Heavy ion action on single cells: Cellular inactivation capability of single accelerated heavy ions

Heavy ions (HZE-particles) constitute an important part of radiation in space. Although their number is small the high amount of energy transferred by individual particles may cause severe biological effects. Their investigation requires special techniques which were tested by experiments performed at the UNILAC at the GSI (Darmstadt). Diploid yeast was used which is a suitable eucaryotic test system because of its resistance to extreme conditions like dryness and vacuum. Cells were placed on nuclear track detector foils and exposed to ions of different atomic number and energy. To assess the action of one single ion on an individual cell, track parameters and the respective colony forming abilities (CFA) were determined with the help of computer aided image analysis. There is mounting evidence that not only the amount of energy deposited along the particle path, commonly given by the LET, is of importance but also the spatial problem of energy deposition at a submicroscopical scale. It is virtually impossible to investigate track structure effects in detail with whole cell populations and (globally applied) high particle fluences. It is, therefore, necessary to detect the action of simple ions in individual cells. The results show that the biological action depends on atomic number and specific energy of the impinging ions, which can be compared with model calculations of recent track structure models

End-Triassic calcification crisis and blooms of organic-walled 'disaster species'

The Triassic–Jurassic (T–J) mass-extinction event is marked by isotope anomalies in organic (δ13Corg) and carbonate carbon (δ13Ccarb) reservoirs. These have been attributed to a (rapid) 4-fold rise in pCO2 as a result of massive flood basalt volcanism and/or methane hydrate dissociation. Here we examine the response of marine photosynthetic phytoplankton to the proposed perturbation in the carbon cycle. Our high-resolution micropalaeontological analysis of T–J boundary beds at St Audrie's Bay in Somerset, UK, provides evidence for a bio-calcification crisis that is characterized by (1) extinction and malformation in calcareous nannoplankton and (2) contemporaneous blooms of organic-walled, green algal 'disaster' species which comprise in one case > 70% of the total palynomorph fraction. Blooms of prasinophytes and acritarchs occur at the onset and in association with a prominent negative shift in δ13Corg values close to the first appearance of the Early Jurassic ammonite Psiloceras planorbis. Across the same interval we obtained palaeotemperature and palaeosalinity estimates from oyster low-Mg calcite based on Mg/Ca, Sr/Ca and δ18O records. The results of our palynological and geochemical analyses strongly suggest that shallow marine basins in NW Europe during this period became salinity stratified, inducing anoxic conditions. The T–J boundary event shows similarities with the Permian–Triassic (P–T) mass-extinction event, which was also marked by extensive flood basalt volcanism, negative excursions in carbon isotope records, a bio-calcification crisis, the development of shallow-marine anoxia and mass abundances of acritarchs in the Early Triassic. This leads us to suggest that the proliferation of green algal phytoplankton may be symptomatic of elevated carbon dioxide levels in the atmosphere and oceans during mass-extinction events

Agency, qualia and life: connecting mind and body biologically

Many believe that a suitably programmed computer could act for its own goals and experience feelings. I challenge this view and argue that agency, mental causation and qualia are all founded in the unique, homeostatic nature of living matter. The theory was formulated for coherence with the concept of an agent, neuroscientific data and laws of physics. By this method, I infer that a successful action is homeostatic for its agent and can be caused by a feeling - which does not motivate as a force, but as a control signal. From brain research and the locality principle of physics, I surmise that qualia are a fundamental, biological form of energy generated in specialized neurons. Subjectivity is explained as thermodynamically necessary on the supposition that, by converting action potentials to feelings, the neural cells avert damage from the electrochemical pulses. In exchange for this entropic benefit, phenomenal energy is spent as and where it is produced - which precludes the objective observation of qualia

Underperforming policy networks : the biopesticides network in the United Kingdom

Loosely integrated and incomplete policy networks have been neglected in the literature. They are important to consider in terms of understanding network underperformance. The effective delivery and formulation of policy requires networks that are not incomplete or underperforming. The biopesticides policy network in the United Kingdom is considered and its components identified with an emphasis on the lack of integration of retailers and environmental groups. The nature of the network constrains the actions of its agents and frustrates the achievement of policy goals. A study of this relatively immature policy network also allows for a focus on network formation. The state, via an external central government department, has been a key factor in the development of the network. Therefore, it is important to incorporate such factors more systematically into understandings of network formation. Feedback efforts from policy have increased interactions between productionist actors but the sphere of consumption remains insufficiently articulated

Gene-modified T cells for adoptive immunotherapy of renal cell cancer maintain transgene-specific immune functions in vivo

Abstract BACKGROUND: We have treated three patients with carboxy-anhydrase-IX (CAIX) positive metastatic renal cell cancer (RCC) by adoptive transfer of autologous T-cells that had been gene-transduced to express a single-chain antibody-G250 chimeric receptor [scFv(G250)], and encountered liver toxicity necessitating adaptation of the treatment protocol. Here, we investigate whether or not the in vivo activity of the infused scFv(G250)(+) T cells is reflected by changes of selected immune parameters measured in peripheral blood. METHODS: ScFv(G250)-chimeric receptor-mediated functions of peripheral blood mononuclear cells (PBMC) obtained from three patients during and after treatment were compared to the same functions of scFv(G250)(+) T lymphocytes prior to infusion, and were correlated with plasma cytokine levels. RESULTS: Prior to infusion, scFv(G250)(+) T lymphocytes showed in vitro high levels of scFv(G250)-chimeric receptor-mediated functions such as killing of CAIX(+) RCC cell lines and cytokine production upon exposure to these cells. High levels of IFN-gamma were produced, whilst production of TNF-alpha, interleukin-4 (IL-4), IL-5 and IL-10 was variable and to lower levels, and that of IL-2 virtually absent. PBMC taken from patients during therapy showed lower levels of in vitro scFv(G250)-receptor-mediated functions as compared to pre-infusion, whilst IFN-gamma was the only detectable cytokine upon in vitro PBMC exposure to CAIX. During treatment, plasma levels of IFN-gamma increased only in the patient with the most prominent liver toxicity. IL-5 plasma levels increased transiently during treatment in all patients, which may have been triggered by the co-administration of IL-2. CONCLUSION: ScFv(G250)-receptor-mediated functions of the scFv(G250)(+) T lymphocytes are, by and large, preserved in vivo upon administration, and may be reflected by fluctuations in plasma IFN-gamma levels

Magnetism, FeS colloids, and Origins of Life

A number of features of living systems: reversible interactions and weak bonds underlying motor-dynamics; gel-sol transitions; cellular connected fractal organization; asymmetry in interactions and organization; quantum coherent phenomena; to name some, can have a natural accounting via $physical$ interactions, which we therefore seek to incorporate by expanding the horizons of `chemistry-only' approaches to the origins of life. It is suggested that the magnetic 'face' of the minerals from the inorganic world, recognized to have played a pivotal role in initiating Life, may throw light on some of these issues. A magnetic environment in the form of rocks in the Hadean Ocean could have enabled the accretion and therefore an ordered confinement of super-paramagnetic colloids within a structured phase. A moderate H-field can help magnetic nano-particles to not only overcome thermal fluctuations but also harness them. Such controlled dynamics brings in the possibility of accessing quantum effects, which together with frustrations in magnetic ordering and hysteresis (a natural mechanism for a primitive memory) could throw light on the birth of biological information which, as Abel argues, requires a combination of order and complexity. This scenario gains strength from observations of scale-free framboidal forms of the greigite mineral, with a magnetic basis of assembly. And greigite's metabolic potential plays a key role in the mound scenario of Russell and coworkers-an expansion of which is suggested for including magnetism.Comment: 42 pages, 5 figures, to be published in A.R. Memorial volume, Ed Krishnaswami Alladi, Springer 201

Clinical course and prognosis of the lymphoproliferative disease of granular lymphocytes. A multicenter study.

Lymphoproliferative disease of granular lymphocytes (LDGL) is a recently recognized, relatively rare atypical lymphocytosis characterized by the presence of over 2000 lymphocytes with cytoplasmic azurophilic granules/mm3 in the peripheral blood. The clinical course is heterogeneous, varying from spontaneous regression to progressive, malignant disease. As a consequence, clinical intervention is not standardized. In a worldwide multicenter study, the authors observed 151 patients with LDGL for a mean follow-up time of 29 months. Forty-three patients were asymptomatic at the time of diagnosis. In the remaining cases, clinical symptoms included fever (41 cases), infections (58), neutropenia (47), anemia (17), and thrombocytopenia (12). In 69 cases, LDGL coexisted with an associated disease. Most patients had a nonprogressive clinical course despite the presence of severe symptoms. In 19 patients, death related to LDGL occurred within 48 months. The authors investigated which features at diagnosis were significantly associated with increased mortality. In the univariate analysis, lymph node and liver enlargement, fever at presentation, skin infiltration, a low (less than or equal to 5000/mm3) or high (greater than 20,000/mm3) peripheral leukocyte count, relatively low (less than or equal to 3000) or high (greater than 7000/mm3) absolute peripheral granular lymphocyte (GL) count, and a low (less than or equal to 15%) percentage of HNK-1-positive cells were found to be predictors of increased mortality. In the multivariate analysis, significant independent predictors were fever at diagnosis, a low (less than or equal to 15%) percentage of HNK-1-positive peripheral blood mononuclear cells (PBMC) and a relatively low (less than or equal to 3000) GL count. These results showed that about 25% of the patients with LDGL were diagnosed after a routine blood count and had no clinical symptoms. The remaining patients were symptomatic, with some experiencing a fatal clinical course. The author's analysis of the significant prognostic features of LDGL may help in understanding the heterogeneous nature of this syndrom