Asymptotic behavior of nonlinear semigroup describing a model of selective cell growth regulation

A new scheme of regulation of cell population growth is considered, called the selective growth regulation. The principle is that cells are withdrawn from proliferation depending on their contents of certain biochemical species. The dynamics of the cell population structured by the contents of this species is described by the functional integral equation model, previously introduced by the authors. The solutions of the model equations generate a semigroup of nonlinear positive operators. The main problem solved in this paper concerns stability of the equilibria of the model. This requires stating and proving of an original abstract result on the spectral radius of a perturbation of a semigroup of positive linear operators. Biological applications are discussed.     

Size of Unfolded and Dissociated Subunits versus that of Native Multimeric Proteins

Two factors, unfolding and dissociation, act in opposition indetermining the size of the unfolded state of multimeric proteins. Ananalysis has been presented to correlate relative expansion of the unfoldedmonomers in absence of disulfide bridges over the native state of differenthomomultimeric proteins of varying molecular weights. The Stoke's radii ofabout 70 proteins of Mw between 6 kDa to 4000 kDa and ranging frommonomers to dodecamers were calculated both under native anddenatured condition induced by 8 M urea or 6 M guanidinium,HClaccording to relations derived by Uversky [Biochemistry 32 (1993), 13288–13298]. Stoke's radii of monomeric proteins were foundto increase by 1.6–2.2 times after denaturation as compared with the nativestate while that of the subunits of dimeric and tetrameric proteins wereincreased by factors 1.1–2.2 under the same conditions. For hexamericproteins this factor lies between 0.96–1.2. In each set the relativeincrement of the Stoke's radii followed a logarithmic relation with molecularweight and reached a minimum limiting value when Stoke's radii of nativeprotein became almost equal to that of the unfolded monomer.     

Why are small homeotherms born naked? Insulation and the critical radius concept

1. 1. For cylinders or spheres smaller than a critical size, a layer of insulation may increase, rather than decrease, the rate of heat exchange.

2. 2. It has been suggested that the critical size for animals insulated with fur or feathers is about 4–7 g body mass, and therefore may explain why many small mammals and birds are born naked. We suggest that this is unlikely.

3. 3. We found that downy feathers on hatchlings as small as 1.6 g body mass retard rates of heat loss. Also, hatchling birds smaller than 4–7 g are not always, or even often, born naked.

4. 4. If a critical size exists at all, it is likely to occur at body masses of 0.6 g or smaller.

Relative importance of tree genetics and microhabitat on macrofungal biodiversity on coarse woody debris

Understanding the contribution of genetic variation within foundation species to community-level pattern and diversity represents the cornerstone of the developing field of community genetics. We assessed the relative importance of intraspecific genetic variation, spatial variation within a forest and microhabitat variation on a macrofungal decay community developing on logs of the Australian forest tree, Eucalyptus globulus. Uniform logs were harvested from trees from eight geographic races of E. globulus growing in a 15-year-old genetic trial. Logs were placed as designed grids within a native E. globulus forest and after 3 years of natural colonisation the presence of 62 macrofungal taxa were recorded from eight microhabitats on each log. The key factor found to drive macrofungal distribution and biodiversity on structurally uniform coarse woody debris was log-microhabitat, explaining 42% of the total variation in richness. Differences between log-microhabitats appeared to be due to variation in aspect, substrate (bark vs wood) and area/time of exposure to colonisation. This findings demonstrates the importance of considering fine-scale (within substrate) variation in the conservation and management of macrofungal biodiversity, an area that has received little previous attention. While a number of recent studies have demonstrated that the genetics of foundation tree species can influence dependent communities, this was not found to be the case for the early log decay community associated with E. globulus. Despite genetic variation in wood and bark properties existing within this species, there was no significant effect of tree genetics on macrofungal community richness or composition. This finding highlights the variation that may exist among guilds of organisms in their response to genetic variation within foundation species, an important consideration in a promising new area of research.     

Norm statement considered harmful: comment on ‘evolution of unconditional dispersal in periodic environments’

The mathematical symbol for the norm, which is heavily overloaded with multiple definitions that have both universal and specific properties, lends itself to confusion. This is manifest in the proof of an important theorem for population dynamics by Schreiber and Li on how dispersal increases population growth in a periodic environment. Here the theorem is placed in context, the proof is clarified, and the confusing but inconsequential errors corrected.     

Early developability screen of therapeutic antibody candidates using Taylor dispersion analysis and UV area imaging detection

Therapeutic antibodies represent one of the fastest growing segments in the pharmaceutical market. They are used in a broad range of disease fields, such as autoimmune diseases, cancer, inflammation and infectious diseases. The growth of the segment has necessitated development of new analytical platforms for faster and better antibody selection and characterization. Early quality control and risk assessment of biophysical parameters help prevent failure in later stages of antibody development, and thus can reduce costs and save time. Critical parameters such as aggregation, conformational stability, colloidal stability and hydrophilicity, are measured during the early phase of antibody generation and guide the selection process of the best lead candidates in terms of technical developability. We report on the use of a novel instrument (ActiPix/Viscosizer) for measuring both the hydrodynamic radius and the absolute viscosity of antibodies based on Taylor dispersion analysis and UV area imaging. The looped microcapillary-based method combines low sample consumption, fast throughput and high precision compared to other conventional methods. From a random panel of 130 antibodies in the early selection process, we identified some with large hydrodynamic radius outside the normal distribution and others with non-Gaussian Taylor dispersion profiles. The antibodies with such abnormal properties were confirmed later in the selection process to show poor developability profiles. Moreover, combining these results with those of the viscosity measurements at high antibody concentrations allows screening, with limited amounts of materials, candidates with potential issues in pre-formulation development.     

Size determination of multienzyme complexes using two-dimensional agarose gel electrophoresis

In studies of the size and structure of multienzyme complexes, a procedure complementary to electron microscopy for determining the molecular dimensions of hydrated multisubunit complexes is needed. For some applications this procedure must be capable of detecting aggregation of complexes and must be applicable to impure preparations. In the present study, a procedure of two-dimensional agarose gel electrophoresis (2d-AGE) (Serwer, P. et al. Anal. Biochem. 152:339-345, 1986) was modified and employed to provide accurate size measurements of several classical multienzyme complexes. To improve band clarity and to achieve required gel pore sizes, a hydroxyethylated agarose was used. The effective pore's radius (PE) as a function of gel concentration was determined for this agarose in the range of PE values needed for multienzyme complexes (effective radius, R = 10-30 nm). Appropriate conditions were established to measure R values +/- 1% of the pyruvate (PDC), alpha-ketoglutarate (alpha-KGDC), and the branched chain alpha-keto acid (BCDC) dehydrogenase multienzyme complexes; the accuracy of R was limited by the accuracy of the determinations of the R value for the size standards. The PDC from bovine heart was found to have an R = 22.4 +/- 0.2 nm following cross-linking with glutaraldehyde that was necessary for stabilization of the complex. Dimers and trimers of PDC, present in the preparations used, were separated from monomeric PDC during 2d-AGE.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bone grafts,bone substitutes and orthobiologics: The bridge between basic science and clinical advancements in fracture healing

The biology of fracture healing is better understood than ever before, with advancements such as the locking screw leading to more predictable and less eventful osseous healing. However, at times one’s intrinsic biological response, and even concurrent surgical stabilization, is inadequate. In hopes of facilitating osseous union, bone grafts, bone substitutes and orthobiologics are being relied on more than ever before. The osteoinductive, osteoconductive and osteogenic properties of these substrates have been elucidated in the basic science literature and validated in clinical orthopaedic practice. Furthermore, an industry built around these items is more successful and in demand than ever before. This review provides a comprehensive overview of the basic science, clinical utility and economics of bone grafts, bone substitutes and orthobiologics.     

Penta- and hexa-coordinate ferric hemoglobins display distinct pH titration profiles measured by Soret peak shifts

Hemoglobins with diverse characteristics have been identified in all kingdoms of life. Their ubiquitous presence indicates that these proteins play important roles in physiology, though function for all hemoglobins are not yet established with certainty. Their physiological role may depend on their ability to bind ligands, which in turn is dictated by their heme chemistry. However, we have an incomplete understanding of the mechanism of ligand binding for these newly discovered hemoglobins and the measurement of their kinetic parameters depend on their coordination at the heme iron. To gain insights into their functional role, it is important to categorize the new hemoglobins into either penta- or hexa-coordinated varieties. We demonstrate that simple pH titration and absorbance measurements can determine the coordination state of heme iron atom in ferric hemoglobins, thus providing unambiguous information about the classification of new globins. This method is rapid, sensitive and requires low concentration of protein. Penta- and hexa-coordinate hemoglobins displayed distinct pH titration profiles as observed in a variety of hemoglobins. The pentacoordinate distal histidine mutant proteins of hexacoordinate hemoglobins and ligand-bound hexacoordinate forms of pentacoordinate hemoglobins reverse the pH titration profiles, thus validating the sensitivity of this spectroscopic technique.