scholarly journals Hedgehog Signaling and Embryonic Craniofacial Disorders

2019 ◽  
Vol 7 (2) ◽  
pp. 9 ◽  
Author(s):  
Abramyan
Keyword(s):  
Hedgehog Signaling ◽  
Developmental Disorders ◽  
Critical Role ◽  
Hedgehog Pathway ◽  
Developmental Defects ◽  
Downstream Target ◽  
Secondary Palate ◽  
The Face ◽  
Range Of Functions ◽  
Key Aspects

Since its initial discovery in a Drosophila mutagenesis screen, the Hedgehog pathway has been revealed to be instrumental in the proper development of the vertebrate face. Vertebrates possess three hedgehog paralogs: Sonic hedgehog (Shh), Indian hedgehog (Ihh), and Desert hedgehog (Dhh). Of the three, Shh has the broadest range of functions both in the face and elsewhere in the embryo, while Ihh and Dhh play more limited roles. The Hedgehog pathway is instrumental from the period of prechordal plate formation early in the embryo, until the fusion of the lip and secondary palate, which complete the major patterning events of the face. Disruption of Hedgehog signaling results in an array of developmental disorders in the face, ranging from minor alterations in the distance between the eyes to more serious conditions such as severe clefting of the lip and palate. Despite its critical role, Hedgehog signaling seems to be disrupted through a number of mechanisms that may either be direct, as in mutation of a downstream target of the Hedgehog ligand, or indirect, such as mutation in a ciliary protein that is otherwise seemingly unrelated to the Hedgehog pathway. A number of teratogens such as alcohol, statins and steroidal alkaloids also disrupt key aspects of Hedgehog signal transduction, leading to developmental defects that are similar, if not identical, to those of Hedgehog pathway mutations. The aim of this review is to highlight the variety of roles that Hedgehog signaling plays in developmental disorders of the vertebrate face.

Particularities of the independent auditor's report on reliability of accounting (financial) statements for 2019: COVID-19 as qualitatively essential information (Part 2)

2020 ◽  
Vol 23 (7) ◽  
pp. 777-799
Author(s):  
O.I. Shvyreva ◽  
Z.I. Kruglyak ◽  
A.V. Petukh
Keyword(s):  
Financial Reporting ◽  
Financial Statements ◽  
Economic Situation ◽  
Risk Disclosure ◽  
Essential Information ◽  
Logical Method ◽  
Annual Reporting ◽  
The Face ◽  
Key Aspects ◽  
The Impact

Subject. This article discusses the issues related to the practice of financial reporting in the face of uncertainties caused by the coronavirus contagion, as well as the specifics of the audit strategy and formation of an audit opinion on this reporting. Objectives. The article aims to identify the quality characteristics of financial reporting prepared in the context of the COVID-19 pandemic and justify the key aspects of assurance engagement completion in an extremely uncertain epidemiological and economic situation. Methods. For the study, we used an abstract-logical method, content analysis techniques, systematization, and classification. Results. Analyzing the impact of the extremely uncertain epidemiological and economic situation on financial statements, the article clarifies aspects of disclosure of events after the reporting date and threats to business continuity in the annual reporting of economic entities. The article identifies possible alternative procedures and algorithms to obtain proper evidence when it is insufficient in the face of the inability to meet certain audit standards requirements in a remote audit environment. The article defines the impact of COVID-19 risk disclosure on the structure of the audit report and opinion. Relevance. The results of the study can be used in the practical activities of economic entities that prepare financial statements in the face of significant uncertainty, as well as auditors and audit organizations.

scholarly journals Ultrafiltration Method for Plasma Protein Binding Studies and Its Limitations

Processes ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 382
Author(s):  
Camelia-Maria Toma ◽  
Silvia Imre ◽  
Camil-Eugen Vari ◽  
Daniela-Lucia Muntean ◽  
Amelia Tero-Vescan
Keyword(s):  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Specific Binding ◽  
Critical Role ◽  
Volume Ratio ◽  
Binding Studies ◽  
Experimental Conditions ◽  
Key Aspects

Plasma protein binding plays a critical role in drug therapy, being a key part in the characterization of any compound. Among other methods, this process is largely studied by ultrafiltration based on its advantages. However, the method also has some limitations that could negatively influence the experimental results. The aim of this study was to underline key aspects regarding the limitations of the ultrafiltration method, and the potential ways to overcome them. The main limitations are given by the non-specific binding of the substances, the effect of the volume ratio obtained, and the need of a rigorous control of the experimental conditions, especially pH and temperature. This review presents a variety of methods that can hypothetically reduce the limitations, and concludes that ultrafiltration remains a reliable method for the study of protein binding. However, the methodology of the study should be carefully chosen.

scholarly journals A critical role of autocrine sonic hedgehog signaling in human CD138+ myeloma cell survival and drug resistance

Blood ◽  
2014 ◽  
Vol 124 (13) ◽  
pp. 2061-2071 ◽  
Author(s):  
Zhiqiang Liu ◽  
Jingda Xu ◽  
Jin He ◽  
Yuhuan Zheng ◽  
Haiyan Li ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Survival ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Critical Role ◽  
Myeloma Cell ◽  
Sonic Hedgehog Signaling ◽  
Key Points

Key Points CD138+ MM cells are a major source of SHH. Autocrine SHH enhances MM drug resistance.

scholarly journals A Tocqueville For the North? André Siegfried and Canada

2005 ◽  
Vol 14 (1) ◽  
pp. 117-136 ◽  
Author(s):  
Sean Kennedy
Keyword(s):  
Critical Role ◽  
Second World War ◽  
Traditional Values ◽  
French Canada ◽  
The North ◽  
Vichy Regime ◽  
The Face ◽  
A Site ◽  
French National Identity ◽  
Second World

Abstract This paper argues that André Siegfried’s writings on Canada played a critical role in shaping his vision of French national identity. Siegfried’s studies of Canada have long been praised for their insight, but recent scholarship has emphasized his role in promoting both anti-Americanism and an exclusionary vision of what it meant to be French during the first half of the twentieth century. For Siegfried, Canada represented a site of managed contestation between British and French culture but also an early example of the deleterious effects of Americanization. His problematic view of French Canada as essentially conservative and unchanging in the face of such challenges reinforced his conviction that France itself should remain true to “traditional” values. The exclusionary implications of his ideas were most evident when Siegfried appeared to accommodate himself to the Vichy regime, but they also persisted after the Second World War.

scholarly journals The integrin coactivator Kindlin-2 plays a critical role in angiogenesis in mice and zebrafish

Blood ◽  
2011 ◽  
Vol 117 (18) ◽  
pp. 4978-4987 ◽  
Author(s):  
Elzbieta Pluskota ◽  
James J. Dowling ◽  
Natalie Gordon ◽  
Jeffrey A. Golden ◽  
Dorota Szpak ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Critical Role ◽  
Integrin Αvβ3 ◽  
Tube Formation ◽  
Basement Membranes ◽  
Cytoskeletal Protein ◽  
Integrin Expression ◽  
Partial Reduction ◽  
Wild Type ◽  
Developmental Defects

Abstract Kindlin-2, a widely distributed cytoskeletal protein, has been implicated in integrin activation, and its absence is embryonically lethal in mice and causes severe developmental defects in zebrafish. Knockdown of kindlin-2 levels in endothelial cells resulted in defective adhesive and migratory responses, suggesting that angiogenesis might be aberrant even with partial reduction of kindlin-2. This hypothesis has now been tested in the kindlin-2+/− mice. RM1 prostate tumors grown in kindlin-2+/− mice had fewer blood vessels, which were thinner and shorter and supported less tumor growth compared with wild-type littermates. The vessels that did form in the kindlin-2+/− mice lacked smooth muscle cells and pericytes and had thinner basement membranes, indicative of immature vessels. VEGF-induced angiogenesis in matrigel implants was also abnormal in the kindlin-2+/− mice. Vessels in the kindlin-2+/− mice were leaky, and BM transplantation from kindlin-2+/− to WT mice did not correct this defect. Endothelial cells derived from kindlin-2+/− mice had integrin expression levels similar to WT mice but reduced αVβ3-dependent signaling, migration, adhesion, spreading, and tube formation. Developmental angiogenesis was markedly impaired by kindlin-2 morpholinos in zebrafish. Taken together, kindlin-2 plays an important role in pathologic and developmental angiogenesis, which arises from defective activation of integrin αVβ3.

scholarly journals Dosage-Dependent Effects of Akt1/Protein Kinase Bα (PKBα) and Akt3/PKBγ on Thymus, Skin, and Cardiovascular and Nervous System Development in Mice

2005 ◽  
Vol 25 (23) ◽  
pp. 10407-10418 ◽  
Author(s):  
Zhong-Zhou Yang ◽  
Oliver Tschopp ◽  
Nicolas Di-Poï ◽  
Elisabeth Bruder ◽  
Anne Baudry ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cell Cycle Progression ◽  
System Development ◽  
Critical Role ◽  
Nervous System Development ◽  
Mouse Development ◽  
Double Knockout ◽  
Developmental Defects ◽  
Regulation Of Metabolism ◽  
Survival And Development

ABSTRACT Akt/protein kinase B (PKB) plays a critical role in the regulation of metabolism, transcription, cell migration, cell cycle progression, and cell survival. The existence of viable knockout mice for each of the three isoforms suggests functional redundancy. We generated mice with combined mutant alleles of Akt1 and Akt3 to study their effects on mouse development. Here we show that Akt1 − / − Akt3 +/ − mice display multiple defects in the thymus, heart, and skin and die within several days after birth, while Akt1 +/ − Akt3 − / − mice survive normally. Double knockout (Akt1 − / − Akt3 − / −) causes embryonic lethality at around embryonic days 11 and 12, with more severe developmental defects in the cardiovascular and nervous systems. Increased apoptosis was found in the developing brain of double mutant embryos. These data indicate that the Akt1 gene is more essential than Akt3 for embryonic development and survival but that both are required for embryo development. Our results indicate isoform-specific and dosage-dependent effects of Akt on animal survival and development.

scholarly journals Calcium Signaling in Vertebrate Development and Its Role in Disease

2018 ◽  
Vol 19 (11) ◽  
pp. 3390 ◽  
Author(s):  
Sudip Paudel ◽  
Regan Sindelar ◽  
Margaret Saha
Keyword(s):  
Calcium Signaling ◽  
Critical Role ◽  
Molecular Techniques ◽  
Model Organisms ◽  
Vertebrate Development ◽  
Developmental Defects ◽  
Calcium Activity ◽  
Human Genes ◽  
Underlying Mechanisms

Accumulating evidence over the past three decades suggests that altered calcium signaling during development may be a major driving force for adult pathophysiological events. Well over a hundred human genes encode proteins that are specifically dedicated to calcium homeostasis and calcium signaling, and the majority of these are expressed during embryonic development. Recent advances in molecular techniques have identified impaired calcium signaling during development due to either mutations or dysregulation of these proteins. This impaired signaling has been implicated in various human diseases ranging from cardiac malformations to epilepsy. Although the molecular basis of these and other diseases have been well studied in adult systems, the potential developmental origins of such diseases are less well characterized. In this review, we will discuss the recent evidence that examines different patterns of calcium activity during early development, as well as potential medical conditions associated with its dysregulation. Studies performed using various model organisms, including zebrafish, Xenopus, and mouse, have underscored the critical role of calcium activity in infertility, abortive pregnancy, developmental defects, and a range of diseases which manifest later in life. Understanding the underlying mechanisms by which calcium regulates these diverse developmental processes remains a challenge; however, this knowledge will potentially enable calcium signaling to be used as a therapeutic target in regenerative and personalized medicine.

scholarly journals INVESTIGATION OF THE EFFECT OF FATHER EDUCATION ON THE PERCEPTION OF FATHERHOOD IN THE LIFELONG LEARNING PROCESS

2020 ◽  
Vol 7 (12) ◽  
Author(s):  
Yeşim Şölen ◽  
Yıldız Öztan Ulusoy
Keyword(s):  
Lifelong Learning ◽  
Learning Process ◽  
Critical Role ◽  
Structured Interview ◽  
Healthy Individuals ◽  
Face To Face ◽  
Preschool Period ◽  
The Face ◽  
Academic Year ◽  
Patriarchal Social Structure

In this study, the perceptions of fathers with children in the preschool period towards the concept of fatherhood, a lifelong learning process, and father education after the father education they received, were examined. The study was carried out with a qualitative research method. The sample of the study consisted of 14 fathers who had children attending two kindergartens in Kocaeli in the 2018-2019 academic year and volunteering to participate in the study. Fourteen fathers in the group were interviewed after the training program was applied. As a result of the face-to-face interviews with the semi-structured interview form, what they expressed about fatherhood, how they expressed themselves as fathers in the lifelong learning process, and their thoughts on participation in father education were obtained. It is known that the father has a critical role in the formation of the child's personality. Father education should be given importance to raise happy and healthy individuals. Today, it has been observed that there is a transition from the patriarchal social structure to modernity, and the fathers' traditional thoughts have changed, and they have started to think more child-oriented. It has been revealed that fathers gain awareness after education and fatherhood is a conscious and learnable phenomenon when an effort is made. <p> </p><p><strong> Article visualizations:</strong></p><p><img src="/-counters-/edu_01/0720/a.php" alt="Hit counter" /></p>

Targeting Hedgehog signaling and understanding refractory response to treatment with Hedgehog pathway inhibitors

2012 ◽  
Vol 15 (4) ◽  
pp. 211-222 ◽  
Author(s):  
Karla C.S. Queiroz ◽  
C. Arnold Spek ◽  
Maikel P. Peppelenbosch
Keyword(s):  
Hedgehog Signaling ◽  
Hedgehog Pathway ◽  
Response To Treatment
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