Interleukin 7 from Maternal Milk Crosses the Intestinal Barrier and Modulates T- Cell Development in Offspring

Background Breastfeeding protects against illnesses and death in hazardous environments, an effect partly mediated by improved immune function. One hypothesis suggests that factors within milk supplement the inadequate immune response of the offspring, but this has not been able to account for a series of observations showing that factors within maternally derived milk may supplement the development of the immune system through a direct effect on the primary lymphoid organs. In a previous human study we reported evidence suggesting a link between IL-7 in breast milk and the thymic output of infants. Here we report evidence in mice of direct action of maternally-derived IL-7 on T cell development in the offspring. Methods and Findings  We have used recombinant IL-7 labelled with a fluorescent dye to trace the movement in live mice of IL-7 from the stomach across the gut and into the lymphoid tissues. To validate the functional ability of maternally derived IL- 7 we cross fostered IL-7 knock-out mice onto normal wild type mothers. Subsets of thymocytes and populations of peripheral T cells were significantly higher than those found in knock-out mice receiving milk from IL-7 knock-out mothers. Conclusions/Significance Our study provides direct evidence that interleukin 7, a factor which is critical in the development of T lymphocytes, when maternally derived can transfer across the intestine of the offspring, increase T cell production in the thymus and support the survival of T cells in the peripheral secondary lymphoid tissue

Exploring the impact of the level of absorptive capacity in technology development firms

Absorptive capacity (ACAP) is widely recognized as an effective means of obtaining and sustaining a competitive advantage. Although ACAP was globally introduced decades ago, researchers from Central and Eastern Europe have since underestimated its importance. The research objective of this paper is to answer the following questions: how does the level of ACAP influence the performances of technology-driven firms, and how does it catalyse their innovation outputs? Furthermore, we argue that exporting technology-driven firms possess even higher levels of ACAP than those who are weak or not-at-all exporters. ACAP measured value is examined alongside the innovation outputs of firms and their business performance, with an extended focus on exporters. A selected population of >600 Croatian firms were asked to fill in the questionnaire. Out of the 103 firms that completed the survey, 45 were recognized as intensive technology development performers, and 34 were identified as large exporters. Both populations were tested against formulated hypotheses, ultimately proving that higher levels of ACAP can be seen to positively drive innovation performance which, notably, can be seen most clearly with exporters

Green process innovation: Where we are and where we are going

Environmental pollution has worsened in the past few decades, and increasing pressure is being put on firms by different regulatory bodies, customer groups, NGOs and other media outlets to adopt green process innovations (GPcIs), which include clean technologies and end-of-pipe solutions. Although considerable studies have been published on GPcI, the literature is disjointed, and as such, a comprehensive understanding of the issues, challenges and gaps is lacking. A systematic literature review (SLR) involving 80 relevant studies was conducted to extract seven themes: strategic response, organisational learning, institutional pressures, structural issues, outcomes, barriers and methodological choices. The review thus highlights the various gaps in the GPcI literature and illuminates the pathways for future research by proposing a series of potential research questions. This study is of vital importance to business strategy as it provides a comprehensive framework to help firms understand the various contours of GPcI. Likewise, policymakers can use the findings of this study to fill in the loopholes in the existing regulations that firms are exploiting to circumvent taxes and other penalties by locating their operations to emerging economies with less stringent environmental regulations.publishedVersio

Essential thrombocythemia

Essential thrombocythemia (ET) is an acquired myeloproliferative disorder (MPD) characterized by a sustained elevation of platelet number with a tendency for thrombosis and hemorrhage. The prevalence in the general population is approximately 30/100,000. The median age at diagnosis is 65 to 70 years, but the disease may occur at any age. The female to male ratio is about 2:1. The clinical picture is dominated by a predisposition to vascular occlusive events (involving the cerebrovascular, coronary and peripheral circulation) and hemorrhages. Some patients with ET are asymptomatic, others may experience vasomotor (headaches, visual disturbances, lightheadedness, atypical chest pain, distal paresthesias, erythromelalgia), thrombotic, or hemorrhagic disturbances. Arterial and venous thromboses, as well as platelet-mediated transient occlusions of the microcirculation and bleeding, represent the main risks for ET patients. Thromboses of large arteries represent a major cause of mortality associated with ET or can induce severe neurological, cardiac or peripheral artery manifestations. Acute leukemia or myelodysplasia represent only rare and frequently later-onset events. The molecular pathogenesis of ET, which leads to the overproduction of mature blood cells, is similar to that found in other clonal MPDs such as chronic myeloid leukemia, polycythemia vera and myelofibrosis with myeloid metaplasia of the spleen. Polycythemia vera, myelofibrosis with myeloid metaplasia of the spleen and ET are generally associated under the common denomination of Philadelphia (Ph)-negative MPDs. Despite the recent identification of the JAK2 V617F mutation in a subset of patients with Ph-negative MPDs, the detailed pathogenetic mechanism is still a matter of discussion. Therapeutic interventions in ET are limited to decisions concerning the introduction of anti-aggregation therapy and/or starting platelet cytoreduction. The therapeutic value of hydroxycarbamide and aspirin in high risk patients has been supported by controlled studies. Avoiding thromboreduction or opting for anagrelide to postpone the long-term side effects of hydrocarbamide in young or low risk patients represent alternative options. Life expectancy is almost normal and similar to that of a healthy population matched by age and sex

A Comparative Study of Elgamal Based Digital Signature Algorithms

A powerful and practical public-key and digital signature scheme was produced by ElGamal. ElGamal public-key and digital signature scheme were modified from the domain of natural integers, Z, to the domains of Gaussian integers, Z[i], and polynomials over finite fields, F[x]. We implement the classical and modified ElGamal digital signature scheme to compare and to test their functionality, reliability and security. To test the security of the algorithms we use a famous attack algorithm called Baby-Step-Giant algorithm which works in the domain of natural integers. We enhance the Baby-Step-Giant algorithm to work with the modified ElGamal digital signature algorithms.PublishedN/

Teaching effectiveness attributes in business schools

Purpose - Determining the attributes of effective business teachers is critical to schools as they strive to attract and retain students, assure learning, obtain and maintain reputation and accreditations, and place their alumni in the competitive job market. The purpose of this paper is to examine students and faculty perceptions of teaching effectiveness in five culturally disparate countries: Colombia, France, Lebanon, Sweden, and the USA. Design/methodology/approach - A survey was designed based on previous research complemented by an extensive literature review as well as personal communications with faculty in different international business schools. The survey considered 39 teaching attributes related to three specific dimensions: class delivery, class preparation and design, and instructional traits and personal characteristics. The survey targeted students and faculty from seven business schools located in five countries. Findings - This study offers new conceptual and analytical analyses from a cross-country comparative perspective. Rankings of the importance of perceived teaching attributes for both major groups involved in the teaching of business, faculty and students, are reported. The attributes are also ranked by teaching taxonomy and examined across countries. Practical implications - This study provides practical results that can be useful to instructors wishing to increase their teaching effectiveness and to universities considering revising their student evaluation forms. Originality/value - This study includes data collected from faculty and students from several schools located in culturally disparate countries and, thus, increases the applicability of the results in a cross-cultural manner and provides implications for practice internationally

Human Induced Pluripotent Stem Cell-Derived Astrocytes Are Differentially Activated by Multiple Sclerosis-Associated Cytokines.

Recent studies highlighted the importance of astrocytes in neuroinflammatory diseases, interacting closely with other CNS cells but also with the immune system. However, due to the difficulty in obtaining human astrocytes, their role in these pathologies is still poorly characterized. Here, we develop a serum-free protocol to differentiate human induced pluripotent stem cells (hiPSCs) into astrocytes. Gene expression and functional assays show that our protocol consistently yields a highly enriched population of resting mature astrocytes across the 13 hiPSC lines differentiated. Using this model, we first highlight the importance of serum-free media for astrocyte culture to generate resting astrocytes. Second, we assess the astrocytic response to IL-1β, TNF-α, and IL-6, all cytokines important in neuroinflammation, such as multiple sclerosis. Our study reveals very specific profiles of reactive astrocytes depending on the triggering stimulus. This model provides ideal conditions for in-depth and unbiased characterization of astrocyte reactivity in neuroinflammatory conditions

TC-PTP regulates the IL-7 transcriptional response during murine early T cell development

Cytokines play a critical role in directing the discrete and gradual transcriptional changes that define T cell development. The interleukin-7 receptor (IL-7R), via its activation of the JAK-STAT pathway, promotes gene programs that change dynamically as cells progress through T cell differentiation. The molecular mechanism(s) directing differential gene expression downstream of the IL-7R are not fully elucidated. Here, we have identified T cell protein tyrosine phosphatase (TC-PTP), also known as PTPN2, as a negative regulator of IL-7R-STAT signaling in T cell progenitors, contributing to both the quantitative and qualitative nature of STAT-gene targeting. Novel genetic strategies used to modulate TC-PTP expression demonstrate that depletion of TC-PTP expression heightens the phosphorylation of STAT family members, causing aberrant expression of an interferon-response gene profile. Such molecular re-programming results in deregulation of early development checkpoints culminating in inefficient differentiation of CD4CD8 double positive cells. TC-PTP is therefore shown to be required to safeguard the dynamic transcriptome necessary for efficient T cell differentiation.Canadian Institute of Health Research (grant MOP-62887) and from the Canadian Leukemia and Lymphoma Society; Medical Research Council (UK) and Newcastle University Medical School; the Japan Society for the Promotion of Science through the WPI-IFReC Research Program and a KAKENHI grant; the Kishimoto Foundation; and the ETH Zurich–Japan Science and Technology Agency (ETHZ-JST) Japanese-Swiss Cooperative Program.Peer Reviewe