Crimean-Congo hemorrhagic fever: epidemiological trends and controversies in treatment

Crimean-Congo hemorrhagic fever (CCHF) virus has the widest geographic range of all tick-borne viruses and is endemic in more than 30 countries in Eurasia and Africa. Over the past decade, new foci have emerged or re-emerged in the Balkans and neighboring areas. Here we discuss the factors influencing CCHF incidence and focus on the main issue of the use of ribavirin for treating this infection. Given the dynamics of CCHF emergence in the past decade, development of new anti-viral drugs and a vaccine is urgently needed to treat and prevent this acute, life-threatening disease

MTF-1-Mediated Repression of the Zinc Transporter Zip10 Is Alleviated by Zinc Restriction

The regulation of cellular zinc uptake is a key process in the overall mechanism governing mammalian zinc homeostasis and how zinc participates in cellular functions. We analyzed the zinc transporters of the Zip family in both the brain and liver of zinc-deficient animals and found a large, significant increase in Zip10 expression. Additionally, Zip10 expression decreased in response to zinc repletion. Moreover, isolated mouse hepatocytes, AML12 hepatocytes, and Neuro 2A cells also respond differentially to zinc availability in vitro. Measurement of Zip10 hnRNA and actinomycin D inhibition studies indicate that Zip10 was transcriptionally regulated by zinc deficiency. Through luciferase promoter constructs and ChIP analysis, binding of MTF-1 to a metal response element located 17 bp downstream of the transcription start site was shown to be necessary for zinc-induced repression of Zip10. Furthermore, zinc-activated MTF-1 causes down-regulation of Zip10 transcription by physically blocking Pol II movement through the gene. Lastly, ZIP10 is localized to the plasma membrane of hepatocytes and neuro 2A cells. Collectively, these results reveal a novel repressive role for MTF-1 in the regulation of the Zip10 zinc transporter expression by pausing Pol II transcription. ZIP10 may have roles in control of zinc homeostasis in specific sites particularly those of the brain and liver. Within that context ZIP10 may act as an important survival mechanism during periods of zinc inadequacy

Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue.

Genome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer, reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of ongoing abnormal mutational processes, consistent with field effects, underlying carcinogenesis. This mechanism gives rise to extensive branching evolution and cancer clone mixing, as exemplified by the coexistence of multiple cancer lineages harboring distinct ERG fusions within a single cancer nodule. Subsets of mutations were shared either by morphologically normal and malignant tissues or between different ERG lineages, indicating earlier or separate clonal cell expansions. Our observations inform on the origin of multifocal disease and have implications for prostate cancer therapy in individual cases

Flower bud differentiation and development in fruiting and non-fruiting shoots in relation to fruit set in apricot (Prunus armeniaca L.)

30 Pag., 2 Tabl., 8 Fig.Situations of high flower bud drop and low fruit set without apparent causes are common in fruit trees. The term flower quality has been coined to explain differences among flowers in their capacity to set fruit, but the causes underpinning these differences are largely unknown. This lack of knowledge is based on the fact that these differences are established a posteriori and there are no criteria to determine a priori what will make a flower to set a fruit or to drop. In this work, we profit from the empirical knowledge that there are fruiting and non-fruiting shoots to explore to which extent flower bud differentiation and bud development will affect the subsequent fruit set. For this purpose, the processes from flower bud differentiation to fruit set were sequentially analyzed in both types of shoots, over 2 years. More than half of the buds from long shoots aborted development and dropped before flowering. At anthesis, most of the remaining flowers showed underdeveloped pistils that failed to sustain pollen germination or pollen tube growth along the pistil. This unsuccessful development resulted in clear differences in fruit set between both types of branches. These results highlight that flower bud differentiation and development play an important role for fruit set and that developmental timing appears critical to reach anthesis with a fully developed pistil.Financial support for this research was provided by Ministerio de Ciencia e Innovación—EU-FEDER (CICYT AGL2006-13529-CO2-00, AGL2009-12621-C02-00), Gobierno de Aragón (Grupo de Excelencia de Aragón A-43), and Instituto Nacional de Investigación y Tecnología Agroalimentaria (Doctoral fellowship INIA2003-8 to C.J.).Peer reviewe

Non destructive assessment of in situ concrete strength: comparison of approaches through an international benchmark

Strength assessment of concrete in existing structures is a key issue. Many non destructive techniques (NDT) are available which can provide information about the material condition and several approaches can be used to derive strength estimates from NDT test results. However, common practice suffers from many drawbacks: (a) it is difficult to ascertain the level of accuracy/confidence of concrete strength estimates, (b) one lacks established guidelines for estimating the concrete strength variability, (c) the best way to combine NDT methods and coring remains an open issue. The RILEM TC 249 "Non destructive in situ strength assessment of concrete'' is addressing these problems. A benchmark was carried out in order to compare (a) how experts define and can carry out an NDT investigation program and (b) how experts derive strength values from the NDT measurements. The benchmark was based on synthetic simulations which reproduced a synthetic data set corresponding to a grid of twenty 3 m-high columns defining a single-storey building structure. The comparison of the various strategies and the analysis of results enabled identification of the most influential parameters that define an investigation approach and influence its efficiency and accuracy. A special emphasis was placed on the magnitude of the measurement error. A model of the investigation strategy is proposed, that will be detailed in future guidelines. The reader is invited to refer to a companion paper (Alwash et al. in Mater Struct, 1. doi: 10.1617/s11527-016-0962-x), based on more extensive Monte-Carlo simulations of the same case-study, which analyzes and quantifies the efficiency of the investigation strategies with respect to both average strength and strength variability assessment, in order to draw conclusions based on rational analyses rather than on the element of chance