Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression, secretion and antigenic variation of bacterial S‐layer proteins

The function of the S‐layer, a regularly arranged structure on the outside of numerous bacteria, appears to be different for bacteria living in different environments. Almost no similarity exists between the primary sequences of S‐proteins, although their amino acid composition is comparable. S‐protein production is directed by single or multiple promoters in front of the S‐protein gene, yielding stable mRNAs. Most bacteria secrete S‐proteins via the general secretory pathway (GSP). Translocation of S‐protein across the outer membrane of Gram‐negative bacteria sometimes occurs by S‐protein‐specific branches of the GSP. O‐polysaccharide side‐chains of the lipopolysaccharide component of the cell wall of Gram‐negative bacteria appear to function as receptors for attachment of the S‐layer. Silent S‐protein genes have been found in Campylobacter fetus and Lactobacillus acidophilus. These silent genes are placed in the expression site in a fraction of the bacterial population via inversion of a chromosomal segment.
Fixed-term employment in Norway and Sweden: A pathway to labour market marginalization?

We compare the effects of relatively liberal regulations on the use of temporary employment in Sweden and more restrictive rules in Norway. We find not only that temporary work may be a stepping stone out of unemployment but also that fixed-term employees are exposed to significant risks of long-term marginalization. Moreover, fixed-term employees in Sweden face greater risks of long-run unemployment and low earnings compared to those in Norway.
New Molecular Insights into the Genetics of Thrombophilia. Resistance to Activated Protein C Caused by Arg506 to Gin Mutation in Factor V as a Pathogenic Risk Factor for Venous Thrombosis

Genetic risk factors are important in the pathogenesis of venous thrombosis, as demonstrated by the familial clustering of the disease. However, well defined genetic defects were until recently found in less than 10% of the thrombosis patients. In 1993, inherited resistance to activated protein C (APC) was reported as a novel pathogenetic risk factor for thrombosis. It is found in 20-60% of patients with venous thrombosis. APC-resistance is in more than 90% of the cases caused by a single point mutation in the gene for factor V (G to A transition at nucleotide position 1691), which predicts replacement of Arg(R)506 in the APC-cleavage site with a Gln(Q). After activation, mutated factor V, FV:Q506, is less efficiently degraded by APC than normal factor V, which results in increased thrombin generation and a hypercoagulable state. The FV:Q506 mutation is highly prevalent in the general population (5-10%). Heterozygosity for FV:Q506 is associated with a 5-10-fold increased risk of thrombosis, whereas homozygous cases have 50-100-fold increased risk of thrombosis.
Low recurrence rate after deep calf‐vein thrombosis with 6 weeks of oral anticoagulation

Astermark J, Björgell O, Lindén E, Lethagen S, Nilsson P, Berntorp E (University Hospital, Malmö, Sweden). Low recurrence rate after deep calf‐vein thrombosis with 6 weeks of oral anticoagulation. J Intern Med 1998; 244: 79–82.
RNA Editing of the Human Herpesvirus 8 Kaposin Transcript Eliminates Its Transforming Activity and Is Induced during Lytic Replication

ABSTRACT Human herpesvirus 8 is the etiologic agent associated with Kaposi's sarcoma and primary effusion lymphoma (PEL). The K12 RNA, which produces as many as three variants of the kaposin protein, as well as a microRNA, is the most abundant transcript expressed in latent Kaposi's sarcoma-associated herpesvirus infection, and yet it is also induced during lytic replication. The portion of the transcript that includes the microRNA and the kaposin A sequence has been shown to have tumorigenic potential. Genome coordinate 117990, which is within this transcript, has been found to be heterogeneous, primarily in RNAs but also among viral DNA sequences. This sequence heterogeneity affects an amino acid in kaposins A and C and the microRNA. The functional effects of this sequence heterogeneity have not been studied, and its origin has not been definitively settled; both RNA editing and heterogeneity at the level of the viral genome have been proposed. Here, we show that transcripts containing A at position 117990 are tumorigenic, while those with G at this position are not. Using a highly sensitive quantitative assay, we observed that, in PEL cells under conditions where more than 60% of cDNAs derived from K12 RNA transcripts have G at coordinate 117990, there is no detectable G in the viral DNA sequence at this position, only A. This result is consistent with RNA editing by one of the host RNA adenosine deaminases (ADARs). Indeed, we observed that purified human ADAR1 efficiently edits K12 RNA in vitro. Remarkably, the amount of editing correlated with the replicative state of the virus; editing levels were nearly 10-fold higher in cells treated to induce lytic viral replication. These results suggest that RNA editing controls the function of one segment of the kaposin transcript, such that it has transforming activity during latent replication and possibly another, as-yet-undetermined, function during lytic replication.
Media Depictions of Mental Illness: An Analysis of the Use of Dangerousness

Objective: To explore how the commonsense understanding, that those with a mental illness are dangerous, is deployed in a small sample of print media. Method: The print media sample was subjected to a discourse analysis informed by knowledge of media practices. Materials were read closely and references to mental illness were identified, classified and analysed. Results: This non-sensational material was shown to provide repeated confirmations of the commonsense understanding that mental illnesses make people unpredictable and dangerous. Close study of the lead article suggested that it was written so that readers had to draw on such understandings to make sense of the account it presented. Conclusion: The study challenges the notion that media present negative depictions of mental illnesses either because journalists are poorly informed or because ‘sensation sells’. It is concluded that media practices directed at engaging readers require the use of cases and a style of writing that forces readers to draw upon commonsense knowledge of mental illness to understand the text. It is argued that this is a deliberate effort to enlist readers as co-creators of the text and thereby increase their interest.
Charge injection energy barriers and charge mobilities in insulating liquids

An analysis of non-linear I–V conduction characteristics in three different insulating liquids was conducted in the present paper. Apparent mobilities of the charge carriers and the magnitude of energy barriers at the metal liquid interface were derived for these liquids which include mineral transformer oil, Diala D oil and Midel 7131 synthetic ester liquid. It has been shown that /−V characteristics for thesde liquids demonstrate a non-linear behaviour with three possible regions: Ohmic conduction, space charge saturation regime and Fowler Nordheim charge injection.
Characterization of Nda2, a Plastoquinone-reducing Type II NAD(P)H Dehydrogenase in Chlamydomonas Chloroplasts*

Electron transfer pathways associated to oxygenic photosynthesis, including cyclic electron flow around photosystem I and chlororespiration, rely on non-photochemical reduction of plastoquinones (PQs). In higher plant chloroplasts, a bacterial-like NDH complex homologous to complex I is involved in PQ reduction, but such a complex is absent from Chlamydomonas plastids where a type II NAD(P)H dehydrogenase activity has been proposed to operate. With the aim to elucidate the nature of the enzyme-supporting non-photochemical reduction of PQs, one of the type II NAD(P)H dehydrogenases identified in the Chlamydomonas reinhardtii genome (Nda2) was produced as a recombinant protein in Escherichia coli and further characterized. As many type II NAD(P)H dehydrogenases, Nda2 uses NADH as a preferential substrate, but in contrast to the eukaryotic enzymes described so far, contains non-covalently bound FMN as a cofactor. When expressed at a low level, Nda2 complements growth of an E. coli lacking both NDH-1 and NDH-2, but is toxic at high expression levels. Using an antibody raised against the recombinant protein and based on its mass spectrometric identification, we show that Nda2 is localized in thylakoid membranes. Chlorophyll fluorescence measurements performed on thylakoid membranes show that Nda2 is able to interact with thylakoid membranes of C. reinhardtii by reducing PQs from exogenous NADH or NADPH. We discuss the possible involvement of Nda2 in cyclic electron flow around PSI, chlororespiration, and hydrogen production.
Size- and surface-dependent uptake of colloid particles into the lymphatic system.

PURPOSE To examine the effect of particle size and surface characteristics on colloidal particle uptake from subcutaneous tissue into the lymphatic system. MATERIALS AND METHODS Perfluorocarbon emulsion ZY13163 (median particle diameter, 0.08 micron; surfactant, egg yolk phospholipid), ZY13164 (median particle diameter, 0.36 micron; surfactant, egg yolk phospholipid), ZY13199 (0.18 micron, surfactants Tetronic904) and ZY14001 (0.11 micron, surfactant Pluronic L121) were individually injected into the dorsal skin of the hind foot of rabbits. Lymph flow rates and particle concentrations were determined in prenodal lymph fluid after injection, with and without massage of the skin over the injection site. RESULTS In the first 24 hours after injection, the decreasing order of colloid flux without massage was as follows: ZY13199 > ZY14001 > ZY13163 > ZY13164. Lymph flow rates, lymph leukocyte concentrations and colloid concentrations increased substantially with mechanical skin massage. CONCLUSIONS Transport of colloids into lymphatic vessels depends on particle size and surface characteristics. Without massage, colloids with egg yolk phospholipid exhibit size dependent decrease in uptake into lymphatics, while with massage only a weak correlation with particle size is present.
Ultrastructure of the Spermatozoa of the Domestic Duck (Anas platyrhynchos sp.)

The ultrastructure of the spermatozoa of the domestic duck (Anas platyrhynchos sp.) was analysed by transmission and scanning electron microscopies and compared with the results obtained in preliminary studies involving other non‐passerine birds. The spermatozoa were characterised by the presence of a short head, short midpiece and long principal piece. The head consisted of a reduced acrosome that contained moderately electron‐dense homogenous material. The implantation fossa was observed between the base of the nucleus and the proximal centriole. The midpiece contained electron‐dense material associated with the proximal centriole and nuclear membrane, and a long distal centriole surrounded throughout its length by 11–12 elliptical mitochondria. A dense annulus separating the midpiece from the principal piece was visible. Posterior to the annulus, the axoneme was formed surrounded by a dense fibrous sheath, representing the principal piece or flagellum, which was a long segment with a smooth surface and a smaller diameter than the midpiece. The spermatozoon of the domestic duck resembles that of other non‐passerine birds, corresponding to a basic type of spermatozoon similar to that of reptiles, called sauropsid type.
Glucokinase Regulatory Protein May Interact With Glucokinase in the Hepatocyte Nucleus

Glucokinase (GK) plays a central role in the sensing of glucose in pancreatic β-cells and parenchymal cells of the liver. Glucokinase regulatory protein is a physiological inhibitor of GK in the liver. To understand the role of the interaction of these two proteins in glucose sensing, we carried out a series of experiments to localize the protein in the liver cell. The regulatory protein was found to be present mainly in the nucleus of the cell under a variety of conditions that mimicked the glucose status of the fed and fasted state. GK was localized in the nucleus when the cells were exposed to low glucose concentrations. At higher glucose concentrations or in the presence of low concentrations of fructose, GK translocated to the cytoplasm. The effect of fructose was more robust and rapid than the effect of high glucose concentrations. Furthermore, the effect of fructose and high glucose on the translocation of GK from the nucleus could be partially reversed by glucagon. This unusual localization and behavior suggests a role for GK and its regulatory protein in hepatic energy metabolism that may be broader than glucose phosphorylation.
Diatoms dominate the eukaryotic metatranscriptome during spring in coastal ‘dead zone’ sediments

An important characteristic of marine sediments is the oxygen concentration that affects many central metabolic processes. There has been a widespread increase in hypoxia in coastal systems (referred to as ‘dead zones’) mainly caused by eutrophication. Hence, it is central to understand the metabolism and ecology of eukaryotic life in sediments during changing oxygen conditions. Therefore, we sampled coastal ‘dead zone’ Baltic Sea sediment during autumn and spring, and analysed the eukaryotic metatranscriptome from field samples and after incubation in the dark under oxic or anoxic conditions. Bacillariophyta (diatoms) dominated the eukaryotic metatranscriptome in spring and were also abundant during autumn. A large fraction of the diatom RNA reads was associated with the photosystems suggesting a constitutive expression in darkness. Microscope observation showed intact diatom cells and these would, if hatched, represent a significant part of the pelagic phytoplankton biomass. Oxygenation did not significantly change the relative proportion of diatoms nor resulted in any major shifts in metabolic ‘signatures’. By contrast, diatoms rapidly responded when exposed to light suggesting that light is limiting diatom development in hypoxic sediments. Hence, it is suggested that diatoms in hypoxic sediments are on ‘standby’ to exploit the environment if they reach suitable habitats.
In vitro stimulation of articular chondrocyte mRNA and extracellular matrix synthesis by hydrostatic pressure

This study tested the effects of hydrostatic pressure (10 MPa) on adult articular chondrocyte mRNA and extracellular matrix synthesis in vitro. High density primary cultures of bovine chondrocytes were exposed to hydrostatic pressure applied intermittently at 1 Hz or constantly for 4 hours in serum‐free medium or in medium containing 1% fetal bovine serum, mRNAs for aggrecan, types I and II collagen, and β‐actin were analyzed by Northern blots and quantified by slot blots. Proteoglycan synthesis was quantified by 35SO4 uptake into cetylpyridinium chloride‐precipitable glycosaminoglycans, and cell‐associated aggrecan and type‐II collagen were detected by immunohistochemical techniques. In serum‐free medium, intermittent pressure increased aggrecan mRNA signal by 14% and constant pressure decreased type‐II collagen mRNA signal by 16% (p < 0.05). In the presence of 1% fetal bovine serum, intermittent pressure increased aggrecan and type‐II collagen mRNA signals by 31% (p < 0.01) and 36% (p < 0.001), respectively, whereas constant pressure had no effect on either mRNA. Intermittent and constant pressure stimulated glycosaminoglycan synthesis 65% (p < 0.001) and 32% (p < 0.05), respectively. Immunohistochemical detection of cell‐associated aggrecan and type‐II collagen was increased in response to both intermittent and constant pressure. These data support the hypothesis that physiologic hydrostatic pressure directly influences the extracellular matrix metabolism of articular chondrocytes.
Yersinia pseudotuberculosis in a Closed Colony of Egyptian Fruit Bats (Rousettus aegyptiacus)

Abstract An outbreak of Yersinia pseudotuberculosis (Yptb) occurred in a closed colony of Egyptian fruit bats (Rousettus aegyptiacus) and resulted in the death of seven bats over a 6-week period. An initial survey of the remaining bats revealed visceral abscessation characteristic of pseudotuberculosis in five of the 12 bats examined (41.7%), inciting depopulation of the colony. At necropsy, 70% of the 115 bats in the colony exhibited gross evidence suggestive of Yptb infection, including mesenteric lymphadenopathy (ML), hepatic abscessation (HA), and/or splenomegaly (SPM). Thirty of these bats (13 females and 17 males of various ages) were chosen at random and their tissues submitted for bacterial culture and histopathologic examination. Twenty-three of these 30 bats had one or more gross lesions considered consistent with Yptb, including ML, HA, and SPM. On histopathology, four of the 30 bats had necrotizing lesions containing Gram-negative bacteria in multiple organs, while 18 others exhibited mild mesenteric lymphadenitis and hepatitis. Four of the 30 bats had positive cultures for Yptb. Bats with gross evidence of mesenteric lymphadenopathy, splenomegaly, or histopathologic presence of demodicosis or bacteria in tissues were more likely (P < 0.05) to have a positive Yersinia culture. Examination of the correlation between population density and mortality rates of the colony revealed that the mortality rate of subadult bats increased dramatically at the time of the outbreak, when the population density was at its highest. It is suspected that stress, primarily from severe overcrowding, predisposed the bat colony to morbidity and mortality from this organism, which likely originated from a rodent reservoir.
Effects on fibrin network porosity of anticoagulants with different modes of action and reversal by activated coagulation factor concentrate *

Orally available direct thrombin inhibitors (DTI) and direct activated factor X inhibitors (DFXaI) may replace vitamin K antagonists in patients needing long‐term anticoagulant treatment. We investigated the influence on the fibrin network of anticoagulants with different modes of action: AR‐H067637 (DTI), the active metabolite of AZD0837, apixaban (DFXaI), fondaparinux (indirect FXaI) and warfarin. Counteraction of the anticoagulant effect by FEIBA® (Factor Eight Inhibitor Bypass Activity) was also investigated. Tissue factor, phospholipids and calcium were used to initiate coagulation in human platelet poor plasma. The permeability constant (Ks), reflecting the amount of buffer passing through the coagulum, was calculated and the fibrin network was visualized by 3D confocal microscopy. Warfarin (International Normalized Ratio 2‐3) increased Ks in plasma by 28–50% compared with control. ‘Therapeutic’ plasma concentrations of AR‐H067637 (0·3–0·6 μmol/l), apixaban (0·2–0·4 μmol/l) and fondaparinux (0·1–0·3 μmol/l) increased Ks by 72–91%, 58–76% and 36–53% respectively. Addition of FEIBA® totally reversed the warfarin effect but only partially reversed effects of the other anticoagulants at concentrations that increased Ks by 50% or more. Fibrin network observed with 3D confocal microscopy agreed well with the permeability results. In conclusion, all examined anticoagulants rendered the fibrin network more porous. FEIBA® reversed the increased permeability in warfarin plasma but had only partial effects on the other anticoagulants.
Improving function and survival of pancreatic islets by endogenous production of glucagon-like peptide 1 (GLP-1)

Glucagon-like peptide 1 (GLP-1) is a hormone that has received significant attention as a therapy for diabetes because of its ability to stimulate insulin biosynthesis and release and to promote growth and survival of insulin-producing β cells. While GLP-1 is produced from the proglucagon precursor by means of prohormone convertase (PC) 1/3 activity in enteroendocrine L cells, the same precursor is differentially processed by PC2 in pancreatic islet α cells to release glucagon, leaving GLP-1 trapped within a larger fragment with no known function. We hypothesized that we could induce GLP-1 production directly within pancreatic islets by means of delivery of PC1/3 and, further, that this intervention would improve the viability and function of islets. Here, we show that adenovirus-mediated expression of PC1/3 in α cells increases islet GLP-1 secretion, resulting in improved glucose-stimulated insulin secretion and enhanced survival in response to cytokine treatment. PC1/3 expression in α cells also improved performance after islet transplantation in a mouse model of type 1 diabetes, possibly by enhancing nuclear Pdx1 and insulin content of islet β cells. These results demonstrate a unique strategy for liberating GLP-1 from directly within the target organ and highlight the potential for up-regulating islet GLP-1 production as a means of treating diabetes.
Identification of a Functional Link for the p53 Tumor Suppressor Protein in Dexamethasone-induced Growth Suppression*

Serine/threonine phosphatase 5 (PP5) can act as a suppresser of p53-dependent growth suppression and has been reported to associate with several proteins, including the glucocorticoid receptor/heat-shock protein-90 complex. Still, the physiological/pathological roles of PP5 are unclear. To characterize the relationship of PP5, glucocorticoid receptor activation and p53, here we describe the development of chimeric antisense oligonucleotides that potently inhibit human p53 expression. This allowed us to regulate the expression of either p53 (e.g. with ISIS 110332) or PP5 (e.g. with ISIS 15534) in genetically identical cells. Studies with ISIS 110332 revealed that the suppression of p53 expression is associated with a decrease in the basal expression of the cyclin-dependent kinase inhibitor protein, p21WAF1/Cip1, and a concomitant increase in the rate of cell proliferation. Suppression of p53 also blocks dexamethasone-induced p21WAF1/Cip1 expression and G1-growth arrest. Furthermore, treatment with ISIS 110332, but not the mismatched controls, ablates the suppression of growth produced by prior treatment with dexamethasone. Additional studies revealed that dexamethasone-dependent p21WAF1/Cip1 expression occurs without an apparent change in p53 protein levels or the phosphorylation status of p53 at Ser-6, -37, or -392. However, dexamethasone treatment is associated with an increase in p53 phosphorylation at Ser-15. Suppression of PP5 expression with ISIS 15534 also results in the hyperphosphorylation of p53 at Ser-15. Together, these findings indicate that the basal expression of p53 plays a functional role in a glucocorticoid receptor-mediated response regulating the expression of p21Waf1/Cip1 via a mechanism that is suppressed by PP5 and associated with the phosphorylation of p53 at Ser-15.