[Public Health: Setting Goals, Establishing Structures and Improving Health for All]. / Public Health ­ mehr Gesundheit für alle.

Public health is a population- and system-based approach that is needed to improve the health of societies and to decrease health inequalities. In the face of global challenges, the public health approach is essential. In Germany, the importance of public health is only partly reflected by its institutions and institutional arrangements. This applies equally to research, teaching and training, as well as to the public health service. Furthermore, the public health perspective is not sufficiently considered in cross-sectional topics that are relevant for health.There have been several initiatives to overcome structural deficits which can partly be traced back to historical circumstances. The White Paper presented here should encourage discussions about future policy options in public health. The authors represent public health in practice, research, and teaching in Germany.

[Proposal for a Nationwide Johann-Peter Frank Cooperation Model under the National Leopoldina Initiative for Public Health and Global Health]. / Vorschlag für ein bundesweites Johann-Peter Frank Kooperationsmodell im Rahmen der nationalen Leopoldina-Initiative für Public Health und Global Health.

The discussion on the development of public health affairs was invigorated anew by the report on public health in Germany of Leopoldina/Acatech/Union of the German Academies of Sciences and Humanities of the year 2015. The report urges strengthening of public health and global health in Germany and addresses explicitly the Public Health Service (PHS). This indispensable inclusion of the PHS in further strategic planning offers for the first time an opportunity for a comprehensive and sustainable practice/policy transfer on the federal, state and community level, and also a chance for a sustainable network with modern academic public health institutions together with representation of medical specialization in public health at universities, that has been absent so far. A Johann-Peter Frank model for cooperation and stepwise modelling of this transition with the inclusion of the Academies for Public Health Service is presented.

[Medical Care for Refugees by the Public Health Services: Always Ready--But for How Much Longer?]. / Medizinische Versorgung von Flüchtlingen durch den Öffentlichen Gesundheitsdienst: Allzeit bereit--nur wie lange noch?

Refugees continue seeking sanctuary in Germany and it can reasonably be expected that their health will be affected by the conditions they lived in before and during flight. Ensuring nationwide care for refugees should be demand oriented, effective and efficient, which requires tackling mostly similar challenges a community level in a consistent manner. The aim must be providing adequate medical care based on the principle of respect for human dignity and ensuring public health standards. Within the currently situation, this basic expectations are often not sufficiently met. Generally accepted national standards, longer-term strategies and sustainable care are not yet achieved noticeably by public health services in Germany.To warrant permanent and sustainable high-quality medical care for refugees, local networks of involved institutions should be established with a longer-term perspective. Moreover, the financially eroded and personnel thinned public health service will only be able to fulfil statutory requirements and expectations of the local, state and federal policy makers for a limited amount of time only. Safeguarding that services are coping with the size of challenges over longer periods of time and anchoring the acquired expertise of medical care for refugees within the public health services, requires immediately better financial and personnel resources. Then the public health services will be a reliable partner supporting all people in Germany, particularly those that require subsidiary and socially-compensatory supply.

Functional characterization of corticotropin-releasing factor type 1 receptor endogenously expressed in human embryonic kidney 293 cells.

The endogenous expression in human embryonic kidney 293 (HEK293) cells of corticotropin-releasing factor (CRF) receptors was detected. High-affinity binding sites for human CRF (K(i)=3.6 nM), ovine CRF (K(i)=4.6 nM), rat urocortin (K(i)=2.2 nM), sauvagine (K(i)=2.4 nM) and astressin (K(i)=4.3 nM) with the pharmacological characteristics for CRF type 1 (CRF(1)) receptors and B(max) values of approximately 30 fmol/mg protein were determined. The four CRF receptor agonists nonselectively stimulated cAMP production in HEK293 cells at low agonist concentrations, whereas the antagonist astressin shifted the dose-response curve for ovine CRF significantly rightward. Transfection of the pcDNA3 vector into HEK293 cells strongly reduced the expression of the endogenous CRF receptor. Northern blot analysis revealed the expression of a CRF(1) transcript in human neuronal tissues, HEK293, human NTera-2 (NT2) carcinoma, Y-79 retinoblastoma and African green monkey kidney (COS-7) cells. Neither by Northern blot analysis nor by reverse transcriptase PCR (RT-PCR), the expression of CRF(2) could be detected. In cAMP stimulation experiments, functional CRF receptors were detected in these cell lines. These data show that HEK293 and other cell lines endogenously express CRF(1) receptors.

The phosphoprotein DARPP-32 mediates cAMP-dependent potentiation of striatal N-methyl-D-aspartate responses.

The signal transduction pathway underlying the cAMP-dependent modulation of rat striatal N-methyl-D-aspartate (NMDA) responses was investigated by using the two-electrode voltage-clamp technique. In oocytes injected with rat striatal poly(A)+ mRNA, activation of cAMP-dependent protein kinase (PKA) by forskolin potentiated NMDA responses. Inhibition of protein phosphatase 1 (PP1) and/or protein phosphatase 2A (PP2A) by the specific inhibitor calyculin A occluded the PKA-mediated potentiation of striatal NMDA responses, suggesting that the PKA effect was mediated by inhibition of a protein phosphatase. Coinjection of oocytes with striatal mRNA and antisense oligodeoxynucleotides directed against the protein phosphatase inhibitor DARPP-32 dramatically reduced the PKA enhancement of NMDA responses. NMDA responses recorded from oocytes injected with rat hippocampal poly(A)+ mRNA were not affected by stimulation of PKA. When oocytes were coinjected with rat hippocampal poly(A)+ mRNA plus complementary RNA coding for DARPP-32, NMDA responses were potentiated after stimulation of PKA. The results provide evidence that DARPP-32, which is enriched in the striatum, may participate in the signaling between the two major afferent striatal pathways, the glutamatergic and the dopaminergic projections, by the cAMP-dependent regulation of striatal NMDA currents.

Ubiquitous fiber exposure in selected sampling sites in Europe.

OBJECTIVES: This study evaluates personal exposure to respirable inorganic and organic fibers during normal human lifetimes and assesses the order of magnitude of the contribution of inorganic fibers other than asbestos to total fiber exposure from man-made and natural sources. METHODS: Four groups (suburban schoolchildren, rural retired persons, office workers, and taxi drivers), with five persons per group, were monitored for 24 h four times during one year. Personal sampling pumps collected airborne dust on gold-precoated Nuclepore filters. The fibers were analyzed for fiber sizes specified by the World Health Organization. RESULTS: The geometric mean concentrations ranged from 9000 fibers.m-3 (office workers) to 20000 fibers.m-3 (schoolchildren) for organic fibers, and from 600 fibers.m-3 (taxi drivers) to 4000 fibers.m-3 (schoolchildren) for gypsum fibers. For other inorganic fibers the concentrations were around 5000 fibers.m-3. The contribution of fibers with an elemental composition similar to that of man-made vitreous fibers (MMVF) was less than about one-quarter of the content of other inorganic fibers. The fiber size distributions were uniform across the groups, and the organic fibers were the longest and thinnest nonasbestos fibers. CONCLUSIONS: Lifetime exposure to fibers can be ranked as organic fibers > other inorganic fibers > fibers with an elemental composition similar to MMVF > MMVF. Information on the biological effects of fibers is difficult to interpret for use in assessing the health risk from exposure to low levels of ubiquitous fibers, and there is a lack of knowledge on the effects of organic fibers.

Molecular cloning, sequencing, deletion, and overexpression of a methionine aminopeptidase gene from Saccharomyces cerevisiae.

A yeast gene for a methionine aminopeptidase, one of the central enzymes in protein synthesis, was cloned and sequenced. The DNA sequence encodes a precursor protein containing 387 amino acid residues. The mature protein, whose NH2-terminal sequence was confirmed by Edman degradation, consists of 377 amino acids. The function of the 10-residue sequence at the NH2 terminus, containing 1 serine and 6 threonine residues, remains to be established. In contrast to the structure of the prokaryotic enzyme, the yeast methionine aminopeptidase consists of two functional domains: a unique NH2-terminal domain containing two motifs resembling zinc fingers, which may allow the protein to interact with ribosomes, and a catalytic COOH-terminal domain resembling other prokaryotic methionine aminopeptidases. Furthermore, unlike the case for the prokaryotic gene, the deletion of the yeast MAP1 gene is not lethal, suggesting for the first time that alternative NH2-terminal processing pathway(s) exist for cleaving methionine from nascent polypeptide chains in eukaryotic cells.

Purification and characterization of a methionine aminopeptidase from Saccharomyces cerevisiae.

Methionine aminopeptidase (MAP), which catalyzes the removal of NH2-terminal methionine from proteins, was isolated from Saccharomyces cerevisiae. The enzyme was purified 472-fold to apparent homogeneity. The Mr of the native enzyme was estimated to be 36,000 +/- 5,000 by gel filtration chromatography, and the Mr of the denatured protein was estimated to be 34,000 +/- 2,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme has a pH optimum near 7.0, and its pI is 7.8 as determined by chromatofocusing on Mono P. The enzyme was inactivated by metalloprotease inhibitors (EDTA, o-phenanthroline and nitrilotriacetic acid), sulfhydryl-modifying reagents (HgCl2 and p-hydroxymercuribenzoic acid), and Zn2+. Yeast MAP failed to cleave methionine p-nitroanilide. Among 11 Xaa-Ala-Ser analogues (Xaa = Ala, Asp, Gln, Glu, Ile, Leu, Lys, Met, Phe, Pro, and Ser), MAP cleaved only Met-Ala-Ser. MAP also cleaved methionine from other tripeptides whose penultimate amino acid residue is relatively small and/or uncharged (e.g. Pro, Gly, Val, Thr, or Ser) but not when bulky and/or charged (Arg. His, Leu, Met, or Tyr). Yeast MAP displayed similar substrate specificities compared with those of Escherichia coli (Ben-Bassat, A., Bauer, K., Chang, S.Y., Myambo, K., Boosman, A., and Chang, S. (1987) J. Bacteriol. 169, 751-757) and Salmonella typhimurium MAP (Miller, C., Strauch, K. L., Kukral, A. M., Miller, J. L., Wingfield, P. T., Mazzei, G. J., Werlen, R. C., Garber, P., and Movva, N. R. (1987) Proc. Natl, Acad. Sci. U.S.A. 84, 2718-2722). In general, the in vitro specificity of yeast MAP is consistent with the specificity observed in previous in vivo studies in yeast (reviewed in Arfin, S. M., and Bradshaw, R. A. (1988) Biochemistry 27, 7979-7984).

Lysosomal (vacuolar) proteinases of yeast are essential catalysts for protein degradation, differentiation, and cell survival.

Mutants deficient in the vacuolar (lysosomal) endopeptidases proteinase yscA and proteinase yscB of the yeast Saccharomyces cerevisiae exhibit a drastically reduced protein degradation rate under nutritional stress conditions. The differentiation process of sporulation is considerably disturbed by the absence of the two endopeptidases. Also under vegetative growth conditions and under conditions of false protein synthesis, the two vacuolar endopeptidases exhibit some effect on protein degradation, which is, however, much less pronounced as found under starvation conditions. Proteinase yscA deficiency leads to rapid cell death when glucose-grown cells starve for nitrogen or other nutrients. Whereas overall protein degradation is affected in the endopeptidase mutants, degradation of two distinct false proteins analyzed is not altered in the absence of proteinase yscA and proteinase yscB. Also catabolite inactivation and degradation of fructose-1,6-bisphosphatase is not affected to a greater extent in the endopeptidase-deficient strains.

Measurement of inorganic fibrous particulates in ambient air and indoors with the scanning electron microscope.

In the Federal Republic of Germany, the concentration of inorganic fibrous particles in the ambient air is measured by scanning electron microscopy (SEM) in accordance with draft guideline VDI 3492. Fibres of length greater than or equal to 2.5 microns are counted at a magnification of X2000. The concentrations and fibre dimensions of asbestos fibres and other mineral fibres were determined for 231 ambient air samples, 219 indoor air samples taken during asbestos removal and 21 taken at workplaces. In the ambient air measurements in rural and urban areas, the average concentration of other inorganic fibres was greater than 1000 fibres of length greater than or equal to 5 microns per m3. On the average, only about 100 or fewer asbestos fibres of length greater than or equal to 5 microns per m3 were observed. These 'asbestos fibres' from ambient air had low aspect ratios. They differed substantially from asbestos fibres measured in the ambient air close to sources of asbestos emissions, indoors during asbestos removal or at workplaces. Furthermore, the size distribution of these 'asbestos fibres' was similar to that of 'other inorganic fibres'. We suggest, therefore, that a substantial portion of the 'asbestos fibres' observed by SEM analysis in ambient air samples from rural and urban areas should be classified instead as 'other mineral fibres'.

Proteinase yscD mutants of yeast. Isolation and characterization.

Mutants of the yeast Saccharomyces cerevisiae, devoid of proteinase yscD activity, were isolated by screening for the inability of mutagenized cells to hydrolyze Ac-Ala-Ala-Pro-Ala-beta-naphthylamide in situ. One of the selected mutants bears a thermolabile activity pointing to the gene called PRD1 as being the structural gene for proteinase yscD. All mutants isolated fell into one complementation group. The defect segregates 2:2 in meiotic tetrads indicating a single gene mutation, which was shown to be recessive. Diploids heterozygous for PRD1 display gene dosage. The absence of proteinase yscD did not affect mitotic growth under rich or poor growth conditions, neither mating nor ascopore formation. Also growth of mutant cells after a nutritional shift-down was not altered. Inactivation of enzymes tested which are subject to carbon-catabolite inactivation, a process proposed to be of proteolytic nature, is not affected by the absence of proteinase yscD. Protein degradation rates in growing cells, in cells under conditions of differentiation or heat shock, showed no obvious alteration in the absence of proteinase yscD activity. Also inactivation of alpha-factor pheromone was not affected by proteinase yscD absence. Normal growth of mutant cells on glycerol indicates that the enzyme is not involved in any vital event in mitochondrial biogenesis.