A novel PAX5 rearrangement in TCF3-PBX1 acute lymphoblastic leukemia: a case report.

BACKGROUND: Chromosome translocations are a hallmark of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Additional genomic aberrations are also crucial in both BCP-ALL leukemogenesis and treatment management. Herein, we report the phenotypic and molecular cytogenetic characterization of an extremely rare case of BCP-ALL harboring two concomitant leukemia-associated chromosome translocations: t(1;19)(q23;q13.3) and t(9;17)(p13;q11.2). Of note, we described a new rearrangement between exon 6 of PAX5 and a 17q11.2 region, where intron 3 of SPECC1 is located. This rearrangement seems to disrupt PAX5 similarly to a PAX5 deletion. Furthermore, a distinct karyotype between diagnosis and relapse samples was observed, disclosing a complex clonal evolution during leukemia progression. CASE PRESENTATION: A 16-year-old boy was admitted febrile with abdominal and joint pain. At clinical investigation, he presented with anemia, splenomegaly, low white blood cell count and 92% lymphoblast. He was diagnosed with pre-B ALL and treated according to high risk GBTLI-ALL2009. Twelve months after complete remission, he developed a relapse in consequence of a high central nervous system and bone marrow infiltration, and unfortunately died. CONCLUSIONS: To our knowledge, this is the first report of a rearrangement between PAX5 and SPECC1. The presence of TCF3-PBX1 and PAX5-rearrangement at diagnosis and relapse indicates that both might have participated in the malignant transformation disease maintenance and dismal outcome

How Climate Shapes the Functioning of Tropical Montane Cloud Forests

This is the author accepted manuscript. The final version is available from Springer via the DOI in this recordPurpose of Review: Tropical Montane Cloud Forest (TMCF) is a highly vulnerable ecosystem, which occurs at higher elevations in tropical mountains. Many aspects of TMCF vegetation functioning are poorly understood, making it difficult to quantify and project TMCF vulnerability to global change. We compile functional traits data to provide an overview of TMCF functional ecology. We use numerical models to understand the consequences of TMCF functional composition with respect to its responses to climate and link the traits of TMCF to its environmental conditions. Recent Findings: TMCF leaves are small and have low SLA but high Rubisco content per leaf area. This implies that TMCF maximum net leaf carbon assimilation (An) is high but often limited by low temperature and leaf wetting. Cloud immersion provides important water and potentially nutrient inputs to TMCF plants. TMCF species possess low sapwood specific conductivity, which is compensated with a lower tree height and higher sapwood to leaf area ratio. These traits associated with a more conservative stomatal regulation results in a higher hydraulic safety margin than nearby forests not affected by clouds. The architecture of TMCF trees including its proportionally thicker trunks and large root systems increases tree mechanical stability. Summary: The TMCF functional traits can be conceptually linked to its colder and cloudy environment limiting An, growth, water transport and nutrient availability. A hotter climate would drastically affect the abiotic filters shaping TMCF communities and potentially facilitate the invasion of TMCF by more productive lowland species.Newton FundNatural Environment Research Council (NERC)FAPES

A timeband framework for modelling real-time systems

Complex real-time systems must integrate physical processes with digital control, human operation and organisational structures. New scientific foundations are required for specifying, designing and implementing these systems. One key challenge is to cope with the wide range of time scales and dynamics inherent in such systems. To exploit the unique properties of time, with the aim of producing more dependable computer-based systems, it is desirable to explicitly identify distinct time bands in which the system is situated. Such a framework enables the temporal properties and associated dynamic behaviour of existing systems to be described and the requirements for new or modified systems to be specified. A system model based on a finite set of distinct time bands is motivated and developed in this paper

PD-1 Blockade Modulates Functional Activities of Exhausted-Like T Cell in Patients With Cutaneous Leishmaniasis

Patients infected by Leishmania braziliensis develop debilitating skin lesions. The role of inhibitory checkpoint receptors (ICRs) that induce T cell exhaustion during this disease is not known. Transcriptional profiling identified increased expression of ICRs including PD-1, PDL-1, PDL-2, TIM-3, and CTLA-4 in skin lesions of patients that was confirmed by immunohistology where there was increased expression of PD-1, TIM-3, and CTLA-4 in both CD4^{+} and CD8^{+} T cell subsets. Moreover, PDL-1/PDL-2 ligands were increased on skin macrophages compared to healthy controls. The proportions PD1^{+}, but not TIM-3 or CTLA-4 expressing T cells in the circulation were positively correlated with those in the lesions of the same patients, suggesting that PD-1 may regulate T cell function equally in both compartments. Blocking PD-1 signaling in circulating T cells enhanced their proliferative capacity and IFN-γ production, but not TNF-α secretion in response to L. braziliensis recall antigen challenge in vitro. While we previously showed a significant correlation between the accumulation of senescent CD8^{+}CD45RA^{+}CD27^{-} T cells in the circulation and skin lesion size in the patients, there was no such correlation between the extent of PD-1 expression by circulating on T cells and the magnitude of skin lesions suggesting that exhausted-like T cells may not contribute to the cutaneous immunopathology. Nevertheless, we identified exhausted-like T cells in both skin lesions and in the blood. Targeting this population by PD-1 blockade may improve T cell function and thus accelerate parasite clearance that would reduce the cutaneous pathology in cutaneous leishmaniasis

The costs of preventing and treating chagas disease in Colombia

Background: The objective of this study is to report the costs of Chagas disease in Colombia, in terms of vector disease control programmes and the costs of providing care to chronic Chagas disease patients with cardiomyopathy. Methods: Data were collected from Colombia in 2004. A retrospective review of costs for vector control programmes carried out in rural areas included 3,084 houses surveyed for infestation with triatomine bugs and 3,305 houses sprayed with insecticide. A total of 63 patient records from 3 different hospitals were selected for a retrospective review of resource use. Consensus methodology with local experts was used to estimate care seeking behaviour and to complement observed data on utilisation. Findings: The mean cost per house per entomological survey was $4.4 (in US$ of 2004), whereas the mean cost of spraying a house with insecticide was $27. The main cost driver of spraying was the price of the insecticide, which varied greatly. Treatment of a chronic Chagas disease patient costs between$46.4 and $7,981 per year in Colombia, depending on severity and the level of care used. Combining cost and utilisation estimates the expected cost of treatment per patient-year is$1,028, whereas lifetime costs averaged $11,619 per patient. Chronic Chagas disease patients have limited access to healthcare, with an estimated 22% of patients never seeking care. Conclusion: Chagas disease is a preventable condition that affects mostly poor populations living in rural areas. The mean costs of surveying houses for infestation and spraying infested houses were low in comparison to other studies and in line with treatment costs. Care seeking behaviour and the type of insurance affiliation seem to play a role in the facilities and type of care that patients use, thus raising concerns about equitable access to care. Preventing Chagas disease in Colombia would be cost-effective and could contribute to prevent inequalities in health and healthcare.Wellcome Trus

Use and traditional management of Anadenanthera colubrina (Vell.) Brenan in the semi-arid region of northeastern Brazil

The use and management of "angico" (Anadenanthera colubrina (Vell.) Brenan) by a rural community in northeastern Brazil was examined. By employing different techniques of data collection and population structure analysis, it was determined that this species had multiple uses within the local community (especially as timber and for other wood products), and that local management of this species is based on simple maintenance and harvesting of individuals in agroforest homegardens. The study of the population structure of this tree species indicated that management and conservation strategies must include the participation of the local community

Rapid Processing of Both Reward Probability and Reward Uncertainty in the Human Anterior Cingulate Cortex

Reward probability and uncertainty are two fundamental parameters of decision making. Whereas reward probability indicates the prospect of winning, reward uncertainty, measured as the variance of probability, indicates the degree of risk. Several lines of evidence have suggested that the anterior cingulate cortex (ACC) plays an important role in reward processing. What is lacking is a quantitative analysis of the encoding of reward probability and uncertainty in the human ACC. In this study, we addressed this issue by analyzing the feedback-related negativity (FRN), an event-related potential (ERP) component that reflects the ACC activity, in a simple gambling task in which reward probability and uncertainty were parametrically manipulated through predicting cues. Results showed that at the outcome evaluation phase, while both win and loss-related FRN amplitudes increased as the probability of win or loss decreased, only the win-related FRN was modulated by reward uncertainty. This study demonstrates the rapid encoding of reward probability and uncertainty in the human ACC and offers new insights into the functions of the ACC