Characterization of infectious and defective cloned avian hepadnavirus genomes

The infectivity in vivo, replication competence in vitro, and expression of viral genes of several molecularly cloned duck hepatitis B virus (DHBV) genomes were investigated. In addition, replication competence, core protein expression, and secretion of viral proteins were investigated for a grey heron hepatitis B virus genome. Except two, all DHBV isolates tested induced a systemic infection in Pekin ducks when injected as cloned viral DNA into the liver. After transfection of chicken hepatoma cells, both defective DHBV genomes expressed intracellular nucleocapsid and pre-S envelope proteins and secreted DHBs/pre-S particles into the medium. One of the defective DHBV genomes and HHBV produced within the cells replicative intermediates encapsidated in core particles and secreted virions, whereas the other defective DHBV genome did not and was unable to efficiently encapsidate the RNA pregenome. Comparative sequence analysis was performed to identify potential amino acid changes in viral proteins of both defective DHBV genomes. The data obtained demonstrate that most cloned avian hepadnaviruses are infectious or replication competent and suggest defects in envelope, polymerase or encapsidation function, respectively, in two cloned DHBV genomes

Accidental hepatic artery ligation in humans

Despite the vast amount of information from experimental animals, it has been difficult to obtain a clear-cut picture of the effects of ligation of the hepatic artery in humans with relatively normal livers. The last complete review of this subject in 1933 indicated that a mortality in excess of 50 per cent could be expected in non-cirrhotic patients with injury of the hepatic artery or its principal branches. Five cases of dearterialization of the normal human liver have been observed. These were due to accidental interruption of the right hepatic artery in four and the proper hepatic artery in one. The injured vessel was repaired in one case and ligated in the others. In four of the five patients the vascular disruption was the sole injury. In the other the common bile duct was also lacerated. There was no evidence of hepatic necrosis in any case although one patient died from complications of common duct repair. Transient changes in SGOT and temporary low grade bilirubinemia were commonly noted. In addition, all cases of ligation of the hepatic artery reported since 1933 have been compiled. On the basis of reviewed, as well as the presently reported cases, it is concluded that ligation of the hepatic artery or one of its branches in the patient with relatively normal hepatic function is not ordinarily fatal in the otherwise uncomplicated case. Adequate perfusion of the liver can usually be provided by the remaining portal venous flow and whatever arterial collaterals are present, unless additional factors further reduce the portal venous flow or increase hepatic oxygen need. These factors include fever, shock and anoxia. The key to therapy in unreconstructed injuries to the hepatic artery is avoidance of these secondary influences. © 1964

Distribution of calcifying and silicifying phytoplankton in relation to environmental and biogeochemical parameters during the late stages of the 2005 North East Atlantic Spring Bloom

The late stage of the North East Atlantic (NEA) spring bloom was investigated during June 2005 along a transect section from 45 to 66° N between 15 and 20° W in order to characterize the contribution of siliceous and calcareous phytoplankton groups and describe their distribution in relation to environmental factors. We measured several biogeochemical parameters such as nutrients, surface trace metals, algal pigments, biogenic silica (BSi), particulate inorganic carbon (PIC) or calcium carbonate, particulate organic carbon, nitrogen and phosphorus (POC, PON and POP, respectively), as well as transparent exopolymer particles (TEP). Results were compared with other studies undertaken in this area since the JGOFS NABE program. Characteristics of the spring bloom generally agreed well with the accepted scenario for the development of the autotrophic community. The NEA seasonal diatom bloom was in the late stages when we sampled the area and diatoms were constrained to the northern part of our transect, over the Icelandic Basin (IB) and Icelandic Shelf (IS). Coccolithophores dominated the phytoplankton community, with a large distribution over the Rockall-Hatton Plateau (RHP) and IB. The Porcupine Abyssal Plain (PAP) region at the southern end of our transect was the region with the lowest biomass, as demonstrated by very low Chl<i>a</i> concentrations and a community dominated by picophytoplankton. Early depletion of dissolved silicic acid (DSi) and increased stratification of the surface layer most likely triggered the end of the diatom bloom, leading to coccolithophore dominance. The chronic Si deficiency observed in the NEA could be linked to moderate Fe limitation, which increases the efficiency of the Si pump. TEP closely mirrored the distribution of both biogenic silica at depth and prymnesiophytes in the surface layer suggesting the sedimentation of the diatom bloom in the form of aggregates, but the relative contribution of diatoms and coccolithophores to carbon export in this area still needs to be resolved

Block of NMDA receptor channels by endogenous neurosteroids: implications for the agonist induced conformational states of the channel vestibule

N-methyl-D-aspartate receptors (NMDARs) mediate synaptic plasticity, and their dysfunction is implicated in multiple brain disorders. NMDARs can be allosterically modulated by numerous compounds, including endogenous neurosteroid pregnanolone sulfate. Here, we identify the molecular basis of the use-dependent and voltage-independent inhibitory effect of neurosteroids on NMDAR responses. The site of action is located at the extracellular vestibule of the receptor's ion channel pore and is accessible after receptor activation. Mutations in the extracellular vestibule in the SYTANLAAF motif disrupt the inhibitory effect of negatively charged steroids. In contrast, positively charged steroids inhibit mutated NMDAR responses in a voltage-dependent manner. These results, in combination with molecular modeling, characterize structure details of the open configuration of the NMDAR channel. Our results provide a unique opportunity for the development of new therapeutic neurosteroid-based ligands to treat diseases associated with dysfunction of the glutamate system

Somatic Accumulation of GluA1-AMPA Receptors Leads to Selective Cognitive Impairments in Mice

© 2018 Bannerman, Borchardt, Jensen, Rozov, Haj-Yasein, Burnashev, Zamanillo, Bus, Grube, Adelmann, Rawlins and Sprengel. The GluA1 subunit of the L-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) plays a crucial, but highly selective, role in cognitive function. Here we analyzed AMPAR expression, AMPAR distribution and spatial learning in mice (Gria1R/R), expressing the “trafficking compromised” GluA1(Q600R) point mutation. Our analysis revealed somatic accumulation and reduction of GluA1(Q600R) and GluA2, but only slightly reduced CA1 synaptic localization in hippocampi of adult Gria1R/R mice. These immunohistological changes were accompanied by a strong reduction of somatic AMPAR currents in CA1, and a reduction of plasticity (short-term and long-term potentiation, STP and LTP, respectively) in the CA1 subfield following tetanic and theta-burst stimulation. Nevertheless, spatial reference memory acquisition in the Morris water-maze and on an appetitive Y-maze task was unaffected in Gria1R/R mice. In contrast, spatial working/short-term memory during both spontaneous and rewarded alternation tasks was dramatically impaired. These findings identify the GluA1(Q600R) mutation as a loss of function mutation that provides independent evidence for the selective role of GluA1 in the expression of short-term memory

Industrial methodology for process verification in research (IMPROVER): toward systems biology verification

Motivation: Analyses and algorithmic predictions based on high-throughput data are essential for the success of systems biology in academic and industrial settings. Organizations, such as companies and academic consortia, conduct large multi-year scientific studies that entail the collection and analysis of thousands of individual experiments, often over many physical sites and with internal and outsourced components. To extract maximum value, the interested parties need to verify the accuracy and reproducibility of data and methods before the initiation of such large multi-year studies. However, systematic and well-established verification procedures do not exist for automated collection and analysis workflows in systems biology which could lead to inaccurate conclusions