Recombinant factorVIII Fc fusion protein for the prevention and treatment of bleeding in children with severe hemophilia A

This work was supported by funding from Biogen, including funding for the editorial and writing support in the the development of this paper

Multifrequency Strategies for the Identification of Gamma-Ray Sources

More than half the sources in the Third EGRET (3EG) catalog have no firmly established counterparts at other wavelengths and are unidentified. Some of these unidentified sources have remained a mystery since the first surveys of the gamma-ray sky with the COS-B satellite. The unidentified sources generally have large error circles, and finding counterparts has often been a challenging job. A multiwavelength approach, using X-ray, optical, and radio data, is often needed to understand the nature of these sources. This chapter reviews the technique of identification of EGRET sources using multiwavelength studies of the gamma-ray fields.Comment: 35 pages, 22 figures. Chapter prepared for the book "Cosmic Gamma-ray Sources", edited by K.S. Cheng and G.E. Romero, to be published by Kluwer Academic Press, 2004. For complete article and higher resolution figures, go to: http://www.astro.columbia.edu/~muk/mukherjee_multiwave.pd

Entangled-State Cycles of Atomic Collective-Spin States

We study quantum trajectories of collective atomic spin states of $N$ effective two-level atoms driven with laser and cavity fields. We show that interesting ``entangled-state cycles'' arise probabilistically when the (Raman) transition rates between the two atomic levels are set equal. For odd (even) $N$, there are $(N+1)/2$ ($N/2$) possible cycles. During each cycle the $N$-qubit state switches, with each cavity photon emission, between the states $(|N/2,m>\pm |N/2,-m>)/\sqrt{2}$, where $|N/2,m>$ is a Dicke state in a rotated collective basis. The quantum number $m$ ($>0$), which distinguishes the particular cycle, is determined by the photon counting record and varies randomly from one trajectory to the next. For even $N$ it is also possible, under the same conditions, to prepare probabilistically (but in steady state) the Dicke state $|N/2,0>$, i.e., an $N$-qubit state with $N/2$ excitations, which is of particular interest in the context of multipartite entanglement.Comment: 10 pages, 9 figure

Cognition, culture and utility:Plant classification by Paraguayan immigrant farmers in Misiones, Argentina

Background: This study was conducted in three rural communities of small farmers of Paraguayan origin living in the province of Misiones, Argentina. These Criollos (Mestizos) hail chiefly from departments located in the east of Paraguay, where the climate and flora have similar characteristics as those in Misiones. These ecological features contribute to the continuation and maintenance of knowledge and practices related to the use of plants. Methods: Fieldwork was conducted between September 2014 and August 2015. Forty five informants from three rural localities situated along the Parana River participated in an ethno-classification task. For the classification event, photographs of 30 medicinal and edible plants were chosen, specifically those yielding the highest frequency of mention among the members of that community (based on data obtained in the first stage of research in 2014). Variation in local plant classifications was examined and compared using principal component analysis and cluster analysis. Results: We found that people classify plants according to application or use (primarily medicinal, to a lesser extent as edible). Morphology is rarely taken into account, even for very similar and closely-related species such as varieties of palms. In light of our findings, we highlight a dominant functionality model at work in the process of plant cognition and classification among farmers of Paraguayan origin. Salient cultural beliefs and practices associated with rural Paraguayan plant-based medicine are described. Additionally, the manner by which residents’ concepts of plants articulate with local folk epistemology is discussed. Conclusions: Culturally constructed use patterns ultimately override morphological variables in rural Paraguayans’ ethnobotanical classification.Antecedentes: Este trabajo se realizó con pequeños agricultores de origen paraguayo, que habitan en la provincia de Misiones, Argentina. Los criollos (mestizos) en su mayoría provienen de departamentos ubicados al oriente del Paraguay, donde el clima y la flora presentan características similares a la provincia de Misiones. Estas características ecológicas contribuyen a la continuación y el mantenimiento de los conocimientos y las prácticas relacionados al uso de las plantas. Métodos El trabajo de campo se realizó entre septiembre de 2014 y agosto de 2015. En la etnoclasificación participaron 45 informantes, provenientes de tres localidades rurales, situadas a lo largo del río Paraná, frontera entre los dos países. Para la clasificación se utilizaron imágenes fotográficas de 30 especies -comestibles y medicinales- preseleccionadas como las de mayor frecuencia de mención entre los habitantes de la región (a partir de los datos obtenidos en una primera etapa de investigación en el año 2014). Por medio del análisis de componentes principales y el análisis de agrupamiento (cluster) se contrastaron y compararon las variaciones en las etnoclasificaciones locales de plantas. Resultados Se encontró que los pobladores clasifican sus plantas según su aplicación y uso (mayormente asociadas a la categoría medicinal y en menor medida a la comestible). Mientras, la morfología rara vez se tiene en cuenta, incluso en aquellas especies muy similares y estrechamente relacionadas como las palmeras. A la luz de los hallazgos, se destaca un modelo de funcionalidad dominante en el proceso de cognición y de clasificación de las plantas entre los agricultores de origen paraguayo. Se describen las principales creencias y prácticas culturales asociadas a la medicina rural paraguaya. Adicionalmente, se discuten algunos de los conceptos de las plantas que mantienen los paraguayos y su articulación con la epistemología local. Conclusiones En la clasificación etnobotánica de los pobladores de origen paraguayo los patrones de uso construidos culturalmente tienen mayor peso que las variables morfológicas.Fil: Kujawska, Monika. University Of Lodz; ArgentinaFil: Jiménez Escobar, Néstor David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Antropología de Córdoba. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Instituto de Antropología de Córdoba; ArgentinaFil: Nolan, Justin M.. University Of Arkansas; Estados UnidosFil: Arias Mutis, Daniel. University of Groningen; Países Bajo

Protective Efficacy of BCG Overexpressing an L,D-Transpeptidase against M. tuberculosis Infection

Background: M. bovis Bacille Calmette-Guérin (BCG), currently the only available vaccine against tuberculosis (TB), fails to adequately protect individuals from active and latent TB infection. New vaccines are desperately needed to decrease the worldwide burden of TB. Methods and Findings: We created a recombinant strain of BCG that overproduces an L,D-transpeptidase in order to alter the bacterial peptidoglycan layer and consequently increase the ability of this immunogen to protect against virulent M. tuberculosis (Mtb). We demonstrate that this novel recombinant BCG protects mice against virulent Mtb at least as well as control BCG, as measured by its ability to reduce bacterial burden in lungs and spleen, reduce lung histopathology, and prolong survival. A nutrient starved recombinant BCG preparation, while offering comparable protection, elicited a response characterized by elevated levels of select Th1 cytokines. Conclusions: Recombinant BCG overexpressing a L,D-transpeptidase that is nutrient starved elicits a stronger Th1 type response and is at least as protective as parent BCG. Results from this study suggest that nutrient starvation treatment of live BCG vaccines should be further investigated as a way to increase host induction of Th-1 related cytokines in the development of experimental anti-TB vaccines

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Reduced Neutrophil Apoptosis in Diabetic Mice during Staphylococcal Infection Leads to Prolonged Tnfα Production and Reduced Neutrophil Clearance

Diabetes is a frequent underlying medical condition among individuals with Staphylococcus aureus infections, and diabetic patients often suffer from chronic inflammation and prolonged infections. Neutrophils are the most abundant inflammatory cells during the early stages of bacterial diseases, and previous studies have reported deficiencies in neutrophil function in diabetic hosts. We challenged age-matched hyperglycemic and normoglycemic NOD mice intraperitoneally with S. aureus and evaluated the fate of neutrophils recruited to the peritoneal cavity. Neutrophils were more abundant in the peritoneal fluids of infected diabetic mice by 48 h after bacterial inoculation, and they showed prolonged viability ex vivo compared to neutrophils from infected nondiabetic mice. These differences correlated with reduced apoptosis of neutrophils from diabetic mice and were dependent upon the presence of S. aureus and a functional neutrophil respiratory burst. Decreased apoptosis correlated with impaired clearance of neutrophils by macrophages both in vitro and in vivo and prolonged production of proinflammatory tumor necrosis factor alpha by neutrophils from diabetic mice. Our results suggest that defects in neutrophil apoptosis may contribute to the chronic inflammation and the inability to clear staphylococcal infections observed in diabetic patients

Gene Expression in Human Hippocampus from Cocaine Abusers Identifies Genes which Regulate Extracellular Matrix Remodeling

The chronic effects of cocaine abuse on brain structure and function are blamed for the inability of most addicts to remain abstinent. Part of the difficulty in preventing relapse is the persisting memory of the intense euphoria or cocaine “rush”. Most abused drugs and alcohol induce neuroplastic changes in brain pathways subserving emotion and cognition. Such changes may account for the consolidation and structural reconfiguration of synaptic connections with exposure to cocaine. Adaptive hippocampal plasticity could be related to specific patterns of gene expression with chronic cocaine abuse. Here, we compare gene expression profiles in the human hippocampus from cocaine addicts and age-matched drug-free control subjects. Cocaine abusers had 151 gene transcripts upregulated, while 91 gene transcripts were downregulated. Topping the list of cocaine-regulated transcripts was RECK in the human hippocampus (FC = 2.0; p<0.05). RECK is a membrane-anchored MMP inhibitor that is implicated in the coordinated regulation of extracellular matrix integrity and angiogenesis. In keeping with elevated RECK expression, active MMP9 protein levels were decreased in the hippocampus from cocaine abusers. Pathway analysis identified other genes regulated by cocaine that code for proteins involved in the remodeling of the cytomatrix and synaptic connections and the inhibition of blood vessel proliferation (PCDH8, LAMB1, ITGB6, CTGF and EphB4). The observed microarray phenotype in the human hippocampus identified RECK and other region-specific genes that may promote long-lasting structural changes with repeated cocaine abuse. Extracellular matrix remodeling in the hippocampus may be a persisting effect of chronic abuse that contributes to the compulsive and relapsing nature of cocaine addiction

MYC functions are specific in biological subtypes of breast cancer and confers resistance to endocrine therapy in luminal tumours.

BACKGROUND: MYC is amplified in approximately 15% of breast cancers (BCs) and is associated with poor outcome. c-MYC protein is multi-faceted and participates in many aspects of cellular function and is linked with therapeutic response in BCs. We hypothesised that the functional role of c-MYC differs between molecular subtypes of BCs. METHODS: We therefore investigated the correlation between c-MYC protein expression and other proteins involved in different cellular functions together with clinicopathological parameters, patients' outcome and treatments in a large early-stage molecularly characterised series of primary invasive BCs (n=1106) using immunohistochemistry. The METABRIC BC cohort (n=1980) was evaluated for MYC mRNA expression and a systems biology approach utilised to identify genes associated with MYC in the different BC molecular subtypes. RESULTS: High MYC and c-MYC expression was significantly associated with poor prognostic factors, including grade and basal-like BCs. In luminal A tumours, c-MYC was associated with ATM (P=0.005), Cyclin B1 (P=0.002), PIK3CA (P=0.009) and Ki67 (P<0.001). In contrast, in basal-like tumours, c-MYC showed positive association with Cyclin E (P=0.003) and p16 (P=0.042) expression only. c-MYC was an independent predictor of a shorter distant metastases-free survival in luminal A LN+ tumours treated with endocrine therapy (ET; P=0.013). In luminal tumours treated with ET, MYC mRNA expression was associated with BC-specific survival (P=0.001). In ER-positive tumours, MYC was associated with expression of translational genes while in ER-negative tumours it was associated with upregulation of glucose metabolism genes. CONCLUSIONS: c-MYC function is associated with specific molecular subtypes of BCs and its overexpression confers resistance to ET. The diverse mechanisms of c-MYC function in the different molecular classes of BCs warrants further investigation particularly as potential therapeutic targets