Recent progress in the molecular biology of the clonedN-acetylglucosaminyltransferases

Several genes which code for theN-acetylglucosaminyltransferases have been cloned and characterized. Physiological and pathophysiological roles of the genes still remain to be elucidated but accumulated evidence suggests that theN-acetylglucosaminyltransferase genes are implicated in differentiation, morphogenesis and cancer metastasis.     

Cloning and nucleotide sequence of a human Zn-alpha 2-glycoprotein cDNA and chromosomal assignment of its gene

A cDNA clone of Zn-alpha 2-glycoprotein (Zn alpha 2gp) was isolated from a human prostate library. The amino acid sequence of prostate Zn alpha 2gp deduced from the nucleotide sequence was identical to the one previously reported on the Zn alpha 2gp protein purified from human blood plasma, except at three positions: the 65th and 222nd amino acid residues were Gln (----Glu) and Glu (----Gln), and there was a two amino acid insertion (Ile-Phe) between the 75th (Glu) and 76th (Met) amino acids. Southern blot analysis of human genomic DNA, however, suggested a single gene encoding Zn alpha 2gp. Using a panel of rodent-human somatic cell hybrids, the Zn alpha 2 gp gene was assigned to human chromosome 7.     

Increased high‐latitude photosynthetic carbon gain offset by respiration carbon loss during an anomalous warm winter to spring transition

Arctic and boreal ecosystems play an important role in the global carbon (C) budget, and whether they act as a future net C sink or source depends on climate and environmental change. Here, we used complementary in situ measurements, model simulations, and satellite observations to investigate the net carbon dioxide (CO₂) seasonal cycle and its climatic and environmental controls across Alaska and northwestern Canada during the anomalously warm winter to spring conditions of 2015 and 2016 (relative to 2010–2014). In the warm spring, we found that photosynthesis was enhanced more than respiration, leading to greater CO₂ uptake. However, photosynthetic enhancement from spring warming was partially offset by greater ecosystem respiration during the preceding anomalously warm winter, resulting in nearly neutral effects on the annual net CO₂ balance. Eddy covariance CO₂ flux measurements showed that air temperature has a primary influence on net CO₂ exchange in winter and spring, while soil moisture has a primary control on net CO₂ exchange in the fall. The net CO₂ exchange was generally more moisture limited in the boreal region than in the Arctic tundra. Our analysis indicates complex seasonal interactions of underlying C cycle processes in response to changing climate and hydrology that may not manifest in changes in net annual CO₂ exchange. Therefore, a better understanding of the seasonal response of C cycle processes may provide important insights for predicting future carbon–climate feedbacks and their consequences on atmospheric CO₂ dynamics in the northern high latitudes.     

A Particle Model for Prediction of Cement Infiltration of Cancellous Bone in Osteoporotic Bone Augmentation

Femoroplasty is a potential preventive treatment for osteoporotic hip fractures. It involves augmenting mechanical properties of the femur by injecting Polymethylmethacrylate (PMMA) bone cement. To reduce the risks involved and maximize the outcome, however, the procedure needs to be carefully planned and executed. An important part of the planning system is predicting infiltration of cement into the porous medium of cancellous bone. We used the method of Smoothed Particle Hydrodynamics (SPH) to model the flow of PMMA inside porous media. We modified the standard formulation of SPH to incorporate the extreme viscosities associated with bone cement. Darcy creeping flow of fluids through isotropic porous media was simulated and the results were compared with those reported in the literature. Further validation involved injecting PMMA cement inside porous foam blocks — osteoporotic cancellous bone surrogates — and simulating the injections using our proposed SPH model. Millimeter accuracy was obtained in comparing the simulated and actual cement shapes. Also, strong correlations were found between the simulated and the experimental data of spreading distance (R² = 0.86) and normalized pressure (R² = 0.90). Results suggest that the proposed model is suitable for use in an osteoporotic femoral augmentation planning framework.     

Molecular dynamics simulation to investigate the impact of disulfide bond formation on conformational stability of chicken cystatin I66Q mutant

Chicken cystatin (cC) mutant I66Q is located in the hydrophobic core of the protein and increases the propensity for amyloid formation. Here, we demonstrate that under physiological conditions, the replacement of Ile with the Gln in the I66Q mutant increases the susceptibility for the disulfide bond Cys71–Cys81 to be reduced when compared to the wild type (WT) cC. Molecular dynamics (MD) simulations under conditions favoring cC amyloid fibril formation are in agreement with the experimental results. MD simulations were also performed to investigate the impact of disrupting the Cys71–Cys81 disulfide bond on the conformational stability of cC at the atomic level, and highlighted major disruption to the cC appendant structure. Domain swapping and extensive unfolding has been proposed as one of the possible mechanisms initiating amyloid fibril formation by cystatin. Our in silico studies suggest that disulfide bond formation between residues Cys95 and Cys115 is necessary to maintain conformational stability of the I66Q mutant following breakage of the Cys71–Cys81 disulfide bridge. Subsequent breakage of disulfide bond Cys95–Cys115 resulted in large structural destabilization of the I66Q mutant, which increased the α–β interface distance and expanded the hydrophobic core. These experimental and computational studies provide molecular-level insight into the relationship between disulfide bond formation and progressive unfolding of amyloidogenic cC mutant I66Q.

An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:23     

Bio-functional pickles that reduce blood pressure of rats

Addition of γ-aminobutyric acid (GABA) and angiotensin converting enzyme (ACE)-inhibitory peptides to the pickles was studied in order to develop a new type of pickles that reduce blood pressure. Based on the outcome of these studies, a new type of fermentation bed composed of rice bran and white miso has been successfully developed. The advantage of such pickles is that they not only contain both GABA and ACE-inhibitory peptides, but also that their taste and flavor are excellent, with colors close to the original ones. The new type of pickles could temporarily reduce blood pressure in two types of rats, spontaneously hypertensive rats and NaCl-sensitive model rats. Thus, the newly developed pickles appear to be beneficial for pickle business.     

A low trophic position of Japanese eel larvae indicates feeding on marine snow

What eel larvae feed on in the surface layer of the ocean has remained mysterious. Gut contents and bulk nitrogen stable isotope studies suggested that these unusual larvae, called leptocephali, feed at a low level in the oceanic food web, whereas other types of evidence have suggested that small zooplankton are eaten. In this study, we determined the nitrogen isotopic composition of amino acids of both natural larvae and laboratory-reared larvae of the Japanese eel to estimate the trophic position (TP) of leptocephali. We observed a mean TP of 2.4 for natural leptocephali, which is consistent with feeding on particulate organic matter (POM) such as marine snow and discarded appendicularian houses containing bacteria, protozoans and other biological materials. The nitrogen isotope enrichment values of the reared larvae confirm that the primary food source of natural larvae is consistent only with POM. This shows that leptocephali feed on readily available particulate material originating from various sources closely linked to ocean primary production and that leptocephali are a previously unrecognized part of oceanic POM cycling.