Sequential anti-cytomegalovirus response monitoring may allow prediction of cytomegalovirus reactivation after allogeneic stem cell transplantation

Background: Reconstitution of cytomegalovirus-specific CD3+CD8+ T cells (CMV-CTLs) after allogeneic hematopoietic stem cell transplantation (HSCT) is necessary to bring cytomegalovirus (CMV) reactivation under control. However, the parameters determining protective CMV-CTL reconstitution remain unclear to date. Design and Methods: In a prospective tri-center study, CMV-CTL reconstitution was analyzed in the peripheral blood from 278 patients during the year following HSCT using 7 commercially available tetrameric HLA-CMV epitope complexes. All patients included could be monitored with at least CMV-specific tetramer. Results: CMV-CTL reconstitution was detected in 198 patients (71%) after allogeneic HSCT. Most importantly, reconstitution with 1 CMV-CTL per µl blood between day +50 and day +75 post-HSCT discriminated between patients with and without CMV reactivation in the R+/D+ patient group, independent of the CMV-epitope recognized. In addition, CMV-CTLs expanded more daramtaically in patients experiencing only one CMV-reactivation than those without or those with multiple CMV reactivations. Monitoring using at least 2 tetramers was possible in 63% (n = 176) of the patients. The combinations of particular HLA molecules influenced the numbers of CMV-CTLs detected. The highest CMV-CTL count obtained for an individual tetramer also changed over time in 11% of these patients (n = 19) resulting in higher levels of HLA-B*0801 (IE-1) recognizing CMV-CTLs in 14 patients. Conclusions: Our results indicate that 1 CMV-CTL per µl blood between day +50 to +75 marks the beginning of an immune response against CMV in the R+/D+ group. Detection of CMV-CTL expansion thereafter indicates successful resolution of the CMV reactivation. Thus, sequential monitoring of CMV-CTL reconstitution can be used to predict patients at risk for recurrent CMV reactivation

Quantitative and O2 Enhanced MRI of the Pathologic Lung: Findings in Emphysema, Fibrosis, and Cystic Fibrosis

Purpose: beyond the pure morphological visual representation, MR imaging offers the possibility to quantify parameters in the healthy, as well as, in pathologic lung parenchyma. Gas exchange is the primary function of the lung and the transport of oxygen plays a key role in pulmonary physiology and pathophysiology. The purpose of this review is to present a short overview of the relaxation mechanisms of the lung and the current technical concepts of T1 mapping and methods of oxygen enhanced MR imaging. Material and Methods: molecular oxygen has weak paramagnetic properties so that an increase in oxygen concentration results in shortening of the T1 relaxation time and thus to an increase of the signal intensity in T1 weighted images. A possible way to gain deeper insights into the relaxation mechanisms of the lung is the calculation of parameter Maps. T1 Maps based on a snapshot FLASH sequence obtained during the inhalation of various oxygen concentrations provide data for the creation of the so-called oxygen transfer function (OTF), assigning a measurement for local oxygen transfer. T1 weighted single shot TSE sequences also permit expression of the signal changing effects associated with the inhalation of pure oxygen. Results: the average of the mean T1 values over the entire lung in inspiration amounts to 1199 +/− 117 milliseconds, the average of the mean T1 values in expiration was 1333 +/− 167 milliseconds. T1 Maps of patients with emphysema and lung fibrosis show fundamentally different behavior patterns. Oxygen enhanced MRT is able to demonstrate reduced diffusion capacity and diminished oxygen transport in patients with emphysema and cystic fibrosis. Discussion: results published in literature indicate that T1 mapping and oxygen enhanced MR imaging are promising new methods in functional imaging of the lung and when evaluated in conjunction with the pure morphological images can provide additional valuable information

Long-term outcomes of allogeneic haematopoietic stem cell transplantation for adult cerebral X-linked adrenoleukodystrophy

The adult cerebral inflammatory form of X-linked adrenoleukodystrophy is a rapidly progressive neurodegenerative disease, as devastating as childhood cerebral adrenoleukodystrophy. Allogeneic haematopoietic stem cell transplantation has been demonstrated to provide long-term neurological benefits for boys with the childhood cerebral form, but results in adults are sparse and inconclusive. We analysed data from 14 adult males with adult cerebral adrenoleukodystrophy treated with allogeneic haematopoietic stem cell transplantation on a compassionate basis in four European centres. All presented with cerebral demyelinating lesions and gadolinium enhancement. Median age at diagnosis of adult cerebral adrenoleukodystrophy was 33 years (range 21–48 years). In addition to cerebral inflammation, five patients had established severe motor disability from adrenomyeloneuropathy affecting only the spinal cord and peripheral nerves (Expanded Disability Status Scale score ≥ 6). Eight patients survived (estimated survival 57 ± 13%) with a median follow-up of 65 months (minimum 38 months). Death was directly transplant-/infection-related (n = 3), due to primary disease progression in advanced adult cerebral adrenoleukodystrophy (n = 1), or secondary disease progression (n = 2) after transient multi-organ failure or non-engraftment. Specific complications during stem cell transplantation included deterioration of motor and bladder functions (n = 12) as well as behavioural changes (n = 8). Arrest of progressive cerebral demyelination and prevention of severe loss of neurocognition was achieved in all eight survivors, but deterioration of motor function occurred in the majority (n = 5). Limited motor dysfunction (Expanded Disability Status Scale score < 6) prior to transplantation was associated with significantly improved survival [78 ± 14% (n = 9) versus 20 ± 18%(n = 5); P < 0.05] and maintenance of ambulation (Expanded Disability Status Scale score < 7) post-transplant (78% versus 0%; P = 0.021). In contrast, bilateral involvement of the internal capsule on brain MRI was associated with poorer survival [20 ± 18% (n = 5) versus 78 ± 14% (n = 9); P < 0.05]. This study is the first to support the feasibility, complications and potential long-term neurological benefit of allogeneic haematopoietic stem cell transplantation in adult cerebral adrenoleukodystrophy. Further studies are warranted to attempt to improve outcomes through patient selection and optimization of transplantation protocols

8. 皮膚リーシュマニア症を疑った例(第434(B)回千葉医学会例会 第15回千葉皮膚科臨床談話会)

Additional file 3: Technical details on the compilation of the global material flow database

Polynomial algorithms for the Maximal Pairing Problem: efficient phylogenetic targeting on arbitrary trees

Background: The Maximal Pairing Problem (MPP) is the prototype of a class of combinatorial optimization problems that are of considerable interest in bioinformatics: Given an arbitrary phylogenetic tree T and weights ωxy for the paths between any two pairs of leaves (x, y), what is the collection of edge-disjoint paths between pairs of leaves that maximizes the total weight? Special cases of the MPP for binary trees and equal weights have been described previously; algorithms to solve the general MPP are still missing, however. Results: We describe a relatively simple dynamic programming algorithm for the special case of binary trees. We then show that the general case of multifurcating trees can be treated by interleaving solutions to certain auxiliary Maximum Weighted Matching problems with an extension of this dynamic programming approach, resulting in an overall polynomial-time solution of complexity (n^4 log n) w.r.t. the number n of leaves. The source code of a C implementation can be obtained under the GNU Public License from http://www.bioinf.uni-leipzig.de/Software/Targeting. For binary trees, we furthermore discuss several constrained variants of the MPP as well as a partition function approach to the probabilistic version of the MPP. Conclusions: The algorithms introduced here make it possible to solve the MPP also for large trees with high-degree vertices. This has practical relevance in the field of comparative phylogenetics and, for example, in the context of phylogenetic targeting, i.e., data collection with resource limitations.Human Evolutionary Biolog

Transduction of chemical signals in dictyostelium cells

Three different functions of cyclic AMP in D discoideum are known: (1) cAMP acts as a chemoattractant during cell aggregation, (2) it controls cell development, particularly the acquisition of aggregation competence, and (3) it is involved in terminal cell differentiation. In this report we will concentrate on the functions 1 and 2 of cAMP. Chemotaxis requires the recognition of concentration gradients in the environment by attractant binding to cell surface receptors, the processing of signals from the receptors to the contractile system of the cells, extension of pseudopods at one part, and contraction at other parts of the cells in accord with the external gradient. One pathway of signal processing from the receptors to the contractile system involves the regulation of a myosin kinase. The control of development up to aggregation competence is largely dependent on the temporal pattern of cAMP application: Only repetitive pulses enhance development. This effect has been studied using the expression of a membrane glycoprotein called contact site A as a differentiation marker

Increasing impacts of land use on biodiversity and carbon sequestration driven by population and economic growth

Biodiversity and ecosystem service losses driven by land-use change are expected to intensify as a growing and more affluent global population requires more agricultural and forestry products, and teleconnections in the global economy lead to increasing remote environmental responsibility. By combining global biophysical and economic models, we show that, between the years 2000 and 2011, overall population and economic growth resulted in increasing total impacts on bird diversity and carbon sequestration globally, despite a reduction of land-use impacts per unit of gross domestic product (GDP). The exceptions were North America and Western Europe, where there was a reduction of forestry and agriculture impacts on nature accentuated by the 2007-2008 financial crisis. Biodiversity losses occurred predominantly in Central and Southern America, Africa and Asia with international trade an important and growing driver. In 2011, 33% of Central and Southern America and 26% of Africa's biodiversity impacts were driven by consumption in other world regions. Overall, cattle farming is the major driver of biodiversity loss, but oil seed production showed the largest increases in biodiversity impacts. Forestry activities exerted the highest impact on carbon sequestration, and also showed the largest increase in the 2000-2011 period. Our results suggest that to address the biodiversity crisis, governments should take an equitable approach recognizing remote responsibility, and promote a shift of economic development towards activities with low biodiversity impacts

Identifying priority areas for European resource policies: a MRIO-based material footprint assessment

In the context of the transformation toward a "green economy," issues related to natural resource use have rapidly increased in importance in European and international policy debates. The large number of studies applying economy-wide material flow analysis so far mostly produced aggregated national indicators, making the results difficult to connect to policies, which are often designed for single sectors or consumption areas. This paper provides a detailed assessment of the composition of EU's material footprint in its global context, aiming at identifying the main product groups contributing to overall material consumption and specifying the geographical sources for the raw materials required to satisfy EU's final demand. Based on multi-regional input¿output (MRIO) modeling, we apply production layer decomposition to assess supply chains and their structural changes from 1995 to 2011. The global MRIO database used in this study is EXIOBASE 3, which disaggregates 200 products and 163 industries, of which 33 represent material extraction sectors. By that means, we increase the level of detail to a degree where policies can more easily connect to. We find that the generally growing material footprint of the EU was characterized by a dramatic shift regarding the origin of raw materials, with the share of materials extracted within the EU territory falling from 68 % in 1995 to 35 % in 2011. In 2011, raw materials extracted in China to produce exports to the EU already contributed an equal share to EU's material footprint as material extraction within the EU itself. Import dependency is most critical for the material group of metal ores, with only 13 % of all metals required as inputs to EU final demand stemming from within the EU. Regarding product composition, construction was confirmed as the most important sector contributing to the material footprint, followed by the group of manufacturing products based on biomass. Materials embodied in service sector activities together contributed a quarter to the total material footprint in 2011, making services an important, but currently disregarded area for European resource policies. We also find that supply chain structures became more complex over time, with a growing part located outside the EU territory. (authors' abstract

Reply to: Soils need to be considered when assessing the impacts of land-use change on carbon sequestration

Industrial Ecolog