Cancer research,a field on the verge of a paradigm shift?

The theoretical framework for the field of cancer research is based on two main principles. The first is that cancer advances in a stepwise manner, with each alteration driving cells further toward a malignant state. Second, to cure cancer we must target only cancer-specific properties. Here, we analyze the birth and propagation of the cancer research paradigm. We believe the current paradigm is immersed in crisis and that the field would benefit from integrating theories within and outside the normal modes of research to compile a new framework, with the hope of faster progress and significantly fewer cancer-related deaths.     

Making a Mechanical Organism Being the fourth in a series of essays on the materials of nature

Most multicellular organisms can be categorised by two words： hierarchy and composite. The underlying fractal geometry of nature - at least in terms of provision of infrastructure - provides much of the hierarchy, although many materials for which infrastructure is not an integral factor are also strongly hierarchical. Plants can therefore be modelled using recursive computer programs which add structures as the size increases. However, problems with mechanical stability also increase as the structure grows, so the plant changes from deriving stiffness from intevaal pressure to cross-linking the cell wall components permanently. However, this compromises the ability of the plant to grow and repair itself.     

Notes on the zooplankton of a water body on the southern slope of Mt Babia Góra (the Carpathians)

The seepage of water on the Gubernasówka clearing in the forest (alt. about 850 m) was investigated from the point of view of the occurrence of the Paramecium aurelia species complex and other zooplanktonic organisms. Though, none of the species of the complex was found, another morphological species of the Paramecium genus, i.e. Paramecium caudatum was registered.     

Influence of the radial profile of the electric potential on the confinement of a high-β two-component plasma in a gas-dynamic trap

One of the most important problems to be studied in the gas-dynamic trap (GDT) facility is the investigation of MHD stability and cross-field transport in a plasma with a relatively high value of β = πp/B ². Recent experiments demonstrated that the radial electric field produced in the plasma by using radial limiters and coaxial end plasma collectors improves plasma stability in axisymmetric magnetic mirror systems without applying special MHD stabilizers. The experimental data presented in this work show that stable plasma confinement can be achieved by producing a radial potential drop across a narrow region near the plasma boundary. Creating radial electric fields of strength 15–40 V/cm causes a shear plasma flow, thereby substantially increasing the plasma confinement time. When all the radial electrodes were grounded, the confinement was unstable and the plasma confinement time was much shorter than the characteristic time of plasma outflow through the magnetic mirrors. Measurements of cross-field plasma fluxes with the use of a specially designed combined probe show that, in confinement modes with differential plasma rotation, transverse particle losses are negligibly small as compared to longitudinal ones and thus can be ignored. It is also shown that, when the GDT plasma is in electric contact with the radial limiters and end collectors, the growth rate of interchange instability decreases considerably; such a contact, however, does not ensure complete MHD stability when the electrodes are at the same potential.     

Hamsters running on time: is the lateral habenula a part of the clock?

Previous anatomical and physiological studies have implicated the lateral habenula, and especially its medial division (LHbM), as a candidate component of the circadian timing system in rodents. We assayed lateral habenula rhythmicity in rodents using c-FOS immunohistochemistry and found a robust rhythm in immunoreactive cell counts in the LHbM, with higher counts during the dark phase of a light-dark (LD) cycle and during subjective night in constant darkness. We have also observed an obvious asymmetry of c-FOS expression in the LHbM of behaviorally "split" hamsters in constant light, but only during their active phase (when they were running in wheels). Locomotor activity rhythms appear to be regulated by the suprachiasmatic nucleus (SCN) via multiple output pathways, one of which might be diffusible while the other might be neural, involving the lateral habenula.     

Understanding the Impacts of Land-Use Policies on a Threatened Species: Is There a Future for the Bornean Orang-utan?

The geographic distribution of Bornean orang-utans and its overlap with existing land-use categories (protected areas, logging and plantation concessions) is a necessary foundation to prioritize conservation planning. Based on an extensive orang-utan survey dataset and a number of environmental variables, we modelled an orang-utan distribution map. The modelled orang-utan distribution map covers 155,106 km² (21% of Borneo''s landmass) and reveals four distinct distribution areas. The most important environmental predictors are annual rainfall and land cover. The overlap of the orang-utan distribution with land-use categories reveals that only 22% of the distribution lies in protected areas, but that 29% lies in natural forest concessions. A further 19% and 6% occurs in largely undeveloped oil palm and tree plantation concessions, respectively. The remaining 24% of the orang-utan distribution range occurs outside of protected areas and outside of concessions. An estimated 49% of the orang-utan distribution will be lost if all forest outside of protected areas and logging concessions is lost. To avoid this potential decline plantation development in orang-utan habitats must be halted because it infringes on national laws of species protection. Further growth of the plantation sector should be achieved through increasing yields in existing plantations and expansion of new plantations into areas that have already been deforested. To reach this goal a large scale island-wide land-use masterplan is needed that clarifies which possible land uses and managements are allowed in the landscape and provides new standardized strategic conservation policies. Such a process should make much better use of non-market values of ecosystem services of forests such as water provision, flood control, carbon sequestration, and sources of livelihood for rural communities. Presently land use planning is more driven by vested interests and direct and immediate economic gains, rather than by approaches that take into consideration social equity and environmental sustainability.     

Studies on the extracellular p-nitrophenyl β-d-cellobiosidase activity of a thermophilic streptomycete

Summary The activity of ten actinomycete strains against p-nitrophenyl -d-cellobioside (pNPC) was investigated. Intra- and extracellular activities were detected in all strains, although activities were found to vary between strains. Extracellular pNPC activity, detected in the thermophilic Streptomycete EC22 was six times greater than that of the next best strain. Culture supernatant studies on Streptomyces strain EC22 revealed that pNPC activity was optimal at 65° C and between pH 6.0 and pH 8.0, although this temperature value represented a compromise between increased reaction rate and thermal denaturation. At 65° C, the half-life of activity against pNPC was 150 min. The K _m value of pNPC activity was found to be 3.33 mm. Enzyme activity was subject to competitive inhibition by both glucose and cellobiose with substrate inhibition constant (K _i) values of 2.2 mm and 1.4 mm respectively. Fast protein liquid chromatograph (FPLC) of culture supernatants from EC22 using anion exchange chromatography revealed the presence of two proteins with pNPC activity. This result was confirmed using gel-filtration chromatography which estimated the molecular mass of the two proteins to be approximately 48 and 33 kDa, with the specific activity of the 48 kDa enzyme being eight times greater than that of the 33 kDa protein. Offprint requests to: A. S. Ball     

Assessing the radiological load on the environment in the middle Danube river basin on the basis of a study of the Kopački Rit Nature Park,Croatia

A study of the environmental radioactivity in the Kopa?ki Rit Nature Park, Croatia, is presented. This wildlife reserve is part of the Middle Danube River Basin, and it is exposed to various pollutants due to a number of human activities in the surroundings, where there is a nuclear power plant and also urban centres and areas of intense agricultural production. Results for the activity concentrations of soil and surface water samples do not indicate any elevated radioactivity level, which is confirmed by on-site measurements of ambient dose rate equivalent. An assessment of the radiological load on the local biota, carried out using the ERICA tool, implies an overall low radiological risk even if conservative values of the risk quotient are used. Therefore, human activities do not have a significant effect on the radiological load on the Kopa?ki Rit area. A similar conclusion might be made with regard to numerous similar environments in the Middle Danube River Basin.     

Is the Effect of Aerobic Exercise on Cognition a Placebo Effect?

A number of studies and meta-analyses conclude that aerobic fitness (walking) interventions improve cognition. Such interventions typically compare improvements from these interventions to an active control group in which participants engage in non-aerobic activities (typically stretching and toning) for an equivalent amount of time. However, in the absence of a double-blind design, the presence of an active control group does not necessarily control for placebo effects; participants might expect different amounts of improvement for the treatment and control interventions [1]. We conducted a large survey to explore whether people expect greater cognitive benefits from an aerobic exercise intervention compared to a control intervention. If participants expect greater improvement following aerobic exercise, then the benefits of such interventions might be due in part to a placebo effect. In general, expectations did not differ between aerobic and non-aerobic interventions. If anything, some of the results suggest the opposite (e.g., respondents expected the control, non-aerobic intervention to yield bigger memory gains). These results provide the first evidence that cognitive improvements following aerobic fitness training are not due to differential expectations.     

Effect of heterochiral inversions on the structure of a β-hairpin peptide

We study computationally a family of β-hairpin peptides with systematically introduced chiral inversions, in explicit water, and we investigate the extent to which the backbone structure is able to fold in the presence of heterochiral perturbations. In contrast to the recently investigated case of a helical peptide, we do not find a monotonic change in secondary structure content as a function of the number of L- to D-inversions. The effects of L- to D-inversions are instead found to be highly position-specific. Additionally, in contrast to the helical peptide, some inversions increase the stability of the folded peptide: in such cases, we compute an increase in β-sheet content in the aqueous solution equilibrium ensemble. However, the tertiary structures of the stable (folded) configurations for peptides for which inversions cause an increase in β-sheet content show differences from one another, as well as from the native fold of the nonchirally perturbed β-hairpin. Our results suggest that although some chiral perturbations can increase folding stability, chirally perturbed proteins may still underperform functionally, given the relationship between structure and function.     

Current knowledge and phytosociological data on the high-altitude vegetation in the Western Carpathians — a review

Presented survey summarizes the results of the studies published predominantly after 2000, dealing with the plant communities around and above the timberline in (montane) subalpine to alpine (subnival) belt of the Western Carpathians. All of these communities underwent a critical syntaxonomical and nomenclatorical revision, hence the demonstrated overview of high-mountain vegetation of Western Carpathians (mostly from Slovakia, less from Poland border areas) represent the current state of knowledge. The high-altitude vegetation database, which is the part of Slovak National Vegetation Database, SNVD (), incorporated 8,160 published relevés on 15 May 2007 (of the total of 30,469 published relevés in the SNVD). Concerning the unpublished relevés, the individual authors have provided more than 18,400 of them to be stored in SNVD; 2,301 of all unpublished relevés could be assigned to high-altitude vegetation. Mountain and alpine vegetation is in SNVD presented by 15 classes; the most frequent class is Mulgedio-Aconitetea. With its quantity and also the quality of relevés, the high-altitude database, as well as the whole SNVD, represents the unique database within Slovakia, which provides information not only about the locality, floristic composition and variability of individual vegetation types, but also about several environmental variables such as inclination, aspect, geology or soil type, characteristic for individual relevés. Together with other Central European databases, SNVD takes up the leading position in Europe.     

Is the Iron Gate I reservoir on the Danube River a sink for dissolved silica?

Damming rivers changes sediment and nutrient cycles downstream of a dam in many direct and indirect ways. The Iron Gates I reservoir on the Yugoslavian-Romanian border is the largest impoundment by volume on the Danube River holding 3.2billionm³ of water. Silica retention within the reservoir in the form of diatom frustules was postulated to be as high as 600ktyear^–1 in previous studies using indirect methods. This amount of dissolved silicate was not delivered to the coastal Black Sea, and presumably caused a shift in the phytoplankton community there, and subsequent drastic decline in fishery. We directly quantified the amount of dissolved silicate (DSi) entering and leaving the reservoir for 11 continuous months. The budget based on these data reveals two important facts: (1) only about 4% of incoming DSi was retained in the reservoir; (2) the DSi concentrations were relatively low in the rivers upstream of the reservoir compared to regional and global averages. Thus damming the Danube at the Iron Gates could not have caused the decline in DSi concentrations documented downstream of the impoundment. Rather, this change in DSi must have occurred in the headwaters of the Danube River. Potential reasons include the construction of many dams upstream of the Iron Gates, hydrologic changes resulting in lower groundwater levels, and clogging of the riverbed limiting groundwater–river exchange.     

The influence of spin-labeled fluorene compounds on the assembly and toxicity of the aβ peptide

Background

The deposition and oligomerization of amyloid β (Aβ) peptide plays a key role in the pathogenesis of Alzheimer''s disease (AD). Aβ peptide arises from cleavage of the membrane-associated domain of the amyloid precursor protein (APP) by β and γ secretases. Several lines of evidence point to the soluble Aβ oligomer (AβO) as the primary neurotoxic species in the etiology of AD. Recently, we have demonstrated that a class of fluorene molecules specifically disrupts the AβO species.

Methodology/Principal Findings

To achieve a better understanding of the mechanism of action of this disruptive ability, we extend the application of electron paramagnetic resonance (EPR) spectroscopy of site-directed spin labels in the Aβ peptide to investigate the binding and influence of fluorene compounds on AβO structure and dynamics. In addition, we have synthesized a spin-labeled fluorene (SLF) containing a pyrroline nitroxide group that provides both increased cell protection against AβO toxicity and a route to directly observe the binding of the fluorene to the AβO assembly. We also evaluate the ability of fluorenes to target multiple pathological processes involved in the neurodegenerative cascade, such as their ability to block AβO toxicity, scavenge free radicals and diminish the formation of intracellular AβO species.

Conclusions

Fluorene modified with pyrroline nitroxide may be especially useful in counteracting Aβ peptide toxicity, because they posses both antioxidant properties and the ability to disrupt AβO species.     

From the first to the second domain of gelsolin: a common path on the surface of actin?

We present the 2.6 A resolution crystal structure of a complex formed between G-actin and gelsolin fragment Met25-Gln160 (G1+). The structure differs from those of other gelsolin domain 1 (G1) complexes in that an additional six amino acid residues from the crucial linker region into gelsolin domain 2 (G2) are visible and are attached securely to the surface of actin. The linker segment extends away from G1 up the face of actin in a direction that infers G2 will bind along the same long-pitch helical strand as the actin bound to G1. This is consistent with a mechanism whereby G2 attaches gelsolin to the side of a filament and then directs G1 toward a position where it would disrupt actin-actin contacts. Alignment of the sequence of the structurally important residues within the G1-G2 linker with those of WH2 (WASp homology domain 2) domain protein family members (e.g. WASp (Wiscott-Aldridge syndrome protein) and thymosin beta4) suggests that the opposing activities of filament assembly and disassembly may exploit a common patch on the surface of actin.