Review: Ethical responsibilities and transformation strategies of focal companies in the meat supply chain: the implementation dilemma.

In Germany (and other Organisation for Economic Co-operation and Development countries), the need for a fundamental transformation of livestock farming has become increasingly evident in recent years. Two broad-based stakeholder commissions including the German farmers' association, the meat industry, and Non-Governmental Organizations have endorsed this demand. Nevertheless, major steps towards its implementation are still missing - a circumstance we refer to in this paper as the implementation dilemma. In a globalised economy, farmers cannot solve the problem of low animal welfare standards alone although they are important actors. Moreover, consumer behaviour is changing too slowly, and possibilities for granting more subsidies are limited in the face of multiple economic crises. Against this background, we argue for a stronger focus on voluntary (private) sustainability agreements. We therefore analyse how the German meat supply chain is organised and what responsibility and power the individual actors have to push the sector's transformation. Large slaughterhouses, processors, and the retailing sector seem promising due to their high market concentration and power. Especially retailers can influence the transformation of the market through their role as gatekeepers between suppliers and consumers. Based on business ethics principles of taking responsibility, we consider the focus on sustainability obligations of the retail sector to be ethically justified. However, it is then necessary to give the four retail groups dominating the meat chain in Germany more leeway for sustainability agreements in antitrust law.

Biocatalytic methanation of hydrogen and carbon dioxide in an anaerobic three-phase system.

A new type of anaerobic trickle-bed reactor was used for biocatalytic methanation of hydrogen and carbon dioxide under mesophilic temperatures and ambient pressure in a continuous process. The conversion of gaseous substrates through immobilized hydrogenotrophic methanogenic archaea in a biofilm is a unique feature of this type of reactor. Due to the formation of a three-phase system on the carrier surface and operation as a plug flow reactor without gas recirculation, a complete reaction could be observed. With a methane concentration higher than c(CH4) = 98%, the product gas exhibits a very high quality. A specific methane production of P(CH4) = 1.49 Nm(3)/(m(3)(SV) d) was achieved at a hydraulic loading rate of LR(H2) = 6.0 Nm(3)/(m(3)(SV) d). The relation between trickle flow through the reactor and productivity could be shown. An application for methane enrichment in combination with biogas facilities as a source of carbon dioxide has also been positively proven.

Forest ecosystems and the changing patterns of nitrogen input and acid deposition today and in the future based on a scenario.

A global assessment of the impact of the anthropogenic perturbation of the nitrogen and sulfur cycles on forest ecosystems is carried out for both the present-day [1980-1990] and for a projection into the future [2040-2050] under a scenario of economic development which represents a medium path of development according to expert guess [IPCC IS92a]. Results show that forest soils will receive considerably increasing loads of nitrogen and acid deposition and that deposition patterns are likely to change. The regions which are most prone to depletion of soils buffering capacity and supercritical nitrogen deposition are identified in the subtropical and tropical regions of South America and Southeast Asia apart from the well known 'hotspots' North-Eastern America and Central Europe. The forest areas likely to meet these two risks are still a minor fraction of the global forest ecosystems, though. But the bias between eutrophication and acidification will become greater and an enhanced growth triggered by the fertilizing effects of increasing nitrogen input cannot be balanced by the forest soils nutrient pools. Results show increasing loads into forest ecosystems which are likely to account for 46% higher acid loads and 36% higher nitrogen loads in relation to the 1980-1990 situation. Global background deposition of up to 5 kg N ha-1 a-1 will be exceeded at more than 25% of global forest ecosystems and at more than 50% of forest ecosystems on acid sensitive soils. More than 33% of forest ecosystems on acid sensitive soils will receive acid loads which exceeds their buffering capacity. About 25% of forest areas with exceeded acid loads will receive critical nitrogen loads.

Increased chromosomal imbalances in recurrent pituitary adenomas.

Eight pituitary adenomas (four gonadotroph cell adenomas, three prolactin cell adenomas, one null cell adenoma) and their respective recurrences in the same patients were studied by comparative genomic hybridization. Chromosomal imbalances were found in seven of eight patients affecting two of eight primary and seven of eight recurrent tumors. Overall, pituitary adenomas showed an average of 1.6 chromosomal imbalances per primary and 3.4 per recurrent tumor (P < 0.01). Prolactin cell adenomas showed an average of 4.3 chromosomal changes per primary and 6.3 per recurrent tumor, which were significantly more common than in gonadotroph cell adenomas (0 vs 1.7 changes; P < 0.05) and the null cell adenoma (0 vs 1.0 changes; P < 0.05). The most common changes were gains of 4q (in three of eight recurrences), 5q, and 13q (in two of eight recurrences each) as well as losses of chromosome 2 (in both primary and recurring tumors of two patients), 1p, 8q, 10, and 12q (in two of eight recurrences). Minimal common regions associated with recurrent adenomas were gains of 4q31.2-34 (three recurrences), 5q14-23 and 13q21-31 and losses of 12q24.3-qter (two recurrences each). The average MIB-1 proliferation indices were 1.2% for primary and 1.9% for recurrent adenomas (P < 0.005). Our findings suggest that acquisition of certain chromosomal imbalances is related to and may underlie adenoma recurrence.

Effect of urea and osmotic cell shrinkage on Ca2+ entry and contraction of vascular smooth muscle cells.

The present study was performed to elucidate the effects of urea on vascular smooth muscle cells (SMC). Addition of urea (20, 50, 100 mM) to physiological salt solution blunted the vasoconstrictory effect of phenylephrine (by 17, 25 and 30%, respectively) and of an increased extracellular K+ concentration (by 7, 14 and 19%, respectively) without affecting the basal tone of rabbit arterial rings. According to Fura-2 fluorescence in cultured SMC (A7r5), urea had no effect on basal intracellular calcium activity ([Ca2+]i), but significantly blunted the increase of [Ca2+]i following an increase of extracellular K+. Whole-cell patch-clamp studies revealed that the Ca2+ current through voltage-sensitive Ca2+ channels is significantly inhibited in the presence of urea. As evident from calcein fluorescence, addition of urea leads to sustained cell shrinkage. The effects of urea on vascular tone, [Ca2+]i activity, voltage-gated Ca2+ channels and cell volume are mimicked by addition of raffinose or NaCl. However, the cell shrinkage induced by urea is sustained, whereas the addition of equiosmolar NaCl is only transient and followed by a regulatory cell volume increase. Moreover, hypertonic NaCl increases, whereas urea decreases, the transcription of cell-volume-regulated kinase hsgk. In conclusion, urea leads to sustained shrinkage of vascular smooth muscle cells, which is followed by inhibition of voltage-gated Ca2+ channels, a decrease of [Ca2+]i and thus blunts the vasoconstrictory action of phenylephrine and increased extracellular K+ concentration.

Stimulation of CD95 (Fas) blocks T lymphocyte calcium channels through sphingomyelinase and sphingolipids.

Calcium influx through store-operated calcium release-activated calcium channels (CRAC) is required for T cell activation, cytokine synthesis, and proliferation. The CD95 (Apo-1/Fas) receptor plays a role in self-tolerance and tumor immune escape, and it mediates apoptosis in activated T cells. In this paper we show that CD95-stimulation blocks CRAC and Ca(2+) influx in lymphocytes through the activation of acidic sphingomyelinase (ASM) and ceramide release. The block of Ca(2+) entry is lacking in CD95-defective lpr lymphocytes as well as in ASM-defective cells and can be restored by retransfection of ASM. C2 ceramide, C6 ceramide, and sphingosine block CRAC reversibly, whereas the inactive dihydroceramide has no effect. CD95-stimulation or the addition of ceramide prevents store-operated Ca(2+) influx, activation of the transcriptional regulator NFAT, and IL-2 synthesis. The block of CRAC by sphingomyelinase metabolites adds a function to the repertoire of the CD95 receptor inhibiting T cell activation signals.

[Concentrating on weaknesses or compensating by strengths? Comparison of 2 strategies for remediation of children with comprehensive reading-spelling disorder]. / An Schwächen üben oder durch Stärken ausgleichen? Vergleich zweier Strategien in der Förderung von Kindern mit einer umschriebenen Lese-Rechtschreib-Schwäche.

Our study compares the efficiency and acceptance of two different methods of treating dyslexia in children. The first method addresses the most commonly encountered deficits in sequential processing. It relies primarly upon the "Kieler Lese-Rechtschreibaufbau". The second proceeds from the child's relative resources with regard to simultaneous processing as described by Kaufman. Training materials are those prescribed by Kaufman. Normally gifted primary school third-graders were trained in two groups (n = 13 and n = 12) and achieved a mean SIF score of SW = 101 on the K-ABC. As expected, the children scored significantly lower on the SED scale (SW = 95) than on the SGD scale (SW = 105). At the beginning of the respective training program their spelling ability fell 1.5 SD below the class mean. One year of regular weekly one-hour training according to the simultaneous processing method was significantly more successful than training in sequential processing, whereas girls improved significantly more than boys regardless of the method used. Acceptance of the methods did not vary. This result requires careful consideration and should be replicated in younger samples such as first- and second-graders in the early stages of learning to read and write, and/or in children whose dyslexia is more severe than that encountered in the current sample. It underscores that determination of an adequate method of remediation entails more than the mere identification of the underlying deficits.

High-speed random access laser tuning.

We have developed a technique for laser tuning at rates of 100 kHz or more using a pair of acousto-optic modulators. In addition to all-electronic wavelength control, the same modulators also can provide electronically variable Q-switching, cavity length and power stabilization, chirp and linewidth control, and variable output coupling, all at rates far beyond what is possible with conventional mechanically tuned components. Tuning rates of 70 kHz have been demonstrated on a radio-frequency-pumped CO2 laser, with random access to over 50 laser lines spanning a 17% range in wavelength and with wavelength discrimination better than 1 part in 1000. A compact tuner and Q-switch has been deployed in a 5-10-kHz pulsed lidar system. The modulators each operate at a fixed Bragg angle, with the acoustic frequency determining the selected wavelength. This arrangement doubles the wavelength resolution without introducing an undesirable frequency shift.

Mesangial cell hypertrophy induced by NH4Cl: role of depressed activities of cathepsins due to elevated lysosomal pH.

Enhanced ammoniagenesis is currently thought to play an important role in renal hypertrophy and subsequent tubulointerstitial fibrosis. Under certain conditions glomeruli also may be affected by ammonia toxicity. Exposure of glomeruli to augmented ammonia levels may occur: (i) in advanced liver diseases due to elevated blood ammonia concentrations; (ii) in conditions of enhanced tubular ammoniagenesis following cortical "trapping;" and (iii) due to increased ammonia formation in the glomeruli in the presence of impaired renal function. To elucidate the potential role of ammonia in glomerular injury, we investigated the effect of NH4Cl on protein turnover as well as on activities of various cathepsins in cultured rat mesangial cells. The results show that NH4Cl (20 mM) induced cell hypertrophy as defined by an increase in both cell protein content and cell volume (+38% and +10.1%, respectively, after 48 hr). This hypertrophy was associated with suppression of the activities of cathepsins B and L + B (-56.8% and -51.3% after 48 hr) and reduction of protein degradation rate (-61% after 48 hr), but without enhanced protein synthesis. Inhibition of Na+/H+ antiport by amiloride (1 mM) neither prevented the reduction of cathepsin activities nor the hypertrophy of the mesangial cells. Upon NH4Cl application lysosomal pH was elevated. This alkalinization may be causatively involved in the impairment of cathepsin B and L + B due to shifting the lysosomal pH above the optimum of their activities. In conclusion, NH4Cl induces hypertrophy but not hyperplasia in mesangial cells. This hypertrophy is caused by the reduction of protein degradation, mainly due to depressed activities of cathepsin B and L + B in the absence of enhanced protein synthesis. A shift of lysosomal pH above the optimum of the acidic cathepsins seems to be a key factor in their impaired activities in mesangial cells.

Ion channels involved in insulin release are activated by osmotic swelling of pancreatic B-cells.

Measurements of the membrane potential showed that osmotic swelling (-80 mosmol/l) of pancreatic B-cells led to a transient hyperpolarization followed by a more sustained depolarization of the cell membrane. Cell swelling triggers a transient activation of the K+ATP current and of an inward current, carried by Cl-. This current was inhibited by DIDS, D600, and by omission of extracellular Ca2+. The depolarization opens voltage dependent L-type Ca2+ channels, thereby increasing the intracellular Ca2+ activity ([Ca2+]i). This effect was blunted by D600 or abolished by omission of Ca2+. Moreover, osmotic swelling transiently increased the amplitude of the Ca2+ currents. Replacement of NaCl by d-mannitol proved that the observed effects are due to an increase in cell volume and not to a reduction of extracellular Na+ or Cl-. Our results suggest that regulatory volume decrease is achieved by activation of K+ and Cl- currents. The Cl- current is responsible for the previously described depolarization and increase in insulin release induced by osmotic cell swelling.

The diversity of volume regulatory mechanisms.

Mammalian cells utilize a wide variety of cell volume regulatory mechanisms. For rapid adjustment of cell volume cells release or accumulate ions through respective channels and transport systems across the cell membrane. The most widely used mechanisms of cell volume regulatory ion release include ion channels and KCl symport. Ion uptake is most frequently mediated by Na+ channels, Na+, K+, 2Cl- cotransport, and Na+/H+ exchange. Chronic adjustment of cell osmolarity is accomplished by the formation or accumulation of organic osmolytes, molecules specifically designed to create intracellular osmolarity without interfering with cellular function. The most widely occurring osmolytes are sorbitol, inositol, glycerophosphorylcholine, betaine, taurine, and amino acids. The osmolytes are either synthesized by or transported into shrunken cells. During cell swelling osmolytes can be rapidly degraded or released. Any given cell may utilize several volume-regulatory mechanisms. Moreover, different mechanisms are utilized in different tissues. The diversity of cell volume regulatory mechanisms allows the cells to defend the constancy of cell volume against a myriad of challenges with relatively little impairment of cellular function.

Functional significance of cell volume regulatory mechanisms.

To survive, cells have to avoid excessive alterations of cell volume that jeopardize structural integrity and constancy of intracellular milieu. The function of cellular proteins seems specifically sensitive to dilution and concentration, determining the extent of macromolecular crowding. Even at constant extracellular osmolarity, volume constancy of any mammalian cell is permanently challenged by transport of osmotically active substances across the cell membrane and formation or disappearance of cellular osmolarity by metabolism. Thus cell volume constancy requires the continued operation of cell volume regulatory mechanisms, including ion transport across the cell membrane as well as accumulation or disposal of organic osmolytes and metabolites. The various cell volume regulatory mechanisms are triggered by a multitude of intracellular signaling events including alterations of cell membrane potential and of intracellular ion composition, various second messenger cascades, phosphorylation of diverse target proteins, and altered gene expression. Hormones and mediators have been shown to exploit the volume regulatory machinery to exert their effects. Thus cell volume may be considered a second message in the transmission of hormonal signals. Accordingly, alterations of cell volume and volume regulatory mechanisms participate in a wide variety of cellular functions including epithelial transport, metabolism, excitation, hormone release, migration, cell proliferation, and cell death.

Effect of osmolarity on LDL binding and internalization in hepatocytes.

The present study has been performed to elucidate a possible role of cell volume in low-density lipoprotein (LDL) binding and internalization (LDL(b+i)). As shown previously, increase of extracellular osmolarity (OSMe) and K+ depletion, both known to shrink cells, interfere with the formation of clathrin-coated pits and thus with LDL(b+i). On the other hand, alterations of cell volume have been shown to modify lysosomal pH, which is a determinant of LDL(b+i). LDL(b+i) have been estimated from heparin-releasable (binding) or heparin-insensitive (internalization) uptake of 125I-labeled LDL. OSMe was modified by alterations of extracellular concentrations of ions, glucose, urea, or raffinose. When OSMe was altered by varying NaCl concentrations, LDL(b+i) decreased (by 0.5 +/- 0.1%/mM) with increasing OSMe and LDL(b+i) increased (by 1.2 +/- 0.1%/mM) with decreasing OSMe, an effect mainly due to altered affinity; the estimated dissociation constant amounted to 20.6, 48.6, and 131.6 micro/ml at 219, 293, and 435 mosM, respectively. A 25% increase of OSMe increased cytosolic (by 0.46 +/- 0.03) and decreased lysosomal (by 0.14 +/- 0.02) pH. Conversely, a 25% decrease of OSMe decreased cytosolic (by 0.28 +/- 0.02) and increased lysosomal (by 0.17 +/- 0.02) pH. Partial replacement of extracellular Na+ with K+ had little effect on LDL(b+i), although it swelled hepatocytes and increased lysosomal and cytosolic pH. Hypertonic glucose, urea, or raffinose did not exert similar effects despite a shrinking effect of hypertonic raffinose. Monensin, which completely dissipates lysosomal acidity, virtually abolished LDL(b+i). In conclusion, the observations reveal a significant effect of ionic strength on LDL(b+i). The effect is, however, not likely to be mediated by alterations of cell volume or alterations of lysosomal pH.

The role of the IsK protein in the specific pharmacological properties of the IKs channel complex.

IKs channels are composed of IsK and KvLQT1 subunits and underly the slowly activating, voltage-dependent IKs conductance in heart. Although it appears clear that the IsK protein affects both the biophysical properties and regulation of IKs channels, its role in channel pharmacology is unclear. In the present study we demonstrate that KvLQT1 homopolymeric K+ channels are inhibited by the IKs blockers 293B, azimilide and 17-beta-oestradiol. However, IKs channels induced by the coexpression of IsK and KvLQT1 subunits have a 6-100 fold higher affinity for these blockers. Moreover, the IKs activators mefenamic acid and DIDS had little effect on KvLQT1 homopolymeric channels, although they dramatically enhanced steady-state currents through heteropolymeric IKs channels by arresting them in an open state. In summary, the IsK protein modulates the effects of both blockers and activators of IKs channels. This finding is important for the action and specificity of these drugs as IsK protein expression in heart and other tissues is regulated during development and by hormones.

L-selectin regulates actin polymerisation via activation of the small G-protein Rac2.

L-selectin mediated adhesion to endothelial cells is a crucial step in the immune response to pathogens (1, 2) and in lymphocyte homing (3, 4). Selectin molecules mediate leukocyte rolling on endothelial cells, the initial step of adhesion (5, 6). We have previously shown that stimulation of Jurkat T-lymphocytes via L-selectin results in activation of the p21Ras pathway and synthesis of reactive oxygen intermediates (7). Here, we show that cellular stimulation via L-selectin induces a change of cytoskeleton organisation demonstrated by a tenfold increase of actin filament polymerisation. This actin polymerisation is mediated by a Ras and Rac2 regulated pathway, since inhibition of Ras by transient transfection of transdominant inhibitory N17Ras or suppression of Rac2 protein expression by antisense oligonucleotides prevents L-selectin triggered actin polymerisation. Our results point to a signaling cascade from L-selectin via Ras and Rac2 to actin filaments, which might be important for leukocyte adhesion.