in debilitating motor impairment in both familial and sporadic cases. Histone deacetylase (HDAC) inhibitors have been recently implicated as a therapeutic candidate because of their ability to correct the disrupted HDAC activity in PD and other neurodegenerative diseases. Sodium butyrate (SB), an HDAC inhibitor, reduces degeneration of dopaminergic neurons in a mutant alpha-synuclein Drosophila transgenic model of familial PD. Chronic exposure to the pesticide rotenone also causes selective degeneration of dopaminergic neurons and causes locomotor impairment and early mortality in a Drosophila model of chemically-induced PD. This study investigated the effects of sodium butyrate on locomotor impairment and early mortality in a rotenone-induced PD model. We show that treatment with 10 mM SB-supplemented food rescued the rotenone-induced locomotor impairment and early mortality in flies. Additionally, flies with the genetic knockdown of HDAC activity through Sin3A loss-of-function mutation (Sin3Alof) were resistant to rotenone-induced locomotor impairment and early mortality. Furthermore, SB-supplemented Sin3Alof flies had a modest additive effect for improving locomotor impairment. We also show SB-mediated improvement of rotenone-induced locomotor impairment was associated with elevated dopamine levels in the brain. However, the possibility of SB-mediated protective role through mechanisms independent from dopamine system is also discussed. These findings demonstrate that HDAC inhibitors like SB can ameliorate locomotor impairment in a rotenone-induced PD model. PMID:23623990

Can diet-dependent factors help explain fish-to-fish variation in thiamine-dependent early mortality syndrome?

USGS Publications Warehouse

Brown, S.B.; Arts, M.T.; Brown, L.R.; Brown, M.; Moore, K.; Villella, M.; Fitzsimons, J.D.; Honeyfield, D.C.; Tillitt, D.E.; Zajicek, J.L.; Wolgamood, M.; Hnath, J.G.

2005-01-01

To provide insight into the reasons why offspring of certain salmonine females exhibit early mortality syndrome (EMS) in the Great Lakes whereas others do not, we measured the egg concentrations of potential biochemical markers (stable isotopes of nitrogen and carbon, fatty acid signatures, and lipid-soluble carotenoids and vitamins) that are indicative of differing food web and trophic structure. To corroborate the presence of EMS, we also measured the egg content of thiamine vitamers. For all the stocks of coho salmon Oncorhynchus kisutch and Chinook salmon O. tshawytscha we studied, there was a very high correspondence between EMS and low concentrations of unphosphorylated thiamine in unfertilized eggs. For salmonine stocks in the Platte River, Thompson Creek, and the Swan River, Michigan, small but significant shifts occurred in measures of egg carotenoids, retinoids, ??15N depletion, and fatty acid profiles of fish producing normal offspring relative to those exhibiting EMS. Egg thiamine concentrations in Chinook salmon from the Little Manistee River, Michigan, in the low-EMS group were only marginally above the threshold for EMS induction. Along with this small thiamine differential, there was no evidence of differing food web or dietary factors between EMS-positive and normal Chinook salmon from the Little Manistee River. Further investigations are required to determine the potential dietary sources for the observed differences in biochemical markers between EMS-positive and normal fish. These findings are generally consistent with the hypothesis that a more diverse forage base may help to limit overall dietary content of species that contain thiaminase, such as alewives Alosa pseudoharengus, and may lead to improved embryonic survival for feral salmonids. ?? Copyright by the American Fisheries Society 2005.

Effects of temperature on the embryonic and early larval development in tropical species of black sea urchin, Diadema setosum (Leske, 1778).

PubMed

Sarifudin, M; Rahman, M A; Yusoff, F M; Arshad, Aziz; Tan, Soon Guan

2016-07-01

Influence of temperature on the embryonic and early development and growth performance of larva in tropical sea urchin, Diadema setosum was investigated in water temperature ranging between 16 and 34?C under controlled laboratory conditions. The critical lower and higher temperature for embryonic development was found at 16 and 34?C, respectively. Embryos reared in both of these two temperatures exhibited 100% abnormality within 48 hrs post-insemination. The time required to reach these embryonic and larval stages increased with temperature from 28 followed by 31, 25, 22 and 19?C in that order. The developmental times of 2-cell stage until 4-arm pluteus larva showed significant differences (P < 0.05) among the tested temperatures. The larvae in the state of prism and 2-arm pluteus, survived at temperature ranging from 19 to 31?C, while the 4-arm pluteus larvae survived at temperature between 22? to 31?C. However, larval development within a temperature range of 22? to 31?C was acceptable since no abnormalities occurred. The morphometric characteristics from prism to 4-arm pluteus larvae in all the temperatures differed significantly (P > 0.05). Among them, 28?C was found to be the best temperature with respect of the highest larval growth and development at all stages. The findings of the study will not only be helpful to understand the critical limits of temperature, but also to identify the most appropriate temperature for optimum growth and development of embryos and larvae, as well as to facilitate the development of captive breeding and mass seed production of D. setosum and other important sea urchins for commercial aquaculture.

Embryonic Cerebrospinal Fluid Increases Neurogenic Activity in the Brain Ventricular-Subventricular Zone of Adult Mice.

PubMed

Alonso, Maria I; Lamus, Francisco; Carnicero, Estela; Moro, Jose A; de la Mano, Anibal; Fernández, Jose M F; Desmond, Mary E; Gato, Angel

2017-01-01

Neurogenesis is a very intensive process during early embryonic brain development, becoming dramatically restricted in the adult brain in terms of extension and intensity. We have previously demonstrated the key role of embryonic cerebrospinal fluid (CSF) in developing brain neurogenic activity. We also showed that cultured adult brain neural stem cells (NSCs) remain competent when responding to the neurogenic influence of embryonic CSF. However, adult CSF loses its neurogenic inductive properties. Here, by means of an organotypic culture of adult mouse brain sections, we show that local administration of embryonic CSF in the subventricular zone (SVZ) niche is able to trigger a neurogenic program in NSCs. This leads to a significant increase in the number of non-differentiated NSCs, and also in the number of new neurons which show normal migration, differentiation and maturation. These new data reveal that embryonic CSF activates adult brain NSCs, supporting the previous idea that it contains key instructive components which could be useful in adult brain neuroregenerative strategies.

Embryonic Cerebrospinal Fluid Increases Neurogenic Activity in the Brain Ventricular-Subventricular Zone of Adult Mice

PubMed Central

Alonso, Maria I.; Lamus, Francisco; Carnicero, Estela; Moro, Jose A.; de la Mano, Anibal; Fernández, Jose M. F.; Desmond, Mary E.; Gato, Angel

2017-01-01

Neurogenesis is a very intensive process during early embryonic brain development, becoming dramatically restricted in the adult brain in terms of extension and intensity. We have previously demonstrated the key role of embryonic cerebrospinal fluid (CSF) in developing brain neurogenic activity. We also showed that cultured adult brain neural stem cells (NSCs) remain competent when responding to the neurogenic influence of embryonic CSF. However, adult CSF loses its neurogenic inductive properties. Here, by means of an organotypic culture of adult mouse brain sections, we show that local administration of embryonic CSF in the subventricular zone (SVZ) niche is able to trigger a neurogenic program in NSCs. This leads to a significant increase in the number of non-differentiated NSCs, and also in the number of new neurons which show normal migration, differentiation and maturation. These new data reveal that embryonic CSF activates adult brain NSCs, supporting the previous idea that it contains key instructive components which could be useful in adult brain neuroregenerative strategies. PMID:29311854

Evaluation of cardiac surgery mortality rates: 30-day mortality or longer follow-up?

PubMed

Siregar, Sabrina; Groenwold, Rolf H H; de Mol, Bas A J M; Speekenbrink, Ron G H; Versteegh, Michel I M; Brandon Bravo Bruinsma, George J; Bots, Michiel L; van der Graaf, Yolanda; van Herwerden, Lex A

2013-11-01

The aim of our study was to investigate early mortality after cardiac surgery and to determine the most adequate follow-up period for the evaluation of mortality rates. Information on all adult cardiac surgery procedures in 10 of 16 cardiothoracic centres in Netherlands from 2007 until 2010 was extracted from the database of Netherlands Association for Cardio-Thoracic Surgery (n = 33 094). Survival up to 1 year after surgery was obtained from the national death registry. Survival analysis was performed using Kaplan-Meier and Cox regression analysis. Benchmarking was performed using logistic regression with mortality rates at different time points as dependent variables, the logistic EuroSCORE as covariate and a random intercept per centre. In-hospital mortality was 2.94% (n = 972), 30-day mortality 3.02% (n = 998), operative mortality 3.57% (n = 1181), 60-day mortality 3.84% (n = 1271), 6-month mortality 5.16% (n = 1707) and 1-year mortality 6.20% (n = 2052). The survival curves showed a steep initial decline followed by stabilization after ∼60-120 days, depending on the intervention performed, e.g. 60 days for isolated coronary artery bypass grafting (CABG) and 120 days for combined CABG and valve surgery. Benchmark results were affected by the choice of the follow-up period: four hospitals changed outlier status when the follow-up was increased from 30 days to 1 year. In the isolated CABG subgroup, benchmark results were unaffected: no outliers were found using either 30-day or 1-year follow-up. The course of early mortality after cardiac surgery differs across interventions and continues up to ∼120 days. Thirty-day mortality reflects only a part of early mortality after cardiac surgery and should only be used for benchmarking of isolated CABG procedures. The follow-up should be prolonged to capture early mortality of all types of interventions.

Transcriptional Profiling of Ectoderm Specification to Keratinocyte Fate in Human Embryonic Stem Cells

PubMed Central

Tadeu, Ana Mafalda Baptista; Lin, Samantha; Hou, Lin; Chung, Lisa; Zhong, Mei; Zhao, Hongyu; Horsley, Valerie

2015-01-01

In recent years, several studies have shed light into the processes that regulate epidermal specification and homeostasis. We previously showed that a broad-spectrum γ–secretase inhibitor DAPT promoted early keratinocyte specification in human embryonic stem cells triggered to undergo ectoderm specification. Here, we show that DAPT accelerates human embryonic stem cell differentiation and induces expression of the ectoderm protein AP2. Furthermore, we utilize RNA sequencing to identify several candidate regulators of ectoderm specification including those involved in epithelial and epidermal development in human embryonic stem cells. Genes associated with transcriptional regulation and growth factor activity are significantly enriched upon DAPT treatment during specification of human embryonic stem cells to the ectoderm lineage. The human ectoderm cell signature identified in this study contains several genes expressed in ectodermal and epithelial tissues. Importantly, these genes are also associated with skin disorders and ectodermal defects, providing a platform for understanding the biology of human epidermal keratinocyte development under diseased and homeostatic conditions. PMID:25849374

Differential toxicity of copper, zinc, and lead during the embryonic development of Chasmagnathus granulatus (Brachyura, Varunidae).

PubMed

Lavolpe, Mariano; Greco, Laura López; Kesselman, Daniela; Rodríguez, Enrique

2004-04-01

Ovigerous females of the estuarine crab Chasmagnathus granulatus were exposed to copper (0.01 and 1 mg/L), zinc (0.05, 1, and 10 mg/L), or lead (0.01 and 1 mg/L) during early, late, or whole embryonic development. None of the assayed heavy metals produced a significant mortality of females, neither a decrease in the number of hatched larvae nor a decrease in the egg incubation time, but several morphological abnormalities were detected in hatched larvae. The abnormalities were classified in three categories: eye, body pigmentary, and body morphological abnormalities. Those larvae with eye and body pigmentary abnormalities, particularly those involving retinal pigments and chromatophores, showed the highest incidence by exposure to the assayed metals. In addition, embryos were more susceptible to copper and zinc during the late period of development, whereas the effect of lead was greater during the early period of embryogenesis. Some teratogenic effects observed in C. granulatus embryos exposed to heavy metals, particularly the hypertrophy and hypopigmentation of eyes observed in the laboratory at a lead concentration as low as that reported for the natural environment, could be considered as sensitive biomarkers for this kind of pollutant.

Do embryonic polar bodies commit suicide?

PubMed

Fabian, Dušan; Čikoš, Štefan; Rehák, Pavol; Koppel, Juraj

2014-02-01

The extrusion and elimination of unnecessary gametic/embryonic material is one of the key events that determines the success of further development in all living organisms. Oocytes produce the first polar body to fulfill the maturation process just before ovulation, and release the second polar body immediately after fertilization. The aim of this study was to compile a physiological overview of elimination of polar bodies during early preimplantation development in mice. Our results show that three-quarters of the first polar bodies were lost even at the zygotic stage; the 4-cell stage embryos contained only one (second) polar body, and the elimination of second polar bodies proceeded continuously during later development. Both first and second polar bodies showed several typical features of apoptosis: phosphatidylserine redistribution (observed for the first time in the first polar body), specific DNA degradation, condensed nuclear morphology, and inability to exclude cationic dye from the nucleus during the terminal stage of the apoptotic process. Caspase-3 activity was recorded only in the second polar body. From the morphological point of view, mouse polar bodies acted very similarly to damaged embryonic cells which have lost contact with their neighboring blastomeres. In conclusion, polar bodies possess all the molecular equipment necessary for triggering and executing an active suicide process. Furthermore, similarly as in dying embryonic cells, stressing external conditions (culture in vitro) might accelerate and increase the incidence of apoptotic elimination of the polar bodies in embryos.

NFκB signaling regulates embryonic and adult neurogenesis

PubMed Central

ZHANG, Yonggang; HU, Wenhui

2013-01-01

Both embryonic and adult neurogenesis involves the self-renewal/proliferation, survival, migration and lineage differentiation of neural stem/progenitor cells. Such dynamic process is tightly regulated by intrinsic and extrinsic factors and complex signaling pathways. Misregulated neurogenesis contributes much to a large range of neurodevelopmental defects and neurodegenerative diseases. The signaling of NFκB regulates many genes important in inflammation, immunity, cell survival and neural plasticity. During neurogenesis, NFκB signaling mediates the effect of numerous niche factors such as cytokines, chemokines, growth factors, extracellular matrix molecules, but also crosstalks with other signaling pathways such as Notch, Shh, Wnt/β-catenin. This review summarizes current progress on the NFκB signaling in all aspects of neurogenesis, focusing on the novel role of NFκB signaling in initiating early neural differentiation of neural stem cells and embryonic stem cells. PMID:24324484

The effects of triclosan on pluripotency factors and development of mouse embryonic stem cells and zebrafish.

PubMed

Chen, Xiaojiao; Xu, Bo; Han, Xiumei; Mao, Zhilei; Chen, Minjian; Du, Guizhen; Talbot, Prue; Wang, Xinru; Xia, Yankai

2015-04-01

Triclosan (TCS) poses potential risks to reproduction and development due to its endocrine-disrupting properties. However, the mechanism of TCS's effects on early embryonic development is little known. Embryonic stem cells (ESC) and zebrafish embryos provide valuable models for testing the toxic effects of environmental chemicals on early embryogenesis. In this study, mouse embryonic stem cells (mESC) were acutely exposed to TCS for 24 h, and general cytotoxicity and the effect of TCS on pluripotency were then evaluated. In addition, zebrafish embryos were exposed to TCS from 2- to 24-h post-fertilization (hpf), and their morphology was evaluated. In mESC, alkaline phosphatase staining was significantly decreased after treatment with the highest concentration of TCS (50 μM). Although the expression levels of Sox2 mRNA were not changed, the mRNA levels of Oct4 and Nanog in TCS-treated groups were significantly decreased compared to controls. In addition, the protein levels of Oct4, Sox2 and Nanog were significantly reduced in response to TCS treatment. MicroRNA (miR)-134, an expression inhibitor of pluripotency markers, was significantly increased in TCS-treated mESC. In zebrafish experiments, after 24 hpf of treatment, the controls had developed to the late stage of somitogenesis, while embryos exposed to 300 μg/L of TCS were still at the early stage of somitogenesis, and three genes (Oct4, Sox2 and Nanog) were upregulated in treated groups when compared with the controls. The two models demonstrated that TCS may affect early embryonic development by disturbing the expression of the pluripotency markers (Oct4, Sox2 and Nanog).

Early risk of mortality after coronary artery revascularization in patients with left ventricular dysfunction and potential role of the wearable cardioverter defibrillator.

PubMed

Zishiri, Edwin T; Williams, Sarah; Cronin, Edmond M; Blackstone, Eugene H; Ellis, Stephen G; Roselli, Eric E; Smedira, Nicholas G; Gillinov, A Marc; Glad, Jo Ann; Tchou, Patrick J; Szymkiewicz, Steven J; Chung, Mina K

2013-02-01

Implantation of implantable cardioverter defibrillator for prevention of sudden cardiac death is deferred for 90 days after coronary revascularization, but mortality may be highest early after cardiac procedures in patients with ventricular dysfunction. We determined mortality risk in postrevascularization patients with left ventricular ejection fraction ≤35% and compared survival with those discharged with a wearable cardioverter defibrillator (WCD). Hospital survivors after surgical (coronary artery bypass graft surgery) or percutaneous (percutaneous coronary intervention [PCI]) revascularization with left ventricular ejection fraction ≤35% were included from Cleveland Clinic and national WCD registries. Kaplan-Meier, Cox proportional hazards, propensity score-matched survival, and hazard function analyses were performed. Early mortality hazard was higher among 4149 patients discharged without a defibrillator compared with 809 with WCDs (90-day mortality post-coronary artery bypass graft surgery 7% versus 3%, P=0.03; post-PCI 10% versus 2%, P<0.0001). WCD use was associated with adjusted lower risks of long-term mortality in the total cohort (39%, P<0.0001) and both post-coronary artery bypass graft surgery (38%, P=0.048) and post-PCI (57%, P<0.0001) cohorts (mean follow-up, 3.2 years). In propensity-matched analyses, WCD use remained associated with lower mortality (58% post-coronary artery bypass graft surgery, P=0.002; 67% post-PCI, P<0.0001). Mortality differences were not attributable solely to therapies for ventricular arrhythmia. Only 1.3% of the WCD group had a documented appropriate therapy. Patients with left ventricular ejection fraction ≤35% have higher early compared to late mortality after coronary revascularization, particularly after PCI. As early hazard seemed less marked in WCD users, prospective studies in this high-risk population are indicated to confirm whether WCD use as a bridge to left ventricular ejection fraction improvement or

A Role for Caenorhabditis elegans Importin IMA-2 in Germ Line and Embryonic Mitosis

PubMed Central

Geles, Kenneth G.; Johnson, Jeffrey J.; Jong, Sena; Adam, Stephen A.

2002-01-01

The importin α family of nuclear-cytoplasmic transport factors mediates the nuclear localization of proteins containing classical nuclear localization signals. Metazoan animals express multiple importin α proteins, suggesting their possible roles in cell differentiation and development. Adult Caenorhabditis elegans hermaphrodites express three importin α proteins, IMA-1, IMA-2, and IMA-3, each with a distinct expression and localization pattern. IMA-2 was expressed exclusively in germ line cells from the early embryonic through adult stages. The protein has a dynamic pattern of localization dependent on the stage of the cell cycle. In interphase germ cells and embryonic cells, IMA-2 is cytoplasmic and nuclear envelope associated, whereas in developing oocytes, the protein is cytoplasmic and intranuclear. During mitosis in germ line cells and embryos, IMA-2 surrounded the condensed chromosomes but was not directly associated with the mitotic spindle. The timing of IMA-2 nuclear localization suggested that the protein surrounded the chromosomes after fenestration of the nuclear envelope in prometaphase. Depletion of IMA-2 by RNA-mediated gene interference (RNAi) resulted in embryonic lethality and a terminal aneuploid phenotype. ima-2(RNAi) embryos have severe defects in nuclear envelope formation, accumulating nucleoporins and lamin in the cytoplasm. We conclude that IMA-2 is required for proper chromosome dynamics in germ line and early embryonic mitosis and is involved in nuclear envelope assembly at the conclusion of mitosis. PMID:12221121

RISC-mediated control of selected chromatin regulators stabilizes ground state pluripotency of mouse embryonic stem cells.

PubMed

Pandolfini, Luca; Luzi, Ettore; Bressan, Dario; Ucciferri, Nadia; Bertacchi, Michele; Brandi, Rossella; Rocchiccioli, Silvia; D'Onofrio, Mara; Cremisi, Federico

2016-05-06

Embryonic stem cells are intrinsically unstable and differentiate spontaneously if they are not shielded from external stimuli. Although the nature of such instability is still controversial, growing evidence suggests that protein translation control may play a crucial role. We performed an integrated analysis of RNA and proteins at the transition between naïve embryonic stem cells and cells primed to differentiate. During this transition, mRNAs coding for chromatin regulators are specifically released from translational inhibition mediated by RNA-induced silencing complex (RISC). This suggests that, prior to differentiation, the propensity of embryonic stem cells to change their epigenetic status is hampered by RNA interference. The expression of these chromatin regulators is reinstated following acute inactivation of RISC and it correlates with loss of stemness markers and activation of early cell differentiation markers in treated embryonic stem cells. We propose that RISC-mediated inhibition of specific sets of chromatin regulators is a primary mechanism for preserving embryonic stem cell pluripotency while inhibiting the onset of embryonic developmental programs.

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.

Embryonic demise caused by targeted disruption of a cysteine protease Dub-2.

PubMed

Baek, Kwang-Hyun; Lee, Heyjin; Yang, Sunmee; Lim, Soo-Bin; Lee, Wonwoo; Lee, Jeoung Eun; Lim, Jung-Jin; Jun, Kisun; Lee, Dong-Ryul; Chung, Young

2012-01-01

A plethora of biological metabolisms are regulated by the mechanisms of ubiquitination, wherein this process is balanced with the action of deubiquitination system. Dub-2 is an IL-2-inducible, immediate-early gene that encodes a deubiquitinating enzyme with growth regulatory activity. DUB-2 presumably removes ubiquitin from ubiquitin-conjugated target proteins regulating ubiquitin-mediated proteolysis, but its specific target proteins are unknown yet. To elucidate the functional role of Dub-2, we generated genetically modified mice by introducing neo cassette into the second exon of Dub-2 and then homologous recombination was done to completely abrogate the activity of DUB-2 proteins. We generated Dub-2+/- heterozygous mice showing a normal phenotype and are fertile, whereas new born mouse of Dub-2-/- homozygous alleles could not survive. In addition, Dub-2-/- embryo could not be seen between E6.5 and E12.5 stages. Furthermore, the number of embryos showing normal embryonic development for further stages is decreased in heterozygotes. Even embryonic stem cells from inner cell mass of Dub-2-/- embryos could not be established. Our study suggests that the targeted disruption of Dub-2 may cause embryonic lethality during early gestation, possibly due to the failure of cell proliferation during hatching process.

The miR-290-295 cluster as multi-faceted players in mouse embryonic stem cells.

PubMed

Yuan, Kai; Ai, Wen-Bing; Wan, Lin-Yan; Tan, Xiao; Wu, Jiang-Feng

2017-01-01

Increasing evidence indicates that embryonic stem cell specific microRNAs (miRNAs) play an essential role in the early development of embryo. Among them, the miR-290-295 cluster is the most highly expressed in the mouse embryonic stem cells and involved in various biological processes. In this paper, we reviewed the research progress of the function of the miR-290-295 cluster in embryonic stem cells. The miR-290-295 cluster is involved in regulating embryonic stem cell pluripotency maintenance, self-renewal, and reprogramming somatic cells to an embryonic stem cell-like state. Moreover, the miR-290-295 cluster has a latent pro-survival function in embryonic stem cells and involved in tumourigenesis and senescence with a great significance. Elucidating the interaction between the miR-290-295 cluster and other modes of gene regulation will provide us new ideas on the biology of pluripotent stem cells. In the near future, the broad prospects of the miRNA cluster will be shown in the stem cell field, such as altering cell identities with high efficiency through the transient introduction of tissue-specific miRNA cluster.

Cell Cycle Control in the Early Embryonic Development of Aquatic Animal Species

PubMed Central

Siefert, Joseph C.; Clowdus, Emily A.; Sansam, Christopher L.

2016-01-01

The cell cycle is integrated with many aspects of embryonic development. Not only is proper control over the pace of cell proliferation important, but also the timing of cell cycle progression is coordinated with transcription, cell migration, and cell differentiation. Due to the ease with which the embryos of aquatic organisms can be observed and manipulated, they have been a popular choice for embryologists throughout history. In the cell cycle field, aquatic organisms have been extremely important because they have played a major role in the discovery and analysis of key regulators of the cell cycle. In particular, the frog Xenopus laevis has been instrumental for understanding how the basic embryonic cell cycle is regulated. More recently, the zebrafish has been used to understand how the cell cycle is remodeled during vertebrate development and how it is regulated during morphogenesis. This review describes how some of the unique strengths of aquatic species have been leveraged for cell cycle research and suggests how species such as Xenopus and zebrafish will continue to reveal the roles of the cell cycle in human biology and disease. PMID:26475527

Maternal Diabetes Leads to Adaptation in Embryonic Amino Acid Metabolism during Early Pregnancy.

PubMed

Gürke, Jacqueline; Hirche, Frank; Thieme, René; Haucke, Elisa; Schindler, Maria; Stangl, Gabriele I; Fischer, Bernd; Navarrete Santos, Anne

2015-01-01

During pregnancy an adequate amino acid supply is essential for embryo development and fetal growth. We have studied amino acid composition and branched chain amino acid (BCAA) metabolism at day 6 p.c. in diabetic rabbits and blastocysts. In the plasma of diabetic rabbits the concentrations of 12 amino acids were altered in comparison to the controls. Notably, the concentrations of the BCAA leucine, isoleucine and valine were approximately three-fold higher in diabetic rabbits than in the control. In the cavity fluid of blastocysts from diabetic rabbits BCAA concentrations were twice as high as those from controls, indicating a close link between maternal diabetes and embryonic BCAA metabolism. The expression of BCAA oxidizing enzymes and BCAA transporter was analysed in maternal tissues and in blastocysts. The RNA amounts of three oxidizing enzymes, i.e. branched chain aminotransferase 2 (Bcat2), branched chain ketoacid dehydrogenase (Bckdha) and dehydrolipoyl dehydrogenase (Dld), were markedly increased in maternal adipose tissue and decreased in liver and skeletal muscle of diabetic rabbits than in those of controls. Blastocysts of diabetic rabbits revealed a higher Bcat2 mRNA and protein abundance in comparison to control blastocysts. The expression of BCAA transporter LAT1 and LAT2 were unaltered in endometrium of diabetic and healthy rabbits, whereas LAT2 transcripts were increased in blastocysts of diabetic rabbits. In correlation to high embryonic BCAA levels the phosphorylation amount of the nutrient sensor mammalian target of rapamycin (mTOR) was enhanced in blastocysts caused by maternal diabetes. These results demonstrate a direct impact of maternal diabetes on BCAA concentrations and degradation in mammalian blastocysts with influence on embryonic mTOR signalling.

Maternal Diabetes Leads to Adaptation in Embryonic Amino Acid Metabolism during Early Pregnancy

PubMed Central

Gürke, Jacqueline; Hirche, Frank; Thieme, René; Haucke, Elisa; Schindler, Maria; Stangl, Gabriele I.; Fischer, Bernd; Navarrete Santos, Anne

2015-01-01

During pregnancy an adequate amino acid supply is essential for embryo development and fetal growth. We have studied amino acid composition and branched chain amino acid (BCAA) metabolism at day 6 p.c. in diabetic rabbits and blastocysts. In the plasma of diabetic rabbits the concentrations of 12 amino acids were altered in comparison to the controls. Notably, the concentrations of the BCAA leucine, isoleucine and valine were approximately three-fold higher in diabetic rabbits than in the control. In the cavity fluid of blastocysts from diabetic rabbits BCAA concentrations were twice as high as those from controls, indicating a close link between maternal diabetes and embryonic BCAA metabolism. The expression of BCAA oxidizing enzymes and BCAA transporter was analysed in maternal tissues and in blastocysts. The RNA amounts of three oxidizing enzymes, i.e. branched chain aminotransferase 2 (Bcat2), branched chain ketoacid dehydrogenase (Bckdha) and dehydrolipoyl dehydrogenase (Dld), were markedly increased in maternal adipose tissue and decreased in liver and skeletal muscle of diabetic rabbits than in those of controls. Blastocysts of diabetic rabbits revealed a higher Bcat2 mRNA and protein abundance in comparison to control blastocysts. The expression of BCAA transporter LAT1 and LAT2 were unaltered in endometrium of diabetic and healthy rabbits, whereas LAT2 transcripts were increased in blastocysts of diabetic rabbits. In correlation to high embryonic BCAA levels the phosphorylation amount of the nutrient sensor mammalian target of rapamycin (mTOR) was enhanced in blastocysts caused by maternal diabetes. These results demonstrate a direct impact of maternal diabetes on BCAA concentrations and degradation in mammalian blastocysts with influence on embryonic mTOR signalling. PMID:26020623

Tyrosine pathway regulation is host-mediated in the pea aphid symbiosis during late embryonic and early larval development.

PubMed

Rabatel, Andréane; Febvay, Gérard; Gaget, Karen; Duport, Gabrielle; Baa-Puyoulet, Patrice; Sapountzis, Panagiotis; Bendridi, Nadia; Rey, Marjolaine; Rahbé, Yvan; Charles, Hubert; Calevro, Federica; Colella, Stefano

2013-04-10

Nutritional symbioses play a central role in insects' adaptation to specialized diets and in their evolutionary success. The obligatory symbiosis between the pea aphid, Acyrthosiphon pisum, and the bacterium, Buchnera aphidicola, is no exception as it enables this important agricultural pest insect to develop on a diet exclusively based on plant phloem sap. The symbiotic bacteria provide the host with essential amino acids lacking in its diet but necessary for the rapid embryonic growth seen in the parthenogenetic viviparous reproduction of aphids. The aphid furnishes, in exchange, non-essential amino acids and other important metabolites. Understanding the regulations acting on this integrated metabolic system during the development of this insect is essential in elucidating aphid biology. We used a microarray-based approach to analyse gene expression in the late embryonic and the early larval stages of the pea aphid, characterizing, for the first time, the transcriptional profiles in these developmental phases. Our analyses allowed us to identify key genes in the phenylalanine, tyrosine and dopamine pathways and we identified ACYPI004243, one of the four genes encoding for the aspartate transaminase (E.C. 2.6.1.1), as specifically regulated during development. Indeed, the tyrosine biosynthetic pathway is crucial for the symbiotic metabolism as it is shared between the two partners, all the precursors being produced by B. aphidicola. Our microarray data are supported by HPLC amino acid analyses demonstrating an accumulation of tyrosine at the same developmental stages, with an up-regulation of the tyrosine biosynthetic genes. Tyrosine is also essential for the synthesis of cuticular proteins and it is an important precursor for cuticle maturation: together with the up-regulation of tyrosine biosynthesis, we observed an up-regulation of cuticular genes expression. We were also able to identify some amino acid transporter genes which are essential for the switch

Risk factors of early and late mortality after thoracic endovascular aortic repair for complicated stanford B acute aortic dissection.

PubMed

Ruan, Zhong-Bao; Zhu, Li; Yin, Yi-Gang; Chen, Ge-Cai

2014-07-01

The risk factors associated with death in complicated Stanford B acute aortic dissection (AAD) after thoracic endovascular aortic repair (TEVAR) are poorly understood. The aim of this study was to evaluate the early and late events and mortality of complicated Stanford B AAD associated with TEVAR. Sixty-two patients with complicated Stanford B AAD undergoing TEVAR were included in this study. Primary technical success of TEVAR was achieved in 61 (98.39%) cases. The early mortality rate was 9.68%. Procedural type I endoleak (p = 0.007, OR = 7.71, 95% CI: 1.75-34.01) and cardiac tamponade (p = 0.010, OR = 8.86, 95% CI: 1.70-4 6.14) were the significant predictors of early death in the multivariate model. The late mortality was 16.07%. Cox regression analysis revealed rupture of false lumen (p = 0.001, hazard ratio = 21.96, 95% CI: 3.02-82.12), postoperative myocardial infarction (p = 0.001, hazard ratio = 9.86, 95% CI: 2.12-39.64), and acute renal failure (p = 0.024, hazard ratio = 3.98, 95% CI: 1.26-12.11) to be independent risk factors of late mortality. Type I procedural endoleak and cardiac tamponade were the significant predictors of early death in patients of complicated Stanford B AAD undergoing TEVAR. Rupture of false lumen, postoperative myocardial infarction, and acute renal failure were the independent risk factors for late death after TEVAR. © 2014 Wiley Periodicals, Inc.

Genetic and environmental factors influencing first service conception rate and late embryonic/foetal mortality in low fertility dairy herds.

PubMed

Grimard, B; Freret, S; Chevallier, A; Pinto, A; Ponsart, C; Humblot, P

2006-01-01

by specific factors (season, BCS), which were not related to CR. The absence of a relationship between estimated genetic index and LEM in spite of its effect on CR indicates that estimated genetic merit has a greater effect on early embryonic loss or fertilisation failure than on later stages of embryo development.

Characterizing early embryonic development of Brown Tsaiya Ducks (Anas platyrhynchos) in comparison with Taiwan Country Chicken (Gallus gallus domestics)

PubMed Central

Lumsangkul, Chompunut; Fan, Yang-Kwang; Chang, Shen-Chang; Ju, Jyh-Cherng

2018-01-01

Avian embryos are among the most convenient and the primary representatives for the study of classical embryology. It is well-known that the hatching time of duck embryos is approximately one week longer than that of chicken embryos. However, the key features associated with the slower embryonic development in ducks have not been adequately described. This study aimed to characterize the pattern and the speed of early embryogenesis in Brown Tsaiya Ducks (BTD) compared with those in Taiwan Country Chicken (TCC) by using growth parameters including embryonic crown-tail length (ECTL), primitive streak formation, somitogenesis, and other development-related parameters, during the first 72 h of incubation. Three hundred and sixty eggs from BTD and TCC, respectively, were incubated at 37.2°C, and were then dissected hourly to evaluate their developmental stages. We found that morphological changes of TCC embryos shared a major similarity with that of the Hamburger and Hamilton staging system during early chick embryogenesis. The initial primitive streak in TCC emerged between 6 and 7 h post-incubation, but its emergence was delayed until 10 to 13 h post-incubation in BTD. Similarly, the limb primordia (wing and limb buds) were observed at 51 h post-incubation in TCC embryos compared to 64 h post-incubation in BTD embryos. The allantois first appeared around 65 to 68 h in TCC embryos, but it was not observed in BTD embryos. At the 72 h post-incubation, 40 somites were clearly formed in TCC embryos while only 32 somites in BTD embryos. Overall, the BTD embryos developed approximately 16 h slower than the chicken embryo during the first 72 h of development. To our best knowledge, this is the first study to describe two distinct developmental time courses between TCC and BTD, which would facilitate future embryogenesis-related studies of the two important avian species in Taiwan. PMID:29742160

Early mortality in children with acute lymphoblastic leukemia in a developing country: the role of malnutrition at diagnosis. A multicenter cohort MIGICCL study.

PubMed

Martín-Trejo, Jorge Alfonso; Núñez-Enríquez, Juan Carlos; Fajardo-Gutiérrez, Arturo; Medina-Sansón, Aurora; Flores-Lujano, Janet; Jiménez-Hernández, Elva; Amador-Sanchez, Raquel; Peñaloza-Gonzalez, José Gabriel; Alvarez-Rodriguez, Francisco Javier; Bolea-Murga, Victoria; Espinosa-Elizondo, Rosa Martha; de Diego Flores-Chapa, José; Pérez-Saldivar, Maria Luisa; Rodriguez-Zepeda, María Del Carmen; Dorantes-Acosta, Elisa María; Núñez-Villegas, Nora Nancy; Velazquez-Aviña, Martha Margarita; Torres-Nava, José Refugio; Reyes-Zepeda, Nancy Carolina; González-Bonilla, César Raúl; Flores-Villegas, Luz Victoria; Rangel-López, Angélica; Rivera-Luna, Roberto; Paredes-Aguilera, Rogelio; Cárdenas-Cardós, Rocío; Martínez-Avalos, Armando; Gil-Hernández, Ana Elena; Duarte-Rodríguez, David Aldebarán; Mejía-Aranguré, Juan Manuel

2017-04-01

The role of malnutrition at diagnosis as a predictor of early mortality in Mexican leukemia children remains controversial. The objective of present study was to investigate whether malnutrition was a predictor of early mortality during the first year of treatment in Mexican acute lymphoblastic leukemia (ALL) children through the first population-based study. A total of 794 newly diagnosed ALL pediatric patients from public hospitals of Mexico City were enrolled. A multivariate Cox proportional hazards regression model was constructed and adjusted by patient's age at diagnosis, gender, hospital of treatment, and socioeconomic status. Early mortality was high (12.1%) and malnutrition by different indicators was not associated with mortality at induction phase and at 6th month; a high risk of dying (RR = 2.08; 95% CI: 1.08-4.01) was observed in the group of malnourished children with a high-risk ALL.

Huntingtin Protein is Essential for Mitochondrial Metabolism, Bioenergetics and Structure in Murine Embryonic Stem Cells

PubMed Central

Ismailoglu, Ismail; Chen, Qiuying; Popowski, Melissa; Yang, Lili; Gross, Steven S.; Brivanlou, Ali H.

2014-01-01

Mutations in the Huntington locus (htt) have devastating consequences. Gain-of-poly-Q repeats in Htt protein causes Huntington's disease (HD), while htt-/- mutants display early embryonic lethality. Despite its importance, the function of Htt remains elusive. To address this, we compared more than 3,700 compounds in three syngeneic mouse embryonic stem cell (mESC) lines: htt-/-, extended poly-Q (Htt-Q140/7), and wildtype mESCs (Htt-Q7/7) using untargeted metabolite profiling. While Htt-Q140/7 cells, did not show major differences in cellular bioenergetics, we find extensive metabolic aberrations in htt-/- mESCs, including: (i) complete failure of ATP production despite preservation of the mitochondrial membrane potential; (ii) near-maximal glycolysis, with little or no glycolytic reserve; (iii) marked ketogenesis; (iv) depletion of intracellular NTPs; (v) accelerated purine biosynthesis and salvage; and (vi) loss of mitochondrial structural integrity. Together, our findings reveal that Htt is necessary for mitochondrial structure and function from the earliest stages of embryogenesis, providing a molecular explanation for htt-/- early embryonic lethality. PMID:24780625

Huntingtin protein is essential for mitochondrial metabolism, bioenergetics and structure in murine embryonic stem cells.

PubMed

Ismailoglu, Ismail; Chen, Qiuying; Popowski, Melissa; Yang, Lili; Gross, Steven S; Brivanlou, Ali H

2014-07-15

Mutations in the Huntington locus (htt) have devastating consequences. Gain-of-poly-Q repeats in Htt protein causes Huntington's disease (HD), while htt(-/-) mutants display early embryonic lethality. Despite its importance, the function of Htt remains elusive. To address this, we compared more than 3700 compounds in three syngeneic mouse embryonic stem cell (mESC) lines: htt(-/-), extended poly-Q (Htt-Q140/7), and wild-type mESCs (Htt-Q7/7) using untargeted metabolite profiling. While Htt-Q140/7 cells did not show major differences in cellular bioenergetics, we find extensive metabolic aberrations in htt(-/-) mESCs, including (i) complete failure of ATP production despite preservation of the mitochondrial membrane potential; (ii) near-maximal glycolysis, with little or no glycolytic reserve; (iii) marked ketogenesis; (iv) depletion of intracellular NTPs; (v) accelerated purine biosynthesis and salvage; and (vi) loss of mitochondrial structural integrity. Together, our findings reveal that Htt is necessary for mitochondrial structure and function from the earliest stages of embryogenesis, providing a molecular explanation for htt(-/-) early embryonic lethality. Copyright © 2014 Elsevier Inc. All rights reserved.

EMBRYONIC VASCULAR DISRUPTION ADVERSE OUTCOMES: LINKING HIGH THROUGHPUT SIGNALING SIGNATURES WITH FUNCTIONAL CONSEQUENCES

EPA Science Inventory

Embryonic vascular disruption is an important adverse outcome pathway (AOP) given the knowledge that chemical disruption of early cardiovascular system development leads to broad prenatal defects. High throughput screening (HTS) assays provide potential building blocks for AOP d...

Early graft dysfunction and mortality rate in marginal donor liver transplantation.

PubMed

Sarkut, Pmar; Gülcü, Bariş; Işçimen, Remzi; Kiyici, Murat; Türker, Gürkan; Topal, Naile Bolca; Ozen, Yilmaz; Kaya, Ekrem

2014-01-01

To determine the effect of marginal donor livers on mortality and graft survival in liver transplantation (LT) recipients. Donors with any 1 of following were considered marginal donors: age ≥65 years, sodium level ≥ 165 mmol/L and cold ischemia time ≥ 12 h. Donors were classified according to the donor risk index (DRI) < 1.7 and ≥ 1.7. The transplant recipients' model for end-stage liver disease (MELD) scores were considered low if < 20 and high if ≥ 20. Early graft dysfunction (EGD) and mortality rate were evaluated. During the study period 47 patients underwent cadaveric LT. The mean age of the donors and recipients was 45 years (range: 5-72 years) and 46 years (range: 4-66 years), respectively. In all, there were 15 marginal donors and 18 donors with a DRI > 1.7. In total, 4 LT patients that received livers from marginal donors and 5 that received livers from donors with a DRI ≥ 1.7 had EGD. Among the recipients of marginal livers, 5 died, versus 4 of the recipients of standard livers. There was no significant difference in EGD or mortality rate between the patients that received livers from marginal donors or those with a DRI ≥ 1.7 and patients that received standard donor livers. Marginal and DRI ≥ 1.7 donors negatively affected LT outcomes, but not significantly.

Migration and health: a study of effects of early life experiences and current socio-economic situation on mortality of immigrants in Sweden.

PubMed

Klinthäll, Martin; Lindström, Martin

2011-12-01

Previous research has demonstrated mortality differences between immigrants and natives living in Sweden. The aim of this study is to investigate the effects of early life conditions in the country of birth and current socio-economic conditions in adult life in Sweden on cardiovascular, cancer, all other cause and total mortality among immigrants and natives in Sweden. The cohort data concerning individual demographic characteristics and socio-economic conditions stems from the Swedish Longitudinal Immigrant Database (SLI), a register-based representative database, and consists of individuals from 11 countries of birth, born between 1921 and 1939, who were residents in Sweden between 1980 and 2001. The associations between current socio-economic conditions as well as infant mortality rates (IMR) and Gross Domestic Product (GDP) per capita in the year and country of birth, and total, cardiovascular, cancer and 'all other' mortality in 1980-2001 were calculated by survival analysis using Cox proportional hazards regression to calculate hazard rate ratios. The effects of current adult life socio-economic conditions in Sweden on mortality are both stronger and more straightforward than the effects of early life conditions in the sense that higher socio-economic status is significantly associated with lower mortality in all groups of diagnoses; however, we find associations between infant mortality rates (IMR) in the year and country of birth, and cancer mortality among men and women in the final model. Socioeconomic conditions in Sweden are more strongly associated with mortality than early life indicators IMR and GDP per capita in the year of birth in the country of origin. This finding has health policy and other policy implications.

Does early functional outcome predict 1-year mortality in elderly patients with hip fracture?

PubMed

Dubljanin-Raspopović, Emilija; Marković-Denić, Ljiljana; Marinković, Jelena; Nedeljković, Una; Bumbaširević, Marko

2013-08-01

Hip fractures in the elderly are followed by considerable risk of functional decline and mortality. The purposes of this study were to (1) explore predictive factors of functional level at discharge, (2) evaluate 1-year mortality after hip fracture compared with that of the general population, and (3) evaluate the affect of early functional outcome on 1-year mortality in patients operated on for hip fractures. A total of 228 consecutive patients (average age, 77.6 ± 7.4 years) with hip fractures who met the inclusion criteria were enrolled in an open, prospective, observational cohort study. Functional level at discharge was measured with the motor Functional Independence Measure (FIM) score, which is the most widely accepted functional assessment measure in use in the rehabilitation community. Mortality rates in the study population were calculated in absolute numbers and as the standardized mortality ratio. Multivariate regression analysis was used to explore predictive factors for motor FIM score at discharge and for 1-year mortality adjusted for important baseline variables. Age, health status, cognitive level, preinjury functional level, and pressure sores after hip fracture surgery were independently related to lower discharge motor FIM scores. At 1-year followup, 57 patients (25%; 43 women and 14 men) had died. The 1-year hip fracture mortality rate compared with that of the general population was 31% in our population versus 7% for men and 23% in our population versus 5% for women 65 years or older. The 1-year standardized mortality rate was 341.3 (95% CI, 162.5-520.1) for men and 301.6 (95% CI, 212.4-391.8) for women, respectively. The all-cause mortality rate observed in this group was higher in all age groups and in both sexes when compared with the all-cause age-adjusted mortality of the general population. Motor FIM score at discharge was the only independent predictor of 1-year mortality after hip fracture. Functional level at discharge is the main

Embryonic Zebrafish Model - A Well-Established Method for Rapidly Assessing the Toxicity of Homeopathic Drugs

PubMed Central

Gupta, Himanshu R; Patil, Yogesh; Singh, Dipty

2016-01-01

Objectives: Advancements in nanotechnology have led to nanoparticle (NP) use in various fields of medicine. Although the potential of NPs is promising, the lack of documented evidence on the toxicological effects of NPs is concerning. A few studies have documented that homeopathy uses NPs. Unfortunately, very few sound scientific studies have explored the toxic effects of homeopathic drugs. Citing this lack of high-quality scientific evidence, regulatory agencies have been reluctant to endorse homeopathic treatment as an alternative or adjunct treatment. This study aimed to enhance our insight into the impact of commercially-available homeopathic drugs, to study the presence of NPs in those drugs and any deleterious effects they might have, and to determine the distribution pattern of NPs in zebrafish embryos (Danio rerio). Methods: Homeopathic dilutions were studied using high-resolution transmission electron microscopy with selected area electron diffraction (SAED). For the toxicity assessment on Zebrafish, embryos were exposed to a test solution from 4 - 6 hours post-fertilization, and embryos/larvae were assessed up to 5 days post-fertilization (dpf) for viability and morphology. Toxicity was recorded in terms of mortality, hatching delay, phenotypic defects and metal accumulation. Around 5 dpf was found to be the optimum developmental stage for evaluation. Results: The present study aimed to conclusively prove the presence of NPs in all high dilutions of homeopathic drugs. Embryonic zebrafish were exposed to three homeopathic drugs with two potencies (30CH, 200CH) during early embryogenesis. The resulting morphological and cellular responses were observed. Exposure to these potencies produced no visibly significant malformations, pericardial edema, and mortality and no necrotic and apoptotic cellular death. Conclusion: Our findings clearly demonstrate that no toxic effects were observed for these three homeopathic drugs at the potencies and exposure times used

Glutathione reductase gsr-1 is an essential gene required for Caenorhabditis elegans early embryonic development.

PubMed

Mora-Lorca, José Antonio; Sáenz-Narciso, Beatriz; Gaffney, Christopher J; Naranjo-Galindo, Francisco José; Pedrajas, José Rafael; Guerrero-Gómez, David; Dobrzynska, Agnieszka; Askjaer, Peter; Szewczyk, Nathaniel J; Cabello, Juan; Miranda-Vizuete, Antonio

2016-07-01

Glutathione is the most abundant thiol in the vast majority of organisms and is maintained in its reduced form by the flavoenzyme glutathione reductase. In this work, we describe the genetic and functional analysis of the Caenorhabditis elegans gsr-1 gene that encodes the only glutathione reductase protein in this model organism. By using green fluorescent protein reporters we demonstrate that gsr-1 produces two GSR-1 isoforms, one located in the cytoplasm and one in the mitochondria. gsr-1 loss of function mutants display a fully penetrant embryonic lethal phenotype characterized by a progressive and robust cell division delay accompanied by an aberrant distribution of interphasic chromatin in the periphery of the cell nucleus. Maternally expressed GSR-1 is sufficient to support embryonic development but these animals are short-lived, sensitized to chemical stress, have increased mitochondrial fragmentation and lower mitochondrial DNA content. Furthermore, the embryonic lethality of gsr-1 worms is prevented by restoring GSR-1 activity in the cytoplasm but not in mitochondria. Given the fact that the thioredoxin redox systems are dispensable in C. elegans, our data support a prominent role of the glutathione reductase/glutathione pathway in maintaining redox homeostasis in the nematode. Copyright © 2016 Elsevier Inc. All rights reserved.

Detecting early warning signals of tree mortality using multi-scale satellite data: a case study in boreal North Americ

NASA Astrophysics Data System (ADS)

Rogers, B. M.; Hogg, E. H.; Solvik, K.; Ju, J.; Masek, J. G.; Michaelian, M.; Berner, L. T.; Goetz, S. J.

2017-12-01

Tree mortality from drought and biotic infestations represents a fundamental transition for forests at the level of an individual tree, forest stand, and even landscape. Tree mortality precipitates a cascade of ecosystem impacts and has been increasing across the continents, including in the boreal zone where climate changes and feedbacks to the Earth system are relatively large. Despite the importance for science and management communities, our ability to forecast tree mortality at landscape to continental scales is limited. However, two independent information streams have the potential to inform and significantly improve mortality forecasts. Tree-level productivity dynamics are known to precede mortality in predictable ways years to decades before death. Plot-level productivity, in turn, has been related to satellite-based indices such as the Normalized Difference Vegetation Index (NDVI). Here we link these two data sources to show that early warning signals of mortality are evident in several NDVI-based metrics up to 20 years before death. We focus on two repeat forest inventories and three NDVI products across western boreal North America where productivity and mortality dynamics are influenced by periodic drought. These data sources capture a range in forest conditions and spatial resolution to highlight the sensitivity and limitations of our approach. Overall, results indicate potential to use satellite NDVI for early warning signals of mortality. Relationships are broadly consistent across inventories, species, and spatial resolutions, although coarse-scale imagery in the heterogeneous aspen parkland was of limited utility. Longer-term NDVI data and annually re-measured sites with high mortality levels generate the strongest signals, although we still found robust relationships at sites re-measured at a typical five-year frequency. The approach and relationships developed here can be used as a basis for improving forest mortality models and monitoring

High resolution ultrasound-guided microinjection for interventional studies of early embryonic and placental development in vivo in mice

PubMed Central

Slevin, John C; Byers, Lois; Gertsenstein, Marina; Qu, Dawei; Mu, Junwu; Sunn, Nana; Kingdom, John CP; Rossant, Janet; Adamson, S Lee

2006-01-01

similar in sham experiments, 54% (33/61), for which procedures were identical but no microinjection was performed, suggesting that surgery and manipulation of the uterus were the main causes of embryonic death. Conclusion Ultrasound-guided microinjection into the ectoplacental cone region at E6.5 or E7.5 and the amniotic cavity at E7.5 was achieved with a 7 day postnatal survival of ≥60%. Target accuracy of these sites and of the exocoelomic cavity at E7.5 was ≥51%. We suggest that this approach may be useful for exploring gene function during early placental and embryonic development. PMID:16504164

Early Life Stress Affects Mortality Rate More than Social Behavior, Gene Expression or Oxidative Damage in Honey Bee Workers

PubMed Central

Rueppell, Olav; Yousefi, Babak; Collazo, Juan; Smith, Daniel

2017-01-01

Early life stressors can affect aging and life expectancy in positive or negative ways. Individuals can adjust their behavior and molecular physiology based on early life experiences but relatively few studies have connected such mechanisms to demographic patterns in social organisms. Sociality buffers individuals from environmental influences and it is unclear how much early life stress affects later life history. Workers of the honey bee (Apis mellifera L.) were exposed to two stressors, Varroa parasitism and paraquat exposure, early in life. Consequences were measured at the molecular, behavioral, and demographic level. While treatments did not significantly affect levels of oxidative damage, expression of select genes, and titers of the common deformed wing virus, most of these measures were affected by age. Some of the age effects, such as declining levels of deformed wing virus and oxidative damage, were opposite to our predictions but may be explained by demographic selection. Further analyses suggested some influences of worker behavior on mortality and indicated weak treatment effects on behavior. The latter effects were inconsistent among the two experiments. However, mortality rate was consistently reduced by Varroa mite stress during development. Thus, mortality was more responsive to early life stress than our other response variables. The lack of treatment effects on these measures may be due to the social organization of honey bees that buffers the individual from the impact of stressful developmental conditions. PMID:28122251

Early life stress affects mortality rate more than social behavior, gene expression or oxidative damage in honey bee workers.

PubMed

Rueppell, Olav; Yousefi, Babak; Collazo, Juan; Smith, Daniel

2017-04-01

Early life stressors can affect aging and life expectancy in positive or negative ways. Individuals can adjust their behavior and molecular physiology based on early life experiences but relatively few studies have connected such mechanisms to demographic patterns in social organisms. Sociality buffers individuals from environmental influences and it is unclear how much early life stress affects later life history. Workers of the honey bee (Apis mellifera L.) were exposed to two stressors, Varroa parasitism and Paraquat exposure, early in life. Consequences were measured at the molecular, behavioral, and demographic level. While treatments did not significantly affect levels of oxidative damage, expression of select genes, and titers of the common deformed wing virus, most of these measures were affected by age. Some of the age effects, such as declining levels of deformed wing virus and oxidative damage, were opposite to our predictions but may be explained by demographic selection. Further analyses suggested some influences of worker behavior on mortality and indicated weak treatment effects on behavior. The latter effects were inconsistent among the two experiments. However, mortality rate was consistently reduced by Varroa mite stress during development. Thus, mortality was more responsive to early life stress than our other response variables. The lack of treatment effects on these measures may be due to the social organization of honey bees that buffers the individual from the impact of stressful developmental conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

Long-Term Mortality Effect of Early Pacemaker Implantation After Surgical Aortic Valve Replacement.

PubMed

Greason, Kevin L; Lahr, Brian D; Stulak, John M; Cha, Yong-Mei; Rea, Robert F; Schaff, Hartzell V; Dearani, Joseph A

2017-10-01

The need for pacemaker implantation is a well-described complication of aortic valve replacement. Not so well described is the effect such an event has on long-term outcome. This study reviewed a 21-year experience at the Mayo Clinic (Rochester, Minnesota) with aortic valve replacement to understand the influence of early postoperative pacemaker implantation on long-term mortality rates more clearly. This study retrospectively reviewed the records of 5,842 patients without previous pacemaker implantation who underwent surgical aortic valve replacement from January 1993 through June 2014. The median age of these patients was 73 years (range, 65 to 79 years), the median ejection fraction was 62% (range, 53% to 68%), 3,853 patients were male (66%), and coronary artery bypass graft operation was performed in 2,553 (44%) of the patients studied. Early pacemaker implantation occurred in 146 patients (2.5%) within 30 days of surgical aortic valve replacement. The median follow-up of patients was 11.1 years (range, 5.8 to 16.5 years), and all-cause mortality rates were 2.4% at 30 days, 6.4% at 1 year, 23.1% at 5 years, 48.3% at 10 years, and 67.9% at 15 years postoperatively. Early pacemaker implantation was associated with an increased risk of death after multivariable adjustment for baseline patients' characteristics (hazard ratio, 1.49; 95% confidence interval, 1.20, 1.84; p < 0.001). Early pacemaker implantation as a complication of surgical aortic valve replacement is associated with an increased risk of long-term death. Valve replacement-related pacemaker implantation rates should be important considerations with respect to new valve replacement paradigms, especially in younger and lower-risk patients. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

The fine structure of human germ layers in vivo: clues to the early differentiation of embryonic stem cells in vitro.

PubMed

Sathananthan, Henry; Selvaraj, Kamala; Clark, Joan

2011-08-01

The fine structure of the three germ layers in human ectopic embryos (stage 7) have been documented by digital light and electron microscopy. The formation of ectoderm, endoderm and mesoderm and notochordal cells, and also the extraembryonic membranes, amnion and yolk sac, are imaged. The germ layers give rise to all the cells and tissues of the human body. Possible clues to the early differentiation of embryonic stem cells (ESC) in vitro were obtained, since these events are more or less mimicked in cultures of ESC derived from the inner cell mass of human blastocysts. The findings are discussed with reference to previous studies on the fine structure of ESC using the same technique. Copyright © 2011. Published by Elsevier Ltd.

Serum Phosphate Predicts Early Mortality among Underweight Adults Starting ART in Zambia: A Novel Context for Refeeding Syndrome?

PubMed Central

Koethe, John R.; Blevins, Meridith; Nyirenda, Christopher K.; Kabagambe, Edmond K.; Chiasera, Janelle M.; Shepherd, Bryan E.; Zulu, Isaac; Heimburger, Douglas C.

2013-01-01

Background. Low body mass index (BMI) at antiretroviral therapy (ART) initiation is associated with early mortality, but the etiology is not well understood. We hypothesized that low pretreatment serum phosphate, a critical cellular metabolism intermediate primarily stored in skeletal muscle, may predict mortality within the first 12 weeks of ART. Methods. We prospectively studied 352 HIV-infected adults initiating ART in Lusaka, Zambia to estimate the odds of death for each 0.1 mmol/L decrease in baseline phosphate after adjusting for established predictors of mortality. Results. The distribution of phosphate values was similar across BMI categories (median value 1.2 mmol/L). Among the 145 participants with BMI <18.5 kg/m2, 28 (19%) died within 12 weeks. Lower pretreatment serum phosphate was associated with increased mortality (odds ratio (OR) 1.24 per 0.1 mmol/L decrement, 95% CI: 1.05 to 1.47; P = 0.01) after adjusting for sex, age, and CD4+ lymphocyte count. A similar relationship was not observed among participants with BMI ≥18.5 kg/m2 (OR 0.96, 95% CI: 0.76 to 1.21; P = 0.74). Conclusions. The association of low pretreatment serum phosphate level and early ART mortality among undernourished individuals may represent a variant of the refeeding syndrome. Further studies of cellular metabolism in this population are needed. PMID:23691292

Early mortality in adults initiating antiretroviral therapy (ART) in low- and middle-income countries (LMIC): a systematic review and meta-analysis.

PubMed

Gupta, Amita; Nadkarni, Girish; Yang, Wei-Teng; Chandrasekhar, Aditya; Gupte, Nikhil; Bisson, Gregory P; Hosseinipour, Mina; Gummadi, Naveen

2011-01-01

We systematically reviewed observational studies of early mortality post-antiretroviral therapy (ART) initiation in low- and middle-income countries (LMIC) in Asia, Africa, and Central and South America, as defined by the World Bank, to summarize what is known. Studies published in English between January 1996 and December 2010 were searched in Medline and EMBASE. Three independent reviewers examined studies of mortality within one year post-ART. An article was included if the study was conducted in a LMIC, participants were initiating ART in a non-clinical trial setting and were ≥15 years. Fifty studies were included; 38 (76%) from sub-Saharan Africa (SSA), 5 (10%) from Asia, 2 (4%) from the Americas, and 5 (10%) were multi-regional. Median follow-up time and pre-ART CD4 cell count ranged from 3-55 months and 11-192 cells/mm(3), respectively. Loss-to-follow-up, reported in 40 (80%) studies, ranged from 0.3%-27%. Overall, SSA had the highest pooled 12-month mortality probability of 0.17 (95% CI 0.11-0.24) versus 0.11 (95% CI 0.10-0.13) for Asia, and 0.07 (95% CI 0.007-0.20) for the Americas. Of 14 (28%) studies reporting cause-specific mortality, tuberculosis (TB) (5%-44%), wasting (5%-53%), advanced HIV (20%-37%), and chronic diarrhea (10%-25%) were most common. Independent factors associated with early mortality in 30 (60%) studies included: low baseline CD4 cell count, male sex, advanced World Health Organization clinical stage, low body mass index, anemia, age greater than 40 years, and pre-ART quantitative HIV RNA. Significant heterogeneity in outcomes and in methods of reporting outcomes exist among published studies evaluating mortality in the first year after ART initiation in LMIC. Early mortality rates are highest in SSA, and opportunistic illnesses such as TB and wasting syndrome are the most common reported causes of death. Strategies addressing modifiable risk factors associated with early death are urgently needed.

Autonomous assembly of epithelial structures by subrenal implantation of dissociated embryonic inner-ear cells.

PubMed

Wang, Li; Zhang, Kaiqing; Zhu, Helen He; Gao, Wei-Qiang

2015-05-27

Microenvironment and cell-cell interactions play an important role during embryogenesis and are required for the stemness and differentiation of stem cells. The inner-ear sensory epithelium, containing hair cells and supporting cells, is derived from the stem cells within the otic vesicle at early embryonic stages. However, whether or not such microenvironment or cell-cell interactions within the embryonic otic tissue have the capacity to regulate the proliferation and differentiation of stem cells and to autonomously reassemble the cells into epithelial structures is unknown. Here, we report that on enzymatic digestion and dissociation to harvest all the single cells from 13.5-day-old rat embryonic (E13.5) inner-ear tissue as well as on implantation of these cells under renal capsules; the dissociated cells are able to reassemble themselves to form epithelial structures as early as 7 days after implantation. By 25 days after implantation, more mature epithelial structures are formed. Immunostaining with cell-type-specific markers reveals that hair cells and supporting cells are not only formed, but are also well aligned with the hair cells located in the apical layer surrounded by the supporting cells. These findings suggest that microenvironment and cell-cell interactions within the embryonic inner-ear tissue have the autonomous signals to induce the formation of sensory epithelial structures. This method may also provide a useful system to study the potential of stem cells to differentiate into hair cells in vivo.

LOW PRETERM BIRTH RATE WITH DECREASING EARLY NEONATAL MORTALITY IN BOSNIA AND HERZEGOVINA DURING 2007-2014

PubMed Central

Hudic, Igor; Stray-Pedersen, Babill; Skokic, Fahrija; Fatusic, Zlatan; Zildzic-Moralic, Aida; Skokic, Maida; Fatusic, Jasenko

2016-01-01

The aim: of the study was to determine the situation of preterm births and early neonatal mortality during 2007-2014 in Tuzla Canton, Bosnia and Herzegovina. Methods: The study covers a 8-year period and is based on the protocols at the Tuzla Clinic for Gynecology and Obstetrics that covers all birth in Tuzla Canton area. We analyzed the gestational age of all newborns and recorded the number of neonatal deaths in the first week after birth. Demographics, pregnancy and birth characteristics were collected from the maternal records. Results: The total number of births in the period was 32738. Preterm birth was identified in 2401 (7.3%) cases with 12,5% occurring before 32 gestational weeks and 64% in 35-36 gestational weeks. The mothers of the 24-31 gws preterm group were significantly younger that those in the 32-36 group. In the 32-36 group there were significantly greater proportions of mothers with assisted reproductive technology and pre-eclampsia and 16.7% was medical induced preterm births versus 11.4 % in the 24-31 PTB group, p<0.05. The incidence of PTB did no vary significantly during the period, the lowest rate was found in 2010 (6.4%). A total of 221 children died giving a early mortality rate of 6.8 per 1000 live born over the 8 years. The majority 156 dying infants (70.6%) were preterm, only 5.7% died being born in the 35-36 gestational week (5.9 per 1000). Overall the preterm early mortality (7.3 per 1000) has shown a decreasing tendency during the latter years. Conclusion: During the last 8 years there have been no significant decline in preterm birth in the Tuzla region while a decline in early neonatal death has been registered. PMID:27047264

Effect of temperature during embryonic development and first feeding of Trichogaster leeri larvae.

PubMed

Pereira, Samuel Louzada; de Andrade, Dalcio Ricardo; Radael, Marcella Costa; Fosse Filho, João Carlos; de Azevedo, Rafael Vieira; Mattos, Douglas da Cruz; Vidal Junior, Manuel Vazquez

2016-10-01

Temperature is an environmental factor that influences the development of fish, and when changed abruptly can lead to high mortality. Some species of fish are influenced by this factor, exhibiting a longer time for embryonic development and time to first feeding. This study aims to evaluate the effect of water temperature on embryonic and larval development up to first feeding, to describe the time in hours post fertilization (hpf) of the emergence of different structures and to determine the best hatching rate and survival of animals under different treatments. Five different egg incubation temperatures were used (24, 26, 28, 30 or 32°C, respectively). The eggs were observed at regular intervals of 30 min up to 24 h, every 2 h until 48 h and every 4 h until the display of first feeding in all treatments. Embryonic development was longer for eggs incubated at 24°C and the best results for hatching rate and survival of spawning efficiency were at 28°C. We recommend that incubation of Trichogaster leeri eggs is carried out at 28°C up to the first feeding of larvae.

Normal embryonic and germ cell development in mice lacking alpha 1,3-fucosyltransferase IX (Fut9) which show disappearance of stage-specific embryonic antigen 1.

PubMed

Kudo, Takashi; Kaneko, Mika; Iwasaki, Hiroko; Togayachi, Akira; Nishihara, Shoko; Abe, Kuniya; Narimatsu, Hisashi

2004-05-01

Stage-specific embryonic antigen 1 (SSEA-1), an antigenic epitope defined as a Lewis x carbohydrate structure, is expressed during the 8-cell to blastocyst stages in mouse embryos and in primordial germ cells, undifferentiated embryonic stem cells, and embryonic carcinoma cells. For many years, SSEA-1 has been implicated in the development of mouse embryos as a functional carbohydrate epitope in cell-to-cell interaction during morula compaction. In a previous study, alpha 1,3-fucosyltransferase IX (Fut9) exhibited very strong activity for the synthesis of Lewis x compared to other alpha 1,3-fucosyltransferases in an in vitro substrate specificity assay. Fut4 and Fut9 transcripts were expressed in mouse embryos. The Fut9 transcript was detected in embryonic-day-13.5 gonads containing primordial germ cells, but the Fut4 transcript was not. In order to identify the role of SSEA-1 and determine the key enzyme for SSEA-1 synthesis in vivo, we have generated Fut9-deficient (Fut9(-/-)) mice. Fut9(-/-) mice develop normally, with no gross phenotypic abnormalities, and are fertile. Immunohistochemical analysis revealed an absence of SSEA-1 expression in early embryos and primordial germ cells of Fut9(-/-) mice. Therefore, we conclude that expression of the SSEA-1 epitope in the developing mouse embryo is not essential for embryogenesis in vivo.

Socio-economic patterning in early mortality of patients aged 0-49 years diagnosed with primary bone cancer in Great Britain, 1985-2008.

PubMed

Blakey, Karen; Feltbower, Richard G; James, Peter W; Libby, Gillian; Stiller, Charles; Norman, Paul; Gerrand, Craig; McNally, Richard J Q

2018-04-01

Studies have shown marked improvements in survival between 1981 and 2000 for Ewing sarcoma patients but not for osteosarcoma. This study aimed to explore socio-economic patterning in early mortality rates for both tumours. The study analysed all 2432 osteosarcoma and 1619 Ewing sarcoma cases, aged 0-49 years, diagnosed in Great Britain 1985-2008 and followed to 31/12/2009. Logistic regression models were used to calculate risk of dying within three months, six months, one year, three years and five years after diagnosis. Associations with Townsend deprivation score and its components were examined at small-area level. Urban/rural status was studied at larger regional level. For osteosarcoma, after age adjustment, mortality at three months, six months and one year was associated with higher area unemployment, OR = 1.05 (95% CI 1.00, 1.10), OR = 1.04 (95% CI 1.01, 1.08) and OR = 1.04 (95% CI 1.02, 1.06) respectively per 1% increase in unemployment. Mortality at six months was associated with greater household non-car ownership, OR = 1.02 (95% CI 1.00, 1.03). For Ewing sarcoma, there were no significant associations between mortality and overall Townsend score, nor its components for any time period. For both tumours increasing mortality was associated with less urban and more remote rural areas. This study found that for osteosarcoma, early mortality was associated with residence at diagnosis in areas of higher unemployment, suggesting risk of early death may be socio-economically determined. For both tumours, distance from urban centres may lead to greater risk of early death. Copyright © 2018 Elsevier Ltd. All rights reserved.

Critical early roles for col27a1a and col27a1b in zebrafish notochord morphogenesis, vertebral mineralization and post-embryonic axial growth.

PubMed

Christiansen, Helena E; Lang, Michael R; Pace, James M; Parichy, David M

2009-12-29

Fibrillar collagens are well known for their links to human diseases, with which all have been associated except for the two most recently identified fibrillar collagens, type XXIV collagen and type XXVII collagen. To assess functions and potential disease phenotypes of type XXVII collagen, we examined its roles in zebrafish embryonic and post-embryonic development. We identified two type XXVII collagen genes in zebrafish, col27a1a and col27a1b. Both col27a1a and col27a1b were expressed in notochord and cartilage in the embryo and early larva. To determine sites of type XXVII collagen function, col27a1a and col27a1b were knocked down using morpholino antisense oligonucleotides. Knockdown of col27a1a singly or in conjunction with col27a1b resulted in curvature of the notochord at early stages and formation of scoliotic curves as well as dysmorphic vertebrae at later stages. These defects were accompanied by abnormal distributions of cells and protein localization in the notochord, as visualized by transmission electron microscopy, as well as delayed vertebral mineralization as detected histologically. Together, our findings indicate a key role for type XXVII collagen in notochord morphogenesis and axial skeletogenesis and suggest a possible human disease phenotype.

Embryonic origin of adult stem cells required for tissue homeostasis and regeneration

PubMed Central

Davies, Erin L; Lei, Kai; Seidel, Christopher W; Kroesen, Amanda E; McKinney, Sean A; Guo, Longhua; Robb, Sofia MC; Ross, Eric J; Gotting, Kirsten; Alvarado, Alejandro Sánchez

2017-01-01

Planarian neoblasts are pluripotent, adult somatic stem cells and lineage-primed progenitors that are required for the production and maintenance of all differentiated cell types, including the germline. Neoblasts, originally defined as undifferentiated cells residing in the adult parenchyma, are frequently compared to embryonic stem cells yet their developmental origin remains obscure. We investigated the provenance of neoblasts during Schmidtea mediterranea embryogenesis, and report that neoblasts arise from an anarchic, cycling piwi-1+ population wholly responsible for production of all temporary and definitive organs during embryogenesis. Early embryonic piwi-1+ cells are molecularly and functionally distinct from neoblasts: they express unique cohorts of early embryo enriched transcripts and behave differently than neoblasts in cell transplantation assays. Neoblast lineages arise as organogenesis begins and are required for construction of all major organ systems during embryogenesis. These subpopulations are continuously generated during adulthood, where they act as agents of tissue homeostasis and regeneration. DOI: http://dx.doi.org/10.7554/eLife.21052.001 PMID:28072387

Radiation Exposure and Mortality from Cardiovascular Disease and Cancer in Early NASA Astronauts: Space for Exploration

NASA Technical Reports Server (NTRS)

Elgart, S. R.; Little, M. P.; Campbell, L. J.; Milder, C. M.; Shavers, M. R.; Huff, J. L.; Patel, Z. S.

2018-01-01

Of the many possible health challenges posed during extended exploratory missions to space, the effects of space radiation on cardiovascular disease and cancer are of particular concern. There are unique challenges to estimating those radiation risks; care and appropriate and rigorous methodology should be applied when considering small cohorts such as the NASA astronaut population. The objective of this work was to establish whether there is evidence for excess cardiovascular disease or cancer mortality in an early NASA astronaut cohort and determine if a correlation exists between space radiation exposure and mortality.

Trajectories of functional limitation in early rheumatoid arthritis and their association with mortality.

PubMed

Norton, Sam; Sacker, Amanda; Dixey, Josh; Done, John; Williams, Peter; Young, Adam

2013-11-01

This study aimed to identify subgroups with distinct trajectories of functional (HAQ) progression over 10 years following diagnosis of RA and identify baseline characteristics associated with the trajectories and their prognostic value for mortality. Between 1986 and 1998, 1460 patients with RA symptoms <2 years and prior to disease-modifying treatment (DMARDs) were recruited to an inception cohort (Early RA Study). Standard clinical, functional and laboratory assessments were performed at presentation and annually. Deaths were tracked by the National Health Service Central Register. Growth mixture modelling was used to identify distinct trajectories of HAQ score progression and survival analysis employed to compare all-cause mortality across the trajectory classes. Four HAQ score progression classes were identified: moderate increasing (46%), low stable (6%), moderate stable (28%) and high stable (20%). Only the moderate-increasing class exhibited an accelerated decline in function over normal ageing. Compared with the moderate-increasing class, individuals with high-stable HAQ scores were more likely to be female, have more severe disease and other coexistent conditions. Low-stable class patients were more likely to be male and report less pain. The high-stable class had increased risk of mortality compared with the moderate-increasing class after adjusting for potential confounding factors, whereas low-stable and moderate-stable classes were at reduced mortality risk. The effect of RA on function is set within the first few years and is affected by comorbidity. Identifying distinct groups of patients may help to target those at greater risk of poor functional outcome and mortality.

DNA methylation, an epigenetic mechanism connecting folate to healthy embryonic development and aging

USDA-ARS?s Scientific Manuscript database

Experimental studies demonstrated that maternal environmental factors including diet during early embryonic development can influence the phenotype of offspring as well as the risk of disease development at the later life. DNA methylation, an epigenetic phenomenon, has been suggested as a mechanism ...

Early resuscitation intensity as a surrogate for bleeding severity and early mortality in the PRospective, Observational, Multicenter, Major Trauma Transfusion (PROMMTT) Study

PubMed Central

Rahbar, Elaheh; Fox, Erin E.; del Junco, Deborah J.; Harvin, John A.; Holcomb, John B.; Wade, Charles E.; Schreiber, Martin A.; Rahbar, Mohammad H.; Bulger, Eileen M.; Phelan, Herb A.; Brasel, Karen J.; Alarcon, Louis H.; Myers, John G.; Cohen, Mitchell J.; Muskat, Peter; Cotton, Bryan A.

2013-01-01

Background The classic definition of MT, ≥10 units red blood cells (RBCs) in 24 hours, has never been demonstrated as a valid surrogate for severe hemorrhage and can introduce survival bias. In addition, the definition fails to capture other products that the clinician may have immediately available during the initial resuscitation. Assuming that units of resuscitative fluids reflect patient illness, our objective was to identify a rate of resuscitation intensity (RI) that could serve as an early surrogate of sickness for patients with substantial bleeding post-injury. Methods Adult patients surviving at least 30 minutes post-admission and receiving ≥1 RBC within 6 hours of admission from ten US Level 1 trauma centers were enrolled in the PRospective Observational Multicenter Major Trauma Transfusion study. Total fluid units were calculated as the sum of the number of crystalloid units (1 L=1 unit), colloids (0.5 L=1 unit) and blood products (1 RBC=1 unit, 1 plasma=1 unit, 6 pack platelets=1 unit). Univariable and multivariable logistic regressions were used to evaluate associations between RI and 6-hour mortality, adjusting for age, center, penetrating injury, weighted Revised Trauma Score, and Injury Severity Score. Results 1096 eligible patients received resuscitative fluids within 30 minutes, including 620 transfused with blood products. Despite varying products utilized, the total fluid RI was similar across all sites (3.2±2.5 units). Patients who received ≥4 units of any resuscitative fluid had a 6-hour mortality rate of 14.4% vs. 4.5% in patients who received <4 units. The adjusted odds ratio of 6-hour mortality for patients receiving ≥4 units within 30 minutes was 2.1 (95% Confidence Interval: 1.2–3.5). Conclusions Resuscitation with ≥4 units of any fluid was significantly associated with 6-hour mortality. This study suggests that early RI regardless of fluid type can be used as a surrogate for sickness and mortality in severely bleeding

No evidence of temperature-dependent sex determination or sex-biased embryo mortality in the chicken.

PubMed

Collins, K E; Jordan, B J; McLendon, B L; Navara, K J; Beckstead, R B; Wilson, J L

2013-12-01

Skewing the sex ratio at hatch in commercial poultry would be economically beneficial to the poultry industry. The existence of temperature-dependent sex determination is uncertain in birds. This experiment investigated if incubation temperatures skew sex ratios of commercial broilers. Three incubators were each set at a hot (38.3°C), standard (37.5°C), or cool (36.7°C) single-stage incubation temperature one time over 3 trials to eliminate incubator effect as a Latin square design. Sex ratios of hatched chicks and dead embryos were monitored. In one trial, embryo weights were evaluated. The percentages of male hatched chicks did not differ based on incubation temperature (P = 0.4486; 49.5% in the hot treatment, 51.4% at standard temperature, and 49.8% in the cool treatment). The percent hatch of eggs set was lower in the hot treatment (83.6%) than the standard (93.5%) and cool (91.6%) treatments (P < 0.0001) with greater late embryonic mortality in the hot treatment (P < 0.0001); however, the sex ratio of dead embryos did not differ among treatments (P = 0.9863). Pooled data of embryo mortality found no sex-biased embryo mortality with a female/male sex ratio of 1.22:1 (χ(2) = 1.27; P = 0.2596). Embryos from the hot treatment were heavier than those from the standard treatment by d 14 of incubation and were heavier than the embryos from the cool treatment by d 9 of incubation (P < 0.0001). These data indicate that incubation temperature affects embryonic mortality and embryonic growth rate, but it does not affect the sex ratio of broiler chickens. Additionally, no evidence was found for sex-biased embryo mortality in commercial broilers even at the incubation temperatures of this study.

Changes in the antioxidant metabolism in the embryonic development of the common South American toad Bufo arenarum: differential responses to pesticide in early embryos and autonomous-feeding larvae.

PubMed

Ferrari, Ana; Anguiano, Liliana; Lascano, Cecilia; Sotomayor, Verónica; Rosenbaum, Enrique; Venturino, Andrés

2008-01-01

Amphibians may be critically challenged by aquatic contaminants during their embryonic development. Many classes of compounds, including organophosphorus pesticides, are able to cause oxidative stress that affects the delicate cellular redox balance regulating tissue modeling. We determined the progression of antioxidant defenses during the embryonic development of the South American common toad, Bufo arenarum. Superoxide dismutase (SOD) and catalase (CAT) activities were high in the unfertilized eggs, and remained constant during the first stages of development. SOD showed a significant increase when the gills were completely active and opercular folds began to form. Reductase (GR) activity was low in the oocytes and increased significantly when gills and mouth were entirely developed and the embryos presented a higher exposure to pro-oxidant conditions suggesting an environmental control. Reduced glutathione (GSH) content was also initially low, and rose continuously pointing out an increasing participation of GSH-related enzymes in the control of oxidative stress. GSH peroxidases and GSH-S-transferases showed relatively high and constant activities, probably related to lipid peroxide control. B. arenarum embryos have plenty of yolk platelets containing lipids, which provide the energy and are actively transferred to the newly synthesized membranes during the early embryonic development. Exposure to the pro-oxidant pesticide malathion during 48 h did not significantly affect the activity of antioxidant enzymes in early embryos, but decreased the activities of CAT, GR, and the pool of GSH in larvae. Previous work indicated that lipid peroxide levels were kept low in malathion-exposed larvae, thus we conclude that oxidative stress is overcome by the antioxidant defenses. The increase in the antioxidant metabolism observed in the posthatching phase of development of B. arenarum embryo, thus constitutes a defense against natural and human-generated pro

A trade-off between embryonic development rate and immune function of avian offspring is concealed by embryonic temperature

USGS Publications Warehouse

Martin, Thomas E.; Arriero, Elena; Majewska, Ania

2011-01-01

Long embryonic periods are assumed to reflect slower intrinsic development that are thought to trade off to allow enhanced physiological systems, such as immune function. Yet, the relatively rare studies of this trade-off in avian offspring have not found the expected trade-off. Theory and tests have not taken into account the strong extrinsic effects of temperature on embryonic periods of birds. Here, we show that length of the embryonic period did not explain variation in two measures of immune function when temperature was ignored, based on studies of 34 Passerine species in tropical Venezuela (23 species) and north temperate Arizona (11 species). Variation in immune function was explained when embryonic periods were corrected for average embryonic temperature, in order to better estimate intrinsic rates of development. Immune function of offspring trades off with intrinsic rates of embryonic development once the extrinsic effects of embryonic temperatures are taken into account.

Embryonic Origins of the Mouse Superior Olivary Complex

PubMed Central

Howell, David M.; Spirou, George A.; Mathers, Peter H.

2014-01-01

Many areas of the central nervous system are organized into clusters of cell groups, with component cell groups exhibiting diverse but related functions. One such cluster, the superior olivary complex (SOC), is located in the ventral auditory brainstem in mammals. The SOC is an obligatory contact point for most projection neurons of the ventral cochlear nucleus and plays central roles in many aspects of monaural and binaural information processing. Despite their important interrelated functions, little is known about the embryonic origins of SOC nuclei, due in part to a paucity of developmental markers to distinguish individual cell groups. In this report, we present a collection of novel markers for the developing SOC nuclei in mice, including the transcription factors FoxP1, MafB, and Sox2, and the lineage-marking transgenic line En1-Cre. We use these definitive markers to examine the rhombic lip and rhombomeric origins of SOC nuclei and demonstrate that they can serve to uniquely identify SOC nuclei and subnuclei in newborn pups. The markers are also useful in identifying distinct nuclear domains within the presumptive SOC as early as embryonic day (E) 14.5, well before morphological distinction of individual nuclei is evident. These findings indicate that the mediolateral and dorsoventral position of SOC nuclei characteristic of the adult brainstem is established during early neurogenesis. PMID:23303740

Mapping hardwood mortality for the early detection of P. ramorum: an assessment of aerial surveys and object-oriented image analysis

Treesearch

Erik Haunreiter; Zhanfeng Liu; Jeff Mai; Zachary Heath; Lisa Fischer

2008-01-01

Effective monitoring and identification of areas of hardwood mortality is a critical component in the management of sudden oak death (SOD). From 2001 to 2005, aerial surveys covering 13.5 million acres in California were conducted to map and monitor hardwood mortality for the early detection of Phytophthora ramorum, the pathogen responsible for SOD....

Hematopoietic cell differentiation from embryonic and induced pluripotent stem cells

PubMed Central

2013-01-01

Pluripotent stem cells, both embryonic stem cells and induced pluripotent stem cells, are undifferentiated cells that can self-renew and potentially differentiate into all hematopoietic lineages, such as hematopoietic stem cells (HSCs), hematopoietic progenitor cells and mature hematopoietic cells in the presence of a suitable culture system. Establishment of pluripotent stem cells provides a comprehensive model to study early hematopoietic development and has emerged as a powerful research tool to explore regenerative medicine. Nowadays, HSC transplantation and hematopoietic cell transfusion have successfully cured some patients, especially in malignant hematological diseases. Owing to a shortage of donors and a limited number of the cells, hematopoietic cell induction from pluripotent stem cells has been regarded as an alternative source of HSCs and mature hematopoietic cells for intended therapeutic purposes. Pluripotent stem cells are therefore extensively utilized to facilitate better understanding in hematopoietic development by recapitulating embryonic development in vivo, in which efficient strategies can be easily designed and deployed for the generation of hematopoietic lineages in vitro. We hereby review the current progress of hematopoietic cell induction from embryonic stem/induced pluripotent stem cells. PMID:23796405

Microfluidic-based patterning of embryonic stem cells for in vitro development studies.

PubMed

Suri, Shalu; Singh, Ankur; Nguyen, Anh H; Bratt-Leal, Andres M; McDevitt, Todd C; Lu, Hang

2013-12-07

In vitro recapitulation of mammalian embryogenesis and examination of the emerging behaviours of embryonic structures require both the means to engineer complexity and accurately assess phenotypes of multicellular aggregates. Current approaches to study multicellular populations in 3D configurations are limited by the inability to create complex (i.e. spatially heterogeneous) environments in a reproducible manner with high fidelity thus impeding the ability to engineer microenvironments and combinations of cells with similar complexity to that found during morphogenic processes such as development, remodelling and wound healing. Here, we develop a multicellular embryoid body (EB) fusion technique as a higher-throughput in vitro tool, compared to a manual assembly, to generate developmentally relevant embryonic patterns. We describe the physical principles of the EB fusion microfluidic device design; we demonstrate that >60 conjoined EBs can be generated overnight and emulate a development process analogous to mouse gastrulation during early embryogenesis. Using temporal delivery of bone morphogenic protein 4 (BMP4) to embryoid bodies, we recapitulate embryonic day 6.5 (E6.5) during mouse embryo development with induced mesoderm differentiation in murine embryonic stem cells leading to expression of Brachyury-T-green fluorescent protein (T-GFP), an indicator of primitive streak development and mesoderm differentiation during gastrulation. The proposed microfluidic approach could be used to manipulate hundreds or more of individual embryonic cell aggregates in a rapid fashion, thereby allowing controlled differentiation patterns in fused multicellular assemblies to generate complex yet spatially controlled microenvironments.

Microfluidic-based patterning of embryonic stem cells for in vitro development studies

PubMed Central

Suri, Shalu; Singh, Ankur; Nguyen, Anh H.; Bratt-Leal, Andres M.; McDevitt, Todd C.

2013-01-01

In vitro recapitulation of mammalian embryogenesis and examination of the emerging behaviours of embryonic structures require both the means to engineer complexity and accurately assess phenotypes of multicellular aggregates. Current approaches to study multicellular populations in 3D configurations are limited by the inability to create complex (i.e. spatially heterogeneous) environments in a reproducible manner with high fidelity thus impeding the ability to engineer microenvironments and combinations of cells with similar complexity to that found during morphogenic processes such as development, remodelling and wound healing. Here, we develop a multicellular embryoid body (EB) fusion technique as a higher-throughput in vitro tool, compared to a manual assembly, to generate developmentally relevant embryonic patterns. We describe the physical principles of the EB fusion microfluidic device design; we demonstrate that >60 conjoined EBs can be generated overnight and emulate a development process analogous to mouse gastrulation during early embryogenesis. Using temporal delivery of bone morphogenic protein 4 (BMP4) to embryoid bodies, we recapitulate embryonic day 6.5 (E6.5) during mouse embryo development with induced mesoderm differentiation in murine embryonic stem cells leading to expression of Brachyury-T-green fluorescent protein (T-GFP), an indicator of primitive streak development and mesoderm differentiation during gastrulation. The proposed microfluidic approach could be used to manipulate hundreds or more of individual embryonic cell aggregates in a rapid fashion, thereby allowing controlled differentiation patterns in fused multicellular assemblies to generate complex yet spatially controlled microenvironments. PMID:24113509

Somatic mutations reveal asymmetric cellular dynamics in the early human embryo

DOE PAGES

Ju, Young Seok; Martincorena, Inigo; Gerstung, Moritz; ...

2017-03-22

Somatic cells acquire mutations throughout the course of an individual’s life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and theirmore » contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetrically to adult blood at an approximately 2:1 ratio. As a result, this study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.« less

Somatic mutations reveal asymmetric cellular dynamics in the early human embryo

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

Ju, Young Seok; Martincorena, Inigo; Gerstung, Moritz

Somatic cells acquire mutations throughout the course of an individual’s life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and theirmore » contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetrically to adult blood at an approximately 2:1 ratio. As a result, this study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.« less

Based serum metabolomics analysis reveals simultaneous interconnecting changes during chicken embryonic development.

PubMed

Peng, M L; Li, S N; He, Q Q; Zhao, J L; Li, L L; Ma, H T

2018-05-28

Metabolic disorder is a major health problem and is associated with a number of metabolic diseases. Due to native hyperglycaemia and resistance to exogenous insulin, chickens as a model had used in the studies of adipose tissue biology, metabolism and obesity. But no detailed information is available about the comprehensive changes of serum metabolites at different stages of chicken embryonic development. This study employed LC/MS-QTOF to determine the changes of major functional metabolites at incubation day 14 (E14d), 19 (E19d) and hatching day 1 (H1d), and the associated pathways of differential metabolites during chicken embryonic development were analysed using Metabolite Set Enrichment Analysis method. Results showed that 39 metabolites were significantly changed from E14d to E19d and 68 metabolites were significantly altered from E19d to H1d in chicken embryos. Protein synthesis was promoted by increasing the concentrations of L-glutamine and threonine, and gonadal development was promoted through increasing oestrone content from E14d to E19d in chicken embryos, which indicated that serum glutamine, threonine and oestrone contents may be considered as the candidate indicators for assessment of early embryonic development. 2-oxoglutaric acid mainly contributed to enhancing the citric cycle, and it plays an important role in improving the growth of chicken embryos at the late development; the decreasing of L-glutamine, L-isoleucine and L-leucine contents from E19d to H1d in chicken embryonic development implied their possible functions as the feed additive during early posthatch period of broiler chickens to satisfy the growth. These results provided insights into understand the roles of serum metabolites at different developmental stages of chicken embryos, it also provides available information for chicken as a model to study metabolic disease or human obesity. © 2018 Blackwell Verlag GmbH.

Embryonic duplications in sheep.

PubMed

Dennis, S M

1975-02-01

Twenty-seven embryonic duplications were examined during a 3-year investigation into the causes of perinatal lamb mortality. Twenty of the 27 were anomalous twins with 19 being conjoined (diplopagus 9 and heteropagus 10). The various duplications were: haloacardius acephalus 1, diprosopus 2, dicephalus 2, dipypus 3, diprosopus dipygus 1, syncephalus dipygus 1, pygopagus parasiticus 1, heteropagus dipygus 3, melodidymus 6, polyury 4, penile duplication 2, and bilateral otognathia 1. Four lambs were living and the time of death of the others was: parturient 8, and post-parturient 15. Average dry weight of the lambs was 3.35 kg (range 1.59 to 5.45 kg). Breed distribution was: Merino 77.8%, Crossbred 14.8%, Dorset Horn 3.7%, and Corriedale 3.7%. The caudal region was involved in 10 of the conjoined twins (52.6%), anterior region in 7 (36.9%), and both anterior and caudal regions in 2 (10.5%). Associated defects were present in 70.4% of the 27 lambs, the most common being atresia ani.

Silver nanoparticles induce developmental stage-specific embryonic phenotypes in zebrafish

NASA Astrophysics Data System (ADS)

Lee, Kerry J.; Browning, Lauren M.; Nallathamby, Prakash D.; Osgood, Christopher J.; Xu, Xiao-Hong Nancy

2013-11-01

Much is anticipated from the development and deployment of nanomaterials in biological organisms, but concerns remain regarding their biocompatibility and target specificity. Here we report our study of the transport, biocompatibility and toxicity of purified and stable silver nanoparticles (Ag NPs, 13.1 +/- 2.5 nm in diameter) upon the specific developmental stages of zebrafish embryos using single NP plasmonic spectroscopy. We find that single Ag NPs passively diffuse into five different developmental stages of embryos (cleavage, early-gastrula, early-segmentation, late-segmentation, and hatching stages), showing stage-independent diffusion modes and diffusion coefficients. Notably, the Ag NPs induce distinctive stage and dose-dependent phenotypes and nanotoxicity, upon their acute exposure to the Ag NPs (0-0.7 nM) for only 2 h. The late-segmentation embryos are most sensitive to the NPs with the lowest critical concentration (CNP,c << 0.02 nM) and highest percentages of cardiac abnormalities, followed by early-segmentation embryos (CNP,c < 0.02 nM), suggesting that disruption of cell differentiation by the NPs causes the most toxic effects on embryonic development. The cleavage-stage embryos treated with the NPs develop into a wide variety of phenotypes (abnormal finfold, tail/spinal cord flexure, cardiac malformation/edema, yolk sac edema, and acephaly). These organ structures are not yet developed in cleavage-stage embryos, suggesting that the earliest determinative events to create these structures are ongoing, and disrupted by NPs, which leads to the downstream effects. In contrast, the hatching embryos are most resistant to the Ag NPs, and majority of embryos (94%) develop normally, and none of them develop abnormally. Interestingly, early-gastrula embryos are less sensitive to the NPs than cleavage and segmentation stage embryos, and do not develop abnormally. These important findings suggest that the Ag NPs are not simple poisons, and they can target

Redeployment of germ layers related TFs shows regionalized expression during two non-embryonic developments.

PubMed

Ricci, Lorenzo; Cabrera, Fabien; Lotito, Sonia; Tiozzo, Stefano

2016-08-01

In all non-vertebrate metazoan phyla, species that evolved non-embryonic developmental pathways as means of propagation or regeneration can be found. In this context, new bodies arise through asexual reproduction processes (such as budding) or whole body regeneration, that lack the familiar temporal and spatial cues classically associated with embryogenesis, like maternal determinants, or gastrulation. The molecular mechanisms underlying those non-embryonic developments (i.e., regeneration and asexual reproduction), and their relationship to those deployed during embryogenesis are poorly understood. We have addressed this question in the colonial ascidian Botryllus schlosseri, which undergoes an asexual reproductive process via palleal budding (PB), as well as a whole body regeneration by vascular budding (VB). We identified early regenerative structures during VB and then followed the fate of differentiating tissues during both non-embryonic developments (PB and VB) by monitoring the expression of genes known to play key functions in germ layer specification with well conserved expression patterns in solitary ascidian embryogenesis. The expression patterns of FoxA1, GATAa, GATAb, Otx, Bra, Gsc and Tbx2/3 were analysed during both PB and VB. We found that the majority of these transcription factors were expressed during both non-embryonic developmental processes, revealing a regionalization of the palleal and vascular buds. Knockdown of GATAa by siRNA in palleal buds confirmed that preventing the correct development of one of these regions blocks further tissue specification. Our results indicate that during both normal and injury-induced budding, a similar alternative developmental program operates via early commitment of epithelial regions. Copyright © 2016. Published by Elsevier Inc.

Early Mortality in Adults Initiating Antiretroviral Therapy (ART) in Low- and Middle-Income Countries (LMIC): A Systematic Review and Meta-Analysis

PubMed Central

Gupta, Amita; Nadkarni, Girish; Yang, Wei-Teng; Chandrasekhar, Aditya; Gupte, Nikhil; Bisson, Gregory P.; Hosseinipour, Mina; Gummadi, Naveen

2011-01-01

Background We systematically reviewed observational studies of early mortality post-antiretroviral therapy (ART) initiation in low- and middle-income countries (LMIC) in Asia, Africa, and Central and South America, as defined by the World Bank, to summarize what is known. Methods and Findings Studies published in English between January 1996 and December 2010 were searched in Medline and EMBASE. Three independent reviewers examined studies of mortality within one year post-ART. An article was included if the study was conducted in a LMIC, participants were initiating ART in a non-clinical trial setting and were ≥15 years. Fifty studies were included; 38 (76%) from sub-Saharan Africa (SSA), 5 (10%) from Asia, 2 (4%) from the Americas, and 5 (10%) were multi-regional. Median follow-up time and pre-ART CD4 cell count ranged from 3–55 months and 11–192 cells/mm3, respectively. Loss-to-follow-up, reported in 40 (80%) studies, ranged from 0.3%–27%. Overall, SSA had the highest pooled 12-month mortality probability of 0.17 (95% CI 0.11–0.24) versus 0.11 (95% CI 0.10–0.13) for Asia, and 0.07 (95% CI 0.007–0.20) for the Americas. Of 14 (28%) studies reporting cause-specific mortality, tuberculosis (TB) (5%–44%), wasting (5%–53%), advanced HIV (20%–37%), and chronic diarrhea (10%–25%) were most common. Independent factors associated with early mortality in 30 (60%) studies included: low baseline CD4 cell count, male sex, advanced World Health Organization clinical stage, low body mass index, anemia, age greater than 40 years, and pre-ART quantitative HIV RNA. Conclusions Significant heterogeneity in outcomes and in methods of reporting outcomes exist among published studies evaluating mortality in the first year after ART initiation in LMIC. Early mortality rates are highest in SSA, and opportunistic illnesses such as TB and wasting syndrome are the most common reported causes of death. Strategies addressing modifiable risk factors associated with early

Acute toxicity of arsenic and oxidative stress responses in the embryonic development of the common South American toad Rhinella arenarum.

PubMed

Mardirosian, Mariana Noelia; Lascano, Cecilia Inés; Ferrari, Ana; Bongiovanni, Guillermina Azucena; Venturino, Andrés

2015-05-01

Arsenic (As), a natural element of ecological relevance, is found in natural water sources throughout Argentina in concentrations between 0.01 mg/L and 15 mg/L. The autochthonous toad Rhinella arenarum was selected to study the acute toxicity of As and the biochemical responses elicited by the exposure to As in water during its embryonic development. The median lethal concentration (LC50) value averaged 24.3 mg/L As and remained constant along the embryonic development. However, As toxicity drastically decreased when embryos were exposed from heartbeat-stage on day 4 of development, suggesting the onset of detoxification mechanisms. Given the environmental concentrations of As in Argentina, there is a probability of exceeding lethal levels at 1% of sites. Arsenic at sublethal concentrations caused a significant decrease in the total antioxidant potential but generated an increase in endogenous glutathione (GSH) content and glutathione S-transferase (GST) activity. This protective response might prevent a deeper decline in the antioxidant system and further oxidative damage. Alternatively, it might be linked to As conjugation with GSH for its excretion. The authors conclude that toad embryos are more sensitive to As during early developmental stages and that relatively high concentrations of this toxic element are required to elicit mortality, but oxidative stress may be an adverse effect at sublethal concentrations. © 2014 SETAC.

Survival of priceless cells: active and passive protection of embryonic stem cells against immune destruction.

PubMed

Utermöhlen, Olaf; Krönke, Martin

2007-06-15

This review focuses on our current knowledge of the mechanisms employed by embryonic stem (ES) cells to avoid destruction by cell-mediated immune responses. Recently, ES cells have been found to shield themselves against cytotoxic effector cells by expressing CD95L and serine protease inhibitor SPI-6 mediating apoptosis of the cytotoxic cells and inactivation of granzyme B, respectively. These findings are discussed in view of their implications for using ES cell-derived transplants in regenerative medicine as well as for our understanding of early embryonic stages during invasion and implantation.

Exploring mechanisms of excess mortality with early fluid resuscitation: insights from the FEAST trial

PubMed Central

2013-01-01

Background Early rapid fluid resuscitation (boluses) in African children with severe febrile illnesses increases the 48-hour mortality by 3.3% compared with controls (no bolus). We explored the effect of boluses on 48-hour all-cause mortality by clinical presentation at enrolment, hemodynamic changes over the first hour, and on different modes of death, according to terminal clinical events. We hypothesize that boluses may cause excess deaths from neurological or respiratory events relating to fluid overload. Methods Pre-defined presentation syndromes (PS; severe acidosis or severe shock, respiratory, neurological) and predominant terminal clinical events (cardiovascular collapse, respiratory, neurological) were described by randomized arm (bolus versus control) in 3,141 severely ill febrile children with shock enrolled in the Fluid Expansion as Supportive Therapy (FEAST) trial. Landmark analyses were used to compare early mortality in treatment groups, conditional on changes in shock and hypoxia parameters. Competing risks methods were used to estimate cumulative incidence curves and sub-hazard ratios to compare treatment groups in terms of terminal clinical events. Results Of 2,396 out of 3,141 (76%) classifiable participants, 1,647 (69%) had a severe metabolic acidosis or severe shock PS, 625 (26%) had a respiratory PS and 976 (41%) had a neurological PS, either alone or in combination. Mortality was greatest among children fulfilling criteria for all three PS (28% bolus, 21% control) and lowest for lone respiratory (2% bolus, 5% control) or neurological (3% bolus, 0% control) presentations. Excess mortality in bolus arms versus control was apparent for all three PS, including all their component features. By one hour, shock had resolved (responders) more frequently in bolus versus control groups (43% versus 32%, P <0.001), but excess mortality with boluses was evident in responders (relative risk 1.98, 95% confidence interval 0.94 to 4.17, P = 0.06) and 'non

Exploring mechanisms of excess mortality with early fluid resuscitation: insights from the FEAST trial.

PubMed

Maitland, Kathryn; George, Elizabeth C; Evans, Jennifer A; Kiguli, Sarah; Olupot-Olupot, Peter; Akech, Samuel O; Opoka, Robert O; Engoru, Charles; Nyeko, Richard; Mtove, George; Reyburn, Hugh; Brent, Bernadette; Nteziyaremye, Julius; Mpoya, Ayub; Prevatt, Natalie; Dambisya, Cornelius M; Semakula, Daniel; Ddungu, Ahmed; Okuuny, Vicent; Wokulira, Ronald; Timbwa, Molline; Otii, Benedict; Levin, Michael; Crawley, Jane; Babiker, Abdel G; Gibb, Diana M

2013-03-14

Early rapid fluid resuscitation (boluses) in African children with severe febrile illnesses increases the 48-hour mortality by 3.3% compared with controls (no bolus). We explored the effect of boluses on 48-hour all-cause mortality by clinical presentation at enrolment, hemodynamic changes over the first hour, and on different modes of death, according to terminal clinical events. We hypothesize that boluses may cause excess deaths from neurological or respiratory events relating to fluid overload. Pre-defined presentation syndromes (PS; severe acidosis or severe shock, respiratory, neurological) and predominant terminal clinical events (cardiovascular collapse, respiratory, neurological) were described by randomized arm (bolus versus control) in 3,141 severely ill febrile children with shock enrolled in the Fluid Expansion as Supportive Therapy (FEAST) trial. Landmark analyses were used to compare early mortality in treatment groups, conditional on changes in shock and hypoxia parameters. Competing risks methods were used to estimate cumulative incidence curves and sub-hazard ratios to compare treatment groups in terms of terminal clinical events. Of 2,396 out of 3,141 (76%) classifiable participants, 1,647 (69%) had a severe metabolic acidosis or severe shock PS, 625 (26%) had a respiratory PS and 976 (41%) had a neurological PS, either alone or in combination. Mortality was greatest among children fulfilling criteria for all three PS (28% bolus, 21% control) and lowest for lone respiratory (2% bolus, 5% control) or neurological (3% bolus, 0% control) presentations. Excess mortality in bolus arms versus control was apparent for all three PS, including all their component features. By one hour, shock had resolved (responders) more frequently in bolus versus control groups (43% versus 32%, P <0.001), but excess mortality with boluses was evident in responders (relative risk 1.98, 95% confidence interval 0.94 to 4.17, P = 0.06) and 'non-responders' (relative risk 1

Part II: morphological analysis of embryonic development following femtosecond laser manipulation

NASA Astrophysics Data System (ADS)

Kohli, V.; Elezzabi, A. Y.

2008-02-01

The zebrafish (Danio rerio) is an attractive model system that has received wide attention for its usefulness in the study of development and disease. This organism represents a closer analog to humans than the common invetebrates Drosophila melanogaster and Caenorhabditis elegans, making this species an ideal model for human health research. Non-invasive manipulation of the zebrafish has been challenging, owing to the outer proteinaceous membrane and multiple embryonic barriers. A novel tool capable of manipulating early cleavage stage embryonic cells would be important for future advancements in medial research and the aquaculture industry. Herein, we demonstrate the laser surgery of early cleavage stage (2-cell) blastomere cells using a range of average laser powers and beam dwell times. Since the novelty of this manipulation tool depends on its non-invasive application, we examined short- and long-term laser-induced developmental defects following embryonic surgery. Laser-manipulated embryos were reared to 2 and 7 days post-fertilization and compared to control embryos at the same developmental stages. Morphological analysis was performed using light microscopy and scanning electron microscopy. Developmental features that were examined included the antero- and dorsal-lateral whole body views of the larvae, the olfactory pit, dorsal, ventral and pectoral fins, notochord, pectoral fin buds, otic capsule, otic vesicle, neuromast patterning, and kinocilia of the olfactory pit rim and cristae of the lateral wall of the ear. Laser-manipulated embryos developed normally relative to the controls, with developmental patterning and morphology at 2 and 7 days indistinguishable from control larvae.

Hemodynamic flow visualization of early embryonic great vessels using μPIV.

PubMed

Goktas, Selda; Chen, Chia-Yuan; Kowalski, William J; Pekkan, Kerem

2015-01-01

Microparticle image velocimetry (μPIV) is an evolving quantitative methodology to closely and accurately monitor the cardiac flow dynamics and mechanotransduction during vascular morphogenesis. While PIV technique has a long history, contemporary developments in advanced microscopy have significantly expanded its power. This chapter includes three new methods for μPIV acquisition in selected embryonic structures achieved through advanced optical imaging: (1) high-speed confocal scanning of transgenic zebrafish embryos, where the transgenic erythrocytes act as the tracing particles; (2) microinjection of artificial seeding particles in chick embryos visualized with stereomicroscopy; and (3) real-time, time-resolved optical coherence tomography acquisition of vitelline vessel flow profiles in chick embryos, tracking the erythrocytes.

In vitro fertilization, the Nobel Prize, and human embryonic stem cells.

PubMed

Gearhart, John; Coutifaris, Christos

2011-01-07

Robert Edwards was awarded the 2010 Nobel Prize in Physiology or Medicine for the development of human in vitro fertilization. His work not only provided the means to overcome many forms of infertility, but it also enabled research on early stages of human embryos and the derivation of human embryonic stem cells. Copyright © 2011 Elsevier Inc. All rights reserved.

Embryonic development and inviability phenotype of chicken-Japanese quail F1 hybrids

PubMed Central

Ishishita, Satoshi; Kinoshita, Keiji; Nakano, Mikiharu; Matsuda, Yoichi

2016-01-01

Interspecific hybrid incompatibility, including inviability and sterility, is important in speciation; however, its genetic basis remains largely unknown in vertebrates. Crosses between male chickens and female Japanese quails using artificial insemination can generate intergeneric hybrids; however, the hatching rate is low, and hatched hybrids are only sterile males. Hybrid development is arrested frequently during the early embryonic stages, and the sex ratio of living embryos is male-biased. However, the development and sex ratio of hybrid embryos have not been comprehensively analyzed. In the present study, we observed delayed embryonic development of chicken-quail hybrids during the early stage, compared with that of chickens and quails. The survival rate of hybrids decreased markedly during the blastoderm-to-pre-circulation stage and then decreased gradually through the subsequent stages. Hybrid females were observed at more than 10 d of incubation; however, the sex ratio of hybrids became male-biased from 10 d of incubation. Severely malformed embryos were observed frequently in hybrids. These results suggest that developmental arrest occurs at various stages in hybrid embryos, including a sexually non-biased arrest during the early stage and a female-biased arrest during the late stage. We discuss the genetic basis for hybrid inviability and its sex bias. PMID:27199007

Wnt affects symmetry and morphogenesis during post-embryonic development in colonial chordates.

PubMed

Di Maio, Alessandro; Setar, Leah; Tiozzo, Stefano; De Tomaso, Anthony W

2015-01-01

Wnt signaling is one of the earliest and most highly conserved regulatory pathways for the establishment of the body axes during regeneration and early development. In regeneration, body axes determination occurs independently of tissue rearrangement and early developmental cues. Modulation of the Wnt signaling in either process has shown to result in unusual body axis phenotypes. Botryllus schlosseri is a colonial ascidian that can regenerate its entire body through asexual budding. This processes leads to an adult body via a stereotypical developmental pathway (called blastogenesis), without proceeding through any embryonic developmental stages. In this study, we describe the role of the canonical Wnt pathway during the early stages of asexual development. We characterized expression of three Wnt ligands (Wnt2B, Wnt5A, and Wnt9A) by in situ hybridization and qRT-PCR. Chemical manipulation of the pathway resulted in atypical budding due to the duplication of the A/P axes, supernumerary budding, and loss of the overall cell apical-basal polarity. Our results suggest that Wnt signaling is used for equivalent developmental processes both during embryogenesis and asexual development in an adult organism, suggesting that patterning mechanisms driving morphogenesis are conserved, independent of embryonic, or regenerative development.

Early warning score independently predicts adverse outcome and mortality in patients with acute pancreatitis.

PubMed

Jones, Michael J; Neal, Christopher P; Ngu, Wee Sing; Dennison, Ashley R; Garcea, Giuseppe

2017-08-01

The aim of this study was to compare the prognostic value of established scoring systems with early warning scores in a large cohort of patients with acute pancreatitis. In patients presenting with acute pancreatitis, age, sex, American Society of Anaesthesiologists (ASA) grade, Modified Glasgow Score, Ranson criteria, APACHE II scores and early warning score (EWS) were recorded for the first 72 h following admission. These variables were compared between survivors and non-survivors, between patients with mild/moderate and severe pancreatitis (based on the 2012 Atlanta Classification) and between patients with a favourable or adverse outcome. A total of 629 patients were identified. EWS was the best predictor of adverse outcome amongst all of the assessed variables (area under curve (AUC) values 0.81, 0.84 and 0.83 for days 1, 2 and 3, respectively) and was the most accurate predictor of mortality on both days 2 and 3 (AUC values of 0.88 and 0.89, respectively). Multivariable analysis revealed that an EWS ≥2 was independently associated with severity of pancreatitis, adverse outcome and mortality. This study confirms the usefulness of EWS in predicting the outcome of acute pancreatitis. It should become the mainstay of risk stratification in patients with acute pancreatitis.

Clonal analysis of Notch1-expressing cells reveals the existence of unipotent stem cells that retain long-term plasticity in the embryonic mammary gland.

PubMed

Lilja, Anna M; Rodilla, Veronica; Huyghe, Mathilde; Hannezo, Edouard; Landragin, Camille; Renaud, Olivier; Leroy, Olivier; Rulands, Steffen; Simons, Benjamin D; Fre, Silvia

2018-06-01

Recent lineage tracing studies have revealed that mammary gland homeostasis relies on unipotent stem cells. However, whether and when lineage restriction occurs during embryonic mammary development, and which signals orchestrate cell fate specification, remain unknown. Using a combination of in vivo clonal analysis with whole mount immunofluorescence and mathematical modelling of clonal dynamics, we found that embryonic multipotent mammary cells become lineage-restricted surprisingly early in development, with evidence for unipotency as early as E12.5 and no statistically discernable bipotency after E15.5. To gain insights into the mechanisms governing the switch from multipotency to unipotency, we used gain-of-function Notch1 mice and demonstrated that Notch activation cell autonomously dictates luminal cell fate specification to both embryonic and basally committed mammary cells. These functional studies have important implications for understanding the signals underlying cell plasticity and serve to clarify how reactivation of embryonic programs in adult cells can lead to cancer.

Early kit mortality and growth in farmed mink are affected by litter size rather than nest climate.

PubMed

Schou, T M; Malmkvist, J

2017-09-01

We investigated the effects of nest box climate on early mink kit mortality and growth. We hypothesised that litters in warm nest boxes experience less hypothermia-induced mortality and higher growth rates during the 1st week of life. This study included data from 749, 1-year-old breeding dams with access to nesting materials. Kits were weighed on days 1 and 7, dead kits were collected daily from birth until day 7 after birth, and nest climate was measured continuously from days 1 to 6. We tested the influences of the following daily temperature (T) and humidity (H) parameters on the number of live-born kit deaths and kit growth: T mean, T min, T max, T var (fluctuation) and H mean. The nest microclimate experienced by the kits was buffered against the ambient climate, with higher temperatures and reduced climate fluctuation. Most (77.0%) live-born kit deaths in the 1st week occurred on days 0 and 1. Seven of 15 climate parameters on days 1 to 3 had significant effects on live-born kit mortality. However, conflicting effects among days, marginal effects and late effects indicated that climate was not the primary cause of kit mortality. Five of 30 climate parameters had significant effects on kit growth. Few and conflicting effects indicated that the climate effect on growth was negligible. One exception was that large nest temperature fluctuations on day 1 were associated with reduced deaths of live-born kit (P<0.001) and increased kit growth (P=0.003). Litter size affected kit vitality; larger total litter size at birth was associated with greater risks of kit death (P<0.001) and reduced growth (P<0.001). The number of living kits in litters had the opposite effect, as kits in large liveborn litters had a reduced risk of death (P<0.001) and those with large mean litter size on days 1 to 7 had increased growth (P=0.026). Nest box temperature had little effect on early kit survival and growth, which could be due to dams' additional maternal behaviour. Therefore, we

Anterograde Tracing Method using DiI to Label Vagal Innervation of the Embryonic and Early Postnatal Mouse Gastrointestinal Tract

PubMed Central

Murphy, Michelle C.; Fox, Edward A.

2007-01-01

The mouse is an extremely valuable model for studying vagal development in relation to strain differences, genetic variation, gene manipulations, or pharmacological manipulations. Therefore, a method using 1, 1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) was developed for labeling vagal innervation of the gastrointestinal (GI) tract in embryonic and postnatal mice. DiI labeling was adapted and optimized for this purpose by varying several facets of the method. For example, insertion and crushing of DiI crystals into the nerve led to faster DiI diffusion along vagal axons and diffusion over longer distances as compared with piercing the nerve with a micropipette tip coated with dried DiI oil. Moreover, inclusion of EDTA in the fixative reduced leakage of DiI out of nerve fibers that occurred with long incubations. Also, mounting labeled tissue in PBS was superior to glycerol with n-propyl gallate, which resulted in reduced clarity of DiI labeling that may have been due to DiI leaking out of fibers. Optical sectioning of flattened wholemounts permitted examination of individual tissue layers of the GI tract wall. This procedure aided identification of nerve ending types because in most instances each type innervates a different tissue layer. Between embryonic day 12.5 and postnatal day 8, growth of axons into the GI tract, formation and patterning of fiber bundles in the myenteric plexus and early formation of putative afferent and efferent nerve terminals were observed. Thus, the DiI tracing method developed here has opened up a window for investigation during an important phase of vagal development. PMID:17418900

Production of embryonic and fetal-like red blood cells from human induced pluripotent stem cells.

PubMed

Chang, Chan-Jung; Mitra, Koyel; Koya, Mariko; Velho, Michelle; Desprat, Romain; Lenz, Jack; Bouhassira, Eric E

2011-01-01

We have previously shown that human embryonic stem cells can be differentiated into embryonic and fetal type of red blood cells that sequentially express three types of hemoglobins recapitulating early human erythropoiesis. We report here that we have produced iPS from three somatic cell types: adult skin fibroblasts as well as embryonic and fetal mesenchymal stem cells. We show that regardless of the age of the donor cells, the iPS produced are fully reprogrammed into a pluripotent state that is undistinguishable from that of hESCs by low and high-throughput expression and detailed analysis of globin expression patterns by HPLC. This suggests that reprogramming with the four original Yamanaka pluripotency factors leads to complete erasure of all functionally important epigenetic marks associated with erythroid differentiation regardless of the age or the tissue type of the donor cells, at least as detected in these assays. The ability to produce large number of erythroid cells with embryonic and fetal-like characteristics is likely to have many translational applications.

Embryonic development of connections in turtle pallium.

PubMed

Cordery, P; Molnár, Z

1999-10-11

We are interested in similarities and conserved mechanisms in early development of the reptilian and mammalian thalamocortical connections. We set out to analyse connectivity in embryonic turtle brains (Pseudemys scripta elegans, between stages 17 and 25), by using carbocyanine dye tracing. From the earliest stages studied, labelling from dorsal and ventral thalamus revealed backlabelled cells among developing thalamic fibres within the lateral forebrain bundle and striatum, which had similar morphology to backlabelled internal capsule cells in embryonic rat (Molnár and Cordery, 1999). However, thalamic crystal placements did not label cells in the dorsal ventricular ridge (DVR) at any stage examined. Crystal placements into both dorsal and lateral cortex labelled cells in the DVR and, reciprocally, DVR crystal placements labelled cells in the dorsal and lateral cortices. Retrograde labelling revealed that thalamic fibres arrive in the DVR and dorsal cortex by stage 19. The DVR received projections from the nucleus rotundus and the dorsal cortex exclusively from the perirotundal complex (including lateral geniculate nucleus). Thalamic fibres show this remarkable degree of specificity from the earliest stage we could examine with selective retrograde labelling (stage 19). Our study demonstrates that axons of similar cells are among the first to reach dorsal and ventral thalamus in mammals and reptiles. Our connectional analysis in turtle suggests that some cells of the mammalian primitive internal capsule are homologous to a cell group within the reptilian lateral forebrain bundle and striatum and that diverse vertebrate brains might use a highly conserved pattern of early thalamocortical development. Copyright 1999 Wiley-Liss, Inc.

FGF/EGF signaling regulates the renewal of early nephron progenitors during embryonic development.

PubMed

Brown, Aaron C; Adams, Derek; de Caestecker, Mark; Yang, Xuehui; Friesel, Robert; Oxburgh, Leif

2011-12-01

Recent studies indicate that nephron progenitor cells of the embryonic kidney are arranged in a series of compartments of an increasing state of differentiation. The earliest progenitor compartment, distinguished by expression of CITED1, possesses greater capacity for renewal and differentiation than later compartments. Signaling events governing progression of nephron progenitor cells through stages of increasing differentiation are poorly understood, and their elucidation will provide key insights into normal and dysregulated nephrogenesis, as well as into regenerative processes that follow kidney injury. In this study, we found that the mouse CITED1(+) progenitor compartment is maintained in response to receptor tyrosine kinase (RTK) ligands that activate both FGF and EGF receptors. This RTK signaling function is dependent on RAS and PI3K signaling but not ERK. In vivo, RAS inactivation by expression of sprouty 1 (Spry1) in CITED1(+) nephron progenitors results in loss of characteristic molecular marker expression and in increased death of progenitor cells. Lineage tracing shows that surviving Spry1-expressing progenitor cells are impaired in their subsequent epithelial differentiation, infrequently contributing to epithelial structures. These findings demonstrate that the survival and developmental potential of cells in the earliest embryonic nephron progenitor cell compartment are dependent on FGF/EGF signaling through RAS.

Effect of primary ovarian insufficiency and early natural menopause on mortality: a meta-analysis.

PubMed

Tao, X-Y; Zuo, A-Z; Wang, J-Q; Tao, F-B

2016-01-01

The aim of this review was to systematically evaluate the associations of all-cause, cardiovascular and all-cancer mortality with primary ovarian insufficiency (POI) and early natural menopause (ENM). Electronic databases for relevant studies were searched up to February 28, 2015. POI and ENM were usually defined as spontaneous menopause before age 40 years and at age 40-44 years, respectively. A total of nine articles were derived from seven prospective cohort studies. In all studies, age of menopause was self-reported. Our meta-analysis showed that POI women had a higher risk of death from all causes (pooled relative risk (RR) 1.39, 95% confidence interval (CI) 1.10-1.77) and ischemic heart disease (IHD) (pooled RR 1.48, 95% CI 1.02-2.16) when compared with women at normal age at natural menopause (ANM). No significant association was detected from stroke and all-cancer mortality between POI women and normal ANM women. Only a slightly higher risk of death from IHD (pooled RR 1.09, 95% CI 1.00-1.18) was found when ENM women were compared with normal ANM women. The results of our study demonstrated that POI was associated with a higher risk of IHD and all-cause mortality; ENM was only associated with a slightly higher risk of IHD mortality.

Seasonal Variation in Solar Ultra Violet Radiation and Early Mortality in Extremely Preterm Infants.

PubMed

Salas, Ariel A; Smith, Kelly A; Rodgers, Mackenzie D; Phillips, Vivien; Ambalavanan, Namasivayam

2015-11-01

Vitamin D production during pregnancy promotes fetal lung development, a major determinant of infant survival after preterm birth. Because vitamin D synthesis in humans is regulated by solar ultraviolet B (UVB) radiation, we hypothesized that seasonal variation in solar UVB doses during fetal development would be associated with variation in neonatal mortality rates. This cohort study included infants born alive with gestational age (GA) between 23 and 28 weeks gestation admitted to a neonatal unit between 1996 and 2010. Three infant cohort groups were defined according to increasing intensities of solar UVB doses at 17 and 22 weeks gestation. The primary outcome was death during the first 28 days after birth. Outcome data of 2,319 infants were analyzed. Mean birth weight was 830 ± 230 g and median gestational age was 26 weeks. Mortality rates were significantly different across groups (p = 0.04). High-intensity solar UVB doses were associated with lower mortality when compared with normal intensity solar UVB doses (hazard ratio: 0.70; 95% confidence interval: 0.54-0.91; p = 0.01). High-intensity solar UVB doses during fetal development seem to be associated with risk reduction of early mortality in preterm infants. Prospective studies are needed to validate these preliminary findings. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Air pollution in early life and adult mortality from chronic rheumatic heart disease.

PubMed

Phillips, David I W; Osmond, Clive; Williams, Martin L; Jones, Alexander

2017-08-01

Chronic rheumatic heart disease (RHD) remains a globally important cause of heart disease. The reasons for the continuing high prevalence of this disease are obscure, but it may have its origins in the poor social and economic conditions with which the disease has been consistently and strongly linked. Mortality studies from the UK have suggested the importance of adverse environmental factors in early life; these studies demonstrated specific geographical associations between high rates of chest infection during infancy and subsequent RHD. They raised the possibility that early air pollution, which is known to be strongly linked with chest infection during infancy, may predispose to RHD. We related estimates of air pollution and social conditions developed by Daly in 1951-52 for 78 urban areas in England and Wales to their subsequent RHD mortality rates at ages 35-74 in men and women during 1993-2012. There were strong relationships between domestic air pollution and RHD [relative risk per standard deviation (SD) increase in pollution 1.168, 95% confidence interval (CI): 1.128 to 1.210, P < 0.001). Inclusion of published data on social class, education, crowding and population density in multiple regression analyses showed that the air pollution association was independent of these; only overcrowding was separately linked with RHD. We present the first evidence of an association between air pollution in early life and RHD. Although there are several limitations to this study, the strength and consistency of the results, together with their biological plausibility, suggest a causal link. This deserves attention because it may have important consequences for the control of RHD in resource-poor countries where widespread use of biomass fuels and domestic pollution remain a problem. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

Early Therapy Intensity Level (TIL) Predicts Mortality in Spontaneous Intracerebral Hemorrhage.

PubMed

Ziai, Wendy C; Siddiqui, Aazim A; Ullman, Natalie; Herrick, Daniel B; Yenokyan, Gayane; McBee, Nichol; Lane, Karen; Hanley, Daniel F

2015-10-01

Outcome from spontaneous intracerebral hemorrhage (sICH) may depend on patient-care variability. We developed as ICH-specific therapy intensity level (TIL) metric using evidence-based elements in a high severity sICH cohort. This is a cohort study of 170 patients with sICH and any intraventricular hemorrhage treated in 2 academic neuroICUs. Pre-defined quality indicators were identified based on current guidelines, scientific evidence, and likelihood of care documentation in first 72 h of hospital admission. We assessed performance on each indicator and association with discharge mortality. Significant indicators were aggregated to develop a TIL score. The predictive validity of the best fit TIL score was tested with threefold cross-validation of multivariate logistic regression models of in-hospital survival and good outcome (modified Rankin score 0-3). Median ICH score was 3; discharge mortality was 51.2%. Five/19 tested variables were significantly associated with lower discharge mortality: no DNR/withdrawal of treatment within 24 h of admission, target glucose within 4 h of high glucose, no recurrent hyperpyrexia, clinical reversal of herniation/intracranial pressure >20 mmHg within 60 min of detection, and reversal of INR (<1.4) within 2 h of first elevation. One point was given for each or if not applicable. Median TIL score was significantly higher in survivors versus non-survivors (5[1] vs. 3[1]; P < 0.001). A 4-point aggregated TIL score was most predictive of discharge survival (area under receiving operating characteristic curve 0.85, 95% CI 0.80-0.90) and good outcome (AUC 0.84) and was an independent predictor of both (survival: OR 7.10; 95% CI 3.57-14.11; P < 0.001; good outcome: OR 3.10; 95% CI 1.06-8.79; P < 0.001). A simplified TIL score using evidenced-based patient-care parameters within first 3 days of admission after sICH was significantly associated with early mortality and good outcome. The next step is prospective validation of the

Growth trajectories of the human embryonic head and periconceptional maternal conditions.

PubMed

Koning, I V; Baken, L; Groenenberg, I A L; Husen, S C; Dudink, J; Willemsen, S P; Gijtenbeek, M; Koning, A H J; Reiss, I K M; Steegers, E A P; Steegers-Theunissen, R P M

2016-05-01

studied in the general population. Assessment of growth trajectories of the embryonic head may be of benefit in future early antenatal care. This study was funded by the Department of Obstetrics and Gynaecology, Erasmus MC University Medical Centre and Sophia Foundation for Medical Research, Rotterdam, The Netherlands (SSWO grant number 644). No competing interests are declared. © 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 email: journals.permissions@oup.com.

The influence of IVF/ICSI treatment on human embryonic growth trajectories.

PubMed

Eindhoven, S C; van Uitert, E M; Laven, J S E; Willemsen, S P; Koning, A H J; Eilers, P H C; Exalto, N; Steegers, E A P; Steegers-Theunissen, R P M

2014-12-01

groups (βIVF/ICSI = 6 g; P = 0.36 and βIVF/ICSI = 80 g; P = 0.24, respectively). Variations in embryonic growth trajectories of spontaneously conceived pregnancies with reliable pregnancy dating may partially be a result of less precise pregnancy dating and differences in endometrium receptivity compared with IVF/ICSI pregnancies. The absence of a significant difference in embryonic and fetal growth trajectories suggests safety of IVF/ICSI treatment with regard to early embryonic growth. However, further research is warranted to ascertain the influence of IVF/ICSI treatments in a larger study population, and to estimate the impact of the underlying causes of the subfertility and other periconceptional exposures on human embryonic and fetal growth trajectories. This study was supported by the Department of Obstetrics and Gynaecology of the Erasmus MC, University Medical Centre. No competing interests are declared. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effect of early versus late or no tracheostomy on mortality and pneumonia of critically ill patients receiving mechanical ventilation: a systematic review and meta-analysis.

PubMed

Siempos, Ilias I; Ntaidou, Theodora K; Filippidis, Filippos T; Choi, Augustine M K

2015-02-01

Delay of tracheostomy for roughly 2 weeks after translaryngeal intubation of critically ill patients is the presently recommended practice and is supported by findings from large trials. However, these trials were suboptimally powered to detect small but clinically important effects on mortality. We aimed to assess the benefit of early versus late or no tracheostomy on mortality and pneumonia in critically ill patients who need mechanical ventilation. We systematically searched PubMed, CINAHL, Embase, Web of Science, DOAJ, the Cochrane Library, references of relevant articles, scientific conference proceedings, and grey literature up to Aug 31, 2013, to identify randomised controlled trials comparing early tracheostomy (done within 1 week after translaryngeal intubation) with late (done any time after the first week of mechanical ventilation) or no tracheostomy and reporting on mortality or incidence of pneumonia in critically ill patients under mechanical ventilation. Our primary outcomes were all-cause mortality during the stay in the intensive-care unit and incidence of ventilator-associated pneumonia. Mortality during the stay in the intensive-care unit was a composite endpoint of definite intensive-care-unit mortality, presumed intensive-care-unit mortality, and 28-day mortality. We calculated pooled odds ratios (OR), pooled risk ratios (RR), and 95% CIs with a random-effects model. All but complications analyses were done on an intention-to-treat basis. Analyses of 13 trials (2434 patients, 648 deaths) showed that all-cause mortality in the intensive-care unit was not significantly lower in patients assigned to the early versus the late or no tracheostomy group (OR 0·80, 95% CI 0·59-1·09; p=0·16). This result persisted when we considered only trials with a low risk of bias (511 deaths; OR 0·80, 95% CI 0·59-1·09; p=0·16; eight trials with 1934 patients). Incidence of ventilator-associated pneumonia was lower in mechanically ventilated patients assigned

Early trends in serum phosphate and creatinine levels are associated with mortality following major hepatectomy.

PubMed

Herbert, Garth S; Prussing, Kara B; Simpson, Amber L; D'Angelica, Michael I; Allen, Peter J; DeMatteo, Ronald P; Jarnagin, William R; Kingham, T Peter

2015-12-01

Mortality after major hepatectomy remains high and is frequently related to post-hepatectomy liver failure (PHLF). Other than pre-existing liver disease and a small future liver remnant, few patient factors or early postoperative indicators identify patients at elevated risk for PHLF and mortality. Data on demographics, comorbidities, operative procedures and postoperative laboratory trends were reviewed for patients submitted to major hepatectomy (at least three Couinaud segments) for malignancy during 1998-2013. These factors were compared among patients who died within 90 days, survivors who met the 50-50 criteria and all remaining survivors. A total of 1528 patients underwent major hepatectomy during the study period. Of these, 947 had metastatic colorectal cancer and underwent resection of a median of four segments. Overall, 49 patients (3.2%) died within 90 days of surgery and 48 patients (3.1%) met the 50-50 criteria for PHLF; 30 of these patients survived 90 days. Operative blood loss was higher in patients who died within 90 days compared with survivors (1.0 l versus 0.5 l; P < 0.001). Despite equivalent perioperative resuscitation and urine output, non-survivors had higher creatinine and phosphate levels than survivors on postoperative day (PoD) 1 (1.1 mg/dl versus 0.9 mg/dl and 4.6 mg/dl versus 3.7 mg/dl, respectively; P < 0.001). Early trends in creatinine and phosphate (between the day of surgery and PoD 1) identify patients at risk for PHLF and mortality. © 2015 International Hepato-Pancreato-Biliary Association.

The embryonic origin of the ampullate silk glands of the spider Cupiennius salei.

PubMed

Hilbrant, Maarten; Damen, Wim G M

2015-05-01

Silk production in spiders is considered a key innovation, and to have been vital for the diversification of the clade. The evolutionary origin of the organs involved in spider silk production, however, and in particular of the silk glands, is poorly understood. Homologies have been proposed between these and other glands found in arachnids, but lacking knowledge of the embryonic development of spider silk glands hampers an evaluation of hypotheses. This study focuses on the embryonic origin of the largest silk glands of the spider Cupiennius salei, the major and minor ampullate glands. We show how the ampullate glands originate from ectodermal invaginations on the embryonic spinneret limb buds, in relation to morphogenesis of these buds. Moreover, we visualize the subsequent growth of the ampullate glands in sections of the early postembryonic stages. The invaginations are shown to correlate with expression of the proneural gene CsASH2, which is remarkable since it has been proposed that spider silk glands and their nozzles originate from sensory bristles. Hence, by confirming the ectodermal origin of spider silk glands, and by describing the (post-)embryonic morphogenesis of the ampullate glands, this work provides a starting point for further investigating into the genetic program that underlies their development. Copyright © 2015 Elsevier Ltd. All rights reserved.

Simultaneous cell death and desquamation of the embryonic diffusion barrier during epidermal development.

PubMed

Saathoff, Manuela; Blum, Barbara; Quast, Thomas; Kirfel, Gregor; Herzog, Volker

2004-10-01

The periderm is an epithelial layer covering the emerging epidermis in early embryogenesis of vertebrates. In the chicken embryo, an additional cellular layer, the subperiderm, occurs at later embryonic stages underneath the periderm. The questions arose what is the function of both epithelial layers and, as they are transitory structures, by which mechanism are they removed. By immunocytochemistry, the tight junction (TJ) proteins occludin and claudin-1 were localized in the periderm and in the subperiderm, and sites of close contact between adjacent cells were detected by electron microscopy. Using horseradish peroxidase (HRP) as tracer, these contacts were identified as tight junctions involved in the formation of the embryonic diffusion barrier. This barrier was lost by desquamation at the end of the embryonic period, when the cornified envelope of the emerging epidermis was formed. By TUNEL and DNA ladder assays, we detected simultaneous cell death in the periderm and the subperiderm shortly before hatching. The absence of caspases-3, -6, and -7 activity, key enzymes of apoptosis, and the lack of typical morphological criteria of apoptosis such as cell fragmentation or membrane blebbing point to a special form of programmed cell death (PCD) leading to the desquamation of the embryonic diffusion barrier. Copyright 2004 Elsevier Inc.

Observation of human embryonic behavior in vitro by high-resolution time-lapse cinematography.

PubMed

Iwata, Kyoko; Mio, Yasuyuki

2016-07-01

Assisted reproductive technology (ART) has yielded vast amounts of information and knowledge on human embryonic development in vitro; however, still images provide limited data on dynamic changes in the developing embryos. Using our high-resolution time-lapse cinematography (hR-TLC) system, we were able to describe normal human embryonic development continuously from the fertilization process to the hatched blastocyst stage in detail. Our hR-TLC observation also showed the embryonic abnormality of a third polar body (PB)-like substance likely containing a small pronucleus being extruded and resulting in single-pronucleus (1PN) formation, while our molecular biological investigations suggested the possibility that some 1PN embryos could be diploid, carrying both maternal and paternal genomes. Furthermore, in some embryos the extruded third PB-like substance was eventually re-absorbed into the ooplasm resulting in the formation of an uneven-sized, two-PN zygote. In addition, other hR-TLC observations showed that cytokinetic failure was correlated with equal-sized, multi-nucleated blastomeres that were also observed in the embryo showing early initiation of compaction. Assessment combining our hR-TLC with molecular biological techniques enables a better understanding of embryonic development and potential improvements in ART outcomes.

Paternal identity impacts embryonic development for two species of freshwater fish.

PubMed

Siddique, Mohammad Abdul Momin; Linhart, Otomar; Krejszeff, Sławomir; Żarski, Daniel; Pitcher, Trevor E; Politis, Sebastian Nikitas; Butts, Ian Anthony Ernest

2017-05-01

Paternal, compared to maternal, contributions were believed to have only a limited influence on embryonic development and larval fitness traits in fishes. Therefore, the perspective of male influence on early life history traits has come under scrutiny. This study was conducted to determine parental effects on the rate of eyed embryos of Ide Leuciscus idus and Northern pike Esox lucius. Five sires and five dams from each species were crossed using a quantitative genetic breeding design and the resulting 25 sib groups of each species were reared to the embryonic eyed stage. We then partition variation in embryonic phenotypic performance to maternal, paternal, and parental interactions using the Restricted Maximum Likelihood (REML) model. Results showed that paternal, maternal, and the paternal×maternal interaction terms were highly significant for both species; clearly demonstrating that certain family combinations were more compatible than others. Paternal effects explained 20.24% of the total variance, which was 2-fold higher than the maternal effects (10.73%) in Ide, while paternal effects explained 18.9% of the total variance, which was 15-fold higher than the maternal effects (1.3%) in Northern pike. Together, these results indicate that male effects are of major importance during embryonic development for these species. Furthermore, this study demonstrates that genetic compatibility between sires and dams plays an important role and needs to be taken into consideration for reproduction of these and likely other economically important fish species. Copyright © 2016 Elsevier Inc. All rights reserved.

Generation of structures formed by lens and retinal cells differentiating from embryonic stem cells.

PubMed

Hirano, Mariko; Yamamoto, Akitsugu; Yoshimura, Naoko; Tokunaga, Tomoyuki; Motohashi, Tsutomu; Ishizaki, Katsuhiko; Yoshida, Hisahiro; Okazaki, Kenji; Yamazaki, Hidetoshi; Hayashi, Shin-Ichi; Kunisada, Takahiro

2003-12-01

Embryonic stem cells have the potential to give rise to all cell lineages when introduced into the early embryo. They also give rise to a limited number of different cell types in vitro in specialized culture systems. In this study, we established a culture system in which a structure consisting of lens, neural retina, and pigmented retina was efficiently induced from embryonic stem cells. Refractile cell masses containing lens and neural retina were surrounded by retinal pigment epithelium layers and, thus, designated as eye-like structures. Developmental processes required for eye development appear to proceed in this culture system, because the formation of the eye-like structures depended on the expression of Pax6, a key transcription factor for eye development. The present culture system opens up the possibility of examining early stages of eye development and also of producing cells for use in cellular therapy for various diseases of the eye. Copyright 2003 Wiley-Liss, Inc.

Early embryo mortality in natural human reproduction: What the data say

PubMed Central

Jarvis, Gavin E.

2017-01-01

How many human embryos die between fertilisation and birth under natural conditions? It is widely accepted that natural human embryo mortality is high, particularly during the first weeks after fertilisation, with total prenatal losses of 70% and higher frequently claimed. However, the first external sign of pregnancy occurs two weeks after fertilisation with a missed menstrual period, and establishing the fate of embryos before this is challenging. Calculations are additionally hampered by a lack of data on the efficiency of fertilisation under natural conditions. Four distinct sources are used to justify quantitative claims regarding embryo loss: (i) a hypothesis published by Roberts & Lowe in The Lancet  is widely cited but has no practical quantitative value; (ii) life table analyses give consistent assessments of clinical pregnancy loss, but cannot illuminate losses at earlier stages of development; (iii) studies that measure human chorionic gonadotrophin (hCG) reveal losses in the second week of development and beyond, but not before; and (iv) the classic studies of Hertig and Rock offer the only direct insight into the fate of human embryos from fertilisation under natural conditions. Re-examination of Hertig’s data demonstrates that his estimates for fertilisation rate and early embryo loss are highly imprecise and casts doubt on the validity of his numerical analysis. A recent re-analysis of hCG study data concluded that approximately 40-60% of embryos may be lost between fertilisation and birth, although this will vary substantially between individual women. In conclusion, natural human embryo mortality is lower than often claimed and widely accepted. Estimates for total prenatal mortality of 70% or higher are exaggerated and not supported by the available data. PMID:28580126

Changes in Acetyl CoA Levels during the Early Embryonic Development of Xenopus laevis

PubMed Central

Tsuchiya, Yugo; Pham, Uyen; Hu, Wanzhou; Ohnuma, Shin-ichi; Gout, Ivan

2014-01-01

Coenzyme A (CoA) is a ubiquitous and fundamental intracellular cofactor. CoA acts as a carrier of metabolically important carboxylic acids in the form of CoA thioesters and is an obligatory component of a multitude of catabolic and anabolic reactions. Acetyl CoA is a CoA thioester derived from catabolism of all major carbon fuels. This metabolite is at a metabolic crossroads, either being further metabolised as an energy source or used as a building block for biosynthesis of lipids and cholesterol. In addition, acetyl CoA serves as the acetyl donor in protein acetylation reactions, linking metabolism to protein post-translational modifications. Recent studies in yeast and cultured mammalian cells have suggested that the intracellular level of acetyl CoA may play a role in the regulation of cell growth, proliferation and apoptosis, by affecting protein acetylation reactions. Yet, how the levels of this metabolite change in vivo during the development of a vertebrate is not known. We measured levels of acetyl CoA, free CoA and total short chain CoA esters during the early embryonic development of Xenopus laevis using HPLC. Acetyl CoA and total short chain CoA esters start to increase around midblastula transition (MBT) and continue to increase through stages of gastrulation, neurulation and early organogenesis. Pre-MBT embryos contain more free CoA relative to acetyl CoA but there is a shift in the ratio of acetyl CoA to CoA after MBT, suggesting a metabolic transition that results in net accumulation of acetyl CoA. At the whole-embryo level, there is an apparent correlation between the levels of acetyl CoA and levels of acetylation of a number of proteins including histones H3 and H2B. This suggests the level of acetyl CoA may be a factor, which determines the degree of acetylation of these proteins, hence may play a role in the regulation of embryogenesis. PMID:24831956

Mapping conduction velocity of early embryonic hearts with a robust fitting algorithm

PubMed Central

Gu, Shi; Wang, Yves T; Ma, Pei; Werdich, Andreas A; Rollins, Andrew M; Jenkins, Michael W

2015-01-01

Cardiac conduction maturation is an important and integral component of heart development. Optical mapping with voltage-sensitive dyes allows sensitive measurements of electrophysiological signals over the entire heart. However, accurate measurements of conduction velocity during early cardiac development is typically hindered by low signal-to-noise ratio (SNR) measurements of action potentials. Here, we present a novel image processing approach based on least squares optimizations, which enables high-resolution, low-noise conduction velocity mapping of smaller tubular hearts. First, the action potential trace measured at each pixel is fit to a curve consisting of two cumulative normal distribution functions. Then, the activation time at each pixel is determined based on the fit, and the spatial gradient of activation time is determined with a two-dimensional (2D) linear fit over a square-shaped window. The size of the window is adaptively enlarged until the gradients can be determined within a preset precision. Finally, the conduction velocity is calculated based on the activation time gradient, and further corrected for three-dimensional (3D) geometry that can be obtained by optical coherence tomography (OCT). We validated the approach using published activation potential traces based on computer simulations. We further validated the method by adding artificially generated noise to the signal to simulate various SNR conditions using a curved simulated image (digital phantom) that resembles a tubular heart. This method proved to be robust, even at very low SNR conditions (SNR = 2-5). We also established an empirical equation to estimate the maximum conduction velocity that can be accurately measured under different conditions (e.g. sampling rate, SNR, and pixel size). Finally, we demonstrated high-resolution conduction velocity maps of the quail embryonic heart at a looping stage of development. PMID:26114034

[Prognostic factors of early 30-day mortality in elderly patients admitted to an emergency department].

PubMed

Morales Erazo, Alexander; Cardona Arango, Doris

The main aim of this study was to identify the variables related to early mortality in the elderly at the time of admission to the emergency department. Using probability sampling, the study included patients 60 years old or older of both genders who were admitted for observation to the emergency department of the University Hospital of Nariño, ¿Colombia? in 2015. Using a questionnaire designed for this study, some multidimensional features that affect the health of the elderly were collected (demographic, clinical, psychological, functional, and social variables). The patients were then followed-up for 30 days in order to determine the mortality rate during this time. Univariate and multivariate logistic regressions and survival analysis were performed. Data were collected from 246 patients, with a mean age of 75.27 years and the majority female. The 30-day mortality rate was 15%. The variables most associated with death were: being female, temperature problems, initial diagnosis of neoplasia, and unable to walk independently in the emergency department. It is possible to determine the multidimensional factors present in the older patient admitted to an emergency department that could affect their 30-day mortality prognosis. and which should be intervened. Copyright © 2017 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

FGF signaling via MAPK is required early and improves Activin A-induced definitive endoderm formation from human embryonic stem cells

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

Sui, Lina, E-mail: linasui@vub.ac.be; Mfopou, Josue K.; Geens, Mieke

2012-09-28

Highlights: Black-Right-Pointing-Pointer Deep study the FGF signaling role during DE specification in the context of hESCs. Black-Right-Pointing-Pointer DE differentiation from hESCs has an early dependence on FGF signaling. Black-Right-Pointing-Pointer A serum-free DE protocol is developed based on the findings. Black-Right-Pointing-Pointer The DE cells showed potential to differentiate into pancreatic progenitor cells. -- Abstract: Considering their unlimited proliferation and pluripotency properties, human embryonic stem cells (hESCs) constitute a promising resource applicable for cell replacement therapy. To facilitate this clinical translation, it is critical to study and understand the early stage of hESCs differentiation wherein germ layers are defined. In this study,more » we examined the role of FGF signaling in Activin A-induced definitive endoderm (DE) differentiation in the absence of supplemented animal serum. We found that activated FGF/MAPK signaling is required at the early time point of Activin A-induced DE formation. In addition, FGF activation increased the number of DE cells compared to Activin A alone. These DE cells could further differentiate into PDX1 and NKX6.1 positive pancreatic progenitors in vitro. We conclude that Activin A combined with FGF/MAPK signaling efficiently induce DE cells in the absence of serum. These findings improve our understanding of human endoderm formation, and constitute a step forward in the generation of clinical grade hESCs progenies for cell therapy.« less

Changing Nuclear Landscape and Unique PML Structures During Early Epigenetic Transitions of Human Embryonic Stem Cells

PubMed Central

Butler, John T.; Hall, Lisa L.; Smith, Kelly P.; Lawrence, Jeanne B.

2010-01-01

The complex nuclear structure of somatic cells is important to epigenomic regulation, yet little is known about nuclear organization of human embryonic stem cells (hESC). Here we surveyed several nuclear structures in pluripotent and transitioning hESC. Observations of centromeres, telomeres, SC35 speckles, Cajal Bodies, lamin A/C and emerin, nuclear shape and size demonstrate a very different “nuclear landscape” in hESC. This landscape is remodeled during a brief transitional window, concomitant with or just prior to differentiation onset. Notably, hESC initially contain abundant signal for spliceosome assembly factor, SC35, but lack discrete SC35 domains; these form as cells begin to specialize, likely reflecting cell-type specific genomic organization. Concomitantly, nuclear size increases and shape changes as lamin A/C and emerin incorporate into the lamina. During this brief window, hESC exhibit dramatically different PML-defined structures, which in somatic cells are linked to gene regulation and cancer. Unlike the numerous, spherical somatic PML bodies, hES cells often display ~1–3 large PML structures of two morphological types: long linear “rods” or elaborate “rosettes”, which lack substantial SUMO-1, Daxx, and Sp100.These occur primarily between Day 0–2 of differentiation and become rare thereafter. PML rods may be “taut” between other structures, such as centromeres, but clearly show some relationship with the lamina, where PML often abuts or fills a “gap” in early lamin A/C staining. Findings demonstrate that pluripotent hES cells have a markedly different overall nuclear architecture, remodeling of which is linked to early epigenomic programming and involves formation of unique PML-defined structures. PMID:19449340

Circulating bovine pregnancy associated glycoproteins (bPAGs) are associated with late embryonic/fetal survival but not ovulatory follicle size in suckled beef cows

USDA-ARS?s Scientific Manuscript database

GnRH-induced ovulation of small dominant follicles resulted in increased late embryonic/fetal mortality. The objective of this study was to examine the relationship between ovulatory follicle size, embryo/fetal survival, and circulating concentrations of bPAGs (detects presence of an embryo/fetus a...

Cohort-specific trends in stroke mortality in seven European countries were related to infant mortality rates.

PubMed

Amiri, M; Kunst, A E; Janssen, F; Mackenbach, J P

2006-12-01

To assess, in a population-based study, whether secular trends in cardiovascular disease mortality in seven European countries were correlated with past trends in infant mortality rate (IMR) in these countries. Data on ischemic heart disease (IHD) and stroke mortality in 1950-1999 in the Netherlands, England & Wales, France, and four Nordic countries were analyzed. We used Poisson regression to describe trends in mortality according to birth cohort, for the cohorts born between 1860 and 1939. Pearson correlation coefficients were calculated to determine associations between IMR and IHD, or stroke mortality. IHD mortality increased for successive cohorts up to 1900, and then started to decline. Stroke mortality levels were virtually stable among birth cohorts up to 1880, but declined rapidly among later cohorts. A strong positive association was found between cohort-specific IMR levels and stroke mortality rates. There were no strong cohort-wise associations between IMR and IHD mortality. These results support other studies in suggesting that living conditions in early childhood may influence population levels of stroke mortality. Future studies should determine the contribution of specific early life factors to the mortality decline in IHD and especially stroke.

FGF signalling controls anterior extraembryonic and embryonic fate in the beetle Tribolium.

PubMed

Sharma, Rahul; Beermann, Anke; Schröder, Reinhard

2013-09-01

Fibroblast growth factor (FGF) signalling plays a key role in early embryonic development and cell migration in vertebrates and in invertebrates. To gain novel insights into FGF signalling in an arthropod, we characterized the fgf1b ortholog in the beetle Tribolium that is not represented in the Drosophila genome. We found that FGF1b dependent signalling organizes the anterior to posterior axis of the early embryo. The loss of Tc-fgf1b function in Tribolium by RNA interference resulted in the reduction of the anteriormost extraembryonic fate, in an anterior shift of embryonic fate and in the loss or malformation of anterior embryonic structures. Without intact extraembryonic membranes the serosa and the amnion, Tc-fgf1b(RNAi) embryos did not undergo morphogenetic movements and remained posteriorly localized throughout embryogenesis. Only weakly affected embryos developed into a cuticle that show dorsally curved bodies with head defects and a dorsal opening. Except for the posterior dorsal amnion, the overall topology of the dorsal-ventral axis seemed unaffected. Moreover, FGF signalling was not required for the onset of mesoderm formation but for fine-tuning this tissue during later development. We also show that in affected embryos the dorsal epidermis was expanded and expressed Tc-dpp at a higher level. We conclude that in the Tribolium blastoderm embryo, FGF1-signalling organizes patterning along the AP-axis and also balances the expression level of Dpp in the dorsal epidermis, a tissue critically involved in dorsal closure. Copyright © 2013 Elsevier Inc. All rights reserved.

Localization of DNA methyltransferase-1 during oocyte differentiation, in vitro maturation and early embryonic development in cow

PubMed Central

Lodde, V.; Modina, S.C.; Franciosi, F.; Zuccari, E.; Tessaro, I.; Luciano, A.M.

2009-01-01

DNA methyltransferase-1 (Dnmt1) is involved in the maintenance of DNA methylation patterns and is crucial for normal mammalian development. The aim of the present study was to assess the localization of Dnmt1 in cow, during the latest phases of oocyte differentiation and during the early stages of segmentation. Dnmt1 expression and localization were assessed in oocytes according to the chromatin configuration, which in turn provides an important epigenetic mechanism for the control of global gene expression and represents a morphological marker of oocyte differentiation. We found that the initial chromatin condensation was accompanied by a slight increase in the level of global DNA methylation, as assessed by 5-methyl-cytosine immunostaining followed by laser scanning confocal microscopy analysis (LSCM). RT-PCR confirmed the presence of Dnmt1 transcripts throughout this phase of oocyte differentiation. Analogously, Dnmt1 immunodetection and LSCM indicated that the protein was always present and localized in the cytoplasm, regardless the chromatin configuration and the level of global DNA methylation. Moreover, our data indicate that while Dnmt1 is retained in the cytoplasm in metaphase II stage oocytes and zygotes, it enters the nuclei of 8–16 cell stage embryos. As suggested in mouse, the functional meaning of the presence of Dnmt1 in the bovine embryo nuclei could be the maintainement of the methylation pattern of imprinted genes. In conclusion, the present work provides useful elements for the study of Dnmt1 function during the late stage of oocyte differentiation, maturation and early embryonic development in mammals. PMID:22073356

The embryonic mir-35 family of microRNAs promotes multiple aspects of fecundity in Caenorhabditis elegans.

PubMed

McJunkin, Katherine; Ambros, Victor

2014-07-21

MicroRNAs guide many aspects of development in all metazoan species. Frequently, microRNAs are expressed during a specific developmental stage to perform a temporally defined function. The C. elegans mir-35-42 microRNAs are expressed abundantly in oocytes and early embryos and are essential for embryonic development. Here, we show that these embryonic microRNAs surprisingly also function to control the number of progeny produced by adult hermaphrodites. Using a temperature-sensitive mir-35-42 family mutant (a deletion of the mir-35-41 cluster), we demonstrate three distinct defects in hermaphrodite fecundity. At permissive temperatures, a mild sperm defect partially reduces hermaphrodite fecundity. At restrictive temperatures, somatic gonad dysfunction combined with a severe sperm defect sharply reduces fecundity. Multiple lines of evidence, including a late embryonic temperature-sensitive period, support a role for mir-35-41 early during development to promote subsequent sperm production in later larval stages. We further show that the predicted mir-35 family target sup-26 (suppressor-26) acts downstream of mir-35-41 in this process, suggesting that sup-26 de-repression in mir-35-41 deletion mutants may contribute to temperature-sensitive loss of fecundity. In addition, these microRNAs play a role in male fertility, promoting proper morphogenesis of male-specific mating structures. Overall, our results demonstrate that robust activity of the mir-35-42 family microRNAs not only is essential for embryonic development across a range of temperatures but also enables the worm to subsequently develop full reproductive capacity. Copyright © 2014 McJunkin and Ambros.

Expression pattern of pluripotent markers in different embryonic developmental stages of buffalo (Bubalus bubalis) embryos and putative embryonic stem cells generated by parthenogenetic activation.

PubMed

Singh, Karn P; Kaushik, Ramakant; Garg, Veena; Sharma, Ruchi; George, Aman; Singh, Manoj K; Manik, Radhey S; Palta, Prabhat; Singla, Suresh K; Chauhan, Manmohan S

2012-12-01

In this study, we describe the production of buffalo parthenogenetic blastocysts and subsequent isolation of parthenogenetic embryonic stem cell (PGESC)-like cells. PGESC colonies exhibited dome-shaped morphology and were clearly distinguishable from the feeder layer cells. Different stages of development of parthenogenetic embryos and derived embryonic stem cell (ESC)-like cells expressed key ESC-specific markers, including OCT-4, NANOG, SOX-2, FOXD3, REX-1, STAT-3, TELOMERASE, NUCLEOSTEMIN, and cMYC. Immunofluorescence-based studies revealed that the PGESCs were positive for surface-based pluripotent markers, viz., SSEA-3, SSEA-4, TRA 1-80, TRA 1-60, CD-9, and CD-90 and exhibited high alkaline phosphatase (ALP) activity. PGEC cell-like cells formed embryoid body (EB)-like structures in hanging drop cultures and when cultured for extended period of time spontaneously differentiated into derivatives of three embryonic germ layers as confirmed by RT-PCR for ectodermal (CYTOKERATIN8, NF-68), mesodermal (MSX1, BMP-4, ASA), and endodermal markers (AFP, HNF-4, GATA-4). Differentiation of PGESCs toward the neuronal lineage was successfully directed by supplementation of serum-containing media with retinoic acid. Our results indicate that the isolated ESC-like cells from parthenogenetic blastocyst hold properties of ESCs and express markers of pluripotency. The pluripotency markers were also expressed by early cleavage-stage of buffalo embryos.

Embryonic death is linked to maternal identity in the leatherback turtle (Dermochelys coriacea).

PubMed

Rafferty, Anthony R; Santidrián Tomillo, Pilar; Spotila, James R; Paladino, Frank V; Reina, Richard D

2011-01-01

Leatherback turtles have an average global hatching success rate of ~50%, lower than other marine turtle species. Embryonic death has been linked to environmental factors such as precipitation and temperature, although, there is still a lot of variability that remains to be explained. We examined how nesting season, the time of nesting each season, the relative position of each clutch laid by each female each season, maternal identity and associated factors such as reproductive experience of the female (new nester versus remigrant) and period of egg retention between clutches (interclutch interval) affected hatching success and stage of embryonic death in failed eggs of leatherback turtles nesting at Playa Grande, Costa Rica. Data were collected during five nesting seasons from 2004/05 to 2008/09. Mean hatching success was 50.4%. Nesting season significantly influenced hatching success in addition to early and late stage embryonic death. Neither clutch position nor nesting time during the season had a significant affect on hatching success or the stage of embryonic death. Some leatherback females consistently produced nests with higher hatching success rates than others. Remigrant females arrived earlier to nest, produced more clutches and had higher rates of hatching success than new nesters. Reproductive experience did not affect stage of death or the duration of the interclutch interval. The length of interclutch interval had a significant affect on the proportion of eggs that failed in each clutch and the developmental stage they died at. Intrinsic factors such as maternal identity are playing a role in affecting embryonic death in the leatherback turtle.

Stability of citrate-capped silver nanoparticles in exposure media and their effects on the development of embryonic zebrafish (Danio rerio)

PubMed Central

Park, Kwangsik; Tuttle, George; Sinche, Federico; Harper, Stace L.

2014-01-01

The stability of citrate-capped silver nanoparticles (AgNPs) and the embryonic developmental toxicity were evaluated in the fish test water. Serious aggregation of AgNPs was observed in undiluted fish water (DM-100) in which high concentration of ionic salts exist. However, AgNPs were found to be stable for 7 days in DM-10, prepared by diluting the original fish water (DM-100) with deionized water to 10%. The normal physiology of zebrafish embryos were evaluated in DM-10 to see if DM-10 can be used as a control vehicle for the embryonic fish toxicity test. As results, DM-10 without AgNPs did not induce any significant adverse effects on embryonic development of zebrafish determined by mortality, hatching, malformations and heart rate. When embryonic toxicity of AgNPs was tested in both DM-10 and in DM-100, AgNPs showed higher toxicity in DM-10 than in DM-100. This means that the big-sized aggregates of AgNPs were low toxic compared to the nano-sized AgNPs. AgNPs induced delayed hatching, decreased heart rate, pericardial edema, and embryo death. Accumulation of AgNPs in the embryo bodies was also observed. Based on this study, citrate-capped AgNPs are not aggregated in DM-10 and it can be used as a control vehicle in the toxicity test of fish embryonic development. PMID:23325492

Teratogenic effects of 4-nonylphenol on early embryonic and larval development of the catfish Heteropneustes fossilis.

PubMed

Chaube, Radha; Gautam, Geeta J; Joy, Keerikattil P

2013-05-01

Alkylphenol polyethoxylates (APEs), which are widely used in detergents, paints, herbicides, insecticides, and in many other formulations, have been widely detected in aquatic environments. 4-Nonylphenol (NP) is an important APE detected at microgram levels per litre (0.1-336 μg/L) in water. The objective of the present study was to evaluate NP's toxic effects at low and high sublethal concentrations (0.1 and 1 μg/L) on embryonic development of the catfish Heteropneustes fossilis at different time intervals. The data show that fertilization rate was decreased and cleavage and blastula were severely affected leading to complete mortality of embryos. NP exposure resulted in various body malformations in larvae, such as vertebral deformations, e.g., fin blistering/necrosis, axial deformities (lordosis, kyphosis, and scoliosis) of the spine in the abdominal and caudal region, tail curved completely backward, shortened body, severe spinal and yolk sac malformations, C-shaped severe spinal curvature, cranial malformation with undeveloped head, and failure of eye development. The level of body malformations increased with the concentration and exposure time. After 72 h of exposure, all larvae were dead at both concentrations. Scanning electron microscope study showed that epidermal cells (keratinocytes) were severely damaged in both low- and high-dose treatments throughout development, leading to development of numerous depressions representing sinking holes on the skin. Mucous glands increased significantly in treatment groups compared with control groups. The present study highlights the severe teratogenic effects of NP. The prevalence of the contaminant, if not checked, can lead to decreased population and ultimate disappearance of the species.

Assessment of diclofenac LC50 reference values in juvenile and embryonic stages of the zebrafish (Danio rerio).

PubMed

Praskova, E; Voslarova, E; Siroka, Z; Plhalova, L; Macova, S; Marsalek, P; Pistekova, V; Svobodova, Z

2011-01-01

The aim of the study was to compare the acute toxicity of diclofenac to juvenile and embryonic stages of the zebrafish (Danio rerio). Acute toxicity tests were performed on the aquarium fish Danio rerio, which is one of the model organisms most commonly used in toxicity testing. The tests were performed using a semi-static method according to OECD guideline No. 203 (Fish, acute toxicity test). Embryo toxicity tests were performed in zebrafish embryos (Danio rerio) in compliance with OECD No. 212 methodology (Fish, short-term toxicity test on embryo and sac-fry stages). The results were subjected to a probit analysis using the EKO-TOX 5.2 programme to determine 96hLC50 and 144hLC50 (median lethal concentration, 50% mortality after a 96 h or 144 h interval, respectively) values of diclofenac. The statistical significance of the difference between LC50 values in juvenile and embryonic stages of Danio rerio was tested using the Mann-Whitney non-parametric test implemented in the Unistat 5.1 programme. The LC50 mean value of diclofenac was 166.6 +/- 9.8 mg/L in juvenile Danio rerio, and 6.11 +/- 2.48 mg/L in embryonic stages of Danio rerio. The study demonstrated a statistically higher sensitivity to diclofenac (P < 0.05) in embryonic stages compared to the juvenile fish.

The effect of excess expression of GFP in a novel heart-specific green fluorescence zebrafish regulated by nppa enhancer at early embryonic development.

PubMed

Huang, Wen; Deng, Yun; Dong, Wei; Yuan, Wuzhou; Wan, Yongqi; Mo, Xiaoyan; Li, Yongqing; Wang, Zequn; Wang, Yuequn; Ocorr, Karen; Zhang, Bo; Lin, Shuo; Wu, Xiushan

2011-02-01

In order to study the impalpable effect of GFP in homozygous heart-specific GFP-positive zebrafish during the early stage, the researchers analyzed the heart function of morphology and physiology at the first 3 days after fertilization. This zebrafish line was produced by a large-scale Tol2 transposon mediated enhancer trap screen that generated a transgenic zebrafish with a heart-specific expression of green fluorescent protein (GFP)-tagged under control of the nppa enhancer. In situ hybridization experiments showed that the nppa:GFP line faithfully recapitulated both the spatial and temporal expressions of the endogenous nppa. Green fluorescence was intensively and specifically expressed in the myocardial cells located both in the heart chambers and in the atrioventricular canal. The embryonic heart of nppa:GFP line developed normally compared with those in the wild type. There was no difference between the nappa:GFP and wild type lines with respect to heart rate, overall size, ejection volume, and fractional shortening. Thus the excess expression of GFP in this transgenic line seemed to exert no detrimental effects on zebrafish hearts during the early stages.

Altered glucose transport to utero-embryonic unit in relation to delayed embryonic development in the Indian short-nosed fruit bat, Cynopterus sphinx.

PubMed

Arnab, Banerjee; Amitabh, Krishna

2011-02-10

The aim of this study was to compare the changes in concentration of glucose and glucose transporters (GLUTs) in the utero-embryonic unit, consisting of decidua, trophoblast and embryo, during delayed and non-delayed periods to understand the possible cause of delayed embryonic development in Cynopterus sphinx. The results showed a significantly decreased concentration of glucose in the utero-embryonic unit due to decline in the expression of insulin receptor (IR) and GLUT 3, 4 and 8 proteins in the utero-embryonic unit during delayed period. The in vitro study showed suppressive effect of insulin on expression of GLUTs 4 and 8 in the utero-embryonic unit and a significant positive correlation between the decreased amount of glucose consumed by the utero-embryonic unit and decreased expression of GLUTs 4 (r=0.99; p<0.05) and 8 (r=0.98; p<0.05). The in vivo study showed expression of IR and GLUT 4 proteins in adipose tissue during November suggesting increased transport of glucose to adipose tissue for adipogenesis. This study showed increased expression of HSL and OCTN2 and increased availability of l-carnitine to utero-embryonic unit suggesting increased transport of fatty acid to utero-embryonic unit during the period of delayed embryonic development. Hence it appears that due to increased transport of glucose for adipogenesis prior to winter, glucose utilization by utero-embryonic unit declines and this may be responsible for delayed embryonic development in C. sphinx. Increased supply of fatty acid to the delayed embryo may be responsible for its survival under low glucose condition but unable to promote embryonic development in C. sphinx. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Mortality Dynamics of Spodoptera frugiperda (Lepidoptera: Noctuidae) Immatures in Maize.

PubMed

Varella, Andrea Corrêa; Menezes-Netto, Alexandre Carlos; Alonso, Juliana Duarte de Souza; Caixeta, Daniel Ferreira; Peterson, Robert K D; Fernandes, Odair Aparecido

2015-01-01

We characterized the dynamics of mortality factors affecting immature developmental stages of the fall armyworm, Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae). Multiple decrement life tables for egg and early larval stages of S. frugiperda in maize (Zea mays L.) fields were developed with and without augmentative releases of Telenomus remus Nixon (Hymenoptera: Platygastridae) from 2009 to 2011. Total egg mortality ranged from 73 to 81% and the greatest egg mortality was due to inviability, dislodgement, and predation. Parasitoids did not cause significant mortality in egg or early larval stages and the releases of T. remus did not increase egg mortality. Greater than 95% of early larvae died from predation, drowning, and dislodgment by rainfall. Total mortality due to these factors was largely irreplaceable. Results indicate that a greater effect in reducing generational survival may be achieved by adding mortality to the early larval stage of S. frugiperda.

Mortality Dynamics of Spodoptera frugiperda (Lepidoptera: Noctuidae) Immatures in Maize

PubMed Central

Varella, Andrea Corrêa; Menezes-Netto, Alexandre Carlos; Alonso, Juliana Duarte de Souza; Caixeta, Daniel Ferreira; Peterson, Robert K. D.; Fernandes, Odair Aparecido

2015-01-01

We characterized the dynamics of mortality factors affecting immature developmental stages of the fall armyworm, Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae). Multiple decrement life tables for egg and early larval stages of S. frugiperda in maize (Zea mays L.) fields were developed with and without augmentative releases of Telenomus remus Nixon (Hymenoptera: Platygastridae) from 2009 to 2011. Total egg mortality ranged from 73 to 81% and the greatest egg mortality was due to inviability, dislodgement, and predation. Parasitoids did not cause significant mortality in egg or early larval stages and the releases of T. remus did not increase egg mortality. Greater than 95% of early larvae died from predation, drowning, and dislodgment by rainfall. Total mortality due to these factors was largely irreplaceable. Results indicate that a greater effect in reducing generational survival may be achieved by adding mortality to the early larval stage of S. frugiperda. PMID:26098422

[Crucial stages of embryogenesis of R. arvalis: Part 1. Linear measurements of embryonic structures].

PubMed

Severtsova, E A; Severtsov, A S

2011-01-01

Investigations of individual variability have allowed us to reveal the crucial (= nodal) stages in embryogenesis of the moor frog (Rana arvalis Nills.). These crucial stages are: the late gastrula stage (stages 18-20), the hatching stages (stages 32-33) and, apparently, early metamorphosis (stage 39). Moreover, we have found that each embryonic structure passes through its specific crucial stages. For example, stage 34 is crucial for the trait "tail width" but is internodal for all other embryonic traits. At this stage, larva passes from an attached to a free-swimming life style. We also found considerable differences between the different frog populations in the the level of developmental variability. These differences were associated with internodal developmental stages.

A staging table for the embryonic development of the brownbanded bamboo shark (Chiloscyllium punctatum)

PubMed Central

Onimaru, Koh; Motone, Fumio; Kiyatake, Itsuki; Nishida, Kiyonori

2018-01-01

Background: Studying cartilaginous fishes (chondrichthyans) has helped us understand vertebrate evolution and diversity. However, resources such as genome sequences, embryos, and detailed staging tables are limited for species within this clade. To overcome these limitations, we have focused on a species, the brownbanded bamboo shark (Chiloscyllium punctatum), which is a relatively common aquarium species that lays eggs continuously throughout the year. In addition, because of its relatively small genome size, this species is promising for molecular studies. Results: To enhance biological studies of cartilaginous fishes, we establish a normal staging table for the embryonic development of the brownbanded bamboo shark. Bamboo shark embryos take around 118 days to reach the hatching period at 25°C, which is approximately 1.5 times as fast as the small‐spotted catshark (Scyliorhinus canicula) takes. Our staging table divides the embryonic period into 38 stages. Furthermore, we found culture conditions that allow early embryos to grow in partially opened egg cases. Conclusions: In addition to the embryonic staging table, we show that bamboo shark embryos exhibit relatively fast embryonic growth and are amenable to culture, key characteristics that enhance their experimental utility. Therefore, the present study is a foundation for cartilaginous fish research. Developmental Dynamics 247:712–723, 2018. © 2017 Wiley Periodicals, Inc. PMID:29396887

Subretinally transplanted embryonic stem cells rescue photoreceptor cells from degeneration in the RCS rats.

PubMed

Schraermeyer, U; Thumann, G; Luther, T; Kociok, N; Armhold, S; Kruttwig, K; Andressen, C; Addicks, K; Bartz-Schmidt, K U

2001-01-01

The Royal College of Surgeons (RCS) rat is an animal model for retinal degeneration such as the age-related macular degeneration. The RCS rat undergoes a progressive retinal degeneration during the early postnatal period. A potential treatment to prevent this retinal degeneration is the transplantation into the subretinal space of cells that would replace functions of the degenerating retinal pigment epithelium (RPE) cells or may form neurotrophic factors. In this study we have investigated the potential of subretinally transplanted embryonic stem cells to prevent the genetically determined photoreceptor cell degeneration in the RCS rat. Embryonic stem cells from the inner cell mass of the mouse blastocyst were allowed to differentiate to neural precursor cells in vitro and were then transplanted into the subretinal space of 20-day-old RCS rats. Transplanted and sham-operated rats were sacrificed 2 months following cell transplantation. The eyes were enucleated and photoreceptor degeneration was quantified by analyzing and determining the thickness of the outer nuclear layer by light and electron microscopy. In the eyes transplanted with embryonic cells up to 8 rows of photoreceptor cell nuclei were observed, whereas in nontreated control eyes the outer nuclear layer had degenerated completely. Transplantation of embryonic stem cells appears to delay photoreceptor cell degeneration in RCS rats.

Changes in the concentrations of four maternal steroids during embryonic development in the threespined stickleback (Gasterosteus aculeatus).

PubMed

Paitz, Ryan Thomas; Mommer, Brett Christian; Suhr, Elissa; Bell, Alison Marie

2015-08-01

Embryonic exposure to steroids often leads to long-term phenotypic effects. It has been hypothesized that mothers may be able to create a steroid environment that adjusts the phenotypes of offspring to current environmental conditions. Complicating this hypothesis is the potential for developing embryos to modulate their early endocrine environment. This study utilized the threespined stickleback (Gasterosteus aculeatus) to characterize the early endocrine environment within eggs by measuring four steroids (progesterone, testosterone, estradiol, and cortisol) of maternal origin. We then examined how the concentrations of these four steroids changed over the first 12 days post fertilization (dpf). Progesterone, testosterone, estradiol, and cortisol of maternal origin could be detected within unfertilized eggs and levels of all four steroids declined in the first 3 days following fertilization. While levels of progesterone, testosterone, and estradiol remained low after the initial decline, levels of cortisol rose again by 8 dpf. These results demonstrate that G. aculeatus embryos begin development in the presence of a number of maternal steroids but levels begin to change quickly following fertilization. This suggests that embryonic processes change the early endocrine environment and hence influence the ability of maternal steroids to affect development. With these findings, G. aculeatus becomes an intriguing system in which to study how selection may act on both maternal and embryonic processes to shape the evolutionary consequence of steroid-mediated maternal effects. © 2015 Wiley Periodicals, Inc.

Embryonic Zebrafish Model - A Well-Established Method for Rapidly Assessing the Toxicity of Homeopathic Drugs: - Toxicity Evaluation of Homeopathic Drugs Using Zebrafish Embryo Model.

PubMed

Gupta, Himanshu R; Patil, Yogesh; Singh, Dipty; Thakur, Mansee

2016-12-01

Advancements in nanotechnology have led to nanoparticle (NP) use in various fields of medicine. Although the potential of NPs is promising, the lack of documented evidence on the toxicological effects of NPs is concerning. A few studies have documented that homeopathy uses NPs. Unfortunately, very few sound scientific studies have explored the toxic effects of homeopathic drugs. Citing this lack of high-quality scientific evidence, regulatory agencies have been reluctant to endorse homeopathic treatment as an alternative or adjunct treatment. This study aimed to enhance our insight into the impact of commercially-available homeopathic drugs, to study the presence of NPs in those drugs and any deleterious effects they might have, and to determine the distribution pattern of NPs in zebrafish embryos ( Danio rerio ). Homeopathic dilutions were studied using high-resolution transmission electron microscopy with selected area electron diffraction (SAED). For the toxicity assessment on Zebrafish, embryos were exposed to a test solution from 4 - 6 hours post-fertilization, and embryos/larvae were assessed up to 5 days post-fertilization (dpf) for viability and morphology. Toxicity was recorded in terms of mortality, hatching delay, phenotypic defects and metal accumulation. Around 5 dpf was found to be the optimum developmental stage for evaluation. The present study aimed to conclusively prove the presence of NPs in all high dilutions of homeopathic drugs. Embryonic zebrafish were exposed to three homeopathic drugs with two potencies (30CH, 200CH) during early embryogenesis. The resulting morphological and cellular responses were observed. Exposure to these potencies produced no visibly significant malformations, pericardial edema, and mortality and no necrotic and apoptotic cellular death. Our findings clearly demonstrate that no toxic effects were observed for these three homeopathic drugs at the potencies and exposure times used in this study. The embryonic zebrafish

Early Standard Electroencephalogram Abnormalities Predict Mortality in Septic Intensive Care Unit Patients.

PubMed

Azabou, Eric; Magalhaes, Eric; Braconnier, Antoine; Yahiaoui, Lyria; Moneger, Guy; Heming, Nicholas; Annane, Djillali; Mantz, Jean; Chrétien, Fabrice; Durand, Marie-Christine; Lofaso, Frédéric; Porcher, Raphael; Sharshar, Tarek

2015-01-01

Sepsis is associated with increased mortality, delirium and long-term cognitive impairment in intensive care unit (ICU) patients. Electroencephalogram (EEG) abnormalities occurring at the acute stage of sepsis may correlate with severity of brain dysfunction. Predictive value of early standard EEG abnormalities for mortality in ICU septic patients remains to be assessed. In this prospective, single center, observational study, standard EEG was performed, analyzed and classified according to both Synek and Young EEG scales, in consecutive patients acutely admitted in ICU for sepsis. Delirium, coma and the level of sedation were assessed at the time of EEG recording; and duration of sedation, occurrence of in-ICU delirium or death were assessed during follow-up. Adjusted analyses were carried out using multiple logistic regression. One hundred ten patients were included, mean age 63.8 (±18.1) years, median SAPS-II score 38 (29-55). At the time of EEG recording, 46 patients (42%) were sedated and 22 (20%) suffered from delirium. Overall, 54 patients (49%) developed delirium, of which 32 (29%) in the days after EEG recording. 23 (21%) patients died in the ICU. Absence of EEG reactivity was observed in 27 patients (25%), periodic discharges (PDs) in 21 (19%) and electrographic seizures (ESZ) in 17 (15%). ICU mortality was independently associated with a delta-predominant background (OR: 3.36; 95% CI [1.08 to 10.4]), absence of EEG reactivity (OR: 4.44; 95% CI [1.37-14.3], PDs (OR: 3.24; 95% CI [1.03 to 10.2]), Synek grade ≥ 3 (OR: 5.35; 95% CI [1.66-17.2]) and Young grade > 1 (OR: 3.44; 95% CI [1.09-10.8]) after adjustment to Simplified Acute Physiology Score (SAPS-II) at admission and level of sedation. Delirium at the time of EEG was associated with ESZ in non-sedated patients (32% vs 10%, p = 0.037); with Synek grade ≥ 3 (36% vs 7%, p< 0.05) and Young grade > 1 (36% vs 17%, p< 0.001). Occurrence of delirium in the days after EEG was associated with a delta

Beta-hydroxybutyrate increases reactive oxygen species in late but not in early postimplantation embryonic cells in vitro.

PubMed

Forsberg, H; Eriksson, U J; Melefors, O; Welsh, N

1998-02-01

Embryonic dysmorphogenesis has been blocked by antioxidant treatment in vivo and in vitro, suggesting that embryonic excess of reactive oxygen species (ROS) has a role in the teratogenic process of diabetic pregnancy. We report that the basal levels of ROS in dispersed rat embryonic cells in vitro, as determined by fluorescence of dichlorofluorescein (DCF), were not different in cells from control and diabetic pregnancy at day 10 or 12. Beta-hydroxybutyrate (beta-HB) and succinic acid monomethyl ester both augmented DCF fluorescence in cells from day 12 embryos of normal and diabetic rats but not from day 10 embryos. Cells of day 10 and day 12 embryos from normal and diabetic rats responded to increasing glucose concentrations with a dosage-dependent alleviation of DCF fluorescence. Day 10 embryonic cells exhibited high glucose utilization rates and high pentose phosphate shunt rates, but low mitochondrial oxidation rates. Moreover, in vitro culture of embryos between gestational days 9 and 10 in the presence of 20% oxygen induced an increased and glucose-sensitive oxidation of glucose compared with embryos not cultured in vitro. At gestation day 12, however, pentose phosphate shunt rates showed a decrease, whereas the mitochondrial beta-HB oxidation rates were increased compared with those at gestation day 10. This was paralleled by a lower expression of glucose 6-phosphate dehydrogenase- and phosphofructokinase-mRNA levels at day 12 than at day 10. On the other hand, H-ferritin mRNA expression at day 12 was high compared with day 10. None of the mRNA species investigated were affected by the diabetic state of the mother. It was concluded that beta-HB-induced stimulation of mitochondrial oxidative events may lead to the generation of ROS at gestational day 12, but probably not at day 10, when only a minute amount of mitochondrial activity occurs. Thus our results do not support the notion of diabetes-induced mitochondrial oxidative stress before the development of

A Prospective Study of PTSD and Early-Age Heart Disease Mortality Among Vietnam Veterans: Implications for Surveillance and Prevention

PubMed Central

Boscarino, Joseph A.

2013-01-01

Objective To examine prospectively early-age heart disease (HD) among a national random sample of 4328 male Vietnam veterans, who did not have HD at baseline in 1985. Studies have suggested that posttraumatic stress disorder (PTSD) may result in cardiovascular disease. However, many past studies had important methodological limitations to their designs. Method Using Cox regressions, we assessed PTSD, age, race, intelligence, family history, obesity, smoking, alcohol abuse, antisocial personality, and depression in predicting HD mortality at follow-up in December 31, 2000. The men were <65 years old at follow-up. Results Using two PTSD measures, a Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition (DSM-III) measure (D-PTSD) and one developed by Keane (K-PTSD), we found that among Vietnam theater and era veterans combined (era veterans had no Vietnam service), having PTSD was associated with HD mortality for D-PTSD (hazard ratio (HR) = 2.25, p = .045) and approached significance for K-PTSD (HR = 2.16, p = .066). However, having higher PTSD symptoms on either scale was associated with mortality, with a 5-point increase associated with ~20% increase in mortality risk (all p < .05). Controlling for lifetime depression only slightly altered the results. The effects for theater veterans alone were stronger (D-PTSD: HR = 2.58, p = .025; K-PTSD: HR = 2.73, p = .022). Among theater veterans, controlling for lifetime depression or combat exposure made little difference. Conclusion PTSD was prospectively associated with HD mortality among veterans free of HD at baseline. This study suggests that early-age HD may be an outcome after military service among PTSD-positive veterans. PMID:18596248

Early embryonic development of the head region of Gryllus assimilis Fabricius, 1775 (Orthoptera, Insecta).

PubMed

Liu, Yu; Maas, Andreas; Waloszek, Dieter

2010-09-01

We report our investigations on the embryonic development of Gryllus assimilis, with particular attention to the head. Significant findings revealed with scanning electron microscopy (SEM) images include: (1) the pre-antennal lobes represent the anterior-most segment that does not bear any appendages; (2) each of the lobes consists of central and marginal regions; (3) the central region thereof develops into the protocerebrum and the optic lobes, whereas the marginal region thereof becomes the anterior portion of the head capsule; (4) the initial position of the antennal segment is posterior to the mouth region; (5) appendage anlagen are transitorily present in the intercalary segment, and they later vanish together with the segment itself; (6) a bulged sternum appears to develop from the ventral surface of the mandibular, maxillary and labial segments. Embryonic features are then compared across the Insecta and further extended to the embryos of a spider (Araneae, Chelicerata). Striking similarities shared by the anterior-most region of the insect and spider embryos lead the authors to conclude that such comparison should be further undertaken to cover the entire Euarthropoda. This will help us to understand the embryology and evolution of the arthropod head. Copyright © 2010 Elsevier Ltd. All rights reserved.

Silver nanoparticles induce developmental stage-specific embryonic phenotypes in zebrafish.

PubMed

Lee, Kerry J; Browning, Lauren M; Nallathamby, Prakash D; Osgood, Christopher J; Xu, Xiao-Hong Nancy

2013-12-07

Much is anticipated from the development and deployment of nanomaterials in biological organisms, but concerns remain regarding their biocompatibility and target specificity. Here we report our study of the transport, biocompatibility and toxicity of purified and stable silver nanoparticles (Ag NPs, 13.1 ± 2.5 nm in diameter) upon the specific developmental stages of zebrafish embryos using single NP plasmonic spectroscopy. We find that single Ag NPs passively diffuse into five different developmental stages of embryos (cleavage, early-gastrula, early-segmentation, late-segmentation, and hatching stages), showing stage-independent diffusion modes and diffusion coefficients. Notably, the Ag NPs induce distinctive stage and dose-dependent phenotypes and nanotoxicity, upon their acute exposure to the Ag NPs (0-0.7 nM) for only 2 h. The late-segmentation embryos are most sensitive to the NPs with the lowest critical concentration (CNP,c < 0.02 nM) and highest percentages of cardiac abnormalities, followed by early-segmentation embryos (CNP,c < 0.02 nM), suggesting that disruption of cell differentiation by the NPs causes the most toxic effects on embryonic development. The cleavage-stage embryos treated with the NPs develop into a wide variety of phenotypes (abnormal finfold, tail/spinal cord flexure, cardiac malformation/edema, yolk sac edema, and acephaly). These organ structures are not yet developed in cleavage-stage embryos, suggesting that the earliest determinative events to create these structures are ongoing, and disrupted by NPs, which leads to the downstream effects. In contrast, the hatching embryos are most resistant to the Ag NPs, and majority of embryos (94%) develop normally, and none of them develop abnormally. Interestingly, early-gastrula embryos are less sensitive to the NPs than cleavage and segmentation stage embryos, and do not develop abnormally. These important findings suggest that the Ag NPs are not simple poisons, and they can target

DNA damage in bovine sperm does not block fertilization and early embryonic development but induces apoptosis after the first cleavages.

PubMed

Fatehi, A N; Bevers, M M; Schoevers, E; Roelen, B A J; Colenbrander, B; Gadella, B M

2006-01-01

The main goal of this study was to investigate whether and at what level damage of paternal DNA influences fertilization of oocytes and early embryonic development. We hypothesized that posttesticular sperm DNA damage will only marginally affect sperm physiology due to the lack of gene expression, but that it will affect embryo development at the stage that embryo genome (including the paternal damaged DNA) expression is initiated. To test this, we artificially induced sperm DNA damage by irradiation with x- or gamma rays (doses of 0-300 Gy). Remarkably, sperm cells survived the irradiation quite well and, when compared with nonirradiated cells, sperm motility and integrity of plasma membrane, acrosome, and mitochondria were not altered by this irradiation treatment. In contrast, a highly significant logarithmic relation between irradiation dose and induced DNA damage to sperm cells was found by both terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) and the acridin orange assay. Despite the DNA damage, irradiated sperm cells did not show any sign of apoptosis (nuclear fragmentation, depolarization of inner mitochondrial membranes, or phospholipid scrambling) and were normally capable of fertilizing oocytes, as there was no reduction in cleavage rates when compared with nonirradiated sperm samples up to irradiation doses of less than 10 Gy. Further embryonic development was completely blocked as the blastocyst rates at days 7 and 9 dropped from 28% (nonirradiated sperm) to less than 3% by greater than 2.5-Gy-irradiated sperm. This block in embryonic development was accompanied with the initiation of apoptosis after the second or third cleavage. Specific signs of apoptosis, such as nuclear fragmentation and aberrations in spindle formation, were observed in all embryos resulting from in vitro fertilization with irradiated sperm (irradiation doses >1.25 Gy). The results show that sperm DNA damage does not impair fertilization of the

MiRNA-mediated regulation of cell signaling and homeostasis in the early mouse embryo.

PubMed

Pernaute, Barbara; Spruce, Thomas; Rodriguez, Tristan A; Manzanares, Miguel

2011-02-15

At the time of implantation the mouse embryo is composed of three tissues the epiblast, trophectoderm and primitive endoderm. As development progresses the epiblast goes on to form the foetus whilst the trophectoderm and primitive endoderm give rise to extra-embryonic structures with important roles in embryo patterning and nutrition. Dramatic changes in gene expression occur during early embryo development and these require regulation at different levels. miRNAs are small non coding RNAs that have emerged over the last decade as important post-transcriptional repressors of gene expression. The roles played by miRNAs during early mammalian development are only starting to be elucidated. In order to gain insight into the function of miRNAs in the different lineages of the early mouse embryo we have analysed in depth the phenotype of embryos and extra-embryonic stem cells mutant for the miRNA maturation protein Dicer. This study revealed that miRNAs are involved in regulating cell signaling and homeostasis in the early embryo. Specifically, we identified a role for miRNAs in regulating the Erk signaling pathway in the extra-embryonic endoderm, cell cycle progression in extra-embryonic tissues and apoptosis in the epiblast.

Spiroplasma infection causes either early or late male killing in Drosophila, depending on maternal host age

NASA Astrophysics Data System (ADS)

Kageyama, Daisuke; Anbutsu, Hisashi; Shimada, Masakazu; Fukatsu, Takema

2007-04-01

Symbiont-induced male-killing phenotypes have been found in a variety of insects. Conventionally, these phenotypes have been divided into two categories according to the timing of action: early male killing at embryonic stages and late male killing at late larval stages. In Drosophila species, endosymbiotic bacteria of the genus Spiroplasma have been known to cause early male killing. Here, we report that a spiroplasma strain normally causing early male killing also induces late male killing depending on the maternal host age: male-specific mortality of larvae and pupae was more frequently observed in the offspring of young females. As the lowest spiroplasma density and occasional male production were also associated with newly emerged females, we proposed the density-dependent hypothesis for the expression of early and late male-killing phenotypes. Our finding suggested that (1) early and late male-killing phenotypes can be caused by the same symbiont and probably by the same mechanism; (2) late male killing may occur as an attenuated expression of early male killing; (3) expression of early and late male-killing phenotypes may be dependent on the symbiont density, and thus, could potentially be affected by the host immunity and regulation; and (4) early male killing and late male killing could be alternative strategies adopted by microbial reproductive manipulators.

Hypoxia delays hematopoiesis: retention of embryonic hemoglobin and erythrocytes in larval rainbow trout, Oncorhynchus mykiss, during chronic hypoxia exposure.

PubMed

Bianchini, Kristin; Wright, Patricia A

2013-12-01

In rainbow trout development, a switch occurs from high-affinity embryonic hemoglobin (Hb) and round, embryonic erythrocytes to lower-affinity adult Hb and oval, adult erythrocytes. Our study investigated the early ontogeny of rainbow trout blood properties and the hypoxia response. We hypothesized that hypoxia exposure would delay the ontogenetic turnover of Hb and erythrocytes because retention of high-affinity embryonic Hb would facilitate oxygen loading. To test this hypothesis we developed a method of efficiently extracting blood from individual embryos and larvae and optimized several techniques for measuring hematological parameters on microliter (0.5-2.0 μl) blood samples. In chronic hypoxia (30% of oxygen saturation), stage-matched embryos and larvae possessed half the Hb concentration, erythrocyte counts and hematocrit observed in normoxia. Hypoxia-reared larvae also had threefold to sixfold higher mRNA expression of the embryonic Hb α-1, β-1 and β-2 subunits relative to stage-matched normoxia-reared larvae. Furthermore, in hypoxia, the round embryonic erythrocytic shape persisted into later developmental stages. Despite these differences, Hb-oxygen affinity (P50), cooperativity and the Root effect were unaltered in hypoxia-reared O. mykiss. The data support our hypothesis that chronic hypoxia delays the ontogenetic turnover of Hb and erythrocytes, but without the predicted functional consequences (i.e. higher than expected P50). These results also suggest that the Hb-oxygen affinity is protected during development in chronic hypoxia to favor oxygen unloading at the tissues. We conclude that in early trout development, the blood-oxygen transport system responds very differently to chronic hypoxia relative to adults, possibly because respiration depends relatively more on oxygen diffusion than convection.

Early increase of neutrophil-to-lymphocyte ratio predicts 30-day mortality in patients with spontaneous intracerebral hemorrhage.

PubMed

Wang, Fei; Xu, Feng; Quan, Ye; Wang, Li; Xia, Jian-Jun; Jiang, Ting-Ting; Shen, Li-Juan; Kang, Wen-Hui; Ding, Yong; Mei, Li-Xia; Ju, Xue-Feng; Hu, Shan-You; Wu, Xiao

2018-05-16

To examine whether early rise of neutrophil-to-lymphocyte ratio (NLR) after patient hospitalization correlates with 30-day mortality in patients with spontaneous intracerebral hemorrhage (ICH). This retrospective study included all patients receiving treatment for spontaneous ICH between January 2015 and September 2016 at the Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences in Shanghai, China. NLR was determined at admission (T1), at 24-48 hours (T2) and 5-7 days (T3). NLR and clinicopathologic features were compared between those who survived for >30 days vs not. Multivariate regression was used to identify risk factors for 30-day mortality. A total of 275 subjects were included in the analysis: 235 survived for at least 30 days; the remaining 40 subjects died within 30 days. The patients who died within 30 days had higher ICH score, larger ICH volume, and lower GCS score (all P < 0.05). In comparison with the baseline (NLR T 1 ), NLR at 24-48 hours (NLR T 2 ) and 5-7 days (NLR T 3 ) was significantly higher in patients who died within 30 days (P < 0.05), but not in patients surviving for >30 days. In the multivariate analysis, the 30-day mortality was associated with both NLR T 2 (OR 1.112, 95%CI 1.032-1.199, P = 0.006) and NLR T 3 (OR 1.163, 95%CI 1.067-1.268, P = 0.001). Spearman correlation analysis showed that both NLR T 2 and NLR T 3 correlated inversely with GCS score and positively with ICH score and ICH volume at the baseline. Early rise of NLR predicts 30-day mortality in patients with spontaneous ICH. © 2018 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.

Egr1 gene knockdown affects embryonic ocular development in zebrafish.

PubMed

Hu, Chao-Yu; Yang, Chang-Hao; Chen, Wei-Yu; Huang, Chiu-Ju; Huang, Hsing-Yen; Chen, Muh-Shy; Tsai, Huai-Jen

2006-10-26

To identify the changes in zebrafish embryonic ocular development after early growth response factor 1 (Egr1) gene knockdown by Egr1-specific translation inhibitor, morpholino oligonucleotides (MO). Two kinds of Egr1-MO were microinjected separately with various dosages into one to four celled zebrafish embryos to find an optimal dose generating an acceptable mortality rate and high frequency of specific phenotype. Chordin-MO served as the positive control; a 5 mismatch MO of Egr1-MO1 and a nonspecific MO served as negative controls. We graded the Egr1 morphants according to their gross abnormalities, and measured their ocular dimensions accordingly. Western blot analysis and synthetic Egr1 mRNA rescue experiments confirmed whether the deformities were caused by Egr1 gene knockdown. Histological examination and three kinds of immunohistochemical staining were applied to identify glutamate receptor one expression in retinal ganglion cells and amacrine cells, to recognize acetylated alpha-tubulin expression which indicated axonogenesis, and to label photoreceptor cells with zpr-1 antibody. After microinjection of 8 ng Egr1-MO1 or 2 ng Egr1-MO2, 81.8% and 97.3% of larvae at 72 h postfertilization had specific defects, respectively. The gross phenotype included string-like heart, flat head, and deformed tail. The more severely deformed larvae had smaller eyes and pupils. Co-injection of 8 ng Egr1-MO1 and supplementary 12 pg synthetic Egr1 mRNA reduced the gross abnormality rate from 84.4% to 29.7%, and decreased the severity of deformities. Egr1 protein appeared in the wildtype and rescued morphants, but was lacking in the Egr1 morphants with specific deformities. Lenses of Egr1 morphants were smaller and had some residual nucleated lens fiber cells. Morphants' retinal cells arranged disorderly and compactly with thin plexiform layers. Immunohistochemical studies showed that morphants had a markedly decreased number of mature retinal ganglion cells, amacrine cells, and

Results of concurrent radio-chemotherapy for the treatment of head and neck squamous cell carcinoma in everyday clinical practice with special reference to early mortality

PubMed Central

2013-01-01

Background Randomized controlled trials have established concurrent chemo-radiotherapy as the preferred treatment option for inoperable local-regionally advanced head and neck squamous cell carcinomas (HNSCCs). Because many patients have multiple co-morbidities and would not fulfill the eligibility criteria of clinical trials, the results need to be re-evaluated in daily clinical practice with special reference to early mortality. Methods 167 consecutive patients with HNSCC who received concurrent chemo-radiotherapy at the Basel University Hospital between 1988 and 2006 were analyzed retrospectively with a special focus on early deaths and risk factors for an unfavorable outcome. Results In our cohort, the 3- and 5-year overall survival rates were 54% and 47%, respectively. The therapy was associated with relevant toxicity and an early mortality rate of 5.4%. Patients dying early were analyzed individually for the cause of death. Patients with elevated white blood cell counts (HR: 2.66 p = 0,016) and vascular co-morbidities (HR: 5.3, p = 0,047) showed significantly worse survival rates. The same factors were associated with a trend toward increased treatment-related mortality. The 3-year survival rate improved from approximately 43% for patients treated before the year 2000 to 65% for patients treated after the year 2000 (Fisher’s exact test p = 0.01). Conclusions Although many patients who received concurrent chemo-radiotherapy would not have qualified for clinical trials, the outcome was favorable and has significantly improved in recent years. However the early mortality was slightly worse than what is described in the literature. PMID:24373220

Different effects of enhanced and reduced expression of pub gene on the formation of embryoid bodies by cultured embryonic mouse stem cell.

PubMed

Novosadova, E V; Manuilova, E S; Arsen'eva, E L; Khaidarova, N V; Dolotov, O V; Inozemtseva, L S; Kozachenkov, K Yu; Tarantul, V Z; Grivennikov, I A

2005-07-01

The effects of pub gene on proliferation and initial stages of differentiation of embryonic mouse stem cells were studied in vitro. To this end we used enhanced expression of human pub gene (hpub) and suppression of expression of mouse endogenous pub gene with RNA-interference in embryonic stem cells. Proliferative activity of genetically modified polyclonal lines of the embryonic stem cells transfected with plasmids carrying expressing hpub gene or plasmids generating small interference RNA to this gene did not differ from that of the control cells. Inhibition of expression of endogenous pub gene in embryonic stem cells using small interference RNA 2-fold decreased the formation of embryoid bodies, at the same time additional expression of exogenous hpub gene almost 2-fold increased their number in comparison with the control. It was hypothesized that pub gene participates in early stages of differentiation of embryonic stem cells leading to the formation of embryoid bodies.

[Embryonic stem cells and therapeutic cloning].

PubMed

Sunde, A; Eftedal, I

2001-08-30

Increased interest in the therapeutic use of human stem cells has emerged following significant progress in ongoing research. The cloning of a sheep, the isolation of human embryonic stem cells, and the discovery that adult stem cells may be reprogrammed taken together give substance to hopes that novel principles of treatment may be developed for a variety of serious conditions. Embryonic stem cells are derived from pre-embryos at the blastocyst stage and may give rise to all bodily tissues and cells. Animal models have demonstrated that embryonic stem cells when transplanted into adult hosts may differentiate and develop into cells and tissues applicable for treatment of a variety of conditions, including Parkinson's disease, multiple sclerosis, spinal injuries, cardiac stroke and cancer. Transplanted embryonic stem cells are exposed to immune reactions similar to those acting on organ transplants, hence immunosuppression of the recipient is generally required. It is, however, possible to obtain embryonic stem cells that are genetically identical to the patient's own cells by means of therapeutic cloning techniques. The nucleus from a somatic cell is transferred into an egg after removal of the egg's own genetic material. Under specific condition the egg will use genetic information from the somatic cell in organising the formation of a blastocyst which in turn generates embryonic stem cells. These cells have a genetic composition identical to that of the patient and are suitable for stem cell therapy.

Structural Complexity of Non-acid Glycosphingolipids in Human Embryonic Stem Cells Grown under Feeder-free Conditions*

PubMed Central

Barone, Angela; Benktander, John; Ångström, Jonas; Aspegren, Anders; Björquist, Petter; Teneberg, Susann; Breimer, Michael. E.

2013-01-01

Due to their pluripotency and growth capability, there are great expectations for human embryonic stem cells, both as a resource for functional studies of early human development and as a renewable source of cells for use in regenerative medicine and transplantation. However, to bring human embryonic stem cells into clinical applications, their cell surface antigen expression and its chemical structural complexity have to be defined. In the present study, total non-acid glycosphingolipid fractions were isolated from two human embryonic stem cell lines (SA121 and SA181) originating from leftover in vitro fertilized human embryos, using large amounts of starting material (1 × 109 cells/cell line). The total non-acid glycosphingolipid fractions were characterized by antibody and lectin binding, mass spectrometry, and proton NMR. In addition to the globo-series and type 1 core chain glycosphingolipids previously described in human embryonic stem cells, a number of type 2 core chain glycosphingolipids (neo-lactotetraosylceramide, the H type 2 pentaosylceramide, the Lex pentaosylceramide, and the Ley hexaosylceramide) were identified as well as the blood group A type 1 hexaosylceramide. Finally, the mono-, di-, and triglycosylceramides were characterized as galactosylceramide, glucosylceramide, lactosylceramide, galabiaosylceramide, globotriaosylceramide, and lactotriaosylceramide. Thus, the glycan diversity of human embryonic stem cells, including cell surface immune determinants, is more complex than previously appreciated. PMID:23404501

[The role of supply-side characteristics of services in AIDS mortality in Mexico].

PubMed

Bautista-Arredondo, Sergio; Serván-Mori, Edson; Silverman-Retana, Omar; Contreras-Loya, David; Romero-Martínez, Martín; Magis-Rodríguez, Carlos; Uribe-Zúñiga, Patricia; Lozano, Rafael

2015-01-01

To document the association between supply-side determinants and AIDS mortality in Mexico between 2008 and 2013. We analyzed the SALVAR database (system for antiretroviral management, logistics and surveillance) as well as data collected through a nationally representative survey in health facilities. We used multivariate logit regression models to estimate the association between supply-side characteristics, namely management, training and experience of health care providers, and AIDS mortality, distinguishing early and non-early mortality and controlling for clinical indicators of the patients. Clinic status of the patients (initial CD4 and viral load) explain 44.4% of the variability of early mortality across clinics and 13.8% of the variability in non-early mortality. Supply-side characteristics increase explanatory power of the models by 16% in the case of early mortality, and 96% in the case of non-early mortality. Aspects of management and implementation of services contribute significantly to explain AIDS mortality in Mexico. Improving these aspects of the national program, can similarly improve its results.

Dead fish swimming: a review of research on the early migration and high premature mortality in adult Fraser River sockeye salmon Oncorhynchus nerka.

PubMed

Hinch, S G; Cooke, S J; Farrell, A P; Miller, K M; Lapointe, M; Patterson, D A

2012-07-01

Adult sockeye salmon Oncorhynchus nerka destined for the Fraser River, British Columbia are some of the most economically important populations but changes in the timing of their homeward migration have led to management challenges and conservation concerns. After a directed migration from the open ocean to the coast, this group historically would mill just off shore for 3-6 weeks prior to migrating up the Fraser River. This milling behaviour changed abruptly in 1995 and thereafter, decreasing to only a few days in some years (termed early migration), with dramatic consequences that have necessitated risk-averse management strategies. Early migrating fish consistently suffer extremely high mortality (exceeding 90% in some years) during freshwater migration and on spawning grounds prior to spawning. This synthesis examines multidisciplinary, collaborative research aimed at understanding what triggers early migration, why it results in high mortality, and how fisheries managers can utilize these scientific results. Tissue analyses from thousands of O. nerka captured along their migration trajectory from ocean to spawning grounds, including hundreds that were tracked with biotelemetry, have revealed that early migrants are more reproductively advanced and ill-prepared for osmoregulatory transition upon their entry into fresh water. Gene array profiles indicate that many early migrants are also immunocompromised and stressed, carrying a genomic profile consistent with a viral infection. The causes of these physiological changes are still under investigation. Early migration brings O. nerka into the river when it is 3-6° C warmer than historical norms, which for some late-run populations approaches or exceeds their critical maxima leading to the collapse of metabolic and cardiac scope, and mortality. As peak spawning dates have not changed, the surviving early migrants tend to mill in warm lakes near to spawning areas. These results in the accumulation of many more

Brief Embryonic Strychnine Exposure in Zebrafish Causes Long-Term Adult Behavioral Impairment with Indications of Embryonic Synaptic Changes

PubMed Central

Roy, Nicole M.; Arpie, Brianna; Lugo, Joseph; Linney, Elwood; Levin, Edward D.; Cerutti, Daniel

2015-01-01

Zebrafish provide a powerful model of the impacts of embryonic toxicant exposure on neural development that may result in long-term behavioral dysfunction. In this study, zebrafish embryos were treated with 1.5 mM strychnine for short embryonic time windows to induce transient changes in inhibitory neural signaling, and were subsequently raised in untreated water until adulthood. PCR analysis showed indications that strychnine exposure altered expression of some genes related to glycinergic, GABAergic and glutamatergic neuronal synapses during embryonic development. In adulthood, treated fish showed significant changes in swimming speed and tank diving behavior compared to controls. Taken together, these data show that a short embryonic exposure to a neurotoxicant can alter development of neural synapses and lead to changes in adult behavior. PMID:23022260

Development and morphogenesis of human wrist joint during embryonic and early fetal period

PubMed Central

Hita-Contreras, Fidel; Martínez-Amat, Antonio; Ortiz, Raúl; Caba, Octavio; Álvarez, Pablo; Prados, José C; Lomas-Vega, Rafael; Aránega, Antonia; Sánchez-Montesinos, Indalecio; Mérida-Velasco, Juan A

2012-01-01

The development of the human wrist joint has been studied widely, with the main focus on carpal chondrogenesis, ligaments and triangular fibrocartilage. However, there are some discrepancies concerning the origin and morphogenetic time-table of these structures, including nerves, muscles and vascular elements. For this study we used serial sections of 57 human embryonic (n = 30) and fetal (n = 27) specimens from O’Rahilly stages 17–23 and 9–14 weeks, respectively. The following phases in carpal morphogenesis have been established: undifferentiated mesenchyme (stage 17), condensated mesenchyme (stages 18 and 19), pre-chondrogenic (stages 19 and 20) and chondrogenic (stages 21 and over). Carpal chondrification and osteogenic processes are similar, starting with capitate and hamate (stage 19) and ending with pisiform (stage 22). In week 14, a vascular bud penetrates into the lunate cartilaginous mold, early sign of the osteogenic process that will be completed after birth. In stage 18, median, ulnar and radial nerves and thenar eminence appear in the hand plate. In stage 21, there are indications of the interosseous muscles, and in stage 22 flexor digitorum superficialis, flexor digitorum profundus and lumbrical muscles, transverse carpal ligament and collateral ligaments emerge. In stage 23, the articular disc, radiocarpal and ulnocarpal ligaments and deep palmar arterial arch become visible. Radiate carpal and interosseous ligaments appear in week 9, and in week 10, dorsal radiocarpal ligament and articular capsule are evident. Finally, synovial membrane is observed in week 13. We have performed a complete analysis of the morphogenesis of the structures of the human wrist joint. Our results present new data on nervous and arterial elements and provide the basis for further investigations on anatomical pathology, comparative morphology and evolutionary anthropology. PMID:22428933

Association of educational attainment with chronic disease and mortality: the Kidney Early Evaluation Program (KEEP).

PubMed

Choi, Andy I; Weekley, Cristin C; Chen, Shu-Cheng; Li, Suying; Tamura, Manjula Kurella; Norris, Keith C; Shlipak, Michael G

2011-08-01

Recent reports have suggested a close relationship between education and health, including mortality, in the United States. Observational cohort. We studied 61,457 participants enrolled in a national health screening initiative, the National Kidney Foundation's Kidney Early Evaluation Program (KEEP). Self-reported educational attainment. Chronic diseases (hypertension, diabetes, cardiovascular disease, reduced kidney function, and albuminuria) and mortality. We evaluated cross-sectional associations between self-reported educational attainment with the chronic diseases listed using logistic regression models adjusted for demographics, access to care, behaviors, and comorbid conditions. The association of educational attainment with survival was determined using multivariable Cox proportional hazards regression. Higher educational attainment was associated with a lower prevalence of each of the chronic conditions listed. In multivariable models, compared with persons not completing high school, college graduates had a lower risk of each chronic condition, ranging from 11% lower odds of decreased kidney function to 37% lower odds of cardiovascular disease. During a mean follow-up of 3.9 (median, 3.7) years, 2,384 (4%) deaths occurred. In the fully adjusted Cox model, those who had completed college had 24% lower mortality compared with participants who had completed at least some high school. Lack of income data does not allow us to disentangle the independent effects of education from income. In this diverse contemporary cohort, higher educational attainment was associated independently with a lower prevalence of chronic diseases and short-term mortality in all age and race/ethnicity groups. Published by Elsevier Inc.

Effects of prenatal micronutrient and early food supplementation on maternal hemoglobin, birth weight, and infant mortality among children in Bangladesh: the MINIMat randomized trial.

PubMed

Persson, Lars Åke; Arifeen, Shams; Ekström, Eva-Charlotte; Rasmussen, Kathleen M; Frongillo, Edward A; Yunus, Md

2012-05-16

Nutritional insult in fetal life and small size at birth are common in low-income countries and are associated with serious health consequences. To test the hypothesis that prenatal multiple micronutrient supplementation (MMS) and an early invitation to food supplementation would increase maternal hemoglobin level and birth weight and decrease infant mortality, and to assess whether a combination of these interventions would further enhance these outcomes. A randomized trial with a factorial design in Matlab, Bangladesh, of 4436 pregnant women, recruited between November 11, 2001, and October 30, 2003, with follow-up until June 23, 2009. Participants were randomized into 6 groups; a double-masked supplementation with capsules of 30 mg of iron and 400 μg of folic acid, 60 mg of iron and 400 μg of folic acid, or MMS containing a daily allowance of 15 micronutrients, including 30 mg of iron and 400 μg of folic acid, was combined with food supplementation (608 kcal 6 days per week) randomized to either early invitation (9 weeks' gestation) or usual invitation (20 weeks' gestation). Maternal hemoglobin level at 30 weeks' gestation, birth weight, and infant mortality. Under 5-year mortality was also assessed. Adjusted maternal hemoglobin level at 30 weeks' gestation was 115.0 g/L (95% CI, 114.4-115.5 g/L), with no significant differences among micronutrient groups. Mean maternal hemoglobin level was lower in the early vs usual invitation groups (114.5 vs 115.4 g/L; difference, -0.9 g/L; 95% CI, -1.7 to -0.1; P = .04). There were 3625 live births out of 4436 pregnancies. Mean birth weight among 3267 singletons was 2694 g (95% CI, 2680-2708 g), with no significant differences among groups. The early invitation with MMS group had an infant mortality rate of 16.8 per 1000 live births vs 44.1 per 1000 live births for usual invitation with 60 mg of iron and 400 μg of folic acid (hazard ratio [HR], 0.38; 95% CI, 0.18-0.78). Early invitation with MMS group had an under 5

Influences of Reduced Expression of Maternal Bone Morphogenetic Protein 2 on Embryonic Development

PubMed Central

Singh, Ajeet P.; Castranio, Trisha; Scott, Greg; Guo, Dayong; Harris, Marie A.; Ray, Manas; Harris, Stephan E.; Mishina, Yuji

2009-01-01

Bone morphogenetic protein 2 (BMP2) was originally found by its osteoinductive ability, and recent genetic analyses have revealed that it plays critical roles during early embryogenesis, cardiogenesis, decidualization as well as skeletogenesis. During a course of evaluation of the conditional allele for Bmp2, we found that the presence of a neo cassette, a selection marker needed for gene targeting events in embryonic stem cells, in the 3’ untranslated region of exon 3 of Bmp2, reduced the expression levels of Bmp2 both in embryonic and maternal tissues. Some of the embryos that were genotyped as transheterozygous for the floxed allele with the neo cassette over the conventional null allele (fn/−) showed a lethal phenotype including defects in cephalic neural tube closure and ventral abdominal wall closure. Embryos exhibiting these abnormalities were increased when genotypes of the pregnant females were different; when expression levels of Bmp2 in maternal tissues were lower, a larger proportion of fn/− embryos exhibit these abnormalities. These results suggest that the expression levels of Bmp2 together in both in embryonic and maternal tissues influence the normal neural tube closure and body wall closure with different thresholds. PMID:18769073

Development of thiamine deficiencies and early mortality syndrome in lake trout by feeding experimental and feral fish diets containing thiaminase

USGS Publications Warehouse

Honeyfield, D.C.; Hinterkopf, J.P.; Fitzsimons, J.D.; Tillitt, D.E.; Zajicek, J.L.; Brown, S.B.

2005-01-01

We conducted a laboratory investigation on the consequences of feeding predatory salmonids either experimental diets low in thiamine or diets containing alewife Alosa pseudoharengus. In experiment 1, adult lake trout Salvelinus namaycush were fed experimental diets containing bacterial thiaminase. In experiment 2, adult lake trout were fed natural prey species, alewives, and bloaters Coregonus hoyi. The diets consisted of four combinations of alewives and bloaters from Lake Michigan (100% alewives, 65% alewives–35% bloaters, 35% alewives–65% bloaters, and 100% bloaters), alewives from Cayuga Lake, a casein bacterial thiaminase, and a commercial trout diet. We assessed the effects of each diet on egg thiamine concentration and incidence of an embryonic early mortality syndrome (EMS). In experiment 1, incidence of EMS ranged from 0% to 100%. Significant relationships were found between the incidence of EMS and thiamine. In experiment 2, adult lake trout fed 100% alewives from either Lake Michigan or Cayuga Lake or fish fed the casein bacterial thiaminase diet produced eggs with low thiamine and swim-up fry with EMS. At either 35% or 65% alewives in the diet, egg thiamine was significantly lowered. The number of females that produced offspring that died from EMS were low but demonstrated the negative potential if feral lake trout foraged on either 35% or 65% alewives. Depleted egg thiamine and the onset of EMS required diets containing thiaminase for a minimum of 2 years in lake trout initially fully thiamine replete. We conclude that EMS can be caused by extensive feeding on 100% alewives and dietary levels of 35% or greater may prove detrimental to sustainable reproduction of salmonids in the Great Lakes. The data are consistent with that observed in feral lake trout, and it is concluded that EMS is the result of a thiamine deficiency.

Brief embryonic strychnine exposure in zebrafish causes long-term adult behavioral impairment with indications of embryonic synaptic changes.

PubMed

Roy, Nicole M; Arpie, Brianna; Lugo, Joseph; Linney, Elwood; Levin, Edward D; Cerutti, Daniel

2012-01-01

Zebrafish provide a powerful model of the impacts of embryonic toxicant exposure on neural development that may result in long-term behavioral dysfunction. In this study, zebrafish embryos were treated with 1.5mM strychnine for short embryonic time windows to induce transient changes in inhibitory neural signaling, and were subsequently raised in untreated water until adulthood. PCR analysis showed indications that strychnine exposure altered expression of some genes related to glycinergic, GABAergic and glutamatergic neuronal synapses during embryonic development. In adulthood, treated fish showed significant changes in swimming speed and tank diving behavior compared to controls. Taken together, these data show that a short embryonic exposure to a neurotoxicant can alter development of neural synapses and lead to changes in adult behavior. Copyright © 2012 Elsevier Inc. All rights reserved.

Early Standard Electroencephalogram Abnormalities Predict Mortality in Septic Intensive Care Unit Patients

PubMed Central

Azabou, Eric; Magalhaes, Eric; Braconnier, Antoine; Yahiaoui, Lyria; Moneger, Guy; Heming, Nicholas; Annane, Djillali; Mantz, Jean; Chrétien, Fabrice; Durand, Marie-Christine; Lofaso, Frédéric; Porcher, Raphael; Sharshar, Tarek

2015-01-01

Introduction Sepsis is associated with increased mortality, delirium and long-term cognitive impairment in intensive care unit (ICU) patients. Electroencephalogram (EEG) abnormalities occurring at the acute stage of sepsis may correlate with severity of brain dysfunction. Predictive value of early standard EEG abnormalities for mortality in ICU septic patients remains to be assessed. Methods In this prospective, single center, observational study, standard EEG was performed, analyzed and classified according to both Synek and Young EEG scales, in consecutive patients acutely admitted in ICU for sepsis. Delirium, coma and the level of sedation were assessed at the time of EEG recording; and duration of sedation, occurrence of in-ICU delirium or death were assessed during follow-up. Adjusted analyses were carried out using multiple logistic regression. Results One hundred ten patients were included, mean age 63.8 (±18.1) years, median SAPS-II score 38 (29–55). At the time of EEG recording, 46 patients (42%) were sedated and 22 (20%) suffered from delirium. Overall, 54 patients (49%) developed delirium, of which 32 (29%) in the days after EEG recording. 23 (21%) patients died in the ICU. Absence of EEG reactivity was observed in 27 patients (25%), periodic discharges (PDs) in 21 (19%) and electrographic seizures (ESZ) in 17 (15%). ICU mortality was independently associated with a delta-predominant background (OR: 3.36; 95% CI [1.08 to 10.4]), absence of EEG reactivity (OR: 4.44; 95% CI [1.37–14.3], PDs (OR: 3.24; 95% CI [1.03 to 10.2]), Synek grade ≥ 3 (OR: 5.35; 95% CI [1.66–17.2]) and Young grade > 1 (OR: 3.44; 95% CI [1.09–10.8]) after adjustment to Simplified Acute Physiology Score (SAPS-II) at admission and level of sedation. Delirium at the time of EEG was associated with ESZ in non-sedated patients (32% vs 10%, p = 0.037); with Synek grade ≥ 3 (36% vs 7%, p< 0.05) and Young grade > 1 (36% vs 17%, p< 0.001). Occurrence of delirium in the days after

Identification of new regulators of embryonic patterning and morphogenesis in Xenopus gastrulae by RNA sequencing.

PubMed

Popov, Ivan K; Kwon, Taejoon; Crossman, David K; Crowley, Michael R; Wallingford, John B; Chang, Chenbei

2017-06-15

During early vertebrate embryogenesis, cell fate specification is often coupled with cell acquisition of specific adhesive, polar and/or motile behaviors. In Xenopus gastrulae, tissues fated to form different axial structures display distinct motility. The cells in the early organizer move collectively and directionally toward the animal pole and contribute to anterior mesendoderm, whereas the dorsal and the ventral-posterior trunk tissues surrounding the blastopore of mid-gastrula embryos undergo convergent extension and convergent thickening movements, respectively. While factors regulating cell lineage specification have been described in some detail, the molecular machinery that controls cell motility is not understood in depth. To gain insight into the gene battery that regulates both cell fates and motility in particular embryonic tissues, we performed RNA sequencing (RNA-seq) to investigate differentially expressed genes in the early organizer, the dorsal and the ventral marginal zone of Xenopus gastrulae. We uncovered many known signaling and transcription factors that have been reported to play roles in embryonic patterning during gastrulation. We also identified many uncharacterized genes as well as genes that encoded extracellular matrix (ECM) proteins or potential regulators of actin cytoskeleton. Co-expression of a selected subset of the differentially expressed genes with activin in animal caps revealed that they had distinct ability to block activin-induced animal cap elongation. Most of these factors did not interfere with mesodermal induction by activin, but an ECM protein, EFEMP2, inhibited activin signaling and acted downstream of the activated type I receptor. By focusing on a secreted protein kinase PKDCC1, we showed with overexpression and knockdown experiments that PKDCC1 regulated gastrulation movements as well as anterior neural patterning during early Xenopus development. Overall, our studies identify many differentially expressed

Berberine impairs embryonic development in vitro and in vivo through oxidative stress-mediated apoptotic processes.

PubMed

Huang, Chien-Hsun; Huang, Zi-Wei; Ho, Feng-Ming; Chan, Wen-Hsiung

2018-03-01

Berberine, an isoquinoline alkaloid isolated from several traditional Chinese herbal medicines, has been shown to suppress growth and induce apoptosis in some tumor cell lines. However, berberine has also been reported to attenuate H 2 O 2 -induced oxidative injury and apoptosis. The basis for these ambiguous effects of berberine-triggering or preventing apoptosis-has not been well characterized to date. In the current investigation, we examined whether berberine exerts cytotoxic effects on mouse embryos at the blastocyst stage and affects subsequent embryonic development in vitro and in vivo. Treatment of blastocysts with berberine (2.5-10 μM) induced a significant increase in apoptosis and a corresponding decrease in trophectoderm cell number. Moreover, the implantation success rate of blastocysts pretreated with berberine was lower than that of their control counterparts. Pretreatment with berberine was also associated with increased resorption of postimplantation embryos and decreased fetal weight. In an animal model, intravenous injection of berberine (2, 4, or 6 mg/kg body weight/d) for 4 days resulted in apoptosis of blastocyst cells and early embryonic developmental injury. Berberine-induced injury of mouse blastocysts appeared to be attributable to oxidative stress-triggered intrinsic apoptotic signaling processes that impaired preimplantation and postimplantation embryonic development. Taken together, our results clearly demonstrate that berberine induces apoptosis and retards early preimplantation and postimplantation development of mouse embryos, both in vitro and in vivo. © 2017 Wiley Periodicals, Inc.

Differential gene expression during early embryonic development in diapause and non-diapause eggs of multivoltine silkworm Bombyx mori.

PubMed

Ponnuvel, Kangayam M; Murthy, Geetha N; Awasthi, Arvind K; Rao, Guruprasad; Vijayaprakash, Nanjappa B

2010-11-01

) revealed differential levels of expression in both the eggs at all stages of embryonic development. The present study thus provides an overview of the differential expression levels of metabolic enzyme and Hsp genes in non-diapause and diapause induced eggs of multivoltine silkworm B. mori within 48 h after oviposition, confirming the major role of in early embryogenesis.

The plurennial life cycles of the European Tettigoniidae (Insecta: Orthoptera) : 1. The effect of temperature on embryonic development and hatching.

PubMed

Ingrisch, Sigfrid

1986-11-01

The effect of temperature on embryonic development, voltinism, and hatching was studied in the laboratory in eggs of 21 Central and Southeastern European Tettigoniidae species. In most species, the embryo has to arrive at a postkatatrepsis stage prior to the onset of cold to be able to hatch in the following spring. The rate of embryonic development differs: quickly developing species need 4 weeks at 24°C (prior to cold) and almost all eggs hatch after the first cold treatment, slowly developing species would need 8-12 weeks to do the same. In Central Europe, warmth is not enough for the slowly developing species to have an univoltine life cycle, but they could have it in southern Europe. Most species make use of a dormancy sequence to pass successive winters as follows: an initial embryonic dormancy (either quiscence or diapause in embryonic stage 4) and a final diapause in embryonic stage 23/24. Additionally, 3 forms of aestivation or summer dormancy were observed facultatively: an initial diapause in embryonic stage 4 (induced and terminated at 30°C), a median dormancy shortly before or after katatrepsis (at 30°C), and a penultimate diapause in embryonic stage 20 (at 24°C).The life cycles of the European Tettigoniidae species can follow one of 3 types: 1. annual life cycle (no initial embryonic dormancy); 2. annual or biennial depending on whether laid early or late; 3. biennial or many year life cycle (up to 8 years due to a prolonged initial diapause).

Mechanistic basis of adaptive maternal effects: egg jelly water balance mediates embryonic adaptation to acidity in Rana arvalis.

PubMed

Shu, Longfei; Suter, Marc J-F; Laurila, Anssi; Räsänen, Katja

2015-11-01

Environmental stress, such as acidification, can challenge persistence of natural populations and act as a powerful evolutionary force at ecological time scales. The ecological and evolutionary responses of natural populations to environmental stress at early life-stages are often mediated via maternal effects. During early life-stages, maternal effects commonly arise from egg coats (the extracellular structures surrounding the embryo), but the role of egg coats has rarely been studied in the context of adaptation to environmental stress. Previous studies on the moor frog Rana arvalis found that the egg coat mediated adaptive divergence along an acidification gradient in embryonic acid stress tolerance. However, the exact mechanisms underlying these adaptive maternal effects remain unknown. Here, we investigated the role of water balance and charge state (zeta potential) of egg jelly coats in embryonic adaptation to acid stress in three populations of R. arvalis. We found that acidic pH causes severe water loss in the egg jelly coat, but that jelly coats from an acid-adapted population retained more water than jelly coats from populations not adapted to acidity. Moreover, embryonic acid tolerance (survival at pH 4.0) correlated with both water loss and charge state of the jelly, indicating that negatively charged glycans influence jelly water balance and contribute to embryonic adaptation to acidity. These results indicate that egg coats can harbor extensive intra-specific variation, probably facilitated in part via strong selection on water balance and glycosylation status of egg jelly coats. These findings shed light on the molecular mechanisms of environmental stress tolerance and adaptive maternal effects.

The pathway to femaleness: current knowledge on embryonic development of the ovary

PubMed Central

Yao, Humphrey Hung-Chang

2014-01-01

Increasing evidence indicates that organogenesis of the ovary is not a passive process arising by default in the absence of the testis pathway. A coordinated interaction is actually in force between somatic cells and female germ cells in embryonic ovaries, thus creating a unique microenvironment that facilitates the formation of follicles. Identification of the functional roles of several novel regulatory elements such as Figα, Foxl2, follistatin, and Wnt4 reveals the complexity of early ovarian organization. Challenges await us to establish the molecular connections of these molecules as well as to discover new candidates in the pathway of early ovarian development. PMID:15664455

Developmental staging of male murine embryonic gonad by SAGE analysis

PubMed Central

Lee, Tin-Lap; Li, Yunmin; Alba, Diana; Vong, Queenie P.; Wu, Shao-Ming; Baxendale, Vanessa; Rennert, Owen M.; Lau, Yun-Fai Chris; Chan, Wai-Yee

2012-01-01

Despite the identification of key genes such as Sry integral to embryonic gonadal development, the genomic classification and identification of chromosomal activation of this process is still poorly understood. To better understand the genetic regulation of gonadal development, we performed Serial Analysis of Gene Expression (SAGE) to profile the genes and novel transcripts, and an average of 152,000 tags from male embryonic gonads at E10.5 (embryonic day 10.5), E11.5, E12.5, E13.5, E15.5 and E17.5 were analyzed. A total of 275,583 non-singleton tags that do not map to any annotated sequence were identified in the six gonad libraries, and 47,255 tags were mapped to 24,975 annotated sequences, among which 987 sequences were uncharacterized. Utilizing an unsupervised pattern identification technique, we established molecular staging of male gonadal development. Rather than providing a static descriptive analysis, we developed algorithms to cluster the SAGE data and assign SAGE tags to a corresponding chromosomal position; these data are displayed in chromosome graphic format. A prominent increase in global genomic activity from E10.5 to E17.5 was observed. Important chromosomal regions related to the developmental processes were identified and validated based on established mouse models with developmental disorders. These regions may represent markers for early diagnosis for disorders of male gonad development as well as potential treatment targets. PMID:19376482

Early Permian mafic dikes in the Nagqu area, central Tibet, China, associated with embryonic oceanic crust of the Meso-Tethys Ocean

NASA Astrophysics Data System (ADS)

Chen, S. S.; Fan, W. M.; Shi, R. D.; Gong, X. H.

2017-12-01

During the latest Carboniferous to early Permian, a mantle plume initiated continental rifting along the northern Gondwana margin, which subsequently developed into the Meso-Tethys Ocean. However, the nature and timing of the embryonic oceanic crust of the Meso-Tethys Ocean remains poorly understood. Here, we present for the first time a combined analysis of petrological, geochronological, geochemical, and Sr-Nd isotopic data for mafic rocks from the Nagqu area, central Tibet. Zircons from the mafic rocks yield a concordant age of ca. 277.8±1.8 Ma, which is slightly younger than the age of mantle plume activity (ca. 300-279 Ma), as represented by the large igneous province (LIP) on the northern Gondwana margin. Geochemical features suggest that the Nagqu mafic rocks, which display normal mid ocean ridge basalt (N-MORB) affinities, are different from those of the LIP, which display oceanic island basalt (OIB)-type affinities. The Nagqu mafic rocks result from a relatively high degree of melting of depleted asthenospheric mantle. Combined with observations from previous studies, we suggest that the late early Permian Nagqu magmatism fully records processes of early stage rifting and incipient formation of oceanic crust. Moreover, the patterns of magmatism are consistent with patterns of rift-related sedimentation that records the transition from predominantly continental to marine deposition in the region during the Carboniferous-Permian. We therefore suggest that rifting of the eastern Cimmerian and northern Gondwana continents started at ca. 277.8 Ma, and the rifting culminated in the opening of the Meso-Tethys Ocean.

No effect of an additional early dose of measles vaccine on hospitalization or mortality in children: A randomized controlled trial.

PubMed

Schoeps, Anja; Nebié, Eric; Fisker, Ane Baerent; Sié, Ali; Zakane, Alphonse; Müller, Olaf; Aaby, Peter; Becher, Heiko

2018-04-05

Non-specific effects (NSEs) of vaccines have increasingly gained attention in recent years. Recent studies suggest that live vaccines, such as measles vaccine (MV), have beneficial effects on health, while inactivated vaccines, such as the diphtheria-tetanus-pertussis (DTP) vaccine, may have harmful effects. If this is the case, it should improve child health to move MV closer to the last vaccination with DTP. The objective of this study was to investigate the NSEs of an additional early dose of MV on hospitalization or mortality. Children were randomized to receive either the standard MV at 9 months (control) or an additional early dose of MV 4 weeks after the third dose of DTP-containing Pentavalent vaccine and the standard MV at 9 months (intervention). In this analysis of a secondary outcome in the trial, we investigated the effect of the intervention on a composite endpoint of over-night hospitalization with or without recovery, or death without previous hospitalization, in children between 4.5 and 36 months of age in the Nouna HDSS in Burkina Faso. We used Cox proportional hazards regression with repeated events and time since study enrolment as underlying time-scale. Among 2258 children in the intervention and 2238 children in the control group we observed a total of 464 episodes of hospitalization or mortality. There was no difference between intervention and control group (HR = 1.00, 95% Confidence Interval (CI) 0.83-1.20). Results from the per-protocol and intention-to-treat analysis were similar. Although no significant, results suggest a possible beneficial effect of early MV in children that had not been exposed to an OPV campaign after enrolment (HR = 0.83, 95% CI 0.55-1.29). We did not detect any effect of early MV on subsequent hospitalization or mortality. However, possible effects of early MV could have been obscured by NSEs of the frequent OPV campaigns. Registration: The trial was registered at ClinicalTrials.gov, NCT01644721

Programmed Effects in Neurobehavior and Antioxidative Physiology in Zebrafish Embryonically Exposed to Cadmium: Observations and Hypothesized Adverse Outcome Pathway Framework

PubMed Central

Ruiter, Sander; Sippel, Josefine; Bouwmeester, Manon C.; Lommelaars, Tobias; Beekhof, Piet; Hodemaekers, Hennie M.; Bakker, Frank; van den Brandhof, Evert-Jan; Pennings, Jeroen L. A.; van der Ven, Leo T. M.

2016-01-01

Non-communicable diseases (NCDs) are a major cause of premature mortality. Recent studies show that predispositions for NCDs may arise from early-life exposure to low concentrations of environmental contaminants. This developmental origins of health and disease (DOHaD) paradigm suggests that programming of an embryo can be disrupted, changing the homeostatic set point of biological functions. Epigenetic alterations are a possible underlying mechanism. Here, we investigated the DOHaD paradigm by exposing zebrafish to subtoxic concentrations of the ubiquitous contaminant cadmium during embryogenesis, followed by growth under normal conditions. Prolonged behavioral responses to physical stress and altered antioxidative physiology were observed approximately ten weeks after termination of embryonal exposure, at concentrations that were 50–3200-fold below the direct embryotoxic concentration, and interpreted as altered developmental programming. Literature was explored for possible mechanistic pathways that link embryonic subtoxic cadmium to the observed apical phenotypes, more specifically, the probability of molecular mechanisms induced by cadmium exposure leading to altered DNA methylation and subsequently to the observed apical phenotypes. This was done using the adverse outcome pathway model framework, and assessing key event relationship plausibility by tailored Bradford-Hill analysis. Thus, cadmium interaction with thiols appeared to be the major contributor to late-life effects. Cadmium-thiol interactions may lead to depletion of the methyl donor S-adenosyl-methionine, resulting in methylome alterations, and may, additionally, result in oxidative stress, which may lead to DNA oxidation, and subsequently altered DNA methyltransferase activity. In this way, DNA methylation may be affected at a critical developmental stage, causing the observed apical phenotypes. PMID:27827847

Programmed Effects in Neurobehavior and Antioxidative Physiology in Zebrafish Embryonically Exposed to Cadmium: Observations and Hypothesized Adverse Outcome Pathway Framework.

PubMed

Ruiter, Sander; Sippel, Josefine; Bouwmeester, Manon C; Lommelaars, Tobias; Beekhof, Piet; Hodemaekers, Hennie M; Bakker, Frank; van den Brandhof, Evert-Jan; Pennings, Jeroen L A; van der Ven, Leo T M

2016-11-02

Non-communicable diseases (NCDs) are a major cause of premature mortality. Recent studies show that predispositions for NCDs may arise from early-life exposure to low concentrations of environmental contaminants. This developmental origins of health and disease (DOHaD) paradigm suggests that programming of an embryo can be disrupted, changing the homeostatic set point of biological functions. Epigenetic alterations are a possible underlying mechanism. Here, we investigated the DOHaD paradigm by exposing zebrafish to subtoxic concentrations of the ubiquitous contaminant cadmium during embryogenesis, followed by growth under normal conditions. Prolonged behavioral responses to physical stress and altered antioxidative physiology were observed approximately ten weeks after termination of embryonal exposure, at concentrations that were 50-3200-fold below the direct embryotoxic concentration, and interpreted as altered developmental programming. Literature was explored for possible mechanistic pathways that link embryonic subtoxic cadmium to the observed apical phenotypes, more specifically, the probability of molecular mechanisms induced by cadmium exposure leading to altered DNA methylation and subsequently to the observed apical phenotypes. This was done using the adverse outcome pathway model framework, and assessing key event relationship plausibility by tailored Bradford-Hill analysis. Thus, cadmium interaction with thiols appeared to be the major contributor to late-life effects. Cadmium-thiol interactions may lead to depletion of the methyl donor S -adenosyl-methionine, resulting in methylome alterations, and may, additionally, result in oxidative stress, which may lead to DNA oxidation, and subsequently altered DNA methyltransferase activity. In this way, DNA methylation may be affected at a critical developmental stage, causing the observed apical phenotypes.

Tree rings provide early warning signals of jack pine mortality across a moisture gradient in the southern boreal forest

NASA Astrophysics Data System (ADS)

Mamet, S. D.; Chun, K. P.; Metsaranta, J. M.; Barr, A. G.; Johnstone, J. F.

2015-08-01

Recent declines in productivity and tree survival have been widely observed in boreal forests. We used early warning signals (EWS) in tree ring data to anticipate premature mortality in jack pine (Pinus banksiana)—an extensive and dominant species occurring across the moisture-limited southern boreal forest in North America. We sampled tree rings from 113 living and 84 dead trees in three soil moisture regimes (subxeric, submesic, subhygric) in central Saskatchewan, Canada. We reconstructed annual increments of tree basal area to investigate (1) whether we could detect EWS related to mortality of individual trees, and (2) how water availability and tree growth history may explain the mortality warning signs. EWS were evident as punctuated changes in growth patterns prior to transition to an alternative state of reduced growth before dying. This transition was likely triggered by a combination of severe drought and insect outbreak. Higher moisture availability associated with a soil moisture gradient did not appear to reduce tree sensitivity to stress-induced mortality. Our results suggest tree rings offer considerable potential for detecting critical transitions in tree growth, which are linked to premature mortality.

Generation of the Dimensional Embryology Application (App) for Visualization of Early Chick and Frog Embryonic Development

ERIC Educational Resources Information Center

Webb, Rebecca L.; Bilitski, James; Zerbee, Alyssa; Symans, Alexandra; Chop, Alexandra; Seitz, Brianne; Tran, Cindy

2015-01-01

The study of embryonic development of multiple organisms, including model organisms such as frogs and chicks, is included in many undergraduate biology programs, as well as in a variety of graduate programs. As our knowledge of biological systems increases and the amount of material to be taught expands, the time spent instructing students about…

[VIABILITY OF MYOCAROIUM AS RISK FACTOR FOR MORTALITY IN EARLY AND LATE PERIOD AFTER BYPASS SURGERY OF CORONARY ARTERIES IN PATIENTS WITH CORONARY HEART DISEASE AND SEVERE LEFT VENTRICULAR DYSFUNCTION].

PubMed

Todurov, B M; Zelenchuk, V; Kuzmich, I M; Ivanyuk, N B; Nikolaichuk, M V

2015-06-01

In coronary heart disease and low ejection fraction of the left ventricle (LV) in patients after coronary artery bypass surgery tend mortality and complication rate higher than preserved LV systolic function. Significant preoperative predictors of early mortality and remote in these patients, and the incidence of complications in the early postoperative period were reveald.

Association of Sepsis-Related Mortality with Early Increase of TIMP-1/MMP-9 Ratio

PubMed Central

Lorente, Leonardo; Martín, María M.; Solé-Violán, Jordi; Blanquer, José; Labarta, Lorenzo; Díaz, César; Borreguero-León, Juan M.; Orbe, Josune; Rodríguez, José A.; Jiménez, Alejandro; Páramo, José A.

2014-01-01

Objective Higher circulating levels of tissue inhibitor of matrix metalloproteinases (TIMP)-1 at the time of severe sepsis diagnosis have been reported in nonsurviving than in surviving patients. However, the following questions remain unanswered: 1) Does TIMP-1/MMP-9 ratio differ throughout the first week of intensive care between surviving and non-surviving patients? 2) Is there an association between TIMP-1/MMP-9 ratio and sepsis severity and mortality during such period? 3) Could TIMP-1/MMP-9 ratio during the first week be used as an early biomarker of sepsis outcome? 4) Is there an association between TIMP-1/MMP-9 ratio and coagulation state and circulating cytokine levels during the first week of intensive care in these patients? The present study sought to answer these questions. Methods Multicenter, observational and prospective study carried out in six Spanish Intensive Care Units (ICUs) of 295 patients with severe sepsis. Were measured circulating levels of TIMP-1, MMP-9, tumour necrosis factor (TNF)-alpha, interleukin (IL)-10 and plasminogen activator inhibitor (PAI)-1 at day 1, 4 and 8. End-point was 30-day mortality. Results We found higher TIMP-1/MMP-9 ratio during the first week in non-surviving (n = 98) than in surviving patients (n = 197) (p<0.01). Logistic regression analyses showed that TIMP-1/MMP-9 ratio at days 1, 4 and 8 was associated with mortality. Receiver operating characteristic (ROC) curves showed that TIMP-1/MMP-9 ratio at days 1, 4 and 8 could predict mortality. There was an association between TIMP-1/MMP-9 ratio and TNF-alpha, IL-10, PAI-1 and lactic acid levels, SOFA score and platelet count at days 1, 4 and 8. Conclusions The novel findings of our study were that non-surviving septic patients showed persistently higher TIMP-1/MMP-9 ratio than survivors ones during the first week, which was associated with severity, coagulation state, circulating cytokine levels and mortality; thus representing a new biomarker of sepsis

Association of sepsis-related mortality with early increase of TIMP-1/MMP-9 ratio.

PubMed

Lorente, Leonardo; Martín, María M; Solé-Violán, Jordi; Blanquer, José; Labarta, Lorenzo; Díaz, César; Borreguero-León, Juan M; Orbe, Josune; Rodríguez, José A; Jiménez, Alejandro; Páramo, José A

2014-01-01

Higher circulating levels of tissue inhibitor of matrix metalloproteinases (TIMP)-1 at the time of severe sepsis diagnosis have been reported in nonsurviving than in surviving patients. However, the following questions remain unanswered: 1) Does TIMP-1/MMP-9 ratio differ throughout the first week of intensive care between surviving and non-surviving patients? 2) Is there an association between TIMP-1/MMP-9 ratio and sepsis severity and mortality during such period? 3) Could TIMP-1/MMP-9 ratio during the first week be used as an early biomarker of sepsis outcome? 4) Is there an association between TIMP-1/MMP-9 ratio and coagulation state and circulating cytokine levels during the first week of intensive care in these patients? The present study sought to answer these questions. Multicenter, observational and prospective study carried out in six Spanish Intensive Care Units (ICUs) of 295 patients with severe sepsis. Were measured circulating levels of TIMP-1, MMP-9, tumour necrosis factor (TNF)-alpha, interleukin (IL)-10 and plasminogen activator inhibitor (PAI)-1 at day 1, 4 and 8. End-point was 30-day mortality. We found higher TIMP-1/MMP-9 ratio during the first week in non-surviving (n = 98) than in surviving patients (n = 197) (p<0.01). Logistic regression analyses showed that TIMP-1/MMP-9 ratio at days 1, 4 and 8 was associated with mortality. Receiver operating characteristic (ROC) curves showed that TIMP-1/MMP-9 ratio at days 1, 4 and 8 could predict mortality. There was an association between TIMP-1/MMP-9 ratio and TNF-alpha, IL-10, PAI-1 and lactic acid levels, SOFA score and platelet count at days 1, 4 and 8. The novel findings of our study were that non-surviving septic patients showed persistently higher TIMP-1/MMP-9 ratio than survivors ones during the first week, which was associated with severity, coagulation state, circulating cytokine levels and mortality; thus representing a new biomarker of sepsis outcome.

Early-life mortality risks in opposite-sex and same-sex twins: a Danish cohort study of the twin testosterone transfer hypothesis

PubMed Central

Ahrenfeldt, Linda Juel; Larsen, Lisbeth Aagaard; Lindahl-Jacobsen, Rune; Skytthe, Axel; Hjelmborg, Jacob v.B.; Möller, Sören; Christensen, Kaare

2017-01-01

Purpose To investigate the twin testosterone transfer (TTT) hypothesis by comparing early-life mortality risks of opposite-sex (OS) and same-sex (SS) twins during the first 15 years of life. Methods We performed a population-based cohort study to compare mortality in OS and SS twins. We included 68,629 live-born Danish twins from 1973 to 2009 identified through the Danish Twin Registry and performed piecewise stratified Cox regression and log-binomial regression. Results Among 1933 deaths, we found significantly higher mortality for twin boys than for twin girls. For both sexes, OS twins had lower mortality than SS twins; the difference persisted for the first year of life for boys and for the first week of life for girls. Conclusions Although the mortality risk for OS boys was in the expected direction according to the TTT hypothesis, the results for OS girls pointed in the opposite direction, providing no clear evidence for the TTT hypothesis. PMID:28024904

Early-life mortality risks in opposite-sex and same-sex twins: a Danish cohort study of the twin testosterone transfer hypothesis.

PubMed

Ahrenfeldt, Linda Juel; Larsen, Lisbeth Aagaard; Lindahl-Jacobsen, Rune; Skytthe, Axel; Hjelmborg, Jacob V B; Möller, Sören; Christensen, Kaare

2017-02-01

To investigate the twin testosterone transfer (TTT) hypothesis by comparing early-life mortality risks of opposite-sex (OS) and same-sex (SS) twins during the first 15 years of life. We performed a population-based cohort study to compare mortality in OS and SS twins. We included 68,629 live-born Danish twins from 1973 to 2009 identified through the Danish Twin Registry and performed piecewise stratified Cox regression and log-binomial regression. Among 1933 deaths, we found significantly higher mortality for twin boys than for twin girls. For both sexes, OS twins had lower mortality than SS twins; the difference persisted for the first year of life for boys and for the first week of life for girls. Although the mortality risk for OS boys was in the expected direction according to the TTT hypothesis, the results for OS girls pointed in the opposite direction, providing no clear evidence for the TTT hypothesis. Copyright © 2016 Elsevier Inc. All rights reserved.

Serial block face-scanning electron microscopy: a tool for studying embryonic development at the cell-matrix interface.

PubMed

Starborg, Tobias; Kadler, Karl E

2015-03-01

Studies of gene regulation, signaling pathways, and stem cell biology are contributing greatly to our understanding of early embryonic vertebrate development. However, much less is known about the events during the latter half of embryonic development, when tissues comprising mostly extracellular matrix (ECM) are formed. The matrix extends far beyond the boundaries of individual cells and is refractory to study by conventional biochemical and molecular techniques; thus major gaps exist in our knowledge of the formation and three-dimensional (3D) organization of the dense tissues that form the bulk of adult vertebrates. Serial block face-scanning electron microscopy (SBF-SEM) has the ability to image volumes of tissue containing numerous cells at a resolution sufficient to study the organization of the ECM. Furthermore, whereas light microscopy was once relatively straightforward and electron microscopy was performed in specialist laboratories, the tables are turned; SBF-SEM is relatively straightforward and is becoming routine in high-end resolution studies of embryonic structures in vivo. In this review, we discuss the emergence of SBF-SEM as a tool for studying embryonic vertebrate development. © 2015 Wiley Periodicals, Inc.

Controversies in cancer stem cells: targeting embryonic signaling pathways.

PubMed

Takebe, Naoko; Ivy, S Percy

2010-06-15

Selectively targeting cancer stem cells (CSC) or tumor-initiating cells (TIC; from this point onward referred to as CSCs) with novel agents is a rapidly emerging field of oncology. Our knowledge of CSCs and their niche microenvironments remains a nascent field. CSC's critical dependence upon self-renewal makes these regulatory signaling pathways ripe for the development of experimental therapeutic agents. Investigational agents targeting the Notch, Hedgehog, and Wnt pathways are currently in late preclinical development stages, with some early phase 1-2 testing in human subjects. This series of articles will provide an overview and summary of the current state of knowledge of CSCs, their interactive microenvironment, and how they may serve as important targets for antitumor therapies. We also examine the scope and stage of development of early experimental agents that specifically target these highly conserved embryonic signaling pathways. (c) 2010 AACR.

Vacuolar status and water relations in embryonic axes of recalcitrant Aesculus hippocastanum seeds during stratification and early germination.

PubMed

Obroucheva, Natalie V; Lityagina, Snezhana V; Novikova, Galina V; Sin'kevich, Irina A

2012-01-01

In tropical recalcitrant seeds, their rapid transition from shedding to germination at high hydration level is of physiological interest but difficult to study because of the time constraint. In recalcitrant horse chestnut seeds produced in central Russia, this transition is much longer and extends through dormancy and dormancy release. This extended time period permits studies of the water relations in embryonic axes during the long recalcitrant period in terms of vacuolar status and water transport. Horse chestnut (Aesculus hippocastanum) seeds sampled in Moscow were stratified in cold wet sand for 4 months. Vacuole presence and development in embryonic axes were examined by vital staining, light and electron microscopy. Aquaporins and vacuolar H(+)-ATPase were identified immunochemically. Water channel operation was tested by water inflow rate. Vacuolar acid invertase was estimated in terms of activity and electrophoretic properties. Throughout the long recalcitrant period after seed shedding, cells of embryonic axes maintained active vacuoles and a high water content. Preservation of enzyme machinery in vacuoles was evident from retention of invertase activity, substrate specificity, molecular mass and subunit composition. Plasmalemma and tonoplast aquaporins and the E subunit of vacuolar H(+)-ATPase were also present. In non-dormant seeds prior to growth initiation, vacuoles enlarged at first in hypocotyls, and then in radicles, with their biogenesis being similar. Vacuolation was accompanied by increasing invertase activity, leading to sugar accumulation and active osmotic functioning. After growth initiation, vacuole enlargement was favoured by enhanced water inflow through water channels formed by aquaporins. Maintenance of high water content and desiccation sensitivity, as well as preservation of active vacuoles in embryonic axes after shedding, can be considered a specific feature of recalcitrant seeds, overlooked when studying tropical recalcitrants due

Vacuolar status and water relations in embryonic axes of recalcitrant Aesculus hippocastanum seeds during stratification and early germination

PubMed Central

Obroucheva, Natalie V.; Lityagina, Snezhana V.; Novikova, Galina V.; Sin'kevich, Irina A.

2012-01-01

Backgrounds and aims In tropical recalcitrant seeds, their rapid transition from shedding to germination at high hydration level is of physiological interest but difficult to study because of the time constraint. In recalcitrant horse chestnut seeds produced in central Russia, this transition is much longer and extends through dormancy and dormancy release. This extended time period permits studies of the water relations in embryonic axes during the long recalcitrant period in terms of vacuolar status and water transport. Methodology Horse chestnut (Aesculus hippocastanum) seeds sampled in Moscow were stratified in cold wet sand for 4 months. Vacuole presence and development in embryonic axes were examined by vital staining, light and electron microscopy. Aquaporins and vacuolar H+-ATPase were identified immunochemically. Water channel operation was tested by water inflow rate. Vacuolar acid invertase was estimated in terms of activity and electrophoretic properties. Principal results Throughout the long recalcitrant period after seed shedding, cells of embryonic axes maintained active vacuoles and a high water content. Preservation of enzyme machinery in vacuoles was evident from retention of invertase activity, substrate specificity, molecular mass and subunit composition. Plasmalemma and tonoplast aquaporins and the E subunit of vacuolar H+-ATPase were also present. In non-dormant seeds prior to growth initiation, vacuoles enlarged at first in hypocotyls, and then in radicles, with their biogenesis being similar. Vacuolation was accompanied by increasing invertase activity, leading to sugar accumulation and active osmotic functioning. After growth initiation, vacuole enlargement was favoured by enhanced water inflow through water channels formed by aquaporins. Conclusions Maintenance of high water content and desiccation sensitivity, as well as preservation of active vacuoles in embryonic axes after shedding, can be considered a specific feature of recalcitrant

UTX regulates mesoderm differentiation of embryonic stem cells independent of H3K27 demethylase activity.

PubMed

Wang, Chaochen; Lee, Ji-Eun; Cho, Young-Wook; Xiao, Ying; Jin, Qihuang; Liu, Chengyu; Ge, Kai

2012-09-18

To investigate the role of histone H3K27 demethylase UTX in embryonic stem (ES) cell differentiation, we have generated UTX knockout (KO) and enzyme-dead knock-in male ES cells. Deletion of the X-chromosome-encoded UTX gene in male ES cells markedly decreases expression of the paralogous UTY gene encoded by Y chromosome, but has no effect on global H3K27me3 level, Hox gene expression, or ES cell self-renewal. However, UTX KO cells show severe defects in mesoderm differentiation and induction of Brachyury, a transcription factor essential for mesoderm development. Surprisingly, UTX regulates mesoderm differentiation and Brachyury expression independent of its enzymatic activity. UTY, which lacks detectable demethylase activity, compensates for the loss of UTX in regulating Brachyury expression. UTX and UTY bind directly to Brachyury promoter and are required for Wnt/β-catenin signaling-induced Brachyury expression in ES cells. Interestingly, male UTX KO embryos express normal levels of UTY and survive until birth. In contrast, female UTX KO mice, which lack the UTY gene, show embryonic lethality before embryonic day 11.5. Female UTX KO embryos show severe defects in both Brachyury expression and embryonic development of mesoderm-derived posterior notochord, cardiac, and hematopoietic tissues. These results indicate that UTX controls mesoderm differentiation and Brachyury expression independent of H3K27 demethylase activity, and suggest that UTX and UTY are functionally redundant in ES cell differentiation and early embryonic development.

Clinical and demographic risk factors associated with mortality during early adulthood in a population-based cohort of childhood-onset type 1 diabetes.

PubMed

Cooper, M N; de Klerk, N H; Jones, T W; Davis, E A

2014-12-01

To calculate standardized mortality ratios and to assess the association between paediatric clinical factors and higher risk of mortality during early adulthood in a population-based cohort of subjects with Type 1 diabetes. Subjects with Type 1 diabetes were identified through the Western Australian Children's Diabetes Database and clinical data for those who reached 18 years of age (n = 1309) were extracted. An age- and sex-matched (without diabetes) comparison cohort (n = 6451) was obtained from the birth registry. Mortality records were obtained from the death registry. Participants were followed up until 31 January 2012. Associations of clinical factors (from clinic visits before 18 years of age) with mortality were assessed using Cox proportional hazard models. The standardized mortality ratio for all-cause mortality was 1.7 (95% CI 0.7-3.3) for male and 10.1 (95% CI 5.2-17.7) for female subjects with Type 1 diabetes (median age at end of study 25.6 years). The adjusted hazard ratio was 1.5 (95% CI 1.1-2.1) for a 1% increase in mean paediatric HbA1c level, 3.8 (95% CI 0.9-15.3) for four episodes of severe hypoglycaemia relative to zero episodes, and 6.21 (95% CI 1.4-28.4) for a low-level socio-economic background relative to a high-level background. People with childhood-onset Type 1 diabetes have higher mortality rates in early adulthood. At particularly high risk are women, those with a history of poor HbA1c levels, those with recurrent severe hypoglycaemia during paediatric management, and those from a low socio-economic background. These groups may benefit from intensified management during transition from paediatric to adult care facilities. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

Embryonic senescence and laminopathies in a progeroid zebrafish model.

PubMed

Koshimizu, Eriko; Imamura, Shintaro; Qi, Jie; Toure, Jamal; Valdez, Delgado M; Carr, Christopher E; Hanai, Jun-ichi; Kishi, Shuji

2011-03-30

Mutations that disrupt the conversion of prelamin A to mature lamin A cause the rare genetic disorder Hutchinson-Gilford progeria syndrome and a group of laminopathies. Our understanding of how A-type lamins function in vivo during early vertebrate development through aging remains limited, and would benefit from a suitable experimental model. The zebrafish has proven to be a tractable model organism for studying both development and aging at the molecular genetic level. Zebrafish show an array of senescence symptoms resembling those in humans, which can be targeted to specific aging pathways conserved in vertebrates. However, no zebrafish models bearing human premature senescence currently exist. We describe the induction of embryonic senescence and laminopathies in zebrafish harboring disturbed expressions of the lamin A gene (LMNA). Impairments in these fish arise in the skin, muscle and adipose tissue, and sometimes in the cartilage. Reduced function of lamin A/C by translational blocking of the LMNA gene induced apoptosis, cell-cycle arrest, and craniofacial abnormalities/cartilage defects. By contrast, induced cryptic splicing of LMNA, which generates the deletion of 8 amino acid residues lamin A (zlamin A-Δ8), showed embryonic senescence and S-phase accumulation/arrest. Interestingly, the abnormal muscle and lipodystrophic phenotypes were common in both cases. Hence, both decrease-of-function of lamin A/C and gain-of-function of aberrant lamin A protein induced laminopathies that are associated with mesenchymal cell lineages during zebrafish early development. Visualization of individual cells expressing zebrafish progerin (zProgerin/zlamin A-Δ37) fused to green fluorescent protein further revealed misshapen nuclear membrane. A farnesyltransferase inhibitor reduced these nuclear abnormalities and significantly prevented embryonic senescence and muscle fiber damage induced by zProgerin. Importantly, the adult Progerin fish survived and remained fertile with

Zika Virus Selectively Kills Aggressive Human Embryonal CNS Tumor Cells In Vitro and In Vivo.

PubMed

Kaid, Carolini; Goulart, Ernesto; Caires-Júnior, Luiz C; Araujo, Bruno H S; Soares-Schanoski, Alessandra; Bueno, Heloisa M S; Telles-Silva, Kayque A; Astray, Renato M; Assoni, Amanda F; Júnior, Antônio F R; Ventini, Daniella C; Puglia, Ana L P; Gomes, Roselane P; Zatz, Mayana; Okamoto, Oswaldo K

2018-06-15

Zika virus (ZIKV) is largely known for causing brain abnormalities due to its ability to infect neural progenitor stem cells during early development. Here, we show that ZIKV is also capable of infecting and destroying stem-like cancer cells from aggressive human embryonal tumors of the central nervous system (CNS). When evaluating the oncolytic properties of Brazilian Zika virus strain (ZIKV BR ) against human breast, prostate, colorectal, and embryonal CNS tumor cell lines, we verified a selective infection of CNS tumor cells followed by massive tumor cell death. ZIKV BR was more efficient in destroying embryonal CNS tumorspheres than normal stem cell neurospheres. A single intracerebroventricular injection of ZIKV BR in BALB/c nude mice bearing orthotopic human embryonal CNS tumor xenografts resulted in a significantly longer survival, decreased tumor burden, fewer metastasis, and complete remission in some animals. Tumor cells closely resembling neural stem cells at the molecular level with activated Wnt signaling were more susceptible to the oncolytic effects of ZIKV BR Furthermore, modulation of Wnt signaling pathway significantly affected ZIKV BR -induced tumor cell death and viral shedding. Altogether, these preclinical findings indicate that ZIKV BR could be an efficient agent to treat aggressive forms of embryonal CNS tumors and could provide mechanistic insights regarding its oncolytic effects. Significance: Brazilian Zika virus strain kills aggressive metastatic forms of human CNS tumors and could be a potential oncolytic agent for cancer therapy. Cancer Res; 78(12); 3363-74. ©2018 AACR . ©2018 American Association for Cancer Research.

Single nucleotide polymorphisms in candidate genes associated with fertilizing ability of sperm and subsequent embryonic development in cattle

USDA-ARS?s Scientific Manuscript database

Fertilization and development of the preimplantation embryo is under genetic control. The goal of the current study was to test 434 single nucleotide polymorphisms (SNPs) for association with genetic variation in fertilization and early embryonic development. The approach was to produce embryos from...

Awareness that early cancer lump is painless could decrease breast cancer mortality in developing countries.

PubMed

Garg, Pankaj

2016-06-10

There are several factors which contribute to patients' reporting late to healthcare facility even after detecting the breast lump (patient delay). Amongst these, one of the important factors in low- and middle-income countries is lack of awareness that early cancer lump is painless (ECLIPs). Pain is often taken as a danger sign and absence of pain is often not taken seriously. The studies have shown that up to 98% of women in low-income countries are unaware that a painless lump could be a warning sign of early breast cancer. This fact is significant because this could be one of the prime reasons for the women having discovered a painless lump in the breast, accidentally or by breast self-examination, presume it to be harmless and don't report early to health care facility. Therefore, creating awareness about ECLIPs could be an effective strategy to reduce mortality due to breast cancer in low- and middle-income countries. Moreover, unlike modifying risk factors which requires long term behavior modification, creating awareness about ECLIPs is easy and cost effective.

RETRACTED: Effect of early versus late or no tracheostomy on mortality of critically ill patients receiving mechanical ventilation: a systematic review and meta-analysis.

PubMed

Siempos, Ilias I; Ntaidou, Theodora K; Filippidis, Filippos T; Choi, Augustine M K

2014-06-26

Delay of tracheostomy for roughly 2 weeks after translaryngeal intubation of critically ill patients is the presently recommended practice and is supported by findings from large trials. However, these trials were suboptimally powered to detect small but clinically important effects on mortality. We aimed to assess the mortality benefit of early versus late or no tracheostomy in critically ill patients who need mechanical ventilation. We systematically searched PubMed, CINAHL, Embase, Web of Science, DOAJ, the Cochrane Library, references of relevant articles, scientific conference proceedings, and grey literature up to Aug 31, 2013, to identify randomised controlled trials comparing early tracheostomy (done within 1 week after translaryngeal intubation) with late (done any time after the first week of mechanical ventilation) or no tracheostomy and reporting on mortality or incidence of pneumonia in critically ill patients under mechanical ventilation. Our primary outcomes were all-cause mortality during the stay in the intensive-care unit and incidence of ventilator-associated pneumonia. We calculated pooled odds ratios (OR), pooled risk ratios (RR), and 95% CIs with a random-effects model. All but complications analyses were done on an intention-to-treat basis. Analyses of 13 trials (2434 patients, 800 deaths) showed that all-cause mortality in the intensive-care unit was significantly lower in patients assigned to the early versus the late or no tracheostomy group (OR 0·72, 95% CI 0·53-0·98; p=0·04). This finding represents an 18% reduction in the relative risk of death, translating to a 5% absolute improvement in survival (from 65% to 70%). This result persisted when we considered only trials with a low risk of bias (663 deaths; OR 0·68, 95% CI 0·49-0·95; p=0·02; eight trials with 1934 patients). There was no evidence of a difference between the compared groups for 1-year mortality (788 deaths; RR 0·93, 95% CI 0·85-1·02; p=0·14; three trials with

Effects of tributyltin on early life-stage, reproduction, and gonadal sex differentiation in Japanese medaka (Oryzias latipes).

PubMed

Horie, Yoshifumi; Yamagishi, Takahiro; Shintaku, Yoko; Iguchi, Taisen; Tatarazako, Norihisa

2018-07-01

Tributyltin, an organotin compound, was used worldwide as an antifouling agent in aquatic environments and there has been much concern about the toxicological and ecotoxicological properties of organotin compounds. Even though it has been prohibited worldwide, tributyltin is still detected at low concentrations in aquatic environments. Here we investigated the effects of tributyltin on the early life-stage, reproduction, and gonadal sex differentiation in Japanese medaka (Oryzias latipes). In adults, exposure to tributyltin at 3.82 μg/L suppressed fecundity and fertility and increased mortality. At 10.48 μg/L all medaka died by the sixth day of exposure. Exposure to tributyltin during early life-stages induced no significant differences in mortality or embryonic development, but growth was suppressed in groups exposed to 0.13 and 0.68 μg/L. Furthermore, there was no abnormal gonadal development in Japanese medaka exposed to tributyltin. These results provide evidence of the negative effects of tributyltin on reproduction in a teleost fish. Tributyltin did not affect gonadal sex differentiation in Japanese medaka, but fecundity and fertility were suppressed, although it is not clear whether this suppression resulted from the endocrine-disrupting action of tributyltin or its toxicity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Morphogenetic Implications of Peristalsis-Driven Fluid Flow in the Embryonic Lung

PubMed Central

Bokka, Kishore K.; Jesudason, Edwin C.; Lozoya, Oswaldo A.; Guilak, Farshid; Warburton, David; Lubkin, Sharon R.

2015-01-01

Epithelial organs are almost universally secretory. The lung secretes mucus of extremely variable consistency. In the early prenatal period, the secretions are of largely unknown composition, consistency, and flow rates. In addition to net outflow from secretion, the embryonic lung exhibits transient reversing flows from peristalsis. Airway peristalsis (AP) begins as soon as the smooth muscle forms, and persists until birth. Since the prenatal lung is liquid-filled, smooth muscle action can transport fluid far from the immediately adjacent tissues. The sensation of internal fluid flows has been shown to have potent morphogenetic effects, as has the transport of morphogens. We hypothesize that these effects play an important role in lung morphogenesis. To test these hypotheses in a quantitative framework, we analyzed the fluid-structure interactions between embryonic tissues and lumen fluid resulting from peristaltic waves that partially occlude the airway. We found that if the airway is closed, fluid transport is minimal; by contrast, if the trachea is open, shear rates can be very high, particularly at the stenosis. We performed a parametric analysis of flow characteristics' dependence on tissue stiffnesses, smooth muscle force, geometry, and fluid viscosity, and found that most of these relationships are governed by simple ratios. We measured the viscosity of prenatal lung fluid with passive bead microrheology. This paper reports the first measurements of the viscosity of embryonic lung lumen fluid. In the range tested, lumen fluid can be considered Newtonian, with a viscosity of 0.016 ± 0.008 Pa-s. We analyzed the interaction between the internal flows and diffusion and conclude that AP has a strong effect on flow sensing away from the tip and on transport of morphogens. These effects may be the intermediate mechanisms for the enhancement of branching seen in occluded embryonic lungs. PMID:26147967

Lethal and Sublethal Effects of the Herbicide Atrazine in the Early Stages of Development of Physalaemus gracilis (Anura: Leptodactylidae).

PubMed

Rutkoski, Camila F; Macagnan, Natani; Kolcenti, Cassiane; Vanzetto, Guilherme V; Sturza, Paola F; Hartmann, Paulo A; Hartmann, Marilia T

2018-05-01

Water sources used as reproductive sites by crying frog, Physalaemus gracilis, are extensively associated with agroecosystems in which the herbicide atrazine is employed. To evaluate the lethal and sublethal effects of atrazine commercial formulation, acute and chronic toxicity tests were performed in the embryonic phase and the beginning of the larval phase of P. gracilis. Tests were started on stage 19 of Gosner (Herpetologica 16:183-190, 1960) and performed in 24-well cell culture plates. Acute tests had a duration of 96 h with embryo mortality monitoring every 24 h. Chronic assays contemplated the transition from the embryonic to larval stages and lasted 168 h. Every 24 h the embryos/larvae were observed for mortality, mobility, and malformations. The LC50 of atrazine determined for P. gracilis embryos was 229.34 mg L -1 . The sublethal concentrations did not affect the development of the larvae but were observed effects on mobility and malformations, such as spasmodic contractions, reduced mobility, malformations in mouth and intestine, and edema arising. From 1 mg L -1 atrazine, the exposed larvae began to have changes in mobility and malformations. The atrazine commercial formulation has caused early life effects of P. gracilis that may compromise the survival of this species but at higher concentrations than recorded in the environment, so P. gracilis can be considered tolerant to this herbicide at environmentally relevant concentrations.

Effects of Krenite? brush control agent (fosamine ammonium) on embryonic development in mallards and bobwhite

USGS Publications Warehouse

Hoffman, D.J.

1988-01-01

Fosamine ammonium (Krenite) is a highly water-soluble carbamoylphosphonate herbicide used to control woody brush. It has been reported to be teratogenic to avian embryos following spray application of the eggs. The embryotoxic and teratogenic potential of Krenite was examined in mallards (Anas platyrhynchos) and bobwhite (Colinus virginianus). At 96 h of development, eggs were briefly immersed in distilled water or in Krenite formulation in distilled water at concentrations of 1.5, 6.5, or 30% fosamine ammonium. At 6.5% active ingredient (a.i.), Krenite reduced hatching success in bobwhite and mallards to 85 and 33% of that in the distilled-water controls. At 30% a.i., Krenite caused 95 to 100% mortality in both species by the time of hatching. Early embryonic growth was impaired by 30% Krenite in both species. There was no evidence of teratogenesis of the axial skeleton, as reported previously in chickens and Japanese quail (Coturnix japonica). Most abnormal embryos had severe edema and some stunting. Mallard hatchlings from the 1.5 and 6.5% Krenite groups weighed significantly less than controls and had lower plasma alanine aminotransferase and aspartate aminotransferase activities, with elevated plasma glucose and cholesterol concentrations. Brain acetylcholinesterase activity was unaffected by Krenite in embryos and hatchlings.

Establishment of autologous embryonic stem cells derived from preantral follicle culture and oocyte parthenogenesis.

PubMed

Lee, Seung Tae; Choi, Mun Hwan; Lee, Eun Ju; Gong, Seung Pyo; Jang, Mi; Park, Sang Hyun; Jee, Hyang; Kim, Dae Yong; Han, Jae Yong; Lim, Jeong Mook

2008-11-01

To evaluate whether autologous embryonic stem cells can be established without generating clone embryos. Prospective model study. Gamete and stem cell biotechnology laboratory in Seoul National University, Seoul, Korea. F1 hybrid B6D2F1 mice. Preantral follicles were cultured, and oocytes matured in the follicles were parthenogenetically activated. Preimplantation development and stem cell characterization. More intrafollicular oocytes that were retrieved from secondary follicles matured and developed into blastocysts after parthenogenesis than those that were retrieved from primary follicles. Of those 35 blastocysts derived from 193 parthenotes, one line of colony-forming cells was established from the culturing of early secondary follicles. The established cells were positive for embryonic stem cell-specific markers and had normal diploid karyotype and telomerase activity. They differentiated into embryoid bodies in vitro and teratomas in vivo. Inducible differentiation of the established cells into neuronal lineage cells also was possible. Autologous embryonic stem cells can be established by preantral follicle culture and oocyte parthenogenesis. A combined technique of follicle culture and oocyte parthenogenesis that does not use developmentally competent oocytes has the potential to replace somatic cell nuclear transfer for autologous cell therapy.

Effect of season, late embryonic mortality and progesterone production on pregnancy rates in pluriparous buffaloes (Bubalus bubalis) after artificial insemination with sexed semen.

PubMed

Campanile, Giuseppe; Vecchio, Domenico; Neglia, Gianluca; Bella, Antonino; Prandi, Alberto; Senatore, Elena M; Gasparrini, Bianca; Presicce, Giorgio A

2013-03-01

The use of sexed semen technology in buffaloes is nowadays becoming more and more accepted by farmers, to overcome the burden of unwanted male calves with related costs and to more efficiently improve production and genetic gain. The aim of this study was to verify the coupling of some variables on the efficiency of pregnancy outcome after deposition of sexed semen through AI. Pluriparous buffaloes from two different farms (N = 152) were screened, selected, and subjected to Ovsynch protocol for AI using nonsexed and sexed semen from four tested bulls. AI was performed in two distinct periods of the year: September to October and January to February. Neither farms nor bulls had a significant effect on pregnancy rates pooled from the two periods. The process for sexing sperm cells did not affect pregnancy rates at 28 days after AI, for nonsexed and sexed semen, respectively 44/73 (60.2%) and 50/79 (63.2%), P = 0.70, and at 45 days after AI, for nonsexed and sexed semen, respectively 33/73 (45.2%) and 33/79 (49.3%), P = 0.60. Pregnancy rate at 28 days after AI during the transitional period of January to February was higher when compared with September to October, respectively 47/67 (70.1%) versus 47/85 (55.2%), P = 0.06. When the same pregnant animals were checked at Day 45 after AI, the difference disappeared between the two periods, because of a higher embryonic mortality, respectively 32/67 (47.7%) versus 40/85 (47.0%), P = 0.93. Hematic progesterone concentration at Day 10 after AI did not distinguish animals pregnant at Day 28 that would or would not maintain pregnancy until Day 45 (P = 0.21). On the contrary, when blood samples were taken at Day 20 after AI, the difference in progesterone concentration between pregnant animals that would maintain their pregnancy until Day 45 was significant for both pooled (P = 0.00) and nonsexed (P = 0.00) and sexed semen (P = 0.09). A similar trend was reported when blood samples were taken at Day 25, being highly significant

Gene expression dynamics during embryonic development in rainbow trout

USDA-ARS?s Scientific Manuscript database

The supply of maternal RNAs in fertilized egg and activation of embryonic genome during maternal-zygotic transition (MZT) are important for normal embryonic development. In order to identify genes and gene products that are essential in the regulation of embryonic development in rainbow trout, RNA-S...

Effects of dieldrin treatment on physiological and biochemical aspects of the toad embryonic development

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

Gauna, L.; Caballero de Castro, A.; Chifflet de Llamas, M.

1991-04-01

Dieldrin is a cylclodiene insecticide highly persistent in nature due to its chemical stability. The exposure of toad embryos to Dieldrin induces hyperactivity in the swimming larvae and inhibition of cholinesterases. However, the inhibition of these enzymes during early development is not life threatening. The present report provides a physiological and biochemical study of the noxious effect of Dieldrin on the toad embryonic development.

Epidemiology and predictive factors for early and late mortality in Candida bloodstream infections: a population-based surveillance in Spain.

PubMed

Puig-Asensio, M; Padilla, B; Garnacho-Montero, J; Zaragoza, O; Aguado, J M; Zaragoza, R; Montejo, M; Muñoz, P; Ruiz-Camps, I; Cuenca-Estrella, M; Almirante, B

2014-04-01

A prospective, multicentre, population-based surveillance programme for Candida bloodstream infections was implemented in five metropolitan areas of Spain to determine its incidence and the prevalence of antifungal resistance, and to identify predictors of death. Between May 2010 and April 2011, Candida isolates were centralized to a reference laboratory for species identification by DNA sequencing and for susceptibility testing by EUCAST reference procedure. Prognostic factors associated with early (0-7 days) and late (8-30 days) death were analysed using logistic regression modelling. We detected 773 episodes: annual incidence of 8.1 cases/100 000 inhabitants, 0.89/1000 admissions and 1.36/10 000 patient-days. Highest incidence was found in infants younger than 1 year (96.4/100 000 inhabitants). Candida albicans was the predominant species (45.4%), followed by Candida parapsilosis (24.9%), Candida glabrata (13.4%) and Candida tropicalis (7.7%). Overall, 79% of Candida isolates were susceptible to fluconazole. Cumulative mortality at 7 and 30 days after the first episode of candidaemia was 12.8% and 30.6%, respectively. Multivariate analysis showed that therapeutic measures within the first 48 h may improve early mortality: antifungal treatment (OR 0.51, 95% CI 0.27-0.95) and central venous catheter removal (OR 0.43, 95% CI 0.21-0.87). Predictors of late death included host factors (e.g. patients' comorbid status and signs of organ dysfunction), primary source (OR 1.63, 95% CI 1.03-2.61), and severe sepsis or septic shock (OR 1.77, 95% CI 1.05-3.00). In Spain, the proportion of Candida isolates non-susceptible to fluconazole is higher than in previous reports. Early mortality may be improved with strict adherence to guidelines. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

Paf receptor expression in the marsupial embryo and endometrium during embryonic diapause.

PubMed

Fenelon, Jane C; Shaw, Geoff; O'Neill, Chris; Frankenberg, Stephen; Renfree, Marilyn B

2014-01-01

The control of reactivation from embryonic diapause in the tammar wallaby (Macropus eugenii) involves sequential activation of the corpus luteum, secretion of progesterone that stimulates endometrial secretion and subsequent changes in the uterine environment that activate the embryo. However, the precise signals between the endometrium and the blastocyst are currently unknown. In eutherians, both the phospholipid Paf and its receptor, platelet-activating factor receptor (PTAFR), are present in the embryo and the endometrium. In the tammar, endometrial Paf release in vitro increases around the time of the early progesterone pulse that occurs around the time of reactivation, but whether Paf can reactivate the blastocyst is unknown. We cloned and characterised the expression of PTAFR in the tammar embryo and endometrium at entry into embryonic diapause, during its maintenance and after reactivation. Tammar PTAFR sequence and protein were highly conserved with mammalian orthologues. In the endometrium, PTAFR was expressed at a constant level in the glandular epithelium across all stages and in the luminal epithelium during both diapause and reactivation. Thus, the presence of the receptor appears not to be a limiting factor for Paf actions in the endometrium. However, the low levels of PTAFR in the embryo during diapause, together with its up-regulation and subsequent internalisation at reactivation, supports earlier results suggesting that endometrial Paf could be involved in reactivation of the tammar blastocyst from embryonic diapause.

The Timing of Early Antibiotics and Hospital Mortality in Sepsis.

PubMed

Liu, Vincent X; Fielding-Singh, Vikram; Greene, John D; Baker, Jennifer M; Iwashyna, Theodore J; Bhattacharya, Jay; Escobar, Gabriel J

2017-10-01

Prior sepsis studies evaluating antibiotic timing have shown mixed results. To evaluate the association between antibiotic timing and mortality among patients with sepsis receiving antibiotics within 6 hours of emergency department registration. Retrospective study of 35,000 randomly selected inpatients with sepsis treated at 21 emergency departments between 2010 and 2013 in Northern California. The primary exposure was antibiotics given within 6 hours of emergency department registration. The primary outcome was adjusted in-hospital mortality. We used detailed physiologic data to quantify severity of illness within 1 hour of registration and logistic regression to estimate the odds of hospital mortality based on antibiotic timing and patient factors. The median time to antibiotic administration was 2.1 hours (interquartile range, 1.4-3.1 h). The adjusted odds ratio for hospital mortality based on each hour of delay in antibiotics after registration was 1.09 (95% confidence interval [CI], 1.05-1.13) for each elapsed hour between registration and antibiotic administration. The increase in absolute mortality associated with an hour's delay in antibiotic administration was 0.3% (95% CI, 0.01-0.6%; P = 0.04) for sepsis, 0.4% (95% CI, 0.1-0.8%; P = 0.02) for severe sepsis, and 1.8% (95% CI, 0.8-3.0%; P = 0.001) for shock. In a large, contemporary, and multicenter sample of patients with sepsis in the emergency department, hourly delays in antibiotic administration were associated with increased odds of hospital mortality even among patients who received antibiotics within 6 hours. The odds increased within each sepsis severity strata, and the increased odds of mortality were greatest in septic shock.

N-terminal pro-brain-type natriuretic peptide (NT-pro-BNP) and mortality risk in early inflammatory polyarthritis: results from the Norfolk Arthritis Registry (NOAR)

PubMed Central

Mirjafari, Hoda; Welsh, Paul; Verstappen, Suzanne M M; Wilson, Paddy; Marshall, Tarnya; Edlin, Helena; Bunn, Diane; Chipping, Jacqueline; Lunt, Mark; Symmons, Deborah P M; Sattar, Naveed; Bruce, Ian N

2014-01-01

Background We measured N-terminal pro-brain natriuretic peptide (NT-pro-BNP), a marker of cardiac dysfunction, in an inception cohort with early inflammatory polyarthritis (IP) and assessed its association with disease phenotype, cardiovascular disease (CVD), all-cause and CVD related mortality. Methods Subjects with early IP were recruited to the Norfolk Arthritis Register from January 2000 to December 2008 and followed up to death or until March 2010 including any data from the national death register. The associations of baseline NT-pro-BNP with IP related factors and CVD were assessed by linear regression. Cox proportional hazards models examined the independent association of baseline NT-pro-BNP with all-cause and CVD mortality. Results We studied 960 early IP subjects; 163 (17%) had prior CVD. 373 (39%) patients had a baseline NT-pro-BNP levels ≥100 pg/ml. NT-pro-BNP was associated with age, female gender, HAQ score, CRP, current smoking, history of hypertension, prior CVD and the presence of carotid plaque. 92 (10%) IP subjects died including 31 (3%) from CVD. In an age and gender adjusted analysis, having a raised NT-pro-BNP level (≥100 pg/ml) was associated with both all-cause and CVD mortality (adjusted HR (95% CI) 2.36 (1.42 to 3.94) and 3.40 (1.28 to 9.03), respectively). These findings were robust to adjustment for conventional CVD risk factors and prevalent CVD. Conclusions In early IP patients, elevated NT-pro-BNP is related to HAQ and CRP and predicts all-cause and CVD mortality independently of conventional CVD risk factors. Further study is required to identify whether NT-pro-BNP may be clinically useful in targeting intensive interventions to IP patients at greatest risk of CVD. PMID:23511225

Periodontitis and early mortality among adults treated with hemodialysis: a multinational propensity-matched cohort study.

PubMed

Ruospo, Marinella; Palmer, Suetonia C; Wong, Germaine; Craig, Jonathan C; Petruzzi, Massimo; De Benedittis, Michele; Ford, Pauline; Johnson, David W; Tonelli, Marcello; Natale, Patrizia; Saglimbene, Valeria; Pellegrini, Fabio; Celia, Eduardo; Gelfman, Ruben; Leal, Miguel R; Torok, Marietta; Stroumza, Paul; Bednarek-Skublewska, Anna; Dulawa, Jan; Frantzen, Luc; Del Castillo, Domingo; Schon, Staffan; Bernat, Amparo G; Hegbrant, Jorgen; Wollheim, Charlotta; Gargano, Letizia; Bots, Casper P; Strippoli, Giovanni Fm

2017-05-22

Periodontitis is associated with cardiovascular mortality in the general population and adults with chronic diseases. However, it is unclear whether periodontitis predicts survival in the setting of kidney failure. ORAL-D was a propensity matched analysis in 3338 dentate adults with end-stage kidney disease treated in a hemodialysis network in Europe and South America designed to examine the association between periodontitis and all-cause and cardiovascular-related mortality in people on long-term hemodialysis. Participants were matched 1:1 on their propensity score for moderate to severe periodontitis assessed using the World Health Organization Community Periodontal Index. A random-effects Cox proportional hazards model was fitted with shared frailty to account for clustering of mortality risk within countries. Among the 3338 dentate participants, 1355 (40.6%) had moderate to severe periodontitis at baseline. After using propensity score methods to generate a matched cohort of participants with periodontitis similar to those with none or mild periodontal disease, moderate to severe periodontitis was associated with a lower risk of all-cause (9.1 versus 13.0 per 100 person years, hazard ratio 0.74, 95% confidence interval 0.61 to 0.90) and cardiovascular (4.3 versus 6.9 per 100 person years, hazard ratio 0.67, 0.51 to 0.88) mortality. These associations were not changed substantially when participants were limited to those with 12 or more natural teeth and when accounting for competing causes of cardiovascular death. In contrast to the general population, periodontitis does not appear to be associated with an increased risk of early death in adults treated with hemodialysis.

Giant intrascrotal embryonal rhabdomyosarcoma in an adult: a case report and review of the literature.

PubMed

Gong, Wentao; Gao, Qingqiang; Xu, Zhipeng; Dai, Yutian

2018-05-28

Intrascrotal embryonal rhabdomyosarcoma in adults is a rare tumor with high aggression and a poor prognosis. We report our patient's case and review the relevant literature to improve the understanding of this rare disease. A 21-year-old Han Chinese man presented to our hospital with a right intrascrotal mass of 1 year's duration. His physical examination revealed an enlarged right scrotum containing a huge tender mass measuring about 10 × 7 cm. Ordinary and contrast-enhanced ultrasonography showed a solid mass in the right scrotum, which was suspected to be a malignant tumor. An abdominopelvic computed tomographic scan revealed metastases in the retroperitoneal lymph nodes. The patient was diagnosed with malignant testicular tumor and underwent a right radical orchiectomy by an inguinal approach. Postoperative pathological examination suggested an intrascrotal embryonal rhabdomyosarcoma. Intrascrotal embryonal rhabdomyosarcoma is a rare but highly aggressive tumor. Clinical and imaging manifestations of this tumor are nonspecific, so the definitive diagnosis depends on postoperative pathology and immunohistochemistry. Early suspicion, radical orchiectomy, accurate pathologic diagnosis, and adjuvant chemotherapy and/or radiotherapy are the keys to optimal prognosis.

Scaffolding for Three-Dimensional Embryonic Vasculogenesis

NASA Astrophysics Data System (ADS)

Kraehenbuehl, Thomas P.; Aday, Sezin; Ferreira, Lino S.

Biomaterial scaffolds have great potential to support efficient vascular differentiation of embryonic stem cells. Vascular cell fate-specific biochemical and biophysical cues have been identified and incorporated into three-dimensional (3D) biomaterials to efficiently direct embryonic vasculogenesis. The resulting vascular-like tissue can be used for regenerative medicine applications, further elucidation of biophysical and biochemical cues governing vasculogenesis, and drug discovery. In this chapter, we give an overview on the following: (1) developmental cues for directed differentiation of human embryonic stem cells (hESCs) into vascular cells, (2) 3D vascular differentiation in embryoid bodies (EBs), (3) preparation of 3D scaffolds for the vascular differentiation of hESCs, and (4) the most significant studies combining scaffolding and hESCs for development of vascular-like tissue.

High Exercise Capacity Attenuates the Risk of Early Mortality After a First Myocardial Infarction: The Henry Ford Exercise Testing (FIT) Project.

PubMed

Shaya, Gabriel E; Al-Mallah, Mouaz H; Hung, Rupert K; Nasir, Khurram; Blumenthal, Roger S; Ehrman, Jonathan K; Keteyian, Steven J; Brawner, Clinton A; Qureshi, Waqas T; Blaha, Michael J

2016-02-01

To examine the effect of objectively measured exercise capacity (EC) on early mortality (EM) after a first myocardial infarction (MI). This retrospective cohort study included 2061 patients without a history of MI (mean age, 62±12 years; 38% [n=790] women; 56% [n=1153] white) who underwent clinical treadmill stress testing in the Henry Ford Health System from January 1, 1991, through May 31, 2009, and suffered MI during follow-up (MI event proportion, 3.4%; mean time from the exercise test to MI, 6.1±4.3 years). Exercise capacity was categorized on the basis of peak metabolic equivalents (METs) achieved: less than 6, 6 to 9, 10 to 11, and 12 or more METs. Early mortality was defined as all-cause mortality within 28, 90, or 365 days of MI. Multivariable logistic regression models were used to assess the effect of EC on the risk of mortality at each time point post-MI adjusting for baseline demographic characteristics, cardiovascular risk factors, medication use, indication for stress testing, and year of MI. The 28-day EM rate was 10.6% overall, and 13.9%, 10.7%, 6.9%, and 6.0% in the less than 6, 6 to 9, 10 to 11, and 12 or more METs categories, respectively (P<.001). Patients who died were more likely to be older, be less fit, be nonobese, have treated hypertension, and have a longer duration from baseline to incident MI (P<.05). Adjusted regression analyses revealed a decreased risk of EM with increasing EC categories. A 1-MET higher EC was associated with an 8% to 10% lower risk of mortality across all time points (28 days: odds ratio [OR], 0.92; 95% CI, 0.87-0.98; P=.006; 90 days: OR, 0.90; 95% CI, 0.86-0.95; P<.001; 365 days: OR, 0.91; 95% CI, 0.87-0.94; P<.001). Higher baseline EC was independently associated with a lower risk of early death after a first MI. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Rapamycin efficiently promotes cardiac differentiation of mouse embryonic stem cells.

PubMed

Lu, Qin; Liu, Yinan; Wang, Yang; Wang, Weiping; Yang, Zhe; Li, Tao; Tian, Yuyao; Chen, Ping; Ma, Kangtao; Jia, Zhuqing; Zhou, Chunyan

2017-06-30

To investigate the effects of rapamycin on cardiac differentiation, murine embryonic stem cells (ESCs) were induced into cardiomyocytes by 10 -4 M ascorbic acid (AA), 20 nM rapamycin alone or 0.01% solvent DMSO. We found that rapamycin alone was insufficient to initiate cardiomyogenesis. Then, the ESCs were treated with AA and rapamycin (20 nM) or AA and DMSO (0.01%) as a control. Compared with control, mouse ESCs (mESCs) treated with rapamycin (20 nM) and AA yielded a significantly higher percentage of cardiomyocytes, as confirmed by the percentage of beating embryonic bodies (EBs), the immunofluorescence and FACS analysis. Rapamycin significantly increased the expression of a panel of cardiac markers including Gata 4, α- Mhc , β- Mhc , and Tnnt 2. Additionally, rapamycin enhanced the expression of mesodermal and cardiac transcription factors such as Mesp 1, Brachyury T, Eomes, Isl 1 , Gata 4 , Nkx 2.5 , Tbx 5, and Mef2c. Mechanistic studies showed that rapamycin inhibits Wnt/β-catenin and Notch signaling but promotes the expression of fibroblast growth factor ( Fgf 8), Fgf 10, and Nodal at early stage, and bone morphogenetic protein 2 ( Bmp 2) at later stages. Sequential treatment of rapamycin showed that rapamycin promotes cardiac differentiation at the early and later stages. Interestingly, another mammalian target of rapamycin (mTOR) inhibitor Ku0063794 (1 µM) had similar effects on cardiomyogenesis. In conclusion, our results highlight a practical approach to generate cardiomyocytes from mESCs by rapamycin. © 2017 The Author(s).

Regulation of early Xenopus development by ErbB signaling

PubMed Central

Nie, Shuyi; Chang, Chenbei

2008-01-01

ErbB signaling has long been implicated in cancer formation and progression and is shown to regulate cell division, migration and death during tumorigenesis. The functions of the ErbB pathway during early vertebrate embryogenesis, however, are not well understood. Here we report characterization of ErbB activities during early frog development. Gain-of-function analyses show that EGFR, ErbB2 and ErbB4 induce ectopic tumor-like cell mass that contains increased numbers of mitotic cells. Both the muscle and the neural markers are expressed in these ectopic protrusions. ErbBs also induce mesodermal markers in ectodermal explants. Loss-of-function studies using carboxyl terminal-truncated dominant-negative ErbB receptors demonstrate that blocking ErbB signals leads to defective gastrulation movements and malformation of the embryonic axis with a reduction in the head structures in early frog embryos. These data, together with the observation that ErbBs are expressed early during frog embryogenesis, suggest that ErbBs regulate cell proliferation, movements and embryonic patterning during early Xenopus development. PMID:16258939

Structural requirements for PACSIN/Syndapin operation during zebrafish embryonic notochord development.

PubMed

Edeling, Melissa A; Sanker, Subramaniam; Shima, Takaki; Umasankar, P K; Höning, Stefan; Kim, Hye Y; Davidson, Lance A; Watkins, Simon C; Tsang, Michael; Owen, David J; Traub, Linton M

2009-12-03

PACSIN/Syndapin proteins are membrane-active scaffolds that participate in endocytosis. The structure of the Drosophila Syndapin N-terminal EFC domain reveals a crescent shaped antiparallel dimer with a high affinity for phosphoinositides and a unique membrane-inserting prong upon the concave surface. Combined structural, biochemical and reverse genetic approaches in zebrafish define an important role for Syndapin orthologue, Pacsin3, in the early formation of the notochord during embryonic development. In pacsin3-morphant embryos, midline convergence of notochord precursors is defective as axial mesodermal cells fail to polarize, migrate and differentiate properly. The pacsin3 morphant phenotype of a stunted body axis and contorted trunk is rescued by ectopic expression of Drosophila Syndapin, and depends critically on both the prong that protrudes from the surface of the bowed Syndapin EFC domain and the ability of the antiparallel dimer to bind tightly to phosphoinositides. Our data confirm linkage between directional migration, endocytosis and cell specification during embryonic morphogenesis and highlight a key role for Pacsin3 in this coupling in the notochord.

Morphological and histomorphological structures of testes and ovaries in early developmental stages of the silkworm, Bombyx mori.

PubMed

Sakai, Hiroki; Kirino, Yohei; Katsuma, Susumu; Aoki, Fugaku; Suzuki, Masataka G

2016-01-01

The gonad develops as a testis in male or an ovary in female. In the silkworm, B. mori , little is known about testis and ovary in the embryonic stages and early larval stages. In this study, we performed morphological and histomorphological observations of ovaries and testes from the late embryonic stage to the 1st instar larval stage. Results obtained with lack of accurate information on sex of examined individuals may be misleading, thus we performed phenotypic observations of gonads by utilizing sex-limited strain that enables us to easily discriminate female embryos from male ones based on those egg colors. In testis, four testicular follicles were clearly observed in the testis at the first instar larval stage, and boundary layers were formed between the testicular follicles. At the late embryonic stage, the testis consisted of four testicular follicles, while the boundary layers were still obscure. In ovary, four ovarioles were easily recognizable in the ovary at the first instar larval stage, and boundary layers were formed between the ovarioles. However, in the late embryonic stage, it was quite difficult to identify four ovarioles. Morphological characteristics were almost similar between testis and ovary in early developmental stages. Our present study demonstrates that the most reliable difference between testis and ovary in early developmental stages is the attaching point of the duct. Formation and development of the duct may be sensitive to the sex-determining signal and display sexual dimorphism in early embryonic stages.

Validation of a Molecular and Pathological Model for Five-Year Mortality Risk in Patients with Early Stage Lung Adenocarcinoma

PubMed Central

Bueno, Raphael; Hughes, Elisha; Wagner, Susanne; Gutin, Alexander S.; Lanchbury, Jerry S.; Zheng, Yifan; Archer, Michael A.; Gustafson, Corinne; Jones, Joshua T.; Rushton, Kristen; Saam, Jennifer; Kim, Edward; Barberis, Massimo; Wistuba, Ignacio; Wenstrup, Richard J.; Wallace, William A.; Harrison, David J.

2015-01-01

Introduction: The aim of this study was to validate a molecular expression signature [cell cycle progression (CCP) score] that identifies patients with a higher risk of cancer-related death after surgical resection of early stage (I-II) lung adenocarcinoma in a large patient cohort and evaluate the effectiveness of combining CCP score and pathological stage for predicting lung cancer mortality. Methods: Formalin-fixed paraffin-embedded surgical tumor samples from 650 patients diagnosed with stage I and II adenocarcinoma who underwent definitive surgical treatment without adjuvant chemotherapy were analyzed for 31 proliferation genes by quantitative real-time polymerase chain reaction. The prognostic discrimination of the expression score was assessed by Cox proportional hazards analysis using 5-year lung cancer-specific death as primary outcome. Results: The CCP score was a significant predictor of lung cancer-specific mortality above clinical covariates [hazard ratio (HR) = 1.46 per interquartile range (95% confidence interval = 1.12–1.90; p = 0.0050)]. The prognostic score, a combination of CCP score and pathological stage, was a more significant indicator of lung cancer mortality risk than pathological stage in the full cohort (HR = 2.01; p = 2.8 × 10−11) and in stage I patients (HR = 1.67; p = 0.00027). Using the 85th percentile of the prognostic score as a threshold, there was a significant difference in lung cancer survival between low-risk and high-risk patient groups (p = 3.8 × 10−7). Conclusions: This study validates the CCP score and the prognostic score as independent predictors of lung cancer death in patients with early stage lung adenocarcinoma treated with surgery alone. Patients with resected stage I lung adenocarcinoma and a high prognostic score may be candidates for adjuvant therapy to reduce cancer-related mortality. PMID:25396679

Growth enhancement by embryonic fibroblasts upon cotransplantation of noncommitted pig embryonic tissues with fully committed organs.

PubMed

Cohen, Sivan; Tchorsh-Yutsis, Dalit; Aronovich, Anna; Tal, Orna; Eventov-Friedman, Smadar; Katchman, Helena; Klionsky, Yael; Shezen, Elias; Reisner, Yair

2010-05-27

We recently defined the optimal gestational time windows for the transplantation of several embryonic tissues. We showed that the liver and kidney obtained from E28 pig embryos can grow and differentiate normally after transplantation, whereas 1 week earlier in gestation, these tissues develop into teratoma-like structures or fibrotic mass. In this study, we investigated whether cotransplantation of E28 with E21 tissue could control its tumorogenic potential, or alternatively whether the stem cells derived from the earlier tissue contribute to the growth of the more committed one. Pig embryonic precursors from E21 and E28 gestational age were transplanted alone or together, into nonobese diabetic/severe combined immunodeficiency mice, and their growth and differentiation was evaluated by immunohistology. In situ analysis, based on sex disparity between the E21 and E28 tissues, was used to identify the tissue source. In some experiments, mouse embryonic fibroblasts (MEF) were cotransplanted with E28 liver, and their effect was evaluated. E28 tissues could not abrogate the propensity of the cells within the undifferentiated tissue to form teratoma-like structures. However, E21 kidney or liver tissue markedly enhanced the growth and function of E28 kidney, liver, and heart grafts. Moreover, similar growth enhancement was observed on coimplantation of E28 liver tissue with MEF or on infusion of MEF culture medium, indicating that this enhancement is likely mediated through soluble factors secreted by the fibroblasts. Our results suggest a novel approach for the enhancement of growth and differentiation of transplanted embryonic tissues by the use of soluble factors secreted by embryonic fibroblasts.

Thermally induced chronic developmental stress in coho salmon: Integrating measures of mortality, early growth and fluctuating asymmetry

USGS Publications Warehouse

Campbell, W.B.; Emlen, J.M.; Hershberger, W.K.

1998-01-01

Developmental stability, or homeostasis, facilitates the production of consistent phenotypes by buffering against stress. Fluctuating asymmetry is produced by developmental instability and is manifested as small random departures from bilateral symmetry. Increased fluctuating asymmetry is thought to parallel compromised fitness, in part, because stress promotes energy dissipation. Compensatory energy expenditures within the organism are required to complete development, thus promoting instability through reductions in homeostasis. Increased heterozygosity may enhance developmental stability by reducing energy dissipation from stress through increased metabolic efficiency, possibly by providing greater flexibility in metabolic pathways. Traditionally, fluctuating asymmetry has been used as a bioindicator of chronic stress, provided that selective mortality of less fit individuals did not reduce stress-mediated increases in fluctuating asymmetry to background levels produced by natural developmental error, or create data inconsistencies such as higher asymmetry in groups exposed to lower stress. Unfortunately, absence of selective mortality and its effects, while often assumed, can be difficult to substantiate. We integrated measures of early growth, mortality, fluctuating asymmetry (mandibular pores, pectoral finrays, pelvic finrays, and gillrakers on the upper and lower arms of the first branchial arch) and directional asymmetry (branchiostegal rays) to assess chronic thermal stress (fluctuating temperatures as opposed to ambient temperatures) in developing eggs from two different coho salmon (Oncorhynchus kisutch) stocks and their reciprocal hybrids. Hybridization provided insight on the capacity of heterozygosity to reduce stress during development. Although egg losses were consistently higher in crosses exposed to fluctuating temperatures, egg mortality was predominantly a function of maternal stock of origin. Post-hatch losses were higher in crosses exposed to

[Hospital at home: assessment of early discharge in terms of patients mortality and satisfaction].

PubMed

Damiani, G; Pinnarelli, L; Ricciardi, G

2006-01-01

New organizational models are essentials for European Hospitals because of restraining budget and ageing of population. Hospital at home is an alternative to inpatient care, effective both in clinical and economic ground. The aim of our study was to evaluate the impact of Hospital at Home in terms of decreased mortality and patient satisfaction. We carried out a meta-analysis of the literature about hospital at home interventions. We searched Medline (to December 2002), the Cochrane Controlled Trials Register (to October 2002) and other bibliographical databases, with a supplementary handsearching of literature. We used the following keywords: hospital at home, home hospitalization, mortality, patient satisfaction, cost, acute hospital care, conventional hospitalization. We included studies respecting the following criteria: analytical or experimental studies aimed at compare early discharge to hospital at home and continued care in an acute hospital. Review Manager 4.2 software was used to collect data and perform statistical analysis. We found 2420 articles searching for the chosen keywords. Twelve studies (2048 patients) were included for death outcome and six studies (1382 patients) were included for satisfaction outcome. The selected studies indicated a greater effect size of patient satisfaction in home patients than hospitalized ones (Odds Ratio: 1.58 95% CI: 1.25, 2.00) and showed no difference in terms of mortality (Risk Difference: -0.01 95% CI: -0.03, 0.02). Our results underline the effectiveness of this organizational model, as an alternative to continued care in an acute hospital. Further useful considerations could be drawn by economic evaluation studies carried out on field.

Embryonic Mutant Huntingtin Aggregate Formation in Mouse Models of Huntington's Disease.

PubMed

Osmand, Alexander P; Bichell, Terry Jo; Bowman, Aaron B; Bates, Gillian P

2016-12-15

The role of aggregate formation in the pathophysiology of Huntington's disease (HD) remains uncertain. However, the temporal appearance of aggregates tends to correlate with the onset of symptoms and the numbers of neuropil aggregates correlate with the progression of clinical disease. Using highly sensitive immunohistochemical methods we have detected the appearance of diffuse aggregates during embryonic development in the R6/2 and YAC128 mouse models of HD. These are initially seen in developing axonal tracts and appear to spread throughout the cerebrum in the early neonate.

The early Cambrian fossil embryo Pseudooides is a direct-developing cnidarian, not an early ecdysozoan.

PubMed

Duan, Baichuan; Dong, Xi-Ping; Porras, Luis; Vargas, Kelly; Cunningham, John A; Donoghue, Philip C J

2017-12-20

Early Cambrian Pseudooides prima has been described from embryonic and post-embryonic stages of development, exhibiting long germ-band development. There has been some debate about the pattern of segmentation, but this interpretation, as among the earliest records of ecdysozoans, has been generally accepted. Here, we show that the 'germ band' of P. prima embryos separates along its mid axis during development, with the transverse furrows between the 'somites' unfolding into the polar aperture of the ten-sided theca of Hexaconularia sichuanensis , conventionally interpreted as a scyphozoan cnidarian; co-occurring post-embryonic remains of ecdysozoans are unrelated. We recognize H. sichuanensis as a junior synonym of P. prima as a consequence of identifying these two form-taxa as distinct developmental stages of the same organism. Direct development in P. prima parallels the co-occuring olivooids Olivooides, and Quadrapyrgites and Bayesian phylogenetic analysis of a novel phenotype dataset indicates that, despite differences in their tetra-, penta- and pseudo-hexa-radial symmetry, these hexangulaconulariids comprise a clade of scyphozoan medusozoans, with Arthrochites and conulariids, that all exhibit direct development from embryo to thecate polyp. The affinity of hexangulaconulariids and olivooids to extant scyphozoan medusozoans indicates that the prevalence of tetraradial symmetry and indirect development are a vestige of a broader spectrum of body-plan symmetries and developmental modes that was manifest in their early Phanerozoic counterparts. © 2017 The Authors.

The early Cambrian fossil embryo Pseudooides is a direct-developing cnidarian, not an early ecdysozoan

PubMed Central

2017-01-01

Early Cambrian Pseudooides prima has been described from embryonic and post-embryonic stages of development, exhibiting long germ-band development. There has been some debate about the pattern of segmentation, but this interpretation, as among the earliest records of ecdysozoans, has been generally accepted. Here, we show that the ‘germ band’ of P. prima embryos separates along its mid axis during development, with the transverse furrows between the ‘somites’ unfolding into the polar aperture of the ten-sided theca of Hexaconularia sichuanensis, conventionally interpreted as a scyphozoan cnidarian; co-occurring post-embryonic remains of ecdysozoans are unrelated. We recognize H. sichuanensis as a junior synonym of P. prima as a consequence of identifying these two form-taxa as distinct developmental stages of the same organism. Direct development in P. prima parallels the co-occuring olivooids Olivooides, and Quadrapyrgites and Bayesian phylogenetic analysis of a novel phenotype dataset indicates that, despite differences in their tetra-, penta- and pseudo-hexa-radial symmetry, these hexangulaconulariids comprise a clade of scyphozoan medusozoans, with Arthrochites and conulariids, that all exhibit direct development from embryo to thecate polyp. The affinity of hexangulaconulariids and olivooids to extant scyphozoan medusozoans indicates that the prevalence of tetraradial symmetry and indirect development are a vestige of a broader spectrum of body-plan symmetries and developmental modes that was manifest in their early Phanerozoic counterparts. PMID:29237861

Evaluating the long-term consequences of air pollution in early life: geographical correlations between coal consumption in 1951/1952 and current mortality in England and Wales

PubMed Central

Phillips, David I W; Osmond, Clive; Southall, Humphrey; Aucott, Paula; Jones, Alexander; Holgate, Stephen T

2018-01-01

Objective To evaluate associations between early life air pollution and subsequent mortality. Design Geographical study. Setting Local government districts within England and Wales. Exposure Routinely collected geographical data on the use of coal and related solid fuels in 1951–1952 were used as an index of air pollution. Main outcome measures We evaluated the relationship between these data and both all-cause and disease-specific mortality among men and women aged 35–74 years in local government districts between 1993 and 2012. Results Domestic (household) coal consumption had the most powerful associations with mortality. There were strong correlations between domestic coal use and all-cause mortality (relative risk per SD increase in fuel use 1.124, 95% CI 1.123 to 1.126), and respiratory (1.238, 95% CI 1.234 to 1.242), cardiovascular (1.138, 95% CI 1.136 to 1.140) and cancer mortality (1.073, 95% CI 1.071 to 1.075). These effects persisted after adjustment for socioeconomic indicators in 1951, current socioeconomic indicators and current pollution levels. Conclusion Coal was the major cause of pollution in the UK until the Clean Air Act of 1956 led to a rapid decline in consumption. These data suggest that coal-based pollution, experienced over 60 years ago in early life, affects human health now by increasing mortality from a wide variety of diseases. PMID:29703847

Transfection of embryonated Muscovy duck eggs with a recombinant plasmid is suitable for rescue of infectious Muscovy duck parvovirus.

PubMed

Wang, Jianye; Huang, Yu; Ling, Jueyi; Wang, Zhixiang; Zhu, Guoqiang

2017-12-01

For members of the family Parvoviridae, rescue of infectious virus from recombinant plasmid is usually done in cultured cells. In this study, the whole genome of the pathogenic Muscovy duck parvovirus (MDPV) strain YY was cloned into the pBluescript II (SK) vector, generating recombinant plasmid pYY. With the aid of a transfection reagent, pYY plasmid was inoculated into 11-day-old embryonated Muscovy duck eggs via the chorioallantoic membrane route, resulting in the successful rescue of infectious virus and death of the embryos. The rescued virus exhibited pathogenicity in Muscovy ducklings similar to that of its parental strain, as evaluated based on the mortality rate. The results demonstrate that plasmid transfection in embryonated Muscovy duck eggs is a convenient and efficacious method for rescue of infectious MDPV in comparison to transfection of primary cells, which is somewhat time-consuming and laborious.

Design and validation of a model to predict early mortality in haemodialysis patients.

PubMed

Mauri, Joan M; Clèries, Montse; Vela, Emili

2008-05-01

Mortality and morbidity rates are higher in patients receiving haemodialysis therapy than in the general population. Detection of risk factors related to early death in these patients could be of aid for clinical and administrative decision making. Objectives. The aims of this study were (1) to identify risk factors (comorbidity and variables specific to haemodialysis) associated with death in the first year following the start of haemodialysis and (2) to design and validate a prognostic model to quantify the probability of death for each patient. An analysis was carried out on all patients starting haemodialysis treatment in Catalonia during the period 1997-2003 (n = 5738). The data source was the Renal Registry of Catalonia, a mandatory population registry. Patients were randomly divided into two samples: 60% (n = 3455) of the total were used to develop the prognostic model and the remaining 40% (n = 2283) to validate the model. Logistic regression analysis was used to construct the model. One-year mortality in the total study population was 16.5%. The predictive model included the following variables: age, sex, primary renal disease, grade of functional autonomy, chronic obstructive pulmonary disease, malignant processes, chronic liver disease, cardiovascular disease, initial vascular access and malnutrition. The analyses showed adequate calibration for both the sample to develop the model and the validation sample (Hosmer-Lemeshow statistic 0.97 and P = 0.49, respectively) as well as adequate discrimination (ROC curve 0.78 in both cases). Risk factors implicated in mortality at one year following the start of haemodialysis have been determined and a prognostic model designed. The validated, easy-to-apply model quantifies individual patient risk attributable to various factors, some of them amenable to correction by directed interventions.

Contemporary Sex-Based Differences by Age in Presenting Characteristics, Use of an Early Invasive Strategy, and Inhospital Mortality in Patients With Non-ST-Segment-Elevation Myocardial Infarction in the United States.

PubMed

Gupta, Tanush; Kolte, Dhaval; Khera, Sahil; Agarwal, Nayan; Villablanca, Pedro A; Goel, Kashish; Patel, Kavisha; Aronow, Wilbert S; Wiley, Jose; Bortnick, Anna E; Aronow, Herbert D; Abbott, J Dawn; Pyo, Robert T; Panza, Julio A; Menegus, Mark A; Rihal, Charanjit S; Fonarow, Gregg C; Garcia, Mario J; Bhatt, Deepak L

2018-01-01

Prior studies have reported higher inhospital mortality in women versus men with non-ST-segment-elevation myocardial infarction. Whether this is because of worse baseline risk profile compared with men or sex-based disparities in treatment is not completely understood. We queried the 2003 to 2014 National Inpatient Sample databases to identify all hospitalizations in patients aged ≥18 years with the principal diagnosis of non-ST-segment-elevation myocardial infarction. Complex samples multivariable logistic regression models were used to examine sex differences in use of an early invasive strategy and inhospital mortality. Of 4 765 739 patients with non-ST-segment-elevation myocardial infarction, 2 026 285 (42.5%) were women. Women were on average 6 years older than men and had a higher comorbidity burden. Women were less likely to be treated with an early invasive strategy (29.4% versus 39.2%; adjusted odds ratio, 0.92; 95% confidence interval, 0.91-0.94). Women had higher crude inhospital mortality than men (4.7% versus 3.9%; unadjusted odds ratio, 1.22; 95% confidence interval, 1.20-1.25). After adjustment for age (adjusted odds ratio, 0.96; 95% confidence interval, 0.94-0.98) and additionally for comorbidities, other demographics, and hospital characteristics, women had 10% lower odds of inhospital mortality (adjusted odds ratio, 0.90; 95% confidence interval, 0.89-0.92). Further adjustment for differences in the use of an early invasive strategy did not change the association between female sex and lower risk-adjusted inhospital mortality. Although women were less likely to be treated with an early invasive strategy compared with men, the lower use of an early invasive strategy was not responsible for the higher crude inhospital mortality in women, which could be entirely explained by older age and higher comorbidity burden. © 2018 American Heart Association, Inc.

Ultrasonographically documented early pregnancy loss in an Asian elephant (Elephas maximus).

PubMed

Lueders, Imke; Drews, Barbara; Niemuller, Cheryl; Gray, Charlie; Rich, Peter; Fickel, Jörns; Wibbelt, Gudrun; Göritz, Frank; Hildebrandt, Thomas B

2010-01-01

Early embryonic resorption or fetal loss is known to occur occasionally in captive elephants; however, this has mostly been reported anecdotally. The present study documents the case of a 24-year-old, multiparous Asian elephant cow that suffered embryonic death and resorption at around 18 weeks of gestation. From ovulation onwards, this female was sonographically examined 58 times. Blood was collected twice weekly for progestagen determination via enzyme immunoassay. On Day 42 after ovulation, a small quantity of fluid was detected in the uterine horn, which typically indicates the presence of a developing conceptus. Repeated inspections followed what appeared to be a normal pregnancy until Day 116. However, on Day 124, signs of embryonic life were absent. Progestagen concentrations started declining two weeks later, reaching baseline levels one month after embryonic death. Retrospectively, ultrasound examination revealed several abnormalities in the uterine horn. Besides an existing leiomyoma, multiple small cystic structures had formed in the endometrium at the implantation site and later in the placenta. These pathological findings were considered as possible contributors to the early pregnancy failure. PCR for endotheliotropic elephant herpes virus (EEHV) (which had occurred previously in the herd) as well as serology for other infectious organisms known to cause abortion in domestic animals did not yield any positive results. Although no definitive reason was found for this pregnancy to abort, this ultrasonographically and endocrinologically documented study of an early pregnancy loss provides important insights into the resorption process in Asian elephants.

Association between serum levels of caspase-cleaved cytokeratin-18 and early mortality in patients with severe spontaneous intracerebral hemorrhage.

PubMed

Lorente, Leonardo; Martín, María M; Pérez-Cejas, Antonia; Ramos, Luis; Argueso, Mónica; Solé-Violán, Jordi; Cáceres, Juan J; Jiménez, Alejandro; García-Marín, Victor

2018-04-16

Apoptotic changes after cerebral hemorrhage in brain samples of humans have been found. Caspase-cleaved cytokeratin (CCCK)-18 could be detected in the bloodstream during apoptosis. Higher circulating CCCK-18 levels have been associated with 6-month mortality in patients with basal ganglia hemorrhage. The aim of our study was to determine whether there is an association between serum CCCK-18 levels and early mortality of spontaneous intracerebral hemorrhage (SIH) patients. We performed an observational, prospective and multicentre study. There were included patients with severe SIH defined as Glasgow Coma Scale (GCS) lower than 9. We determined serum CCCK-18 levels at the severe SIH diagnosis moment. We found that non-surviving SIH patients (n = 46) showed lower GCS, and higher serum CCCK-18 levels and APACHE-II score than survivor ones (n = 54). In ROC analysis was found that the area under the curve of serum CCCK-18 levels for 30-day mortality prediction was 90% (95% CI 82-95%; p < 0.001). In the multiple logistic regression analysis, we found an association between serum CCCK-18 levels and 30-day mortality (OR 1.034; 95% CI 1.013-1.055; p = 0.002). The novel finding of our study was that there is an association between high serum CCCK-18 levels and 30-day mortality in severe SIH patients.

Embryonated chicken eggs as an alternative model for mixed Clostridium perfringens and Eimeria tenella infection in chickens.

PubMed

Alnassan, Alaa Aldin; Shehata, Awad Ali; Kotsch, Marianne; Lendner, Matthias; Daugschies, Arwid; Bangoura, Berit

2013-06-01

The chorioallantoic membrane (CAM) of chicken embryo eggs is a suitable model for viral and bacterial infections. In the present study, a new approach for testing the pathogenesis and virulence of Clostridium perfringens and Eimeria tenella dual infections as a model using the CAM of embryonated chicken eggs was developed. For this purpose, 24 specific pathogen-free (SPF) embryonated chicken eggs were divided into four groups (n = 6) and designated group E, group CP, group CPE, and NC. Sporozoites of E. tenella (20,000 sporozoites) were inoculated into 10-day-old embryonated SPF chicken eggs (groups E and CPE) via allantoic sac route. At 15-day-old, eggs of groups CP and CPE were infected with 10 (4)  cfu C. perfringens via the same route. Assessment of pathogenicity was assessed using gross and histopathological lesions. Embryo mortality reached 17 % after mono-infection with C. perfringens and/or E. tenella and 50 % in the mixed-infected group. Lesions in the CAMs were most numerous and most severe in co-infected eggs (group CPE), reaching the maximum score of 3 in 50 % of the inoculated eggs (P < 0.01). In Eimeria spp.-infected eggs (group E), lesions of score were between 1 and 2. Mono-infection with C. perfringens did not lead to a significant occurrence of lesions. Histopathological investigations of the CAM revealed clusters of Gram-positive bacteria, infiltration with leukocytes, lymphocytes, and developmental stages of E. tenella in the co-infected group. These data suggest that embryonated eggs could be an in ovo model for studying the pathogenesis of mixed infection with Eimeria and C. perfringens.

[Low expression of activin A in mouse and human embryonic teratocarcinoma cells].

PubMed

Gordeeva, O F

2014-01-01

TGFP3 family factors play an important role in regulating the balance of self-renewal and differentiation of mouse and human pluripotent stem and embryonic teratocarcinoma cells. The expression patterns of TGFbeta family signaling ligands and functional roles of these signaling pathways differ significantly in mouse and human embryonic stem cells, but the activity and functional role of these factors in mouse and human embryonic teratocarcinoma cells were not sufficiently investigated. Comparative quantitative real-time PCR analysis of the expression of TGF@[beta] family factors in mouse embryonic stem, embryonic germ, and embryonic teratocarcinoma cells showed that embryonic teratocarcinoma cells express lower ActivinA than pluripotent stem cells but similar levels of factors Nodal, Lefty 1, TGFbeta1, BMP4, and GDF3. In human nullipotent embryonic teratocarcinoma PA-1 cells, most factors of the TGFbeta family (ACTIVINA, NODAL, LEFTY 1, BMP4, and GDF3) are expressed at lower levels than in human embryonic stem cells: Thus, in mouse and human nullipotent teratocarcinoma cells, theexpression of ActivinA is significantly reduced com- pared ivith embryonic stem cells. Presumably, these differences may be associated with changes in the functional activity of the respective signaling pathways and deregulation of proliferative and antiproliferative mechanisms in embryonic teratocarcinoma cells.

Early cavopulmonary anastomosis in very young infants after the Norwood procedure: impact on oxygenation, resource utilization, and mortality.

PubMed

Jaquiss, Robert D B; Ghanayem, Nancy S; Hoffman, George M; Fedderly, Raymond T; Cava, Joseph R; Mussatto, Kathleen A; Tweddell, James S

2004-04-01

The optimal timing of second-stage palliation after Norwood operations remains undefined. Advantages of early cavopulmonary anastomosis are early elimination of volume load and shortening the high-risk interstage period. Potential disadvantages include severe cyanosis, prolonged pleural drainage and hospitalization, and excess mortality. We reviewed our recent experience to evaluate the safety of early cavopulmonary anastomosis. Eighty-five consecutive patients undergoing post-Norwood operation cavopulmonary anastomosis were divided into group I (cavopulmonary anastomosis at <4 months; n = 33) and group II (cavopulmonary anastomosis at >4 months; n = 52). Groups were compared for age; size; early and late mortality; preoperative, initial postoperative, and discharge oxygen saturation; and duration of mechanical ventilation, intensive care unit stay, pleural drainage, and hospitalization. Group I patients were younger than group II patients (94 +/- 21 days vs 165 +/- 44 days, respectively; P <.001) and smaller (4.8 +/- 0.8 kg vs 5.8 +/- 0.9 kg; P <.001). The preoperative oxygen saturation was not different (group I, 75% +/- 10%; group II, 78% +/- 8%; P =.142). The oxygen saturation was lower immediately after surgery in group I compared with group II (75% +/- 7% vs 81% +/- 7%, respectively; P <.001) but not by discharge (group I, 79% +/- 4%; group II, 80% +/- 4%). Younger patients were ventilated longer (62 +/- 86 hours vs 19 +/- 42 hours; P =.001), in the intensive care unit longer (130 +/- 111 hours vs 104 +/- 94 hours; P =.049), hospitalized longer (12.5 +/- 11.5 days vs 10.3 +/- 14.8 days; P =.012), and required longer pleural drainage (106 +/- 45 hours vs 104 +/- 93 hours; P =.046). Hospital survival was 100% in both groups. Actuarial survival to 12 months was 96% +/- 4% for group I and 96% +/- 3% for group II. Early cavopulmonary anastomosis after the Norwood operation is safe. Younger patients are more cyanotic initially after surgery and have a longer

Properties of murine embryonic stem cells maintained on human foreskin fibroblasts without LIF.

PubMed

Meng, G L; Zur Nieden, N I; Liu, S Y; Cormier, J T; Kallos, M S; Rancourt, D E

2008-04-01

In embryonic stem (ES) cells, leukemia inhibitory factor (LIF)/STAT3, wnt and nodal/activin signaling are mainly active to control pluripotency during expansion. To maintain pluripotency, ES cells are typically cultured on feeder cells of varying origins. Murine ES cells are commonly cultured on murine embryonic fibroblasts (MEFs), which senesce early and must be frequently prepared. This process is laborious and leads to batch variation presenting a challenge for high-throughput ES cell expansion. Although some cell lines can be sustained by exogenous LIF, this method is costly. We present here a novel and inexpensive culture method for expanding murine ES cells on human foreskin fibroblast (HFF) feeders. After 20 passages on HFFs without LIF, ES cell lines showed normal expression levels of pluripotency markers, maintained a normal karyotype and retained the ability to contribute to the germline. As HFFs do not senesce for at least 62 passages, they present a vast supply of feeders. Copyright 2007 Wiley-Liss, Inc.

Identification of cells expressing OLFM4 and LGR5 mRNA by in situ hybridization in the yolk sac and small intestine of embryonic and early post-hatch chicks.

PubMed

Zhang, H; Wong, E A

2018-02-01

The chicken yolk sac (YS) and small intestine are essential for nutrient absorption during the pre-hatch and post-hatch periods, respectively. Absorptive enterocytes and secretory cells line the intestinal villi and originate from stem cells located in the intestinal crypts. Similarly, in the YS, there are absorptive and secretory cells that presumably originate from a stem cell population. Leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5) and olfactomedin 4 (Olfm4) are 2 widely used markers for intestinal stem cells. The objective of this study was to map the distribution of putative stem cells expressing LGR5 and OLFM4 mRNA in the chicken small intestine from the late embryonic period to early post hatch and the YS during embryogenesis. At embryonic d 11, 13, 15, 17, and 19, the YS was collected (n = 3), and small intestine was collected at embryonic d 19, d of hatch (doh), and d 1, 4, and 7 post hatch (n = 3). Cells expressing OLFM4 and LGR5 mRNA were identified by in situ hybridization. In the YS, cells expressing only LGR5 and not OLFM4 mRNA were localized to the vascular endothelial cells lining the blood vessels. In the small intestine, cells in the intestinal crypt expressed both LGR5 and OLFM4 mRNA. Staining for OLFM4 mRNA was more intense than LGR5 mRNA, demonstrating that Olfm4 is a more robust marker for stem cells than Lgr5. At embryonic d 19 and doh, cells staining for OLFM4 mRNA were already present in the rudimentary crypts, with the greatest staining in the duodenal crypts. The intensity of OLFM4 mRNA staining increased from doh to d 7 post hatch. Dual label staining at doh for the peptide transporter PepT1 and Olfm4 revealed a population of cells above the crypts that did not express Olfm4 or PepT1 mRNA. These cells are likely progenitor transit amplifying cells. Thus, avians and mammals share similarity in the ontogeny of stem cells in the intestinal crypts. © 2017 Poultry Science Association Inc.

Effects of Aminoglycoside Antibiotics on Human Embryonic Stem Cell Viability during Differentiation In Vitro

PubMed Central

Varghese, Divya S.; Parween, Shama; Ardah, Mustafa T.; Emerald, Bright Starling

2017-01-01

Human embryonic stem cells (hESCs) are being used extensively in array of studies to understand different mechanisms such as early human embryogenesis, drug toxicity testing, disease modeling, and cell replacement therapy. The protocols for the directed differentiation of hESCs towards specific cell types often require long-term cell cultures. To avoid bacterial contamination, these protocols include addition of antibiotics such as pen-strep and gentamicin. Although aminoglycosides, streptomycin, and gentamicin have been shown to cause cytotoxicity in various animal models, the effect of these antibiotics on hESCs is not clear. In this study, we found that antibiotics, pen-strep, and gentamicin did not affect hESC cell viability or expression of pluripotency markers. However, during directed differentiation towards neural and hepatic fate, significant cell death was noted through the activation of caspase cascade. Also, the expression of neural progenitor markers Pax6, Emx2, Otx2, and Pou3f2 was significantly reduced suggesting that gentamicin may adversely affect early embryonic neurogenesis whereas no effect was seen on the expression of endoderm or hepatic markers during differentiation. Our results suggest that the use of antibiotics in cell culture media for the maintenance and differentiation of hESCs needs thorough investigation before use to avoid erroneous results. PMID:29147115

Maternal Lifestyle Impairs Embryonic Growth: The Rotterdam Periconception Cohort.

PubMed

Van Dijk, Matthijs R; Borggreven, Nicole V; Willemsen, Sten P; Koning, Anton H J; Steegers-Theunissen, Régine P M; Koster, Maria P H

2018-06-01

Previously, embryonic growth has been assumed to be uniform, but in recent years, it has become more clear that genetic and environmental factors may influence the intrauterine environment and therefore embryonic growth trajectories as well as pregnancy course and outcome. The objective of this study was to investigate associations between modifiable maternal nutrition and lifestyle factors during the periconception period and embryonic growth. We established a prospective cohort including 342 women less than 13 weeks pregnant. At enrollment, women filled out a questionnaire regarding demographic and medical data and a validated food frequency questionnaire. Participants received multiple 3-dimensional ultrasound examinations up until the 12th week of pregnancy, and crown-rump length (CRL) and embryonic volume (EV) were measured offline using V-Scope Virtual Reality software (version 1.0.0) in a Barco I-Space. Associations between maternal periconception vegetable and fruit intake, folic acid supplement use, smoking, and alcohol consumption and embryonic growth measurements were assessed by linear mixed models adjusted for potential confounders. No or postconception initiation of folic acid supplement use was significantly associated with a 0.76 mm (-7.8%) and 1.63 mm (-3.7%) smaller CRL and a 0.01 cm 3 (-19.5%) and 0.86 cm 3 (-12.2%) smaller EV at 7 +0 and 11 +0 weeks of gestation, respectively. Smoking, alcohol consumption, and inadequate fruit and vegetable intake showed weaker associations with embryonic growth parameters. These results emphasize the influence of periconceptional maternal folic acid supplement use on embryonic growth. Results regarding maternal nutrition and lifestyle factors also suggest an association with embryonic growth, but this has to be confirmed in a larger study.

TopBP1 deficiency causes an early embryonic lethality and induces cellular senescence in primary cells.

PubMed

Jeon, Yoon; Ko, Eun; Lee, Kyung Yong; Ko, Min Ji; Park, Seo Young; Kang, Jeeheon; Jeon, Chang Hwan; Lee, Ho; Hwang, Deog Su

2011-02-18

TopBP1 plays important roles in chromosome replication, DNA damage response, and other cellular regulatory functions in vertebrates. Although the roles of TopBP1 have been studied mostly in cancer cell lines, its physiological function remains unclear in mice and untransformed cells. We generated conditional knock-out mice in which exons 5 and 6 of the TopBP1 gene are flanked by loxP sequences. Although TopBP1-deficient embryos developed to the blastocyst stage, no homozygous mutant embryos were recovered at E8.5 or beyond, and completely resorbed embryos were frequent at E7.5, indicating that mutant embryos tend to die at the peri-implantation stage. This finding indicated that TopBP1 is essential for cell proliferation during early embryogenesis. Ablation of TopBP1 in TopBP1(flox/flox) mouse embryonic fibroblasts and 3T3 cells using Cre recombinase-expressing retrovirus arrests cell cycle progression at the G(1), S, and G(2)/M phases. The TopBP1-ablated mouse cells exhibit phosphorylation of H2AX and Chk2, indicating that the cells contain DNA breaks. The TopBP1-ablated mouse cells enter cellular senescence. Although RNA interference-mediated knockdown of TopBP1 induced cellular senescence in human primary cells, it induced apoptosis in cancer cells. Therefore, TopBP1 deficiency in untransformed mouse and human primary cells induces cellular senescence rather than apoptosis. These results indicate that TopBP1 is essential for cell proliferation and maintenance of chromosomal integrity.

Contractile properties of early human embryonic stem cell-derived cardiomyocytes: beta-adrenergic stimulation induces positive chronotropy and lusitropy but not inotropy.

PubMed

Pillekamp, Frank; Haustein, Moritz; Khalil, Markus; Emmelheinz, Markus; Nazzal, Rewa; Adelmann, Roland; Nguemo, Filomain; Rubenchyk, Olga; Pfannkuche, Kurt; Matzkies, Matthias; Reppel, Michael; Bloch, Wilhelm; Brockmeier, Konrad; Hescheler, Juergen

2012-08-10

Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) provide the unique opportunity to study the very early development of the human heart. The aim of this study was to investigate the effect of calcium and beta-adrenergic stimulation on the contractile properties of early hESC-CMs. Beating clusters containing hESC-CMs were co-cultured in vitro with noncontractile slices of neonatal murine ventricles. After 5-7 days, when beating clusters had integrated morphologically into the damaged tissue, isometric force measurements were performed during spontaneous beating as well as during electrical field stimulation. Spontaneous beating stopped when extracellular calcium ([Ca²⁺](ec)) was removed or after administration of the Ca²⁺ channel blocker nifedipine. During field stimulation at a constant rate, the developed force increased with incremental concentrations of [Ca²⁺](ec). During spontaneous beating, rising [Ca²⁺](ec) increased beating rate and developed force up to a [Ca²⁺](ec) of 2.5 mM. When [Ca²⁺](ec) was increased further, spontaneous beating rate decreased, whereas the developed force continued to increase. The beta-adrenergic agonist isoproterenol induced a dose-dependent increase of the frequency of spontaneous beating; however, it did not significantly change the developed force during spontaneous contractions or during electrical stimulation at a constant rate. Force developed by early hESC-CMs depends on [Ca²⁺](ec) and on the L-type Ca²⁺ channel. The lack of an inotropic reaction despite a pronounced chronotropic response after beta-adrenergic stimulation most likely indicates immaturity of the sarcoplasmic reticulum. For cell-replacement strategies, further maturation of cardiac cells has to be achieved either in vitro before or in vivo after transplantation.

Embryonic control of epidermal cell patterning in the root and hypocotyl of Arabidopsis.

PubMed

Lin, Y; Schiefelbein, J

2001-10-01

A position-dependent pattern of epidermal cell types is produced during the development of the Arabidopsis seedling root and hypocotyl. To understand the origin and regulation of this patterning mechanism, we have examined the embryonic expression of the GLABRA2 (GL2) gene, which encodes a cell-type-specific transcription factor. Using in situ RNA hybridization and a sensitive GL2::GFP reporter, we discovered that a position-dependent pattern of GL2 expression is established within protodermal cells at the heart stage and is maintained throughout the remainder of embryogenesis. In addition, we show that an exceptional GL2 expression character and epidermal cell pattern arises during development of the root-hypocotyl junction, which represents an anatomical transition zone. Furthermore, we find that two of the genes regulating seedling epidermal patterning, TRANSPARENT TESTA GLABRA (TTG) and WEREWOLF (WER), also control the embryonic GL2 pattern, whereas the CAPRICE (CPC) and GL2 genes are not required to establish this pattern. These results indicate that position-dependent patterning of epidermal cell types begins at an early stage of embryogenesis, before formation of the apical meristems and shortly after the cellular anatomy of the protoderm and outer ground tissue layer is established. Thus, epidermal cell specification in the Arabidopsis seedling relies on the embryonic establishment of a patterning mechanism that is perpetuated postembryonically.

Automated Prediction of Early Blood Transfusion and Mortality in Trauma Patients

DTIC Science & Technology

2014-09-24

We hypothesized that analysis of pulse oximeter signals could predict blood transfusion and mortality as accurately as conventional vital signs(VSs...to 3-hour transfusion, MT, and mortality no differently from pulse oximeter signals alone. Pulse oximeter features collected in the first 15 minutes...time is an unrealized goal. We hypothesized that analysis of pulse oximeter signals could predict blood transfusion and mortality as accurately as

Evolutionally dynamic L1 regulation in embryonic stem cells

PubMed Central

Castro-Diaz, Nathaly; Ecco, Gabriela; Coluccio, Andrea; Kapopoulou, Adamandia; Yazdanpanah, Benyamin; Friedli, Marc; Duc, Julien; Jang, Suk Min; Turelli, Priscilla; Trono, Didier

2014-01-01

Mobile elements are important evolutionary forces that challenge genomic integrity. Long interspersed element-1 (L1, also known as LINE-1) is the only autonomous transposon still active in the human genome. It displays an unusual pattern of evolution, with, at any given time, a single active L1 lineage amplifying to thousands of copies before getting replaced by a new lineage, likely under pressure of host restriction factors, which act notably by silencing L1 expression during early embryogenesis. Here, we demonstrate that in human embryonic stem (hES) cells, KAP1 (KRAB [Krüppel-associated box domain]-associated protein 1), the master cofactor of KRAB-containing zinc finger proteins (KRAB-ZFPs) previously implicated in the restriction of endogenous retroviruses, represses a discrete subset of L1 lineages predicted to have entered the ancestral genome between 26.8 million and 7.6 million years ago. In mice, we documented a similar chronologically conditioned pattern, albeit with a much contracted time scale. We could further identify an L1-binding KRAB-ZFP, suggesting that this rapidly evolving protein family is more globally responsible for L1 recognition. KAP1 knockdown in hES cells induced the expression of KAP1-bound L1 elements, but their younger, human-specific counterparts (L1Hs) were unaffected. Instead, they were stimulated by depleting DNA methyltransferases, consistent with recent evidence demonstrating that the PIWI–piRNA (PIWI-interacting RNA) pathway regulates L1Hs in hES cells. Altogether, these data indicate that the early embryonic control of L1 is an evolutionarily dynamic process and support a model in which newly emerged lineages are first suppressed by DNA methylation-inducing small RNA-based mechanisms before KAP1-recruiting protein repressors are selected. PMID:24939876

Isolation and expression of homeobox genes from the embryonic chicken eye.

PubMed

Dhawan, R R; Schoen, T J; Beebe, D C

1997-06-11

To identify homeobox-containing genes that may play a role in the differentiation of ocular tissues. Total RNA was isolated from microdissected chicken embryo eye tissues at 3.5 days of development (embryonic day 3.5; E3.5). An "anchor-oligo-dT primer" was used for the synthesis of cDNA. Degenerate oligonucleotides designed from highly-conserved sequences in the third helix of the homeobox and the "anchor-primer" were used to amplify cDNAs by polymerase chain reaction (PCR). PCR products were cloned and sequenced. The spatial and temporal expression of selected transcripts was mapped by whole-mount in situ hybridization and northern blot analysis. After sequencing eighteen clones we identified a member of the distal-less family (dlx-3) in cDNA from presumptive neural retina and three chicken homologs of the Xenopus "anterior neural fold" (Xanf-1) in cDNA from anterior eye tissue. Dlx transcripts were mapped by in situ hybridization. Expression began at Hamburger and Hamilton stage 14 (E2.5) and was widely distributed in embryonic mesenchyme on E3 and E4. Expression increased in the retina during early development and persisted until after hatching. The one anf clone selected for further study was not detected by in situ or northern blot analysis. It is feasible to isolate homeobox cDNAs directly from microdissected embryonic tissues. Chicken dlx-3 mRNA has a wider distribution in the embryo than expected, based on the expression of the mouse homolog. Dlx-3 may play a role in establishing or maintaining the differentiation of the retina.

Oocyte exposure to ZnO nanoparticles inhibits early embryonic development through the γ-H2AX and NF-κB signaling pathways.

PubMed

Liu, Jing; Zhao, Yong; Ge, Wei; Zhang, Pengfei; Liu, Xinqi; Zhang, Weidong; Hao, Yanan; Yu, Shuai; Li, Lan; Chu, Meiqiang; Min, Lingjiang; Zhang, Hongfu; Shen, Wei

2017-06-27

The impacts of zinc oxide nanoparticles on embryonic development following oocyte stage exposure are unknown and the underlying mechanisms are sparsely understood. In the current investigation, intact nanoparticles were detected in ovarian tissue in vivo and cultured cells in vitro under zinc oxide nanoparticles treatment. Zinc oxide nanoparticles exposure during the oocyte stage inhibited embryonic development. Notably, in vitro culture data closely matched in vivo embryonic data, in that the impairments caused by Zinc oxide nanoparticles treatment passed through cell generations; and both gamma-H2AX and NF-kappaB pathways were involved in zinc oxide nanoparticles caused embryo-toxicity. Copper oxide and silicon dioxide nanoparticles have been used to confirm that particles are important for the toxicity of zinc oxide nanoparticles. The toxic effects of zinc oxide nanoparticles emanate from both intact nanoparticles and Zn2+. Our investigation along with others suggests that zinc oxide nanoparticles are toxic to the female reproductive system [ovaries (oocytes)] and subsequently embryo-toxic and that precaution should be taken regarding human exposure to their everyday use.

Oocyte exposure to ZnO nanoparticles inhibits early embryonic development through the γ-H2AX and NF-κB signaling pathways

PubMed Central

Liu, Jing; Zhao, Yong; Ge, Wei; Zhang, Pengfei; Liu, Xinqi; Zhang, Weidong; Hao, Yanan; Yu, Shuai; Li, Lan; Chu, Meiqiang; Min, Lingjiang; Zhang, Hongfu; Shen, Wei

2017-01-01

The impacts of zinc oxide nanoparticles on embryonic development following oocyte stage exposure are unknown and the underlying mechanisms are sparsely understood. In the current investigation, intact nanoparticles were detected in ovarian tissue in vivo and cultured cells in vitro under zinc oxide nanoparticles treatment. Zinc oxide nanoparticles exposure during the oocyte stage inhibited embryonic development. Notably, in vitro culture data closely matched in vivo embryonic data, in that the impairments caused by Zinc oxide nanoparticles treatment passed through cell generations; and both gamma-H2AX and NF-kappaB pathways were involved in zinc oxide nanoparticles caused embryo-toxicity. Copper oxide and silicon dioxide nanoparticles have been used to confirm that particles are important for the toxicity of zinc oxide nanoparticles. The toxic effects of zinc oxide nanoparticles emanate from both intact nanoparticles and Zn2+. Our investigation along with others suggests that zinc oxide nanoparticles are toxic to the female reproductive system [ovaries (oocytes)] and subsequently embryo-toxic and that precaution should be taken regarding human exposure to their everyday use. PMID:28487501

Generation of embryos directly from embryonic stem cells by tetraploid embryo complementation reveals a role for GATA factors in organogenesis.

PubMed

Duncan, S A

2005-12-01

Gene targeting in ES (embryonic stem) cells has been used extensively to study the role of proteins during embryonic development. In the traditional procedure, this requires the generation of chimaeric mice by introducing ES cells into blastocysts and allowing them to develop to term. Once chimaeric mice are produced, they are bred into a recipient mouse strain to establish germline transmission of the allele of interest. Although this approach has been used very successfully, the breeding cycles involved are time consuming. In addition, genes that are essential for organogenesis often have roles in the formation of extra-embryonic tissues that are essential for early stages of post-implantation development. For example, mice lacking the GATA transcription factors, GATA4 or GATA6, arrest during gastrulation due to an essential role for these factors in differentiation of extra-embryonic endoderm. This lethality has frustrated the study of these factors during the development of organs such as the liver and heart. Extraembryonic defects can, however, be circumvented by generating clonal mouse embryos directly from ES cells by tetraploid complementation. Here, we describe the usefulness and efficacy of this approach using GATA factors as an example.

Ethanol Inactivated Mouse Embryonic Fibroblasts Maintain the Self-Renew and Proliferation of Human Embryonic Stem Cells.

PubMed

Huang, Boxian; Ning, Song; Zhuang, Lili; Jiang, Chunyan; Cui, Yugui; Fan, Guoping; Qin, Lianju; Liu, Jiayin

2015-01-01

Conventionally, mouse embryonic fibroblasts (MEFs) inactivated by mitomycin C or irradiation were applied to support the self-renew and proliferation of human embryonic stem cells (hESCs). To avoid the disadvangtages of mitomycin C and irradiation, here MEFs were treated by ethanol (ET). Our data showed that 10% ET-inactivated MEFs (eiMEFs) could well maintain the self-renew and proliferation of hESCs. hESCs grown on eiMEFs expressed stem cell markers of NANOG, octamer-binding protein 4 (OCT4), stage-specific embryonic antigen-4 (SSEA4) and tumour related antigen-1-81 (TRA-1-81), meanwhile maintained normal karyotype after long time culture. Also, hESCs cocultured with eiMEFs were able to form embryoid body (EB) in vitro and develop teratoma in vivo. Moreover, eiMEFs could keep their nutrient functions after long time cryopreservation. Our results indicate that the application of eiMEF in hESCs culture is safe, economical and convenient, thus is a better choice.

Embryonic stem cells: testing the germ-cell theory.

PubMed

Hochedlinger, Konrad

2011-10-25

The exact cellular origin of embryonic stem cells remains elusive. Now a new study provides compelling evidence that embryonic stem cells, established under conventional culture conditions, originate from a transient germ-cell state. Copyright © 2011 Elsevier Ltd. All rights reserved.

Evaluating the long-term consequences of air pollution in early life: geographical correlations between coal consumption in 1951/1952 and current mortality in England and Wales.

PubMed