A near-infrared method for studying hydration changes in aqueous solution: Illustration with protease reactions and protein denaturation

Proteins undergoing protease reactions, heat denaturation, or interactions with sodium dodecyl sulfate (SDS) were used to demonstrate the effectiveness of a near-infrared method for the quantitative study of changes in hydration or water binding during such processes. The spectra of different proteins showed that the liberation of $\text{COO}{}^{\mathrm{?}}\text{and NH}{}_3{}^{\mathrm{+}}$ groups during a protease reaction is associated with a large increase in hydration and excluded volume. On the basis of experiments with model compounds, other spectral changes, including development of continuum absorbance between 1.55 and 1.85 μm and a band with a peak near 2.1 μm, were also attributed to the liberation of these groups. After heat denaturation or in the presence of SDS, the rate of proteolytic hydrolysis was markedly increased, consistent with the view that some preliminary denaturation is necessary for protease activity. The validity of the hydration changes calculated for protease reactions was supported by model studies with l-lysine, and with poly-l-lysine before and after hydrolysis. The near-infrared spectrum of the protein substrate with no added protease was largely unaffected by heat treatment alone, indicating that the hydration as such was not changed to a large extent by the structural modifications of denaturation. In contrast to the protease reaction, the interactions between SDS and the proteins resulted in a decrease in hydration. Results of this paper are compared with those obtained from other methods. Some unique advantages of the near-infrared method for the study of hydration changes during reactions in aqueous solution are described.     

Mitotic drug targets

Mitosis is the key event of the cell cycle during which the sister chromatids are segregated onto two daughter cells. It is well established that abrogation of the normal mitotic progression is a highly efficient concept for anti‐cancer treatment. In fact, various drugs that target microtubules and thus interfere with the function of the mitotic spindle are in clinical use for the treatment of various human malignancies for many years. However, since microtubule inhibitors not only target proliferating cells severe side effects limit their use. Therefore, the identification of novel mitotic drug targets other than microtubules have gained recently much attention. This review will summarize the latest developments on the identification and clinical evaluation of novel mitotic drug targets and will introduce novel concepts for chemotherapy that are based on recent progress in our understanding how mitotic progression is regulated and how anti‐mitotic drugs induce tumor cell death. J. Cell. Biochem. 111: 258–265, 2010. © 2010 Wiley‐Liss, Inc.     

SEX-RATIO BIAS WITH ASYMMETRIC EXCHANGE OF POLLEN BETWEEN DEMES

In a patch of hermaphroditic plants, with a low level of pollen migration between patches, a prevailing wind creates a gradient, within the patch, in the strength of local competition among pollen for reproductive success. This leads to a sex ratio gradient, with a male (pollen) bias in downwind individuals, which can be quite strong even for large patches. The effect can be understood as follows: downwind individuals have relatively low reproductive value and respond by putting more resources into the gamete (pollen) with the best long-range (extra-patch) reproductive success.     

Uncoupling of mitochondrial oxidative phosphorylation by thallium.

The mechanism of integration of λ$\text{bio}$ll, which is deleted of all the known λ recombination genes, was studied using $\text{bio}$ deleted hosts as recipients. The presence of $\text{rec}$BC DNase and $\text{exo}$I in the recipient cells affected the fate of λ$\text{bio}$ll DNA. In nine of ten $\text{imm}\text{λ}{}^{\mathrm{+}}$ transductants, insertion of the λ$\text{bio}$ll genome took place somewhere between J and N and the remaining one had abnormally permuted prophage λ. In this lysogen (#42), the sequence of prophage genes was similar to that of vegetative phage λ. The properties of lysogen #42 were compared with those of other lysogens.     

Seasonal pattern of filial cannibalism by Apogon doederleini mouthbrooding males

In temperate waters of southern Japan, mouthbrooding males of the cardinal fish Apogon doederleini sometimes ate their entire brood within a day of spawning. In spite of annual variation in age structure and length of the breeding season, however, the annual cannibalism rate (broods cannibalized to total broods spawned) was nearly constant, 12–16%. Fish 1 year old frequently cannibalized early broods of the season, especially the first brood, whereas the cannibalism rate by 2 year-old fish did not vary within the season. In contrast, the cannibalism by older males increased late in the season. This tendency was attributed to their different allocation patterns to growth and reproduction. For 1 year-old fish, which can enhance future reproductive success by growth and cannibalizing on early broods instead of mouthbrooding (at relatively low temperatures), this may be a tactic for investing energy in growth. For fish 3 years, which have more breeding cycles and grow little, cannibalizing late broods may be energetic compensation for their poor somatic condition. No seasonal variation of cannibalism by 2 year-old fish can be explained by their intermediate nature of growth and reproduction. Multiple mate availability is one factor facilitating the cannibalism by 2 and 3 + year-old fish whose operational sex ratio is female-biased.     

Assessment of Optimal Selected Prognostic Factors

The identification and assessment of prognostic factors is one of the major tasks in clinical research. The assessment of one single prognostic factor can be done by recently established methods for using optimal cutpoints. Here, we suggest a method to consider an optimal selected prognostic factor from a set of prognostic factors of interest. This can be viewed as a variable selection method and is the underlying decision problem at each node of various tree building algorithms. We propose to use maximally selected statistics where the selection is defined over the set of prognostic factors and over all cutpoints in each prognostic factor. We demonstrate that it is feasible to compute the approximate null distribution. We illustrate the new variable selection test with data of the German Breast Cancer Study Group and of a small study on patients with diffuse large B‐cell lymphoma. Using the null distribution for a p‐value adjusted regression trees algorithm, we adjust for the number of variables analysed at each node as well. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Conditional and Unconditional Simulation of Healthy Patients' Visual Fields

This paper describes a simulation problem, motivated by the study of glaucoma, a very serious and widespread ocular illness. To ascertain whether a patient suffers from glaucoma, a perimetric test is done, but the evolution of the disease is very slow, and large longitudinal sets of tests taken on the same patient are needed to study its evolution, to analyze the efficiency of existing methods to detect the progression of glaucoma and to develop new ones. Simulation can be a very useful procedure to get appropriate data sets to work with. Our aim in this work is to simulate several VFs in a healthy patient to reflect his evolution in time. We use a spatio‐temporal model to simulate from, taking into account the correlation existing between the observed (or simulated) values in space and time. Two different simulation procedures (unconditional and conditional) are studied, and applied to obtain the simulations we are interested in. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)