scholarly journals A Mechanism of Cohesin-Dependent Loop Extrusion Organizes Zygotic Genome Architecture

2017 ◽  
Author(s):  
Johanna Gassler ◽  
Hugo B. Brandão ◽  
Maxim Imakaev ◽  
Ilya M. Flyamer ◽  
Sabrina Ladstätter ◽  
...  
Keyword(s):  
Multiple Scales ◽  
List Type ◽  
Chromatin Loops ◽  
Mouse Knockout ◽  
Cell Embryo ◽  
Mammalian Genomes ◽  
Single Nucleus ◽  
Mouse Zygotes ◽  
The One ◽  
Zygotic Genome

SUMMARYFertilization triggers assembly of higher-order chromatin structure from a naïve genome to generate a totipotent embryo. Chromatin loops and domains are detected in mouse zygotes by single-nucleus Hi-C (snHi-C) but not bulk Hi-C. We resolve this discrepancy by investigating whether a mechanism of cohesin-dependent loop extrusion generates zygotic chromatin conformations. Using snHi-C of mouse knockout embryos, we demonstrate that the zygotic genome folds into loops and domains that depend on Scc1-cohesin and are regulated in size by Wapl. Remarkably, we discovered distinct effects on maternal and paternal chromatin loop sizes, likely reflecting loop extrusion dynamics and epigenetic reprogramming. Polymer simulations based on snHi-C are consistent with a model where cohesin locally compacts chromatin and thus restricts inter-chromosomal interactions by active loop extrusion, whose processivity is controlled by Wapl. Our simulations and experimental data provide evidence that cohesin-dependent loop extrusion organizes mammalian genomes over multiple scales from the one-cell embryo onwards.HighlightsZygotic genomes are organized into cohesin-dependent chromatin loops and TADsLoop extrusion leads to different loop strengths in maternal and paternal genomesCohesin restricts inter-chromosomal interactions by altering chromosome surface areaLoop extrusion organizes chromatin at multiple genomic scales

STUDIES IN CONGENITAL GENERALIZED LIPODYSTROPHY

1973 ◽  
Vol 72 (3) ◽  
pp. 495-505 ◽  
Author(s):  
Oddmund Søvik ◽  
Svein Oseid
Keyword(s):  
Biological Activity ◽  
Insulin Response ◽  
Epididymal Adipose Tissue ◽  
Large Individual ◽  
Immunoreactive Insulin ◽  
List Type ◽  
Glucose Load ◽  
Congenital Generalized Lipodystrophy ◽  
The One

ABSTRACT The biological activity of plasma insulin from 4 cases of congenital generalized lipodystrophy has been studied, using rat diaphragm and epididymal adipose tissue in vivo. The results are compared with previous data on plasma immunoreactive insulin obtained in these patients. 2 of the 4 cases exhibited unusually high biological insulin activities during the fasting state as well as after an intravenous (iv) glucose load. In the fat pad assay activities as high as 10 000 μU insulin per ml were observed. During childhood the biological insulin activities were generally high, although there were large individual variations. However, in the one case studied after the age of puberty, the insulin response to a glucose load was negligible. Taken together, the biological and immunological activities observed strongly suggest the presence of pancreatic insulin in these patients. It appears that the circulating insulin has a fully biological activity. The decreasing insulin activities after cessation of growth are in agreement with the appearance of frank diabetes at this time.

Mouse one-cell embryos undergoing a radiation-induced G2 arrest may re-enter S-phase in the absence of cytokinesis

2002 ◽  
Vol 80 (7) ◽  
pp. 618-624 ◽  
Author(s):  
P Jacquet ◽  
J Buset ◽  
J Vankerkom ◽  
S Baatout ◽  
L de Saint-Georges ◽  
...  
Keyword(s):  
Calyculin A ◽  
Embryonic Cells ◽  
G2 Arrest ◽  
Cell Stage ◽  
Chromosome Fragments ◽  
X Irradiation ◽  
Radiation Induced ◽  
Mouse Zygotes ◽  
The One

PCC (premature chromosome condensation) can be used for visualizing and scoring damage induced by radiation in the chromatin of cells undergoing a G1 or G2 arrest. A method involving the fusion of irradiated single embryonic cells with single MI oocytes was used to induce PCC in mouse zygotes of the BALB/c strain, which suffer a drastic G2 arrest after X-irradiation (dose used 2.5 Gy). Other G2-arrested embryos were exposed in vitro to the phosphatase inhibitor calyculin A. Both methods furnished excellent chromosome preparations of the G2-arrested embryos. The mean number of chromosome fragments did not change significantly during G2 arrest, suggesting that zygotes of this strain are unable to repair DNA damage leading to such aberrations. Forty to fifty percent of the irradiated embryos were unable to cleave after G2 arrest and remained blocked at the one-cell stage for a few days before dying. PCC preparations obtained from such embryos suggested that about 30% of them had undergone a late mitosis not followed by cytokinesis and had entered a new DNA synthesis. These results are discussed in the light of recent observations in irradiated human cells deficient in the p53/14-3-3sigma pathway.Key words: PCC, embryo, oocyte, calyculin A, G2 arrest, cytokinesis.

Depression impact on the sexual desire

2011 ◽  
Vol 26 (S2) ◽  
pp. 1549-1549
Author(s):  
M. Lourenço ◽  
L.P. Azevedo ◽  
J.L. Gouveia
Keyword(s):  
Sexual Desire ◽  
Depressive Symptomatology ◽  
Psychiatric Patients ◽  
Severe Depression ◽  
List Type ◽  
Sexual Performance ◽  
Average Value ◽  
Treatment Of Depression ◽  
The One ◽  
The Relationship

IntroductionDepression as a pathology and the side effects of pharmacology therapy have been pointed proven to be as responsible for the lack of sexual desire. Among the drugs used in the treatment of depression, anti-depressives are the ones mostly connected to sexual dysfunction.Aims /objectivesTo study the relationship between depression and its impact on the sexual desire in psychiatric patients.MethodsThe chosen sample is composed of 89 subjects, 73 females and 16 males, with ages ranging from 21 to 70 years, who present with depressive symptomatology (mild to moderate symptomatology (MMS) and severe symptomatology (SS).To each patient 3 instruments were applied: 1)Questionnaire used to collect demographic and clinical data from the sample;2)Instrument of estimation of the depression degree (BDI - Beck Depression Inventory);3)Instrument of valuation of the sexual desire (SDS - Sexual Desire Scale).ResultsDepression average value obtained with BDI was 25.58 (SD = 11.86). The majority was satisfied with their marital relationship (72.7% and 52.9%, respectively), and the group with most sexual damaged (actual sexual performance regarding sexual desire) being the one with severe depression (54.5% versus 82.4%, respectively). Regarding total SDS value, the group with MMD present with higher levels of sexual desire (M = 54.93; DP = 14.56) than the group with SD (M = 41.82; DP = 11.86).ConclusionsThis study presents an exploratory character and the obtained results revealed that depressive symptomatology severity is directly related with sexual desire, by saying the higher the depression's severity is the lower sexual desire will be.

scholarly journals ROS in tobacco stigma exudate affect pollen proteome and provoke membrane hyperpolarization

2020 ◽  
Author(s):  
Breygina Maria ◽  
Klimenko Ekaterina ◽  
Shilov Eugeny ◽  
Mamaeva Anna ◽  
Zgoda Viktor ◽  
...  
Keyword(s):  
Cell Metabolism ◽  
Pollen Grains ◽  
Plant Reproduction ◽  
List Type ◽  
Membrane Hyperpolarization ◽  
Inhibitory Analysis ◽  
The One ◽  
Cellular Components ◽  
Stigma Exudate

1.AbstractROS are known to be accumulated in stigmas of different species and can possibly perform different functions in plant reproduction. Here we confirm the assumption that they affect pollen by altering ion transport through the plasma membrane; as a more deferred effect, pollen proteome is modified. We detected ROS in stigma exudate, found hyperpolarization in exudate-treated growing pollen tubes and used flow cytometry of pollen protoplasts to compare the effects of fresh exudate and exogenous H2O2 on pollen tube plasmalemma. Exudate causes plasmalemma hyperpolarization similar to the one provoked by H2O2, which is abolished by catalase treatment and ROS quencher MnTMPP. Inhibitory analysis indicates the participation of Ca2+- and K+-conducting channels in the observed hyperpolarization, linking obtained data with previous patch-clamp studies in vitro. For a deeper understanding of pollen response to ROS we analyzed proteome alterations in H2O2-treated pollen grains. We found 50 unique proteins and 20 differently accumulated proteins that are mainly involved in cell metabolism, energetics, protein synthesis and folding. Thus, pollen is getting ready for effective resource usage, construction of cellular components and rapid growth.HighlightsThe active substance in stigma exudate is H2O2H2O2 causes hyperpolarization mediated by the activation of cation channels.H2O2 affects pollen proteome; we found 50 unique proteins.

scholarly journals Inhibition of DRP1 Impedes Zygotic Genome Activation and Preimplantation Development in Mice

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuanyuan Li ◽  
Ning-Hua Mei ◽  
Gui-Ping Cheng ◽  
Jing Yang ◽  
Li-Quan Zhou
Keyword(s):  
Embryo Development ◽  
Preimplantation Embryo ◽  
Preimplantation Embryos ◽  
Dependent Manner ◽  
Zygotic Genome Activation ◽  
Preimplantation Embryo Development ◽  
Cell Embryo ◽  
Embryo Stage ◽  
Genome Activation ◽  
Zygotic Genome

Mitochondrion plays an indispensable role during preimplantation embryo development. Dynamic-related protein 1 (DRP1) is critical for mitochondrial fission and controls oocyte maturation. However, its role in preimplantation embryo development is still lacking. In this study, we demonstrate that inhibition of DRP1 activity by mitochondrial division inhibitor-1, a small molecule reported to specifically inhibit DRP1 activity, can cause severe developmental arrest of preimplantation embryos in a dose-dependent manner in mice. Meanwhile, DRP1 inhibition resulted in mitochondrial dysfunction including decreased mitochondrial activity, loss of mitochondrial membrane potential, reduced mitochondrial copy number and inadequate ATP by disrupting both expression and activity of DRP1 and mitochondrial complex assembly, leading to excessive ROS production, severe DNA damage and cell cycle arrest at 2-cell embryo stage. Furthermore, reduced transcriptional and translational activity and altered histone modifications in DRP1-inhibited embryos contributed to impeded zygotic genome activation, which prevented early embryos from efficient development beyond 2-cell embryo stage. These results show that DRP1 inhibition has potential cytotoxic effects on mammalian reproduction, and DRP1 inhibitor should be used with caution when it is applied to treat diseases. Additionally, this study improves our understanding of the crosstalk between mitochondrial metabolism and zygotic genome activation.

HOMOLOGOUS RADIOIMMUNOASSAY OF THYROTROPHIN IN RAT PLASMA

1974 ◽  
Vol 76 (3) ◽  
pp. 495-505 ◽  
Author(s):  
J. David Kieffer ◽  
Bruce D. Weintraub ◽  
Walter Baigelman ◽  
Susan Leeman ◽  
Farahe Maloof
Keyword(s):  
Zero Point ◽  
Rat Plasma ◽  
Cross Reaction ◽  
The Other ◽  
Male Rats ◽  
List Type ◽  
Specific Effects ◽  
The One ◽  
Bovine Tsh ◽  
Tsh Levels

ABSTRACT An homologous radioimmunoassay (RIA) using the highly purified rat thyrotrophin (TSH) and anti-rat TSH recently made available by NIAMDD is described in detail. Evidence that the assay measures TSH and only TSH includes the following: Treatment of rats with TSH-releasing hormone (TRH) caused a significant increase (averaging 12-fold) and treatment with T4, a significant decrease (averaging 4.5-fold), in plasma TSH. Points for TSH standards and those for dilutions of plasma from TRH-treated rats fell on the same line, and regression lines calculated separately for standards and dilutions of plasma did not depart significantly from parallelism. At 14 days after gonadectomy of male rats, a time when plasma LH and FSH levels are known to be high, the assay showed no increase in plasma TSH. Moreover, reduction of plasma TSH levels by T4 was as great in gonadectomized rats as in controls. Assay of rat LH, rat FSH and rat prolactin, in 7 concentrations each, showed that cross-reaction averaged less than 1 % in all cases. Other workers have calculated values greater than 1 % for TSH contamination of rat LH and FSH. The slopes of regression lines for the 3 hormones tested for cross-reaction did not differ significantly from the slope for TSH standards. This result strengthens the hypothesis that the apparent slight cross-reactions are due to TSH contamination. Findings for T4-treated rats and saline-treated controls show that the homologous RIA is more sensitive than previous, heterologous assays: In previous studies, plasma TSH levels of most or all of rats treated with T4 were not clearly greater than zero. By contrast, in the homologous RIA reported here, values for such rats did not overlap the range of the zero point on the one hand, nor the range for saline-treated controls on the other. Thus, distinct ranges were defined for both normal and low TSH levels. In view of the 1:20 final dilution of plasma during assay, it does not seem likely that non-specific effects of plasma were primarily responsible for the low TSH values of T4-treated rats. Additionally, the useful range of the homologous assay (about 200-fold) is greater than that of earlier assays (about 70-fold, or less). Finally, the use of highly purified rat TSH for standards has avoided inconsistencies previously encountered with bovine TSH standards.

Identification of tablets and capsules

1965 ◽  
Vol 3 (14) ◽  
pp. 53-54
Keyword(s):  
General Practitioner ◽  
General Practitioners ◽  
The Other ◽  
List Type ◽  
Acute Overdose ◽  
Record Card ◽  
The One

Doctors may need to identify an unknown treatment for several reasons: After an acute overdose the drug must be rapidly identified without waiting for time-consuming analysis. In hospital this emergency is not rare.Liaison between the general practitioner and hospital is often imperfect and either party may be unclear about the treatment the patient is receiving from the other. This is much commoner than overdosage.Most general practitioners at some time participate in an arrangement that involves a deputy. One doctor may then see a colleague’s patient without immediate access to the record card. Uncertainty about treatment in such circumstances is experienced by every general practitioner and many consultants seeing patients referred to them.Many patients take more than one kind of preparation: if one is to be changed, or its dosage altered, the patient must be certain which is the one affected.

Nonlinear Vibration Absorber Design: An Asymptotic Approach

2015 ◽  
Author(s):  
Arnaldo Casalotti ◽  
Walter Lacarbonara
Keyword(s):  
Nonlinear Vibration ◽  
Multiple Scales ◽  
Equations Of Motion ◽  
Sensitivity Analyses ◽  
Vibration Absorber ◽  
Asymptotic Approach ◽  
Nonlinear Vibration Absorber ◽  
The One ◽  
Two Degree Of Freedom ◽  
Good Agreement

The one-to-one internal resonance occurring in a two-degree-of-freedom (2DOF) system composed by a damped non-linear primary structure coupled with a nonlinear vibration absorber is studied via the method of multiple scales up to higher order (i.e., the first nonlinear order beyond the internal/external resonances). The periodic response predicted by the asymptotic approach is in good agreement with the numerical results obtained via continuation of the periodic solution of the equations of motion. The asymptotic procedure lends itself to manageable sensitivity analyses and thus to versatile optimization by which different optimal tuning criteria for the vibration absorber can possibly be found in semi-closed form.

DER EINFLUSS DES ANORGANISCHEN BLUTJODES AUF DEN JODUMSATZ DER MENSCHLICHEN SCHILDDRÜSE

1960 ◽  
Vol XXXV (IV) ◽  
pp. 485-494 ◽  
Author(s):  
D. Reinwein ◽  
E. Klein
Keyword(s):  
Iodine Concentration ◽  
Iodine Uptake ◽  
List Type ◽  
Iodide Concentration ◽  
Tracer Dose ◽  
Iodine Metabolism ◽  
The Absolute ◽  
The One

ABSTRACT In 26 euthyroid persons without goiter the influence of various concentrations of iodide in blood on the iodine metabolism of the thyroid was investigated. This iodide level in blood was maintained for 7 days. 1. At a normal iodide level in blood of about 0.8 μg/100 ml the average iodine uptake of the thyroid was 13.3 μg/h. 2. Increasing iodide concentration in blood caused depressed uptake of 131I from a tracer dose as well as decreased T/S ratio. With the exception of 3 cases there was no uptake above 20 μg/100 ml. 3. The absolute iodine uptake of the thyroid depending on the concentration of iodide in blood was stimulated by moderate increases, but inhibited respectively blocked by higher ones. At a middle iodide level of 6.1, 15.1, 34.4 and 86.4 μg/100 ml of the absolute iodine uptake amounts to 82.0, 32.7, 2.0 resp. 2.1 μg/h. 4. The hormonal phase of the thyroidal iodine metabolism remained in most cases unchanged by the one week's iodide medication. In two cases only an activated iodine metabolism was suggested. The hormonal iodine concentration in blood never showed a thyrogenic increment.

scholarly journals RhoGAP RGA-8 supports morphogenesis in C. elegans by polarizing epithelia through CDC-42

2019 ◽  
Author(s):  
Hamidah Raduwan ◽  
Shashikala Sasidharan ◽  
Luigy Cordova Burgos ◽  
Andre G. Wallace ◽  
Martha C. Soto
Keyword(s):  
Cell Shape ◽  
Control Cell ◽  
Molecular Data ◽  
Regulatory Motifs ◽  
C Elegans ◽  
Cell Embryo ◽  
Embryonic Morphogenesis ◽  
The One ◽  
Muscle Myosin ◽  
Shape Changes

AbstractCDC-42 regulation of non-muscle myosin/NMY-2 is required for polarity maintenance in the one-cell embryo of C. elegans. CDC-42 and NMY-2 regulate polarity throughout embryogenesis, but their contribution to later events of morphogenesis are less understood. We have shown that epidermal enclosure requires the GTPase CED-10/Rac1 and WAVE/Scar complex, its effector, to promote protrusions that drive enclosure through the branch actin regulator Arp2/3. Our analysis here of RGA-8, a homolog of SH3BP1/Rich1/ARHGAP17/Nadrin, with BAR and RhoGAP motifs, suggests it regulates CDC-42, so that NMY-2 promotes two events of epidermal morphogenesis: ventral enclosure and elongation. Genetic and molecular data suggest RGA-8 regulates CDC-42, and the CDC-42 effectors WSP-1 and MRCK-1, in parallel to F-BAR proteins TOCA-1 and TOCA-2. The RGA-8-CDC-42-WSP-1 pathway enriches myosin in migrating epidermal cells during ventral enclosure. We propose TOCA proteins and RGA-8 use BAR domains to localize and regenerate CDC-42 activity, thus regulating F-actin levels, through the branched actin regulator WSP-1, and myosin polarity through the myosin kinase MRCK-1. Regulated CDC-42 thus polarizes epithelia, to control cell migrations and cell shape changes of embryonic morphogenesis.SummaryRGA-8, a protein with membrane binding and actin regulatory motifs, promotes embryonic morphogenesis by localizing active CDC-42 in developing epithelia, thus controlling actin and actin motors during cell movements.

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