Function of chlorophyll d in reaction centers of photosystems I and II of the oxygenic photosynthesis of Acaryochloris marina

Reaction center chlorophylls (Chls) in photosystems II and I were studied in the isolated thylakoid membranes of a cyanobacterium, Acaryochloris marina, which contains Chls d and a as the major and minor pigments, respectively. The membranes contained PS I and II complexes at a 1.8:1 molar ratio on the basis of the spin densities on the tyrosine D radical and the photo-oxidized PS I primary donor (P740+). In the presence of ferricyanide, laser excitation induced bleach at 725 nm that recovered with time constants of 25 micros and 1.2 ms. The signal, designated P725, was suppressed by PS II inhibitors DCMU and hydroxylamine. The P725 spectrum was tentatively assigned to the absorption changes of the special pair Chl d, the accessory Chl d, and the acceptor pheophytin a in PS II. The addition of ascorbate induced the additional signal with a slow decay time constant of 4.5 ms. This signal showed a broad bleach at 740 nm and shift-type absorption changes at around 707 and 685 nm, which were assigned to the absorption changes of PS I special pair of Chl d (P740), the accessory Chl d, and the primary acceptor Chl a (A0), respectively. Mechanisms and the evolution of the Chl-d based reaction centers using far-red light are discussed together with the amino acid sequences of PS II D1 and D2 proteins.     

Copy number alterations and allelic ratio in relation to recurrence of rectal cancer

Background

In rectal cancer, total mesorectal excision surgery combined with preoperative (chemo)radiotherapy reduces local recurrence rates but does not improve overall patient survival, a result that may be due to the harmful side effects and/or co-morbidity of preoperative treatment. New biomarkers are needed to facilitate identification of rectal cancer patients at high risk for local recurrent disease. This would allow for preoperative (chemo)radiotherapy to be restricted to high-risk patients, thereby reducing overtreatment and allowing personalized treatment protocols. We analyzed genome-wide DNA copy number (CN) and allelic alterations in 112 tumors from preoperatively untreated rectal cancer patients. Sixty-six patients with local and/or distant recurrent disease were compared to matched controls without recurrence. Results were validated in a second cohort of tumors from 95 matched rectal cancer patients. Additionally, we performed a meta-analysis that included 42 studies reporting on CN alterations in colorectal cancer and compared results to our own data.

Results

The genomic profiles in our study were comparable to other rectal cancer studies. Results of the meta-analysis supported the hypothesis that colon cancer and rectal cancer may be distinct disease entities. In our discovery patient study cohort, allelic retention of chromosome 7 was significantly associated with local recurrent disease. Data from the validation cohort were supportive, albeit not statistically significant, of this finding.

Conclusions

We showed that retention of heterozygosity on chromosome 7 may be associated with local recurrence in rectal cancer. Further research is warranted to elucidate the mechanisms and effect of retention of chromosome 7 on the development of local recurrent disease in rectal cancer.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1550-0) contains supplementary material, which is available to authorized users.     

Design, synthesis and biological activity of selective and orally available TF/FVIIa complex inhibitors containing non-amidine P1 ligands

We found the novel selective and orally available non-amidine TF/FVIIa complex inhibitor 21e, 4-({[(1S)-(aminocarbonyl)-3-methylbutyl]amino}carbonyl)-2'-({[4- (aminomethyl)phenyl]amino}carbonyl)-4'-(methylamino)biphenyl-2- carboxylic acid. The derivatives were synthesized by conversions of the isobutyl moiety and the introduction of alkylamino groups to 4'-position of the central phenyl ring of compounds 2a and 2b reported previously. Some compounds show increased in vitro anti-TF/FVIIa and PT prolongation activities. Among them, compound 21e reached and sustained micromolar plasma concentration levels of up to 2h after oral administration in mice. Moreover, compound 21e did not prolong the bleeding time even at the highest dose level in cynomolgus monkeys, while PT was prolonged 3.7-fold increases at this dose.     

Dose to contralateral breast from whole breast irradiation by automated tangential IMRT planning: comparison of flattening-filter and flattening-filter-free modes

BackgroundThe most common secondary cancer is contralateral breast (CLB) cancer after whole breast irradiation (WBI). The aim of this study was to quantify the reduction of CLB dose in tangential intensity modulated radiotherapy (t-IMRT) for WBI using flattening-filter-free (FFF) beams.Materials and methodsWe generated automated planning of 20 young breast cancer patients with limited user interaction. Dose-volume histograms of the planning target volume (PTV), ipsilateral lung, heart, and CLB were calculated. The dose of PTV, the most medial CLB point, and the CLB point below the nipple was measured using an ionization chamber inserted in a slab phantom. We compared the two t-IMRT plans generated by FFF beams and flattening-filter (FF) beams.ResultsAll plans were clinically acceptable. There was no difference in the conformal index, the homogeneity for FFF was significantly worse. For the ipsilateral lung, the maximum dose (D_max) was significantly higher; however, V₂₀ showed a tendency to be lower in the FFF plan. No differences were found in the D_max and V₃₀ to the heart of the left breast cancer. FF planning showed significantly lower D_max and mean dose to the CLB. In contrast to the calculation results, the measured dose of the most medial CLB point and the CLB point below the nipple were significantly lower in FFF mode than in FF mode, with mean reductions of 21.1% and 20%, respectively.ConclusionsT-IMRT planning using FFF reduced the measured out-of-field dose of the most medial CLB point and the CLB point below the nipple.     

Urea treatment allows dithiothreitol to release the binding subunit of the insulin receptor from the cell membrane: implications for the structural organization of the insulin receptor

The sequence of the human insulin receptor has only one identifiable transmembrane region which is located in the beta subunit. The structure predicts that the alpha subunit, which binds insulin, is attached to the cell only by disulfide bonds to the beta subunit. However, treatment of membranes with dithiothreitol is ineffective at releasing the alpha subunit. If the receptor structure is unfolded with urea, dithiothreitol is able to release the alpha subunit. These data provided confirmatory evidence that the alpha subunit is not a transmembrane protein.     

Electron microscopy of dividing cells

During intranuclear mitosis in plasmodia of Physarum polycephalum the primordium of spindle microtubules which is a somewhat electron opaque, amorphous structure with fibrous or granular elements, occurs in the center of early prophase, 20 to 30 minutes before metaphase. Then, the primordium seems to divide into two parts. Spindle microtubules develop radially from the primordia of spindle microtubules. These spindle microtubules increase in number and length during prophase. Spindle microtubules are completed in about five minutes before metaphase. The nuclear envelope remains intact during prophase, but after metaphase it breaks at the polar regions. The nuclear envelope of the daughter nucleus is re-formed from the original nuclear envelope.The authors wish to express their thanks Professor K. Ueda for valuable advice. They would also like to thank Professor N. Kamiya of Osaka University who kindly supplied the material (Physarum polycephalum) used in the present study.     

Triterpenoids and glycosides from Geum japonicum

Two new glucosides and two known ester glucosides have been isolated from Geum japonicum. The two new glucosides were isolated by formation of their acetates and were identified as glucosides of 2-isopropyl-5-methylhydroquinone by chemical and spectral studies. The two known ester glucosides were identified as niga-ichigoside F1 and suavissimoside F1 by direct comparison with authentic samples. 2α,19α-Dihydroxyursolic acid and the known glycoside, gein, were also isolated from the same plant, in addition to a mixture of 2α-hydroxyursolic acid and 2α-hydroxyoleanolic acid.     

Dynamic exchange between stabilized conformations predicted for hyaluronan tetrasaccharides: comparison of molecular dynamics simulations with available NMR data

Studies of the hyaluronan (HA) tetrasaccharides are important for understanding hydrogen-bonding in the HA polymer, as they are probably the smallest oligomers in which characteristics of the constituent monosaccharides and the polymer are simultaneously exhibited. Here we present extensive molecular dynamics simulations of the two tetrasaccharides of HA in dilute aqueous solution. These simulations have confirmed the existence of intramolecular hydrogen-bonds between the neighboring sugar residues of HA in solution, as proposed by Scott (1989). However, our simulations predict that these intramolecular hydrogen-bonds are not static as previously proposed, but are in constant dynamic exchange on the sub-nanosecond time-scale. This process results in discrete internal motion of the HA tetrasaccharides where they rapidly move between low energy conformations. Specific interactions between water and intramolecular hydrogen-bonds involving the hydroxymethyl group were found to result in differing conformations and dynamics for the two alternative tetrasaccharides of HA. This new observation suggests that this residue may play a key role in the entropy and stability of HA in solution, allowing it to stay soluble up to high concentration. The vicinal coupling constants3 J NHCH of the acetamido groups have been calculated from our aqueous simulations of HA. We found that high values of 3J NHCH approximately 8 Hz, as experimentally measured for HA, are consistent with mixtures of both trans and cis conformations, and thus3 J NHCH cannot be used to imply a purely trans conformation of the acetamido. The rapid exchange of intramolecular hydrogen-bonds indicates that although the structure is at any moment stabilized by these hydrogen-bonds, no one hydrogen-bond exists for an extended period of time. This could explain why NMR often fails to provide evidence for intramolecular hydrogen-bonds in HA and other aqueous carbohydrate structures.