scholarly journals Novel Role of Sphingolipid Synthesis Genes in Regulating Giardial Encystation

2008 ◽  
Vol 76 (7) ◽  
pp. 2939-2949 ◽  
Author(s):  
Yunuen Hernandez ◽  
Max Shpak ◽  
Trevor T. Duarte ◽  
Tavis L. Mendez ◽  
Rosa A. Maldonado ◽  
...  
Keyword(s):  
Gene Duplication ◽  
Giardia Lamblia ◽  
Phylogenetic Analyses ◽  
Cyst Formation ◽  
The Other ◽  
Serine Palmitoyltransferase ◽  
Cyst Production ◽  
Molecular Events ◽  
Key Events

ABSTRACT Although encystation (cyst formation) is important for the survival of Giardia lamblia outside its human host, the molecular events that prompt encystation have not been fully elucidated. Here, we demonstrate that sphingolipids (SLs), which are important for the growth and differentiation of many eukaryotes, play key roles in giardial encystation. Transcriptional analyses showed that only three genes in the SL biosynthesis pathways are expressed and transcribed differentially in nonencysting and encysting Giardia trophozoites. While the putative homologues of giardial serine palmitoyltransferase (gSPT) subunit genes (gspt-1 and -2) are differentially expressed in nonencysting and encysting trophozoites, the giardial ceramide glucosyltransferase 1 gene (gglct-1) is transcribed only in encysting cells. l-Cycloserine, an inhibitor of gSPT, inhibited the endocytosis and endoplasmic reticulum/perinuclear targeting of bodipy-ceramide in trophozoites, and this could be reversed by 3-ketosphinganine. On the other hand, d-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP), an inhibitor of glucosylceramide synthesis, blocked karyokinesis and reduced cyst production in culture. PPMP also altered the expression of cyst wall protein transcripts in encysting cells. Phylogenetic analyses revealed that the gspt genes are paralogs derived from an ancestral spt sequence that underwent gene duplication early in eukaryotic history. This ancestral sequence, in turn, was probably derived from prokaryotic aminoacyl transferases. In contrast, gglct-1 is found in both prokaryotes and eukaryotes without any evidence of gene duplication. These studies indicate that SL synthesis genes are involved in key events in giardial biology and could serve as potential targets for developing new therapies against giardiasis.

scholarly journals A Review of Key Biological and Molecular Events Underpinning Transformation of Melanocytes to Primary and Metastatic Melanoma

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2041 ◽  
Author(s):  
Louise A. Jackett ◽  
Richard A. Scolyer
Keyword(s):  
Treatment Strategies ◽  
Genomic Analysis ◽  
Molecular Therapy ◽  
Health Concern ◽  
Targeted Molecular Therapy ◽  
Public Health Concern ◽  
Molecular Events ◽  
Key Events ◽  
Potential Tool

Melanoma is a major public health concern that is responsible for significant morbidity and mortality, particularly in countries such as New Zealand and Australia where it is the commonest cause of cancer death in young adults. Until recently, there were no effective drug therapies for patients with advanced melanoma however significant advances in our understanding of the biological and molecular basis of melanoma in recent decades have led to the development of revolutionary treatments, including targeted molecular therapy and immunotherapy. This review summarizes our current understanding of the key events in the pathway of melanomagenesis and discusses the role of genomic analysis as a potential tool for improved diagnostic evaluation, prognostication and treatment strategies. Ultimately, it is hoped that a continued deeper understanding of the mechanisms of melanomagenesis will lead to the development of even more effective treatments that continue to provide better outcomes for patients with melanoma.

scholarly journals Reiterative AP2a activity controls sequential steps in the neural crest gene regulatory network

2010 ◽  
Vol 108 (1) ◽  
pp. 155-160 ◽  
Author(s):  
Noémie de Crozé ◽  
Frédérique Maczkowiak ◽  
Anne H. Monsoro-Burq
Keyword(s):  
Transcription Factors ◽  
Neural Crest ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
The Other ◽  
Molecular Events ◽  
Gene Regulatory ◽  
Progenitor Domain ◽  
Multifunctional Molecules

The neural crest (NC) emerges from combinatorial inductive events occurring within its progenitor domain, the neural border (NB). Several transcription factors act early at the NB, but the initiating molecular events remain elusive. Recent data from basal vertebrates suggest that ap2 might have been critical for NC emergence; however, the role of AP2 factors at the NB remains unclear. We show here that AP2a initiates NB patterning and is sufficient to elicit a NB-like pattern in neuralized ectoderm. In contrast, the other early regulators do not participate in ap2a initiation at the NB, but cooperate to further establish a robust NB pattern. The NC regulatory network uses a multistep cascade of secreted inducers and transcription factors, first at the NB and then within the NC progenitors. Here we report that AP2a acts at two distinct steps of this cascade. As the earliest known NB specifier, AP2a mediates Wnt signals to initiate the NB and activate pax3; as a NC specifier, AP2a regulates further NC development independent of and downstream of NB patterning. Our findings reconcile conflicting observations from various vertebrate organisms. AP2a provides a paradigm for the reiterated use of multifunctional molecules, thereby facilitating emergence of the NC in vertebrates.

scholarly journals Role of Leptin in Inflammation and Vice Versa

2020 ◽  
Vol 21 (16) ◽  
pp. 5887 ◽  
Author(s):  
Antonio Pérez-Pérez ◽  
Flora Sánchez-Jiménez ◽  
Teresa Vilariño-García ◽  
Víctor Sánchez-Margalet
Keyword(s):  
Chronic Inflammation ◽  
Weight Control ◽  
Tissue Injury ◽  
The Other ◽  
Leptin Resistance ◽  
Published Data ◽  
Multifactorial Diseases ◽  
Molecular Events ◽  
Mediators Of Inflammation

Inflammation is an essential immune response for the maintenance of tissue homeostasis. In a general sense, acute and chronic inflammation are different types of adaptive response that are called into action when other homeostatic mechanisms are insufficient. Although considerable progress has been made in understanding the cellular and molecular events that are involved in the acute inflammatory response to infection and tissue injury, the causes and mechanisms of systemic chronic inflammation are much less known. The pathogenic capacity of this type of inflammation is puzzling and represents a common link of the multifactorial diseases, such as cardiovascular diseases and type 2 diabetes. In recent years, interest has been raised by the discovery of novel mediators of inflammation, such as microRNAs and adipokines, with different effects on target tissues. In the present review, we discuss the data emerged from research of leptin in obesity as an inflammatory mediator sustaining multifactorial diseases and how this knowledge could be instrumental in the design of leptin-based manipulation strategies to help restoration of abnormal immune responses. On the other direction, chronic inflammation, either from autoimmune or infectious diseases, or impaired microbiota (dysbiosis) may impair the leptin response inducing resistance to the weight control, and therefore it may be a cause of obesity. Thus, we are reviewing the published data regarding the role of leptin in inflammation, and the other way around, the role of inflammation on the development of leptin resistance and obesity

scholarly journals Discovery of viral myosin genes with complex evolutionary history within plankton

2021 ◽  
Author(s):  
Soichiro Kijima ◽  
Tom O. Delmont ◽  
Urara Miyazaki ◽  
Morgan Gaia ◽  
Hisashi Endo ◽  
...  
Keyword(s):  
Evolutionary History ◽  
Viral Particle ◽  
Phylogenetic Analyses ◽  
Viral Proteins ◽  
The Other ◽  
Dna Viruses ◽  
Nucleocytoplasmic Large Dna Viruses ◽  
The One ◽  
Complex Evolutionary History

AbstractNucleocytoplasmic large DNA viruses (NCLDVs) infect diverse eukaryotes and form a group of viruses with capsids encapsulating large genomes. Recent studies are increasingly revealing a spectacular array of functions encoded in their genomes, including genes for energy metabolisms, nutrient uptake, as well as cytoskeleton. Here, we report the discovery of genes homologous to myosins, the major eukaryotic motor proteins previously unrecognized in the virosphere, in environmental genomes of NCLDVs from the surface of the oceans. Interestingly, these genes were often accompanied by kinesin genes in the environmental genomes, suggesting a role of these viral proteins in the intracellular viral particle transport. Phylogenetic analyses indicate that most viral myosins (named “virmyosins”) belong to the Imitervirales order, except for one belonging to the Phycodnaviridae family. On the one hand, the phylogenetic positions of virmyosin-encoding Imitervirales are scattered within the Imitervirales. On the other hand, Imitervirales virmyosin genes form a monophyletic group in the phylogeny of diverse myosin sequences. Furthermore, phylogenetic trends for the virmyosin genes and viruses containing them were incongruent. Based on these results, we argue that multiple transfers of myosin homologs have occurred not only from eukaryotes to viruses but also between viruses, supposedly during co-infections of the same host.

scholarly journals A single cell characterisation of human embryogenesis identifies pluripotency transitions and putative anterior hypoblast centre

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Matteo A. Molè ◽  
Tim H. H. Coorens ◽  
Marta N. Shahbazi ◽  
Antonia Weberling ◽  
Bailey A. T. Weatherbee ◽  
...  
Keyword(s):  
Single Cell ◽  
Human Embryo ◽  
State Transitions ◽  
Functional Studies ◽  
Embryonic Tissues ◽  
Molecular Events ◽  
Fgf Signalling ◽  
Key Events ◽  
Anterior Posterior

AbstractFollowing implantation, the human embryo undergoes major morphogenetic transformations that establish the future body plan. While the molecular events underpinning this process are established in mice, they remain unknown in humans. Here we characterise key events of human embryo morphogenesis, in the period between implantation and gastrulation, using single-cell analyses and functional studies. First, the embryonic epiblast cells transition through different pluripotent states and act as a source of FGF signals that ensure proliferation of both embryonic and extra-embryonic tissues. In a subset of embryos, we identify a group of asymmetrically positioned extra-embryonic hypoblast cells expressing inhibitors of BMP, NODAL and WNT signalling pathways. We suggest that this group of cells can act as the anterior singalling centre to pattern the epiblast. These results provide insights into pluripotency state transitions, the role of FGF signalling and the specification of anterior-posterior axis during human embryo development.

Plasma Levels of Protein S, Protein C, and Factor X: Effects of Sex, Hormonal State and Age

1995 ◽  
Vol 74 (05) ◽  
pp. 1271-1275 ◽  
Author(s):  
C M A Henkens ◽  
V J J Bom ◽  
W van der Schaaf ◽  
P M Pelsma ◽  
C Th Smit Sibinga ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Postmenopausal Women ◽  
Protein C ◽  
Blood Donors ◽  
Premenopausal Women ◽  
Protein S ◽  
The Other ◽  
Factor X ◽  
Normal Ranges

SummaryWe measured total and free protein S (PS), protein C (PC) and factor X (FX) in 393 healthy blood donors to assess differences in relation to sex, hormonal state and age. All measured proteins were lower in women as compared to men, as were levels in premenopausal women as compared to postmenopausal women. Multiple regression analysis showed that both age and subgroup (men, pre- and postmenopausal women) were of significance for the levels of total and free PS and PC, the subgroup effect being caused by the differences between the premenopausal women and the other groups. This indicates a role of sex-hormones, most likely estrogens, in the regulation of levels of pro- and anticoagulant factors under physiologic conditions. These differences should be taken into account in daily clinical practice and may necessitate different normal ranges for men, pre- and postmenopausal women.

On the role of the dispute between "non-possessors" and "Josephites" in the culture of Moscow's prediction

1998 ◽  
pp. 61-62
Author(s):  
N. S. Jurtueva
Keyword(s):  
The Other ◽  
Moral Transformation ◽  
15Th Century ◽  
The Future ◽  
Secular Power

In the XIV century. centripetal tendencies began to appear in the Moscow principality. Inside the Russian church, several areas were distinguished. Part of the clergy supported the specificobar form. The other understood the need for transformations in society. As a result, this led to a split in the Russian church in the 15th century for "non-possessors" and "Josephites". The former linked the fate of the future with the ideology of hesychasm and its moral transformation, while the latter sought support in alliance with a strong secular power.

From Container to Claustrum: Projective Identification in Couples

2014 ◽  
Vol 4 (2) ◽  
Author(s):  
Tamara Feldman
Keyword(s):  
Psychological Health ◽  
Projective Identification ◽  
The Self ◽  
The Other ◽  
Intimate Partners ◽  
And Control ◽  
The Relationship ◽  
As If

This paper is a contribution to the growing literature on the role of projective identification in understanding couples' dynamics. Projective identification as a defence is well suited to couples, as intimate partners provide an ideal location to deposit unwanted parts of the self. This paper illustrates how projective identification functions differently depending on the psychological health of the couple. It elucidates how healthier couples use projective identification more as a form of communication, whereas disturbed couples are inclined to employ it to invade and control the other, as captured by Meltzer's concept of "intrusive identification". These different uses of projective identification affect couples' capacities to provide what Bion called "containment". In disturbed couples, partners serve as what Meltzer termed "claustrums" whereby projections are not contained, but imprisoned or entombed in the other. Applying the concept of claustrum helps illuminate common feelings these couples express, such as feeling suffocated, stifled, trapped, held hostage, or feeling as if the relationship is killing them. Finally, this paper presents treatment challenges in working with more disturbed couples.

Thomas More's “rule” of pleasure before, after, and inUtopia

Moreana ◽  
2017 ◽  
Vol 54 (Number 207) (1) ◽  
pp. 36-56
Author(s):  
Gerard Wegemer
Keyword(s):  
Human Nature ◽  
The Other ◽  
Biblical Allusions ◽  
De Officiis

After establishing a context of More's lifelong engagement with the “calculus” of pleasure, this essay shows how the section devoted to the Utopians' pleasure philosophy is structured around five formulations of a “rule” to calculate “true and honest [honesta]” pleasure in ways that playfully imitate and echo the “rule” Cicero formulates several times in De officiis to discern one's duty when there seems to be a conflict between honestas et utilitas. When followed, the Utopian pleasure calculus shows the necessary role of societas, officii, iustitia, caritas, and the other aspects of human nature, most importantly friendship, that Cicero stresses in his rule and that he argued Epicurus ignored. Much of the irony and humor of this section depends on seeing the predominance of Ciceronian vocabulary in Raphael's unusual defense [patrocinium] of pleasure, rather than a Ciceronian defense of duty rooted in honestas. Throughout, however, this essay also shows how More goes beyond Cicero by including Augustinian and biblical allusions to suggest ways that our final end is not as Epicurus or the Stoics or Cicero claim; the language and allusions of this section point to a level of good cheer and care for neighbors and for God in ways quite different from any classical thinker.

BLOCKADE OF THE SURGE OF PROLACTIN AT PRO-OESTRUS BY ADMINISTRATION OF ANTI-OESTROGENIC SUBSTANCE, MER-25

1973 ◽  
Vol 74 (4) ◽  
pp. 769-774 ◽  
Author(s):  
Akira Yokoyama ◽  
Hiroshi Tomogane ◽  
Katuaki Ôta
Keyword(s):  
Strong Evidence ◽  
The Other ◽  
Other Hand

ABSTRACT A non-steroidal oestrogen antagonist, MER-25, was administered to cycling rats for elucidating the role of oestrogen in the surge of prolactin observed on the afternoon of pro-oestrus (POe). In animals injected with 20 mg of MER-25 intramuscularly on the afternoon (16.30 h) of the first day of dioestrus (D-1), the surge of prolactin was blocked while the level of prolactin on the afternoon of POe of these animals was significantly higher than that of the corresponding controls injected with oil. Ovulation was also blocked in these animals treated with the drug on the afternoon of D-l. On the other hand, treatment on the morning (10.30 h) of the 2nd day of dioestrus failed to prevent not only the surge of prolactin but also ovulation. These observations provide strong evidence for the view that oestrogen is responsible for the surge of prolactin on the afternoon of POe, and that the surge is accompanied by that of LH.

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