scholarly journals Loss of dmrt1 restores zebrafish female fates in the absence of cyp19a1a but not rbpms2a/b

Development ◽  
2020 ◽  
Vol 147 (18) ◽  
pp. dev190942
Author(s):  
Shannon Romano ◽  
Odelya H. Kaufman ◽  
Florence L. Marlow

ABSTRACTSex determination and differentiation is a complex process regulated by multiple factors, including factors from the germline or surrounding somatic tissue. In zebrafish, sex-determination involves establishment of a bipotential ovary that undergoes sex-specific differentiation and maintenance to form the functional adult gonad. However, the relationships among these factors are not fully understood. Here, we identify potential Rbpms2 targets and apply genetic epistasis experiments to decipher the genetic hierarchy of regulators of sex-specific differentiation. We provide genetic evidence that the crucial female factor rbpms2 is epistatic to the male factor dmrt1 in terms of adult sex. Moreover, the role of Rbpms2 in promoting female fates extends beyond repression of Dmrt1, as Rbpms2 is essential for female differentiation even in the absence of Dmrt1. In contrast, female fates can be restored in mutants lacking both cyp19a1a and dmrt1, and prolonged in bmp15 mutants in the absence of dmrt1. Taken together, this work indicates that cyp19a1a-mediated suppression of dmrt1 establishes a bipotential ovary and initiates female fate acquisition. Then, after female fate specification, Cyp19a1a regulates subsequent oocyte maturation and sustains female fates independently of Dmrt1 repression.

2020 ◽  
Author(s):  
Shannon Romano ◽  
Odelya H. Kaufman ◽  
Florence L. Marlow

AbstractSex determination and differentiation is a complex process regulated by multiple factors, including factors from the germline or surrounding somatic tissue. In zebrafish, sex-determination begins with establishment of a bipotential gonad that undergoes sex-specific differentiation and maintenance to form the functional adult gonad. However, the relationships among these factors are not fully understood. Here we identify potential Rbpms2 targets and apply genetic epistasis experiments to decipher the genetic hierarchy of regulators of sex-specific differentiation. We provide evidence that the critical female factor, rbpms2 is epistatic to the male factor dmrt1 in terms of adult sex. Moreover, Rbpms2’s role in promoting female fates extends beyond repression of Dmrt1, as Rbpms2 is essential for female differentiation even in the absence of Dmrt1. In contrast, female fates can be restored in mutants lacking cyp19a1a in the absence of dmrt1. Taken together this work indicates that Cyp19a1a-mediated suppression of Dmrt1 is key to establish a bipotential gonad and initiate female fate acquisition, possibly by promoting rbpms2. Then, after female fate specification, Cyp19a1a regulates subsequent oocyte maturation and sustains female fates independent of Dmrt1 repression.Author SummaryWe show that cyp19a1a-mediated suppression of dmrt1 establishes a bipotential gonad and female fate acquisition, possibly through rbpms2 which is required for female fates, even in the absence of Dmrt1.


Author(s):  
Xiao Zhou ◽  
Xiao-Fei Zhang ◽  
Dong-Yan Guo ◽  
Yan-Jun Yang ◽  
Lin Liu ◽  
...  

Objective: Lingzhu San (LZS) is a traditional Chinese medicine (TCM) prescription which can be effective in treating febrile seizures (FS) and has few researches on the mechanisms. In order to better guide the clinical use of LZS, we used the research ideas and methods of network pharmacology to find the potential core compounds, targets and pathways of LZS in the complex TCM system for the treatment of FS, and predict the mechanism. Materials and Methods: Databases such as BATMAN, TCMSP, TCMID, and SWISS TARGET are used to mine the active compounds and targets of LZS, and the target information of FS was obtained through GENECARDS and OMIM. Using Venny2.1.0 and Cytoscape software to locked the potential core compounds and targets of FS. The R language and ClusterProfiler software package were adopt to enrich and analyze the KEGG and GO pathways of the core targets and the biological processes and potential mechanisms of the core targets were revealed. Results: 187 active compounds and 2113 target proteins of LZS were collected. And 38 potential core compounds, 35 core targets and 775 metabolic and functional pathways were screened which involved in mediating FS. Finally, the role of the core compounds, targets and pivotal pathways of LZS regulated FS in the pathogenesis and therapeutic mechanism of FS was discussed and clarified. Conclusions: In this paper, the multi-compounds, multi-targets and multi-pathways mechanism of LZS in the treatment of FS was preliminarily revealed through the analysis of network pharmacology data, which is consistent with the principle of multi-compounds compatibility of TCM prescriptions and unified treatment of diseases from multiple angles, and it provides a new way for TCM to treat complex diseases caused by multiple factors.


Author(s):  
Walter Pohl

When the Gothic War began in Italy in 535, the country still conserved many features of classical culture and late antique administration. Much of that was lost in the political upheavals of the following decades. Building on Chris Wickham’s work, this contribution sketches an integrated perspective of these changes, attempting to relate the contingency of events to the logic of long-term change, discussing political options in relation to military and economic means, and asking in what ways the erosion of consensus may be understood in a cultural and religious context. What was the role of military entrepreneurs of more or less barbarian or Roman extraction in the distribution or destruction of resources? How did Christianity contribute to the transformation of ancient society? The old model of barbarian invasions can contribute little to understanding this complex process. It is remarkable that for two generations, all political strategies in Italy ultimately failed.


Author(s):  
Hans Liljenström

AbstractWhat is the role of consciousness in volition and decision-making? Are our actions fully determined by brain activity preceding our decisions to act, or can consciousness instead affect the brain activity leading to action? This has been much debated in philosophy, but also in science since the famous experiments by Libet in the 1980s, where the current most common interpretation is that conscious free will is an illusion. It seems that the brain knows, up to several seconds in advance what “you” decide to do. These studies have, however, been criticized, and alternative interpretations of the experiments can be given, some of which are discussed in this paper. In an attempt to elucidate the processes involved in decision-making (DM), as an essential part of volition, we have developed a computational model of relevant brain structures and their neurodynamics. While DM is a complex process, we have particularly focused on the amygdala and orbitofrontal cortex (OFC) for its emotional, and the lateral prefrontal cortex (LPFC) for its cognitive aspects. In this paper, we present a stochastic population model representing the neural information processing of DM. Simulation results seem to confirm the notion that if decisions have to be made fast, emotional processes and aspects dominate, while rational processes are more time consuming and may result in a delayed decision. Finally, some limitations of current science and computational modeling will be discussed, hinting at a future development of science, where consciousness and free will may add to chance and necessity as explanation for what happens in the world.


2012 ◽  
Vol 2 (2) ◽  
pp. 99-103 ◽  
Author(s):  
S Jahan

Infertility is defined as failure to conceive during one year of unprotected frequent intercourse. Leading causes of infertility include tubal disease, ovulatory disorders, uterine or cervical factors, endometriosis and male factor infertility. A laparoscope is a thin fiber optic telescope that is inserted into the abdomen usually through the belly button. The fiber optics allow a light to used to see inside the abdomen. Carbon dioxide (CO2) gas is placed into the abdomen prior to inserting the laparoscope. Generally, laparoscopy should be reserved for couples who have already completed a more basic infertility evaluation including assessing for ovulation, ovarian reserve, ultrasound and hysterosalpingogram for the female and semen analysis for the male. Laparoscopy can help physicians diagnose many gynecological problems including endometriosis, uterine fibroids and other structural abnormalities, ovarian cysts, adhesions (scar tissue), and ectopic pregnancy. Robotic assisted laparoscopic surgery (RAL) is a more recent development and a form of operative laparoscopy. In RAL, the instruments and telescope are very similar to conventional laparoscopy, but they are attached to a robot which in turn is controlled by the surgeon who is seated at a viewing console. Women who have been diagnosed with endometriosis are more likely to experience infertility, and observational studies have shown that the monthly probability of pregnancy in women with endometriosis is about half of the probability in normal women. In spite of this well-documented association, a true cause and effect relationship has not been established. Laparoscopy is used world-wide to investigate infertility. It is an essential part of full assessment and treatment of infertility. It provides direct visualization of the pelvic organs, ovarian and tubal status and can elucidate the site of tubal obstruction. It has got an advantage of direct visualization of the pelvic organs and the peri-tubal status resulting in greater information as compared to hysterosalpingography and ultrasonography. The advance in instrument technology has made this procedure more productive and less hazardous. Laparoscopy is the most dependable tool to investigate pelvic pathology. The role of laparoscopy in diagnosis of infertility both primary as well as secondary is established beyond any doubt.DOI: http://dx.doi.org/10.3329/birdem.v2i2.12324 (Birdem Med J 2012; 2(2): 99-103)


Development ◽  
1995 ◽  
Vol 121 (1) ◽  
pp. 99-111 ◽  
Author(s):  
M.A. Pultz ◽  
B.S. Baker

The hermaphrodite (her) locus has both maternal and zygotic functions required for normal female development in Drosophila. Maternal her function is needed for the viability of female offspring, while zygotic her function is needed for female sexual differentiation. Here we focus on understanding how her fits into the sex determination regulatory hierarchy. Maternal her function is needed early in the hierarchy: genetic interactions of her with the sisterless genes (sis-a and sis-b), with function-specific Sex-lethal (Sxl) alleles and with the constitutive allele SxlM#1 suggest that maternal her function is needed for Sxl initiation. When mothers are defective for her function, their daughters fail to activate a reporter gene for the Sxl early promoter and are deficient in Sxl protein expression. Dosage compensation is misregulated in the moribund daughters: some salivary gland cells show binding of the maleless (mle) dosage compensation regulatory protein to the X chromosome, a binding pattern normally seen only in males. Thus maternal her function is needed early in the hierarchy as a positive regulator of Sxl, and the maternal effects of her on female viability probably reflect Sxl's role in regulating dosage compensation. In contrast to her's maternal function, her's zygotic function in sex determination acts at the end of the hierarchy. This zygotic effect is not rescued by constitutive Sxl expression, nor by constitutive transformer (tra) expression. Moreover, the expression of doublesex (dsx) transcripts appears normal in her mutant females. We conclude that the maternal and zygotic functions of her are needed at two distinctly different levels of the sex determination regulatory hierarchy.


Minerals ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. 370 ◽  
Author(s):  
Jean-Pierre Cuif ◽  
Yannicke Dauphin ◽  
Gilles Luquet ◽  
Kadda Medjoubi ◽  
Andrea Somogyi ◽  
...  

A top-down approach to the mineralized structures and developmental steps that can be separated in the shells of Pinctada margaritifera was carried out. Detailed characterizations show that each of the two major layers usually taken into account (the outer prismatic layer and the inner nacreous layer) is actually the result of a complex process during which the microstructural patterns were progressively established. From its early growing stages in the deeper part of the periostracal grove up to the formation of the most inner nacreous layers, this species provides a demonstrative case study illustrating the leading role of specifically secreted organic structures as determinants of the crystallographic properties of the shell-building units. Gathering data established at various observational scales ranging from morphology to the nanometer level, this study allows for a reexamination of the recent and current biomineralization models.


2014 ◽  
Vol 86 (3) ◽  
pp. 164 ◽  
Author(s):  
Davide Arcaniolo ◽  
Vincenzo Favilla ◽  
Daniele Tiscione ◽  
Francesca Pisano ◽  
Giorgio Bozzini ◽  
...  

Objective: Infertility affects 15% of couples in fertile age. Male factor is a cause of infertility in almost half of cases, mainly due to oligoasthenoteratozoospermia (OAT). The purpose of this study is to review the effects of nutritional supplements as medical treatment for idiopathic male infertility. Material and methods: A Pub Med and Medline review of the published studies utilizing nutritional supplements for the treatment of male infertility has been performed. Results: Clinical trials on Vitamin E, Vitamin A, Vitamin C. Arginine, Carnitine, N-Acetyl-Carnitine, Glutathione, Coenzyme Q10, Selenium and Zinc were reviewed. Although there is a wide variability in selected population, dose regimen and final outcomes, nutritional supplements both alone and in combination seems to be able to improve semen parameters (sperm count, sperm motility and morphology) and pregnancy rate in infertile men. Conclusions: There are rising evidences from published randomized trials and systematic review suggesting that nutritional supplementation may improve semen parameters and the likelihood of pregnancy in men affected by OAT. This improvement, however, is not consistent and there is a wide variation in the treatment regimens used. Well designed and adequately powered RCTs are needed to better clarify the role of nutritional supplements as treatment for male infertility.


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