How the Hox gene Ultrabithorax specifies two different segments: the significance of spatial and temporal regulation within metameres

Development ◽  
1995 ◽  
Vol 121 (9) ◽  
pp. 2973-2982 ◽  
Author(s):  
J. Castelli-Gair ◽  
M. Akam

In Drosophila, the Hox gene Ultrabithorax (Ubx) specifies the development of two different metameres--parasegment 5, which is entirely thoracic, and parasegment 6, which includes most of the first abdominal segment. Here we investigate how a single Hox gene can specify two such different morphologies. We show that, in the early embryo, cells respond similarly to UBX protein in both parasegments. The differences between parasegments 5 and 6 can be explained by the different spatial and temporal pattern of UBX protein expression in these two metameres. We find no evidence for multiple threshold responses to different levels of UBX protein. We examine in particular the role of Ubx in limb development. We show that UBX protein will repress limb primordia before 7 hours, when Ubx is expressed in the abdomen, but not later, when UBX is first expressed in the T3 limb primordium. The regulation of one downstream target of UBX, the Distalless gene, provides a model for this transition at the molecular level.

Development ◽  
1992 ◽  
Vol 115 (2) ◽  
pp. 629-637 ◽  
Author(s):  
C.N. Coelho ◽  
W.B. Upholt ◽  
R.A. Kosher

During early stages of normal chick limb development, the homeobox-containing (HOX) gene GHox-4.6 is expressed throughout the posterior mesoderm of the wing bud from which most of the skeletal elements including the digits will develop, whereas GHox-8 is expressed in the anterior limb bud mesoderm which will not give rise to skeletal elements. In the present study, we have examined the expression of GHox-4.6 and GHox-8 in the wing buds of two polydactylous mutant chick embryos, diplopodia-5 and talpid2, from which supernumerary digits develop from anterior limb mesoderm, and have also examined the expression of these genes in response to polarizing zone grafts and retinoic acid-coated bead implants which induce the formation of supernumerary digits from anterior limb mesoderm. We have found that the formation of supernumerary digits from the anterior mesoderm in mutant and experimentally induced polydactylous limb buds is preceded by the ectopic expression of GHox-4.6 in the anterior mesoderm and the coincident suppression of GHox-8 expression in the anterior mesoderm. These observations suggest that the anterior mesoderm of the polydactylous limb buds is “posteriorized” and support the suggestion that GHox-8 and GHox-4.6, respectively, are involved in specifying the anterior non-skeletal and posterior digit-forming regions of the limb bud. Although the anterior mesodermal domain of GHox-8 expression is severely impaired in the mutant and experimentally induced polydactylous limb buds, this gene is expressed by the prolonged, thickened apical ectodermal ridges of the polydactylous limb buds that extend along the distal anterior as well as the distal posterior mesoderm.(ABSTRACT TRUNCATED AT 250 WORDS)


Author(s):  
Gulbarshyn Chepurko ◽  
Valerii Pylypenko

The paper examines and compares how the major sociological theories treat axiological issues. Value-driven topics are analysed in view of their relevance to society in times of crisis, when both societal life and the very structure of society undergo dramatic change. Nowadays, social scientists around the world are also witnessing such a change due to the emergence of alternative schools of sociological thought (non-classical, interpretive, postmodern, etc.) and, subsequently, the necessity to revise the paradigms that have been existed in sociology so far. Since the above-mentioned approaches are often used to address value-related issues, building a solid theoretical framework for these studies takes on considerable significance. Furthermore, the paradigm revision has been prompted by technological advances changing all areas of people’s lives, especially social interactions. The global human community, integral in nature, is being formed, and production of human values now matters more than production of things; hence the “expansion” of value-focused perspectives in contemporary sociology. The authors give special attention to collectivities which are higher-order units of the social system. These units are described as well-organised action systems where each individual performs his/her specific role. Just as the role of an individual is distinct from that of the collectivity (because the individual and the collectivity are different as units), so too a distinction is drawn between the value and the norm — because they represent different levels of social relationships. Values are the main connecting element between the society’s cultural system and the social sphere while norms, for the most part, belong to the social system. Values serve primarily to maintain the pattern according to which the society is functioning at a given time; norms are essential to social integration. Apart from being the means of regulating social processes and relationships, norms embody the “principles” that can be applied beyond a particular social system. The authors underline that it is important for Ukrainian sociology to keep abreast of the latest developments in the field of axiology and make good use of those ideas because this is a prerequisite for its successful integration into the global sociological community.


Author(s):  
Admink Admink ◽  
Сергій Виткалов ◽  
Валентина Вігула

Розглядається організаційно-культурна діяльність одного з помітних у регіональному просторі Західного Полісся фотомитця – Олександра Купчинського, а саме виставковий її вектор, втілений в презентації артефактів світового фотомистецтва; видавничий, розглянутий у  контексті  друку  різноманітних  фотоальбомів  із  творів експонентів, організація творчих зустрічей художньої інтелігенції міста з питань обговорення актуальних питань культурного розвитку, заснування фотоклубу тощо. Доводиться, що втрата зв’язку з Батьківщиною, у якій би формі це не відбувалося, не дозволяє митцю творчо самореалізуватися повною мірою. The importance and problematic range of local government reform in the regions of the country and ways of its solution in the field of culture are analyzed. The most effective steps are proposed for management structures at different levels to change attitudes of both the management and the local population regarding different cultural practices. Emphasis is placed on the role of sectoral methodological services in the implementation of this reform. The experience of other countries in activating the local population in this process is emphasized. An attempt has been made to offer effective, in the authors' opinion, solutions to the reform. Emphasis is placed on the educational factor.


2020 ◽  
Vol 16 ◽  
Author(s):  
Jean-François Gal ◽  
Pierre-Charles Maria

Background: The ubiquitous Lewis acid/base interactions are important in solution processes. Analytical chemistry may benefit of a better understanding of the role of Lewis basicity, at the molecular level or acting through a bulk solvent effect. Objective: To clearly delineate (i) the basicity at a molecular level, hereafter referred as solute basicity, and (ii) the solvent basicity, which is a bulk-liquid property. Method: The literature that relates Lewis basicity scales and solvent effects is analyzed. A special focus is placed on two extensive scales, the Donor Number, DN, and the BF3 affinity scale, BF3A, which were obtained by calorimetric measurement on molecules as solutes diluted in a quasi-inert solvent, and therefore define a molecular Lewis basicity. We discuss the validity of these solute scales when regarded as solvent scales, in particular when the basicity of strongly associated liquids is discussed. Results: We demonstrate the drawbacks of confusing the Lewis basicity of a solvent molecule, isolated as solute, and that of the bulk liquid solvent itself. Conclusion: Consequently, we recommend a reasoned use of the concept of Lewis basicity taking clearly into account the specificity of the process for which a Lewis basicity effect may be invoked. In particular, the action of the Lewis base, either as an isolated entity, or as a bulk liquid, must be distinguished.


Author(s):  
Shaun Blanchard

This book sheds further light on the nature of church reform and the roots of the Second Vatican Council (1962–65) through a study of eighteenth-century Catholic reformers who anticipated the Council. The most striking of these examples is the Synod of Pistoia (1786), the high-water mark of late Jansenism. Most of the reforms of the Synod were harshly condemned by Pope Pius VI in the bull Auctorem fidei (1794), and late Jansenism was totally discredited in the ultramontane nineteenth-century Church. Nevertheless, much of the Pistoian agenda—such as an exaltation of the role of bishops, an emphasis on infallibility as a gift to the entire Church, religious liberty, a simpler and more comprehensible liturgy that incorporates the vernacular, and the encouragement of lay Bible reading and Christocentric devotions—was officially promulgated at Vatican II. The career of Bishop Scipione de’ Ricci (1741–1810) and the famous Synod he convened are investigated in detail. The international reception (and rejection) of the Synod sheds light on why these reforms failed, and the criteria of Yves Congar are used to judge the Pistoian Synod as “true or false reform.” This book proves that the Synod was a “ghost” present at Vatican II. The council fathers struggled with, and ultimately enacted, many of the same ideas. This study complexifies the story of the roots of the Council and Pope Benedict XVI’s “hermeneutic of reform,” which seeks to interpret Vatican II as in “continuity and discontinuity on different levels” with past teaching and practice.


Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 414
Author(s):  
Didem Kart ◽  
Tuba Reçber ◽  
Emirhan Nemutlu ◽  
Meral Sagiroglu

Introduction: Alternative anti-biofilm agents are needed to combat Pseudomonas aeruginosa infections. The mechanisms behind these new agents also need to be revealed at a molecular level. Materials and methods: The anti-biofilm effects of 10 plant-derived compounds on P. aeruginosa biofilms were investigated using minimum biofilm eradication concentration (MBEC) and virulence assays. The effects of ciprofloxacin and compound combinations on P. aeruginosa in mono and triple biofilms were compared. A metabolomic approach and qRT-PCR were applied to the biofilms treated with ciprofloxacin in combination with baicalein, esculin hydrate, curcumin, and cinnamaldehyde at sub-minimal biofilm inhibitory concentration (MBIC) concentrations to highlight the specific metabolic shifts between the biofilms and to determine the quorum sensing gene expressions, respectively. Results: The combinations of ciprofloxacin with curcumin, baicalein, esculetin, and cinnamaldehyde showed more reduced MBICs than ciprofloxacin alone. The quorum sensing genes were downregulated in the presence of curcumin and cinnamaldehyde, while upregulated in the presence of baicalein and esculin hydrate rather than for ciprofloxacin alone. The combinations exhibited different killing effects on P. aeruginosa in mono and triple biofilms without affecting its virulence. The findings of the decreased metabolite levels related to pyrimidine and lipopolysaccharide synthesis and to down-regulated alginate and lasI expressions strongly indicate the role of multifactorial mechanisms for curcumin-mediated P. aeruginosa growth inhibition. Conclusions: The use of curcumin, baicalein, esculetin, and cinnamaldehyde with ciprofloxacin will help fight against P. aeruginosa biofilms. To the best of our knowledge, this is the first study of its kind to define the effect of plant-based compounds as possible anti-biofilm agents with low MBICs for the treatment of P. aeruginosa biofilms through metabolomic pathways.


Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 45
Author(s):  
Helena Beatriz Ferreira ◽  
Tânia Melo ◽  
Artur Paiva ◽  
Maria do Rosário Domingues

Rheumatoid arthritis (RA) is a highly debilitating chronic inflammatory autoimmune disease most prevalent in women. The true etiology of this disease is complex, multifactorial, and is yet to be completely elucidated. However, oxidative stress and lipid peroxidation are associated with the development and pathogenesis of RA. In this case, oxidative damage biomarkers have been found to be significantly higher in RA patients, associated with the oxidation of biomolecules and the stimulation of inflammatory responses. Lipid peroxidation is one of the major consequences of oxidative stress, with the formation of deleterious lipid hydroperoxides and electrophilic reactive lipid species. Additionally, changes in the lipoprotein profile seem to be common in RA, contributing to cardiovascular diseases and a chronic inflammatory environment. Nevertheless, changes in the lipid profile at a molecular level in RA are still poorly understood. Therefore, the goal of this review was to gather all the information regarding lipid alterations in RA analyzed by mass spectrometry. Studies on the variation of lipid profile in RA using lipidomics showed that fatty acid and phospholipid metabolisms, especially in phosphatidylcholine and phosphatidylethanolamine, are affected in this disease. These promising results could lead to the discovery of new diagnostic lipid biomarkers for early diagnosis of RA and targets for personalized medicine.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1783
Author(s):  
Anna Carrano ◽  
Juan Jose Juarez ◽  
Diego Incontri ◽  
Antonio Ibarra ◽  
Hugo Guerrero Cazares

Sex differences have been well identified in many brain tumors. Even though glioblastoma (GBM) is the most common primary malignant brain tumor in adults and has the worst outcome, well-established differences between men and women are limited to incidence and outcome. Little is known about sex differences in GBM at the disease phenotype and genetical/molecular level. This review focuses on a deep understanding of the pathophysiology of GBM, including hormones, metabolic pathways, the immune system, and molecular changes, along with differences between men and women and how these dimorphisms affect disease outcome. The information analyzed in this review shows a greater incidence and worse outcome in male patients with GBM compared with female patients. We highlight the protective role of estrogen and the upregulation of androgen receptors and testosterone having detrimental effects on GBM. Moreover, hormones and the immune system work in synergy to directly affect the GBM microenvironment. Genetic and molecular differences have also recently been identified. Specific genes and molecular pathways, either upregulated or downregulated depending on sex, could potentially directly dictate GBM outcome differences. It appears that sexual dimorphism in GBM affects patient outcome and requires an individualized approach to management considering the sex of the patient, especially in relation to differences at the molecular level.


Author(s):  
Mohammad Paydar ◽  
Asal Kamani Fard

More than 150 cities around the world have expanded emergency cycling and walking infrastructure to increase their resilience in the face of the COVID 19 pandemic. This tendency toward walking has led it to becoming the predominant daily mode of transport that also contributes to significant changes in the relationships between the hierarchy of walking needs and walking behaviour. These changes need to be addressed in order to increase the resilience of walking environments in the face of such a pandemic. This study was designed as a theoretical and empirical literature review seeking to improve the walking behaviour in relation to the hierarchy of walking needs within the current context of COVID-19. Accordingly, the interrelationship between the main aspects relating to walking-in the context of the pandemic- and the different levels in the hierarchy of walking needs were discussed. Results are presented in five sections of “density, crowding and stress during walking”, “sense of comfort/discomfort and stress in regard to crowded spaces during walking experiences”, “crowded spaces as insecure public spaces and the contribution of the type of urban configuration”, “role of motivational/restorative factors during walking trips to reduce the overload of stress and improve mental health”, and “urban design interventions on arrangement of visual sequences during walking”.


Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1909
Author(s):  
Joachim T. Siaw ◽  
Jonatan L. Gabre ◽  
Ezgi Uçkun ◽  
Marc Vigny ◽  
Wancun Zhang ◽  
...  

Aberrant activation of anaplastic lymphoma kinase (ALK) drives neuroblastoma (NB). Previous work identified the RET receptor tyrosine kinase (RTK) as a downstream target of ALK activity in NB models. We show here that ALK activation in response to ALKAL2 ligand results in the rapid phosphorylation of RET in NB cells, providing additional insight into the contribution of RET to the ALK-driven gene signature in NB. To further address the role of RET in NB, RET knockout (KO) SK-N-AS cells were generated by CRISPR/Cas9 genome engineering. Gene expression analysis of RET KO NB cells identified a reprogramming of NB cells to a mesenchymal (MES) phenotype that was characterized by increased migration and upregulation of the AXL and MNNG HOS transforming gene (MET) RTKs, as well as integrins and extracellular matrix components. Strikingly, the upregulation of AXL in the absence of RET reflects the development timeline observed in the neural crest as progenitor cells undergo differentiation during embryonic development. Together, these findings suggest that a MES phenotype is promoted in mesenchymal NB cells in the absence of RET, reflective of a less differentiated developmental status.


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