Serum tumor markers in bile duct cancer – a review

Abstract

Context: Bile duct cancer (BDC) is a disease with a very grave prognosis, often diagnosed too late.

Objective: The aim of this review is to evaluate available literature on tumor markers in serum from patients with BDC.

Methods: Using the search words “serum markers”, “bile duct cancer”, “cholangiocarcinoma”, “biomarker” and “tumor marker”, a search was carried out.

Results: Seventy-five studies were included in the review.

Conclusion: CA19-9 is by far the most studied and most promising diagnostic and/or prognostic marker in BDC. But also the different mucins are interesting as new markers of BDC in serum.     

Components of the major urinary protein complex of inbred mice: Determination of NH2-terminal sequences and comparison with homologous components from wild mice

The major urinary protein (MUP) complex of normal inbred laboratory mice (Mus musculus musculus) is a family of three electrophoretically distinguishable components, designated 1, 2, and 3 in order of increasing anodal mobility at pH 5.5. Components 1 and 2 are under the control of a single genetic locus; the MUP complex of a given inbred strain consists of component 1 or 2 plus component 3. In this study, the urinary protein of two subspecies of Asian wild mice, Mus musculus molossinus (originally trapped in Japan) and Mus musculus castaneus (originally trapped in Thailand), was examined electrophoretically and ultracentrifugally. The MUP complex of male M. m. molossinus and M. m. castaneus sedimented at approximately the same rate as that of M. m. musculus (s ₂₀ =2.0?2.2S). It consisted of a “fast” (i.e., more anodal than component 3) and an “intermediate” component plus one or more “origin” (i.e., less anodal than component 1) components. The “fast” and “origin” components were isolated chromatographically, and NH₂-terminal sequences spanning the first 36 residues were determined. Comparison with the NH₂-terminal sequences determined for components 1, 2, and 3 isolated from the urine of BALB/c or C57BL/6 mice revealed, except for a single replacement at position 6 in the “origin” component of M. m. molossinus, no differences among the 1, 2, “origin”, and “fast” components. Component 3 was highly homologous but differed from component 1 at nine positions; its residue at position 6 was the same as that of the M. m. molossinus “origin” component.     

Seasonal variations in rheumatoid factor titer in newly hospitalized mental patients

Abstract

Rheumatoid factor titer was determined on 655 newly admitted mental patients, of whom 32.4% were found positive. When the overall findings were divided into “winter readings” obtained from October through March, and “summer readings” obtained from April through September, the prevalence of positive titers in negro and non‐negro males was found to be significantly higher in the former than in the latter. No such seasonal variations were observed in the corresponding female cohorts.     

The gamification of elementary school biology: a case study on increasing understanding of plants

ABSTRACT

This study presents a new technique, the “Which plant am I?” game, which helps to increase pupils’ plant knowledge, while motivate them to become familiar with more plants. On the other hand pupils’ plant knowledge was tested in Serbia.

The “Which Plant Am I?“ game was tested with two groups of pupils (in average 11 years old). Pupils in the experimental group took part in outdoor classes and played the ”Which plant am I?” game. Pupils of the control group observed plants only in the classroom. This technique can deliver significant improvement in pupils’ knowledge about plants and motivate them through an active and playful learning process. This technique can be one possible solution of plant blindness.     

An integrated environment and cost assessment method based on LCA and LCC for mechanical product manufacturing

Purpose

The purpose of this study is to provide an integrated method to identify the resource consumption, environmental emission, and economic cost for mechanical product manufacturing from economic and ecological dimensions and ultimately to provide theoretical and data support of energy conservation and emission reduction for mechanical product manufacturing.

Methods

The applied research methods include environmental life cycle assessment (LCA) and life cycle cost (LCC). In life cycle environmental assessment, the inventory data are referred from Chinese Life Cycle Database and midpoint approach and EDIP2003 and CML2001 models of life cycle impact assessment (LCIA) are selected. In life cycle cost assessment, three cost categories are considered. The proposed environment and cost assessment method is based on the theory of social willingness to pay for potential environmental impacts. With the WD615 Steyr engine as a case, life cycle environment and cost are analyzed and evaluated.

Results and discussion

The case study indicates that, in different life cycle phases, the trend of cost result is generally similar to the environmental impacts; the largest proportion of cost and environmental impact happened in the two phases of “material production” and “component manufacturing” and the smallest proportion in “material transport” and “product assembly.” The environmental impact category of Chinese resource depletion potential (CRDP) accounted for the largest proportion, followed by global warming potential (GWP) and photochemical ozone creation potential (POCP), whereas the impacts of eutrophication potential (EP) and acidification potential (AP) are the smallest. The life cycle “conventional cost” accounted for almost all the highest percentage in each phase (except “material transport” phase), which is more than 80% of the total cost. The “environmental cost” and “possible cost” in each phase are relatively close, and the proportion of which is far below the “conventional cost.”

Conclusions

The proposed method enhanced the conventional LCA. The case results indicate that, in a life cycle framework, the environment and cost analysis results could support each other, and focusing on the environment and cost analysis for mechanical product manufacturing will contribute to a more comprehensive eco-efficiency assessment. Further research on the life cycle can be extended to phases of “early design,” “product use,” and “final disposal.” Other LCIA models and endpoint indicators are advocated for this environmental assessment. Environmental cost can also be further investigated, and the relevant social willingness to pay for more environmental emissions is advocated to be increased.

     

Abstracts: Albany 2007, The 15th Conversation

Abstract

Forty nine molecular dynamics simulations of unfolding trajectories of the segment B1 of streptococcal protein G (GB1) provide a direct demonstration of the diversity of unfolding pathway and give a statistically utmost unfolding pathway under the physical property space. Twelve physical properties of the protein were chosen to construct a 12-dimensional property space. Then the 12-dimentional property space was reduced to a 3-dimentional principle component property space. Under the property space, the multiple unfolding trajectories look like “trees”, which have some common characters. The “root of the tree” corresponds to the native state, the “bole” homologizes the partially unfolded conformations, and the “crown” is in correspondence to the unfolded state. These unfolding trajectories can be divided into three types. The first one has the characters of straight “bole” and “crown” corresponding to a fast two-state unfolding pathway of GB1. The second one has the character of “the standstill in the middle tree bole”, which may correspond to a three-state unfolding pathway. The third one has the character of “the circuitous bole” corresponding to a slow two-state unfolding pathway. The fast two-state unfolding pathway is a statistically utmost unfolding pathway or preferred pathway of GB1, which occupies 53% of 49 unfolding trajectories. In the property space all the unfolding trajectories construct a thermal unfolding pathway ensemble of GB1. The unfolding pathway ensemble resembles a funnel that is gradually emanative from the native state ensemble to the unfolded state ensemble. In the property space, the thermal unfolded state distribution looks like electronic cloud in quantum mechanics. The unfolded states of the independent unfolding simulation trajectories have substantial overlaps, indicating that the thermal unfolded states are confined by the physical property values, and the number of protein unfolded state are much less than that was believed before.     

Oxygen activation by isolated chloroplasts from Euglena gracilis. Ferredoxin-dependent function of a fluorescent compound and photosynthetic electron transport close to photosystem.

Oxygen reduction by isolated chloroplast lamellae from spinach, yielding the superoxide free radical in the light, is stimulated by a fluorescent factor (“compound No. 4”, isolated from Euglena gracilis strain Z) in a ferredoxin-dependent reaction. This reaction is not observed with Euglena chloroplasts, although there is a stimulation by compound No. 4 of ferredoxin-dependent oxygen reduction at the expense of NADPH + H⁺ as electron donor in the dark. Evidence is provided that in Euglena chloroplasts in the absence of NADP as electron acceptor a cyclic electron transport is predominating, including photosystem I, ferredoxin, NADP-ferredoxin reductase, and cytochrome₅₅₂. Isolated spinach chloroplast lamellae show a similar “cyclic” electron transport after treatment with digitonin, depending on the addition of the above cofactors. This result might indicate that Euglena chloroplast lamellae show this cyclic electron transport only as an artifact due to the isolation procedure. The results furthermore indicate that the pteridine-like, fluorescent compound No. 4 is not active as the primary electron acceptor of photosystem I; it may however be involved in oxygen activation by Euglena gracilis chloroplasts.     

Fucose-containing polysaccharides in the brown algae Ascophyllum nodosum and Fucus vesiculosus

The fucose-containing, sulfated polysaccharides from Ascophyllum nodosum and Fucus vesiculosus were isolated by extraction with water adjusted to pH 2. Pure fractions were carefully separated by fractional precipitation with ethanol from aqueous solutions containing magnesium or calcium chloride. Progress in the fractionation efforts and purity of the fractions isolated were established by free-boundary and cellulose acetate clectrophoresis. Ascophyllan, two “complexes”, and a galactofucan were isolated from A. nodosum. An ascophyllan-like fraction, and a “complex” were isolated from F. vesiculosus. Mild, acid hydrolysis (0.02m hydrochloric acid, 1 h, 80°) converted each of the “complexes” into an electrophoretically faster-moving and a slower-moving component. The “complex” from F. vesiculosus comprised a greater proportion of the extract than did the two “complexes” from A. nodosum. In addition, the Fucus “complex” was richer in fucose*. However, the data suggest that neither species contains a pure fucan sulfate in the native state.     

Synthesis of Methylene-Bridged Analogues of Nicotinamide Riboside,Nicotinamide Mononucleotide and Nicotinamide Adenine Dinucleotide

Abstract

5-O-tert-Butyldimethylsilyl-1,2-O-isopropylidene-3(R)-(nicotinamid-2-ylmethyl)-α-D-ribofuranose (11a) and ?3(R)-(nicotinamid-6-ylmethyl)-α-D-ribofuranose (11b) were prepared by condensation of 5-O-tert-butyldimethylsilyl-1,2-O-isopropylidene-α-D-erythro-3-pentulofuranose (10) with lithiated (LDA) 2-methylnicotinamide and 6-methylnicotinamide, respectively, and then deprotected to give 1,2-O-isopropylidene-3-(R)-(nicotinamid-2-ylmethyl)-α-D-ribofuranose(12a) and 1,2-O-isopropylidene-3(R)-(nicotinamid-6-ylmethyl)-α-D-ribofuranose (12b). Benzoylation as well as phosphorylation of compounds 12 afforded the corresponding 5-O-benzoate (13b) and 5-O-monophosphates (14a and 14b). Treatment of 13b with CF₃COOH/H₂O caused 1,2-de-O-isopropylidenation with simultaneous cyclization to the corresponding methylene-bridged cyclic nucleoside - 3′,6-methylene-1-(5-O-benzoyl-β-D-ribofuranose)-3-carboxamidopyridinium trifluoro-acetate (8b) - restricted to the “anti” conformation. In a similar manner compounds 14a and 14b were converted into conformationally restricted 2,3′-methylene-1-(β-D-ribofuranose)-3-carboxamidopyridinium-5′-monophosphate (9a - “syn”) and 3′,6-methylene-1-(β-D-ribofuranose)-3-carboxamido -pyridinium-5′monophosphate (9b - “anti”) respectively. Coupling of derivatives 12a and 12b with the adenosine 5′-methylenediphosphonate (16) afforded the corresponding dinucleotides 17. Upon acidic 1,2-de-O-isopropylidenation of 17b, the conformationally restricted P¹-[6,3′-methylene-1-(β-D-ribofuranos-5-yl)-3-carboxamidopyridinium]-P²-(adenosin-5′-yl)methylenediphosphonate 18b -“anti” was formed. Compound 18b was found to be unstable. Upon addition of water 18b was converted into the anomeric mixture of acyclic dinucleotides, i. e. P¹-[3(R)-nicotinamid-6-ylmethyl-D-ribofuranos-5-yl]-P²-(adenosin-5′-yl)-methylenediphosphonate (19b). In a similar manner, treatment of 17a with CF₃COOH/H₂O and HPLC purification afforded the corresponding dinucleotide 19a.

     

Synthesis and Antiviral Activity of C-5 Substituted Analogues of D4T Bearing Methylamino- or Methyldiamino-Linker Arms

Abstract

A general strategy is reported for the preparation of C-5-methylamino- or methyldiamino-d4T analogues of “different sizes”. Reactions of the 2′,3′-didehydro-2′,3′-dideoxy-C-5 hydroxymethyl precursor (7) with either polymethylene diamines (n = 6, 8, 10 and 12) or propargylamine proceed regioselectively via subtitution reactions at the C-5 position of uracil. The compounds were evaluated for antiviral activity and cytotoxicity. No significant activity was observed for compounds 9, 11, and 13, but 10 and 12 exhibited a weak activity against HIV-1.     

Exhaled breath volatile alterations in pregnancy assessed with electronic nose

Context: Pregnancy-linked accelerated metabolism and oxidative stress may alter the exhaled volatile compound pattern (“breathprint”). Electronic noses can distinguish “breathprints” associated with different disorders.

Objective: This is the first study assessing alterations in “breathprint” during gestation.

Material and methods: 130 women participated in our study (78 pregnant vs. 52 non-pregnant). Breath samples were processed by an electronic nose and analyzed using principal component analysis.

Results: Significant differences were found in exhaled breath pattern between pregnant and non-pregnant women (p?=?0.001).

Conclusion: Pregnancy-induced changes in exhaled gases need to be considered when pregnant women with respiratory disorders carry out breath tests.     

The Changes of “Myosin B” during Storage of Rabbit Muscle

The results of sedimentation studies revealed that “myosin B” extracted from rigor muscle was different from myosin B from fresh muscle; the former contained less contaminating myosin A and less main component but more heavy component than the latter did. The proportion of constitutional myosin A to actin in the former was less than that in the latter.

“Myosin B” from post-rigor muscle was very similar to that from rigor muscle in the sedimentation behaviours.

The extrapolated sedimentation coefficient fresh muscle was 99S.     

Conversion of lipids to fatty alcohols and lysolipids by NaBH4

A variety of fatty acid esters were reacted with NaBH₄ in tetra-hydrofuran (THF) — water mixtures. Although triglycerides and free acids were stable under the conditions employed, more polar lipids were extensively reduced to the corresponding fatty alcohols. Thus when reacted with NaBH₄ for 60 min at 37°C, 94% and 64% respectively of the acyl groups in lecithin and monogalactosyl diglyceride were reduced to fatty alcohols. No discernible reduction or isomerisation of double bonds occurred during the reactions. Reductions in the reaction temperature, and in the THF content of the solvent, both resulted in slower reaction rates.The reactions with complex lipids proceded with the intermediate formation of the corresponding monoacyl (“lyso”) lipids, but the reagent showed no selectivity towards position or structure of the component ester groups.In its proposed form, the method for determining acyl thiolesters in biological tissues by their specific reduction with NaBH₄, is not satisfactory.     

Disturbance-level-dependent post-disturbance succession in a Eurasian steppe

Anthropogenic disturbances may decrease as we take measures to control them. However, the patterns and mechanisms of post-disturbance ecosystem succession have rarely been studied. Here we reported that disturbance level determined the importance of stochastic relative to deterministic changes in ecosystem components (plant community composition, soil microbial community composition, and soil physicochemical indices), and thus predefined the pattern of post-disturbance ecosystem succession. We proposed a theoretical framework with five disturbance levels corresponding to distinct succession patterns. We conducted a nitrogen addition experiment in a temperate steppe, monitored these ecosystem components during “disturbance” treatment (2010–2014) and post-treatment “succession” (2014–2018). The disturbance level experienced by each component in each treatment was inferred by fitting the observed succession patterns into the theoretical framework. The mean disturbance level of these components was found to increase quadratically with nitrogen addition rate. This was because increasing nitrogen addition reduced the importance of stochastic relative to deterministic changes in these components, and these changes had a quadratic relationship with disturbance level. Overall, our results suggested that by monitoring the importance of stochastic relative to deterministic changes in an ecosystem, we can estimate disturbance levels and predict succession patterns, as well as propose disturbance-level-dependent strategies for post-disturbance restoration.

     

Bioreduction of activated alkenes by a novel “ene”-reductase from the thermophilic strain Bacillus coagulans WCP10-4

Abstract

“Ene”-reductase, from the Old Yellow Enzyme (OYE) family, is known to catalyze the asymmetric reduction of the olefinic bond of α,β-unsaturated carbonyl compounds through trans-hydrogenation. Here we report the cloning, expression, and characterization of a novel OYE enzyme named “BcOYE” from the thermophilic strain, Bacillus coagulans WCP10-4. The enzyme was heterologously overexpressed in Escherichia coli with a high yield (84 mg/mL) in shaken flasks. The recombinant BcOYE was purified to homogeneity by one-step His-tag affinity chromatography. The molecular mass of the enzyme was estimated to be 38 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme was most active at 50°C and pH of 7.0, and showed higher activity toward an array of ketones and maleimides. No activity was detected toward 2-cyclohexen-1-one. At 50°C, we demonstrated that BcOYE can produce the (R)-enantiomer of 2-methylcyclohexanone with high yield and optical purity more rapidly than at lower temperature (30°C). We also successfully developed a coenzyme regeneration system with glucose-6-phosphate dehydrogenase isolated from the same thermophilic strain.     

The Changes of “Myosin B” during Storage of Rabbit Muscle

The irreversibility of the dissociation of “myosin B” stored in 0.6 m KCl at pH 5.7 and 3°C was attributed to the rapid denaturation of F-actin dissociated from “myosin B”

F-Actin was less stable than myosin A, in 0.18~0.60 m KCl at pH 5.7 and temperatures between 0 ~3°C.

The decrease in the ability of F-actin to bind with myosin A was slightly dependent on storage temperature, and there was no apparent relation with the decrease in the solubility.

A hypothetical scheme for F-actin denaturation was proposed.     

The Epoxidation of Unsaturated Steroids

Data for several additional instances of epoxidation by biological systems at isolated unsaturated sites on steroid structures are presented.

These systems include the bovine adrenal, Curvularia lunata and a Curvularia species. This reaction predictably occurred only in the presence of enzymes capable of introducing “axial” hydroxyl functions at saturated carbons of corresponding analogous structures. A discussion of the implication of these findings in terms of the mechanism of the enzymatic hydfoxylation reaction is given.     

Steroid-protein interactions. Fluorescence quenching of progesterone-binding globulin and alpha1-acid glycoprotein upon binding of steroids.

The influence of progesterone and four other steroids on the intrinsic fluorescence of progesterone-binding globulin was investigated. The corresponding effect of progesterone on α₁-acid glycoprotein was also studied. The intrinsic fluorescence of the progesterone-binding globulin and of α₁-acid glycoprotein was quenched by about 60 and 17%, respectively, upon forming stoichiometric complexes with progesterone. Graphical analysis of fluorescence quenching titrations with progesterone gave affinity constants at 23 °C of 2 × 10⁹m^?1 for progesterone-binding globulin and 1 × 10⁶m^?1 for α₁-acid glycoprotein. With progesterone-binding globulin, affinity constants of 1 × 10⁹m^?1 were determined for desoxycorticosterone, 1 × 10⁸m^?1 for testosterone, and 2 × 10⁶m^?1 for cortisol. The fluorescence quenching of PBG by 5-pregnen-3β-ol-20-one, 5α-pregnanedione, and 5β-pregnanedione, steroids lacking the Δ⁴-3-keto grouping, was too small to be evaluated; however, binding of the pregnanediones to progesterone-binding globulins was demonstrated when the progesterone-progesterone-binding globulin complex was “unquenched” as a result of competitive displacement of progesterone by addition of the pregnanediones. The quenching phenomenon is assumed to be mainly due to radiationless transfer from protein to the near uv (n → π1) absorption band of steroids containing the Δ⁴-3-keto chromophore.     

Analysis of waving and sound‐production display in the ghost crab,Ocypode stimpsoni

The ghost crab Ocypode stimpsoni displays waving and sound production. Sounds are produced by thumping the sand substratum with the major cheliped, and two types of sounds can be discriminated; one with a low frequency of about 12 Hz, called rapping, and another with a higher frequency (about double), called quivering. In our observations, a sequence of waving and sound emission would sometimes terminate abruptly, or appear as independent components but the component order never changed. The most frequently observed patterns were “waving with rapping and quivering”;, “waving with quivering”; and “quivering only”; quivering sounds being involved in more than 80% displays. Quivering sometimes occurred immediately after crabs emerged from the burrow, or when they returned to the entrance after discarding an excavated sand mass. The occurrence frequency of waving and sounds, the wave amplitude, and the frequency of the sound increased when other crabs approached.     

SHORT-TERM IMPACTS OF FORMULATIONS OF BACILLUS THURINGIENSIS VAR. ISRAELENSIS DE BARJAC AND THE ORGANOPHOSPHATE TEMEPHOS,USED IN BLACKFLY (DIPTERA: SIMULIIDAE) CONTROL,ON RHEOPHILIC BENTHIC MACROINVERTEBRATES IN THE MIDDLE ORANGE RIVER,SOUTH AFRICA

Summary

The impacts of larvicides used in the control of blackflies (Diptera: Simuliidae) on macroinvertebrates in the stones-in-current biotope were assessed during 8 field trials in the middle Orange River, South Africa. Two Bacillus thuringiensis var. israelensis (B.t.i.) products (Vectobac^R 12AS and Teknar^R HP-D) and the organophosphate temephos (Abate^R 200EC) were applied at recommended and high dosages to simulate “operational” and “worst-possible” scenario's respectively. Mortality was evaluated either by direct counting of invertebrates on stones before and after application, or by ranking invertebrates on a 4-point relative abundance scale before and after application. In addition, the re-appearance of benthic invertebrate population densities after temephos application was examined.

At the recommended dosage (1.2 ppm/10 min), B.t.i. significantly reduced blackfly larval numbers (P<0.001) and those of the chironomid Rheotanytarsus fuscus Freeman (P<0.05). At high dosage (20 ppm/10 min), numbers of the filter-feeding mayfly Tricorythus discolor (Burmeister) (P<0.01) and the chironomid Cardiocladius sp. (P<0.05) were also significantly reduced. No Simulium predators were directly affected by B.t.i., but there were indications of food shortage amongst Hydropsychidae and Hirudinea.

Temephos caused significant reductions in the relative abundance of 5 taxa at 0.05 ppm, 3 to 6 taxa at 0.1 ppm, and 9 taxa at 1.0 ppm (P<0.05). “Non-target” organisms which were most affected included the chironomid R. fuscus, the mayflies Baetis glaucus Agnew and Choroterpes elegans Barnard, and the caddisflies Cheumatopsyche thomasseti Ulmer and Amphipsyche scottae Kimmins. The mayfly T. discolor was tolerant of temephos, even at high dosage (1.0 ppm/10 min). In winter, most taxa re-appeared within 19 days, and population densities were back to pre-treatment levels within 35 days.

It is concluded that good reduction of blackfly populations may be obtained with minimal direct impact on the “non-target” fauna, provided recommended dosages of temephos are not exceeded. Overdosing with temephos may result in high mortality of “non-target” organisms, including blackfly predators, and should be avoided.