Land Donations and the Gift of Water. On Temple Landlordism and Irrigation Agriculture in Pre-Colonial Bali

The Batur Temple (Pura Ulun Danu Batur) in Kintamani is located at the geographic apex of a so-called ritual water hierarchy and has conventionally been described as a purely religious institution responsible for the coordination and distribution of the irrigation water. However, an analysis of historical palm leaf manuscripts reveals that the temple had a firm economic base with corresponding interests and that it was one of the most important land-owners in late pre-colonial Bali. The article therefore explores from a socio-political and economic perspective the implications of this form of temple landlordism and its combination with ritual water control, particularly for the peasants and the portion of their annual surplus that they were obliged to deliver to this temple

Similar expression to FGF (Sef) inhibits fibroblast growth factor-induced tumourigenic behaviour in prostate cancer cells and is downregulated in aggressive clinical disease.

BACKGROUND: The fibroblast growth factor (FGF) axis is an important mitogenic stimulus in prostate carcinogenesis. We have previously reported that transcript level of human similar expression to FGF (hSef), a key regulator of this pathway, is downregulated in clinical prostate cancer. In this study we further analysed the role of hSef in prostate cancer. METHODS: hSef function was studied in in vitro and in vivo prostate cancer models using stable over-expression clones. Protein expression of hSef was studied in a comprehensive tissue microarray. RESULTS: Stable over-expression of hSef resulted in reduced in vitro cancer cell proliferation, migration and invasive potential. In an in vivo xenograft model, the expression of hSef significantly retarded prostate tumour growth as compared with empty vector (P=0.03) and non-transfected (P=0.0001) controls. Histological examination further showed a less invasive tumour phenotype and reduced numbers of proliferating cells (P=0.0002). In signalling studies, hSef inhibited FGF-induced ERK phosphorylation, migration to the nucleus and activation of a reporter gene. Constitutively active Ras, however, was able to reverse these effects, suggesting that hSef exerts an effect either above or at the level of Ras in prostate cancer cells. In a large tissue microarray, we observed a significant loss of hSef protein in high-grade (P<0.0001) and metastatic (P<0.0001) prostate cancer. CONCLUSIONS: Considered together, the role of hSef in attenuating FGF signalling and evidence of downregulation in advanced tumours argue strongly for a tumour suppressor function in human prostate cancer

Sprouty2 and Spred1-2 Proteins Inhibit the Activation of the ERK Pathway Elicited by Cyclopentenone Prostanoids

Sprouty and Spred proteins have been widely implicated in the negative regulation of the fibroblast growth factor receptor-extracellular regulated kinase (ERK) pathway. In considering the functional role of these proteins, we explored their effects on ERK activation induced by cyclopentenone prostanoids, which bind to and activate Ras proteins. We therefore found that ectopic overexpression in HeLa cells of human Sprouty2, or human Spred1 or 2, inhibits ERK1/2 and Elk-1 activation triggered by the cyclopentenone prostanoids PGA1 and 15d-PGJ2. Furthermore, we found that in HT cells that do not express Sprouty2 due to hypermethylation of its gene-promoter, PGA1-provoked ERK activation was more intense and sustained compared to other hematopoietic cell lines with unaltered Sprouty2 expression. Cyclopentenone prostanoids did not induce Sprouty2 tyrosine phosphorylation, in agreement with its incapability to activate tyrosine-kinase receptors. However, Sprouty2 Y55F, which acts as a defective mutant upon tyrosine-kinase receptor stimulation, did not inhibit cyclopentenone prostanoids-elicited ERK pathway activation. In addition, Sprouty2 did not affect the Ras-GTP levels promoted by cyclopentenone prostanoids. These results unveil both common and differential features in the activation of Ras-dependent pathways by cyclopentenone prostanoids and growth factors. Moreover, they provide the first evidence that Sprouty and Spred proteins are negative regulators of the ERK/Elk-1 pathway activation induced not only by growth-factors, but also by reactive lipidic mediators

Care of patients with inborn errors of immunity in thirty J Project countries between 2004 and 2021

IntroductionThe J Project (JP) physician education and clinical research collaboration program was started in 2004 and includes by now 32 countries mostly in Eastern and Central Europe (ECE). Until the end of 2021, 344 inborn errors of immunity (IEI)-focused meetings were organized by the JP to raise awareness and facilitate the diagnosis and treatment of patients with IEI.ResultsIn this study, meeting profiles and major diagnostic and treatment parameters were studied. JP center leaders reported patients’ data from 30 countries representing a total population of 506 567 565. Two countries reported patients from JP centers (Konya, Turkey and Cairo University, Egypt). Diagnostic criteria were based on the 2020 update of classification by the IUIS Expert Committee on IEI. The number of JP meetings increased from 6 per year in 2004 and 2005 to 44 and 63 in 2020 and 2021, respectively. The cumulative number of meetings per country varied from 1 to 59 in various countries reflecting partly but not entirely the population of the respective countries. Altogether, 24,879 patients were reported giving an average prevalence of 4.9. Most of the patients had predominantly antibody deficiency (46,32%) followed by patients with combined immunodeficiencies (14.3%). The percentages of patients with bone marrow failure and phenocopies of IEI were less than 1 each. The number of patients was remarkably higher that those reported to the ESID Registry in 13 countries. Immunoglobulin (IgG) substitution was provided to 7,572 patients (5,693 intravenously) and 1,480 patients received hematopoietic stem cell therapy (HSCT). Searching for basic diagnostic parameters revealed the availability of immunochemistry and flow cytometry in 27 and 28 countries, respectively, and targeted gene sequencing and new generation sequencing was available in 21 and 18 countries. The number of IEI centers and experts in the field were 260 and 690, respectively. We found high correlation between the number of IEI centers and patients treated with intravenous IgG (IVIG) (correlation coefficient, cc, 0,916) and with those who were treated with HSCT (cc, 0,905). Similar correlation was found when the number of experts was compared with those treated with HSCT. However, the number of patients treated with subcutaneous Ig (SCIG) only slightly correlated with the number of experts (cc, 0,489) and no correlation was found between the number of centers and patients on SCIG (cc, 0,174).Conclusions1) this is the first study describing major diagnostic and treatment parameters of IEI care in countries of the JP; 2) the data suggest that the JP had tremendous impact on the development of IEI care in ECE; 3) our data help to define major future targets of JP activity in various countries; 4) we suggest that the number of IEI centers and IEI experts closely correlate to the most important treatment parameters; 5) we propose that specialist education among medical professionals plays pivotal role in increasing levels of diagnostics and adequate care of this vulnerable and still highly neglected patient population; 6) this study also provides the basis for further analysis of more specific aspects of IEI care including genetic diagnostics, disease specific prevalence, newborn screening and professional collaboration in JP countries

Probleme der agraren Grundbesitzverfassung auf Bali/Indonesien

Bibliothek Weltwirtschaft Kiel A157,137 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Kooperation und landwirtschaftliche Entwicklung auf Bali, Indonesien

Bibliothek Weltwirtschaft Kiel A 172530 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Primary central nervous system lymphoma in patients with AIDS

Primary central nervous system lymphoma (PCNSL), once considered a rare brain neoplasm, has been steadily increasing in incidence mainly due to an enlarging population of immunosuppressed patients. PCNSL has become the second most common brain space occupying lesion in patients with the acquired immunodeficiency syndrome. A rapid diagnosis of this entity may represent weeks to months of survival to immunosuppressed HIV-positive patients. The radiologist now plays an important role in the noninvasive diagnosis and management of this condition through the accurate interpretation of imaging findings provided by CT, MR, and brain SPECT studies. This article focuses on the pathogenesis, clinical manifestations, neuropathology, and imaging characteristics of this brain neoplasm. New accurate imaging algorithms combining the diagnostic information provided by CT, MR, and T1-201 brain SPECT are discussed

Spred1 and TESK1—Two New Interaction Partners of the Kinase MARKK/TAO1 That Link the Microtubule and Actin Cytoskeleton

The signaling from MARKK/TAO1 to the MAP/microtubule affinity-regulating kinase MARK/Par1 to phosphorylated microtubule associated proteins (MAPs) renders microtubules dynamic and plays a role in neurite outgrowth or polarity development. Because hyperphosphorylation of Tau at MARK target sites is a hallmark of Alzheimer neurodegeneration, we searched for upstream regulators by the yeast two-hybrid approach and identified two new interaction partners of MARKK, the regulatory Sprouty-related protein with EVH-1 domain1 (Spred1) and the testis-specific protein kinase (TESK1). Spred1-MARKK binding has no effect on the activity of MARKK; therefore, it does not change microtubule (MT) stability. Spred1-TESK1 binding causes inhibition of TESK1. Because TESK1 can phosphorylate cofilin and thus stabilizes F-actin stress fibers, the inhibition of TESK1 by Spred1 makes F-actin fibers dynamic. A third element in this interaction triangle is that TESK1 binds to and inhibits MARKK. Thus, in Chinese hamster ovary (CHO) cells the elevation of MARKK results in MT disruption (via activation of MARK/Par1 and phosphorylation of MAPs), but this can be blocked by TESK1. Similarly, enhanced TESK1 activity results in increased stress fibers (via phospho-cofilin), but this can be blocked by elevating Spred1. Thus, the three-way interaction between Spred1, MARKK, and TESK1 represents a pathway that links regulation of both the microtubule- and F-actin cytoskeleton