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The objective of this qualitative study was to observe what importance is assigned by university doctors, that is, those who achieved the highest level of education, to two of these social competencies: Resilience and Leadership. The population was comprised of PhDs from Argentina and other countries who participated in internationalization programs in France. The hypothesis is that the highest level of education achieved, added to the immersion in another culture after having undergone a national process of selection before the mobility academic programme, could result in a greater valuation of the so-called social and management competencies. The assessment of Resilience and Leadership was observed through different techniques, specially the hierarchical evocations technique. The findings show a) Resilience is almost not mentioned despite the fact that the Emotional-Relational dimension enters the core of the representations of PhDs about the fundamental competencies to be developed by universities and companies in the field of hard and soft sciences; b) the same happens with Leadership. These results reveal the gap or distance between the University with respect to the needs of the scientific and productive system. [ABSTRACT FROM AUTHOR]

Women of color (WoC) continue to be underrepresented in engineering programs across the United States. Many scholarly reports on faculty demographic characteristics do not provide measures regarding the representation of WoC faculty due to data reporting restrictions or lack of relevant data. Using 14 years of data from the American Society for Engineering Education, this study examined the trends in the prevalence of WoC faculty and PhDs in engineering between 2005 and 2018. Informed by intersectionality theory and Kanter's theory of proportions, descriptive analyses were used to disaggregate the prevalence of engineering faculty by gender, race/ethnicity, and engineering discipline. Findings indicate that there were slight growths in the representation of African American/Black, Native American/Native Hawaiian, and Hispanic/Latina women engineering faculty. The low representation of WoC is also evident among engineering PhDs. Changes in the shares of WoC in assistant, associate, and full professor ranks and in the production of PhDs provide insights for future demographic shifts in engineering education. Greater efforts and investments are needed in the recruitment of WoC into PhD programs and, subsequently, as assistant professors across engineering disciplines. Although interventions and programs aimed at helping increase the participation of WoC faculty in engineering have made progress, findings suggest that larger scale structural and cultural changes are needed to shift prevailing demographic trends in the engineering professoriate, including expanding student access to doctoral education in engineering. Research findings have the potential to provide foundational information for developing strategies to increase the representation of WoC engineering PhDs and faculty. [ABSTRACT FROM AUTHOR]

In Germany, the final grade of a doctorate is significant for careers inside and outside the academic labor market. Particularly important is the highest grade—summa cum laude. At the same time, doctoral grades are constantly subject to criticism. Thus far, however, neither German nor international studies have examined the determinants of doctoral grades. Drawing on Hu's model of college grades, this study develops a conceptual framework for explaining doctoral grades and investigates the impact of doctorate holders', reviewers', and environmental context characteristics on the probability of doctoral candidates graduating with the highest grade, summa cum laude. Using logistic regression analyses on data from the German PhD Panel Study, the study confirms that high-performing individuals are more likely to achieve the highest doctoral grade. A learning environment that is characterized by supervision security, high expectations to participate in scientific discourse, and strong support in network integration also increases the chances of graduating with a summa cum laude degree. In contrast, being female, having a highly respected reviewer, studying natural sciences, medical studies or engineering, completing an external doctorate, and studying within a learning environment characterized by rigid time constraints are negatively related to the probability of receiving a summa cum laude grade. This study is the first to lend empirical evidence to the critical discussion of doctoral grades and offers insights to ensure the validity of doctoral grades. [ABSTRACT FROM AUTHOR]

The capacity to regenerate entire body parts, tissues, and organs had generally been thought to be lost in evolution with very few exceptions (e.g. the liver) surviving in mammals. The discovery of the MRL mouse and the elucidation of the underlying molecular pathway centering around hypoxia inducible factor, HIF-1α, has allowed a drug and materials approach to regeneration in mice and hopefully humans. The HIF-1α pathway is ancient and permitted the transition from unicellular to multicellular organisms. Furthermore, HIF-1α and its regulation by PHDs, important oxygen sensors in the cell, provides a perfect drug target. We review the historical background of regeneration biology, the discovery of the MRL mouse, and its underlying biology, and novel approaches to drugs, targets, and delivery systems (see Fig. 1).

The spatial mobility of students and academics as part of the internationalisation of higher education is becoming increasingly relevant in securing top-tier positions, especially within academia. While the number of doctoral candidates is rising, new positions are not created at the same rate, leading to scarcer career opportunities in academia and the need to develop alternative career paths. Previous studies have much focused on the connection between mobility and career development among junior academics in the STEM fields, but the significance of mobility for SSH PhD candidates and their career development remains unanswered. Does spatial mobility have any effects there, and if so, which? For this reason, this paper studied doctoral SSH candidates from Germany with mobility experiences in the Netherlands. The findings show that spatial mobility affects the perception of the PhD candidate's career in several, sometimes ambivalent ways. It shows that the experience of mobility narrows the planning to a career in academia, contributes to the informal learning process of the candidate, and expands the horizon for possible opportunities in academia. The perceived asset of mobility varies alongside the internationalisation of disciplines and whether the candidate plans to return to Germany or pursue an international career. [ABSTRACT FROM AUTHOR]

This article describes all kind of problems PhD students might encounter during their PhDtrajectories. Because of these problems many PhD students leave universities without finishing their thesis and without PhD degrees. It leads to great losses of human capital. The author, who worked for 16 years as a university ombuds at a Dutch research university, is very experienced in the guidance of PhD students whose trajectories got stuck. Based on his experiences he describes interventions of an ombuds that might lead to diminishing dropout among PhD students. Although most of his experiences are accumulated at a Dutch university the described problems of PhD students could occur at universities all over the world. The same goes for ombuds interventions and solutions. [ABSTRACT FROM AUTHOR]

Despite the benefits of a PhD for degree-holders as well for society as a whole, doctoral student attrition is a common phenomenon. Unfortunately, the empirical literature on dropout from doctoral education is scant, especially for non-US countries—an omission we address in the current study. Building on Tinto's model of student attrition and rational choice theory, the study empirically assesses the association of different individual, institutional, and external factors with the propensity to leave doctoral studies. Unlike most studies in the field, it draws on longitudinal data using event history modelling, observing doctoral students in multiple disciplines and a wide range of universities. The key results can be summarized as follows: In Germany, women are more likely to dropout than men. The probability of dropping out strongly depends on the discipline and the availability of a scholarship. A close contact with the supervisor and exchange with other PhDs are associated with a lower dropout probability. Moreover, having children increases dropout rates. The study findings provide first empirical guidance for interventions that can possibly help reducing dropout. [ABSTRACT FROM AUTHOR]

The creation and development of new technology-based firms (NTBFs) is at the core of national prosperity, and constitutes a key activity of the innovation policies of advanced and developing economies. Many of these companies are founded by postgraduates that hold a doctorate (PhDs). Governments foster the creation of NTBFs by PhDs to take advantage of the stock of knowledge which exists in universities and research centers. It is assumed that founders with a high level of specialization and knowledge, such as PhDs, will bring strong competitive advantages to the companies they found. The literature in this regard, however, is scarce and inconclusive. We have studied the role of PhDs in founding teams of NTBFs in a specific kind of entrepreneurial process: corporate venturing. Our conclusions suggest that companies with PhDs are significantly more attractive to corporate venture capital. Corporate venturing has a higher propensity to invest in NTBFs with PhDs in the founding teams, and these companies concentrate a higher number of corporate investors, in a kind of accumulative effect. [ABSTRACT FROM AUTHOR]

This research investigates the value of a PhD for employment outside academia by showing how PhD holders create it through the help of intermediations during their thesis preparation. We analyse scientific practice through the use of Cultural Historical Activity Theory (CHAT) to better understand PhDs' employment outside academia. With CHAT, intermediation on labour markets is seen via the lens of activity. Using a qualitative methodology, we interviewed 20 students who completed PhDs at the University of Lyon in France and who now work for private companies. Our findings show how the value of these PhDs is shaped both by what they do during thesis and by what they seek to become in their professional careers. We contribute to the literature by providing a new theoretical stance on intermediation in labour markets, and offer reflections for universities across Europe to tailor their PhD programmes. [ABSTRACT FROM AUTHOR]

Abstract Background Multiple sclerosis (MS) is characterized by a combination of inflammatory and neurodegenerative processes variously dominant in different stages of the disease. Thus, immunosuppression is the goal standard for the inflammatory stage, and novel remyelination therapies are pursued to restore lost function. Cannabinoids such as 9Δ-THC and CBD are multi-target compounds already introduced in the clinical practice for multiple sclerosis (MS). Semisynthetic cannabinoids are designed to improve bioactivities and druggability of their natural precursors. VCE-004.8, an aminoquinone derivative of cannabidiol (CBD), is a dual PPARγ and CB2 agonist with potent anti-inflammatory activity. Activation of the hypoxia-inducible factor (HIF) can have a beneficial role in MS by modulating the immune response and favoring neuroprotection and axonal regeneration. Methods We investigated the effects of VCE-004.8 on the HIF pathway in different cell types. The effect of VCE-004.8 on macrophage polarization and arginase 1 expression was analyzed in RAW264.7 and BV2 cells. COX-2 expression and PGE2 synthesis induced by lipopolysaccharide (LPS) was studied in primary microglia cultures. The efficacy of VCE-004.8 in vivo was evaluated in two murine models of MS such as experimental autoimmune encephalomyelitis (EAE) and Theiler’s virus-induced encephalopathy (TMEV). Results Herein, we provide evidence that VCE-004.8 stabilizes HIF-1α and HIF-2α and activates the HIF pathway in human microvascular endothelial cells, oligodendrocytes, and microglia cells. The stabilization of HIF-1α is produced by the inhibition of the prolyl-4-hydrolase activity of PHD1 and PDH2. VCE-004.8 upregulates the expression of HIF-dependent genes such as erythropoietin and VEGFA, induces angiogenesis, and enhances migration of oligodendrocytes. Moreover, VCE-004.8 blunts IL-17-induced M1 polarization, inhibits LPS-induced COX-2 expression and PGE2 synthesis, and induces expression of arginase 1 in macrophages and microglia. In vivo experiments showed efficacy of VCE-004.8 in EAE and TMEV. Histopathological analysis revealed that VCE-004.8 treatments prevented demyelination, axonal damage, and immune cells infiltration. In addition, VCE-004.8 downregulated the expression of several genes closely associated with MS physiopathology, including those underlying the production of chemokines, cytokines, and adhesion molecules. Conclusions This study provides new significant insights about the potential role of VCE-004.8 for MS treatment by ameliorating neuroinflammation and demyelination.

Doctoral employment outside universities has been increasing, as universities cannot employ all doctorate holders. Nevertheless, it has been argued that the shift from doctoral programs to the non-academic labour market has been limited. In this qualitative study, more than 800 verbal answers given by doctorate holders to a pair of open-ended questions were content-analysed to explore doctorate holders' perceptions of the non-academic labour market and the reputational problems they relate to their employment. The study identifies four reputational problems which doctorate holders relate to their employment: the oversupply problem, the overeducation problem, the consistency problem and the communication problem. By identifying potential reputational problems on the doctorate holders level, this research contributes novel information in terms of both theory development and practitioner insights. [ABSTRACT FROM AUTHOR]

The importance of oxygen for the survival of multicellular and aerobic organisms is well established and documented. Over the years, increased knowledge of its use for bioenergetics has placed oxygen at the centre of research on mitochondria and ATP‐generating processes. Understanding the molecular mechanisms governing cellular oxygen sensing and response has allowed for the discovery of novel pathways oxygen is involved in, culminating with the award of the Nobel Prize for Medicine and Physiology in 2019 to the pioneers of this field, Greg Semenza, Peter Ratcliffe and William Kaelin. However, it is now beginning to be appreciated that oxygen can be a signalling molecule involved in a vast array of molecular processes, most of which impinge on gene expression control. This review will focus on the knowns and unknowns of oxygen as a signalling molecule, highlighting the role of 2‐oxoglutarate‐dependent dioxygenases as central players in the cellular response to deviations in oxygen tension. [ABSTRACT FROM AUTHOR]

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Hypoxia is the most critical factor for maintaining stemness. During embryonic development, neural stem cells (NSCs) reside in hypoxic niches, and different levels of oxygen pressure and time of hypoxia exposure play important roles in the development of NSCs. Such hypoxic niches exist in adult brain tissue, where the neural precursors originate. Hypoxia-inducible factors (HIFs) are key transcription heterodimers consisting of regulatory α-subunits (HIF-1α, HIF-2α, HIF-3α) and a constitutive β-subunit (HIF-β). Regulation of downstream targets determines the fate of NSCs. In turn, the stability of HIFs-α is regulated by prolyl hydroxylases (PHDs), whose activity is principally modulated by PHD substrates like oxygen (O2), α-ketoglutarate (α-KG), and the co-factors ascorbate (ASC) and ferrous iron (Fe2+). It follows that the transcriptional activity of HIFs is actually determined by the contents of O2, α-KG, ASC, and Fe2+. In normoxia, HIFs-α are rapidly degraded via the ubiquitin-proteasome pathway, in which PHDs, activated by O2, lead to hydroxylation of HIFs-α at residues 402 and 564, followed by recognition by the tumor suppressor protein von Hippel–Lindau (pVHL) as an E3 ligase and ubiquitin labeling. Conversely, in hypoxia, the activity of PHDs is inhibited by low O2 levels and HIFs-α can thus be stabilized. Hence, suppression of PHD activity in normoxic conditions, mimicking the effect of hypoxia, might be beneficial for preserving the stemness of NSCs, and it is clinically relevant as a therapeutic approach for enhancing the number of NSCs in vitro and for cerebral ischemia injury in vivo. This study will review the putative role of PHD inhibitors on the self-renewal of NSCs.

Hypoxia is a common feature in solid tumors and is associated with cancer progression. The main regulators of the hypoxic response are hypoxia-inducible transcription factors (HIFs) that guide the cellular adaptation to hypoxia by gene activation. The actual oxygen sensing is performed by HIF prolyl hydroxylases (PHDs) that under normoxic conditions mark the HIF-α subunit for degradation. Cancer progression is not regulated only by the cancer cells themselves but also by the whole tumor microenvironment, which consists of cellular and extracellular components. Hypoxic conditions also affect the stromal compartment, where stromal cells are in close contact with the cancer cells. The important function of HIF in cancer cells has been shown by many animal models and described in hundreds of reviews, but less in known about PHDs and even less PHDs in stromal cells. Here, we review hypoxic signaling in tumors, mainly in the tumor stroma, with a focus on HIFs and PHDs.

Hypoxia is a common feature in solid tumors and is associated with cancer progression. The main regulators of the hypoxic response are hypoxia-inducible transcription factors (HIFs) that guide the cellular adaptation to hypoxia by gene activation. The actual oxygen sensing is performed by HIF prolyl hydroxylases (PHDs) that under normoxic conditions mark the HIF-α subunit for degradation. Cancer progression is not regulated only by the cancer cells themselves but also by the whole tumor microenvironment, which consists of cellular and extracellular components. Hypoxic conditions also affect the stromal compartment, where stromal cells are in close contact with the cancer cells. The important function of HIF in cancer cells has been shown by many animal models and described in hundreds of reviews, but less in known about PHDs and even less PHDs in stromal cells. Here, we review hypoxic signaling in tumors, mainly in the tumor stroma, with a focus on HIFs and PHDs. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is characterized by a combination of inflammatory and neurodegenerative processes variously dominant in different stages of the disease. Thus, immunosuppression is the goal standard for the inflammatory stage, and novel remyelination therapies are pursued to restore lost function. Cannabinoids such as 9Δ-THC and CBD are multi-target compounds already introduced in the clinical practice for multiple sclerosis (MS). Semisynthetic cannabinoids are designed to improve bioactivities and druggability of their natural precursors. VCE-004.8, an aminoquinone derivative of cannabidiol (CBD), is a dual PPARγ and CB2 agonist with potent anti-inflammatory activity. Activation of the hypoxia-inducible factor (HIF) can have a beneficial role in MS by modulating the immune response and favoring neuroprotection and axonal regeneration.Methods: We investigated the effects of VCE-004.8 on the HIF pathway in different cell types. The effect of VCE-004.8 on macrophage polarization and arginase 1 expression was analyzed in RAW264.7 and BV2 cells. COX-2 expression and PGE2 synthesis induced by lipopolysaccharide (LPS) was studied in primary microglia cultures. The efficacy of VCE-004.8 in vivo was evaluated in two murine models of MS such as experimental autoimmune encephalomyelitis (EAE) and Theiler's virus-induced encephalopathy (TMEV).Results: Herein, we provide evidence that VCE-004.8 stabilizes HIF-1α and HIF-2α and activates the HIF pathway in human microvascular endothelial cells, oligodendrocytes, and microglia cells. The stabilization of HIF-1α is produced by the inhibition of the prolyl-4-hydrolase activity of PHD1 and PDH2. VCE-004.8 upregulates the expression of HIF-dependent genes such as erythropoietin and VEGFA, induces angiogenesis, and enhances migration of oligodendrocytes. Moreover, VCE-004.8 blunts IL-17-induced M1 polarization, inhibits LPS-induced COX-2 expression and PGE2 synthesis, and induces expression of arginase 1 in macrophages and microglia. In vivo experiments showed efficacy of VCE-004.8 in EAE and TMEV. Histopathological analysis revealed that VCE-004.8 treatments prevented demyelination, axonal damage, and immune cells infiltration. In addition, VCE-004.8 downregulated the expression of several genes closely associated with MS physiopathology, including those underlying the production of chemokines, cytokines, and adhesion molecules.Conclusions: This study provides new significant insights about the potential role of VCE-004.8 for MS treatment by ameliorating neuroinflammation and demyelination. [ABSTRACT FROM AUTHOR]

The pres ent article addresses the research and innovation issues in the university, its relation with doctoral training and its contribution to the social and economic development. The article stands for a better integration of PhD training with university research and of the PhD issues with relevant research projects. Some considerations are stated aimed at strengthening university research, to train more physicians and to achieve an important impact as to the economic and social topics in terms of the contribution to an inclusive sustainable development in Cuban conditions. [ABSTRACT FROM AUTHOR]

In this paper we investigate individual income differences between individuals with Master and PhD degrees over the first 20 years of a career. We compare monthly incomes of Dutch higher education graduates with the same years of experience, gender and field of study. It turns out that over the first 20 years of experience, the average annual return to a PhD education is not significantly different from zero. During the PhD track and the first years after PhD graduation PhDs earn less than Masters, but this is compensated by higher earnings in later years. Income differences differ strongly by sex. [ABSTRACT FROM AUTHOR]

The publishing activity of doctors on medical and biological sciences working in branch and academic sectors of Novosibirsk academic and high school institutions is investigated. The information source for analysis is the database «Scientific potential of the Novosibirsk region», generated by the Department of the State Public Scientific and Technical Library of SB RAS.

In our knowledge society and economy, doctoral education is increasingly considered as a means to produce knowledge workers to feed the needs of the global employment market. This raises concerns about the competencies developed through doctoral training. Surprisingly, only a few studies have addressed this question and most of them are restricted to very limited populations or lack empirical evidences. In this context, we performed a national survey answered by 2794 PhDs. From the data collected, we built a reference framework containing 111 competencies organized in 6 main categories. From statistical analysis, we identified a set of 'core' competencies that are shared by doctorate holders (Microsoft Excel spreadsheet Chi squared goodness-of-fit test, alpha level .05). This study therefore demonstrates that PhDs develop a set of common competencies and delineate its boundaries. [ABSTRACT FROM AUTHOR]

As Nuclear Factor-κB (NF-κB) is a major transcription factor responding to cellular stress, it is perhaps not surprising that is activated by hypoxia, or decreased oxygen availability. However, how NF-κB becomes activated in hypoxia is still not completely understood. Several mechanisms have been proposed and this review will focus on the main findings highlighting the molecules that have been identified in the process of hypoxia induced NF-κB. In addition, we will discuss the role of NF-κB in the control of the cellular response to hypoxia. [ABSTRACT FROM AUTHOR]

PhD graduates can help companies transfer knowledge from universities to firms. Scholars have analysed the determinants of PhD recruitment by firms and its effects on their innovation activities. However, little is known about what happens when a firm loses employees with PhDs. The aim of this paper is to compare the effects on the relationships of firms with universities when these firms lose PhDs versus when they hire PhDs to work in R&D. These effects may be symmetrical or non-symmetrical depending on the abilities of firms to retain the connections and knowledge acquired by hiring PhDs. We consider four types of relationships: collaboration with universities, universities as a source of innovation, academic journals as a source of innovation and the purchase of R&D services from universities. We use data from the Spanish Technological Innovation Panel (PITEC) for the period 2006 to 2015. The results illustrate the central role of PhDs in the linkages between industry and academia. The recruitment of PhDs has a positive effect on collaboration between firms and universities and on the purchase of R&D services from universities. By contrast, the loss of PhDs has a negative effect on collaboration with universities but not on the acquisition of R&D. • PhDs play a key role in university–industry relationships. • The effects of PhDs differ depending on the type of university–industry linkage. • Hiring PhDs encourages cooperation and the purchase of R&D services from universities. • The loss of PhDs has a negative effect on cooperation in innovation with universities. [ABSTRACT FROM AUTHOR]

This paper analyses the knowledge transfer process in technology centres (TCs) through the employment of PhD holders. In particular, a study of nine TCs located in four Spanish regions was essential to conclude that PhDs are not only involved in the acquisition of scientific knowledge but also in other stages of knowledge transfer (communication, application, acceptance or assimilation), as well as in business and commercial activities that require continuous exchanges with clients. Moreover, the introduction of academic culture into the organisation (a process known as 'collegialisation') and the promotion of a dual socialisation of PhDs in both the academic and industrial contexts constitute two enabling conditions that improve the quality of knowledge diffusion across organisations. As a result of these patterns, TCs are redefining their mission in regional innovation systems to adopt a more proactive position. Thus, they can anticipate the future demands of their potential clients. [ABSTRACT FROM AUTHOR]

The hypoxia signaling pathway is an evolutionarily conserved cellular signaling pathway present in animals ranging from Caenorhabditis elegans to mammals. The pathway is crucial for oxygen homeostasis maintenance. Hypoxia-inducible factors (HIF-1α and HIF-2α) are master regulators in the hypoxia signaling pathway. Oxygen concentrations vary a lot in the aquatic environment. To deal with this, fishes have adapted and developed varying strategies for living in hypoxic conditions. Investigations into the strategies and mechanisms of hypoxia adaptation in fishes will allow us to understand fish speciation and breed hypoxia-tolerant fish species/strains. This review summarizes the process of the hypoxia signaling pathway and its regulation, as well as the mechanism of hypoxia adaptation in fishes. [ABSTRACT FROM AUTHOR]

This paper analyses the determining factors of PhDs' career success. Earnings have been used as an objective measure, and a subjective measure of success was constructed based on the individuals' assessments of broader aspects of their job position. When analysing the data by field of knowledge and gender, it was found that males and PhD holders in the field of sciences achieve greater career success in terms of earnings. However, the theory of the glass ceiling does not appear to apply. On the basis of a subjective measure of career success, on the other hand, it is women and PhD holders in humanities and social sciences that are more successful. Regardless of the measure of success used, the most important determining factor in career success is job satisfaction, thus reinforcing the theory that PhD holders are a group of workers with a more complex conception of career success. [ABSTRACT FROM AUTHOR]

Many Higher Degree by Research candidates find the experience of searching the literature overwhelming and stressful. Experienced researchers draw on deep disciplinary knowledge, prior experience, and their networks to locate relevant information and sources. Inexperienced researchers may lack access to internal roadmaps of terms, authors and methodologies and require informed guidance. Advanced information literacy is a critical factor for student success, particularly to support the literature review process, and the need for effective information management skills has never been greater. The quality of doctoral candidates' literature reviews, and their ability to undertake substantive and ‘do-able’ research is linked. Whilst do-it-yourself ICT and ‘Google-like’ search engines have led to easier information access, are Higher Degree by Research (HDR) students equipped to effectively navigate through, and manage the plethora of research sources available? This paper shares findings and recommendations of a case study profiling PhD candidate usage of the University of Melbourne Library's research consultation service. The study explored whether consultations conducted at the ‘point of need’ make a difference in the early stages of PhD candidature and questioned whether consultations contribute to improved research ability and successful outcomes. The paper also questions assumptions made by candidates and supervisors in relation to information-related research skills. [ABSTRACT FROM PUBLISHER]

The public university education in Bacau, represented by “Vasile Alecsandri” University from Bacau has developed over the past two years not only in terms of student numbers, but as human and material resources available to them. After the number of students per teacher, public higher education from Bacau is situated on the second place after Iasi, the number of teachers representing 1% of the country. The structure by scientific degrees of teachers has improved in the last year, reaching over 36% professors and lecturers and 144 PhDs. Over 55% of the teachers are younger than 40 years. The material basis has improved both quantitatively and qualitatively by putting into use a new building, bringing an additional 27 classrooms and 11 seminar rooms and providing the conditions of modern higher education.

Oxygen is vital for the normal function of cells and is transported to all parts of the body through red blood cells in the vasculature. Abnormal oxygen concentrations can lead to many complications, and reestablishing oxygen balance is essential for cell biological functions. Mammalian cells have evolved to adapt to hypoxia and sense oxygen levels during hypoxia to maintain and coordinate different biological responses. The best mechanism for studying the hypoxia response involves hypoxia-inducible factors (HIFs), which control the expression of many hypoxia-inducible genes. Recent studies have found that other epigenetic modifier enzymes and metabolite signaling pathways can also sense dynamic changes in oxygen. The mammalian intrauterine oxygen concentration and the mechanisms controlling oxygen homeostasis affect placental development, structure and function. In this review, we focus on how mammalian cells sense oxygen levels and produce anoxic-dependent adaptive responses and explore the relationship between hypoxia and placental development during early pregnancy. • Epigenetic modifying enzymes and metabolite signaling pathways can sense oxygen levels. • Accurate control of oxygen level is essential for the normal growth of placenta and embryo. • Abnormal placental hypoxia can lead to different pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Purpose – The purpose of this paper is to investigate to what extent male and female PhDs choose academic vs non-academic employment. Further, it analyses gender earnings differences in the academic and non-academic labour markets. Design/methodology/approach – Rich Swedish cross-sectional register data on the stock of PhDs in 2004 is used for investigating differences between male and female PhDs in earnings levels and in the choice of labour market (in academia or outside academia). Findings – No significant gender differences prevail for the probability of becoming academically employed. On average, women earn 16 per cent less than men, and the academically employed earn 26 per cent less than PhDs outside academia. In the non-academic labour market, women earn approximately 25 per cent less than men, and this gender gap stays constant over time. Within academia, men and women start at similar earnings levels, but higher returns to graduate experience for men causes the gender earnings differences to increase over time to approximately 18 per cent by ten years after graduation. Practical implications – Provides background information relevant for efforts to make efficient use of female scientific human capital. Originality/value – The study is the first to investigate career-choice and earnings of Swedish PhDs. Further, the study is the first to investigate both the academic and the non-academic labour markets. [ABSTRACT FROM AUTHOR]

Abstract: The transcription factor complex Hypoxia inducible factor 1 (HIF-1) controls the expression of most genes involved in adaptation to hypoxic conditions. Oxygen-dependency is maintained by prolyl- and asparagyl-4-hydroxylases (PHDs/FIH-1) belonging to the superfamily of iron(II) and 2-oxoglutarate dependent dioxygenases. Hydroxylation of the HIF-1α subunit by PHDs and FIH-1 leads to its degradation and inactivation. By hydroxylating HIF-1α in an oxygen-dependent manner PHDs and FIH-1 function as oxygen-sensing enzymes of HIF signalling. Besides molecular oxygen nitric oxide (NO), a mediator of the inflammatory response, can regulate HIF-1α accumulation, HIF-1 activity and HIF-1 dependent target gene expression. Recent studies addressing regulation of HIF-1 by NO revealed a complex and paradoxical picture. Acute exposure of cells to high doses of NO increased HIF-1α levels irrespective of the residing oxygen concentration whereas prolonged exposure to NO or low doses of this radical reduced HIF-1α accumulation even under hypoxic conditions. Several mechanisms were found to contribute to this paradoxical role of NO in regulating HIF-1. More recent studies support the view that NO regulates HIF-1 by modulating the activity of the oxygen-sensor enzymes PHDs and FIH-1. NO dependent HIF-1α accumulation under normoxia was due to direct inhibition of PHDs and FIH-1 most likely by competitive binding of NO to the ferrous iron in the catalytically active center of the enzymes. In contrast, reduced HIF-1α accumulation by NO under hypoxia was mainly due to enhanced HIF-1α degradation by induction of PHD activity. Three major mechanisms are discussed to be involved in enhancing the PHD activity despite the lack of oxygen: (1) NO mediated induction of a HIF-1 dependent feedback loop leading to newly expressed PHD2 and enhanced nuclear localization, (2) O2-redistribution towards PHDs after inhibition of mitochondrial respiration by NO, (3) reactivation of PHD activity by a NO mediated increase of iron and 2-oxoglutarate and/or involvement of reactive oxygen and/or nitrogen species. [Copyright &y& Elsevier]

The ternary complex factor Net/Elk3 is downregulated in hypoxia and participates in the induction by hypoxia of several genes, including c-fos, vascular endothelial growth factor and egr-1. However, the global role of Net in hypoxia remains to be elucidated. We have identified, in a large-scale analysis of RNA expression using microarrays, more than 370 genes that are regulated by Net in hypoxia. In order to gain insights into the role of Net in hypoxia, we have analysed in parallel the genes regulated by HIF-1α, the classical factor involved in the response to hypoxia. We identified about 190 genes that are regulated by HIF-1α in hypoxia. Surprisingly, when we compare the genes induced by hypoxia that require either Net or HIF-1α, the majority are the same (75%), suggesting that the functions of both factors are closely linked. Interestingly, in hypoxia, Net regulates the expression of several genes known to control HIF-1α stability, including PHD2, PHD3 and Siah2, suggesting that Net regulates the stability of HIF-1α. We found that inhibition of Net by RNAi leads to decreased HIF-1α expression at the protein level in hypoxia. These results indicate that Net participates in the transcriptional response to hypoxia by regulation of HIF-1α protein stability.Oncogene (2008) 27, 1333–1341; doi:10.1038/sj.onc.1210736; published online 20 August 2007 [ABSTRACT FROM AUTHOR]