Complex grade III astrocytoma with granular cells and PXA features in a patient with tuberous sclerosis complex (Bourneville-Pringle syndrome) - case report and review of literature.

Tuberous sclerosis complex (Bourneville-Pringle syndrome) is a rare genetic condition included in the group of diseases called phakomatoses. Most of the patients are diagnosed with abnormalities within the central nervous system and tend to develop tumors more frequently, especially gliomas. We present a case of 50-year-old patient suffering from tuberous sclerosis complex, who had been diagnosed with pleomorphic xanthoastrocytoma (PXA). The patient underwent surgery and adjuvant radiotherapy and has remained free from local recurrence for 5 years.

Bilateral synchronous breast cancer developed as metachronous malignancy after therapy of other primaries.

OBJECTIVES: Cancer morbidity rates have been increasing steadily. A longer lifespan and easier access to modern diagnostic and therapeutic methods are the main reasons for the growing number of cancer survivors. Additionally, some types of oncological treatment, such as radiotherapy or immunosuppression, may also increase the risk of secondary tumors. These factors have resulted in an increased incidence of primary multiple cancers. Multiple primary cancers are generally under-stood as either synchronous, in which the cancers occur at the same time, or metachronous, in which the cancers follow in sequence (for instance, more than 2 months apart).The results published in other studies show that between 2% and 15.8% of all cancer patients have more primary multiple cancers. Within this group with multiple primary cancers, some have bilateral breast cancer, and our study focuses on patients from this group. MATERIAL AND METHODS: Our study describes 10 patients who were treated for bilateral synchronous breast cancer at the Cracow Branch of the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology during the years 1992-2014 and who developed another primary tumor after their treatment bilateral synchronous breast cancer. RESULTS: In our discussion we present detailed data on the incidence of metachronous cancers in the 10 patients, including breast cancer, following the treatment of their other primary tumors. CONCLUSION: The 10 cases of our study, and clinical experiences and publications in general show how important it is for patients to continue medical follow-up after treatment of primary tumors, not only to detect recurrences as early as pos-sible, but also to diagnose any other malignancies occurring in other sites, including secondary, treatment-related tumors.

Output-input ratio in thermally fluctuating biomolecular machines.

Biological molecular machines are proteins that operate under isothermal conditions and hence are referred to as free energy transducers. They can be formally considered as enzymes that simultaneously catalyze two chemical reactions: the free energy-donating (input) reaction and the free energy-accepting (output) one. Most if not all biologically active proteins display a slow stochastic dynamics of transitions between a variety of conformational substates composing their native state. This makes the description of the enzymatic reaction kinetics in terms of conventional rate constants insufficient. In the steady state, upon taking advantage of the assumption that each reaction proceeds through a single pair (the gate) of transition conformational substates of the enzyme-substrates complex, the degree of coupling between the output and the input reaction fluxes has been expressed in terms of the mean first-passage times on a conformational transition network between the distinguished substates. The theory is confronted with the results of random-walk simulations on the five-dimensional hypercube. The formal proof is given that, for single input and output gates, the output-input degree of coupling cannot exceed unity. As some experiments suggest such exceeding, looking for the conditions for increasing the degree of coupling value over unity challenges the theory. Performed simulations of random walks on several model networks involving more extended gates indicate that the case of the degree of coupling value higher than 1 is realized in a natural way on critical branching trees extended by long-range shortcuts. Such networks are scale-free and display the property of the small world. For short-range shortcuts, the networks are scale-free and fractal, representing a reasonable model for biomolecular machines displaying tight coupling, i.e., the degree of coupling equal exactly to unity. A hypothesis is stated that the protein conformational transition networks, as just as higher-level biological networks, the protein interaction network, and the metabolic network, have evolved in the process of self-organized criticality.

RaTrav: a tool for calculating mean first-passage times on biochemical networks.

BACKGROUND: The concept of mean first-passage times (MFPTs) occupies an important place in the theory of stochastic processes, with the methods of their calculation being equally important in theoretical physics, chemistry and biology. We present here a software tool designed to support computational biology studies where Markovian dynamics takes place and MFPTs between initial and single or multiple final states in network-like systems are used. Two methods are made available for which their efficiency is strongly dependent on the topology of the defined network: the combinatorial Hill technique and the Monte Carlo simulation method. RESULTS: After a brief introduction to RaTrav, we highlight the utility of MFPT calculations by providing two examples (accompanied by Additional file 1) where they are deemed to be of importance: analysis of a protein-protein docking funnel and interpretation of the free energy transduction between two coupled enzymatic reactions controlled by the dynamics of transition between enzyme conformational states. CONCLUSIONS: RaTrav is a versatile and easy to use software tool for calculating MFPTs across biochemical networks. The user simply prepares a text file with the structure of a given network, along with some additional basic parameters such as transition probabilities, waiting probabilities (if any) and local times (weights of edges), which define explicitly the stochastic dynamics on the network. The RaTrav tool can then be applied in order to compute desired MFPTs. For the provided examples, we were able to find the favourable binding path within a protein-protein docking funnel and to calculate the degree of coupling for two chemical reactions catalysed simultaneously by the same protein enzyme. However, the list of possible applications is much wider.

Temperature and detection-wavelength dependence of the electron transfer rates in initial stages of photosynthesis.

Unusual temperature behavior, observed in the initial electron transfer stages in the photosynthetic reaction centers of the purple bacteria, and a strong probing pulse wavelength dependence of transfer rates, determined in transient absorption spectroscopy, can easily be explained on assuming that the transfer takes place from dynamically unrelaxed states of protein environment. The transitions from the primary special pair (P) to a single bacteriochlorophyll (B) and next to a bacteriopheophytin (H) are controlled by diffusion down the energy value of underdamped vibrational modes of frequency 200 K, probably determining distances between the succeeding cofactors. The subsequent transition to the quinone A (Q) is controlled by diffusion in the position value of an overdamped conformational mode, probably corresponding to the local polarization. From the fit of available experimental data to simple theoretical formulas, the important physical conclusion arises that the very electronic transitions are fast as compared to the relaxation processes and, in the first approximation, only the latter contribute to the overall times of the initial electron transfer stages in photosynthesis.

Statistical properties of the dichotomous noise generated in biochemical processes.

Dichotomous noise detected with the help of various single-molecule techniques convincingly reveals the actual occurrence of a multitude of conformational substates composing the native state of proteins. The nature of the stochastic dynamics of transitions between these substates is determined by the particular statistical properties of the noise observed. These involve nonexponential and possibly oscillatory time decay of the second order autocorrelation function, its relation to the third order autocorrelation function, and a relationship to dwell-time distribution densities and their correlations. Processes gated by specific conformational substates are distinguished from those with fluctuating barriers. This study throws light on the intriguing matter of the possibility of multiple stepping of the myosin motor along the actin filament per ATP molecule hydrolyzed.

Underdamped vibrations control the primary electron transfer in photosynthesis at low temperatures.

Measurements performed with the help of ultrafast laser spectroscopy have clearly shown that the primary electron transfer in photosynthesis lasts no longer than a few picoseconds. Equally fast are processes of vibrational relaxation which have to be taken into account in the correct description of the phenomenon. Here, we consider a simple theory combining the electron transfer process with diffusion in the energy space of a chosen underdamped vibrational mode of protein environment. Analytical formulas for effective transition rate constants are derived, and a transient kinetics is considered. The quality of analytical approximations is verified by numerical simulations for various physical conditions. Efficient parallel computations have been applied. The model can explain a peculiar temperature dependence of pump-probe spectra observed.