The homogenous alternative to biomineralization: Zn- and Mn-rich materials enable sharp organismal "tools" that reduce force requirements.

We measured hardness, modulus of elasticity, and, for the first time, loss tangent, energy of fracture, abrasion resistance, and impact resistance of zinc- and manganese-enriched materials from fangs, stings and other "tools" of an ant, spider, scorpion and nereid worm. The mechanical properties of the Zn- and Mn-materials tended to cluster together between plain and biomineralized "tool" materials, with the hardness reaching, and most abrasion resistance values exceeding, those of calcified salmon teeth and crab claws. Atom probe tomography indicated that Zn was distributed homogeneously on a nanometer scale and likely bound as individual atoms to more than » of the protein residues in ant mandibular teeth. This homogeneity appears to enable sharper, more precisely sculpted "tools" than materials with biomineral inclusions do, and also eliminates interfaces with the inclusions that could be susceptible to fracture. Based on contact mechanics and simplified models, we hypothesize that, relative to plain materials, the higher elastic modulus, hardness and abrasion resistance minimize temporary or permanent tool blunting, resulting in a roughly 2/3 reduction in the force, energy, and muscle mass required to initiate puncture of stiff materials, and even greater force reductions when the cumulative effects of abrasion are considered. We suggest that the sharpness-related force reductions lead to significant energy savings, and can also enable organisms, especially smaller ones, to puncture, cut, and grasp objects that would not be accessible with plain or biomineralized "tools".

The role of parathyroid hormone and insulin-like growth factors in hematopoietic niches: physiology and pharmacology.

Hematopoietic stem cells (HSC) capable of both self-renewal and differentiation into all blood lineages reside within the bone marrow in specialized microenvironmental niches. While the precise location and composition of these niches largely remains unknown, it is now believed that osteoblasts at the endosteal surface play critical roles. Among the molecules demonstrated to influence the function of these niches are parathyroid hormone (PTH) and the insulin-like growth factors (IGF). Administration of PTH to both mice and men expands the number of bone marrow HSC, and an increase in the number of those cells in peripheral blood following treatment with mobilizing agents. Several molecules downstream of PTH are capable of signaling to HSC, including IGF that appear to regulate both the survival and expansion of hematopoietic stem and progenitor cells. As our current understanding of the role for PTH and IGF in hematopoietic niches is limited, we believe it is important that both their physiological importance and pharmacological potential be more fully investigated.

Hydrogel lens monomer constituents modulate protein sorption.

PURPOSE: To examine the effect of hydrogel lens monomer constituents on protein sorption. METHODS: A series of hydroxyethylmethacrylate (HEMA)-based hydrogels with various amounts of methacrylic acid (MAA) or N-vinyl pyrrolidone (NVP) were synthesized. A radiolabel tracer technique was used to measure the amount of protein adsorbed on or penetrating into the hydrogels. Penetration of fluorescence-labeled proteins in the hydrogels was studied by laser scanning confocal microscopy. Single-protein solutions of human serum albumin (HSA) and hen egg lysozyme were studied. RESULTS: Inclusion of the comonomers MAA or NVP in hydrogels resulted in an increase in water content and also had a strong impact on protein sorption. An increase in the amount of MAA in the poly(HEMA-co-MAA) hydrogels increased lysozyme adsorption and penetration but reduced HSA adsorption. However, the amount of protein adsorbed for both HSA and lysozyme increased with the amount of NVP in the poly(HEMA-co-NVP) hydrogels. In contrast to the marked effect of MAA on protein sorption, in particular, on lysozyme sorption, NVP had little influence on protein sorption. When a hydrogel contains both MAA and NVP, MAA has the dominant effect on protein sorption-in particular, on lysozyme sorption. Furthermore, a large difference was observed in the amount of lysozyme adsorbed on the hydrogels that had similar water contents but little variation in adsorption of HSA. CONCLUSIONS: Negatively charged carboxyl groups of the MAA constituent may influence lysozyme sorption in two ways: by electrostatic attraction and by increasing the possibility for the small lysozyme molecule to penetrate the hydrogels. Interactions of the surface lactam groups of NVP with proteins may be attributable to the attraction of proteins to NVP. Water content is not a primary factor in determining protein adsorption. It appears that the monomer constituents, such as MAA or NVP, control protein adsorption.

Lysozyme sorption in hydrogel contact lenses.

PURPOSE: To examine the processes involved in formation of protein deposits on hydrogel contact lenses. METHODS: The adsorption and/or penetration of lysozyme on or into three types of contact lenses, etafilcon A, vifilcon A, and tefilcon, were investigated in vitro using a radiolabel-tracer technique, x-ray photoelectron spectroscopy, and laser scanning confocal microscopy. RESULTS: Binding of lysozyme to high-water-content, ionic contact lenses (etafilcon A and vifilcon A) was dominated by a penetration process. The extent of this penetration was a function of charge density of the lenses, so that there was a higher degree of penetration of lysozyme in etafilcon A than in vifilcon A lenses. In contrast, the binding of lysozyme to tefilcon lenses was a surface adsorption process. The adsorption and desorption kinetics showed similar trends to those found in human serum albumin (HSA) adsorption on lens surfaces. However, the extent of lysozyme adsorption on tefilcon is much higher than HSA adsorption, probably because of the self-association of lysozyme on the tefilcon lens surface. Furthermore, either penetration or adsorption of lysozyme involved reversible and irreversible processes and were both time dependent. CONCLUSIONS: Binding of lysozyme to hydrogel lenses involves surface adsorption or matrix penetration. These processes may be reversible or irreversible. The properties of the lens materials, such as charge density (ionicity) and porosity (water content) of the lenses, determine the type and rates of these processes.

Irreversible adsorption of human serum albumin to hydrogel contact lenses: a study using electron spin resonance spectroscopy.

Human serum albumin (HSA) was specifically spin labelled with 4-maleimido-tempo (MSL) at its cysteine 34 residue (HSA-MSL). The irreversible adsorption of HSA-MSL to hydrogel contact lenses (etafilcon A, tefilcon and vifilcon A) was investigated using electron spin resonance (ESR) spectroscopy. Changes in ESR spectral characteristics of adsorbed HSA-MSL as compared to HSA-MSL in solution displayed an additional immobilisation of the spin label due to the adsorption. This immobilisation of MSL corresponds to a large conformational alteration of the HSA-MSL near the modified Cys 34 residue. For both etafilcon A and tefilcon, the rate of irreversible adsorption was relatively slow compared with that of vifilcon A where the maximum state of immobilisation and hence conformational change occurred within the first hour of adsorption. Furthermore, tefilcon produced markedly different ESR spectra where a strong conformational change to a less mobile protein was apparent. This supported a model where the direct irreversible adsorption of HSA from solution dominated on tefilcon as opposed to conversion of the adsorbed protein from the reversible to the irreversible state on both etafilcon A and vifilcon A. HSA-MSL adsorption onto hydrophobic poly(methylmethacrylate) (PMMA) and hydrophilic poly(N-ter-butylacrylamide) (PTBAM) latex beads was also investigated. The spin label MSL was found to be less mobile when HSA was adsorbed onto PMMA compared with PTBAM beads. It was also found that the rate of irreversible adsorption of HSA is far higher onto PMMA surfaces than onto PTBAM surfaces.

Borderline personality disorder.

The lives of patients with borderline personality disorder are characterized by turmoil, and their interpersonal relationships by conflict. As a result, these patients can be very difficult to treat. However, an accurate diagnosis and an understanding of the psychodynamics and emotional development of borderline patients can lead to improved management.