Prx1andPrx2are upstream regulators of sonic hedgehog and control cell proliferation during mandibular arch morphogenesis

Development ◽  
2001 ◽  
Vol 128 (15) ◽  
pp. 2929-2938 ◽  
Author(s):  
Derk ten Berge ◽  
Antje Brouwer ◽  
Jeroen Korving ◽  
Mark J. Reijnen ◽  
Estia J. van Raaij ◽  
...  

The aristaless-related homeobox genes Prx1 and Prx2 are required for correct skeletogenesis in many structures. Mice that lack both Prx1 and Prx2 functions display reduction or absence of skeletal elements in the skull, face, limbs and vertebral column. A striking phenotype is found in the lower jaw, which shows loss of midline structures, and the presence of a single, medially located incisor. We investigated development of the mandibular arch of Prx1−/−Prx2−/− mutants to obtain insight into the molecular basis of the lower jaw abnormalities. We observed in mutant embryos a local decrease in proliferation of mandibular arch mesenchyme in a medial area. Interestingly, in the oral epithelium adjacent to this mesenchyme, sonic hedgehog (Shh) expression was strongly reduced, indicative of a function for Prx genes in indirect regulation of Shh. Wild-type embryos that were exposed to the hedgehog-pathway inhibitor, jervine, partially phenocopied the lower jaw defects of Prx1−/−Prx2−/− mutants. In addition, this treatment led to loss of the mandibular incisors. We present a model that describes how loss of Shh expression in Prx1−/−Prx2−/− mutants leads to abnormal morphogenesis of the mandibular arch.

Author(s):  
Tamara Green

Much of the literature, policies, programs, and investment has been made on mental health, case management, and suicide prevention of veterans. The Australian “veteran community is facing a suicide epidemic for the reasons that are extremely complex and beyond the scope of those currently dealing with them.” (Menz, D: 2019). Only limited work has considered the digital transformation of loosely and manual-based historical records and no enablement of Artificial Intelligence (A.I) and machine learning to suicide risk prediction and control for serving military members and veterans to date. This paper presents issues and challenges in suicide prevention and management of veterans, from the standing of policymakers to stakeholders, campaigners of veteran suicide prevention, science and big data, and an opportunity for the digital transformation of case management.


Author(s):  
David D. Nolte

Galileo Unbound: A Path Across Life, The Universe and Everything traces the journey that brought us from Galileo’s law of free fall to today’s geneticists measuring evolutionary drift, entangled quantum particles moving among many worlds, and our lives as trajectories traversing a health space with thousands of dimensions. Remarkably, common themes persist that predict the evolution of species as readily as the orbits of planets or the collapse of stars into black holes. This book tells the history of spaces of expanding dimension and increasing abstraction and how they continue today to give new insight into the physics of complex systems. Galileo published the first modern law of motion, the Law of Fall, that was ideal and simple, laying the foundation upon which Newton built the first theory of dynamics. Early in the twentieth century, geometry became the cause of motion rather than the result when Einstein envisioned the fabric of space-time warped by mass and energy, forcing light rays to bend past the Sun. Possibly more radical was Feynman’s dilemma of quantum particles taking all paths at once—setting the stage for the modern fields of quantum field theory and quantum computing. Yet as concepts of motion have evolved, one thing has remained constant, the need to track ever more complex changes and to capture their essence, to find patterns in the chaos as we try to predict and control our world.


Author(s):  
Andreas Müller ◽  
Shivesh Kumar

AbstractDerivatives of equations of motion (EOM) describing the dynamics of rigid body systems are becoming increasingly relevant for the robotics community and find many applications in design and control of robotic systems. Controlling robots, and multibody systems comprising elastic components in particular, not only requires smooth trajectories but also the time derivatives of the control forces/torques, hence of the EOM. This paper presents the time derivatives of the EOM in closed form up to second-order as an alternative formulation to the existing recursive algorithms for this purpose, which provides a direct insight into the structure of the derivatives. The Lie group formulation for rigid body systems is used giving rise to very compact and easily parameterized equations.


2019 ◽  
Vol 8 (12) ◽  
pp. 2217 ◽  
Author(s):  
Parviz Mammadzada ◽  
Juliette Bayle ◽  
Johann Gudmundsson ◽  
Anders Kvanta ◽  
Helder André

MicroRNAs (miRNAs) can provide insight into the pathophysiological states of ocular tissues such as proliferative diabetic retinopathy (PDR). In this study, differences in miRNA expression in vitreous from PDR patients with and without incidence of recurrent vitreous hemorrhage (RVH) after the initial pars-plana vitrectomy (PPV) were analyzed, with the aim of identifying biomarkers for RVH. Fifty-four consented vitreous samples were analyzed from patients undergoing PPV for PDR, of which eighteen samples underwent a second surgery due to RVH. Ten of the sixty-six expressed miRNAs (miRNAs-19a, -20a, -22, -27a, -29a, -93, -126, -128, -130a, and -150) displayed divergences between the PDR vitreous groups and to the control. A significant increase in the miRNA-19a and -27a expression was determined in PDR patients undergoing PPV as compared to the controls. miRNA-20a and -93 were significantly upregulated in primary PPV vitreous samples of patients afflicted with RVH. Moreover, this observed upregulation was not significant between the non-RVH and control group, thus emphasizing the association with RVH incidence. miRNA-19a and -27a were detected as putative vitreous biomarkers for PDR, and elevated levels of miRNA-20a and -93 in vitreous with RVH suggest their biomarker potential for major PDR complications such as recurrent hemorrhage incidence.


2008 ◽  
Vol 22 (18n19) ◽  
pp. 3069-3081 ◽  
Author(s):  
SHAHAB FAGHIHI ◽  
HOJATOLLAH VALI ◽  
MARYAM TABRIZIAN

The aim of this study is to investigate the effect of atomic structure of polycrystalline materials on cell-substrate interactions. Samples are prepared from rods and sheets of Ti -6 Al -4 V substrates with predominately two distinct crystallographic orientations as well as nano-structured and annealed titanium fabricated through high-pressure torsion and heat treatment processes. The degree of preosteoblast attachment and rate of growth, which are regulated through the activity and interaction of proteins present in the extracellular matrix, are notably increased on the nano-structured titanium and substrate having predominant [Formula: see text] orientation. The improved cell activity is attributed to the nano-structured feature of these substrates consisting of ultra-fine crystals (< 50 nm) and specific atomic order of [Formula: see text] substrate which provide higher degree of surface wettability. These findings demonstrate the advantages of nano-structured titanium over the conventional and coated titanium implants, as both mechanical properties and cellular response are improved. Furthermore, crystal orientation of the substrates can influence cell responses and, therefore, substrate engineering can be used to improve and control cell-substrate interactions.


2021 ◽  
Vol 1 (38) ◽  
pp. 36-40
Author(s):  
A. A. Sletov ◽  
D. V. Mikhalchenko ◽  
A. V. Zhidovinov ◽  
A. S. Serbin ◽  
K. A. Aleshanov ◽  
...  

Cancer of the lower jaw is one of the most common causes of the development of total defects. There are many indices and indicators to assess the quality of life of patients with this pathology, but they do not fully describe the features of their postoperative rehabilitation. The question of developing an evaluation criterion for the introduction of a special device in patients with subtotal defects of the lower jaw remains open.Material and methods. In the period from 2010 to 2021, 100 patients with subtotal defects of the lower jaw, aged 30 to 65 years old, who are being treated in the Department of Maxillofacial Surgery at the Department of Maxillofacial Surgery of the GBUZ SKKKB, were interviewed. All patients were divided into 2 groups of 50 people each. In the main rehabilitation was carried out using a special device to optimize the biomechanics of the lower jaw, in the control group, rehabilitation was carried out without one. The article presents the results of assessing the quality of life, which were carried out using a special questionnaire.Conclusions. This questionnaire makes it possible to assess the standard of living of patients using a special device at the stages of rehabilitation.


Author(s):  
Ariella Meltzer ◽  
Helen Dickinson ◽  
Eleanor Malbon ◽  
Gemma Carey

Background: Many countries use market forces to drive reform across disability supports and services. Over the last few decades, many countries have individualised budgets and devolved these to people with disability, so that they can purchase their own choice of supports from an available market of services.Key points for discussion: Such individualised, market-based schemes aim to extend choice and control to people with disability, but this is only achievable if the market operates effectively. Market stewardship has therefore become an important function of government in guiding markets and ensuring they operate effectively.The type of evidence that governments tend to draw on in market stewardship is typically limited to inputs and outputs and has less insight into the outcomes services do or do not achieve. While this is a typical approach to market stewardship, we argue it is problematic and that a greater focus on outcomes is necessary.Conclusions and implications: To include a focus on outcomes, we argue that market stewards need to take account of the lived experience of people with disability. We present a framework for doing this, drawing on precedents where people with disability have contributed lived experience evidence within other policy, research, knowledge production and advocacy contexts.With the lived experience evidence of people with disability included, market stewardship will be better able to take account of outcomes as they play out in the lives of those using the market and, ultimately, achieve greater choice and control for people with disability.<br />Key messages<br /><ul><li>Market stewardship is key to guiding quasi-markets, including in the disability sector;</li><br /><li>Evidence guiding market stewardship is often about inputs and outputs only;</li><br /><li>It would be beneficial to also include lived experience evidence from people with disability;</li><br /><li>We propose a framework for the inclusion of lived experience evidence in market stewardship.</li></ul>


Author(s):  
Steven M. Ortiz

Male professional athletes captivate fans and profoundly influence today’s society as part of the $1.3 trillion global sport industry. Although these athletes’ lives and careers are widely reported, scholarly knowledge about the women who support them—their wives—is extremely limited. Because these women’s voices have historically been stifled, their marriages are shockingly misunderstood. Based on findings from the first and only longitudinal study on the sport marriage, this book corrects the abundance of misinformation reported by all forms of media, dispels undeserved stereotypes, and addresses inaccurate assumptions about the heteronormative sport marriage. It demonstrates how, despite major changes in society and sport since the end of the last century, the fundamental nature of the heteronormative sport marriage has not changed. Sport wives remain isolated and subordinate, even while they make significant contributions to their husbands’ careers. Identifying the sport marriage as a career-dominated marriage, the book allows us into these women’s public and private lives, including their need to conform to unwritten rules and codes, adapt to abundant power and control issues, cope with groupies from all walks of life, and find ways to deal with their oft-justified fears about their husbands’ infidelity. The book shares intimate stories about, and provides rare and unflinching insight into, what it is like to be married to these highly visible men, what it means to be a woman in the male-dominated world of professional sports, and why women remain in a sport marriage at great cost to themselves.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Stephen C Kolwicz ◽  
Rong Tian

Introduction: Previous studies using cell culture models identified cyto-toxic effects of palmitate and that supplementation with oleate was protective by redirecting palmitate into triacylglycerol (TAG) stores. However, other cull culture studies reported that diacylglycerol transferase 1 (DGAT1), the last enzyme in TAG synthesis, demonstrated a preference for oleate. At present, it is not clear whether the supply of exogenous fatty acids (FA) to the heart is differentially allocated into the endogenous TAG pool. Therefore, the purpose of the present study is to examine the influence of palmitate and/or oleate on cardiac TAG incorporation. METHODS/RESULTS: Hearts were isolated from DGAT1-transgenic (DGAT) and control littermates (CON) and perfused in Langendorff mode with a mixed substrate buffer consisting of glucose, lactate, insulin, and FAs. The FA supply was varied with 0.2mM of both labeled (13C) and unlabeled (12C) FAs in 4 different experiments: 1) 13C/12C palmitate; 2) 13C/12C oleate; 3) 13C palmitate/12C oleate; 4) 13C oleate/12C palmitate. The incorporation of 13C palmitate or 13C oleate into the TAG pool was monitored by 13C NMR spectroscopy. In CON hearts (n=3), the incorporation of palmitate was ~65% higher than oleate when the perfusate contained a homogenous supply of FA. This was also observed in DGAT hearts (n=4) although the incorporation of both palmitate and oleate was ~75% higher compared to CON (P <0.05). In the presence of oleate, palmitate incorporation decreased 25-30% in both CON and DGAT hearts. In contrast, oleate incorporation was diminished by ~50% and ~100% in CON and DGAT hearts, respectively, in the presence of palmitate. CONCLUSIONS: These data suggest that when palmitate and oleate are provided in equal concentrations, palmitate is more readily utilized in the synthesis of endogenous TAG stores in the heart. Furthermore, although overexpression of DGAT increases both oleate and palmitate incorporation, the DGAT1 enzyme demonstrates a preference for palmitate. These findings provide insight into the relationship between exogenous FA supply and endogenous TAG dynamics in the contracting heart.


2012 ◽  
Vol 44 (12) ◽  
pp. 638-650 ◽  
Author(s):  
Pani A. Apostolidis ◽  
Stephan Lindsey ◽  
William M. Miller ◽  
Eleftherios T. Papoutsakis

During endomitosis, megakaryocytes undergo several rounds of DNA synthesis without division leading to polyploidization. In primary megakaryocytes and in the megakaryocytic cell line CHRF, loss or knock-down of p53 enhances cell cycling and inhibits apoptosis, leading to increased polyploidization. To support the hypothesis that p53 suppresses megakaryocytic polyploidization, we show that stable expression of wild-type p53 in K562 cells (a p53-null cell line) attenuates the cells' ability to undergo polyploidization during megakaryocytic differentiation due to diminished DNA synthesis and greater apoptosis. This suggested that p53's effects during megakaryopoiesis are mediated through cell cycle- and apoptosis-related target genes, possibly by arresting DNA synthesis and promoting apoptosis. To identify candidate genes through which p53 mediates these effects, gene expression was compared between p53 knock-down (p53-KD) and control CHRF cells induced to undergo terminal megakaryocytic differentiation using microarray analysis. Among substantially downregulated p53 targets in p53-KD megakaryocytes were cell cycle regulators CDKN1A (p21) and PLK2, proapoptotic FAS, TNFRSF10B, CASP8, NOTCH1, TP53INP1, TP53I3, DRAM1, ZMAT3 and PHLDA3, DNA-damage-related RRM2B and SESN1, and actin component ACTA2, while antiapoptotic CKS1B, BCL2, GTSE1, and p53 family member TP63 were upregulated in p53-KD cells. Additionally, a number of cell cycle-related, proapoptotic, and cytoskeleton-related genes with known functions in megakaryocytes but not known to carry p53-responsive elements were differentially expressed between p53-KD and control CHRF cells. Our data support a model whereby p53 expression during megakaryopoiesis serves to control polyploidization and the transition from endomitosis to apoptosis by impeding cell cycling and promoting apoptosis. Furthermore, we identify a putative p53 regulon that is proposed to orchestrate these effects.


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