Structure model of core proteins in photosystem I inferred from the comparison with those in photosystem II and bacteria; an application of principal component analysis to detect the similar regions between distantly related families of proteins.

A principal component analysis based on the physico-chemical properties of amino acid residues is developed to assign similar regions between distantly related families of proteins, taking account of the species diversities in respective families. The most important advantage of this analysis should be that it reflects different physico-chemical properties and thus can predict more detailed structural properties, including the transmembrane helices, than the hydropathy analysis. Its first application reconfirms the similarity between the core proteins of photosynthetic reaction center in purple bacteria and those of photosystem II, indicating that the low percentage of identical amino acid residues estimated previously between them is due to much allowance for amino acid substitutions in purple bacteria. The application of this analysis to the core proteins of photosystem I reveals that any of these proteins includes two domains, each showing high similarity to the amino acid sequences of core proteins in photosystem II and purple bacteria. A core structure model of A1 and A2 proteins folded into four layers of sheets of transmembrane helices is proposed to provide a molecular basis for the electron pathway suggested by spectroscopic experiments as well as for the interaction sites with plastocyanin, 9 kDa protein and LHC proteins.     

Evaluation of dimerization–inhibitory activities of cyclic peptides containing a β-hairpin loop sequence of the EGF receptor

Structure–activity relationships of cyclic peptides mimicking the β-hairpin structure of the ‘dimerization arm’ at residues 242–259 of the EGF receptor are examined. Cyclic peptides containing the arm head of the β-hairpin loop showed inhibitory activity toward the EGF receptor’s dimerization. Cyclic peptides containing a Retro-Inverso sequence of the dimerization arm showed clear inhibitory effects on the dimerization in vitro and efficiently suppressed the proliferation of A431 cells, which abundantly express the EGF receptor on their surface. The effects at a specific hydrophobic site of the loop structure were expected to enhance the interactions with the receptor.     

Risk Factors and Adverse Perinatal Outcomes among Term and Preterm Infants Born Small-for-Gestational-Age: Secondary Analyses of the WHO Multi-Country Survey on Maternal and Newborn Health

Background

Small for gestational age (SGA) is not only a major indicator of perinatal mortality and morbidity, but also the morbidity risks in later in life. We aim to estimate the association between the birth of SGA infants and the risk factors and adverse perinatal outcomes among twenty-nine countries in Africa, Latin America, the Middle East and Asia in 359 health facilities in 2010–11.

Methods

We analysed facility-based, cross-sectional data from the WHO Multi-country Survey on Maternal and Newborn Health. We constructed multilevel logistic regression models with random effects for facilities and countries to estimate the risk factors for SGA infants using country-specific birthweight reference standards in preterm and term delivery, and SGA’s association with adverse perinatal outcomes. We compared the risks and adverse perinatal outcomes with appropriate for gestational age (AGA) infants categorized by preterm and term delivery.

Results

A total of 295,829 singleton infants delivered were analysed. The overall prevalence of SGA was highest in Cambodia (18.8%), Nepal (17.9%), the Occupied Palestinian Territory (16.1%), and Japan (16.0%), while the lowest was observed in Afghanistan (4.8%), Uganda (6.6%) and Thailand (9.7%). The risk of preterm SGA infants was significantly higher among nulliparous mothers and mothers with chronic hypertension and preeclampsia/eclampsia (aOR: 2.89; 95% CI: 2.55–3.28) compared with AGA infants. Higher risks of term SGA were observed among sociodemographic factors and women with preeclampsia/eclampsia, anaemia and other medical conditions. Multiparity (> = 3) (AOR: 0.88; 95% CI: 0.83–0.92) was a protective factor for term SGA. The risk of perinatal mortality was significantly higher in preterm SGA deliveries in low to high HDI countries.

Conclusion

Preterm SGA is associated with medical conditions related to preeclampsia, but not with sociodemographic status. Term SGA is associated with sociodemographic status and various medical conditions.     

Design,synthesis and structure-activity relationships of dual inhibitors of acetylcholinesterase and serotonin transporter as potential agents for Alzheimer's disease

We have designed and synthesized a dual inhibitor of acetylcholinesterase (AChE) and serotonin transporter (SERT) as a novel class of treatment drugs for Alzheimer's disease on the basis of a hypothetical model of the AChE active site. Dual inhibitions of AChE and SERT would bring about greater therapeutic effects than AChE inhibition alone and avoid adverse peripheral effects caused by excessive AChE inhibition. Compound (S)-6j exhibited potent inhibitory activities against AChE (IC(50)=101 nM) and SERT (IC(50)=42 nM). Furthermore, (S)-6j showed inhibitory activities of both AChE and SERT in mice brain following oral administration.     

Repetitive preischemic infusion of phosphodiesterase III inhibitor olprinone elicits cardioprotective effects in the failing heart after myocardial infarction

Beta-adrenergic (BA) signaling including cAMP-protein kinase A (PKA) pathway has been implicated in the mechanism of ischemic preconditioning (IPC). However, effect of IPC on the failing heart, in which BA signaling is supposed to be altered, is left to be determined. To assess a role of BA signaling in IPC, levels of beta2-adrenergic receptor (B2AR) mRNA were quantified by real time RT-PCR, and in vivo intracardiac function was evaluated in post-MI heart. The effect of IPC on post-MI heart was then determined with an isolated heart perfusion system. Finally, cardioprotective effect of repetitive preischemic infusion of phosphodiesterase III inhibitor olprinone (30 M), which is known to increase myocardial cAMP levels, was evaluated with/without PKA inhibitor H-89 (2 M). B2AR mRNA levels in post-MI heart were significantly reduced compared to non-MI heart. IPC was not effective in post-MI heart. Repetitive preischemic infusion of olprinone increased peak developed pressure (94.6 ± 6.3 vs. 62.8 ± 4.9%, OLP vs. control, p < 0.05) and decreased infect size (15.2 ± 0.4 vs. 33.5 ± 2.5%, OLP vs. control, p < 0.01). These effects were abolished by H-89. These results may indicate that repetitive preischemic infusion of olprinone mimics IPC through cAMP-PKA pathway in post-MI heart, and that BA signaling plays a crucial role in IPC response.     

Isolation of individual egg cells and zygotes in Alstroemeria followed by manual selection with a microcapillary-connected micropump

AIMS: To develop a procedure for isolating living egg cells and zygotes from Alstroemeria ovules. SCOPE: An attempt was made to isolate egg cells and zygotes from the ovules of Alstroemeria aurea. The ovules were histologically observed using a clearing procedure which revealed the localization and sizes of the embryo sacs and egg apparatus within the ovules. For the isolation of egg cells, ovules were cut into sections with a surgical blade and treated with an enzyme solution. Subsequently, these ovule sections were dissected using a glass needle under an inverted microscope. Egg cells successfully isolated by this procedure were collected using microcapillaries connected to a micropump. For zygote isolation, ovules were excised from ovaries 24 h after self-pollination. By treating excised ovules with an enzyme solution and subsequently dissecting them using a glass needle, zygotes were successfully isolated from the ovules and collected with a microcapillary. The isolated zygotes were associated with pollen tubes and one of the synergids. Egg cells and zygotes were viable for up to 2 h following isolation, as determined by fluorescein diacetate staining. CONCLUSIONS: The procedures for isolating egg cells and zygotes in Alstroemeria were established, and each egg cell and zygote was captured with a microcapillary.     

Lymphatic microcirculation in frog lung

Lymphatic microvessels were microscopically observed on the surface of frog lungs. Magnified images of lymphatic microvessels were recorded on video tapes. The lymphatic microcirculation was studied on a TV monitor at the magnification of 1500 times. 1) valves were observed in lymphatic microvessels, whose diameter was 15 micron, in frog lungs, 2) the valves were incompetent, 3) contained particles repeatedly flowed backwards and forwards in each lymphatic section, 4) after repetition of the movements, particles passed through the outlet valve, 5) particles seldom flowed back through the inlet valve into the preceding section of the lymphatic, 6) the peak flow velocity of particles attained 0.5 mm/sec, and 7) the mean flow velocity was 11 +/- 4 micron on an average and +/- SD, 8) the diameter of a localized portion of the lymphatic microvessels changed periodically.