844 research outputs found

    Frequent induction of chromosomal aberrations in in vivo skin fibroblasts after allogeneic stem cell transplantation: hints to chromosomal instability after irradiation

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    BACKGROUND: Total body irradiation (TBI) has been part of standard conditioning regimens before allogeneic stem cell transplantation for many years. Its effect on normal tissue in these patients has not been studied extensively. METHOD: We studied the in vivo cytogenetic effects of TBI and high-dose chemotherapy on skin fibroblasts from 35 allogeneic stem cell transplantation (SCT) patients. Biopsies were obtained prospectively (n = 18 patients) before, 3 and 12 months after allogeneic SCT and retrospectively (n = 17 patients) 23-65 months after SCT for G-banded chromosome analysis. RESULTS: Chromosomal aberrations were detected in 2/18 patients (11 %) before allogeneic SCT, in 12/13 patients (92 %) after 3 months, in all patients after 12 months and in all patients in the retrospective group after allogeneic SCT. The percentage of aberrant cells was significantly higher at all times after allogeneic SCT compared to baseline analysis. Reciprocal translocations were the most common aberrations, but all other types of stable, structural chromosomal aberrations were also observed. Clonal aberrations were observed, but only in three cases they were detected in independently cultured flasks. A tendency to non-random clustering throughout the genome was observed. The percentage of aberrant cells was not different between patients with and without secondary malignancies in this study group. CONCLUSION: High-dose chemotherapy and TBI leads to severe chromosomal damage in skin fibroblasts of patients after SCT. Our long-term data suggest that this damage increases with time, possibly due to in vivo radiation-induced chromosomal instability

    hints to chromosomal instability after irradiation

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    Background Total body irradiation (TBI) has been part of standard conditioning regimens before allogeneic stem cell transplantation for many years. Its effect on normal tissue in these patients has not been studied extensively. Method We studied the in vivo cytogenetic effects of TBI and high-dose chemotherapy on skin fibroblasts from 35 allogeneic stem cell transplantation (SCT) patients. Biopsies were obtained prospectively (n = 18 patients) before, 3 and 12 months after allogeneic SCT and retrospectively (n = 17 patients) 23–65 months after SCT for G-banded chromosome analysis. Results Chromosomal aberrations were detected in 2/18 patients (11 %) before allogeneic SCT, in 12/13 patients (92 %) after 3 months, in all patients after 12 months and in all patients in the retrospective group after allogeneic SCT. The percentage of aberrant cells was significantly higher at all times after allogeneic SCT compared to baseline analysis. Reciprocal translocations were the most common aberrations, but all other types of stable, structural chromosomal aberrations were also observed. Clonal aberrations were observed, but only in three cases they were detected in independently cultured flasks. A tendency to non-random clustering throughout the genome was observed. The percentage of aberrant cells was not different between patients with and without secondary malignancies in this study group. Conclusion High-dose chemotherapy and TBI leads to severe chromosomal damage in skin fibroblasts of patients after SCT. Our long-term data suggest that this damage increases with time, possibly due to in vivo radiation-induced chromosomal instability

    Reconciling the Greenland ice-core and radiocarbon timescales through the Laschamp geomagnetic excursion

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    Cosmogenic radionuclides, such as 10Be and 14C, share a common production signal, with their formation in the Earth's upper atmosphere modulated by changes to the geomagnetic field, as well as variations in the intensity of the solar wind. Here, we use this common production signal to compare between the radiocarbon (IntCal) and Greenland ice-core (GICC05) timescales, utilising the most pronounced cosmogenic production peak of the last 100,000 years – that associated with the Laschamp geomagnetic excursion circa 41,000 years ago. We present 54 new 14C measurements from a peat core (‘TP-2005’) from Tenaghi Philippon, NE Greece, contiguously spanning between circa 47,300 and 39,600 cal. BP, demonstrating a distinctive tripartite structure in the build up to the principal Laschamp production maximum that is not present in the consensus IntCal13 calibration curve. This is the first time that a continuous, non-reservoir corrected 14C dataset has been generated over such a long time span for this, the oldest portion of the radiocarbon timescale. This period is critical for both palaeoenvironmental and archaeological applications, with the replacement of Neanderthals by anatomically modern humans in Europe around this time. By placing our Tenaghi Philippon 14C dataset on to the Hulu Cave U-series timescale of Cheng et al. (2018) via Bayesian statistical modelling, the comparison of TP-2005 14C with Greenland 10Be fluxes also implicitly relates the underlying U-series and GICC05 timescales themselves. This comparison suggests that whilst these two timescales are broadly coherent, the IntCal13 timescale contains erroneous structure circa 40,000 cal. BP

    Sedimentological evidence for pronounced glacial‐interglacial climate fluctuations in NE Tibet in the latest Pliocene to early Pleistocene

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    The intensification of Northern Hemisphere glaciation (iNHG) and uplift of the Tibetan Plateau have been argued to be among the main drivers of climate change in midlatitude Central Asia during the Pliocene/Pleistocene. While most proxy records that support this hypothesis are from regions outside the Tibetan Plateau (such as from the Chinese Loess Plateau), detailed paleoclimatic information for the plateau itself during that time has yet remained elusive. Here we present a temporally highly resolved (~500 years) sedimentological record from the Qaidam Basin situated on the northeastern Tibetan Plateau that shows pronounced glacial‐interglacial climate variability during the interval from 2.7 to 2.1 Ma. Glacial (interglacial) intervals are generally characterized by coarser (finer) grain size, minima (maxima) in organic matter content, and maxima (minima) in carbonate content. Comparison of our results with Earth's orbital parameters and proxy records from the Chinese Loess Plateau suggests that the observed climate fluctuations were mainly driven by changes in the Siberian High/East Asian winter monsoon system as a response to the iNHG. They are further proposed to be enhanced by the topography of the Tibetan Plateau and its impact on the position and intensity of the westerlies

    Thermocline state change in the eastern equatorial Pacific during the late Pliocene/early Pleistocene intensification of Northern Hemisphere glaciation

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    The late Pliocene/early Pleistocene intensification of Northern Hemisphere glaciation (iNHG)  ∼ 2.5 million years ago (marine isotope stages, MIS, 100–96) stands out as an important tipping point in Earth's climate history, which strongly influenced oceanographic and climatic patterns including trade wind and upwelling strength in the eastern equatorial Pacific (EEP). The thermocline depth in the EEP, in turn, plays a pivotal role in the Earth's climate system: small changes in its depth associated with short-term climate phenomena such as the El Niño–Southern Oscillation can affect surface-water properties and the ocean–atmosphere exchange. However, thermocline dynamics in the EEP during the iNHG still remain unclear. While numerous studies have suggested a link between a thermocline shoaling in the EEP and Northern Hemisphere ice growth, other studies have indicated a stable thermocline depth during the iNHG; consequently, a causal relationship between thermocline dynamics and ice-sheet growth has been excluded. In light of these contradictory views, we have generated geochemical (planktic foraminiferal δ18O, δ13C and Mg&thinsp;∕&thinsp;Ca), sedimentological (sand accumulation rates) and faunal (abundance data of thermocline-dwelling foraminifera) records for Ocean Drilling Program Site 849 located in the central region of the EEP. Our records span the interval from  ∼ 2.75 to 2.4&thinsp;Ma (MIS G7–95), which is critical for understanding thermocline dynamics during the final phase of the iNHG. Our new records document a thermocline shoaling from  ∼ 2.64 to 2.55&thinsp;Ma (MIS G2–101) and a relatively shallow thermocline from  ∼ 2.55&thinsp;Ma onwards (MIS 101–95). This indicates a state change in thermocline depth at Site 849 shortly before the final phase of the iNHG. Ultimately, our data support the hypothesis that (sub-)tropical thermocline shoaling may have contributed to the development of large Northern Hemisphere ice sheets.</p

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

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    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

    Agency, qualia and life: connecting mind and body biologically

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    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
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