Worrying Ourselves Sick: Biological, Psychological, and Social Components to Stress-Related Disease

This thesis has three main objectives: first, the author explains the physiological mechanisms behind the inborn stress response, setting the stage for a discussion about the diverse ways in which excessive stress physically undermines long-term health, and primarily focuses upon its effects on the cardiovascular, endocrine, immune, nervous, and digestive systems. In the next section, the author considers why people with a lower socioeconomic status (SES) are more likely to suffer from the undesirable consequences of chronic stress. Finally, it argues that being stressed out is not an inescapable part of life. Whereas coping mechanisms such as predictability, controllability, the presence of outlets, and social support have un-ignorable caveats, human internal perception of the world can help manage stress most effectively

Osteochondral defects : present situation and tissue engineering approaches

Articular cartilage is often damaged due to trauma or degenerative diseases, resulting in severe pain and disability. Most clinical approaches have been shown to have limited capacity to treat cartilage lesions. Tissue engineering (TE) has been proposed as an alternative strategy to repair cartilage. Cartilage defects often penetrate to the subchondral bone, or full-thickness defects are also produced in some therapeutic procedures. Therefore, in TE strategies one should also consider the need for a simultaneous regeneration of both cartilage and subchondral bone in situations where osteochondral defects are present, or to provide an enhanced support for the cartilage hybrid construct. In this review, different concepts related to TE in osteochondral regeneration will be discussed. The focus is on the need to produce new biphasic scaffolds that will provide differentiated and adequate conditions for guiding the growth of the two tissues, satisfying their different biological and functional requirements

Facebook, stress, and incidence of upper respiratory infection in undergraduate college students

Having a large social network is generally beneficial to health. However, it is unclear how Internet-based social networks might influence health. Chronic stress can have negative health consequences, and some data suggest that Facebook could be a new source of psychological stress. Thus, we examined undergraduate college student perceptions of Facebook use and incidence of upper respiratory infections (URIs). We hypothesized that subjects with more diverse networks (i.e., more friends on Facebook) would have fewer URIs than their less diverse counterparts; that subjects reporting Facebook-induced stress would be more susceptible to URIs; and that subjects with more diverse networks who report Facebook-induced stress would be less susceptible to URIs than subjects with less diverse social networks who reported Facebook-induced stress. In this prospective study, healthy college students completed online questionnaires that assessed use and perceptions of Facebook and technology, and then were interviewed weekly for 10 weeks to track incidence of URI. URI episodes were defined by a symptom-based criterion. The social network size was significantly related to the rate of URI, such that, the larger the social network, the greater the incidence rate of URI. Most (85.7 percent) respondents experienced some degree of Facebook-induced stress. The effects of Facebook-induced stress on incidence of URI varied across the social network size, such that, the impact of stress on the URI incidence rate increased with the size of the social network. These results are largely in contrast to our hypotheses, but clearly suggest an association between Facebook use, psychological stress, and health. © Copyright 2012, Mary Ann Liebert, Inc. 2012

Metal ion coordination in the E. coli Nudix hydrolase dihydroneopterin triphosphate pyrophosphatase: New clues into catalytic mechanism.

Dihydroneopterin triphosphate pyrophosphatase (DHNTPase), a member of the Mg2+ dependent Nudix hydrolase superfamily, is the recently-discovered enzyme that functions in the second step of the pterin branch of the folate biosynthetic pathway in E. coli. DHNTPase is of interest because inhibition of enzymes in bacterial folate biosynthetic pathways is a strategy for antibiotic development. We determined crystal structures of DHNTPase with and without activating, Mg2+-mimicking metals Co2+ and Ni2+. Four metal ions, identified by anomalous scattering, and stoichiometrically confirmed in solution by isothermal titration calorimetry, are held in place by Glu56 and Glu60 within the Nudix sequence motif, Glu117, waters, and a sulfate ion, of which the latter is further stabilized by a salt bridge with Lys7. In silico docking of the DHNTP substrate reveals a binding mode in which the pterin ring moiety is nestled in a largely hydrophobic pocket, the β-phosphate activated for nucleophilic attack overlays with the crystallographic sulfate and is in line with an activated water molecule, and remaining phosphate groups are stabilized by all four identified metal ions. The structures and binding data provide new details regarding DHNTPase metal requirements, mechanism, and suggest a strategy for efficient inhibition

Thermodynamic parameters for metals binding to DHNTPase.

<p>Thermodynamic parameters for metals binding to DHNTPase.</p

Data collection and refinement statistics.

<p>Data collection and refinement statistics.</p

DHNTPase metal cluster.

<p>(a) Left: Final 2Fo-Fc electron density map (blue) for Co-bound DHNTPase contoured at 1 sigma superimposed with Fo-Fc map (green) contoured at 3 σ (generated by using only the final polypeptide chain) and an anomalous Fourier map (yellow) contoured at 5 σ. Right: Fo-Fc and anomalous maps only. (b) Superposition of Ni-bound DHNTPase (magenta) and Co-bound DHNTPase (cyan) zoomed into the metal binding site. Dashed lines are selected interactions ≤2.5 Å from protein, sulfate, and/or metal. (c) Chemdraw representation of all ~2.5 Å interactions observed crystallographically in the Co²⁺-bound structure. Numbered metals are referenced in text. W = water. (d) Superposition of DHNTPase solved previously with PPi (orange stick) and Na⁺ (purple ball) from PDB code 2O5W chain A (pale yellow cartoon) and Co-bound DHNTPase (cyan) zoomed into metal centers. (e) Left: Superposition of Ap4A (light green) and Co-bound DHNTPase (cyan) zoomed into metal centers. Both structures contain four metals and a bound sulfate or phosphate. Middle: Comparison of metal binding region of RppH (orange) and Co-bound DHNTPase. RppH was crystallized with three metals overlapping with M1-3 in our structure; the DHNTPase sulfate overlays well with the pyrophosphate leaving group of the cocrystallized substrate analog in RppH. Right: Superposition of all three structures highlighting key coordinating residues to metal and substrate. All three structures have a modeled solvent molecule in line with a putative catalytic base. A unique feature of DHNTPase in this region is involvement of Lys7 at the N-terminus.</p

Biochemical characterization of metal binding to DHNTPase.

<p>(a) Enzyme assays with varying metals (left) and dose dependence with increasing concentrations of Mg²⁺. (b) Typical ITC binding analysis between DHNTPase and Co²⁺ (left) and Ni²⁺ (right). (c) Fraction unfolded DHNTPase as a function of temperature. Thermal CD scans were performed as described in Methods. Open triangles, Wild-type apo DHNTPase; Closed circles, DHNTPase/SO₄^2-/Ni²⁺; Open circles, DHNTPase/SO₄^2-/Co²⁺; Closed triangles, DHNTPase/SO₄^2-. (d) Typical ITC binding analysis between apo DHNTPase and SO₄^2-. Thermodynamic parameters for ITC experiments in (b) and (d) are listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0180241#pone.0180241.t004" target="_blank">Table 4</a>.</p